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Translocation of full-length Her2 receptor into nucleus was reported by some studies. Here, we tested whether nuclear Her2 contributes to paclitaxel resistance in Her2-overexpressing breast cancer cells. Breast cancer cell was transfected with plasmids containing cDNA of wild-type Her2 or mutant-type Her2 lacking the nuclear localization signal (NLS) sequence which is required for Her2 nuclear transport. Cell resistance to paclitaxel was analyzed. Paclitaxel-resistant breast cancer cell was also developed and nuclear Her2 expression was tested. Then, correlation between nuclear Her2 and resistance to paclitaxel were analyzed. Expression of importin β1 was decreased to downregulate nuclear Her2 level and cell resistance to paclitaxel was tested. We found that Her2 overexpression increases Her2 nuclear expression and cells resistance to paclitaxel in MCF-7 cells. In the paclitaxel resistant cell (SK-BR-3/R), nuclear Her2 expression is upregulated compared with parental SK-BR-3 cells. Increased expression of nuclear Her2 after short-time (48 h) treatment of paclitaxel was also observed in SK-BR-3 cells. Further downregulation of Her2 nuclear expression through blocking expression of importin β1 sensitizes the cells to paclitaxel. The analysis showed that the Her2 nuclear expression increases the survivin expression which leads to resistance to paclitaxel. Her2 nuclear expression decreases paclitaxel-induced apoptosis. However, co-immunoprecipitation was applied, and the physical interaction of nuclear Her2 and survivin was not detected. We show for the first time that nuclear Her2 contributes to paclitaxel resistance in breast cancer cells which suggests that nuclear Her2 as a potential target to sensitize breast cancers to paclitaxel treatment., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). At the request of the authors, this article has been retracted following questions of data ownership that were brought to the Editor’s attention after publication. Concerns were raised over whether all data were generated in the authors’ lab, and over ownership of the models used. The authors were unable to reach a resolution with other labs involved, and as a result all authors have agreed to a retraction of this article., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

COVID-19 vaccines from multiple manufacturers are needed to cope with the problem of insufficient supply. We did two single-center, randomised, double-blind, placebo-controlled phase 1 and phase 2 trials to assess the safety, tolerability and immunogenicity of a recombinant COVID-19 vaccine (Sf9 cells) in healthy population aged 18 years or older in China. Eligible participants were enrolled, the ratio of candidate vaccine and placebo within each dose group was 3:1 (phase 1) or 5:1 (phase 2). From August 28, 2020, 168 participants were sequentially enrolled and randomly assigned to receive the low dose vaccine, high dose vaccine or placebo with the schedule of 0, 28 days or 0, 14, 28 days in phase 1 trial. From November 18, 2020, 960 participants were randomly assigned to receive the low dose vaccine, high dose vaccine or placebo with the schedule of 0, 21 days or 0, 14, 28 days in phase 2 trial. The most common solicited injection site adverse reaction within 7 days in both trials was pain. The most common solicited systematic adverse reactions within 7 days were fatigue, cough, sore throat, fever and headache. ELISA antibodies and neutralising antibodies increased at 14 days, and peaked at 28 days (phase 1) or 30 days (phase 2) after the last dose vaccination. The GMTs of neutralising antibody against live SARS-CoV-2 at 28 days or 30 days after the last dose vaccination were highest in the adult high dose group (0, 14, 28 days), with 102.9 (95% CI 61.9-171.2) and 102.6 (95% CI 75.2-140.1) in phase 1 and phase 2 trials, respectively. Specific T-cell response peaked at 14 days after the last dose vaccination in phase 1 trial. This vaccine is safe, and induced significant immune responses after three doses of vaccination., (© 2021. The Author(s).)

Impaired amyloid-β (Aβ) clearance is believed to be a primary cause of Alzheimer's disease (AD), and peripheral abnormalities in Aβ clearance have recently been linked to AD pathogenesis and progression. Data from recent genome-wide association studies have linked genetic risk factors associated with altered functions of more immune cells to AD pathology. Here, we first identified correlations of Smad3 signaling activation in peripheral macrophages with AD progression and phagocytosis of Aβ. Then, manipulating the Smad3 signaling regulated macrophage phagocytosis of Aβ and induced switch of macrophage inflammatory phenotypes in our cell cultures. In our mouse models, flag-tagged or fluorescent-dye conjugated Aβ was injected into the lateral ventricles or tail veins, and traced. Interestingly, blocking Smad3 signaling efficiently increased Aβ clearance by macrophages, reduced Aβ in the periphery and thereby enhanced Aβ efflux from the brain. Moreover, in our APP/PS1 transgenic AD model mice, Smad3 inhibition significantly attenuated Aβ deposition and neuroinflammation, and ameliorated cognitive deficits, probably by enhancing the peripheral clearance of Aβ. In conclusion, enhancing Aβ clearance by peripheral macrophages through Smad3 inhibition attenuated AD-related pathology and cognitive deficits, which may provide a new perspective for understanding AD and finding novel therapeutic approaches., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Since doenjang quality depends on the bacterial composition, which ambient bacteria in the environment and production conditions influence, a complete understanding of the bacteria community in traditionally madetraditionally made doenjang (TMD) from different regions is needed. We aimed to investigate the bacteria composition and quality of TMD in the following areas: Chonbuk (CB), Chonnam (CN), Kyungsang (KS), Kangwon (KW), Chungchung (CC) provinces, and Jeju island (JJ) of Korea. Twenty-nine TMD samples from different regions were used to assess biogenic amine contents, bacteria composition using next-generation methods, and metabolic functions of the bacteria using Picrust2. Bacillus spp. were isolated, and their antioxidant and fibrinolytic activities were determined. Most TMD contained high amounts of beneficial bacteria ( Bacillus , Lactobacillus , Pediococcus and Weissella ). However, some KS samples contained harmful bacteria ( Cronobacter , Proteus and Acinetobacter ) and less beneficial B. velezensis bacteria. There was no similarity among the regional groups, and each TMD showed a different bacteria composition. Shannon index, α-diversity index, was lower in TMD from JJ and CB than the other areas, but there was no β-diversity among TMD from the six area groups. Picrust2 analysis revealed that the functional potential for arachidonic acid metabolism was lowest in JJ and CN, that for supporting insulin action was highest in KS and JJ, and that for carbohydrate digestion and absorption was lowest in CB and JJ among all groups ( p < 0.05) according to the Kyoto Encyclopedia of Genes and Genomes Orthology. Histamine contents were lower in CN and CC, and tyramine contents did not differ significantly. B. velezensis , B. subtilis , B. licheniformis , B. siamensis , and B. amyloliquefaciens were isolated from TMD. None of the isolated Bacillus spp. contained the B. cereus gene. B. subtilis from CN had the highest fibrinolytic activity, and B. velezensis from CB had the highest antioxidant activity. In conclusion, TMD mainly contained various Bacillus spp., and the predominant one was B. velezensis , which had antioxidant and fibrinolytic activity regardless of the regional origin.

Objective: To investigate the feasibility, clinical efficacy and safety of endobronchial ultasound (EBUS) in children. Methods: The radiological features, EBUS images, pathological results and intraoperative and postoperative complications of 3 cases who underwent EBUS examination and 1 case who underwent EBUS guided transbronchial needle aspiration (EBUS-TBNA) were retrospectively analyzed. Results: Among the 4 cases, 2 were males and 2 were females, with the onset age of 7.4-9.2 years. The child who underwent successful EBUS-TBNA was presented with fever and diagnosed with mediastinal lymphadenopathy before the operation, and the postoperative pathology indicated histiocytic necrotic lymphadenitis (HNL). The other 3 children diagnosed with primary airway tumors, whose pre-operative CT imaging found no infiltration in extra-bronchial structures, had the masses resected through EBUS. According to postoperative pathological findings, two were diagnosed with mucoepidermoid carcinoma and one with bronchial leiomyoma. The lesions were located at the opening of the right main bronchus in 1 case and at the main airway in 2 cases. EBUS showed abnormal echogenicity of the tracheal wall in the 3 cases, including hyperechoic area in the water capsule and mucous layer, relatively hypoechoic area in the submucosal smooth muscle layer, hyperechoic area in the inner cartilage layer, hypoechoic in the cartilage layer and hyperechoic in the outer cartilage layer. In one case, structural disorder of the submucosal smooth muscle layer and partial disruption of the cartilage layer of the tracheal wall were found at the lesion site, while the other 2 cases had intact tracheal wall structure. There were no postoperative complications such as pneumothorax or hemoptysis in the 4 children. Conclusion: EBUS is a safe and feasible technique for evaluating mediastinal lymph node enlargement and the degree of airway wall infiltration in primary airway tumor.

In this work, a novel amino functionalized Cu(II) ion-imprinted organic-inorganic hybrid monolithic column (Cu(II)-IIHMC) was prepared via one-pot co-condensation and the combination of sol-gel and ion-imprinting techniques in a fused capillary. The Cu(II)-IIHMC was used as solid phase microextraction (SPME) matrix followed by inductively coupled plasma-mass spectrometry (ICP-MS) for the analysis of trace Cu(II). The prepared Cu(II)-IIHMC has good mechanical strength, stable imprinting sites and homogeneous structure of network skeleton with large flow-through pores by optimizing the synthesis process. Under the optimized conditions, the Cu(II)-IIHMC can selectively adsorb Cu(II) with the adsorption capacity of 3.13 mg g -1 . With enrichment factor of 10-fold, the calibration curve was established in the range of 0.05-50 μg L -1 with r 2 of 0.9992 and the detection limit was 0.008 μg L -1 for Cu(II). Compared with the non-imprinted hybrid monolithic column (Cu(II)-NIHMC), the Cu(II)-IIHMC possesses better selectivity, anti-interference ability and adsorption capacity. The Cu(II)-IIHMC can specifically capture the target ion in the presence of competitive ions, with the selectivity coefficients exceeding 39.4. The protocol was validated by analyzing Certified Reference Materials of standard sediment, soil and iron ore, and the results were in good agreement with certified values. Moreover, the proposed in-tube SPME procedure can not only preconcentrate trace Cu(II), but also effectively reduce the matrix effect and powerfully eliminate the interference from the main metals in real samples. Therefore, the developed SPME-ICP-MS method with facile preparation, specific selectivity, high sensitivity and efficient analysis, was applied in the determination of trace Cu(II) in environmental and mineral samples with the recoveries of 89.8-111.8% in all spiked samples., 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 © 2021 Elsevier B.V. All rights reserved.)

Biofilm formation represents a significant cause of concern as it has been associated with increased morbidity and mortality, thereby imposing a huge burden on public healthcare system throughout the world. As biofilms are usually resistant to various conventional antimicrobial interventions, they may result in severe and persistent infections, which necessitates the development of novel therapeutic strategies to combat biofilm-based infections. Physicochemical modification of the biomaterials utilized in medical devices to mitigate initial microbial attachment has been proposed as a promising strategy in combating polymicrobial infections, as the adhesion of microorganisms is typically the first step for the formation of biofilms. For instance, superhydrophobic surfaces have been shown to possess substantial anti-biofilm properties attributed to the presence of nanostructures. In this article, we provide an insight into the mechanisms underlying biofilm formation and their composition, as well as the applications of nanomaterials as superhydrophobic nanocoatings for the development of novel anti-biofilm therapies.

Background: This study evaluated maintenance treatment with niraparib, a potent inhibitor of poly(ADP-ribose) polymerase 1/2, in patients with platinum-sensitive recurrent ovarian cancer., Patients and Methods: In this phase III, double-blind, placebo-controlled study conducted at 30 centers in China, adults with platinum-sensitive recurrent ovarian cancer who had responded to their most recent platinum-containing chemotherapy were randomized 2 : 1 to receive oral niraparib (300 mg/day) or matched placebo until disease progression or unacceptable toxicity (NCT03705156). Following a protocol amendment, patients with a bodyweight <77 kg or a platelet count <150 × 10 3 /μl received 200 mg/day, and all other patients 300 mg/day, as an individualized starting dose (ISD). Randomization was carried out by an interactive web response system and stratified by BRCA mutation, time to recurrence following penultimate chemotherapy, and response to most recent chemotherapy. The primary endpoint was progression-free survival (PFS) assessed by blinded independent central review., Results: Between 26 September 2017 and 2 February 2019, 265 patients were randomized to receive niraparib (n = 177) or placebo (n = 88); 249 patients received an ISD (300 mg, n = 14; 200 mg, n = 235) as per protocol. In the intention-to-treat population, median PFS was significantly longer for patients receiving niraparib versus placebo: 18.3 [95% confidence interval (CI), 10.9-not evaluable] versus 5.4 (95% CI, 3.7-5.7) months [hazard ratio (HR) = 0.32; 95% CI, 0.23-0.45; P < 0.0001], and a similar PFS benefit was observed in patients receiving an ISD, regardless of BRCA mutation status. Grade ≥3 treatment-emergent adverse events occurred in 50.8% and 19.3% of patients who received niraparib and placebo, respectively; the most common events were neutrophil count decreased (20.3% versus 8.0%) and anemia (14.7% versus 2.3%)., Conclusions: Niraparib maintenance treatment reduced the risk of disease progression or death by 68% and prolonged PFS compared to placebo in patients with platinum-sensitive recurrent ovarian cancer. Individualized niraparib dosing is effective and safe and should be considered standard practice in this setting., Competing Interests: Disclosure MRM has received fees for serving on advisory boards from Tesaro, GSK, Clovis Oncology, AstraZeneca, and Zai Lab and speaker fees from AstraZeneca, Tesaro, GSK, Zai Lab, and Roche. The other authors have declared no conflicts of interest. Data sharing From the publication date, upon reasonable request to the corresponding author (researchers who provide a methodologically sound proposal and assuming use of the data to meet the goals of this proposal), individual participant data that underlie the results reported in this article (text, tables, and figures) can be made available after de-identification. The study protocol can also be made available with reasonable request., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Aim: The use of heparin and 0.9% saline solution is always controversial for central venous catheters. However, there is no systematic review or guideline about whether saline solution can replace heparin solution in adult cancer patients with totally implantable venous access ports (TIVAPs). The purpose of this review is to evaluate whether saline solution can replace heparin saline to lock TIVAPs., Methods: The following databases were searched: PubMed, the Cochrane Library, Web of Science, Embase, CINAHL and Ovid (January 1, 1982, and February 21, 2020). All statistical analyses of the meta-analysis were completed using the Review Manager 5.3., Results: A total of 201 studies were identified from these databases after initial review, and four studies met inclusion criteria, including 2652 cases. There was little heterogeneity among the included studies (I 2 < 30%), and all analyses were conducted by the fixed-effects model. The total complications, catheter occlusions, catheter-related bloodstream infections and other complication rates in the heparin solution group were higher than in the saline solution group. In the subgroup analysis of heparin concentration, total complication rates in the saline solution group were higher than with 50 U of heparin and lower than with 100 U of heparin. However, the differences in these complications were small, and no significant difference was observed (all P > 0.05)., Conclusions: Based on existing clinical studies, we recommend that saline solution can replace 50 or 100 U/ml of heparin as a safe and effective flush solution for TIVAPs., (© 2021 John Wiley & Sons Australia, Ltd.)

Background: Adding clomiphene citrate (CC) and/or letrozole (LE) to in vitro fertilization (IVF) cycles for mild ovarian stimulation is a general approach. Although lots of researches have demonstrated partial benefits of the strategy, all-around effects of oral medications remained deficient. This paper aims to assess whether an addition of oral medication will result in considerable outcomes on T-Gn (total dose of gonadotropin), Gn days, total retrieved ova, high quality embryos, blastocyst number, ovarian hyperstimulation syndrome (OHSS) rate, clinical pregnancy rate and cumulative pregnancy rate, even if it was not conventional mild/minimal stimulations., Results: Participants were categorized to three diverse populations as high responders, normal responders and poor responders according to basal antral follicle count. T-Gn in patients treated with CC/LE distinctly decreased from 2496.96 IU/d to 1827.68 IU/d, from 2860.28 IU/d to 2119.99 IU/d, and from 3182.15 IU/d to 1802.84 IU/d, respectively. For high ovary responders and normal responders, the OHSS incidence rate also declined from 29.2 to 4.3% (P < 0.001) and from 1.1 to 0.0% (P = 0.090). Other, there was no statistical difference with respect to the T-retrieved ova (total retrieved ova), high quality embryos, cultured blastocyst and blastocyst number in high responders. For normal responders and poor ovary responders, T-Gn, Gn days, T-retrieved ova, high quality embryos, cultured blastocyst and blastocysts number in oral medications group all apparently decreased. Clinical pregnancy rate per fresh cycle of poor responders with prior oral medications was significantly decreased (25.7% vs. 50.8%, P = 0.005), and no significant differences in high responders and normal responders were expressed (52.5% vs. 44.2%, P = 0.310; 51.9% vs. 42.4%, P = 0.163) between two groups of participants. The numbers of cumulative pregnancy rates were lower in the conventional group compared to the add group for high (75.90% versus 81.03%, P = 0.279), normal (62.69% versus 71.36%, P = 0.016) and poor (39.74% versus 68.21%, P < 0.001) responders., Conclusions: The addition of CC/LE to the ovulation induction during IVF has certain efficacy in terms of low cost, low OHSS incidence. CC/LE deserves more recommendations as a responsible strategy in high responders due to advantageous pregnancy outcomes. For normal responders, the strategy needs to be considered with more comprehensive factors.

Objective: To retrospectively analyze the clinical efficacy of external fixation in the treatment of femoral neck fracture with two different pin layout., Methods: From April 2000 to April 2018, 140 cases of femoral neck fracture were treated with closed reduction and percutaneous pin external fixation, among them 121 cases were followed up for more than 1 year, including 31 cases in traditional group, 12 males and 19 females, aged 45 to 74(65.4±8.4) years;90 cases in modified group, 39 males and 51 females, aged 12 to 75 (64.5±7.8) years. In traditional group, the first needle was put on the femoral talus, the second and third needles were put under the tension line, and the three needles were not on the same line in the lateral phase; in modified group, the first needle was drilled into the lateralcortex of the femur, obliquely penetrating the distal and proximal end of the femoral talus fracture, and the other two needles were drilled into the medial cortex of the femoral neck and the femoral talus, respectively. The operation time, hospital stay, postoperative ambulation time, femoral neck shortening rate, fracture healing time, fracture healing rate and femoral head necrosis rate of the two groups were observed and compared. Harris hip function score was used one year after operation., Results: These 121 patients were followed-up, the follow up time of traditional group was 13 to 45(30.5±11.4) months;the follow-up time of modified group was 14 to 120(34.5±12.5) months. There was no significant difference in operation time, hospital stay and femoral head necrosis rate between two groups ( P >0.05). There were significant differences between two groups in the time of going to the ground, shortening rate of femoral neck, fracture healing time, fracture healing rate and Harris functional score of the hip 1 year after operation ( P <0.05)., Conclusion: Compared with the traditional group, the modified group has the advantages of lower femoral neck shortening rate, shorter fracture healing time, higher fracture healing rate and higher Harris hip function score.

Background : Guan-Xin-Shu-Tong capsule (GXSTC) is a traditional Chinese medicine (TCM) that has been used to treat coronary heart disease (CHD) for many years in China. However, the holistic mechanism of GXSTC against CHD is still unclear. Therefore, the purpose of this paper was to systematically explore the mechanism of action GXSTC in the treatment of CHD rats using a metabolomics strategy. Methods : A CHD model was induced by ligation of the left anterior descending coronary artery (LAD). In each group, echocardiography was performed; the contents of creatine kinase (CK), lactate dehydrogenase (LDH) and aspartate transaminase (AST) in serum were determined; and the myocardial infarct size was measured. The metabolites in plasma were analyzed by UHPLC-MS/MS-based untargeted metabolomics. Then, multivariate statistical analysis was performed to screen potential biomarkers associated with the GXSTC treatment in the LAD-induced rat CHD model. Finally, the MetaboAnalyst 4.0 platform was used for metabolic pathway enrichment analysis. Results : GXSTC was able to regulate the contents of CK, LDH and AST; restore impaired cardiac function; and significantly reduce the myocardial infarction area in model rats. Twenty-two biomarkers and nine metabolic pathways of GXSTC in the treatment of CHD were identified through UHPLC-MS/MS-based untargeted metabolomics analysis. Conclusion : GXSTC regulates metabolic disorders of endogenous components in LAD-induced CHD rats. The anti-CHD mechanism of GXSTC is mainly related to the regulation of amino acid, lipid and hormonal metabolism. This study provides an overall view of the mechanism underlying the action of GXSTC against CHD., 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 © 2021 Wang, Shi, Ge, Wei, Liu, Wang, Zhou, Yang, Wang, Zhang, Zhu, Zhang, Li, Gong, Wu and Duan.)

Medical devices are indispensable in the healthcare setting, ranging from diagnostic tools to therapeutic instruments, and even supporting equipment. However, these medical devices may be associated with life-threatening complications when exposed to blood. To date, medical device-related infections have been a major drawback causing high mortality. Device-induced hemolysis, albeit often neglected, results in negative impacts, including thrombotic events. Various strategies have been approached to overcome these issues, but the outcomes are yet to be considered as successful. Recently, superhydrophobic materials or coatings have been brought to attention in various fields. Superhydrophobic surfaces are proposed to be ideal blood-compatible biomaterials attributed to their beneficial characteristics. Reports have substantiated the blood repellence of a superhydrophobic surface, which helps to prevent damage on blood cells upon cell-surface interaction, thereby alleviating subsequent complications. The anti-biofouling effect of superhydrophobic surfaces is also desired in medical devices as it resists the adhesion of organic substances, such as blood cells and microorganisms. In this review, we will focus on the discussion about the potential contribution of superhydrophobic surfaces on enhancing the hemocompatibility of blood-contacting medical devices.

On the basis of the previous work of the research group, the orthogonal design method was further used to optimize the processing technology for reducing toxicity of fried Tripterygium wilfordii in Lysimachia christinae Decoction. A total of 9 processed products of T.wilfordii in L.christinae decoction were prepared by four factors and three levels orthogonal design table. The contents of triptolide in T.wilfordii were determined by high performance liquid chromatography(HPLC) before and after processing: 4.27, 3.92, 3.57, 2.75, 2.42, 2.66, 3.51, 1.87, 1.75, 2.03 μg·g~(-1). On this basis, the above processed products were orally given to mice for 28 days. 12 hours after the last administration, food fasting except water was provided, and 24 hours later, the eyeballs were taken for blood and liver tissue. Serum biochemical indexes, liver lipid peroxidation and antioxidant related indexes were detected by kit method. Twenty-eight days after oral administration of raw T.wilfordii, the levels of serum alanine aminotransferase(AST), alanine aminotransferase(ALT), alkaline phosphatase(ALP) and liver malondialdehyde(MDA) in mice increased by 91%(P&lt;0.01), 46%(P&lt;0.05), 73%(P&lt;0.01) and 99%(P&lt;0.01), while the liver antioxidant indexes such as superoxide dismutase(SOD), glutathione(GSH), glutathione peroxidase(GPX) and glutathione-S transferase(GST) significantly decreased(P&lt;0.01). After administration of the processed products, the above indexes were significantly reversed(P&lt;0.01 or P&lt;0.05). Especially, the processing conditions of A&#95;3B&#95;2C&#95;1D&#95;3 had the best detoxification effect on T.wilfordii, which decreased the high levels of AST, ALT, ALP and MDA by 49%(P&lt;0.01), 32%(P&lt;0.01), 42%(P&lt;0.01), and 17%(P&lt;0.05). Therefore, the best processing conditions for T.wilfordii in L.christinae decoction were A&#95;3B&#95;2C&#95;1D&#95;3, namely &quot;15% mass fraction of L.christinae, 1 h moistening time, 160 ℃ frying temperature, and 9 min frying time&quot;.

Background: Xpert Bladder Cancer is a detection method developed in recent years, designed with the functions of integrating sample automatically, nucleic acid amplification, and target sequence detection. It is a urine assay targeting five mRNAs (CRH, IGF2, UPK1B, ANXA10, and ABL1). The purpose of this article is to review the accuracy of Xpert Bladder Cancer in the follow-up diagnosis of bladder cancer and evaluate the role of Xpert Bladder Cancer in detecting the recurrence of non-muscle-invasive bladder cancer in the round., Methods: In the database of Embase, PubMed, Web of Science, and Cochrane Library, the articles published up to October 13, 2020, were searched and screened based on the exclusion and inclusion criteria, and data were extracted from the included studies. The sensitivity, specificity, negative likelihood ratio, positive likelihood ratio summary of receiver operating characteristic curves, and diagnostic odds ratio were combined by the Meta-DiSc 1.4 software. The Stata 12.0 software was used to obtain the assessment of publication bias., Results: A total of 8 articles involving eight fourfold tables were finally identified. The pooled sensitivity and specificity of Xpert Bladder Cancer in the diagnosis of bladder cancer were 0.71 and 0.81, respectively. The positive likelihood ratio and negative likelihood ratio were 3.74 and 0.34, respectively. The area under the curve was 0.8407. The diagnostic odds ratio was 11.99. Deeks' funnel plot asymmetry test manifested no publication bias., Conclusions: In summary, Xpert Bladder Cancer presents high accuracy and specificity in monitoring bladder cancer compared with cystoscopy. More researches are still required to further confirm this conclusion.

Chimeric antigen receptor (CAR) T therapy represents a form of immune cellular therapy with clinical efficacy and a specific target. A typical chimeric antigen receptor (CAR) construct consists of an antigen binding domain, a transmembrane domain, and a cytoplasmic domain. Nanobodies have been widely applied as the antigen binding domain of CAR-T due to their small size, optimal stability, high affinity, and manufacturing feasibility. The nanobody-based CAR structure has shown a proven function in more than ten different tumor-specific targets. After being transduced in Jurkat cells, natural killer cells, or primary T cells, the resulting nanobody-based CAR-T or CAR-NK cells demonstrate anti-tumor effects both in vitro and in vivo. Interestingly, anti-BCMA CAR-T modulated by a single nanobody or bi-valent nanobody displays comparable clinical effects with that of single-chain variable fragment (scFv)-modulated CAR-T. The application of nanobodies in CAR-T therapy has been well demonstrated from bench to bedside and displays great potential in forming advanced CAR-T for more challenging tasks.

In the 21st century, enteric fever is still causing a significant number of mortalities, especially in high-risk regions of the world. Genetic studies involving the genome and transcriptome have revealed a broad set of candidate genetic polymorphisms associated with susceptibility to and the severity of enteric fever. This review attempted to explain and discuss the past and the most recent findings on human genetic variants affecting the progression of Salmonella typhoidal species infection, particularly toll-like receptor (TLR) 4, TLR5, interleukin (IL-) 4, natural resistance-associated macrophage protein 1 (NRAMP1), VAC14, PARK2/PACRG, cystic fibrosis transmembrane conductance regulator (CFTR), major-histocompatibility-complex (MHC) class II and class III. These polymorphisms on disease susceptibility or progression in patients could be related to multiple mechanisms in eliminating both intracellular and extracellular Salmonella typhoidal species. Here, we also highlighted the limitations in the studies reported, which led to inconclusive results in association studies. Nevertheless, the knowledge obtained through this review may shed some light on the development of risk prediction tools, novel therapies as well as strategies towards developing a personalised typhoid vaccine.

We explored the effects of drought stress on photosynthetic characteristics and non-structural carbohydrate (NSC) accumulation of the timberline tree species Betula ermanii in Changbai Mountain with a drought control experiment. The results showed that drought significantly reduced the net photosynthetic rate and stomatal conductance, but increased water use efficiency (WUE) of B. ermanii seedlings. Drought dramatically improved the contents of soluble sugar and total NSC in leaves, barks, stems, and roots of B. ermanii seedlings, but significantly reduced their starch content. The stomatal conductance, photosynthetic rate and WUE decreased rapidly as the drought continued, whereas the contents of soluble sugar, starch and NSC increased and then declined. At the end of the experiment, 90% of the leaves turned yellow, and the ratios of soluble sugar to starch in the stems, barks and roots under the drought treatment were significantly higher than those in the control. These results demonstrated that B. ermanii might be a drought-avoidance species that could reduce water loss by rapidly reducing stomatal conductance and improving WUE under drought stress. B. ermanii might have evolved priority storage strategy to cope with water deficit through improving the content of soluble sugar in organs and increasing the transformation rate between starch and sugar. With the extension of drought stress, seedlings tended to die, since water stress might exceed the threshold of the plant self-regulation capacity. However, the content of NSC in organs did not decrease, suggesting that the death of B. ermanii under drought stress might not be caused by carbon starvation.

Autotrophic carbon dioxide (CO 2 ) fixation by microbes is ubiquitous in the environment and potentially contributes to the soil organic carbon (SOC) pool. However, the multiple autotrophic pathways of microbial carbon assimilation and fixation in paddy soils remain poorly characterized. In this study, we combine metagenomic analysis with 14 C-labelling to investigate all known autotrophic pathways and CO 2 assimilation mechanisms in five typical paddy soils from southern China. Marker genes of six autotrophic pathways are detected in all soil samples, which are dominated by the cbbL genes (67%-82%) coding the ribulose-bisphosphate carboxylase large chain in the Calvin cycle. These marker genes are associated with a broad range of phototrophic and chemotrophic genera. Significant amounts of 14 C-CO 2 are assimilated into SOC (74.3-175.8 mg 14 C kg -1 ) and microbial biomass (5.2-24.1 mg 14 C kg -1 ) after 45 days incubation, where more than 70% of 14 C-SOC was concentrated in the relatively stable humin fractions. These results show that paddy soil microbes contain the genetic potential for autotrophic carbon fixation spreading over broad taxonomic ranges, and can incorporate atmospheric carbon into organic components, which ultimately contribute to the stable SOC pool., (© 2020 Society for Applied Microbiology and John Wiley & Sons Ltd.)

Objective: In order to elucidate the biological activity of the co-cultured adventitious roots (ARs) of Echinacea pallida and Echinacea purpurea and provide theoretical basis for its application, and the anti-inflammatory activities and potential mechanisms of co-cultured ARs were studied., Methods: The experimental materials were obtained by bioreactor co-culture technology and used in the activity research. In this study, mouse macrophages induced by lipopolysaccharide (LPS) were used as in vitro model. Different concentrations of AR extract (50-400 g/mL) were used to treat cells. The expression of pro-inflammatory cytokines was determined using enzyme linked immunosorbent assay. The inducible nitric oxide synthase and cyclooxygenase-2 expression, mitogen-activated protein kinase (MAPK) phosphorylation, and the inhibitor of nuclear factor-kappa B-α levels were determined by the Western blot analysis., Results: In the co-cultured ARs, total flavonoids and total caffeic acid were determined, and the contents of both bioactive compounds were significantly higher than those ARs from the single-species culture. Compared with the control group, the large amount of pro-inflammatory mediators was released after LPS stimulation. However, in the extract groups with different concentrations (25, 50, and 100 g/mL), the production of these pro-inflammatory mediators was inhibited in a dose-dependent manner. Furthermore, the levels of phosphorylation of MAPK proteins, including p-p38, p-c-Jun N-terminal kinase, and p-extracellular regulated protein kinases were significantly ( P  < 0.05) decreased in the extract groups, revealing that the AR extract probably involved in regulating the MAPK signaling pathway., Conclusion: Collectively, our findings suggested that the co-cultured ARs of E. pallida and E. purpurea can inhibit production of pro-inflammatory mediators in mouse peritoneal macrophages and possess the anti-inflammatory effect by regulating MAPK signaling pathways., Competing Interests: 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., (© 2021 Tianjin Press of Chinese Herbal Medicines. Published by ELSEVIER B.V.)

Aim: To compare the visual outcomes of children with small (≤3 mm) posterior polar cataracts (PPC) and posterior lenticonus who had cataract extraction surgery with the visual outcomes of those who were managed conservatively., Methods: Children who initially had small PPC and posterior lenticonus who were followed up over 1-year period were retrospective reviewed in the study. Patients receiving surgery were compared with those receiving conservative therapy. The axial length, keratometry, refraction, best-corrected visual acuity (BCVA), and strabismus measurements were recorded. Lens morphology, i.e. , the location, size, and depth of the cataract lesion, was measured with a Scheimpflug imaging system. To help control for baseline differences in the groups, patients were matched with controls by propensity score methodology., Results: The study evaluated 60 patients (30 in the surgery group and 30 in the conservative therapy group) after matching by propensity score. Patients who underwent cataract surgery showed greater BCVA improvements (0.36±0.24 logMAR) than patients who were treated without surgery (0.22±0.26 logMAR; P =0.036). Surgery was effective in patients with a rear projection length (RPL) less than 1.0 mm and a pretreatment BCVA worse than 0.52 logMAR., Conclusion: Children with small PPC and posterior lenticonus who undergo cataract surgery experience greater BCVA improvements than those managed conservatively. Certain patients presenting with a RPL less than 1.0 mm and a pretreatment BCVA of 0.52 logMAR or worse may benefit from surgery., (International Journal of Ophthalmology Press.)

Background: A number of studies have reported the association between dietary patterns and the risk of chronic kidney disease (CKD), however a consistent perspective hasn't been established to date. Herein, we conducted this systematic review and meta-analysis of observational studies to assess the association between dietary patterns and CKD., Methods: MEDLINE, EBSCO and references from eligible studies were searched for relevant articles published up to 9 May 2020 that examined the association of common dietary patterns and CKD. The heterogeneity among studies was assessed by Cochran's Q test and I 2 methods., Results: Seventeen eligible studies, involving 149,958 participants, were included in our systematic review and meta-analysis. The highest compared with the lowest category of healthy dietary pattern was significantly associated with a lower risk of CKD (OR=0.69; CI: 0.57, 0.84; P=0.0001). A higher risk of CKD was shown for the highest compared with the lowest categories of Western-type dietary pattern (OR=1.86; CI: 1.21, 2.86; P=0.005). There were evidence of a lower risk of CKD in the highest compared with the lowest categories of light-moderate drinking pattern (OR=0.76; CI: 0.71, 0.81; P< 0.0001) and heavy drinking pattern (OR=0.67; CI: 0.56, 0.80; P< 0.0001)., Conclusions: The results of this systematic review and meta-analysis show that a healthy dietary pattern and alcohol drinking were associated with lower risk of CKD, whereas a Western-type dietary pattern was associated with higher risk of CKD.

Background: With the development of radiological technologies, radiotherapy has been gradually widely used in the clinic to intracranial tumours and become standardised. However, the related central nervous system disorders are still the most obvious complications after radiotherapy. This study aims to quantify the effectiveness of anlotinib, a small molecule inhibitor of multiple receptor tyrosine kinases, in mitigating acute phase of radiation-induced brain injury (RBI) in a mouse model., Methods: The onset and progression of RBI were investigated in vivo. All mice, (except for the sham group) were irradiated at a single-fraction of 20 Gy and treated with different doses of anlotinib (0, 0.2 and 0.8 mg/kg, respectively). The expression levels of glial fibrillary acidic protein (GFAP), hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF), and phosphorylated vascular endothelial growth factor receptor-2 (p-VEGFR2) were assessed by western blot. Histological changes were identified by luxol fast blue (LFB) staining., Results: The expression levels of GFAP, HIF-1α, and VEGF were downregulated following treatment with anlotinib. However, anlotinib failed to inhibit the development of demyelination. Cerebral edema [as measured by brain water content (BWC)] was also mitigated following treatment with anlotinib., Conclusions: In summary, treatment with anlotinib significantly mitigated the adverse effects of acute RBI in a dose-dependent manner by downregulating the activation of astrocytes, improving brain hypoxia, and alleviating cerebral edema.

Astragaloside (AST) is derived from the Chinese herb Astragalus membranaceus, and studies have demonstrated that it promotes differentiation of bone marrow‑derived mesenchymal stem cells (BMSCs). To the best of our knowledge, however, the functions of the component AST‑IV in osteogenesis have not previously been elucidated. The present study aimed to verify the effects of AST‑IV in osteogenesis. First, the proliferation and differentiation status of human BMSCs incubated with AST‑IV were analysed and compared with a control (no AST‑IV treatment). In order to determine the involvement of the glycogen synthase kinase (GSK)3β signalling pathway in AST‑IV, overexpression and inhibition of GSK3β was induced during incubation of BMSCs with AST‑IV. In order to investigate how neuronal growth factor (NGF) contributes to BMSCs differentiation, BMSCs were co‑incubated with an anti‑NGF antibody and AST IV, and then levels of osteogenesis markers were assessed. The results demonstrated for the first time that AST‑IV contributed to BMSCs differentiation. Furthermore, the GSK3β/β‑catenin signalling pathway was revealed to be involved in AST‑IV‑induced osteogenesis; moreover, AST‑IV accelerated differentiation by enhancing the expression levels of NGF. In summary, the present study demonstrated that AST‑IV promotes BMSCs differentiation, thus providing a potential target for the treatment of osteoporosis.

Our previous study found that mutations in the PTGIS gene contributed high susceptibility to pulmonary arterial hypertension (PAH). We have generated disease-specific induced pluripotent stem cell (iPSC) lines from a PAH patient carrying the heterozygous c.1339 G > A mutation in PTGIS gene. The generated iPSC lines can be differentiated into endothelial cells to investigate the pathogenesis of PAH associated with PTGIS gene, which could provide valuable resources for personalized medicine., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

With the advent of wearable microelectronic devices in the interdisciplinary bio-electronics research field, synaptic devices with capability of neuromorphic computing are attracting more and more attention as the building blocks for the next generation computing structure. Conventional flash-like synaptic transistors are built on rigid solid-state substrates, and the inorganic materials and the high-temperature processing steps have severely limited their applications in various flexible electronic devices and systems. Here, flexible organic flash-like synaptic devices have been fabricated on a flexible substrate with the organic C8-BTBT as the conducting channel. The device exhibits a memory window greater than 20 V and excellent synaptic functions including short/long-term synaptic plasticity and spike-timing-dependent plasticity. In addition, even under the bending condition (7 mm bending radius), the transistor can still stably achieve a variety of synaptic functions. This work shows that low-temperature processing technology with the integration of organic materials can pave a promising pathway for the realization of flexible synaptic systems and the future development of wearable electronic devices.

Objective: The aim of this study was to explore the regulatory effect of micro ribonucleic acid (miR)-20a on nuclear factor-κB (NF-кB) in liver cancer Huh-7 cells, and to elucidate its influence on the chemosensitivity of Huh-7 cells., Materials and Methods: Huh-7 cells with overexpression of miR-20a or knockout of miR-20a were first constructed. Quantitative polymerase chain reaction (qPCR) was adopted to detect the expression level of miR-20a in each group of cells. The sensitivity of cells to cisplatin and doxorubicin in each group was measured using methyl thiazolyl tetrazolium (MTT) assay, and the 50% inhibitory concentration (IC50) was calculated. Hoechst 33258 staining was performed to detect the apoptosis of cells in each group. Furthermore, the expression levels of apoptosis-associated proteins and the NF-кB signaling pathway-related proteins in each group of cells were determined via Western blotting., Results: The expression level of miR-20a in blank control group was considerably higher than that in knockout group (p<0.01). Meanwhile, cells in overexpression group exhibited a notably higher expression level of miR-20a than blank control group (p<0.01). Cells in knockout group had dramatically enhanced sensitivity to doxorubicin and cisplatin (p<0.01), with a prominently decreased IC50 value (p<0.01). However, cells in overexpression group exhibited remarkably weakened sensitivity (p<0.01) and increased IC50 value (p<0.01). After treatment with doxorubicin and cisplatin, the apoptosis level of cells rose substantially in knockout group (p<0.01), whereas declined significantly in overexpression group (p<0.01). Moreover, knockout group exhibited a notably elevated expression level of Caspase-3 (p<0.01), and a considerably decreased ratio of B-cell lymphoma 2 (Bcl-2)/Bcl-2 associated X protein (Bax) (p<0.01). The expression level of Caspase-3 declined remarkably (p<0.01), however, the ratio of Bcl2/Bax increased substantially (p<0.01) in overexpression group. The expression level of NF-кB inhibitor beta (NF-кBIB) was markedly up-regulated (p<0.01), while the expression levels of Livin and Survivin declined remarkably (p<0.01) in knockout group. Furthermore, overexpression group had a considerably decreased expression level of NF-кBIB (p<0.01), but notably increased expression levels of Livin and Survivin (p<0.01)., Conclusions: MiR-20a up-regulates the expressions of the downstream proteins Livin and Survivin, decreases the expressions of apoptosis-associated proteins, weakens the sensitivity of cells to chemotherapy drugs and lowers the apoptosis level of cells by activating the NF-кB signaling pathway in liver cancer Huh-7 cells.

Objective: To investigate the value of optic disc retinal nerve fiber layer (RNFL) thickness in the diagnosis of diabetic peripheral neuropathy (DPN)., Methods: Ninety patients with type 2 diabetes, including 60 patients without DPN (NDPN group) and 30 patients with DPN (DPN group), and 30 healthy participants (normal group) were enrolled. Optical coherence tomography (OCT) was used to measure the four quadrants and the overall average RNFL thickness of the optic disc. The receiver operator characteristic curve was drawn and the area under the curve (AUC) was calculated to evaluate the diagnostic value of RNFL thickness in the optic disc area for DPN., Results: The RNFL thickness of the DPN group was thinner than those of the normal and NDPN groups in the overall average ((101.07± 12.40) µm vs. (111.07±6.99) µm and (109.25±6.90) µm), superior quadrant ((123.00±19.04) µm vs. (138.93±14.16) µm and (134.47±14.34) µm), and inferior quadrant ((129.37±17.50) µm vs. (143.60±12.22) µm and (144.48±14.10) µm), and the differences were statistically significant. The diagnostic efficiencies of the overall average, superior quadrant, and inferior quadrant RNFL thicknesses, and a combined index of superior and inferior quadrant RNFL thicknesses were similar, and the AUCs were 0.739 (95% confidence interval (CI) 0.635-0.826), 0.683 (95% CI 0.576-0.778), 0.755 (95% CI 0.652-0.840), and 0.773 (95% CI 0.672-0.854), respectively. The diagnostic sensitivity of RNFL thickness in the superior quadrant reached 93.33%., Conclusions: The thickness of the RNFL in the optic disc can be used as a diagnostic method for DPN.

Background: PEGylated granulocyte colony-stimulating factor (G-CSF) is a safe alternative to G-CSF to improve chemotherapy-induced neutropenia (CIN). This superiority has resulted in its increased use by physicians; however, the superiority of PEGylated G-CSF for CIN in breast cancer has not been conclusively determined., Objectives: To assess the superiority of PEGylated G-CSF for CIN in breast cancer in terms of effectiveness and safety via a systematic review and meta-analysis., Methods: A literature search in PubMed, Embase, Cochrane Library, and Web of Science was performed for eligible studies published from database inception to December 2019. All studies comparing PEGylated G-CSF and G-CSF for CIN of breast cancer were reviewed. After literature selection, data extraction and quality assessment were performed by two reviewers independently. Meta-analysis was conducted using Revman, version 5.2., Results: Nine randomized controlled trials were finally identified. The publication bias of these studies was acceptable. For the endpoint of effectiveness, analysis of the incidence/duration of grade ≥ 3 neutropenia, the duration of grade 4 neutropenia, the incidence of febrile neutropenia (FN), and the time to absolute neutrophil count recovery showed no advantage of PEGylated G-CSF over G-CSF for CIN of breast cancer (P > 0.05), with the premise of a sufficient dose of G-CSF according to the guidelines. No significant differences in grade 4 adverse events were observed between the groups (P = 0.29), and PEGylated G-CSF did not increase the incidence of skeletal and/or muscle pain compared with G-CSF (P = 0.32)., Conclusion: PEGylated G-CSF was as effective and safe as G-CSF to reduce CIN in breast cancer but did not show an obvious superiority. However, in clinical practice, PEGylated G-CSF has an obvious advantage in terms of convenience, which could improve patient's quality of life.

Aim: To compare the efficacy, safety, and tolerability of abemaciclib plus endocrine therapy (ET) versus ET alone in postmenopausal women with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer (ABC) from China, Brazil, India, and South Africa., Methods: This randomized, double-blind, phase III study was conducted between 9 December 2016 and 29 March 2019. Postmenopausal women with HR-positive, HER2-negative ABC with no prior systemic therapy in an advanced setting (cohort A) or progression on prior ET (cohort B) received abemaciclib (150 mg twice daily) or placebo plus: anastrozole (1 mg/day) or letrozole (2.5 mg/day) (cohort A) or fulvestrant (500 mg per label) (cohort B). The primary endpoint was progression-free survival (PFS) in cohort A, analyzed using the stratified log-rank test. Secondary endpoints were PFS in cohort B (key secondary endpoint), objective response rate (ORR), and safety. This interim analysis was planned after 119 PFS events in cohort A., Results: In cohort A, 207 patients were randomly assigned to the abemaciclib arm and 99 to the placebo arm. Abemaciclib significantly improved PFS versus placebo (median: not reached versus 14.7 months; hazard ratio 0.499; 95% confidence intervals (CI) 0.346-0.719; p  = 0.0001). ORR was 65.9% in the abemaciclib arm and 36.1% in the placebo arm ( p  < 0.0001, measurable disease population). In cohort B, 104 patients were randomly assigned to the abemaciclib arm and 53 to the placebo arm. Abemaciclib significantly improved PFS versus placebo (median: 11.5 versus 5.6 months; hazard ratio 0.376; 95% CI 0.240-0.588; p  < 0.0001). ORR was 50.0% in the abemaciclib arm and 10.5% in the placebo arm ( p  < 0.0001, measurable disease population). The most frequent grade ⩾3 adverse events in the abemaciclib arms were neutropenia, leukopenia, and anemia (both cohorts), and lymphocytopenia (cohort B)., Conclusion: The addition of abemaciclib to ET demonstrated significant and clinically meaningful improvement in PFS and ORR, without new safety signals observed in this population. Trial Registration: ClinicalTrials.gov identifier: NCT02763566., Competing Interests: Conflict of interest: RBH, YL and HDC are employees and minor shareholders of Eli Lilly and Company. XHW has received research funding from Eli Lilly and Company. QYZ, TS, YMY, HPL, MY, ZST, CPO, YPL, RC, ML, YC, QCO, XC, NL, XJW, JFF, RH, GBK, MAC-P, ZJ and XCH have no conflicts of interest to declare., (© The Author(s), 2020.)

Background: Deep dead space may be thought as an independent risk factor of the poor infection control after flap reconstruction in complex limb wounds. But it can be easily neglected. The conventional skin flap and musculocutaneous flap are difficult to obliterate the deep dead space in irregular shape effectively. It was investigated that the clinical application of chimeric anterolateral thigh perforator flap in the treatment of complex wounds complicated with deep dead space of the extremities in the paper., Methods: Fifty-six cases complicated with deep dead space wounds were registered in group. Following thorough debridement and treatment with VSD, the granulation tissues grew with well-controlled infection. And then the chimeric anterolateral thigh perforator flap was used to obliterate the deep dead space and repair the wounds. The postoperative flap survival and infection conditions were evaluated., Results: Overall, the infection was effectively controlled, without persistent exudation or sinus tract formation after wound healing. While 5 cases lost to follow-up, the remaining 51 cases were followed up until 15 months on average. Generally, the affected extremities recovered satisfactorily with normal appearances and texture of the flaps, along with normal functions. Importantly, no recurrence of infection was observed., Conclusion: During the grafting of chimeric perforator flap pedicled with lateral thigh muscle flap, the muscle flap is recommended to obliterate the deep dead space while the skin flap is being used to cover the wound. The combination of these two technologies performed well in the repair and reconstruction of the complex wounds of the extremities, possessing potential for broader clinical application.

To elucidate potential roles of UDP-glucose pyrophosphorylase (UGP) in mycelial growth and polysaccharide synthesis of Grifola frondosa, a putative 2036-bp UDP-glucose pyrophosphorylase gene gfugp encoding a 53.17-kDa protein was cloned and re-annotated. Two dual promoter RNA silencing vectors of pAN7-iUGP-P-dual and pAN7-iUGP-C-dual were constructed to down-regulate gfugp expression by targeting its promoter or conserved functional sequences, respectively. Results showed that silence of gfugp promoter sequence had a higher down-regulating efficiency with slower mycelial growth and polysaccharide production than those of conserved sequence. The monosaccharide compositions/percentages of mycelial and exo-polysaccharides significantly changed with the increase of galactose and arabinose contents possibly due to block of UDP-glucose supply by gfugp silence and alteration of sugar metabolism via up-regulation of UDP-glucose-4-epimerase (gfuge) and UDP-xylose-4-epimerase (gfuxe) transcription. Our findings would provide a reference to know the biosynthesis pathway of mushroom polysaccharides and improve their production by metabolic regulation., Competing Interests: Declaration of competing interest All authors declare that they have no conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objective: To observe the preventive effect of medicated plaster at Dazhui (GV 14) on preventing perioperative hypothermia in patients undergoing plasmakinetic resection of prostate (PKRP) and ureteroscopic laser lithotripsy., Methods: A total of 300 patients with ASA gradeⅠorⅡreceiving ureteroscopic laser lithotripsy or PKRP under total intravenous anesthesia (TIVA) were randomly divided into an observation group and a control group, 150 cases in each group. The patients in the control group received routine heat preservation measures, while on the basis of the control group, the patients in the observation group were treated with medicated plaster at Dazhui (GV 14) 30 min before operation. The temperature (ear temperature), mean arterial pressure (MAP), heart rate and blood oxygen saturation (SpO 2 ) at each time point (resting state before operation, 5, 10 min into operation, at the end of operation, 5 and 10 min after operation) were recorded; the number of hypothermia, the classification of postoperative shivering degree, operation time, propofol dosage, intraoperative infusion volume and intraoperative flushing fluid volume were recorded., Results: The temperature at 5 and 10 min into operation as well as at the end of operation in the two groups was all lower than that before operation and at previous time point ( P <0.01). The temperature at 5 and 10 min after operation in the two groups was all higher than that at previous time point ( P <0.01), but still lower than that before operation ( P <0.01). The temperature at 10 min into operation, at the end of operation, 5 and 10 min after operation in the observation group was higher than that in the control group ( P <0.01, P <0.05). The total incidence rate of hypothermia in the observation group was 2.0% (3/150), which was significantly lower than 13.3% (20/150) in the control group ( P <0.01). The total incidence rate of shivering was 18.0% (27/150) in the observation group and 28.7% (43/150) in the control group ( P >0.05)., Conclusion: The medicated plaster at Dazhui (GV 14) can effectively prevent perioperative hypothermia and improve comfort in patients undergoing PKRP and ureteroscopic laser lithotripsy.

Neonatal calvarial bone has been widely used for investigating the biological behaviour of intramembranous bones. This work evaluated the bone formation of neonatal calvarial bone by microcomputed tomography (micro-CT) and histomorphometry. Moreover, the viability of neonatal calvarial bone and the effect of micro-CT radiation exposure on neonatal calvarial bone viability were investigated. The calvarial bones of 4-day-old CD-1 mice were cultured in Dulbecco's modified Eagle's medium (DMEM) or osteogenic medium (OM) for 23 days. Micro-CT scanning and histological analysis were performed on days 2, 9, 16 and 23. An "OM-control" group was scanned only on days 2 and 23 to evaluate the effect of a single micro-CT radiation dose on calvarial bones. Histomorphometric measurements revealed that the number of osteoblasts per unit bone surface area (N. Ob/BS, /mm 2 ) (days 9, 16 and 23) and the number of osteoclasts per unit bone surface area (N. Oc/BS, /mm 2 ) (days 9 and 16) were higher and lower, respectively, in the OM group than in the DMEM group. Moreover, the calvarial bone survived for at least 16 days in vitro, as indicated by tartrate-resistant acid phosphatase (TRAP)-positive staining. Micro-CT assessment revealed that the bone surface (BS), bone volume (BV), bone surface density (BS/TV(Tissue volume)) and percent bone volume (BV/TV) were greater in the OM group than in the DMEM group except at baseline on day 2. All bone parameters of calvariae cultured in OM and OM-control conditions were not significantly different on days 2 and 23. Thus, the radiation dose from micro-CT in our study design had no perceptible effect on the formation of mouse calvarial bone in vitro., (Copyright © 2020 Elsevier GmbH. All rights reserved.)

Skeletal muscle atrophy is a common and serious complication of chronic kidney disease (CKD). Oxidative stress and autophagy are the primary molecular mechanisms involved in muscle atrophy. Calycosin, a major component of Radix astragali, exerts anti-inflammatory, anti-oxidative stress and anti-autophagy effects. We investigated the effects and mechanisms of calycosin on skeletal muscle atrophy in vivo and in vitro. 5/6 nephrectomy (5/6 Nx) rats were used as a model of CKD. We evaluated bodyweight and levels of serum creatinine (SCr), blood urea nitrogen (BUN) and serum albumin (Alb). H&E staining, cell apoptosis, oxidative stress biomarkers, autophagosome and LC3A/B levels were performed and evaluated in skeletal muscle of CKD rat. Calycosin treatment improved bodyweight and renal function, alleviated muscle atrophy (decreased the levels of MuRF1 and MAFbx), increased superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activity and reduced malondialdehyde (MDA) levels in skeletal muscle of CKD rats. Importantly, calycosin reduced autophagosome formation, down-regulated the expression of LC3A/B and ATG7 through inhibition of AMPK and FOXO3a, and increased SKP2, which resulted in decreased expression of CARM1, H3R17me2a. Similar results were observed in C2C12 cells treated with TNF-α and calycosin. Our findings showed that calycosin inhibited oxidative stress and autophagy in CKD induced skeletal muscle atrophy and in TNF-α-induced C2C12 myotube atrophy, partially by regulating the AMPK/SKP2/CARM1 signalling pathway., (© 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Background and Aims: Research evidence supports a positive link between sugar-containing soft beverages and hyperuricemia. However, data thus far are mostly from Caucasian populations. And in sugar-containing soft beverages overall, sugar-containing carbonated beverages are purchased most often. Therefore, we investigated whether the high consumption of sugar-containing carbonated beverages was associated with the prevalence of hyperuricemia among adults in China., Methods and Results: A cross-sectional study was conducted with 25,507 adults (13,013 men and 12,494 women) in Tianjin, China. Sugar-containing carbonated beverages intake was assessed by a validated semi-quantitative food frequency questionnaire. Hyperuricemia was defined as serum uric acid levels ≥7.0 mg/dL in men and ≥ 6 mg/dL in women. The association between carbonated beverages consumption and hyperuricemia was assessed by multiple logistic regression analysis. The prevalence of hyperuricemia in men and women was 23.4% and 8.2%, respectively. After adjustments for potential confounding factors, the odds ratios (95% confidence interval) for hyperuricemia across sugar-containing carbonated beverages consumption were 1.00 (reference) for almost never, 1.18 (1.05, 1.32) for <1-3 cups/week, 1.49 (1.25, 1.77) for ≥4 cups/week in men (P for trend < 0.005) and 1.11 (0.91, 1.34) for <1-3 cups/week (P for trend = 0.27), 1.70 (1.23, 2.31) for ≥4 cups/week in women (P for trend < 0.001), respectively., Conclusions: This cross-sectional survey demonstrated that increased consumption of sugar-containing carbonated beverages is associated with hyperuricemia among adults in China. Restricted sugar-containing carbonated beverages intake might be beneficial to the prevention of hyperuricemia in the general population., Competing Interests: Declaration of Competing Interest None of the authors has any potential conflict of interest., (Copyright © 2020. Published by Elsevier B.V.)

Rationale: Coronavirus disease 2019 (COVID-19) was first announced in Wuhan, and has rapidly evolved into a pandemic. However, the risk factors associated with the severity and mortality of COVID-19 are yet to be described in detail. Methods: We retrospectively reviewed the information of 1525 cases from the Leishenshan Hospital in Wuhan. Univariate and multivariate Cox regression analyses were generated to explore the relationship between procalcitonin (PCT) level and the progression and prognosis of COVID-19. Univariate and multivariate logistic regression analyses were performed to explore the relationship between disease severity in hospitalized patients and their PCT levels. Survival curves and the cumulative hazard function for COVID-19 progression were conducted in the two groups. To further detect the relationship between the computed tomography score and survival days, curve-fitting analyses were performed. Results: Patients in the elevated PCT group had a higher incidence of severe and critical severity conditions ( P < 0.001), death, and higher computed tomography (CT) scores. There was an association between elevated PCT levels and mortality in the univariate ((hazard ratio [1], 3.377; 95% confidence interval [2], 1.012-10.344; P = 0.033) and multivariate Cox regression analysis (HR, 4.933; 95% CI, 1.170-20.788; P = 0.030). Similarly, patients with elevated PCT were more likely to have critically severe disease conditions in the univariate (odds ratio [2], 7.247; 95% CI, 3.559-14.757; P < 0.001) and multivariate logistic regression analysis (OR, 10.679; 95% CI, 4.562-25.000; P < 0.001). Kaplan-Meier curves showed poorer prognosis for patients with elevated PCT ( P = 0.024). The CT score 1 for patients with elevated PCT peaked at day 40 following the onset of symptoms then decreased gradually, while their total CT score was relatively stable. Conclusion: PCT level was shown as an independent risk factor of in-hospital mortality among COVID-19 patients. Compared with inpatients with normal PCT levels, inpatients with elevated PCT levels had a higher risk for overall mortality and critically severe disease. These findings may provide guidance for improving the prognosis of patients with critically severe COVID-19., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Background: This is the first randomised controlled trial for assessment of the immunogenicity and safety of a candidate non-replicating adenovirus type-5 (Ad5)-vectored COVID-19 vaccine, aiming to determine an appropriate dose of the candidate vaccine for an efficacy study., Methods: This randomised, double-blind, placebo-controlled, phase 2 trial of the Ad5-vectored COVID-19 vaccine was done in a single centre in Wuhan, China. Healthy adults aged 18 years or older, who were HIV-negative and previous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection-free, were eligible to participate and were randomly assigned to receive the vaccine at a dose of 1 × 10 11 viral particles per mL or 5 × 10 10 viral particles per mL, or placebo. Investigators allocated participants at a ratio of 2:1:1 to receive a single injection intramuscularly in the arm. The randomisation list (block size 4) was generated by an independent statistician. Participants, investigators, and staff undertaking laboratory analyses were masked to group allocation. The primary endpoints for immunogenicity were the geometric mean titres (GMTs) of specific ELISA antibody responses to the receptor binding domain (RBD) and neutralising antibody responses at day 28. The primary endpoint for safety evaluation was the incidence of adverse reactions within 14 days. All recruited participants who received at least one dose were included in the primary and safety analyses. This study is registered with ClinicalTrials.gov, NCT04341389., Findings: 603 volunteers were recruited and screened for eligibility between April 11 and 16, 2020. 508 eligible participants (50% male; mean age 39·7 years, SD 12·5) consented to participate in the trial and were randomly assigned to receive the vaccine (1 × 10 11 viral particles n=253; 5 × 10 10 viral particles n=129) or placebo (n=126). In the 1 × 10 11 and 5 × 10 10 viral particles dose groups, the RBD-specific ELISA antibodies peaked at 656·5 (95% CI 575·2-749·2) and 571·0 (467·6-697·3), with seroconversion rates at 96% (95% CI 93-98) and 97% (92-99), respectively, at day 28. Both doses of the vaccine induced significant neutralising antibody responses to live SARS-CoV-2, with GMTs of 19·5 (95% CI 16·8-22·7) and 18·3 (14·4-23·3) in participants receiving 1 × 10 11 and 5 × 10 10 viral particles, respectively. Specific interferon γ enzyme-linked immunospot assay responses post vaccination were observed in 227 (90%, 95% CI 85-93) of 253 and 113 (88%, 81-92) of 129 participants in the 1 × 10 11 and 5 × 10 10 viral particles dose groups, respectively. Solicited adverse reactions were reported by 183 (72%) of 253 and 96 (74%) of 129 participants in the 1 × 10 11 and 5 × 10 10 viral particles dose groups, respectively. Severe adverse reactions were reported by 24 (9%) participants in the 1 × 10 11 viral particles dose group and one (1%) participant in the 5 × 10 10 viral particles dose group. No serious adverse reactions were documented., Interpretation: The Ad5-vectored COVID-19 vaccine at 5 × 10 10 viral particles is safe, and induced significant immune responses in the majority of recipients after a single immunisation., Funding: National Key R&D Programme of China, National Science and Technology Major Project, and CanSino Biologics., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

The spontaneous formation of discrete spherical nanosized molecules is ubiquitous in nature; however, the actual structural imitation of such high-symmetry polyhedra from the edge sharing of regular polygons has still proved to be elusive. Herein, two high-nuclearity metal clusters, namely (TTB) 4 ·M 26 Br 38 (M = Cu ( 1 ), Ag ( 2 ), TTB·Br 3 = 1, 3, 5-tris(triethylammoniomethyl)benzene tribromide), have been rationally and solvothermally synthesized and structurally characterized. Single-crystal X-ray analysis confirmed that 1 has I 4̅3 m symmetry with a (Cu 25 Br 34 ) 12- anion shell enwrapping a CuBr 4 tetrahedron and 2 has I 4̅3 m symmetry with a [Ag 26 Br 34 ] 12- anion shell enwrapping a Br 4 pyramid. The diffuse-reflectance UV-vis measurements showed that both compounds possess proper semiconductor behaviors with tunable band gaps of 1.87 eV for 1 and 1.90 eV for 2 . Interestingly, all the samples feature distinct adsorption speed and compound 1 shows good adsorption activity for methyl orange (MO) under the same reaction conditions. The effects of pH, temperature, and cyclicity on dye adsorption, together with the thermal stabilities and luminescence properties of the compounds, were also studied. From the cyclic adsorption of compound 1 to the anionic dye MO, it was found that the adsorption of MO was good over three cycles, and the third adsorption rate was still 93.90%.

Understanding and controlling charge transport across multiple parallel molecules are fundamental to the creation of innovative functional electronic components, as future molecular devices will likely be multimolecular. The smallest possible molecular ensemble to address this challenge is a dual-molecule junction device, which has potential to unravel the effects of intermolecular crosstalk on electronic transport at the molecular level that cannot be elucidated using either conventional single-molecule or self-assembled monolayer (SAM) techniques. Herein, we demonstrate the fabrication of a scanning tunneling microscopy (STM) dual-molecule junction device, which utilizes noncovalent interactions and allows for direct comparison to the conventional STM single-molecule device. STM-break junction (BJ) measurements reveal a decrease in conductance of 10% per molecule from the dual-molecule to the single-molecule junction device. Quantum transport simulations indicate that this decrease is attributable to intermolecular crosstalk (i.e., intermolecular π-π interactions), with possible contributions from substrate-mediated coupling (i.e., molecule-electrode). This study provides the first experimental evidence to interpret intermolecular crosstalk in electronic transport at the STM-BJ level and translates the experimental observations into meaningful molecular information to enhance our fundamental knowledge of this subject matter. This approach is pertinent to the design and development of future multimolecular electronic components and also to other dual-molecular systems where such crosstalk is mediated by various noncovalent intermolecular interactions (e.g., electrostatic and hydrogen bonding).

Background: Shen Gui capsule (SGC) is a new national drug in China that is widely used in clinical practice and has significant therapeutic effects on coronary heart disease (CHD). However, its active ingredients and mechanism of action for treating coronary heart disease remain unknown. Therefore, the purpose of this paper is to systematically explore the mechanism and efficacy of SGC in the "multicomponent-multitarget- multipathway" treatment for CHD using network pharmacology technology., Methods: The potential active ingredients of SGC were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and screened by pharmacokinetic parameters. Their possible targets were predicted using the TCMSP and DrugBank database. The CHD-related targets were identified from Comparative Toxicogenomics Database (CTD), UniProt, and PharmGKB database. The compound-target-disease network was constructed using Cytoscape for visualization. Additionally, the protein functional annotation and identification of signaling pathways of potential targets were performed by Gene Ontology (GO) and KEGG enrichment analysis using the Metascape platform., Results: The 61 active ingredients of SGC were found to regulate neuroactive ligand-receptor interaction, fluid shear stress and atherosclerosis, estrogen signaling pathway and other pathways through 62 targets. SGC is involved in regulating the circulatory system, nervous system and immune system and other aspects of the body, and thus plays a significant role in the treatment of CHD and its complications, showing the mechanism of SGC's "multicomponent, multitarget, and multipathway" prevention and treatment of CHD. In addition, three predictive components were first found to have potential biological activity by this method., Conclusion: The studies we have performed successfully predict the effective components and potential targets of SGC in the prevention and treatment of CHD, which helped to systematically clarify its mechanism of action and provided a direction for future research on the modern mechanism of SGC in the treatment of CHD., Competing Interests: Declaration of competing interest There is no conflict of interest declared., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Sharp eyespot, caused by Rhizoctonia cerealis , has become one of the most severe diseases affecting global wheat production in recent decades. Quick and efficient screening methods are required to accelerate the development of cultivars for sharp eyespot resistance in wheat breeding. Here, a two-step colonized wheat kernels (TSCWK) method for the inoculation and classification of sharp eyespot resistance in seedlings was established in a greenhouse. After preliminary verification of the reliability of the method in two replicates, 196 wheat cultivars were assessed for sharp eyespot resistance, and significant correlations were identified among the four replicates ( r = 0.78 to 0.84; P < 0.01). Furthermore, the 196 cultivars were scored for sharp eyespot resistance at the milk-ripe stage using traditional toothpick inoculation in the field. Correlation and linear regression analysis showed that the application of this approach at the seedling stage showed good consistency with the traditional field method. Moreover, the scoring of 442 cultivars using the TSCWK method indicated that most cultivars from the Huanghuai valley were susceptible to R. cerealis , suggesting an urgent need to improve sharp eyespot resistance in this region. Additionally, the relative resistance index of sharp eyespot decreased in the surveyed cultivars of the region with time. This study offers a rapid and effective approach for the identification of wheat sharp eyespot resistance and provides valuable germplasm for improving sharp eyespot resistance in wheat breeding.

Different responsive abilities of different types of eels (cultured, cultured feminized, and wild silver eels) during artificial maturation are recognized, and maturity status at the beginning of artificial maturation might be important. Maturity may represented by the distribution pattern of oocyte diameters. Androgens have been demonstrated to stimulate ovarian development in eels. To determine the initial status, operations were performed on eels to identify sex and to sample ovarian tissue. The recovered eels were then treated with 17α-methyltestosterone (17MT), and the responses of individual eels to 17MT were determined by the fold change in the mean oocyte diameter before and after treatment. Sampled ovarian tissues were fixed in Bouin's solution, oocytes were isolated, and the diameter of isolated oocytes was measured. The ovarian status, determined by kernel density estimation (KDE), was presented by the probability density of measured oocyte diameters; compared with histograms, a description method, KDE, provided more subtle information on the investigated ovary. Our data indicated a correlation between the initial ovarian status (density pattern) and the consequence of treatment (change of ovary); we also argued the semelparity of the Japanese eel. Our results supported the hypothesis that the initial ovarian status is an important factor affecting artificial maturation and that androgens could ameliorate the initial status of the eel ovary.

Objective: To elucidate the effects of ISO-α-acids (IAAs), a PPAR-γ agonist, on ICH rats and its potential mechanism., Material and Methods: The Sprague Dawley rats ICH model was induced by stereotactic injecting of 100 μl autologous artery blood. Ninety male rats were randomly allocated to five groups: autologous blood and IAAs (IAA); received autologous blood, IAAs and PPAR-γ inhibitor (IAA + GW9662); autologous blood and normal Saline (Saline); only autologous blood (Mock); and only needle injection (Sham). Neurological functions were assessed by mNSS. Hematoma volume, brain water content, surface proteins and inflammatory factors were detected. The microglia anti-inflammatory abilities were also evaluated., Results: IAAs were able to significantly decrease ICH rat's mNSS scores, alleviate brain water content, improve hematoma resolution than Saline, Mock (p < 0.05). More "M2" microglial/macrophage can be induced by IAAs. The expression of CD 36 was statistically higher in IAA than other groups (p < 0.05). Injection of IAAs led to a greatly increasing in CD 11b and CD 206 double-positive anti-inflammatory type microglial/macrophage, moreover, a reduction of inflammatory cytokines expression (p < 0.05). Such protective effects can be relieved by GW9662., Conclusions: This is the first study to elucidate the relationship between IAAs and ICH. IAAs were able to accelerate hematoma absorption, alleviate brain edema, suppress peri-hematoma inflammations and finally improved the outcome of ICH rats. The phenotype was due to the IAAs induction of "M2" microglial/macrophage via activating of PPAR-γ and increasing CD 36 expression., Competing Interests: Declaration of Competing Interest The authors declared that there is no conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The preparation of an amino-functionalized hybrid monolithic column (TEOS-co-AEAPTES) via one-pot co-condensation of tetraethoxysilane (TEOS) and N-(β-aminoethyl)-γ-aminopropyltriethoxysilane (AEAPTES) in a capillary is descibed. It was used as solid-phase microextraction (SPME) matrix followed by inductively coupled plasma-mass spectrometry (ICP-MS) for determination of trace metals. Under optimum conditions, the amino-functionalized SPME material can simultaneously retain Cu(II), Zn(II), Au(III), and Pb(II) with adsorption capacities of 148, 60, 81, and 64 μg m -1 , respectively. Subsequently, these four metal ions can be quantitatively eluted using 1 mol L -1 HNO 3 containing 1% thiourea. The retention mechanism of Cu(II), Zn(II), Au(III), and Pb(II) on the amino-functionalized hybrid monolith was explained as the combination of electrostatic and coordination interactions. With a 10-fold enrichment factor, the calibration curves were established in the range 0.5-100 μg L -1 with linear correlation coefficients above 0.9943 and the limits of quantitation were 0.05 μg L -1 for four target analytes. The limits of detection were 0.006, 0.012, 0.004, and 0.007 μg L -1 for Cu(II), Zn(II), Au(III), and Pb(II), respectively. The protocol was validated by analyzing Certified Reference Materials including standard sediment, soil, and nickel ore, and the results were in good agreement with their certified values. The relative standard deviations of the method were in the range 0.22-17.6%. The recoveries of the four metal ions in spiked samples were in the range 88.0-113.8%. Compared to direct ICP-MS determination, the proposed in-tube SPME procedure can effectively eliminate the interference from complex matrix, especially from those ores with very high content of main metal to improve the accuracy of analysis. Therefore the method is suitable for the simultaneous determination of ultra-trace Cu(II), Zn(II), Au(III), and Pb(II) in environmental and mineral samples. Graphical abstract The preparation of the TEOS-co-AEAPTES monolithic column and the SPME procedure of Cu(II), Zn(II), Au(III), and Pb(II).

Background: Recently, we reported that some dairy cows could produce high amounts of milk with high amounts of protein (defined as milk protein yield [MPY]) when a population was raised under the same nutritional and management condition, a potential new trait that can be used to increase high-quality milk production. It is unknown to what extent the rumen microbiome and its metabolites, as well as the host metabolism, contribute to MPY. Here, analysis of rumen metagenomics and metabolomics, together with serum metabolomics was performed to identify potential regulatory mechanisms of MPY at both the rumen microbiome and host levels., Results: Metagenomics analysis revealed that several Prevotella species were significantly more abundant in the rumen of high-MPY cows, contributing to improved functions related to branched-chain amino acid biosynthesis. In addition, the rumen microbiome of high-MPY cows had lower relative abundances of organisms with methanogen and methanogenesis functions, suggesting that these cows may produce less methane. Metabolomics analysis revealed that the relative concentrations of rumen microbial metabolites (mainly amino acids, carboxylic acids, and fatty acids) and the absolute concentrations of volatile fatty acids were higher in the high-MPY cows. By associating the rumen microbiome with the rumen metabolome, we found that specific microbial taxa (mainly Prevotella species) were positively correlated with ruminal microbial metabolites, including the amino acids and carbohydrates involved in glutathione, phenylalanine, starch, sucrose, and galactose metabolism. To detect the interactions between the rumen microbiome and host metabolism, we associated the rumen microbiome with the host serum metabolome and found that Prevotella species may affect the host's metabolism of amino acids (including glycine, serine, threonine, alanine, aspartate, glutamate, cysteine, and methionine). Further analysis using the linear mixed effect model estimated contributions to the variation in MPY based on different omics and revealed that the rumen microbial composition, functions, and metabolites, and the serum metabolites contributed 17.81, 21.56, 29.76, and 26.78%, respectively, to the host MPY., Conclusions: These findings provide a fundamental understanding of how the microbiome-dependent and host-dependent mechanisms contribute to varied individualized performance in the milk production quality of dairy cows under the same management condition. This fundamental information is vital for the development of potential manipulation strategies to improve milk quality and production through precision feeding. Video Abstract.

Objective: To assess the effectiveness of influenza vaccine in children aged 6-72 months. Methods: The cohort study was conducted based on community child vaccination clinics in Yiwu and Yongkang counties of Zhejiang province. From October 2017 to December 2017, a total of 1 752 children aged 6-72 months were enrolled from 10 child vaccination clinics. The questionnaire survey was conducted after the written consents were obtained from the parents or legal guardians of the children. Then, a follow up was conducted for enrolle children until 30 April 2018, the influenza vaccination status and the number of influenza-like illness (ILI) cases, hospital visit due to ILI, self-medication due to ILI were observed and recorded every month. Vaccine effectiveness (VE) was estimated by using the generalized linear model (GLM) where dependent variables were the number of ILI cases, hospital visit and self-medication respectively. Results: Of the 1 752 children, 925 (52.80%) were boys and the median age was 30.00 months. The cumulative observation was 308 166 person days at the end of 2017-2018 season, with 5.27 ILI cases per 1 000 person days, 3.41 hospital visit due to ILI per 1 000 person days, 1.45 self-medication due to ILI per 1 000 person days. Of the 1 752 children, 643 received the influenza vaccination in 2017-2018 season. Compared with unvaccinated children, the VE was 23.5% against ILI case number (95% CI : 15.1%-31.1%), 19.3% against hospital visit due to ILI (95% CI : 8.2%-29.1%) and 25.8% against self-medication due to ILI (95% CI : 9.3%- 39.3%). Modeling splitting 643 children with 2017-2018 vaccination into those before and after vaccination, the influenza VE was 31.9% against ILI case number (95% CI : 12.7%-46.9%), 32.6% against hospital visit due to ILI (95% CI : 8.6%-50.3%) and 44.3% against self-medication due to ILI (95% CI : 11.9%-64.8%) in children aged 36-72 months. However, the children aged 6-35 months showed no significant VEs. For the VE analysis in children with different vaccination status, the VEs were significant if they received vaccination in both 2016-2017 season and 2017-2018 season or only in 2017-2018 seasons. The VE was not demonstrated among the children who were immunized only in 2016-2017 season. Conclusion: Influenza vaccination is moderate effective in preventing the incidence of ILI and hospital visit and self-medication in children in influenza season, the protection effect in children aged 36-72 months is better than that in children aged 6-35 months.