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Zhenpeng Liao,1,* Wei Liao,1,* Kai Sen Tan,2,* Yueqi Sun,3 Aiqing Peng,1 Yingxian Zhu,4 Haixin He,1 Shuowei Yang,1 Guangfu Xu,1 Rongfei Su,1 Jinyu Yao,3 Yunping Fan,1 Qintai Yang,5 Haiyu Hong1 1Department of Otolaryngology, Allergy Center, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, People’s Republic of China; 2Department of Otolaryngology, National University of Singapore, National University Health System, Singapore, Singapore; 3Department of Otolaryngology, Otorhinolaryngology Hospital, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, People’s Republic of China; 4Department of Anesthesiology, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, People’s Republic of China; 5Department of Otolaryngology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, People’s Republic of China *These authors contributed equally to this work Objective: Septoplasty has been the definitive treatment for nasal septum deviation, but its postoperative procedure may affect patients’ quality of life. While new procedures in general surgery, such as enhanced recovery after surgery (ERAS), can speed up postoperative rehabilitations to improve quality of life, it is rarely applied in the ear–nose–throat field. This study therefore aims to evaluate the application of ERAS in patients with nasal septum deviation as a means of improving perioperative outcomes. Materials and methods: Fifty patients with nasal septum deviation undergoing septoplasty were randomized as ERAS or control group (25 patients in both groups). Patients were investigated for outcomes including length of stay, operating time, bleeding volume, total cost, complications, and Self-Rating Anxiety Scale (SAS) and visual analog symptom score of nasal obstruction, sleep disturbance, and head facial pain. Results: The preoperative anxiety in ERAS group (SAS 35.4±6.2) was lower than the control group (SAS 43.6±8.6). The anxiety levels in ERAS group (SAS 31.6±5.4) was also reduced compared to the control group (SAS 38.1±10.4) in the 3 days postsurgery, but showed no significant difference thereafter at 7 days postsurgery. In addition, the length of stay and total cost were significantly lower for the ERAS group as well. The visual analog symptom score of nasal obstruction, sleep disturbance, and head facial pain in ERAS group were all also found to be lower than the control group. The only outcomes with no significant differences were the operation time, blood volume, and complications between the groups. Conclusion: Our study indicated ERAS application can reduce hospital charges and postoperative pain in septoplasty, thereby improving patient quality of life and hospital expenses at the same time. Keywords: enhanced recovery after surgery, hospital charges, nasal septum deviation, postoperative pain, septoplasty

Wenjie Dong,1 Jing Luo,2 Hongxuan He,2 Long Jiang11Beijing National Laboratory for Molecular Science, Institute of Chemistry, Chinese Academy of Sciences, Beijing, People's Republic of China; 2National Research Center for Wildlife Born Diseases, Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, People's Republic of ChinaAbstract: In this study, we immobilized polydiacetylene vesicles (PDAVs) onto the surface of polystyrene microspheres (1 µm in diameter) by using both electrical charge and conjugated forces to form a reinforced composite structure. These reinforced complexes could be easily washed, separated by centrifugation, and resuspended by gentle agitation. After passing through a narrow 200 µm-diameter channel, the composite structures maintained their original shape, demonstrating their resilience and potential for use in microfluidic technologies. The number of PDAVs in the composite structure could be mediated by changing the extent of layer deposition, which affected the sensitivity of detection. It showed that PDAVs did not change their blue color after addition of detecting probes such as anti-H5N1, which was of great importance in the fabrication and modification of stable color-changeable biosensors based on PDAVs. By conjugating anti-H5N1 antibodies to the PS@PDAV via N-hydroxysuccinimide and 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide chemistry, a stable blue complex, anti-H5N1 microsphere (PS@PDAV-anti-H5N1) was formed. A target antigen of H5N1 (HAQ [H5N1 strain A/environment/Qinghai/1/2008{H5N1} in clade 0]) was detected by PS@PDAV-anti-H5N1. At an optimal PDAV deposition level of three layers, the limit of detection was determined to be approximately 30 ng/mL of HAQ by using optical spectrum measurement and visual inspection, meeting the needs of fast and simple color-changeable detection. However, a much lower limitation of detection (1 ng/mL) was able to be obtained using laser-scanning confocal microscopy, which could be compared with the results obtained with other sophisticated equipment.Keywords: reinforced composite structure, polystyrene, polydiacetylene, H5N1 virus detection

The cycloaddition reaction involving bicyclo[1.1.0]butanes (BCBs) offers a versatile and efficient synthetic platform for producing C(sp 3 )-rich rigid bridged ring scaffolds, which act as phenyl bioisosteres. However, there is a scarcity of catalytic asymmetric cycloadditions of BCBs to fulfill the need for enantioenriched saturated bicycles in drug design and development. In this study, an efficient synthesis of valuable azabicyclo[2.1.1]hexanes (aza-BCHs) by an enantioselective zinc-catalyzed (3+2) cycloadditions of BCBs with imines is reported. The reaction proceeds effectively with a novel type of BCB that incorporates a 2-acyl imidazole group and a diverse array of alkynyl- and aryl-substituted imines. The target aza-BCHs, which consist of α-chiral amine fragments and two quaternary carbon centers, are efficiently synthesized with up to 94 % and 96.5:3.5 er under mild conditions. Experimental and computational studies reveal that the reaction follows a concerted nucleophilic ring-opening mechanism of BCBs with imines. This mechanism is distinct from previous studies on Lewis acid-catalyzed cycloadditions of BCBs., (© 2024 Wiley-VCH GmbH.)

The synthesis of bicyclic scaffolds has garnered considerable interest in drug discovery because of their ability to mimic benzene bioisosteres. Herein, we introduce a new approach that utilizes a Lewis acid (Sc(OTf) 3 )-catalyzed σ-bond cross-exchange reaction between the C-C bond of bicyclobutanes and the C-N bond of diaziridines to produce multifunctionalized and medicinally interesting azabicyclo[3.1.1]heptane derivatives. The reaction proceeds well with different bicyclobutanes and a broad range of aryl- as well as alkenyl-, but also alkyl-substituted diaziridines (up to 98 % yield). Conducting a scale-up experiment and exploring the synthetic transformations of the cycloadducts emphasized the practical application of the synthesis. Furthermore, a zinc-based chiral Lewis acid catalytic system was developed for the enantioselective version of this reaction (up to 96 % ee)., (© 2024 Wiley-VCH GmbH.)

Background: A series of multi-sensory interventions are proved to be effective in reducing pain among premature infants. Nevertheless, there lacks a comparison of these interventions to find the most suitable and optimal one for clinical decision-making., Objective: This systematic review and network meta-analysis aims to compare the effectiveness of various multi-sensory interventions, and to identify the optimal intervention for alleviating pain in premature infants., Methods: A comprehensive literature search was performed on August 19, 2024 to identify pertinent clinical trials. The Cochrane Risk of Bias (version 2) was used to assess the quality and potential bias of each included study. Network meta-analysis was used to assess the effectiveness of various interventions and to identify the optimal ones., Results: A total of 18 clinical trials involving 1408 premature infants were included. Three multi-sensory interventions were shown to be superior to routine practice in reducing pain among premature infants, including tactile-kinesthetic intervention, tactile-auditory intervention and tactile-visual-gustatory-olfactory intervention (all, P < 0.05). Among these interventions, tactile-kinesthetic intervention ranks the best for its effectiveness in alleviating procedural pain among premature infants. Subgroup network meta-analysis demonstrated that the tactile-visual-gustatory-auditory-olfactory intervention ranked the best for its effectiveness in reducing pain from invasive procedures, with the tactile-auditory intervention best for non-invasive procedures., Conclusions: Our study suggests that cautious assessment and identification should be prioritized to select appropriate multi-sensory interventions based on pain procedures, thus to effectively reduce pain in premature infants. Subsequent studies are needed to refine and optimize these strategies for broader application., Prospero Registry: CRD42024510352., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

The absence of catalytic asymmetric methods for synthesizing chiral (hetero)bicyclo[n.1.1]alkanes has hindered their application in new drug discovery. Here we demonstrate the achievability of an asymmetric polar cycloaddition of bicyclo[1.1.0]butane using a chiral Lewis acid catalyst and a bidentate chelating bicyclo[1.1.0]butane substrate, as exemplified by the current enantioselective formal (3 + 3) cycloaddition of bicyclo[1.1.0]butanes with nitrones. In addition to the diverse bicyclo[1.1.0]butanes incorporating an acyl imidazole group or an acyl pyrazole moiety, a wide array of nitrones are compatible with this Lewis acid catalysis, successfully assembling two congested quaternary carbon centers and a chiral aza-trisubstituted carbon center in the pharmaceutically important hetero-bicyclo[3.1.1]heptane product with up to 99% yield and >99% ee., (© 2024. The Author(s).)

Herein, we report the synthesis of a novel carbaporphyrin incorporating perylene diimide (PDI) and dipyrromethane units. The twisted plane of the PDI subunits imbues carbaporphyrin with intriguing conformational chirality and stable chiroptical properties. Both experimental and theoretical studies reveal that the unique properties arise from the rigidly conjugated macrocyclic architecture and the reduced interchromophoric distance. This work successfully integrates PDIs into carbaporphyrins, thereby expanding their structural diversity and functional potential.

Background: Many systematic reviews (SRs) have reported the efficacy of acupuncture in improving Parkinson's disease (PD), but the quality of evidence is unknown. Therefore, it is necessary to comprehensively summarize and objectively evaluate the evidence of acupuncture for PD., Methods: Seven databases were searched to retrieve SRs on the acupuncture for PD. Two reviewers independently completed literature retrieval, screening, and data extraction. The methodological quality, risk of bias (RoB), evidence quality of the included SRs were assessed by the Assessing the Methodological Quality of Systematic Reviews 2 (AMSTAR 2), the Risk of Bias in Systematic Reviews (ROBIS), the Grading of Recommendations Assessment, Development and Evaluation (GRADE) tool., Results: A total of 24 SRs were included. According to AMSTAR 2, 6 (25%) were rated as high quality, 6 (25%) were rated as moderate quality, and 12 (50%) were rated as very low quality. The application of the ROBIS tool showed that 12 (25%) SRs were at low risk of bias. The results of GRADE showed that 8 (7.62%) outcomes provided high quality evidence, 23 (21.9%) outcomes provided moderate quality evidence, 42 (40%) outcomes provided low quality evidence, and 32 (30.48%) outcomes provided very low quality evidence., Conclusion: The overview indicates that acupuncture shows promise as a treatment for PD, although the evidence is limited and inconclusive due to methodological flaws and the heterogeneity of existing studies. Future research should focus on fully reporting methodological details and following review guidelines to produce more reliable and consistent evidence on the effectiveness of acupuncture for PD., Systematic Review Registration: https://inplasy.com, identifier INPLASY202480049., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Xue, He, Wu, Fan and Li.)

Objective: To explore the levels of regulatory T cells (Tregs) and cytokines IL-35, TGF-β and IL-10 in peripheral blood of hemophilia A(HA) patients with FⅧ inhibitor and their clinical significance., Methods: 43 HA patients admitted to the Hematology Department of the Affiliated Hospital of North China University of Science and Technology from October 2019 to December 2020 were selected, including 6 cases with FⅧ inhibitor and 37 cases without FⅧ inhibitor. In addition, 20 healthy males who underwent physical examinations were selected as healthy controls. Flow cytometry was used to detect the levels of CD4 + CD25 + CD127 - Tregs in peripheral blood of the HA patients and healthy controls, and ELISA assay was used to detect the expression levels of IL-35, TGF-β and IL-10 in serum, and their differences between different groups were compared., Results: Compared with the healthy control group, the level of Tregs in HA patients was decreased, and the level of Tregs in the FⅧ inhibitor positive group was the lowest, the difference was statistically significant ( P <0.05). There was no significant difference in the expression level of Tregs in HA patients of different severity levels. The serum IL-35, TGF-β, and IL-10 levels in both FⅧ inhibitor negative and positive groups were significantly lower than those in healthy control group, and those in FⅧ inhibitor positive group were significantly lower than those in FⅧ inhibitor negative group (all P <0.05)., Conclusion: The decrease of Tregs, IL-35, TGF-β, and IL-10 levels in HA patients may be related to the formation of FⅧ inhibitors.

Background: Many systematic reviews (SRs) and meta-analysis (MAs) have reported the efficacy of acupuncture treatment for primary trigeminal neuralgia (PTN), but the quality of evidence is unknown and therefore needs to be evaluated comprehensively., Methods: Eight electronic databases were searched from their inception until January 5, 2024. The methodological quality, reporting quality, and risk of bias of the included SRs were assessed by the assessment of multiple systematic reviews 2 (AMSTAR-2), the Risk of Bias in Systematic Reviews (ROBIS) tool, and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). The quality of evidence for outcome measures was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE)., Results: We identified 13 SRs/MAs met inclusion criteria. According to the results of the AMSTAR-2, six were rated as critically low quality and seven as low quality. According to ROBIS assessment, 8 SRs/MAs were classified as low risk, and 5 SRs/MAs were found to be high risk. The PRISMA report still has some reporting deficiencies in aspects such as protocol and registration, search strategy, risk of bias, additional analyzes and funding. According to the GRADE system, no high-quality evidence was found, 1 was of moderate quality, 4 were of low quality, and 8 were of critical low quality., Conclusion: Based on the evidence collected, acupuncture shows promise as a treatment for PTN patients. However, it is important to note that the included SRs/MAs generally have low methodological quality and evidence quality. Therefore, caution must be exercised when interpreting this conclusion. To enhance future research in this area, it is recommended to adequately report methodological details and adhere to guidelines for conducting SRs/MAs. Systematic review registration : https://www.crd.york.ac.uk/prospero/, identifier CRD42024499280., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 He, Li, Xiao, Fan and Xue.)

IRF9 can play an antibacterial role by regulating the type I interferon (IFN) pathway. Streptococcus iniae can cause many deaths of yellowfin seabream, Acanthopagrus latus in pond farming. Nevertheless, the regulatory mechanism of type I IFN signalling by A. latus IRF9 (AlIRF9) against S. iniae remains elucidated. In our study, AlIRF9 has a total cDNA length of 3200 bp and contains a 1311 bp ORF encoding a presumed 436 amino acids (aa). The genomic DNA sequence of AlIRF9 has nine exons and eight introns, and AlIRF9 was expressed in various tissues, containing the stomach, spleen, brain, skin, and liver, among which the highest expression was in the spleen. Moreover, AlIRF9 transcriptions in the spleen, liver, kidney, and brain were increased by S. iniae infection. By overexpression of AlIRF9, AlIRF9 is shown as a whole-cell distribution, mainly concentrated in the nucleus. Moreover, the promoter fragments of -415 to +192 bp and -311 to +196 bp were regarded as core sequences from two AlIFNa3s. The point mutation analyses verified that AlIFNa3 and AlIFNa3-like transcriptions are dependent on both M3 sites with AlIRF9. In addition, AlIRF9 could greatly reduce two AlIFNa3s and interferon signalling factors expressions. These results showed that in A. latus, both AlIFNa3 and AlIFNa3-like can mediate the regulation of AlIRF9 in the process of infection with S. iniae., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024. Published by Elsevier Ltd.)

The performance of covalent-organic frameworks (COFs) for the photocatalytic extraction of uranium is greatly limited by the number of adsorption sites. Herein, inspired by electronegative redox reactions, we designed a nitrogen-oxygen rich pyrazine connected COF (TQY-COF) with multiple redox sites as a platform for extracting uranium via combining superaffinity and enhanced photoinduction. The preorganized bisnitrogen-bisoxygen donor configuration on TQY-COF is entirely matched with the typical geometric coordination of hexavalent uranyl ions, which demonstrates high affinity (tetra-coordination). In addition, the presence of the carbonyl group and pyrazine ring effectively stores and controls electron flow, which efficaciously facilitates the separation of e - /h + and enhances photocatalytic performance. The experimental results show that TQY-COF removes up to 99.8% of uranyl ions from actual uranium mine wastewater under the light conditions without a sacrificial agent, and the separation coefficient reaches 1.73 × 10 6 mL g -1 in the presence of multiple metal ions, which realizes the precise separation in the complex environment. Importantly, DFT calculations further elucidate the coordination mechanism of uranium and demonstrate the necessity of the presence of N/O atoms in the photocatalytic adsorption of uranium.

The gut microbiota significantly influences host physiology and provides essential ecosystem services. While diet can affect the composition of the gut microbiota, the gut microbiota can also help the host adapt to specific dietary habits. The carrion crow ( Corvus corone ), an urban facultative scavenger bird, hosts an abundance of pathogens due to its scavenging behavior. Despite this, carrion crows infrequently exhibit illness, a phenomenon related to their unique physiological adaptability. At present, however, the role of the gut microbiota remains incompletely understood. In this study, we performed a comparative analysis using 16S rRNA amplicon sequencing technology to assess colonic content in carrion crows and 16 other bird species with different diets in Beijing, China. Our findings revealed that the dominant gut microbiota in carrion crows was primarily composed of Proteobacteria (75.51%) and Firmicutes (22.37%). Significant differences were observed in the relative abundance of Enterococcus faecalis among groups, highlighting its potential as a biomarker of facultative scavenging behavior in carrion crows. Subsequently, E. faecalis isolated from carrion crows was transplanted into model mice to explore the protective effects of this bacterial community against Salmonella enterica infection. Results showed that E. faecalis down-regulated the expression of pro-inflammatory cytokines tumor necrosis factor alpha (TNF-α), interferon gamma (IFN-γ), and interleukin 6 (IL-6), prevented S. enterica colonization, and regulated the composition of gut microbiota in mice, thereby modulating the host's immune regulatory capacity. Therefore, E. faecalis exerts immunoregulatory and anti-pathogenic functions in carrion crows engaged in scavenging behavior, offering a representative case of how the gut microbiota contributes to the protection of hosts with specialized diets.

Background: Tui Na (Chinese massage) is a relatively simple, inexpensive, and non-invasive intervention, and has been used to treat stroke patients for many years in China. Tui Na acts on specific parts of the body which are called meridians and acupoints to achieve the role of treating diseases. Yet the underlying neural mechanism associated with Tui Na is not clear due to the lack of detection methods., Objective: Functional near-infrared spectroscopy (fNIRS) was used to explore the changes of sensorimotor cortical neural activity in patients with upper limb motor dysfunction of stroke and healthy control groups during Tui Na Hegu Point., Methods: Ten patients with unilateral upper limb motor dysfunction after stroke and eight healthy subjects received Tui Na. fNIRS was used to record the hemodynamic data in the sensorimotor cortex and the changes in blood flow were calculated based on oxygenated hemoglobin (Oxy-Hb), the task session involved repetitive Tui Na on Hegu acupoint, using a block design [six cycles: rest (20 seconds); Tui Na (20 seconds); rest (30 seconds)]. The changes in neural activity in sensorimotor cortex could be inferred according to the principle of neurovascular coupling, and the number of activated channels in the bilateral hemisphere was used to calculate the lateralization index., Result: 1. For hemodynamic response induced by Hegu acupoint Tui Na, a dominant increase in the contralesional primary sensorimotor cortex during Hegu point Tui Na of the less affected arm in stroke patients was observed, as well as that in healthy controls, while this contralateral pattern was absent during Hegu point Tui Na of the affected arm in stroke patients. 2. Concerning the lateralization index in stroke patients, a significant difference was observed between lateralization index values for the affected arm and the less affected arm (P < 0.05). Wilcoxon tests showed a significant difference between lateralization index values for the affected arm in stroke patients and lateralization index values for the dominant upper limb in healthy controls (P < 0.05), and no significant difference between lateralization index values for the less affected arm in stroke patients and that in healthy controls (P = 0.36)., Conclusion: The combination of Tui Na and fNIRS has the potential to reflect the functional status of sensorimotor neural circuits. The changes of neuroactivity in the sensorimotor cortex when Tui Na Hegu acupoint indicate that there is a certain correlation between acupoints in traditional Chinese medicine and neural circuits., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Interferon regulatory factor 7 (IRF7) regulates type I interferon (IFN) genes via combining to the ISRE region in the immune response against bacteria. Streptococcus iniae is one of the dominant pathogenic bacteria of yellowfin seabream, Acanthopagrus latus. However, the regulatory mechanisms of A. latus IRF7 (AlIRF7) mediated by the type I IFN signalling pathway against S. iniae was ambiguously. In the present study, IRF7, and two IFNa3s (IFNa3 and IFNa3-like) were authenticated from A. latus. The total length of AlIRF7 cDNA is 2142 bp, containing a 1314 bp open reading frame (ORF) encoding an inferred 437 amino acids (aa). Three typical regions, a serine-rich domain (SRD), a DNA-binding domain (DBD), and an IRF association domain (IAD), are conserved in AlIRF7. Furthermore, AlIRF7 is fundamentally expressed in various kinds of organs, with high levels in the spleen and liver. Additionally, S. iniae challenge promoted AlIRF7 expression in the spleen, liver, kidney, and brain. AlIRF7 is confirmed to be located at the nucleus and cytoplasm by overexpression of AlIRF7. Moreover, truncation mutation analyses shows that the regions, -821 bp to +192 bp and -928 bp to +196 bp, were known as core promoters from AlIFNa3 and AlIFNa3-like, respectively. The point mutation analyses and electrophoretic mobile shift assay (EMSA) verified that AlIFNa3 and AlIFNa3-like transcriptions are depended on the M2/5 and M2/3/4 binding sites with AlIRF7 regulation, respectively. Additionally, an overexpression experiment showed that AlIRF7 can dramatically decrease the mRNA levels of two AlIFNa3s and interferon signalling molecules. These results suggest that two IFNa3s may mediate the regulation of AlIRF7 in the immune responses of A. latus against S. iniae infection., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2023 Elsevier B.V. All rights reserved.)

This study aims to present a sustainably releasing system of exosomes-fibrin combinate loaded on tantalum-coating titanium implants. We hope to investigate potential effects of the system on osseointegration between tantalum coating titanium implants and its surrounding bone tissue. Exosomes derived from rabbit bone marrow stromal cells (rBMSCs) and fibrin were deposited onto the micro-nanostructure tantalum coating surface (Ta + exo + FI) and compared to control groups, including tantalum coating (Ta), tantalum coating loaded exosomes (Ta + exo) and tantalum coating loaded fibrin (Ta + FI). The optimal concentration of loading exosomes, exosomes uptake capacity by BMSCs, and the effect of controlled-release by fibrin were assessed by laser scanning confocal microscope (LCSM) and microplate reader. The optimal concentration of exosomes was 1 μg/μL. Adhesion, proliferation, and osteogenic differentiation ability of BMSCs on different materials were assessed in vitro . Finally, osseointegrative capacity of Ta, Ta + exo, Ta + FI, Ta + exo + FI implants in rabbit tibia were respectively evaluated with histology and bone-implant contact ratio (BIC%). It was demonstrated that exosome sustained-release system with fibrin loading on the tantalum coating was successfully established. Fibrin contribute to exosomes release extension from 2d to 6d. Furthermore, Ta + exo + FI significantly promoted adhesion, proliferation, and osteogenic differentiation of BMSCs. In vivo , the implants in Ta + exo + FI group displayed the highest osseointegrative capability than those in other groups. It is concluded that this exosome delivery system on the implants may be an effective way for tantalum coating titanium implants to promote osseointegration between implant and its surrounding bone tissue., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Cui, Wang, Mu, Huang, Wang, Luo and He.)

Two novel prenylated acetophenones with new carbon skeletons, acronyrones A and B (1 and 2), and a new analogue, acronyrone C (3), together with two known compounds (4 and 5) were isolated from the leaves of Acronychia pedunculata. Their structures with absolute configurations were identified by interpretation of spectroscopic data, single crystal X-ray diffraction, and electronic circular dichroism (ECD) calculations. Compounds 1 and 2 represent the first example of prenylated acetophenones possessed a C 7 (1) and a C 6 (2) side chain, forming a 4-isobutylchroman-2-one unit and a 3-(2-methylpropylidene)benzofuran-2(3H)-one moiety with the acetophenone core, respectively. In addition, compound 4 exhibited significant dose-dependent transcriptional activation effect against retinoid X receptor-α (RXRα), and could be regarded as a new type of non-classical RXR ligand., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2022. Published by Elsevier B.V.)

Ulcerative colitis (UC) is a chronic nonspecific inflammatory bowel disease characterized by chronic inflammation and ulceration of the colonic mucosa, frequent relapse, and cancerization that is difficult to cure. In recent years, the incidence of UC has increased. However, its etiology and pathogenesis are still not completely clear. In this study, dextran sodium sulfate (DSS) was used to induce the model, and GSK-J1 and dexamethasone were administered to the mice. A variety of molecular biology and immunological techniques, such as immunofluorescence, PCR and chromatin immunoprecipitation (ChIP), were used to examine JMJD3/H3K27me3-mediated regulation of Th17/Treg cell differentiation in UC by targeting histone modification. This study will provide an important theoretical basis for understanding the pathogenesis and potential therapeutic targets of UC., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

The Qinghai-Tibet Plateau Area (QTPA) has a complex natural ecosystem, causing a greatly increased risk of spreading various tick-borne diseases including rickettsial infections, which are regarded as one of the oldest known vector-borne zoonoses. However, the information of one of its pathogen, spotted fever group Rickettsia (SFG Rickettsia ), is limited in tick vectors and animals in this area. Therefore, this study focused on the investigation of SFG Rickettsia in tick vectors, yaks ( Bos grunniens ), and Tibetan sheep ( Ovis aries ) in the QTPA. A total of 1,000 samples were collected from nine sampling sites, including 425 of yaks, 309 of Tibetan sheep, 266 of ticks. By morphological examination, PCR, and sequencing, we confirmed the species of all collected ticks. All tick samples, all yak and Tibetan sheep blood samples were detected based on SFG Rickettsia ompA and sca4 gene. The results showed that all tick samples were identified to be Haemaphysalis qinghaiensis , and the positive rates of SFG Rickettsia were 5.9% (25/425), 0.3% (1/309), and 54.1% (144/266) in yaks, Tibetan sheep, and ticks, respectively. All positive samples were sequenced, and BLASTn analysis of the ompA gene sequences of SFG Rickettsia showed that all positive samples from animals and ticks had 99.04-100% identity with yak and horse isolates from Qinghai Province, China. BLASTn analysis of the sca4 gene sequences of SFG Rickettsia showed that all positive samples had 97.60-98.72% identity with tick isolates from Ukraine. In addition, the phylogenetic analysis showed that all the SFG Rickettsia ompA and sca4 sequences obtained from this study belong to the same clade as Rickettsia raoultii isolated from livestock and ticks from China and other countries. Molecularly, this study detected and characterized SFG Rickettsia both in the tick vectors and animals, suggesting that the relationship between SFG Rickettsia , tick species and animal hosts should be explored to understand their interrelationships, which provide a theoretical basis for preventing control of this pathogen., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 He, Li, Sun, Kang, He, Guo, Ma, Wei, Li, Chen, Chen, Li, Qi, Yang, Zhang, Wang, Cai, Zhao, Hu, Chen and Li.)

There is an urgent need to address the critical demand for qualified Chinese language teachers against the background of China's seeking greater Sino-foreign cultural and educational cooperation. The literature on integrating technological pedagogical content knowledge (TPACK) in language teaching has been increasing in the last few years. However, most of these studies focus on English language teachers. The objective of this study was to examine pre-service teachers' understanding of TPACK for teaching Chinese as a second language (TCSL). This study investigated the TPACK factor structure of 286 pre-service TCSL teachers via exploratory factor analysis, which yielded a six-factor structure. The results revealed that the teachers could not distinguish the boundaries between technological pedagogical knowledge (TPK) and technological content knowledge (TCK); and TPK and synthesized TPACK. Further, confirmatory factor analysis using structural equation modeling substantiated the validity and reliability of the adapted 32-item TCSL-TPACK survey instrument. The study also found that the teachers were slightly satisfied with their overall TPACK but were least confident of their technological knowledge (TK), and the more experienced teachers exhibited higher confidence in all six factors. These findings not only remind educators and policymakers of the need to revise current teacher training programs but also persuade TCSL student teachers to explore methods that can help integrate technology into lesson designs., Competing Interests: Conflicts of InterestThe authors declare no conflict of interest., (© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2022.)

Purpose: Some studies have indicated that using 500 mg/m 2 rituximab combined with CHOP-14 may be beneficial for elderly men but not women with diffuse large B-cell lymphoma (DLBCL). The purpose of this study was to investigate the potential benefit of escalated doses of rituximab with CHOP-21 as the first-line treatment in male patients with DLBCL., Methods: We performed a retrospective cohort study to analyze the survival benefit of rituximab 500 mg/m 2 plus the CHOP-21 regimen (Escalated-R-CHOP-21) as the first-line treatment compared with using rituximab 375 mg/m 2 plus the CHOP-21 regimen (Standard-R-CHOP-21) in men with DLBCL. We used propensity score matching to maximize the balance of the observed covariables. The primary endpoints of this study were the progression-free survival (PFS) rate and overall survival (OS) rate at 3 years., Results: After a median follow-up of 47 months (IQR 31-65), no significant difference in PFS and OS was found for men treated with Escalated-R-CHOP-21 compared with Standard-R-CHOP-21 [3-year PFS: 69.7% versus 71.9%, p = 0.867; 3-year OS: 83.0% versus 82.4%, p = 0.660]. After 1:1 propensity score matching, we found that the patients using Escalated-R-CHOP-21 had statistically significant survival benefits relative to Standard-R-CHOP-21 among the 96 matched elderly male patients for 3-year PFS [75.5% (95% CI 62.8-88.2) versus 58.2% (95% CI 44.3-72.1); p = 0.019] and 3-year OS [86.6% (95% CI 76.4-96.8) versus 65.8% (95% CI 52.1-79.5); p = 0.017]. However, no differences in survival were observed for younger male patients. Furthermore, the dose effect in PFS of Escalated-R-CHOP-21 was more obvious for elderly male patients with no high-risk extranodal sites (p = 0.005 and interaction p = 0.030)., Conclusion: Escalated-R-CHOP-21 could be a safe and effective option for treating elderly male patients with DLBCL. This study provides new insight into optimizing the standard treatment regimen, which may have important therapeutic implications in elderly male patients with DLBCL., (© 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Peri-engraftment respiratory distress syndrome (PERDS) is a kind of potentially life-threatening complication of autologous stem cell transplantation (ASCT). PERDS is characterized by fever, dyspnea, and hypoxemia during neutrophil engraftment. In order to identify the high-risk factors for PERDS, we retrospectively analyzed 260 patients with lymphoma undergoing ASCT in recent five years. The conditioning regimen was BuCyE (busulfan, cyclophosphamide, and etoposide). There were 16 patients (6.1%) diagnosed as PERDS. In multivariate analysis, prior anti-programmed death-1 (PD-1) therapy (hazard ratio [HR] = 8.852, 95% confidence interval [CI]: 2.954-26.527, P < 0.001) and history of pulmonary disease (HR = 3.718, 95% CI: 1.197-11.545, P = 0.023) were independent risk factors for PERDS. Patients with prior anti-PD-1 therapy (n = 31) had higher incidence of engraftment syndrome (77.4% vs. 33.4%, P < 0.001), PERDS (25.8% vs. 3.5%, P < 0.001), and transplant-related mortality (9.7% vs. 0.4%, P < 0.001), compared with those without prior anti-PD-1 therapy (n = 229). Subgroup analysis showed that sintilimab seemed to be associated with higher incidence of PERDS (42.9% vs. 11.8%, P = 0.06) compared with non-sintilimab group (pembrolizumab or toripalimab). C-reactive protein might be a feasible early predictor for PERDS. In conclusion, our study suggests that prior anti-PD-1 therapy may be a strong risk factor for life-threatening PERDS in patients with lymphoma undergoing ASCT.

Although PD-1/PD-L1 blockade therapy confers salutary effects across cancer types, their efficacy in Extranodal Natural killer/T-cell lymphoma (ENKTCL) patients is limited and unpredictable. Here, we comprehensively evaluated the expression profile of a panel of immune-regulatory makers to identify novel prognostic biomarkers and/or therapeutic targets for this malignancy. Using immunohistochemistry and multiplex immunofluorescence, we found that the expression of VISTA (88.1%) was predominantly in CD68+ macrophages and much higher than PD-L1 expression (68.7%) in ENKTCL. B7-H4 and HHLA2 proteins were not detected in ENKTCL. B7-H3 was expressed in minority of ENKTCL patients (13.7%) and mainly colocalized with CD31. A close correlation was detected between VISTA and PD-L1, but they were not co-expressed in the same cells. High expressions of VISTA or PD-L1 were significantly associated with detrimental clinicopathological characteristics, dismal prognosis, and high density of CD8+ TILs, and high VISTA expression was also significantly associated with high density of Foxp3+ TILs. VISTA combined with PD-L1 was an independent prognostic factor for PFS and OS. Moreover, the patients with high VISTA showed a poor response to PD-1 blockades in ENKTCL. In conclusion, these findings provide a rationale for VISTA as an ideal immunotherapeutic target next to PD-L1 for ENKTCL., (© 2021 The Author(s). Published with license by Taylor & Francis Group, LLC.)

Melophagus ovinus (sheep ked) is a hematophagous ectoparasite that mainly parasitizes sheep. In addition to causing inflammation, wool loss, and skin damage to the animal hosts, M. ovinus also serves as a vector for a variety of pathogens and is highly likely to participate in the life and transmission cycle of pathogenic organisms. Herein, we investigated the presence and molecular characterization of vector-borne pathogens in M. ovinus from Qinghai-Tibet Plateau, China. A total of 92 M. ovinus pools collected from the Qinghai province of China were screened for the presence of selected vector-borne pathogens. The overall positive rate of A. ovis , A. bovis , A. phagocytophilum , and T. ovis in M. ovinus was 39.1%, 17.4%, 9.8%, and 89.1%, respectively. All of the samples were negative for Border disease virus (BDV), other Anaplasma species, Babesia spp., Rickettsia spp., and Borrelia spp. Co-infection of different Anaplasma species and T. ovis occurred in 51.2% of all samples with T. ovis . The positive rates of A. ovis , A. bovis , and A. phagocytophilum in different regions and altitudes of the sampling sites were significantly different. Sequence and phylogenetic analysis of target genes confirmed their identity with corresponding pathogens. Our results elucidate the occurrence and molecular characterization of Anaplasma spp. and Theileria spp. in M. ovinus , which could act as potential zoonotic reservoirs. To the best of our knowledge, this is the first report of the detection of A. bovis and A. phagocytophilum DNA in M. ovinus . This study gives the first extensive molecular survey of vector-borne pathogens with veterinary and public health significance in M. ovinus from the Qinghai-Tibet Plateau, China.

Background: Compound sophorae decoction (CSD), a Chinese Herbal decoction, is frequently clinically prescribed for patients suffered from ulcerative colitis (UC) characterized by bloody diarrhea. Yet, the underlying mechanism about how this formulae works is remain elusive., Methods: In the present study, the experimental colitis in C57BL/6 J mice was induced by oral administration of standard diets containing 3% dextran sodium sulfate (DSS), and CSD was given orally for treatment at the same time. The clinical symptoms including stool and body weight were recorded each day, and colon length and its histopathological changes were observed. Apoptosis of colonic epithelium was studied by detecting protein expression of cleaved caspase-3, and cell proliferation by Ki-67 immunohistochemistry. Tight junction complex like ZO-1 and occludin were also determined by transmission electron microscope and immunofluorescence. The concentration of FITC-dextran 4000 was measured to evaluate intestinal barrier permeability and possible signaling pathway was investigated. Mucin2 (MUC2) and notch pathway were tested through western blot. The M1/M2 ratio in spleen and mesenteric lymph nodes were detected by flow cytometry. And the mRNA levels of iNOS and Arg1 were examined by qRT-PCR., Results: CSD could significantly alleviate the clinical manifestations and pathological damage. Body weight loss and DAI score of mice with colitis were improved and shortening of colon was inhibited. The administration of CSD was able to reduce apoptotic epithelial cells and facilitate epithelial cell regeneration. Increased intestinal permeability was reduced in DSS-induced colitis mice. In addition, CSD treatment obviously up-regulated the expression of ZO-1 and occludin and the secretion of MUC2, regulated notch signaling, and decreased the ratio of M1/M2., Conclusions: These data together suggest that CSD can effectively mitigate intestinal inflammation, promote phenotypic change in macrophage phenotype and enhance colonic mucosal barrier function by, at least in part, regulating notch signaling in mice affected by DSS-induced colitis., (Copyright © 2020. Published by Elsevier Masson SAS.)

Objective: To investigate the success rate, safety and repeatability of gadolinium (Gd)-enhanced inner ear magnetic resonance (MR) by tympanic membrane puncture. Methods: The imaging and clinical data of 1 126 cases with Gd-enhanced inner ear MR by tympanic membrane puncture from February 2010 to June 2020 were retrospectively analyzed. All cases were reexamined in the outpatient clinic after MR gadolinium contrast to check the tympanic membrane and external auditory canal. The success rate was identified by whether there was gadolinium contrast in the labyrinth. Meanwhile, the pure tone hearing threshold data of asymptomatic ears before and after gadolinium contrast was collected and compared. The consistency in the scores of the asymptomatic ears in patients who underwent twice Gd-enhanced MR was analyzed, in which the scores of vestibular, cochlea, and semicircular canals were acquired respectively. Results: Among 1 126 patients [including 506 males and 620 females, aged (54±17) years old], 45 were reviewed once, while 4 patients were reviewed twice. There were 958 cases who were examined on both sides, and 168 cases were checked only on one side. There were 166 cases of Meniere's disease (14.7%), 219 cases of sudden sensorineural hearing loss (19.5%) and 741 cases of being remained to be investigated (65.8%), respectively. A total of 2 084 ears underwent first gadolinium angiography, of which 63 ears had no contrast agent in the labyrinth, with a success rate of 97.0% (2 021/2 084). Only 1 case had tympanic membrane perforation while the rest had no complications. The hearing threshold before and after otography in 57 asymptomatic ears had no differences at any frequency (all P >0.05). Moreover, the consistency in the scores of two radiography within the 21 asymptomatic ears in vestibular and cochlea was good [both intraclass correlation coefficient (ICC) values>0.75]. Conclusion: The success rate and safety of Gd-enhanced inner ear MR is high by tympanic membrane puncture, and the results can be repeated well.

At present, autologous stem cell transplantation (ASCT) is considered as an optional consolidation therapy for natural killer/T-cell lymphoma (NKTCL). However, the high-risk patients undergoing ASCT are not clear enough. In this study, 56 patients with advanced staged or relapsed/refractory (R/R) NKTCL undergoing ASCT were reviewed. All patients achieved clinical complete response (CR) before ASCT. The median follow-up time was 36 months (range, 3-192 months). The three-year overall survival (OS) and three-year progression-free survival (PFS) were 70.2% and 56.5%, respectively. The independent prognostic factors for OS included prior testis involvement and pre-ASCT EBV-DNA. Patients without prior testis involvement and negative pre-ASCT EBV-DNA (group A) had better three-year OS (86.3% vs. 47.6%, p  < .001) than the rest patients (group B). In conclusion, our study suggests that testis involvement and elevated EBV-DNA might be strong adverse prognostic factors for NKTCL. Patients without the above risk factors are more likely to benefit from ASCT.

Abstract: Objective To construct a discriminant analysis model based on the differential expression of multiple microRNAs （miRNAs） in two kinds of blood samples （peripheral blood and menstrual blood） and three non-blood samples （saliva, semen and vaginal secretion）, to form an identification solution for peripheral blood and menstrual blood. Methods Six kinds of miRNA （miR-451a, miR-144-3p, miR-144-5p, miR-214-3p, miR-203-3p and miR-205-5p） were selected from literature, the samples of five kinds of body fluids commonly seen in forensic practice （peripheral blood, menstrual blood, saliva, semen, vaginal secretion） were collected, then the samples were divided into training set and testing set and detected by SYBR Green real-time qPCR. A discriminant analysis model was set up based on the expression data of training set and the expression data of testing set was used to examine the accuracy of the model. Results A discriminant analysis statistical model that could distinguish blood samples from non-blood samples and distinguish peripheral blood samples from menstrual blood samples at the same time was successfully constructed. The identification accuracy of the model was over 99%. Conclusion This study provides a scientific and accurate identification strategy for forensic fluid identification of peripheral blood and menstrual blood samples and could be used in forensic practice., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Forensic Medicine.)

Background: Although clear cell renal cell carcinoma (ccRCC) is well known as a highly immunogenic tumor, only a small subset of patients could benefit from current immunotherapy, which might be due to the heterogeneity of immune microenvironment in ccRCC. So, it is meaningful to explore novel immunotherapy or combination therapy for improving therapeutic efficacy. HHLA2, a newly discovered B7 family member, is prevalently expressed in numerous tumors, including ccRCC. This study aimed to investigate the prognostic impact of HHLA2/PD-L1 co-expression and its relationship with tumor-infiltrating lymphocytes (TILs)., Methods: The expression levels of HHLA2, PD-L1, CD8, and CD4 in cancer tissues from cases (206 in the training cohort and 197 in the validation cohort) with surgically resectable primary ccRCC were evaluated by immunohistochemistry., Results: The positive rates of HHLA2 were much higher than those of PD-L1 in ccRCC tissues. HHLA2-positive expression was significantly associated with necrosis, microvascular invasion, advanced Fuhrman nuclear, and TNM stage and indicated a shorter progression-free survival (PFS) and overall survival (OS) in both cohorts. Moreover, patients with HHLA2/PD-L1 co-expression suffered the highest risk of disease progression and death by a significant margin. Besides, HHLA2/PD-L1 co-expression was significantly associated with a high density of CD8 + and CD4 + TILs. Notably, a new immune classification, based on HHLA2/PD-L1 co-expression and TILs, successfully stratified PFS and OS, especially in patients with TILs positivity., Conclusions: The expression of HHLA2 is more frequent than PD-L1 in ccRCC. HHLA2/PD-L1 co-expression had an adverse impact on the prognoses of patients with ccRCC; this finding provides a rationale for combination immunotherapy with anti-HHLA2 and PD-L1 blockage for patients with ccRCC in the future., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.)

Objective: The fabrication of bioactive coatings on metallic implants to enhance osseointegration has become a topic of general interest in orthopedics and dentistry. Hydroxyapatite (HA) coating has been shown to induce bone formation and promote bone-implant integration. Unfortunately, poor mechanical performance has hindered this from becoming a favorable coating material. The majority of present studies have focused in incorporating different elements into HA coatings to improve mechanical properties. In recent years, tantalum (Ta) has received increasing attention due to its excellent biocompatibility and corrosion resistance. The aim of on the present study was to investigate the fabrication and biological performance of Ta-incorporated HA coatings., Methods: Ta-incorporated HA coatings were fabricated using the plasma spray technique on a titanium substrate, and the surface characteristics and mechanical properties were examined. In addition, the effects of Ta-incorporated HA coatings on the biological behavior of mesenchymal stem cells (BMSCs) were investigated., Results: Ta-incorporated HA coatings with microporous structure had higher roughness and wettability. In addition, the bonding strength of Ta/HA coatings with the substrate was substantially superior to HA coatings. Furthermore, Ta-incorporated HA coatings not only facilitated initial cell adhesion and faster proliferation, but also promoted the osteogenic differentiation of BMSCs., Conclusion: These results indicate that the incorporation of Ta could improve mechanical performance and increase the osteogenic activity of HA coatings. The Ta-incorporated HA coating fabricated by plasma spraying is expected to be a promising bio-coating material for metallic implants.

High uniformity of un-doped and Ni-doped CuSe nanowires have been fabricated by smelting the bulk and injecting the molten liquid into the anodic aluminum oxide (AAO) template. The Ni dopant concentration and morphology of CuSe nanowires can be well controlled via preparing the bulk materials and the channel size of the AAO template, respectively. The cathodoluminescence peaks of the un-doped, 0.5 at% and 1.0 at% Ni-doped CuSe nanowires showed a redshift of about 26 nm and 42 nm, respectively, from un-doped CuSe nanowires (579 nm). Furthermore, above room temperature ferromagnetism was observed in 1.0 at% Ni-doped CuSe nanowires at 300 K. The facile injection molding method fabricated nanowires with tunable optical and magnetic properties which could be applied to prepare various nanomaterials for spintronic devices in the future.

Mildew resistance locus O ( Mlo ) gene was first found in barley as a powdery mildew susceptibility gene, and recessive mlo alleles confer durable resistance to barley powdery mildew. To identify candidate Mlo susceptibility genes in rubber tree, HbMlo12 was cloned from rubber tree clone CATAS7-33-97, which is susceptible to powdery mildew. Protein architecture analysis showed that HbMlo12 was a typical Mlo protein with seven transmembrane domains. Protein blast search in the Arabidopsis thaliana proteome database showed that HbMlo12 shared the highest similarity with AtMlo12, with 63% sequence identity. Furthermore, HbMlo12 together with the dicot powdery mildew susceptible Mlo proteins (including AtMlo2, AtMlo6, AtMlo12, tomato SlMlo1, pepper CaMlo2, pea PsMlo1, etc.) were grouped into clade V. Subcellular localization analysis in tobacco epidermal cells revealed that HbMlo12 was localized to the endoplasmic reticulum membrane. HbMlo12 was preferentially expressed in the flower and leaf of rubber tree. Moreover, its expression was significantly upregulated in response to powdery mildew inoculation. Application of exogenous ethephon caused a distinct increase in HbMlo12 expression. Additionally, HbMlo12 transcript was quickly induced by spraying salicylic acid and gibberellic acid and reached the maximum at 0.5 h after treatments. By contrast, HbMlo12 expression was downregulated by methyl jasmonate, abscisic acid, and drought stress treatments. There was no significant change in HbMlo12 expression after indole-3-acetic acid, H 2 O 2 , and wounding stimuli. Taken together, these results suggested that HbMlo12 might be a candidate Mlo gene conferring susceptibility to powdery mildew in rubber tree. The results of this study are vital in understanding Mlo gene evolution and developing new rubber tree varieties with powdery mildew resistance using reverse genetics.

Tumor cells metabolize more glucose to lactate in aerobic or hypoxic conditions than normal cells. Pyruvate kinase isoenzyme type M2 (PKM2) is crucial for tumor cell aerobic glycolysis. We established a role for let-7a-5p/Stat3/hnRNP-A1/PKM2 signaling in breast cancer cell glucose metabolism. PKM2 depletion via small interfering RNA (siRNA) inhibits cell proliferation and aerobic glycolysis in breast cancer cells. Signal transducer and activator of transcription 3 (Stat3) promotes upregulation of heterogeneous nuclear ribonucleoprotein (hnRNP)-A1 expression, hnRNP-A1 binding to pyruvate kinase isoenzyme (PKM) pre messenger RNA, and the subsequent formation of PKM2. This pathway is downregulated by the microRNA let-7a-5p, which functionally targets Stat3, whereas hnRNP-A1 blocks the biogenesis of let-7a-5p to counteract its ability to downregulate the Stat3/hnRNP-A1/PKM2 signaling pathway. The downregulation of Stat3/hnRNP-A1/PKM2 by let-7a-5p is verified using a breast cancer. These results suggest that let-7a-5p, Stat3, and hnRNP-A1 form a feedback loop, thereby regulating PKM2 expression to modulate glucose metabolism of breast cancer cells. These findings elucidate a new pathway mediating aerobic glycolysis in breast cancers and provide an attractive potential target for breast cancer therapeutic intervention., (© 2018 Wiley Periodicals, Inc.)

Enterocytozoon bieneusi and Cryptosporidium spp. are important pathogens causing diarrhea in humans and animals. However, few studies have been conducted on the infection of E. bieneusi and Cryptosporidium spp. in peafowl up to now. The purpose of the present study was to determine the prevalence and the involved genotypes of Cryptosporidium spp. and E. bieneusi in peafowl in Beijing and Jiangxi Province, China. In total, 258 peafowl fecal samples were collected. Overall, both Cryptosporidium spp. and E. bieneusi had the same prevalence, i.e. 6.59% (17/258). Higher infection rates of E. bieneusi and Cryptosporidium spp. were found in the adolescent peafowl. The prevalence of E. bieneusi in Beijing and Jiangxi Province was 5.23% and 8.57% respectively. For Cryptosporidium spp., the prevalence was 4.58% and 9.52% in Beijing and Jiangxi Province, respectively. Three zoonotic genotypes of E. bieneusi were confirmed, including two known genotypes, genotype Peru 6 and D, and one novel genotype, JXP1. Two avian specific species/genotypes of Cryptosporidium , Avian genotype Ⅲ and Goose genotype Ⅰ, were identified. To our knowledge, this is the first report of E. bieneusi and Cryptosporidium spp. occurrence in peafowl in China. The findings suggest that peafowl could be reservoirs of E. bieneusi and Cryptosporidium spp. which could be potentially transmitted to humans and other animals, and the present survey have implications for controlling E. bieneusi and Cryptosporidium spp. infection in peafowl.

A field experiment was conducted to examine the effects of plastic film mulching (PM), straw retention (SR), and planting green manure (GM) on winter wheat grain yield and soil fertility. The results showed that PM did not have consistently positive effect on the grain yield, when compared to the traditional patterns (TP). No difference of average grain yield was observed between them over three years. Soil total nitrogen (N), available phosphorus (P), potassium (K), sulfur (S), zinc (Zn) and manganese (Mn) were decreased in 20-40 cm layer in PM than those in TP, while no difference was observed for soil organic matter, nitrate (NO 3 - -N), available iron (Fe) and copper (Cu). The mean grain yield of three years decreased by 12.1% in SR than that in TP treatment. At maturity stage of winter wheat, soil total N and available Cu was increased by 5.8% in 0-20 cm and 6.2% in 20-40 cm layer, respectively, while soil available P and Mn were decreased by 36.1% and 10.2%, respectively. No difference was observed between SR and TP treatments for soil organic matter, NO 3 - -N, available K, S, Zn and Fe at anthesis and maturity stages. Compared to the TP treatment, the mean grain yield was decreased by 12.1% in GM treatment. Soil pH, available P and S were decreased, while the soil organic matter, total N, NO 3 - -N, and available Zn and Mn were increased. No difference was observed for soil available K, Fe and Cu. In conclusion, the PM and SR were not beneficial for the improvement of soil fertility, and thus inhibited the grain yield increase in dryland with low soil fertility level. The GM has greater potential to increase soil nutrients, but it should be paid more attention to the risk of grain yield reduction due to insufficient annual precipitation.

Trichomonas gallinae is a globally distributed protozoan parasite, mainly affect the upper avian digestive tract and can bring huge economic losses to pigeon industry. The objective of the present study was to determine the prevalence and genotypes of T. gallinae in Beijing, China. A total of 569 samples of throat swabs of pigeon were collected from pigeon farms in Shunyi District, Fangshan District, Daxing District and Miyun District of Beijing. The overall prevalence was 28.30%. The significant difference in infection rates was not observed between regions, but was found between age groups. The highest prevalence was nestling pigeons (33.16%), followed by adolescent pigeons (30.05%) and breeding pigeons (20.59%). Moreover, genotype A and B of T. gallinae were identified by sequencing the ITS1/5.8S/ITS2 regions and phylogenetic analysis. To our knowledge, this is the first report to display the prevalence and genotype of T. gallinae from Beijing, China., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Three series of novel 3-methyl-2-alkylthio benzothiazolyl ionic liquids (ILs) were synthesized for the first time. After structural identification, their melting point, solubility, and thermostability together with antibiotic activity were determined successively. As a result, 3-methyl-2-alkylthio benzothiazolyl p -toluene sulfonate was found to have the highest antibacterial activity among the three series of ILs. Meanwhile, it has a good solubility in water as well. On the basis of comprehensive comparison with similar compounds, the effect of cations and anions of these benzothiazolium ILs on typical physical properties together with antibiotic performance was explored and discussed, which is very beneficial to take the greatest advantage of their structural designability for various purposes. Furthermore, the experiment data preliminarily discovered the relationships of the structure-properties/activities of the above three kinds ILs to a certain extent, which can provide useful references for future research and for the potential application of these new ILs as surfactant antiseptics or agricultural chemicals.

Background: Nanotechnology is emerging as a promising tool to perform noninvasive therapy and optical imaging. However, nanomedicine may pose a potential risk of toxicity during in vivo applications. In this study, we aimed to investigate the potential toxicity of rare-earth nanoparticles (RENPs) using mice as models., Methods: We synthesized RENPs through a typical co-precipitation method. Institute of Cancer Research (ICR) mice were randomly divided into seven groups including a control group and six experimental groups (10 mice per group). ICR mice were intravenously injected with bare RENPs at a daily dose of 0, 0.5, 1.0, and 1.5 mg/kg for 7 days. To evaluate the toxicity of these nanoparticles in mice, magnetic resonance imaging (MRI) was performed to assess their uptake in mice. In addition, hematological and biochemical analyses were conducted to evaluate any impairment in the organ functions of ICR mice. The analysis of variance (ANOVA) followed by a one-way ANOVA test was used in this study. A repeated measures' analysis was used to determine any significant differences in white blood cell (WBC), alanine aminotransferase (ALT), and creatinine (CREA) levels at different evaluation times in each group., Results: We demonstrated the successful synthesis of two different sizes (10 nm and 100 nm) of RENPs. Their physical properties were characterized by transmission electron microscopy and a 980 nm laser diode. Results of MRI study revealed the distribution and circulation of the RENPs in the liver. In addition, the hematological analysis found an increase of WBCs to (8.69 ± 0.85) × 10 9 /L at the 28 th day, which is indicative of inflammation in the mouse treated with 1.5 mg/kg NaYbF 4 :Er nanoparticles. Furthermore, the biochemical analysis indicated increased levels of ALT ([64.20 ± 15.50] U/L) and CREA ([27.80 ± 3.56] μmol/L) at the 28 th day, particularly those injected with 1.5 mg/kg NaYbF 4 :Er nanoparticles. These results suggested the physiological and pathological damage caused by these nanoparticles to the organs and tissues of mice, especially to liver and kidney., Conclusion: The use of bare RENPs may cause possible hepatotoxicity and nephritictoxicity in mice., Competing Interests: There are no conflicts of interest

A field experiment was conducted to examine the effects of plastic film mulching (PM), straw retention (SR) and planting green manure (GM) on grain yield and nutrient concentrations of winter wheat. Compared to the traditional pattern (TP), plastic film mulching showed no significant effect on the average yield over the three years but increased the average phosphorus (P) uptake and concentration in grain by 8.4% and 13.0%, respectively. The average uptake of nitrogen (N), sulfur (S) and iron (Fe) was decreased by 12.6%, 15.0% and 11.1%, and the corresponding concentration was decreased by 12.1%, 12.9% and 10.1%, respectively. There was no significant effect on grain zinc (Zn) concentration. Straw retention decreased grain yield by 12.1%, reduced the average uptake of N, S and Fe decreased by 22.5%, 21.0% and 19.8%, and their corresponding concentration by 10.1%, 9.4% and 3.8%, respectively. The average uptake of P in grain was decreased by 9.8% with straw retention, while the P concentration was increased by 5.0%. There was no significant effect of straw retention on Zn concentration in grain. Planting green manure decreased the grain yield by 12.1%. It had no significant effect on the average uptake of N and Zn, but increased the grain N and Zn concentration by 12.1% and 12.6%, respectively. It showed no impact on P, S and Fe concentration in grain. The discordance between variation of grain yield and its nutrient uptake under different cultivations was the key reason for the changes of their nutrient concentration. Considering the potential adverse effects of plastic film mulching and straw retention on the quantity and quality of grain yield, suitable N fertilization should be applied to ensure the nutrient requirement for grain yield and regulate the uptake and utilization of N, S and Fe for improving the grain quality. Planting green manure could improve soil fertility and increase grain N and Zn concentration, but the yield reduction deserves more attention.

Background: Luminescent rare-earth-based nanoparticles have been increasingly used in nanomedicine due to their excellent physicochemical properties, such as biomedical imaging agents, drug carriers, and biomarkers. However, biological safety of the rare-earth-based nanomedicine is of great significance for future development in practical applications. In particular, biological effects of rare-earth nanoparticles on human's central nervous system are still unclear. This study aimed to investigate the potential toxicity of rare-earth nanoparticles in nervous system function in the case of continuous exposure., Methods: Adult ICR mice were randomly divided into seven groups, including control group (receiving 0.9% normal saline) and six experimental groups (10 mice in each group). Luminescent rare-earth-based nanoparticles were synthesized by a reported co-precipitation method. Two different sizes of the nanoparticles were obtained, and then exposed to ICR mice through caudal vein injection at 0.5, 1.0, and 1.5 mg/kg body weight in each day for 7 days. Next, a Morris water maze test was employed to evaluate impaired behaviors of their spatial recognition memory. Finally, histopathological examination was implemented to study how the nanoparticles can affect the brain tissue of the ICR mice., Results: Two different sizes of rare-earth nanoparticles have been successfully obtained, and their physical properties including luminescence spectra and nanoparticle sizes have been characterized. In these experiments, the rare-earth nanoparticles were taken up in the mouse liver using the magnetic resonance imaging characterization. Most importantly, the experimental results of the Morris water maze tests and histopathological analysis clearly showed that rare-earth nanoparticles could induce toxicity on mouse brain and impair the behaviors of spatial recognition memory. Finally, the mechanism of adenosine triphosphate quenching by the rare-earth nanoparticles was provided to illustrate the toxicity on the mouse brain., Conclusions: This study suggested that long-term exposure of high-dose bare rare-earth nanoparticles caused an obvious damage on the spatial recognition memory in the mice.

Morganella morganii is an important opportunistic human pathogen and belongs to the family of Enterobacteriaceae. Although it is widely distribution, it only be considered a rare cause of human infections. We report the isolate of M. morganii from Naja naja atra following infections of heart, lung and liver. Seven strains were confirmed using 16S rDNA amplified and sequences. Antimicrobial susceptibility testing of M. morganii isolates demonstrated ubiquitous resistance to ampicillin, amoxicillin/clavulanic acid, cefazolin, cephalothin, sulfamethoxazole/trimethoprim, sulfamethoxazole et al. However, M. morganii ubiquitous susceptible to piperacillin, ampicillin/sulbactam, piperacillin/tazobactam, cefixime et al. Further investigate display gyr B and Sul2 genes presence in all M. morganii isolates. AAC(3)-II was found in E2, E3 and E6 M. morganii. gyrA and qnrB expression in M3 and M6 M. morganii. This is the first description in M. morganii carrying AAC(3)-II, gyrB, gyrA, qnrB, and Sul2 genes from Naja naja atra, which suggests the increasing risk of pathogen transmission between humans and wildlife.

The interferon-induced transmembrane (IFITM) proteins usually protect cells from many virus infections by viral entry and replication. Thus, the present study aimed to identification novel regulation factors of IFITM genes. Our data showed up-regulation of IFITM1, IFITM2, and IFITM3 genes in A549 by H5N1 virus infection. However, IFITM1 was not affected, IFITM2 and IFITM3 increases expression following different concentration H5N1 virus infection in HEK293T cells. This is the first time to find differences of IFITM1 transcription in different cells with the H5N1 virus infection. Moreover, experiments showed that H5N1 virus promotes expression of KLF4 and KLF5 in both A549 and HEK293T cells, but H5N1 virus NS1, M1, NP or PB2 alone has no obvious effect on transcription of KLF5. Overexpression of KLF5 increases transcription of IFITM1, IFITM2, and IFITM3 in A549 cells, however, it does not affect transcription of IFITM1, IFITM2, and IFITM3 in HEK293T cells. In addition, results for the first time displayed that KLF4 can up-regulate expression of IFITM5 in both A549 and HEK293T cells. In conclusion, we revealed KLF5 is involved in transcription of IFITM1, 2, and 3 thus making it a potential therapeutic activator in the future to treat viral infections through promoting the innate immune response.

Microbial transformation of the oleanolic acid (1) using Trichothecium roseum (pers.) Link (M 95.56) has resulted in the isolation of two new hydroxylated type metabolites, characterized as 15α-hydroxy-3-oxo-olean-12-en-28-oic acid (2) and 7β,15α-dihydroxy-3-oxo-olean-12-en-28-oic acid (3). The structure elucidation of these metabolites was based primarily on HR-EIMS, 1D NMR, and 2D NMR analyses.