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An improved method was developed for the detection of 16 polycyclic aromatic hydrocarbons (PAHs) in mainstream cigarette smoke during combustion. The methodological approach involved matrix matching standard solution preparation, direct injection of the extraction solution, and measurement of standard linearity curves to quantitatively analyze the release of target compounds. Considering the diverse physical and chemical properties as well as distribution patterns of the 16 PAHs in cigarette smoke, the impact of room temperature and high-temperature ion sources on the response of target compounds was investigated. Additionally, the preparation methods of matrix solvents and the matrix effects on the quantitative results of target compounds were also explored. Furthermore, a systematic study was conducted on the smoke release distribution of commercially available cigarettes with different circumferences. The results demonstrated that direct injection of sample extract eliminates the need for sample purification, concentration, and other processing steps employed in current detection methods. This simplifies sample pretreatment procedures while reducing organic solvent usage and consumables consumption. Moreover, it resolves issues related to low operational efficiency when dealing with large quantities of samples. The use of matrix solvent to prepare standard solution effectively reduces the influence of matrix effect, and solves the technical problem of low recovery of target substance in flue gas caused by no purification treatment when using gas chromatography-tandem mass spectrometry (GC-MS/MS) to analyze 16 kinds of PAHs. Under the normal working parameters of the instrument, the electron impact ion source (EI) was used under high temperature to improve the ionization efficiency of the targets in complex matrix and to ensure the accurate analysis of targets with low concentrations. The correlation coefficients (R2) of the calibration curves for 16 PAHs are 0.996 4-0.999 8, the limits of dectection and the limits of quantification are 0.29-1.48, 0.95-4.94 ng/cigarette, respectively. Under different concentration levels, the average recovery is 87.71%-123.26%, and the precision is within 1.58%-9.45%. By analyzing the reference cigarette 3R4F, there is no significant difference between this method and those reported in the literature. The total amount of PAHs released from 58 brands of cigarette samples are 742.76-1 505.99 ng/cigarette. At the same time, with the decrease of tar content in cigarette, the release of PAHs will be reduced accordingly. This method is simple, practical, stable, and accurate, providing more technical means for the detection of trace PAHs in cigarette smoke.

This study aimed to explore the effects of a lexical approach to Chinese English major students' reading comprehension ability as well as students' opinions of this approach. A quasiexperimental study was carried out in a Normal University in southern China for 11 weeks. An intact class of 45 first-year English major students at intermediate level participated in the study. They were instructed using a lexical approach to study four long reading texts. The instruments included reading comprehension tests, a questionnaire, and a semistructured interview. The results showed that students made much progress in reading comprehension after the treatment and they had positive opinions of the lexical approach. It can be concluded from this that the lexical approach had positive impacts on Chinese English major students' reading comprehension ability and it suggests that this approach could be implemented in English language teaching and learning for English majors in higher education.

Whole-brain dynamic functional connectivity is a growing area in neuroimaging research, encompassing data-driven methods for investigating how large-scale brain networks dynamically reorganize during resting states. However, this approach has been rarely applied to functional magnetic resonance imaging (fMRI) data acquired during task performance. In this study, we first combined the psychophysiological interactions (PPI) and sliding-window methods to analyze dynamic effective connectivity of fMRI data obtained from subjects performing the N-back task within the Human Connectome Project dataset. We then proposed a hypothetical model called Condition Activated Specific Trajectory (CAST) to represent a series of spatiotemporal synchronous changes in significantly activated connections across time windows, which we refer to as a trajectory. Our finding demonstrate that the CAST model outperforms other models in terms of intra-group consistency of individual spatial pattern of PPI connectivity, overall representational ability of temporal variability and hierarchy for individual task performance and cognitive traits. This dynamic view afforded by the CAST model reflects the intrinsic nature of coherent brain activities.

Abstract Background Although GqPCR activation often leads to cell survival by activating the PI3K/AKT pathway, it was previously shown that in several cell types AKT activity is reduced and leads to JNK activation and apoptosis. The mechanism of AKT inactivation in these cells involves an IGBP1-coupled PP2Ac switch that induces the dephosphorylation and inactivation of both PI3K and AKT. However, the machinery involved in the initiation of PP2A switch is not known. Methods We used phospho-mass spectrometry to identify the phosphorylation site of PP2Ac, and raised specific antibodies to follow the regulation of this phosphorylation. Other phosphorylations were monitored by commercial antibodies. In addition, we used coimmunoprecipitation and proximity ligation assays to follow protein–protein interactions. Apoptosis was detected by a TUNEL assay as well as PARP1 cleavage using SDS-PAGE and Western blotting. Results We identified Ser24 as a phosphorylation site in PP2Ac. The phosphorylation is mediated mainly by classical PKCs (PKCα and PKCβ) but not by novel PKCs (PKCδ and PKCε). By replacing the phosphorylated residue with either unphosphorylatable or phosphomimetic residues (S24A and S24E), we found that this phosphorylation event is necessary and sufficient to mediate the PP2A switch, which ultimately induces AKT inactivation, and a robust JNK-dependent apoptosis. Conclusion Our results show that the PP2A switch is induced by PKC-mediated phosphorylation of Ser24-PP2Ac and that this phosphorylation leads to apoptosis upon GqPCR induction of various cells. We propose that this mechanism may provide an unexpected way to treat some cancer types or problems in the endocrine machinery.

Abstract The Thermomyces lanuginosus lipase (TLLs) was successfully immobilized within a novel hydrogel matrix through a two-step crosslinking method. TLLs were initially crosslinked through the Schiff base reaction by oxidized carboxymethyl cellulose (OCMC). The water-soluble OCMC@TLLs complex was subsequently crosslinked by carboxymethyl chitosan (CMCSH) in a microfluidic apparatus to form the CMCHS/OCMC@TLLs microspheres. The CD (Circular Dichroism, CD) and FT-IR (Fourier Transform infrared spectroscopy, FT-IR) spectra demonstrated that the crosslinking of TLLs with OCMC resulted in a less significant impact on their structure compared to that with glutaraldehyde. CMCHS/OCMC@TLLs showed decreased catalytic performance due to the mass transfer resistance, while its thermal stability was greatly improved. The CMCHS/OCMC@TLLs were used to catalyze the lauroylation of arbutin in tetrahydrofuran. After 12 h of reaction under optimal conditions, the yield of 6′-O-lauryl arbutin reached an impressive 92.12%. The prepared 6′-O-lauryl arbutin has high lipophilicity and exhibits similar tyrosinase inhibitory activity and higher antioxidant activity compared to its parent compound. Graphical Abstract

Objective To investigate the “Precision Treatment for Oncology” course, which is offered by Peking Union Medical College.The course is aiming for collecting students′ opinions and suggestions to optimize the course setting and improve the teaching quality. Methods This investigation collected data by questionnaire survey and interviewing from Dec.2021 to Feb.2022. The questionnaire data and interview data were analysed. Results Thirty-six quantitative questionnaires and five qualitative questionnaires were included. Improving professional knowledge and personal interests were two main reasons for students to choose courses, which existed statistical differences on different aspects of course evaluation. The overall score evaluated by medical students was 9.22 and 94.4% of the students thought the course achieved the desired goal. The scores of teachers′ teaching attitude, frontier and practicality of course content were 9.81, 9.08 and 8.86 points respectively. The students hoped to increase the case analysis practice and thematic discussion activities to enrich the teaching form. Conclusions This elective course for graduate is recognized and accepted by students. More efforts are needed in future to optimize curriculum settings, innovate teaching methods, improve teaching quality and explore new pathways for medical graduate education matching the needs of students.

Abstract Background The present study aimed to investigate the differences in chronobiology and prevention between patients with acute type-A aortic dissection (ATAAD) complicated with sleep apnea syndrome (SAS) and without sleep apnea syndrome (non-SAS). Methods We retrospectively analyzed the clinical information of ATAAD patients using hospital medical records and regional meteorological and chronological information between January 2013 and December 2019. Results An early mortality rate of 16.9% (196 out of 1160 cases) was observed, comprising 95 cases of aortic rupture before surgery and 101 surgery-related deaths. Eighty-one of the 964 survivors were screened for SAS using complete morphological characteristics. Of these patients, 291 (33.0%) suffered from SAS, while 590 (67.0%) had no SAS. Based on a Circular Von Mises distribution analysis, the non-SAS patients experienced a significant morning peak in the occurrence of ATAAD at 10:04 (r1 = 0.148, p 0.05). Furthermore, SAS patients experienced a peak on Fridays (χ2 = 36.419, p

Abstract Ulva is one of the main green algae causing green tide disasters. Ulvan is the primarily component polysaccharide of the cell wall of Ulva and its complex structure and monosaccharide composition resulted in various biological activities. However, the high-value and effective utilization of extracted ulvan have been obstructed by limitations ranging from large molecular weight and low solubility to poor bioavailability. Ulva oligosaccharide obtained by degrading ulvan can not only ideally retain the various biological activities of ulvan very well but also effectively solve the problems of low solubility and poor bioavailability. The preparation and biological activity studies of ulvan and Ulva oligosaccharides have become a hot spot in the field of marine biological resources development research. At present, the comprehensive reviews of ulvan and Ulva oligosaccharides are still scarce. What are overviewed in this paper are the chemical composition, structure, extraction, and purification of ulvan and Ulva oligosaccharides, where research progress on the biological activities of ulvan and Ulva oligosaccharides is summarized and prospected. A theoretical and practical basis has been provided for further research on ulvan and Ulva oligosaccharides, as well as the high-value development and effective utilization of marine algae resources. Graphical Abstract

High-temperature vapour-phase acetylation (HTVPA) is a simultaneous acetylation and heat treatment process for wood modification. This study was the first investigation into the impact of HTVPA treatment on the resistance of wood to biological degradation. In the termite resistance test, untreated wood exhibited a mass loss (MLt) of 20.3%, while HTVPA-modified wood showed a reduced MLt of 6.6–3.2%, which decreased with an increase in weight percent gain (WPG), and the termite mortality reached 95–100%. Furthermore, after a 12-week decay resistance test against brown-rot fungi (Laetiporus sulfureus and Fomitopsis pinicola), untreated wood exhibited mass loss (MLd) values of 39.6% and 54.5%, respectively, while HTVPA-modified wood exhibited MLd values of 0.2–0.9% and −0.2–0.3%, respectively, with no significant influence from WPG. Similar results were observed in decay resistance tests against white-rot fungi (Lenzites betulina and Trametes versicolor). The results of this study demonstrated that HTVPA treatment not only effectively enhanced the decay resistance of wood but also offered superior enhancement relative to separate heat treatment or acetylation processes. In addition, all the HTVPA-modified wood specimens prepared in this study met the requirements of the CNS 6717 wood preservative standard, with an MLd of less than 3% for decay-resistant materials.

Summary: Ferroptosis is a form of regulated cell death with roles in degenerative diseases and cancer. Excessive iron-catalyzed peroxidation of membrane phospholipids, especially those containing the polyunsaturated fatty acid arachidonic acid (AA), is central in driving ferroptosis. Here, we reveal that an understudied Golgi-resident scaffold protein, MMD, promotes susceptibility to ferroptosis in ovarian and renal carcinoma cells in an ACSL4- and MBOAT7-dependent manner. Mechanistically, MMD physically interacts with both ACSL4 and MBOAT7, two enzymes that catalyze sequential steps to incorporate AA in phosphatidylinositol (PI) lipids. Thus, MMD increases the flux of AA into PI, resulting in heightened cellular levels of AA-PI and other AA-containing phospholipid species. This molecular mechanism points to a pro-ferroptotic role for MBOAT7 and AA-PI, with potential therapeutic implications, and reveals that MMD is an important regulator of cellular lipid metabolism.

Abstract Background Aortic arch pathologies are concerning clinical conditions with poor prognoses. The use of thoracic endovascular aortic repair (TEVAR) has been investigated to treat aortic arch pathologies. Nonetheless, cerebral blood flow regulation during endovascular aortic arch repair therapy remains challenging. Castor, a unique single-branched stent graft, has been proven effective for retaining the left subclavian artery (LSA). This study aimed to determine whether endovascular therapy for pathologies involving the aortic arch using Castor in combination with the in-vitro fenestration technique is promising, effective, and safe. Methods Eligible patients were enrolled between June 2018 and December 2021. All patients underwent TEVAR with an evaluated proximal landing zone for “Castor” located in Ishimaru zones 0–1. Moreover, the supra-aortic branches (SABs) were reconstructed using the Castor in combination with the in-vitro fenestration technique. Results Herein, 57 patients with aortic arch lesions were treated with Castor in combination with the in-vitro fenestration technique. Innominate artery and the left carotid artery (LCA) were reconstructed in 5 patients, LCA and left subclavian artery (LSA) were reconstructed in 22 patients, and the total SABs were effectively reconstructed in 30 patients (including a hybrid arch repair case). Among them (excluding a hybrid arch repair case) were in-vitro fenestration methodologies for LCA in 32 of 34 cases (2 switched to in-situ fenestration) and LSA in 51 of 56 cases (3 switched to in-situ fenestration and 2 converted to spring coil caulking); furthermore, LCA and LSA in-vitro fenestration were simultaneously successfully performed in 27 of 34 cases. There were no surgical-related neurological complications, and early mortality was estimated at 5.26%. At a mean follow-up of 3.75 months, computed tomography (CTA) images confirmed that each branch stent remained patent. There were no signs of endoleaks, migrative manifestations, or the need for secondary endovascular intervention or conversion to open surgical procedures. Conclusion Castor, in combination with in-vitro fenestration, reflects a feasible, efficient procedure for re-developing SABs.

Rapid extraction and concentration systems based on green materials such as cellulose or lignin are promising. However, there is still a need to optimize the material properties and production processes. Unlike conventional cellulose or lignin sorbent materials, aquatic reed root cells can concentrate external organic pollutants in the water and accumulate them in the plant. Inspired by this, a new nanocellulose–lignin aerogel (NLAG) was designed, in which nanocellulose was used as a substrate and lignin and polyamide epoxy chloropropane were used to crosslink cellulose in order to enhance the strength of the NLGA, resulting in good mechanical stability and water–oil amphiphilic properties. In practical applications, the organic membrane on the NLAG can transport organic pollutants from water to the NLAG, where they are immobilized. This is evidenced by the fact that the aerogel can remove more than 93% of exogenous phenol within a few minutes, highly enriching it inside. In addition, the aerogel facilitates filtration and shape recovery for reuse. This work establishes a novel biopolymer–aerogel-based extraction system with the advantages of sustainability, high efficiency, stability, and easy detachability, which are hard for the traditional adsorbent materials to attain.

Objective: To investigate the effect of the screw configuration on the polylactic acid flow field on the structural parameters of the screw on the end face of the screw in the meshing counter rotating twin screw extruder. Methods: The theoretical model of the heterodirectional double-ended threaded element was established by Solidworks software and the geometry of the threaded element after adjusting the structural parameters in two different ways. The established three-dimensional model was imported into Gambit software for meshing, and then Polyflow software was applied to the flow field simulation calculation. Finally, the flow field distribution results were extracted by Fieldview software, and the effects of the adjustment of the structural parameters on the end surface of the threaded element during correction were compared and analyzed on the shear rate field, viscosity field and speed field. Results: The structural parameters of the threaded element during correction will affect the polylactic acid flow field after being adjusted in two ways. The two adjustment methods of structural parameters have reduced the shear rate gradient in the runner to varying degrees, and the first method has also caused the viscosity of the polymer lactic acid in the runner to be reduced. Conclusion: From the perspective of the influence on the shear rate field, viscosity field and speed field, the threaded element adjusted by mode one is more conducive to extrusion, while the solid configuration of the threaded element adjusted by mode two is closer to the theoretical configuration of the threaded component.

Abstract Background Cryptosporidium spp., Giardia duodenalis and Enterocytozoon bieneusi can cause important intestinal diseases in ruminants. However, data on the distribution of these three protozoan pathogens in Tibetan sheep are limited. Methods We collected 761 fecal samples from Tibetan sheep across four seasons in Qinghai Province, China, and screened the samples for Cryptosporidium spp., G. duodenalis and E. bieneusi using PCR-based sequence analysis of the genes encoding 18S ribosomal RNA, triosephosphate isomerase and the internal transcribed spacer, respectively. Results The positivity rates of Cryptosporidium spp., G. duodenalis and E. bieneusi in Tibetan sheep were 3.68% (28/761 samples), 1.58% (12/761) and 6.44% (49/761), respectively. Four species of Cryptosporidium were identified: C. xiaoi (n = 13 samples), C. ubiquitum (n = 8), C. bovis (n = 6) and C. ryanae (n = 1). Two G. duodenalis assemblages, namely the A (n = 2 samples) and E (n = 10) assemblages, were detected. Five zoonotic E. bieneusi genotypes were found: BEB6 (n = 21 samples), COS-I (n = 14), CHS3 (n = 11) and CGS1 (n = 2) from group 2, and PIGEBITS5 (n = 1) from group 1. Geographic differences in the distribution of E. bieneusi, and seasonal differences for all the three protozoan pathogens were noted. Conclusions Our results elucidate the prevalence and genetic diversity of these three pathogens in Tibetan sheep across different regions and seasons, including zoonotic pathogens such as C. ubiquitum, C. ryanae, G. duodenalis assemblage A and five genotypes of E. bieneusi. Graphical Abstract

Neutralisation assays are key to understanding immune responses to SARS-CoV-2 infection or vaccination. Here, the authors report a surrogate virus neutralization assay called Neu-SATiN, which measures neutralization directly from sera, and allows easy adaptation to variant-specific testing.

Objective: Explore the effects of different combinations of forward screw elements in the melt conveying section on the melt conveying characteristics of reverse screw elements. Methods: Two different models were constructed by changing the lead, using SolidWorks software to establish a three-dimensional model, and using Polyflow software to numerically simulate the extrusion process of the two models in the melt conveying section. The effects of the screw groove width and screw edge thickness of the screw elements on the flow field under different lead lengths and the changes in the flow field at different rotational speeds were analyzed, and the effects of rotational speed on the material mixing were verified through experiments. Results: The constructed model can allow the melt to pass through the reverse threaded element. At the same screw speed, the pressure building capacity and conveying capacity of model one constructed from large lead screw elements were stronger than that of model two constructed from small lead screw elements. Model one was superior to Model two in terms of decentralized mixing ability, and weaker than Model two in terms of distributed mixing ability. Under the same pressure difference at both ends, increasing the rotational speed could improve the dispersion and mixing effects of materials. Conclusion: Using model one in the improved processing of polylactic acid and increasing the rotational speed of the screw can further crush the material and improve the quality of the extrusion.

Abstract Background The percutaneous device closure of patent ductus arteriosus (PDA) is widely used in clinical practice, however full data on the changes in myocardial injury and systemic inflammatory markers’ levels after PDA in children are not fully reported. Methods We have conducted a retrospective analysis of the medical records of 385 pediatric patients in our hospital from January 2017 to December 2019. The patients were distributed into five groups. The first four (A, B, C and D) included patients divided by the type of the surgical closure methods, namely ligation, clamping, ligation-combined suturing and ligation-combined clamping, respectively. The fifth group E comprised of percutaneous device PDA patients. All recorded medical and trial data from the five groups were statistically studied. Results No serious complications in the patients regardless of the classification group were reported. Our results suggested that there were no considerable differences between the groups at the baseline (with all P > 0.05). Group E demonstrated a significantly smaller operative time (42.39 ± 3.88, min) and length of hospital stay (LOS) (4.49 ± 0.50, day), less intraoperative blood loss (7.12 ± 2.09, ml) while on the other hand, a higher total hospital cost (24,001.35 ± 1152.80, RMB) than the other four groups (with all P 0.05) among the four groups. On the contrary, when the aforementioned factors and markers of all the surgical groups were compared to those in group E, we observed significantly higher speed and magnitude of changes in group E than those in groups A, B, C, and D (with all P

Abstract Background G protein-coupled receptors (GPCRs) usually regulate cellular processes via activation of intracellular signaling pathways. However, we have previously shown that in several cell lines, GqPCRs induce immediate inactivation of the AKT pathway, which leads to JNK-dependent apoptosis. This apoptosis-inducing AKT inactivation is essential for physiological functions of several GqPCRs, including those for PGF2α and GnRH. Methods Here we used kinase activity assays of PI3K and followed phosphorylation state of proteins using specific antibodies. In addition, we used coimmunoprecipitation and proximity ligation assays to follow protein–protein interactions. Apoptosis was detected by TUNEL assay and PARP1 cleavage. Results We identified the mechanism that allows the unique stimulated inactivation of AKT and show that the main regulator of this process is the phosphatase PP2A, operating with the non-canonical regulatory subunit IGBP1. In resting cells, an IGBP1-PP2Ac dimer binds to PI3K, dephosphorylates the inhibitory pSer608-p85 of PI3K and thus maintains its high basal activity. Upon GqPCR activation, the PP2Ac-IGBP1 dimer detaches from PI3K and thus allows the inhibitory dephosphorylation. At this stage, the free PP2Ac together with IGBP1 and PP2Aa binds to AKT, causing its dephosphorylation and inactivation. Conclusion Our results show a stimulated shift of PP2Ac from PI3K to AKT termed “PP2A switch” that represses the PI3K/AKT pathway, providing a unique mechanism of GPCR-stimulated dephosphorylation. Video Abstract

Understanding customer needs is of great significance to enhance service quality and competitive advantage. However, for the tourism industry, it is still unclear how to mine service improvement strategies from tourist-generated online reviews. This paper aims to develop a data-driven approach to conduct a fine-grained dimension analysis of customer satisfaction with tourism services. First, this paper uses Latent Dirichlet Allocation to explore the key dimensions of tourist satisfaction from online reviews. Next, based on the Chinese sentiment dictionary, tourists’ emotional attitudes towards each service dimension can be identified. Then, the backpropagation neural network is used to measure the complex relationship between tourists’ sentiment orientations towards different dimensions and their satisfaction. Finally, according to the improved Kano model, multi-dimensional attribute classification is realized to support the strategic analysis of tourism service quality improvement. The proposed method is empirically verified through a real tourism review dataset. The results exhibit the theoretical and practical implications of our method.

This study focused on analyzing the complexities and risk spillovers that arise among financial institutions due to the development of financial markets. The research employed the conditional value at risk (CoVaR) methodology to quantify the extent of tail risk spillover and constructed a risk spillover network encompassing Chinese financial institutions. The study further investigated the characteristics, transmission paths, and dynamic evolution of this network under different risk conditions. The empirical findings of this research highlighted several important insights. First, financial institutions play distinct roles in the risk spillover process, with the securities and banking sectors as risk exporters and the insurance and diversified financial sectors as risk takers. The closest risk spillover relationships were observed between banking and insurance and between securities and diversified financial sectors. Second, in high-risk scenarios, there is significant intrasectoral risk transmission between banks and the diversified financial sector, as well as dual-sectoral risk contagion between banks and securities, with the most-common transmission occurring between diversified financial and securities sectors. Finally, the securities sector acts as the pivotal node for risk spillovers, being the main transmitter of intersectoral risks. The formation and evolution of risk spillover networks are influenced by endogenous mechanisms, in particular the convergence effect.

Summary: Met is an oncogene aberrantly activated in multiple cancers. Therefore, to better understand Met biology and its role in disease we applied the Mammalian Membrane Two-Hybrid (MaMTH) to generate a targeted interactome map of its interactions with human SH2/PTB-domain-containing proteins. We identified thirty interaction partners, including sixteen that were previously unreported. Non-small cell lung cancer (NSCLC)-focused functional characterization of a Met-interacting protein, BLNK, revealed that BLNK is a positive regulator of Met signaling, and modulates localization, including ligand-dependent trafficking of Met in NSCLC cell lines. Furthermore, the interaction between Met and GRB2 is increased in the presence of BLNK, and the constitutive interaction between BLNK and GRB2 is increased in the presence of active Met. Tumor phenotypical assays uncovered roles for BLNK in anchorage-independent growth and chemotaxis of NSCLC cell lines. Cumulatively, this study provides a Met-interactome and delineates a role for BLNK in regulating Met biology in NSCLC context.

Objective: Osteoarthritis (OA) is a degenerative joint disease. Excessive nitric oxide (NO) mediates the chondrocyte inflammatory response, apoptosis, and extracellular matrix (ECM) degradation during the occurrence and development of OA. NO in chondrocytes is mainly produced by inducible nitric oxide synthase (iNOS). The aim of this study was to design and synthesize an iNOS dimerization inhibitor and evaluate its effects on chondrocyte inflammation and articular cartilage injury in OA via in vitro and in vivo experiments.Design: The title compound 22o was designed, synthesized, and screened based on a previous study. The effects of different concentrations (5, 10, and 20 μM) of compound 22o on chondrocyte inflammatory response and ECM anabolism or catabolism were evaluated by Western blot and real-time quantitative reverse transcription-polymerase chain reaction using the rat chondrocyte model of IL-1β-induced OA. Furthermore, different doses (40 and 80 mg/kg) of compound 22o were administered by gavage to a rat OA model induced by anterior cruciate ligament transection (ACLT), and their protective effects on the articular cartilage were evaluated by histopathology and immunohistochemistry.Results: Compound 22o showed effective iNOS inhibitory activity by inhibiting the dimerization of iNOS. It inhibited the IL-1β-induced expression of cyclooxygenase-2 (COX-2) and matrix metalloproteinase 3 (MMP3) in the chondrocytes, decreased NO production, and significantly increased the expression levels of the ECM anabolic markers, aggrecan (ACAN), and collagen type II (COL2A1). Gavage with compound 22o was found to be effective in the rat OA model induced by ACLT, wherein it regulated the anabolism and catabolism and exerted a protective effect on the articular cartilage.Conclusions: Compound 22o inhibited the inflammatory response and catabolism of the chondrocytes and reduced articular cartilage injury in the rat OA model, indicating its potential as a disease-modifying OA drug.

The enzymatic degradation of seaweed polysaccharides is gaining interest for its potential in the production of functional oligosaccharides and fermentable sugars. Herein, a novel alginate lyase, AlyRm3, was cloned from a marine strain, Rhodothermus marinus DSM 4252. The AlyRm3 showed optimal activity (37,315.08 U/mg) at 70 °C and pH 8.0, with the sodium alginate used as a substrate. Noticeably, AlyRm3 was stable at 65 °C and also exhibited 30% of maximal activity at 90 °C. These results indicated that AlyRm3 is a thermophilic alginate lyase that efficiently degrades alginate at high industrial temperatures (>60 °C). The FPLC and ESI−MS analyses suggested that AlyRm3 primarily released disaccharides and trisaccharides from the alginate, polyM, and polyG in an endolytic manner. In the saccharification process of sodium alginate (0.5%, w/v), the AlyRm3 yielded numerous reducing sugars (1.73 g/L) after 2 h of reaction. These results indicated that AlyRm3 has a high enzymatic capacity for saccharifying the alginate, and could be used to saccharify the alginate biomass before the main fermentation process for biofuels. These properties make AlyRm3 a valuable candidate for both fundamental research and industrial applications.

Serological tests are important diagnostic and disease surveillance tools for addressing the COVID-19 pandemic. Here, the authors present a tri-part Nanoluciferase based assay to detect antibodies against SARS-CoV-2.

Resibufogenin (RB) is a major active ingredient in the traditional Chinese medicine Chansu and has garnered considerable attention for its efficacy in the treatment of cancer. However, the anticancer effects and underlying mechanisms of RB on glioblastoma (GBM) remain unknown. Here, we found that RB induced G2/M phase arrest and inhibited invasion in a primary GBM cell line, P3#GBM, and two GBM cell lines, U251 and A172. Subsequently, we demonstrated that RB-induced G2/M phase arrest occurred through downregulation of CDC25C and upregulation of p21, which was caused by activation of the MAPK/ERK pathway, and that RB inhibited GBM invasion by elevating intercellular Ca2+ to suppress the Src/FAK/Paxillin focal adhesion pathway. Intriguingly, we confirmed that upon RB binding to ATP1A1, Na+-K+-ATPase was activated as a receptor and then triggered the intracellular MAPK/ERK pathway and Ca2+-mediated Src/FAK/Paxillin focal adhesion pathway, which led to G2/M phase arrest and inhibited the invasion of GBM cells. Taken together, our findings reveal the antitumor mechanism of RB by targeting the ATP1A1 signaling cascade and two key signaling pathways and highlight the potential of RB as a new class of promising anticancer agents.

Air quality plays a vital role in people’s health, and air quality forecasting can assist in decision making for government planning and sustainable development. In contrast, it is challenging to multi-step forecast accurately due to its complex and nonlinear caused by both temporal and spatial dimensions. Deep models, with their ability to model strong nonlinearities, have become the primary methods for air quality forecasting. However, because of the lack of mechanism-based analysis, uninterpretability forecasting makes decisions risky, especially when the government makes decisions. This paper proposes an interpretable variational Bayesian deep learning model with information self-screening for PM2.5 forecasting. Firstly, based on factors related to PM2.5 concentration, e.g., temperature, humidity, wind speed, spatial distribution, etc., an interpretable multivariate data screening structure for PM2.5 forecasting was established to catch as much helpful information as possible. Secondly, the self-screening layer was implanted in the deep learning network to optimize the selection of input variables. Further, following implantation of the screening layer, a variational Bayesian gated recurrent unit (GRU) network was constructed to overcome the complex distribution of PM2.5 and achieve accurate multi-step forecasting. The high accuracy of the proposed method is verified by PM2.5 data in Beijing, China, which provides an effective way, with multiple factors for PM2.5 forecasting determined using deep learning technology.

The environment and development are major issues of general concern. After much suffering from the harm of environmental pollution, human beings began to pay attention to environmental protection and started to carry out pollutant prediction research. A large number of air pollutant predictions have tried to predict pollutants by revealing their evolution patterns, emphasizing the fitting analysis of time series but ignoring the spatial transmission effect of adjacent areas, leading to low prediction accuracy. To solve this problem, we propose a time series prediction network with the self-optimization ability of a spatio-temporal graph neural network (BGGRU) to mine the changing pattern of the time series and the spatial propagation effect. The proposed network includes spatial and temporal modules. The spatial module uses a graph sampling and aggregation network (GraphSAGE) in order to extract the spatial information of the data. The temporal module uses a Bayesian graph gated recurrent unit (BGraphGRU), which applies a graph network to the gated recurrent unit (GRU) so as to fit the data’s temporal information. In addition, this study used Bayesian optimization to solve the problem of the model’s inaccuracy caused by inappropriate hyperparameters of the model. The high accuracy of the proposed method was verified by the actual PM2.5 data of Beijing, China, which provided an effective method for predicting the PM2.5 concentration.

Augmented reality (AR) technology has been used and is of great benefit to the formulation of operation planning, simulation of operation scheme, improvement of operation outcome and reduction of risk in joint surgery, and also creates favorable conditions for the understanding of common diseases in joint surgery and training of practical operation skills of young orthopedic surgeons.

Abstract Background Practitioners of complementary and alternative medicine have suggested that electroacupuncture (EA) could improve post-stroke cognitive impairment, based on the clinical evidence. This study protocol is aimed at showing the effectiveness of theta and gamma EA for post-stroke patients on working memory (WM) and electrophysiology. Methods After assessing their eligibility, 66 patients with stroke will be enrolled from two Chinese medicine hospitals and randomly divided into theta frequency EA group, gamma frequency EA group, and sham-EA group according to the ratio of 1:1:1. All patients will receive 20 sessions of EA procedures for 4 weeks. Patients in three groups will receive EA at two same acupoints in the head: Baihui (GV20) and Shenting (GV24). The frequency of the three groups of EA is set as follows: 6 Hz (theta-EA group), 40 Hz (gamma-EA group), and no current through the electrodes (sham EA). Patients and assessors will be blinded throughout the entire study. The primary outcome is the performance accuracy of 1-back task which is a frequently used measure of WM in cognitive neuroscience research contexts. Secondary outcome measures will include the response time of 1-back task, the Rivermead Behavioral Memory Test, Trail Making Test, Loewenstein Occupational Therapy Cognitive Assessment Scale, modified Barthel Index, and electroencephalogram (EEG) signals during 1-back tasks. A blinding index will be assessed. Data will be statistically analyzed by one-way ANOVA, at 5% of significance level. Discussion We expect this double-center, randomized, patient- and assessor-blinded, sham-controlled, parallel, clinical trial to explore the effectiveness of theta and gamma EA therapy, compared with sham EA, for post-stroke WM. Trial registration Chinese Clinical Trial Registry, ChiCTR2000031995 . Registered on 17 April 2020.

Abstract Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) is a chloride and bicarbonate channel in secretory epithelia with a critical role in maintaining fluid homeostasis. Mutations in CFTR are associated with Cystic Fibrosis (CF), the most common lethal autosomal recessive disorder in Caucasians. While remarkable treatment advances have been made recently in the form of modulator drugs directly rescuing CFTR dysfunction, there is still considerable scope for improvement of therapeutic effectiveness. Here, we report the application of a high‐throughput screening variant of the Mammalian Membrane Two‐Hybrid (MaMTH‐HTS) to map the protein–protein interactions of wild‐type (wt) and mutant CFTR (F508del), in an effort to better understand CF cellular effects and identify new drug targets for patient‐specific treatments. Combined with functional validation in multiple disease models, we have uncovered candidate proteins with potential roles in CFTR function/CF pathophysiology, including Fibrinogen Like 2 (FGL2), which we demonstrate in patient‐derived intestinal organoids has a significant effect on CFTR functional expression.

Efficient lubrication is the key to reducing tool friction and wear, decreasing cutting force and enhancing tool cutting performance. To find a more efficient way to improve the lubrication performance of the tools in high-speed cutting hard-cutting materials, YG6X cemented carbide milling inserts textured with micro-groove parallel to the main cutting edge and Fe3O4 nanofluids with a mass concentration of 0.5% were fabricated, the friction and wear tests and contact angle tests were carried out to investigate the coupling lubrication effects of micro-textures and nanofluids. Results obtained in this work indicated that the friction coefficient of micro-texture sample under nanofluids lubrication was reduced by 92.2% when compared with the un-textured sample under dry friction, and the contact angle of the nanofluids droplet on micro-texture surface was 72.1% lower than that of the emulsion droplet on un-textured surface. Based on the results, a series of experiments were further carried out on high-speed milling Ti6Al4V using micro-texture milling cutter under the nanofluids lubrication. The results showed that cutting forces of micro-texture milling cutters under nanofluids lubrication were reduced by 19.1%, 30.8%, 37.7% and 30.0% when compared with un-textured milling cutters under emulsion lubrication at the spindle speeds of 1000r/min, 2000r/min, 3000r/min and 4000r/min.

Protein-protein interactions are fundamental to the regulation of protein activity and cellular phyisology. Here the authors present Split Intein-Mediated Protein Ligation, which uses bait and prey proteins fused to intein fragments to generate single intact proteins upon interaction.

The hydrodynamic characteristic of transonic motion projectiles with different head diameters are investigated by numerical simulation. Compressibility effect in liquid-phase water are modeled using the Tait state equation. The result shows that with increasing of velocity the compression waves transfer to shock waves，which cause the significant increasing of pressure and decreasing the dimensions of supercavities. While the increasing of head diameter, the thickness, the vapor volume fraction and the drag coefficient of supercavities are all enhanced, which is conducive to the stability of transonic-speed projectiles. The cavity dynamics of the different head projectiles are compared, and the results shows when Mach number is in high region, the truncated cone head projectile is enveloped by a cavity which results in less drag and better stability.