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Danni Bao,1 Xiaohong Xu,1 Yizhang Wang,1 Fengjiao Zhu,1 Yanhong Wu,1 Hongzhang Li2 1Department of Clinical Laboratory, Sanmen People’s Hospital, Taizhou, Zhejiang, People’s Republic of China; 2Department of Gastroenterology, Sanmen People’s Hospital, Taizhou, Zhejiang, People’s Republic of ChinaCorrespondence: Hongzhang Li, Department of Gastroenterology, Sanmen People’s Hospital, Taizhou, Zhejiang, People’s Republic of China, Email lihongzhang@zjsmyy.comAbstract: We report a case of Clostridium ramosum bacteremia in a 73-year-old patient with SARS-CoV-2 infection and right lower abdominal tenderness in China. The microbiological features and genomic epidemiological characteristics of C. ramosum worldwide were investigated to identify the possible sources of infection. Whole-genome sequencing of C. ramosum WD-I2 was performed using an Illumina NovaSeq 6000 platform. Phylogenetic analysis of C. ramosum WD-I2 and other publicly available C. ramosum isolates was performed and visualized using the interactive Tree of Life (iTOL) web server. The resistome of C. ramosum WD-I2 consists of two antimicrobial resistance genes (tetM and ermB), which explains the antimicrobial resistance trait to tetracycline and macrolides. Phylogenetic analysis showed that the strain closest to our isolated strain WD-I2 was SUG1069, recovered from a pig feces sample from Canada, which differed by 589 SNPs. To our knowledge, this is the first report of C. ramosum bacteremia in China. Our findings highlight the potential risk of invasive C. ramosum infections during the COVID-19 pandemic.Keywords: Clostridium ramosum, bacteremia, antimicrobial resistance, SARS-CoV-2, whole genome sequencing

Xiaohong Xu,1,* Rongping Zhu,1,* Siyan Lian,1 Hui Zhang,2 Xin Chen,2 Lingfang Fan,1 Peisong Chen,2 Yingping Cao1 1Department of Clinical Laboratory, Fujian Medical University Union Hospital, Fuzhou, Fujian, People’s Republic of China; 2Medical Technology and Engineering, Fujian Medical University, Fuzhou, Fujian, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yingping Cao, Department of Clinical Laboratory, Fujian Medical University Union Hospital, Fuzhou, Fujian, People’s Republic of China, Tel +86-133-6591-0806, Email caoyingping@aliyun.comBackground: The emergence of polymyxin B resistance among carbapenem-resistant Klebsiella pneumoniae (CRKP) causes clinical treatment to be more difficult. We aimed to investigate the risk factors and resistance mechanisms in the polymyxin resistant CRKP (PR-CRKP) strains.Methods: From January 2021 to January 2022, 239 CRKP strains were selected, all of which were analyzed using antimicrobial susceptibility testing and clinical data. Polymerase chain reaction (PCR) was performed for the detection of resistance genes. RT-qPCR was used to quantify transcriptional levels of polymyxin resistance genes. Risk factors for polymyxin B resistant isolates were identified by logistic regression analysis.Results: The resistance rate of polymyxin B was 5.02%. In all CRKP strains, 41.84% came from the ICU. The percentage of carbapenemase producing strains was 93.72%. The main carbapenem resistance gene was blaKPC (90.79%). In the 12 strains of PR-CRKP screened, pmrB and pmrK were overexpressed in all samples which were linked with polymyxin B resistance. Multivariate analysis showed that coronary heart disease may be an independent risk factor predisposing patients to polymyxin B resistance.Conclusion: We determine the multifaceted mechanism and risk factors of polymyxin B resistance in CRKP. Polymyxin resistance is a complex and changing problem, and more research is required.Keywords: polymyxin B resistance, carbapenem-resistantKlebsiella pneumoniae, risk factors, mechanism

Danni Bao, Xiaohong Xu, Yizhang Wang, Fengjiao Zhu Department of Clinical Laboratory, Sanmen People’s Hospital, Taizhou, Zhejiang, People’s Republic of ChinaCorrespondence: Fengjiao Zhu, Department of Clinical Laboratory, Sanmen People’s Hospital, Taizhou, Zhejiang, People’s Republic of China, Email sm.zfj@foxmail.comBackground: Carbapenem-resistant Enterobacterales (CRE) are a significant threat to worldwide public health, resulting in increased morbidity, death, hospitalization time and healthcare expenses. Here, the genomic and phylogenetic characteristics of a multidrug-resistant Escherichia coli isolate carrying both the new mcr-1.33 variant and blaNDM-5 gene obtained from a urinary tract infection in China are investigated.Methods: Antimicrobial susceptibility of E. coli 779 was evaluated by using the broth microdilution method. Short-read Illumina NovaSeq 6000 and long-read Oxford Nanopore MinION platforms were applied to sequence the bacterial whole genomic DNA and then de novo assembled. The genome sequence was annotated using the NCBI Prokaryotic Genome Annotation Pipeline and further subjected to identify the sequence type (ST), capsular type, and antibiotic resistance genes. BacWGSTdb 2.0 was used to perform the core genome multilocus sequence typing (cgMLST) analysis with other closely related E. coli isolates deposited in the public database.Results: E. coli 779 was resistant to aztreonam, levofloxacin, fosfomycin, cefoxitin, cefepime, cefotaxime, imipenem, meropenem, polymyxin, and tigecycline. The complete genome sequence of E. coli 779 is made up of nine contigs totaling 5,667,876 bp, including one chromosome and eight plasmids. The isolate was assigned to ST101, serotype O-:H31, and phylogroup B1. The colistin resistance gene mcr-1.33 (located in a 242,460 bp IncHI2/IncHI2A plasmid) and the β-lactam resistance gene blaNDM-5 (located in a 46,161 bp IncX3 plasmid) were among the 27 antimicrobial resistance genes discovered. The closest relative of E. coli 779, another ST101 strain (E. coli 443) obtained from a sewage sample in Shandong, China in 2015, differs by only 24 cgMLST alleles.Conclusion: We discovered the first multidrug-resistant ST101 E. coli strain with plasmid-mediated mcr-1.33 variant and blaNDM-5 gene in China. These findings would help us to better understanding the genomic traits, antimicrobial resistance mechanisms and epidemiological aspects of this bacterial pathogen.Keywords: whole genome sequencing, Escherichia coli, multidrug-resistance, mcr-1.33, blaNDM-5, urinary tract infection

Additional file 1: Table S1. Experimental design and basic sequencing statistics for samples collected from five plant species. Table S3. Experimental design and basic sequencing statistics for samples collected from tomato plants at different growth stages. Table S9. Experimental design and basic traits for samples collected from tomato plants amended with different nitrogen sources. Table S11. Experimental design and basic sequencing statistics from metaproteomic analyses. Figure S1. Order-level community comparison and OTU-based hierarchical clustering analysis of healthy and nematode parasitized samples in five plant species. Figure S2. Unconstrained PCoA (for principal coordinates PCo1 and PCo2) with Bray–Curtis distance showing the root-associated bacteria of healthy and parasitized samples, for each plant species. Figure S3. The composition and relative abundance of major bacterial orders of the tomato root-associated microbiota at different developmental stages. Figure S4. Pairwise analysis for the variation of root-associated microbiota over time at different growth and RKN parasitism stages in tomato. Figure S5. The shared OTUs number and taxonomic composition of the depleted and enriched OUTs in the parasitized root samples (IRH and IRK) comparing with healthy roots (HRC).

Supplemental material, sj-docx-1-tct-10.1177_15330338231157156 for MicroRNA-592 Inhibits the Growth of Ovarian Cancer Cells by Targeting ERBB3 by Qiong Jin, Ning Zhang, Yang Zhan, Xiaohong Xu, Chao Han, Hui Zhao and Xiaodi Hu, Hongbo Tang, Yumei Wu in Technology in Cancer Research & Treatment

Supplemental material, sj-docx-1-tct-10.1177_15330338231157156 for MicroRNA-592 Inhibits the Growth of Ovarian Cancer Cells by Targeting ERBB3 by Qiong Jin, Ning Zhang, Yang Zhan, Xiaohong Xu, Chao Han, Hui Zhao and Xiaodi Hu, Hongbo Tang, Yumei Wu in Technology in Cancer Research & Treatment

Multiferroic tunnel junctions (MFTJs) based on two-dimensional (2D) van der Waals heterostructures with sharp and clean interfaces at the atomic scale are crucial for applications in nanoscale multi-resistive logic memory devices. The recently discovered sliding ferroelectricity in 2D van der Waals materials has opened new avenues for ferroelectric-based devices. Here, we theoretically investigate the spin-dependent electronic transport properties of Fe$_3$GeTe$_2$/graphene/bilayer-$h$-BN/graphene/CrI$_3$ (FGT/Gr-BBN-Gr/CrI) all-vdW MFTJs by employing the nonequilibrium Green's function combined with density functional theory. We demonstrate that such FGT/Gr-BBN-Gr/CrI MFTJs exhibit four non-volatile resistance states associated with different staking orders of sliding ferroelectric BBN and magnetization alignment of ferromagnetic free layer CrI$_3$, with a maximum tunnel magnetoresistance (electroresistance) ratio, i.e., TMR (TER) up to $\sim$$3.36\times10^{4}$\% ($\sim$$6.68\times10^{3}$\%) at a specific bias voltage. Furthermore, the perfect spin filtering and remarkable negative differential resistance effects are evident in our MFTJs. We further discover that the TMR, TER, and spin polarization ratio under an equilibrium state can be enhanced by the application of in-plane biaxial strain. This work shows that the giant tunneling resistance ratio, multiple resistance states, and excellent spin-polarized transport properties of sliding ferroelectric BBN-based MFTJs indicate its significant potential in nonvolatile memories., Comment: 8 pages, 8 figures

Curcumin (CUR) shows great potential in the management of alcohol-use disorders. However, the hydrophobicity and poor oral bioavailability result in the limited therapeutic efficacy of CUR against alcohol-induced tissue injury. Here, self-assembled Soluplus® micelles (Ms) were developed for the enhanced oral delivery of CUR. CUR-loaded Soluplus® micelles (CUR-Ms) were prepared using a thin-film hydration method and these micelles displayed nearly spherical shape with an average size of 62.80 ± 1.29 nm. CUR in micelles showed the greater stability, solubility and dissolution than free CUR. With the increased water solubility of CUR-Ms and P glycoprotein inhibition of Soluplus®, the absorption rate constant (Ka) and apparent permeability coefficient (Papp) of CUR-Ms in intestines was respectively 3.50 and 4.10 times higher than that of free CUR. Pharmacokinetic studies showed that CUR-Ms significantly improved the oral bioavailability of CUR. Specifically, the AUC0-∞ and Cmax of CUR-Ms were increased by 9.45 and 47.38 folds compared to free CUR, respectively. In mice with alcohol-induced tissue injury, the oral administration of CUR-Ms greatly reduced oxidative stress, and significantly defended liver and gastric mucosa from alcoholic damages. The results demonstrated CUR-Ms with good oral bioavailability could represent a promising strategy for the management of alcohol-induced tissue injury.

The introduction and inoculation of beneficial bacteria in plants have consistently been considered as one of the most important ways to improve plant health and production. However, the effects of bacterial inoculation on the community assembly and composition of the root endophytic microbiome remain largely unknown. In this study, 55 strains were randomly isolated from tomato roots and then inoculated into wheat seeds singly or in combination. Most of the isolated bacterial strains showed an ability to produce lignocellulose-decomposing enzymes and promote plant growth. The results demonstrated that bacterial inoculation had a significant effect on the wheat root endophytic microbiome. The wheat root samples inoculated with single-bacterial species were significantly separated into two groups (A and B) that had different community structures and compositions. Among these, root endophytic communities for most wheat samples inoculated with a single-bacterial strain (Group A) were predominated by one or several bacterial species, mainly belonging to Enterobacterales. In contrast, only a few of the root samples inoculated with a single-bacterial strain (Group B) harbored a rich bacterial flora with relatively high bacterial diversity. However, wheat roots inoculated with a mixed bacterial complex were colonized by a more diverse and abundant bacterial flora, which was mainly composed of Enterobacterales, Actinomycetales, Bacillales, Pseudomonadales, and Rhizobiales. The results demonstrated that inoculation with bacterial complexes could help plants establish more balanced and beneficial endophytic communities. In most cases, bacterial inoculation does not result in successful colonization by the target bacterium in wheat roots. However, bacterial inoculation consistently had a significant effect on the root microbiome in plants. CAP analysis demonstrated that the variation in wheat root endophytic communities was significantly related to the taxonomic status and lignocellulose decomposition ability of the inoculated bacterial strain (p < 0.05). To reveal the role of lignocellulose degradation in shaping the root endophytic microbiome in wheat, four bacterial strains with different colonization abilities were selected for further transcriptome sequencing analysis. The results showed that, compared with that in the dominant bacterial species Ent_181 and Ent_189 of Group A, the expression of lignocellulose-decomposing enzymes was significantly downregulated in Bac_133 and Bac_71 (p < 0.05). In addition, we found that the dominant bacterial species of the tomato endophytic microbiome were more likely to become dominant populations in the wheat root microbiome. In general, our results demonstrated that lignocellulose-decomposing enzymes played a vital role in the formation of endophytes and their successful colonization of root tissues. This finding establishes a theoretical foundation for the development of broad-spectrum probiotics.

Two-dimensional (2D) few-layer VSe2, V1−xFexSe2 nanosheets have been synthesized by a high-temperature organic solution-phase method. The thickness of VSe2 nanosheets can be tuned from 12 to 5 layers by decreasing the precursor concentrations. The few-layer VSe2 nanosheets show the room-temperature ferromagnetism. The coercivity and magnetization reach 0.024 T and 0.036 mA·m2·g−1 at room temperature. The charge-density wave behavior is also confirmed in VSe2 by the hysteresis loops and zero-field-cooling curve. V1−xFexSe2 nanosheets can be obtained by doping Fe(acac)3 in the reaction process. The room-temperature coercivity and magnetization of V0.8Fe0.2Se2 nanosheets are 5 times higher than those of the pure VSe2 nanosheets without destroying the structures. The enhancement of magnetization is due to the coupling interaction of 3d orbits between V and Fe atoms. Higher Fe concentration is beneficial to improve the coercivity, which is attributed to the formation of the second phase Fe3Se4. This simple chemical preparation method can be extended to prepare the other 2D materials.

Ambient fine particulate matter (PM2.5) levels in Windsor, Ontario, Canada, are impacted by local emissions and regional/transboundary transport input and also attributable to secondary formation. PM2.5-bound elements were monitored hourly in Windsor from April to October 2021. Observed concentrations of the elements were generally comparable to historical measurements at urban sites in Ontario. A clear diurnal pattern was observed for most of the elements, i.e., high in the morning and low in the afternoon, mostly related to evolution of atmospheric mixing heights and local anthropogenic activities. Conversely, sulfur showed elevated levels in the afternoon, suggesting conversion of gaseous sulfur dioxide to particulate sulphate was enhanced by increased ambient temperatures. Five source factors were resolved using the US EPA positive matrix factorization model, including three traffic-related sources (i.e., vehicular exhaust, crustal dust, and vehicle tire and brake wear factors) and two industrial sources (i.e., coal/heavy oil burning and metal processing factors). Overall, the three traffic-related sources were mostly local and contributed to 47% of the total elemental concentrations, while the two industrial sources may originate from regional/transboundary sources and contributed to 53%. Measures to control both local traffic emissions and regional/transboundary industrial sources would help reduce levels of PM2.5-bound elements in Windsor.

In 2010, quantum anomalous Hall effect (QAHE) in graphene was proposed in the presence of Rashba spin-orbit coupling and ferromagnetic exchange field. After a decade's experimental exploration, the anomalous Hall conductance can only reach about 0.25 in the units of $2e^2/h$, which was attributed to the tiny Rashba spin-orbit coupling. Here, we theoretically show that Re-intercalation in graphene/CrI$_3$ heterostructure can not only induce sizeable Rashba spin-orbit coupling ($>$ 40~meV), but also open up large band gaps at valleys $K$ (22.2 meV) and $K' $ (30.3 meV), and a global band gap over 5.5 meV (19.5 meV with random Re distribution) hosting QAHE. A low-energy continuum model is constructed to explain the underlying physical mechanism. We find that Rashba spin-orbit coupling is robust against external stress whereas a tensile strain can increase the global bulk gap. Furthermore, we also show that Re-intercalated graphene with hexagonal boron-nitride can also realize QAHE with bulk gap over 40~meV, indicating the tunability of $5d$-intercalated graphene-based heterostructure. Our finding makes a great leap towards the experimental realization of graphene-based QAHE, and will definitely accelerate the practical application of graphene-based low-power electronics.

In vibration testing, the time domain integral is a key issue. A kind of recursive Simpson integral method is presented in this paper, which combines Newton–Leibniz formula and 3/8 Simpson formula ...

Osteosarcoma (OS) is the most common primary bone tumor. Its high mortality rate and metastasis rate seriously threaten human health. Currently, the treatment has reached a plateau, hence we urgently need to explore new therapeutic directions. In this paper, we found that Trio was highly expressed in osteosarcoma than normal tissues and promoted the proliferation, migration, and invasion of osteosarcoma cells. Furthermore, Trio inhibited osteosarcoma cells’ osteogenic differentiation in vitro and accelerated the growth of osteosarcoma in vivo. Given Trio contains two GEF domains, which have been reported as the regulators of RhoGTPases, we further discovered that Trio could regulate osteosarcoma progression and osteogenic differentiation through activating RhoGTPases. In summary, all our preliminary results showed that Trio could be a potential target and prognostic marker of osteosarcoma.

Topological magnetic excitations rooted in Dzyaloshinskii-Moriya interaction (DMI) are promising information carriers for next-generation memory and spintronic devices. The recently discovered two-dimensional (2D) magnets provide fertile new platforms for revealing rich physical phenomena with atomic-scale precision, as exemplified by the enhanced DMI associated with an effective electric field that breaks the inversion symmetry. Here we use first-principles calculations to establish a conceptually difierent compositional engineering approach to induce giant DMI in a representative CrMnI$_6$ 2D magnet, and the underlying mechanism is rooted in the spontaneous inversion symmetry breaking in the bipartite system. Using atomistic magnetics simulations, we further reveal that bimeronic excitations can emerge upon cooling a spin random state or perturbing a ferromagnetic state. Strikingly, the bimeron can exhibit unidirectional soliton-like propagation, and such a ratchet phenomenon is highly desirable for racetrack memories. These findings may prove instrumental in developing novel devices for quantum information based on 2D magnets.

The modulation of topological electronic states by an external magnetic field is highly desired for condensed matter physics. Schemes to achieve this have been proposed theoretically, but few can be realized experimentally. Here, combining transverse transport, theoretical calculations, and scanning tunneling microscopy/spectroscopy (STM/S) investigations, we provide an observation that the topological electronic states, accompanied by an emergent magneto-transport phenomenon, were modulated by applying magnetic fields through induced non-collinear magnetism in the magnetic Weyl semimetal EuB6. A giant unconventional anomalous Hall effect (UAHE) is found during the magnetisation re-orientation from easy axis to hard ones in magnetic fields, with a UAHE peak around the low field of 5 kOe. Under the reasonable spin-canting effect, the folding of the topological anti-crossing bands occurs, generating a strong Berry curvature that accounts for the observed UAHE. Field-dependent STM/S reveals a highly synchronous evolution of electronic density of states, with a dI/dV peak around the same field of 5 kOe, which provides evidence to the folded bands and excited UAHE by external magnetic fields. This finding elucidates the connection between the real-space non-collinear magnetism and the k-space topological electronic states and establishes a novel manner to engineer the magneto-transport behaviours of correlated electrons for future topological spintronics., 13 pages, 4 figures

The Ordinary Kriging method is a common spatial interpolation algorithm in geostatistics. Because the semivariogram required for kriging interpolation greatly influences this process, optimal fitting of the semivariogram is of major significance for improving the theoretical accuracy of spatial interpolation. A deep neural network is a machine learning algorithm that can, in principle, be applied to any function, including a semivariogram. Accordingly, a novel spatial interpolation method based on a deep neural network and Ordinary Kriging was proposed in this research, and elevation data were used as a case study. Compared with the semivariogram fitted by the traditional exponential model, spherical model, and Gaussian model, the kriging variance in the proposed method is smaller, which means that the interpolation results are closer to the theoretical results of Ordinary Kriging interpolation. At the same time, this research can simplify processes for a variety of semivariogram analyses.

Dihydromyricetin (DMY) is highly effective in counteracting acute alcohol intoxication. However, its poor aqueous solubility and permeability lead to the low oral bioavailability and limit its clinic application. The aim of this work is to use Solutol®HS15 (HS 15) as surfactant to develop novel micelle to enhance the oral bioavailability of DMY by improving its solubility and permeability. The DMY-loaded Solutol®HS15 micelles (DMY-Ms) were prepared by the thin-film hydration method. The particle size of DMY-Ms was 13.97 ± 0.82 nm with an acceptable polydispersity index of 0.197 ± 0.015. Upon entrapped in micelles, the solubility of DMY in water was increased more than 25-fold. The DMY-Ms had better sustained release property than that of pure DMY. In single-pass intestinal perfusion models, the absorption rate constant (Ka) and permeability coefficient (Papp) of DMY-Ms were 5.5-fold and 3.0-fold than that of pure DMY, respectively. The relative bioavailability of the DMY-Ms (AUC0-∞) was 205% compared with that of pure DMY (AUC0-∞), indicating potential for clinical application. After administering DMY-Ms, there was much lower blood alcohol level and shorter duration of the loss of righting relax (LORR) in drunk animals compared with that treated by pure DMY. In addition, the oral administration of DMY-Ms greatly reduced oxidative stress, and significantly defended liver and gastric mucosa from alcoholic damages in mice with alcohol-induced tissue injury. Taken together, HS 15-based micelle system greatly improves the bioavailability of DMY and represents a promising strategy for the management of acute alcoholism. Graphical abstract.

The interlayer antiferromagnetic coupling hinders the observation of quantum anomalous Hall effect in magnetic topological insulator MnBi$_2$Te$_4$. We demonstrate that interlayer \textit{ferromagnetism} can be established by utilizing the \textit{p}-doping method in MnBi$_2$Te$_4$ multilayers. In two septuple-layers system, the interlayer ferromagnetic coupling appears by doping nonmagnetic elements (e.g., N, P, As, Na, Mg, K, and Ca), due to the redistribution of orbital occupations of Mn. We further find that Mg and Ca elements are the most suitable candidates because of their low formation energy. Although, the \textit{p}-doped two septuple layers exhibit topologically trivial band structure, the increase of layer thickness to three (four) septuple layers with Ca (Mg) dopants leads to the formation of the quantum anomalous Hall effect. Our proposed \textit{p}-doping strategy not only makes MnBi$_2$Te$_4$ become an ideal platform to realize the high-temperature quantum anomalous Hall effect without external magnetic field, but also can compensate the electrons from the intrinsic \textit{n}-type defects in MnBi$_2$Te$_4$.

Two-dimensional (2D) magnetic materials empowered with nontrivial band topology may lead to the emergence of exotic quantum states with significant application potentials. Here we predict a family tree of 2D magnetic materials with tunable topological properties, starting from the parental materials of CrI3 and CrBr3. The underlying design principle is that, by substituting the alternating sites of the Cr honeycomb lattice sandwiched between the halogen layers with V or Mn, the parental materials of trivial ferromagnetic insulators are ripe to be converted into topological systems. Specifically, our first-principles calculations show that, due to the elegant interplay between bandgap narrowing and spin-orbital coupling, CrI3 branches into high-temperature quantum anomalous Hall insulators of CrVI6 and CrMnI6 with different topological invariants, while CrBr3 branches into topological half-metals of CrVBr6 and CrMnBr6. Those novel 2D magnets are also shown to be easily exfoliated from their bulk counterparts. The present study is thus geared to advance the field of 2D magnetic materials into the topologically nontrivial realm.

Additional file 1

This paper applies modern statistical methods in the prediction of the next-day maximum ozone concentration, as well as the maximum 8-hour-mean ozone concentration of the next day. The model uses a large number of candidate features, including the present day's hourly concentration level of various pollutants, as well as the meteorological variables of the present day's observation and the future day's forecast values. In order to solve such an ultra-high dimensional problem, the least absolute shrinkage and selection operator (Lasso) was applied. The $L_1$ nature of this methodology enables the automatic feature dimension reduction, and a resultant sparse model. The model trained by 3-years data demonstrates relatively good prediction accuracy, with RMSE= 5.63 ppb, MAE= 4.42 ppb for predicting the next-day's maximum $O_3$ concentration, and RMSE= 5.68 ppb, MAE= 4.52 ppb for predicting the next-day's maximum 8-hour-mean $O_3$ concentration. Our modeling approach is also compared with several other methods recently applied in the field and demonstrates superiority in the prediction accuracy.

BACKGROUND: Multiple myeloma (MM) is a B-lymphocyte-derived malignancy. It ranks as the second most common hematological malignancy, with relatively high morbidity and mortality. However, the molecular mechanisms of MM occurrence and development remain elusive. This study found that long non-coding RNA AL928768.3 (lncRNA AL) was abnormally expressed in MM samples. However, the effect and molecular mechanism of lncRNA AL on the occurrence and development of MM remains unclear. METHODS: Bone marrow fluids of MM patients (n=54) and volunteers (n=13) were collected and CD138(+) cells were isolated. The expression level of lncRNA AL in MM cells was detected by quantitative real-time polymerase chain reaction (qRT-PCR), and the correlation between the expression level of lncRNA AL and the clinicopathological features of patients was analyzed. Lentiviral vectors targeting lncRNA AL knockdown were constructed and transfected into cells. After transfection, the effects of lncRNA AL knockdown on MM cell proliferation and the cell cycle were detected by the CCK-8 assay, clone formation assay, and flow cytometry. The effect of lncRNA AL knockdown on MM cell cycle-related proteins was detected by Western blot. In addition, tumorigenicity experiments were performed in nude mice to detect the effect of lncRNA AL knockdown on MM cell proliferation in vivo. RESULTS: LncRNA AL was highly expressed in MM patient samples and cell lines, and was significantly correlated with the disease stage of patients. Knockdown of lncRNA AL significantly inhibited the proliferation and colony formation of MM cells and induced cell cycle arrest in G0/G1 phase. Western blot analysis showed that knockdown of lncRNA AL significantly inhibited the expression of CDK2 and cyclin D1 and promoted the expression of cyclin suppressor p21. Knockdown of lncRNA AL significantly inhibited the proliferation of MM cells in nude mice. CONCLUSIONS: LncRNA AL was highly expressed in MM patients. Knockdown of this gene significantly inhibited the proliferative ability of MM cells and induced cell cycle arrest in G0/G1 phase. Therefore, lncRNA AL may be a novel biological target molecule for the early diagnosis, treatment, and prognostic evaluation of MM patients.

Background: Currently, the global number of infected novel coronavirus has exceeded 2.6 million and the death toll has exceeded 170,000, but the specific drug for the treatment of COVID-19 has been not appears. In the process of fighting COVID-19 in China, JHQG has been promoted by the Chinese government and widely used in the treatment of COVID-19. The purpose of this study is to systematically evaluate the efficacy and safety of JHQG for COVID-19. Methods: We are going to search the electronic databases: PubMed, EMBASE, Cochrane library, Web of Science (WOS), Google scholar, China National Knowledge Infrastructure (CNKI), Chinese Biomedical literature Database (CBM), Chinese Scientific and Journal Database (VIP), Wan Fang database (Wanfang) for published clinical trails and search clinical trials register platforms of Chinese Clinical Trial Registry (ChiCTR) and ClinicalTrials.gov (www.ClinicalTrials.gov/) for ongoing trials of Jinhua Qinggan granule for COVID-19. The primary outcomes of the included studies contain Clinical symptom disappearance rate and the secondary outcomes obtain: TCM syndrome scale score, Hamilton anxiety scale score, and adverse events. We will use RevMan V5.3 software to perform the calculations. PRISMA-P checklist was used in writing this report. Results: The study results will be submitted to a peer-reviewed journal for publication. Conclusion: This study will provide a high-quality evidence of the efficacy and safety of Jinhua Qinggan granule on patients with COVID-19. PROSPERO registration number: CRD42020181919.

Purpose: Voriconazole nanoparticles (API-NPs) were prepared by nanospray drying to improve the solubility of voriconazole and reduce its interindividual variability.Methods: The preparation procedure was optimized by central composite design-response surface methodology. The properties of the nanoparticles were characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD), differential scanning calorimetry (DSC), and Fourier transform infrared (FTIR) analyses. The solubility, dissolution, and stability of the API-NPs were determined experimentally. The pharmacokinetics were assessed based on rat plasma levels of voriconazole. An acute oral toxicity test of the API-NPs was performed in mice.Results: The powers were formulated using cetyltrimethylammonium chloride (CTAC) as the carrier material. SEM and particle size results showed that the API-NPs had a narrow particle size distribution. The XRD, DSC, and FTIR analyses show a decrease in crystallinity and a polymorphic transformation of the nanoparticles after nanospray drying. The solubility in water was approximately 15 times higher than that of voriconazole. The API-NP tablets exhibited significantly higher plasma exposure, namely, longer acting times and lower variability. The acute administration of voriconazole showed no toxic histopathological effects on organ tissue.Conclusion: The solubility of voriconazole was greatly improved, it showed higher bioavailability and safety, and the interindividual variability in voriconazole pharmacokinetics was reduced by nanospray drying.

Vinothkumar Rajamanickam,* Tao Yan,* Liangrong Wu, Yanni Zhao, Xiaohong Xu, Heping Zhu, Xi Chen, Meihong Wang, Zhoudi Liu, Zhiguo Liu, Guang Liang, Yi Wang Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yi WangChemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, People’s Republic of ChinaTel/Fax +86- 577-85773060Email yi.wang1122@wmu.edu.cnBackground: Gastric cancer is one of the leading causes of cancer-related deaths. Allylated monocarbonyl analogs of curcumin (MACs) have been reported to selectively inhibit a broad range of human cancers including gastric cancer. However, the precise molecular mechanisms underlying the inhibitory activities of MACs are not fully known.Methods: In this study, we examined the anti-tumor activities of an allylated MAC, CA6, on gastric cancer cells and gastric cancer xenograft mouse model. The potential molecular anti-tumor mechanisms of CA6 were also elucidated.Results: Our data show that CA6 exhibited significant cytotoxicity in gastric cancer cells, which was seen as an induction of G2/M cell cycle arrest and apoptosis. These activities were mediated through an elaboration of ROS levels in gastric cancer cells and induction of endoplasmic reticulum stress. CA6 increased ROS levels through directly binding to and inhibiting thioredoxin reductase R1 (TrxR1). Also, CA6-generated ROS inhibited Akt and activated forkhead O3A (FoxO3a), causing cytotoxicity in gastric cancer cells. Finally, CA6 treatment dose-dependently reduced the growth of gastric cancer xenografts in tumor-bearing mice, which was associated with reduced TrxR1 activity and increased ROS in the tumor.Conclusion: In summary, our studies demonstrate that CA6 inhibited gastric cancer growth by inhibiting TrxR1 and increasing ROS, which in turn activated FoxO3a through suppressing Akt. CA6 is a potential candidate for the treatment of gastric cancer.Keywords: gastric cancer, curcumin analog, reactive oxygen species, TrxR1, FOXO3a

Budesonide is a glucocorticoid for the treatment of ulcerative colitis (UC). The current study aims to develop a thermosensitive in situ and adhesive gel for rectal delivery of budesonide. HPMC K4M was selected as the adhesive agent based on the adhesive force and the effect on gel performance. The formulation of gel was optimized by using the central composite design-response surface methodology (CCD-RSM); a mathematical model was successfully developed to predict desired formulations as well as to analyze relationships between the amount of Pluronic F-127, Pluronic F-68, and HPMC K4M and the performances of gel. Based on CCD-RSM, a thermosensitive in situ and adhesive gel consisting of 0.002% budesonide, 0.74% HPMC, 4.87% F-68, and 19.0% F-127 was developed. Furthermore, the in vivo behavior of gel was evaluated in Sprague-Dawley rats. In comparison with budesonide solution, rectal administration of budesonide gel at 0.1 mg/kg in rats showed relative bioavailability of 230% with significant increase in rectum uptake.

Xiaohong Xu,1 Vinothkumar Rajamanickam,1 Sheng Shu,1 Zhoudi Liu,1 Tao Yan,1 Jinxin He,1 Zhiguo Liu,1 Guilong Guo,2 Guang Liang,1 Yi Wang1 1Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, People’s Republic of China; 2Department of Surgical Oncology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, People’s Republic of ChinaCorrespondence: Yi WangChemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, People’s Republic of ChinaTel/Fax +8657785773060Email yi.wang1122@wmu.edu.cnBackground: Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer which is associated with poor patient outcome and lack of targeted therapy. Our laboratory has synthesized a series of indole-2-carboxamide derivatives. Among this series, compound LG25 showed a favorable pharmacological profile against sepsis and inflammatory diseases. In the present study, we investigated the chemotherapeutic potential of LG25 against TNBC utilizing in vitro and in vivo models.Methods: Changes in cell viability, cell cycle phases and apoptosis were analyzed using MTT, clonogenic assay, FACS and Western blotting assays. The anti-cancer effects of LG25 were further determined in a xenograft mouse model.Results: Our findings reveal that LG25 reduced TNBC viability in a dose-dependent manner. Flow cytometric and Western blot analyses showed that LG25 enhances G2/M cell cycle arrest and induced cell apoptosis. In addition, LG25 treatment significantly inhibited Akt/mTOR phosphorylation and nuclear translocation of nuclear factor-κB (NF-κB). These inhibitory activities of LG25 were confirmed in mice implanted MDA-MB-231 TNBC cells.Conclusion: Our studies provide experimental evidence that indole-2-carboxamide derivative LG25 effectively targeted TNBC in preclinical models by inducing cell cycle arrest and apoptosis, through suppressing Akt/mTOR/NF-κB signaling pathway.Keywords: indole analog, triple-negative breast cancer, cell cycle arrest, apoptosis, Akt, mTOR

Background In this study, we investigated the role of artemin, a member of the glial cell‐derived neurotrophic factor of ligands, in the malignant phenotype of lung cancer. Methods Artemin expression was examined in various types of lung cancer and normal lung tissues, as well as in lung cancer cell lines by immunohistochemistry and semi‐quantitative PCR. Functional studies were performed using artemin overexpression or knockdown vectors in lung cancer cell lines. Methyl thiazolyl tetrazolium, flow cytometry, wound healing, and transwell assays were conducted to evaluate the contribution of artemin on tumor cell proliferation, migration, and invasion. Results Artemin is broadly expressed in lung cancer tissues, and is associated with tumor staging. Overexpression of artemin in NL9980 large cell lung cancer cells increased proliferating cells and enhanced migrating capability in wound healing and transwell assays, as well as demonstrating enhanced invasion capability. Silencing artemin in LTEP‐α‐2 adenocarcinoma cell lines decreased cellular proliferation, migration, and invasion capabilities. Conclusion Artemin could promote the proliferation and invasiveness of lung cancer cells in vitro and therefore could be a new potential target to combat lung cancer.

Liposomes possess good biocompatibility and excellent tumor-targeting capacity. However, the rapid premature release of lipophilic drugs from the lipid bilayer of liposomes has negative effect on the tumor-targeted drug delivery of liposomes. In this study, a lipophilic antitumor drug-chlorambucil (CHL)-was encapsulated into the aqueous interior of liposomes with the aid of albumin to obtain the CHL-loaded liposomes/albumin hybrid nanoparticles (CHL-Hybrids). The in vitro accumulative release rate of CHL from CHL-Hybrids was less than 50% within 48 h, while the accumulative CHL release was more than 80% for CHL-loaded liposomes (CHL-Lip). After intravenous injection into rats, the half-life (t 1/2β = 5.68 h) and maximum blood concentration (C max = 4.58 μg/mL) of CHL-Hybrids were respectively 1.1 times and 3.5 times higher than that of CHL-Lip. In addition, CHL-Hybrids had better tumor-targeting capacity for it significantly increased the drug accumulation in B16F10 tumors, which contributed to the significantly control of tumor growth compared with CHL-Lip. Furthermore, CHL-Hybrid-treated B16F10 melanoma-bearing mice displayed the longest median survival time of 30.0 days among all the treated groups. Our results illustrated that the proposed hybrids drug delivery system would be a promising strategy to maintain the controlled release of lipophilic antitumor drugs from liposomes and simultaneously facilitate the tumor-targeted drug delivery.

Objective This study aimed to investigate the pathogenesis of geriatric asthma through immunoglobulin E (IgE), interleukin-17A (IL-17A), IL-17F, and glucocorticoid receptor-β (GR-β) expression. Methods We studied 51 geriatric male patients with asthma and 50 young male patients with asthma. We also included 21 normal geriatric males and 21 normal young males. All geriatric and young patients were divided into groups according to pulmonary function. Levels of cytokines, such as IgE, IL-17A, IL-17F, and GR-β, were measured. Pulmonary function was assessed. The results from patients were compared with those from the 42 healthy subjects. Results Serum IgE, IL-17A, IL-17F, and GR-β levels in geriatric patients with moderate or severe asthma were significantly higher than those in young patients with moderate asthma and in the normal population. Geriatric patients with asthma had higher asthma control test scores than did young patients with asthma. Conclusion Hormone resistance in geriatric male patients with asthma is more serious than that in young male patients with asthma. Airway inflammation and airway remodeling in geriatric male patients with asthma may be more serious than those in young male patients with asthma, even when there is similar pulmonary function.

Gastric cancer (GC) is one of the most common malignant neoplasms and is the third leading cause of cancer-related death around the world. Metformin has been well reported to have an inhibitory effect on the growth of various cancers by regulating the expression of microRNAs (miRNAs). However, the specific miRNA(s) regulated by metformin in GC have not been identified. In this study, real-time reverse transcription polymerase chain reaction (RT-PCR) analysis

Two-dimensional (2D) device structures have recently attracted considerable attention. Here, we show that most 2D device structures, regardless vertical or lateral, act as a lateral monolayer-bilayer-monolayer junction in their operation. In particular, a vertical structure cannot function as a vertical junction as having been widely believed in the literature. Moreover, due to a larger electrostatic screening, the bilayer region in the junction always has a smaller band gap than its monolayer counterpart. As a result, a potential well, aside from the usual potential barrier, will form universally in the bilayer region to affect the hole or electron quantum transport in the form of transmission or reflection. Taking black phosphorus as an example, we show that an oscillation in the transmission coefficient can be clearly resolved in a two-electrode prototypical device by non-equilibrium Green function combined with density functional theory calculations and the results can be qualitatively understood using a simple quantum well model. The presence of the quantum well is vital to 2D device design, including the effective tuning of quantum transmission by a vertical electric field.

Quantum anomalous Hall effect (QAHE) is a fundamental quantum transport phenomenon in condensed matter physics. Until now, the only experimental realization of the QAHE has been observed for Cr/V-doped (Bi,Sb)$_2$Te$_3$ but at extremely low observational temperature, thereby limiting its potential application in dissipationless quantum electronics. Employing first-principles calculations, we study the electronic structures of graphene codoped with 5\textit{d} transition metal and boron (B) atoms based on a compensated \textit{n}--\textit{p} codoping scheme. Our findings are as follows. 1) The electrostatic attraction between the \textit{n}- and \textit{p}-type dopants effectively enhances the adsorption of metal adatoms and suppresses their undesirable clustering. 2) Hf--B and Os--B codoped graphene systems can establish long-range ferromagnetic order and open nontrivial band gaps because of the spin-orbit coupling with the non-vanishing Berry curvatures to host the QAHE. 3) The calculated Rashba splitting energy in Re--B and Pt--B codoped graphene systems can reach up to 158 and 85~meV, respectively, which is several orders of magnitude higher than the reported intrinsic spin-orbit coupling strength.

Numerous studies have examined the pathogenesis of osteoporosis. The causes of osteoporosis include endocrine factors, nutritional status, genetic factors, physical factors, and immune factors. Recent osteoimmunology studies demonstrated that the immune system and immune factors play important regulatory roles in the occurrence of osteoporosis, and people should pay more attention to the relationship between immunity and osteoporosis. Immune and bone cells are located in the bone marrow and share numerous regulatory molecules, signaling molecules, and transcription factors. Abnormal activation of the immune system alters the balance between osteoblasts and osteoclasts, which results in an imbalance of bone remodeling and osteoporosis. The incidence of osteoporosis is also increasing with the aging of China’s population, and traditional Chinese medicine has played a vital role in the prevention and treatment of osteoporosis for centuries. Chinese medicinal plants possess unique advantages in the regulation of the immune system and the relationships between osteoporosis and the immune system. In this review, we provide a general overview of Chinese medicinal plants in the prevention and treatment of osteoporosis, focusing on immunological aspects.

In the surface measurement system, the data acquisition is key part and the anti-aliasing analog filter is necessary. This paper deals with the design of the anti-aliasing analog filter. Based on the principle of anti-aliasing filtering, the parameters of filter are computed, the filter circuit is designed, and the frequency characteristic is drawn. Combined with digital filter, the filtering can maintain the low frequency components very well and suppress effectively the high frequency signals in the original surface profile, which reduces the distortion caused by noise and makes the filtering effect better. This method has been applied in the surface measurement system and the actually measured data verified the performance of the filter.

Using first-principles calculation methods, we study the possibility of realizing quantum anomalous Hall effect in graphene from stable 3\textit{d}-atomic adsorption via charge-compensated \textit{n}-\textit{p} codoping scheme. As concrete examples, we show that long-range ferromagnetism can be established by codoping 3\textit{d} transition metal and boron atoms, but only the Ni codopants can open up a global bulk gap to harbour the quantum anomalous Hall effect. Our estimated ferromagnetic Curie transition temperature can reach over 10 Kelvin for various codoping concentrations.

Artificial heterostructures based on LaNiO3 (LNO) have been widely investigated with the aim to realize the insulating antiferromagnetic state of LNO. In this work, we grew [(La0.7Sr0.3MnO3)5-(LaNiO3)n]12 superlattices on (001)-oriented SrTiO3 substrates by pulsed laser deposition and observed an unexpected exchange bias effect in field-cooled hysteresis loops. Through X-ray absorption spectroscopy and magnetic circular dichroism experiments, we found that the charge transfer at the interfacial Mn and Ni ions can induce a localized magnetic moment. A remarkable increase of exchange bias field and a transition from metal to insulator were simultaneously observed upon decreasing the thickness of the LNO layer, indicating the antiferromagnetic insulator state in 2 unit cells LNO ultrathin layers. The robust exchange bias of 745 Oe in the superlattice is caused by an interfacial localized magnetic moment and an antiferromagnetic state in the ultrathin LNO layer, pinning the ferromagnetic La0.7Sr0.3MnO3 layers together. Our results demonstrate that artificial interface engineering is a useful method to realize novel magnetic and transport properties.

Bacteria and fungi grow indoors when sufficient moisture is available, causing indoor air pollution. The aims of this study were to determine the total viable bacterial count and fungi levels at the l... abs and faculty offices of the Islamic University of Gaza (IUG). Twenty-six air samples were collected from the IUG labs and faculty offices using air samplers. The results show that the highest bacterial count was observed at the Medical Science Labs with 1365 colony-forming unit (CFU)/m3 while the highest fungal count was detected at the Environment Science Labs with 425 CFU/m3. The majority of the monitored labs and offices have higher bacterial and fungal levels than the WHO standards of 500 CFU/m3. Lab users should wear face masks to reduce any potential health impacts due to the microbial pollution. 続きを見る

Diabetic nephropathy (DN) is manifested as increased urinary protein level, decreased glomerular filtration rate, and final renal dysfunction. DN is the leading cause of end-stage renal disease worldwide and causes a huge societal healthcare burden. Since satisfied treatments are still limited, exploring new strategies for the treatment of this disease is urgently needed. Oxidative stress takes part in the initiation and development of DN. In addition, nuclear factor erythroid 2-related factor 2 (Nrf2) plays a key role in the cellular response to oxidative stress. Thus, activation of Nrf2 seems to be a new choice for the treatment of DN. In current review, we discussed and summarized the therapeutic effects of Nrf2 activation on DN from both basic and clinical studies.

Loss of soil and water from sloped farmland is a major cause of regional soil degradation and declining productivity. We conducted a preliminary study on the characteristics of sloped farmland in the black soil region of Northeast China using natural rainfall-runoff plot experiments in the field. In 0-20 cm soil depth, clay content (0.05 mm), 0.02 to 0.05 mm and 0.05 to 0.25 mm microaggregates content, tended to decline. This suggests that soil material and nutrients were gradually transported from the top to the bottom of the slope because of erosion, soil tended toward desertification in texture, and fertility was degraded. The content of available phosphorus and total phosphorus was positively linearly related to clay content, specific surface area, and 0.002 to 0.02 mm microaggregates content. This indicates that soil nutrients migrated down with fine particles. Therefore, soil erosion leads to the migration and loss of soil nutrients

The soil and water conservation practices of ecological restoration (ER), fish scale pit (FP), furrow and ridge tillage across the slope (FR), shrub strips (SS), and vegetation-covered ridge (VR) are characteristic of the Jixing small watershed of the low mountain and hilly region of Jilin Province, Northeast China. This study aims to elucidate the effects of soil and water conservation practices on soil conditions after the short-term implementation of practices. Soil samples were collected from five soil and water conservation sites (ER, FP, FR, SS, and VR) and two controls (BL and CT) to investigate their properties. To evaluate the influence of soil and water conservation practices on soil quality, an integrated quantitative index, soil quality index (QI), was developed to compare the soil quality under the different soil and water conservation practices. The results show that not all soil and water conservation practices can improve the soil conditions and not all soil properties, especially soil organic carbon (SOC), can be recovered under soil and water conservation practice in short-term. Moreover, the QI in the five soil and water conservation practices and two controls was in the following order: ER > VR > BL > FR > CT > SS > FP. ER exhibited a higher soil quality value on a slope scale. In the low mountain and hilly region of Northeast China, ER is a better choice than the conversion of farmlands to planted grasslands and woodlands early in the soil and water conservation program.

The effect of Bisphenol-A on the brain and behavioral development has attracted extensive attention.This study was to investigate the anxiety and depressive behaviors of adult offspring mice following maternal exposed to BPA(0.4 or 4 mg/kg/day) from gestation day 7(GD 7) to GD 20 or postnatal day(PND) 1 to PND 14.The anxiety behavior of BPA-treated mice on PND 56 were tested using open field,dark-light transition,mirrored maze,and elevated plus maze;and depressive behavior was tested using forced swim task.The results showed that,both gestational and lactational exposure to BPA increased anxiety in both sexes of adult offspring but the effect pattern was different due to the exposure period and gender.The females those gestational exposed to BPA exhibited an increased anxiety in all of the 4 models,while the females those lactational exposed to BPA and the males of gestational or lactational exposure to BPA exhibited an increased anxiety in 2 of the 4 models.Gestational exposure to BPA significantly prolonged the immobile time in the forced swim test of both sexes of offspring,and the same effect was induced by lactational exposure to BPA only at 4 mg/kg/day.Furthermore,Western blot analyses showed that gestational or lactational exposure to BPA significantly inhibited the expression of AMPA receptor subunit GluR1 in the hippocampus and amygdale.These results suggest that both gestational and lactational exposure BPA increased anxiety and depression in both sexes of adult offspring mice,and gestational exposure to BPA has stronger effect on the anxiety and depression.The inhibition of GluR1 level in the hippocampus and amygdale might be associated with the BPA-induced anxiety and depressive behaviors of adult offspring mice.