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Pterostilbene is a derivative of resveratrol with a higher bioavailability and biological activity, which shows antioxidant, anti-inflammatory, antitumor, and antiaging activities. Here, directed evolution and host strain engineering were used to improve the production of pterostilbene in Escherichia coli . First, the heterologous biosynthetic pathway enzymes of pterostilbene, including tyrosine ammonia lyase, p -coumarate: CoA ligase, stilbene synthase, and resveratrol O-methyltransferase, were successively directly evolved through error-prone polymerase chain reaction (PCR). Four mutant enzymes with higher activities of in vivo and in vitro were obtained. The directed evolution of the pathway enzymes increased the pterostilbene production by 13.7-fold. Then, a biosensor-guided genome shuffling strategy was used to improve the availability of the precursor L-tyrosine of the host strain E. coli TYR-30 used for the production of pterostilbene. A shuffled E. coli strain with higher L-tyrosine production was obtained. The shuffled strain harboring the evolved pathway produced 80.04 ± 5.58 mg/l pterostilbene, which is about 2.3-fold the highest titer reported in literatures., 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 Yan, Liang, Niu, Shen and Liu.)

Human bodily movements are primarily controlled by the contractions of skeletal muscles. Unlike joint or skeletal movements that are generally performed in the large displacement range, the contractions of the skeletal muscles that underpin these movements are subtle in intensity yet high in frequency. This subtlety of movement makes it a formidable challenge to develop wearable and durable soft materials to electrically monitor such motions with high fidelity for the purpose of, for example, muscle/neuromuscular disease diagnosis. Here we report that an intrinsically fragile ultralow-density graphene-based cellular monolith sandwiched between silicone rubbers can exhibit a highly effective stress and strain transfer mechanism at its interface with the rubber, with a remarkable improvement in stretchability (>100%). In particular, this hybrid also exhibits a highly sensitive, broadband-frequency electrical response (up to 180 Hz) for a wide range of strains. By correlating the mechanical signal of muscle movements obtained from this hybrid material with electromyography, we demonstrate that the strain sensor based on this hybrid material may provide a new, soft and wearable mechanomyography approach for real-time monitoring of complex neuromuscular-skeletal interactions in a broad range of healthcare and human-machine interface applications. This work also provides a new architecture-enabled functional soft material platform for wearable electronics., (© The Author(s) 2021. Published by Oxford University Press on behalf of China Science Publishing & Media Ltd.)

Abstract: Cell death occurs in various tissues and organs in the body. It is a physiological or pathological process that has different effects. It is of great significance in maintaining the morphological function of cells and clearing abnormal cells. Pyroptosis, apoptosis, and necrosis are all modes of cell death that have been studied extensively by many experts and scholars, including studies on their effects on the liver, kidney, the heart, other organs, and even the whole body. The heart, as the most important organ of the body, should be a particular focus. This review summarizes the mechanisms underlying the various cell death modes and the relationship between the various mechanisms and heart diseases. The current research status for heart therapy is discussed from the perspective of pathogenesis., (Copyright © 2021 The Chinese Medical Association, produced by Wolters Kluwer, Inc. under the CC-BY-NC-ND license.)

This study investigated the possibility of coupling anaerobic hydrolysis in an anaerobic membrane bioreactor (AnMBR) with mixotrophic microalgae cultivation in a membrane photobioreactor (MPBR) for the sustainable treatment of municipal wastewater. Using the hydrolyzed wastewater discharged from AnMBR, Chlorella pyrenoidosa in MPBR grew in a mixotrophic mode and realized rapid growth. During the stable operation, MPBR achieved average carbon capture rate of 42.82 mg L -1 d -1 and algal lipid production rate of 19.66 mg L -1 d -1 . The average reduction in TN, TP, and TOC during stable operation was 96.7%, 98.0%, and 95.9%, respectively. Mass balance analysis showed that the overall system captured 14.76 mg of carbon from the atmosphere per liter of wastewater treated. Therefore, this AnMBR-MPBR hybrid system simultaneously realized advanced treatment of municipal wastewater, efficient production of algal lipid, and carbon capture from atmosphere, and thus has a good potential in the sustainable treatment of municipal wastewater., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Transarterial chemoembolization (TACE) is an effective treatment for patients with hepatocellular carcinoma (HCC). However, the impact of hepatitis B viral (HBV) infection and body mass index (BMI) on TACE is controversial. The present study aimed to compare the influence of HBV and high BMI on TACE outcomes in advanced HCC., Methods: Based on HBV infection history and BMI, patients were assigned to different subgroups. Blood samples were collected and analyzed by an enzyme-linked immunosorbent assay (ELISA) kit. The primary endpoint was progression-free survival (PFS) and the overall survival (OS) in the population., Results: Compared to overweight combined HBV patients who received TACE, people with normal weight or no viral infection had significantly better OS and PFS. Sex, age, portal vein tumor thrombus, BCLC, ECOG, and tumor diameter are the main risk factors affecting PFS and OS. Except for the postoperative fever, no significant difference was detected in adverse reactions. Irrespective of TACE, the average expression of HMGB1 in hepatitis or obesity patients was higher than that in normal individuals and did not show upregulation after TACE. Patients without overweight or HBV infection had a low expression of serum HMGB1 that was substantially upregulated after TACE., Conclusions: In this study, overweight combined HBV infection patients had shorter PFS and OS than other HCC patients. Thus, HBV and BMI maybe two factors affecting the efficacy of TACE via upregulated HMGB1., (© 2021. The Author(s).)

Nitrogen (N 2 ) rejection from methane (CH 4 ) is the most challenging step in natural gas processing because of the close similarity of their physical-chemical properties. For decades, efforts to find a functioning material that can selectively discriminate N 2 had little outcome. Here, we report a molecular trapdoor zeolite K-ZSM-25 that has the largest unit cell among all zeolites, with the ability to capture N 2 in favor of CH 4 with a selectivity as high as 34. This zeolite was found to show a temperature-regulated gas adsorption wherein gas molecules' accessibility to the internal pores of the crystal is determined by the effect of the gas-cation interaction on the thermal oscillation of the "door-keeping" cation. N 2 and CH 4 molecules were differentiated by different admission-trigger temperatures. A mild working temperature range of 240-300 K was determined wherein N 2 gas molecules were able to access the internal pores of K-ZSM-25 while CH 4 was rejected. As confirmed by experimental, molecular dynamic, and ab initio density functional theory studies, the outstanding N 2 /CH 4 selectivity is achieved within a specific temperature range where the thermal oscillation of door-blocking K + provides enough space only for the relatively smaller molecule (N 2 ) to diffuse into and through the zeolite supercages. Such temperature-regulated adsorption of the K-ZSM-25 trapdoor zeolite opens up a new approach for rejecting N 2 from CH 4 in the gas industry without deploying energy-intensive cryogenic distillation around 100 K.

A high output impedance current source with a wide bandwidth is needed in electrical impedance tomography systems. Limitations appear mainly at higher frequencies and non-simple loads. In order to adjust the output current, the amplitude and phase are made to achieve the expected value automatically. A current source based on the field programmable gate array is designed. In this paper, we proposed a double DAC differential current source structure. By measuring the voltage of the sampling resistor in series with the load and using the proposed dynamic reference point demodulation algorithm, the actual current amplitude and phase on the load can be quickly obtained. Through the adaptive compensation module, the output current is adjusted to the expected value. The experimental results show that the output resistance of the current source can reach 10 MΩ and the output capacitance can be less than 0.8 pF in the frequency range of 10 kHz-1.28 MHz. At the same time, the current amplitude attenuation is less than 0.016%, and the phase error is less than 0.0025° after compensation. Therefore, the proposed current source achieves widebands, biocompatibility, and high precision.

The 2019 coronavirus disease (COVID-19) caused by SARS-CoV-2 virus infection has posed a serious danger to global health and the economy. However, SARS-CoV-2 medications that are specific and effective are still being developed. Honokiol is a bioactive component from Magnoliae officinalis Cortex with damp-drying effect. To develop new potent antiviral molecules, a series of novel honokiol analogues were synthesized by introducing various 3-((5-phenyl-1,3,4-oxadiazol-2-yl)methyl)oxazol-2(3 H )-ones to its molecule. In a SARS-CoV-2 pseudovirus model, all honokiol derivatives were examined for their antiviral entry activities. As a result, 6a and 6p demonstrated antiviral entry effect with IC 50 values of 29.23 and 9.82 µM, respectively. However, the parental honokiol had a very weak antiviral activity with an IC 50 value more than 50 µM. A biolayer interfero-metry (BLI) binding assay and molecular docking study revealed that 6p binds to human ACE2 protein with higher binding affinity and lower binding energy than the parental honokiol. A competitive ELISA assay confirmed the inhibitory effect of 6p on SARS-CoV-2 spike RBD's binding with ACE2. Importantly, 6a and 6p (TC 50 > 100 μM) also had higher biological safety for host cells than honokiol (TC 50 of 48.23 μM). This research may contribute to the discovery of potential viral entrance inhibitors for the SARS-CoV-2 virus, although 6p 's antiviral efficacy needs to be validated on SARS-CoV-2 viral strains in a biosafety level 3 facility.

A novel cell-free biosynthesis system based on a mixture of chassis cell extracts and purified Spy-cyclized enzymes (CFBS-mixture) was developed. As a demonstration, the CFBS-mixture was applied to chlorogenic acid (CGA) biosynthesis. The mix-and-match and Plackett-Burman experiments demonstrated that Lonicera japonica hydroxycinnamate-CoA quinate transferase and p -hydroxyphenylacetate 3-hydroxylase were the key enzymes for the production of CGA. After optimization of the concentrations of the biosynthetic enzymes in the CFBS-mixture reaction using the Plackett-Burman experimental design and the path of the steepest ascent, 711.26 ± 15.63 mg/L CGA was produced after 16 h, which is 71.1-fold the yield obtained using the conventional crude extract-based CFBS and 9.1-fold the reported yield obtained using the living cells. Based on the CFBS-mixture results, the production of CGA was further enhanced in engineered Escherichia coli . The CFBS-mixture strategy is highly effective and will be useful for high-level CFBS of natural products.

Antibiotic-coated intramedullary nails have been popularized in recent decades for treating long-bone infections. They are especially useful in treating diaphyseal infections requiring stability, such as those involving fractures and nonunions. The nails are made by injecting antibiotic-impregnated polymethylmethacrylate or "cement" around a metal core using a silicone tube as a mold. There are a variety of techniques that can be used to customize the nail to the affected site. Antibiotic cement has long been demonstrated as an effective local antibiotic delivery system. It is able to elute high concentrations of antibiotics while having little systemic toxicity. Several case series have reported good outcomes using this technique, defined by bone union and infection control. Further research is needed to determine the amount of weight that can safely be transferred through the nail and to optimize antibiotic elution., (Copyright © 2021 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Orthopaedic Trauma Association.)

To explore the technical process and the therapeutic effect of using sequential surgical guide with independent intellectual property rights assisting immediate implantation and restoration of the full arch, with the support from the periodontal splint for mobile supporting teeth, patients with severe periodontitis who planned to undergo immediate full arch implantation were recruited from August 2019 to December 2020 at the Department of Prosthodontics, Department of Periodontology, Department of Implantology and First Clinical Division, Peking University School and Hospital of Stomatology. Through the procedure of collecting preoperative maxillofacial data, making systematic diagnostic design, making periodontal splints fixation, producing surgical guide, and carrying out guided surgery for full arch immediate implantation, eight cases were included. By registering the postoperative cone-beam CT (CBCT) with the preoperative data, the difference between the actual three-dimensional position of the implants and the virtual design was observed, and the accuracy of the implant placement position guided by the sequential guide was statistically analyzed using SPSS 25.0 software. Analysis indicators include coronal and apical global displacement, coronal horizontal and vertical displacement, apical horizontal and vertical displacement, and angular deviation. Results revealed that the 8 patients [2 males and 6 females, aged (49.0±9.3) years (38-65 years)] of recruited cases included 7 cases of maxilla and 1 cases of mandible. A total of 48 implants, of which 44 implants were placed upright and 4 were placed tilted, 16 implants in the anterior region and 32 implants in the posterior region. No guide plate fracture or damage to important anatomical structures were reported. The overall displacement at the coronal point [(0.83±0.48) mm] and the global displacement at the apical point [(1.36±0.57) mm] were within the clinically acceptable safety range, and the horizontal displacement and vertical displacement at the coronal point, horizontal displacement and vertical displacement at the apical point, and the angle deviation of implants axial have no statistic significant difference in the anterior and posterior region ( P >0.05). Periodontal splints combined with sequential surgical guides to assist patients with severe periodontitis for immediate full arch implantation and immediate restoration can expand the indications of guide assisted implant surgery. It meets the safety requirements in clinical applications.

Background: Haemaphysalis longicornis is an obligate hematophagous ectoparasite that transmits a variety of pathogens causing life-threatening diseases in humans and animals. Paramyosin (Pmy) is not only an invertebrate-specific myofibrillar protein but also an important immunomodulatory protein. Therefore, it is one of the ideal candidate antigens for vaccines., Methods: We conducted two vaccine trials to evaluate the protective efficacy of Pmy recombinant protein (rPmy) and peptide vaccine (KLH-LEE). Each rabbit was immunized with three doses of rPmy or KLH-LEE adjuvanted with Freund's complete/incomplete at 500 μg/dose at 2-week intervals before challenge with 40 female H. longicornis/rabbit. PBS plus adjuvant, Trx or KLH was used as control group. The antibodies of rabbits were detected by ELISA. Then, female ticks were fed on the rabbits until detachment., Results: ELISA results showed that both vaccines induced rabbits to produce antibodies. Compared with the Trx group, the engorgement weight, oviposition and hatchability of the rPmy group decreased by 8.87%, 26.83% and 38.86%, respectively. On the other hand, engorgement weight, oviposition and hatchability of female ticks in the KLH-LEE group correspondingly resulted in 27.03%, 53.15% and 38.40% reduction compared with that of the KLH group. Considering the cumulative effect of vaccination on the evaluated parameters, results showed 60.37% efficacy of the rPmy vaccine formulation and 70.86% efficacy in the KLH-LEE group., Conclusions: Pmy and particularly epitope LEE have potential for further development of an effective candidate vaccine to protect the host against tick infection. GRAPHIC ABSTARCT.

Abstract: This study aims to describe the occurrence, severity degree, and correlated risk factors of dental fluorosis among the 12-year-old schoolchildren of Jilin, China.We conducted a cross-sectional, observational, and descriptive study among 960 12-year-old schoolchildren in Jilin. The Dean index was utilized to evaluate the severity degree of dental fluorosis. A questionnaire was sent to the guardians of children. Community fluorosis index was measured to estimate the importance of enamel fluorosis for the whole population's public health. The logistic regression analysis was also utilized to identify the correlation between fluorotic teeth and the independent variables.Nine hundred sixty children were assessed. Among them, 480 (50%) were female. 30.5% of subjects had dental fluorosis, 7.19% had very mild dental fluorosis, 10.73% experienced mild dental fluorosis, 9.58% suffered moderate dental fluorosis, and 3.02% encountered severe dental fluorosis. The overall community fluorosis index was 0.73. The results of logistic regression showed that schoolchildren who brushed teeth more frequently (OR: 2.012, 95% CI 1.767-2.342), deficiency of parental supervision (OR: 4.219, 95% CI 3.887-4.573), and lived in rural areas (OR: 2.776, 95% CI 2.163-3.489) were more correlated with enamel fluorosis. Moreover, schoolchildren whose mothers or fathers were of high education level (OR: 0.336, 95% CI 0.217-0.413 and 0.346, 95% CI 0.113-0.512) and only child (OR: 0.378, 95% CI 0.213-0.415) were protective factors for dental fluorosis.In the Jilin province of China, the risk indicators for dental fluorosis include rural areas, more frequency of brushing, low educational background of parents, and deficiency of parental supervision., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Development of an effective vaccine against the leading human bacterial pathogen group A Streptococcus (GAS) is a public health priority. The species defining group A cell wall carbohydrate (GAC, Lancefield antigen) can be engineered to remove its immunodominant N-acetylglucosamine (GlcNAc) side chain, implicated in provoking autoimmune cross-reactivity in rheumatic heart disease, leaving its polyrhamnose core (GAC PR ). Here we generate a novel protein conjugate of the GAC PR and test the utility of this conjugate antigen in active immunization. Instead of conjugation to a standard carrier protein, we selected SpyAD, a highly conserved GAS surface protein containing both B-cell and T-cell epitopes relevant to the bacterium that itself shows promise as a vaccine antigen. SpyAD was synthesized using the XpressTM cell-free protein expression system, incorporating a non-natural amino acid to which GAC PR was conjugated by site-specific click chemistry to yield high molecular mass SpyAD-GAC PR conjugates and avoid disruption of important T-cell and B-cell immunological epitopes. The conjugated SpyAD-GAC PR elicited antibodies that bound the surface of multiple GAS strains of diverse M types and promoted opsonophagocytic killing by human neutrophils. Active immunization of mice with a multivalent vaccine consisting of SpyAD-GAC PR , together with candidate vaccine antigens streptolysin O and C5a peptidase, protected against GAS challenge in a systemic infection model and localized skin infection model, without evidence of cross reactivity to human heart or brain tissue epitopes. This general approach may allow GAC to be safely and effectively included in future GAS subunit vaccine formulations with the goal of broad protection without autoreactivity., Competing Interests: LP, LB, AB, JF, and NK are employees of Vaxcyte, Inc. Some studies at UC San Diego were supported by a sponsored research agreement with Vaxcyte, Inc. VN previously received fees as a consultant for SutroVax, Inc., a former name of Vaxcyte.

This study aims to evaluate acceptance of COVID-19 vaccines and the impact of risk perception on vaccine acceptance and personal health protective behaviors in Taiwan. A nationwide cross-sectional study was conducted from 19 to 30 October 2020; 1020 participants were included in the final analysis; chi-square and logistic regression analyses were conducted. In total, 52.7% of participants were willing to receive COVID-19 vaccines, 63.5% perceived the severity of COVID-19 in Taiwan as "not serious", and nearly 40% were worried about COVID-19 infection. Participants with higher perceived severity of COVID-19 had significantly higher odds of refusing the vaccine (OR = 1.546), while those worried about infection had lower odds of poor health protective behaviors (OR = 0.685). Vaccine refusal reasons included "the EUA process is not strict enough" (48.7%) and "side effects" (30.3%). Those who had previously refused other vaccinations were 2.44 times more likely to refuse the COVID-19 vaccines. Participants' age had an influence on COVID-19 vaccine acceptance. In general, the Taiwanese public's acceptance of the vaccine was lower than that in other high-income countries. Elderly participants and those with college-level education and above who had previously refused vaccines had lower willingness to receive a COVID-19 vaccine. Risk perception was positively associated with personal health protective behaviors but negatively associated with COVID-19 vaccine acceptance.

Microplastics are an emerging hazard in the marine environment, and considered to eventually sink into sediments. An investigation into the long-term variation of microplastic accumulation in sediment cores is essential for understanding the historical trend of this contamination and its response to human activities. In this study, the multidecadal changes of microplastic abundances in two sediment cores from the inner shelf of the East China Sea (ECS) were revealed by two methods, i.e., a visual enumeration method based on scanning electron microscopy-energy dispersive X-ray spectroscopy (SEM-EDS) and a quantitative method based on microplastic-derived carbon (MPC) abundances. The features of microplastics were determined via SEM-EDS and micro-Fourier transform infrared spectroscopy (μ-FTIR). The results reveal a multidecadal increasing trend of microplastic accumulation in the coastal sediments of the ECS since the 1960s, which may be jointly governed by the release of plastic wastes and oceanographic dynamics. Meanwhile, the breakpoint of the exponential growth of microplastics in the ECS occurs in 2000 AD, which well matches the rapid increasing of plastic production and consumption in China. Further, based on the MPC contents in sediments, the influence of microplastics on the quantitative evaluation of carbon storage in the ECS has been examined for the first time, revealing an insignificant (<2% before 2014 AD) but potentially-increasing (6.8% by 2025 AD) contribution of microplastics to carbon burial. Our results may provide the important data for evaluating and mitigating the impact of microplastics on the marine environment., 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 © 2020 Elsevier Ltd. All rights reserved.)

Objective: To verify horizontal jaw relations using anatomical marks on a cast and evaluate the efficiency and accuracy of the test on checking the horizontal relation., Methods: A total of 200 patients with a loss of posterior occlusion were recruited. After casts were made and the horizontal jaw relation was recorded, the pterygomaxillary notch and retromolar pad were identified bilaterally on the maxillary and mandibular casts. On each cast, a vertical line was drawn to bisect the anatomical landmarks and the distance between the two vertical lines was measured. Using the result of the wax try-in appointment and the corresponding measurements, a diagnostic test was conducted. A receiver operating curve was created and the maximum horizontal distance between bisecting points that still obtained correct jaw relations was determined to be a criterion. The accuracy of the test to verify horizontal jaw relations was evaluated., Results: The area under the curve of the receiver operating curve was 0.833 (P < 0.05). With a maximum Youden index, the d value threshold was 1.0 mm. Using 1.0 mm as a criterion to check the horizontal relation, the sensitivity of the test was 0.76 and the specificity was 0.93. The kappa value for different researchers was calculated to be 0.79 (P < 0.05). The intraexaminer 1 reliability gave a kappa value of 0.76 (P < 0.05), and intraexaminer 2 gave a value of 0.81 (P < 0.05)., Conclusion: The test for verifying the accuracy of horizontal jaw relations is reliable. If horizontal distance is measured as greater than 1.0 mm at the jaw relation record appointment, the recorded horizontal jaw relationship may be wrong and need to be reexamined.

Background: 4-Hydroxyphenylacetic acid (4HPAA) is an important raw material for the synthesis of drugs, pesticides and biochemicals. Microbial biotechnology would be an attractive approach for 4HPAA production, and cofactors play an important role in biosynthesis., Results: We developed a novel strategy called cofactor engineering based on clustered regularly interspaced short palindromic repeat interference (CRISPRi) screening (CECRiS) for improving NADPH and/or ATP availability, enhancing the production of 4HPAA. All NADPH-consuming and ATP-consuming enzyme-encoding genes of E. coli were repressed through CRISPRi. After CRISPRi screening, 6 NADPH-consuming and 19 ATP-consuming enzyme-encoding genes were identified. The deletion of the NADPH-consuming enzyme-encoding gene yahK and the ATP-consuming enzyme-encoding gene fecE increased the production of 4HPAA from 6.32 to 7.76 g/L. Automatically downregulating the expression of the pabA gene using the Esa-P esaS quorum-sensing-repressing system further improved the production of 4HPAA. The final strain E. coli 4HPAA-∆yfp produced 28.57 g/L of 4HPAA with a yield of 27.64% (mol/mol) in 2-L bioreactor fed-batch fermentations. The titer and yield are the highest values to date., Conclusion: This CECRiS strategy will be useful in engineering microorganisms for the high-level production of bioproducts.

At present, the issues regarding multi-center clinical trials of new drugs of traditional Chinese medicine(TCM) remain: the lack of agreement on the content and scope of the ethical review among the ethics committee members of the center and the participating units results in repeated review, which leads to a time-consuming ethical review process. Moreover, the review capabilities of the ethics committees of various research centers are uneven, which is not necessarily beneficial to the protection of subjects' rights and safety. In view of the existing problems, to improve the efficiency of ethical review of multi-center clinical trials of new drugs of TCM and avoid repeated reviews, the TCM Clinical Evaluation Professional Committee of Chinese Pharmaceutical Association organized experts to formulate the &quot;Consensus on collaborative ethical review of multi-center clinical trials of new drugs of TCM(version 1.0)&quot;(hereinafter referred to as &quot;Consensus&quot;). The &quot;Consensus&quot; is formulated in accordance with the requirements of relevant documents such as but not limited to &quot;the opinions on deepening the reform of the evaluation and approval system to encourage the innovation of pharmaceutical medical devices&quot;, &quot;the regulations of ethical review of biomedical research involving human subjects&quot;. The &quot;Consensus&quot; covers the scope of application, formulation principles, conditions for the ethics committee of the center, sharing of ethical review resources, scope and procedure of collaborative review, rights and obligations, etc. The aims of the &quot;Consensus&quot; is to preliminarily explore and establish a scientific and operable ethical review procedure. Additionally, on the basis of fully protecting the rights and interests of the subjects, a collaborative ethical review agreement needs to be signed to clarify the ethical review responsibilities of all parties, to avoid repeated review, and to improve the efficiency and quality of ethical review in multi-center clinical trials of new drugs of TCM.

Microplastic pollution in marine environments is of particular concern on its risk to the ecosystem. To assess and manage microplastic contaminants, their quantitative detection in environmental samples is a high priority. However, uncertainties of current methods still exist when estimating their abundances, particularly with fine-grained (<1 mm) microplastics. This work reports a novel thermoanalytical method for quantifying microplastics by measuring the contents of microplastic-derived carbon (MPC) in samples under the premise of nearly eliminating the limit of their particle appearances. After validating the method via samples with the spiked microplastics, we have conducted a case study on sediment core H43 that spanned 1925-2009 CE from the Yellow Sea for further illustrating the high reliability and practicability of this method for quantifying microplastics in natural samples. Our results have demonstrated that the proposed method may be a promising technique to determine the mass-related concentrations of the total microplastics in marine sediments for evaluating their pollution status and quantitative contribution to marine carbon storage., 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 © 2020 Elsevier B.V. All rights reserved.)

Genome-wide association studies have discovered numerous genomic loci associated with Alzheimer's disease (AD); yet the causal genes and variants are incompletely identified. We performed an updated genome-wide AD meta-analysis, which identified 37 risk loci, including new associations near CCDC6, TSPAN14, NCK2 and SPRED2. Using three SNP-level fine-mapping methods, we identified 21 SNPs with >50% probability each of being causally involved in AD risk and others strongly suggested by functional annotation. We followed this with colocalization analyses across 109 gene expression quantitative trait loci datasets and prioritization of genes by using protein interaction networks and tissue-specific expression. Combining this information into a quantitative score, we found that evidence converged on likely causal genes, including the above four genes, and those at previously discovered AD loci, including BIN1, APH1B, PTK2B, PILRA and CASS4.

Background: Osteoporosis is a common phenomenon in HIV patients on tenofovir treatment, but its underlying mechanisms remain to be explored., Methods: Quantitative real-time PCR was performed to analyze the expression of miR-302, miR-101, miR-145 and osteoclast-specific genes in the serum of HIV patients treated with tenofovir and ZOL. ELISA was used to evaluate the expression of RANKL, SMAD3 and PRKACB in the serum of these patients. Luciferase assay was carried out to explore the inhibitory effects of miR-302, miR-101 and miR-145 on the expression of PRKACB, RANKL and SMAD3, respectively. Western blot was used to examine the expression of genes involved in NF‑κB and JNK signaling pathways., Results: ZOL treatment significantly suppressed the expression of CTx and osteocalcin in HIV patients treated with tenofovir. The BMD loss of HIV patients treated with tenofovir was effectively hindered by ZOL treatment. Mechanistically, the expression of miR-302, miR-101, miR-145, RANKL, SMAD3 and PRKACB in the serum was remarkably activated by ZOL treatment. Luciferase assays showed that miR-302, miR-101 and miR-145 effectively suppressed the expression of PRKACB, RANKL and SMAD3, respectively, through binding to their 3' UTR. Furthermore, ZOL treatment notably restored the normal expression of osteoclast‑specific genes while activating NF‑κB and JNK signaling pathways., Conclusion: The findings of this study demonstrated that administration of ZOL suppressed the expression of RANKL via modulating signaling pathways of miR-101-3p/RANKL, miR-302/PRKACB/RANKL and miR-145/SMAD3/RANKL. Furthermore, down-regulated expression of RANKL by ZOL treatment alleviated osteoporosis in HIV-positive subjects treated with tenofovir.

Background: Previous studies have showed that red cell distribution width (RDW) may be an inflammatory status, and it may be used to predict prognosis of acute pancreatitis (AP). However, there are no systematic reviews for the evidence, and the association between RDW and AP is still not completely understood. Therefore, we will undertake a systematic review of the literature to summarize previous evidence regarding this topic, in order to clarify the value of RDW predicting prognosis of patients with AP., Methods: We will search EMBASE, Web of Knowledge, PubMed, ClinicalTrials.gov and Cochrane Library from their inception to Mar 2021 to retrieve relevant studies. Two authors independently judged study eligibility and extracted data. Heterogeneity will be examined by computing the Q statistic and I2 statistic., Results: This study proved the Efficiency of RDW in predicting mortality and severity of patients with AP. And provided easy method for clinical evaluation for AP patients., Conclusions: The findings of this systematic review will show the value of RDW predicting prognosis of patients with AP., Ethics and Dissemination: Ethical approval is unnecessary as this protocol is only for systematic review and does not involve privacy data. The findings of this study will be disseminated electronically through a peer-review publication or presented at a relevant conference., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

S-nitrosoglutathione reductase 1 (GSNOR1) is the key enzyme that regulates cellular homeostasis of S- nitrosylation. Although extensively studied in Arabidopsis , the roles of GSNOR1 in tetraploid Nicotiana species have not been investigated previously. To study the function of Nt GSNOR1, we knocked out two NtGSNOR1 genes simultaneously in Nicotiana tabacum using clustered regularly interspaced short palindromic repeats (CRISPR)/caspase 9 (Cas9) technology. To our surprise, spontaneous cell death occurred on the leaves of the CRISPR/Cas9 lines but not on those of the wild-type (WT) plants, suggesting that Nt GSNOR1 negatively regulates cell death. The natural cell death on the CRISPR/Cas9 lines could be a result from interactions between overaccumulated nitric oxide (NO) and hydrogen peroxide (H 2 O 2 ). This spontaneous cell death phenotype was not affected by knocking out two Enhanced disease susceptibility 1 genes (NtEDS11a/1b) and thus was independent of the salicylic acid (SA) pathway. Unexpectedly, we found that the NtGSNOR1a/1b knockout plants displayed a significantly ( p < 0.001) enhanced resistance to paraquat-induced cell death compared to WT plants, suggesting that Nt GSNOR1 functions as a positive regulator of the paraquat-induced cell death. The increased resistance to the paraquat-induced cell death of the NtGSNOR1a/1b knockout plants was correlated with the reduced level of H 2 O 2 accumulation. Interestingly, whereas the N gene-mediated resistance to Tobacco mosaic virus (TMV) was significantly enhanced ( p < 0.001), the resistance to Pseudomonas syringae pv. tomato DC3000 was significantly reduced ( p < 0.01) in the NtGSNOR1a/1b knockout lines. In summary, our results indicate that Nt GSNOR1 functions as both positive and negative regulator of cell death under different conditions and displays distinct effects on resistance against viral and bacterial pathogens., 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 Li, Ren, Guo, Ran, Ren, Wu, Xu, Liu and Liu.)

Speech could be used, because it was a neuromuscular movement without teeth contact. The method was stable, however it was used more in vertical relation deciding. More study was needed in the horizontal relation deciding. This article was to explain why and how to use phonetic method to decide jaws relation, through literature review.

To describe distributions of immune markers in children and young adults by sex and HIV status, and within groups, investigate associations of immune markers with bone density across Tanner stage. Using data and samples from 353 participants in a cross-sectional study in youth with perinatally acquired HIV (PHIV) and matched HIV-negative controls, distributions of inflammation and activation immune markers were described by sex and HIV status. Correlations and structural equation models (SEM) were used to explore marginal and multivariable associations of the immune markers with bone density and to assess whether patterns of association varied by sex and HIV status. Immune marker distributions did not differ by sex, but there were some differences by HIV status. Correlation patterns among bone, body composition, and immune markers were similar across the sex and HIV status groups. Conclusions from SEMs were limited by small sample sizes, but there was some indication that patterns of association between bone density and certain immune markers differed in male PHIV with more advanced Tanner stage compared to the other three groups. In conclusion, distributions of bone density, body composition, and immune markers may vary by sex and HIV status, although associations among these outcomes within sex and HIV status groups appear similar. Bone density of male PHIV appears to be more negatively affected than females, regardless of female HIV status. Larger longitudinal studies across Tanner stages are needed to further explore potential biological relationships between immune markers and bone density in youth living with HIV.

CH 3 NH 3 PbI 3 is one of the most widely studied and most promising photoelectric conversion materials for large-scale application. However, once it is discharged into the aquatic environment, it will release a variety of lethal substances to the aquatic organisms. Herein, two typical aquatic pollution indicators, Scenedesmus obliquus (a typical phytoplankton) and Daphnia magna (a typical zooplankton), were used to assess the acute effects of CH 3 NH 3 PbI 3 perovskite on aquatic organisms. The results showed that, when the initial CH 3 NH 3 PbI 3 perovskite level (CPL) was 40 mg L -1 or higher, the growth of S. obliquus would be remarkably inhibited with significant decreases of chlorophyll content and protein content. And when the CPL was over 5 mg L -1 , the survival of D. magna would be notably threatened. Specifically, the 72 h EC-50 of CH 3 NH 3 PbI 3 perovskite to S. obliquus was calculated as 37.21 mg L -1 , and the 24 h LC-50 of this perovskite to D. magna adults and neonates were calculated as 37.53 mg L -1 and 18.55 mg L -1 , respectively. Moreover, remarkably solution pH declination and large amounts of lead bio-accumulation was observed in the both acute experiments, which could be the main reasons causing the above acute effects. Considering the strong acute effects of these CH 3 NH 3 PbI 3 perovskite materials and their attractive application prospect, more attentions should be paid on their harmness to the environment., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Sr 3.8 Fe 25.7 O 70.4 -chitosan magnetic microparticles (Sr 3.8 Fe 25.7 O 70.4 -CMNs) with a core-shell structure were synthesized, characterized and applied for the removal of two model cationic dyes. The results showed that these magnetic microparticles possess fast adsorption rate and high adsorption efficiency for both crystal violet (CV) and basic red 9 (BR9) at a temperature ranging 30 °C to 40 °C and suitable pH range (pH ≥ 7). The maximum removal efficiency for CV and BR9 attained to 94.5% and 97.5% in 30 min, which was significantly faster and higher than that of chitosan (<50% in 60 min) (P<0.01). And its maximum adsorption capacity for CV and BR9 reached 29.46 mg/g and 32.16 mg/g, respectively. The adsorption process of Sr 3.8 Fe 25.7 O 70.4 -CMNs follows the Langmuir isotherm with a high correlation coefficient (R 2  > 0.97) and the pseudo-second-order model. Additionally, the synthesized Sr 3.8 Fe 25.7 O 70.4 -CMNs were easy to regeneration and reuse, and the removal rate remained above 90% after 5 recycle times. This study would provide a new more environmental friendly material and method for the treatment of wastewater containing toxic dyes., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2020. Published by Elsevier B.V.)

Discovering drugs that efficiently treat brain diseases has been challenging. Genetic variants that modulate the expression of potential drug targets can be utilized to assess the efficacy of therapeutic interventions. We therefore employed Mendelian Randomization (MR) on gene expression measured in brain tissue to identify drug targets involved in neurological and psychiatric diseases. We conducted a two-sample MR using cis-acting brain-derived expression quantitative trait loci (eQTLs) from the Accelerating Medicines Partnership for Alzheimer's Disease consortium (AMP-AD) and the CommonMind Consortium (CMC) meta-analysis study (n = 1,286) as genetic instruments to predict the effects of 7,137 genes on 12 neurological and psychiatric disorders. We conducted Bayesian colocalization analysis on the top MR findings (using P<6x10-7 as evidence threshold, Bonferroni-corrected for 80,557 MR tests) to confirm sharing of the same causal variants between gene expression and trait in each genomic region. We then intersected the colocalized genes with known monogenic disease genes recorded in Online Mendelian Inheritance in Man (OMIM) and with genes annotated as drug targets in the Open Targets platform to identify promising drug targets. 80 eQTLs showed MR evidence of a causal effect, from which we prioritised 47 genes based on colocalization with the trait. We causally linked the expression of 23 genes with schizophrenia and a single gene each with anorexia, bipolar disorder and major depressive disorder within the psychiatric diseases and 9 genes with Alzheimer's disease, 6 genes with Parkinson's disease, 4 genes with multiple sclerosis and two genes with amyotrophic lateral sclerosis within the neurological diseases we tested. From these we identified five genes (ACE, GPNMB, KCNQ5, RERE and SUOX) as attractive drug targets that may warrant follow-up in functional studies and clinical trials, demonstrating the value of this study design for discovering drug targets in neuropsychiatric diseases., Competing Interests: JZL, C-YC and HR are employees and shareholders in Biogen. KE is an employee at BioMarin Pharmaceuticals. DAB is employed on a grant funded by Biogen. TRG and GDS received funding from Biogen for the work described here. The other authors have no competing interests to declare.

Objective: To investigate the blood pressure and heart rate changes and influencing factors during single dental implant surgery., Methods: A retrospective cohort study was conducted. Six hundred and forty cases underwent single dental implant placement in Department of Prosthodontics, Peking University School and Hospital of Stomatology from January 2016 to December 2016 were recruited in this study according to the inclusion and exclusion criteria. They were divided into different groups according to the exposure factors which were patient characteristics (gender, age) and surgical procedures (immediate placement, flap elevation, bone grafting). The correlation between blood pressure and heart rate variability during single dental implant surgery and the patient characteristics and surgical procedures were analyzed., Results: The average systolic blood pressure variability was 9.47%±6.45% (maximum 46.04%), the average diastolic blood pressure variability was 12.18%±9.39% (maximum 88.00%), and the average heart rate variability was 10.59%±7.68% (maximum 49.12%). The effects of age and bone grafting on blood pressure variability, and of gender and immediate placement on heart rate variability, were statistically significant ( P < 0.05), respectively. The incidence of abnormal intraoperative blood pressure rise was 4.69%, of which there were 4 cases (0.63%) of systolic blood pressure ≥180 mmHg and/or diastolic blood pressure ≥110 mmHg. The incidence of abnormal intraoperative heart rate rise was 6.72%. Hierarchical analysis showed a higher risk of abnormal intraoperative blood pressure rise in the elderly (≥60 years) male patients [ P < 0.05, RR =3.409 (95% CI : 1.155-10.062) ] and flap elevation with bone grafting cases [ P < 0.05, RR =2.382 (95% CI : 1.126-5.040)], respectively. There was no statistically significant association between abnormal heart rate rise and patient characteristics or surgical procedures ( P >0.05)., Conclusion: There was a certain risk of blood pressure and heart rate variability during dental implant surgery. Elderly male patients and flap elevation with bone grafting were risk factors of abnormal intraoperative blood pressure rise.

HMGB1 is an important mediator of inflammation during ischemia-reperfusion injury on organs. The serum expression of HMGB1 was increased significantly on the 1st day after TACE and decreased significantly which was lower on the 30th day after TACE. Tumor markers of post-DEB-TACE decreased significantly. The correlational analysis showed that patients with low HMGB1 expression had lower risks of fever and liver injury compared those with the higher expression, while the ORR is relatively worse. Patients with lower expression of HMGB1 had longer PFS, better efficacy, and higher quality of life. With the high post-expression, the low expression had lower incidence of fever and liver injury too. There was no statistical difference in the one-year survival among the different groups. The quality of life of all patients was improved significantly. The over-expression of HMGB1 in LMCRC is an adverse prognostic feature and a positive predictor of response to TACE., 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 © 2020 Sun, Zhang, Chen, Wu, Zhang, Xu, Liu and Han.)

Effects of dietary supplemental stachyose on caecal skatole concentration, hepatic cytochrome P450 (CYP450, CYP) mRNA expressions and enzymatic activities in broilers were evaluated. Arbor Acre commercial mixed male and female chicks were assigned randomly into six treatments. The positive control (PC) diet was based on maize-soyabean meal, and the negative control (NC) diet was based on maize-non-soyabean meal. The NC diet was then supplemented with 4, 5, 6 and 7 g/kg stachyose to create experimental diets, named S-4, S-5, S-6 and S-7, respectively. Each diet was fed to six replicates of ten birds from days 1 to 49. On day 49, the caecal skatole concentrations in the PC, S-4, S-5, S-6 and S-7 groups were lower than those in the NC group by 42·28, 23·68, 46·09, 15·31 and 45·14 % (P < 0·01), respectively. The lowest pH value was observed in the S-5 group (P < 0·05). The stachyose-fed groups of broilers had higher caecal acetate and propionate levels compared with control groups, and propionate levels in the S-6 and S-7 groups were higher than those in the S-4 and S-5 groups (P < 0·001). The highest CYP3A4 expression was found in the S-7 group (P < 0·05), but this was not different from PC, S-4, S-5 and S-6 treatments. There was no significant difference in CYP450 (1A2, 2D6 and 3A4) enzymatic activities among the groups (P > 0·05). In conclusion, caecal skatole levels can be influenced by dietary stachyose levels, and 5 g/kg of stachyose in the diet was suggested.

Here, we first developed a combined strain improvement strategy of biosensor-guided atmospheric and room-temperature plasma mutagenesis and genome shuffling. Application of this strategy resulted in a 2.7-fold increase in the production of shikimic acid (SA) and a 2.0-fold increase in growth relative to those of the starting strain. Whole-cell resequencing of the shuffled strain and confirmation using CRISPRa/CRISPRi revealed that some membrane protein-related mutant genes are identified as being closely related to the higher SA titer. The engineered shuffling strain produced 18.58 ± 0.56 g/L SA from glucose with a yield of 68% (mol/mol) by fed-batch whole-cell biocatalysis, achieving 79% of the theoretical maximum. Sucrose-utilizing Escherichia coli was engineered for SA production by introducing Mannheimia succiniciproducens β-fructofuranosidase gene. The resulting sucrose-utilizing E. coli strain produced 24.64 ± 0.32 g/L SA from sucrose with a yield of 1.42 mol/mol by fed-batch whole-cell biocatalysis, achieving 83% of the theoretical maximum.

Objective: To investigate the clinical effect of minimally invasive surgery in the treatment of professional drivers with lumbar disc herniation. Methods: 126 patients with lumbar disc herniation admitted to hospital from June 1, 2015 to December 30, 2018 were selected and divided into observation group (59 cases treated by percutaneous transforaminal endoscopy) and control group (67 cases treated with conventional conservative treatment) according to the treatment methods. The Visual Analogue Scale (VAS) and Japanese Orthopaedic Association Scores (JOA) before and after treatment were analyzed retrospectively. Length of stay, time out of bed, hospitalization expenses and recurrence rate were evaluated. The measurement data was expressed by x ± s , the comparison between groups was performed by t test, and the count data were analyzed by descriptive analysis. Results: Before treatment, there was no significant difference in gender, age, VAS score and JOA score between the two groups ( P >0.05) . After treatment, compared with the control group, the VAS score of the observation group was lower, the JOA score was higher, the time out of bed was shorter, the average hospitalization time was reduced, the average hospitalization cost was higher, and the recurrence rates after Six months and one year were lower in the observation group, the differences were statistically significant ( P <0.05) . Conclusion: The clinical effect of percutaneous transforaminal endoscopic treatment is better than that of conventional conservative treatment for driver＇s lumbar disc herniation.

Peripheral blood lymphocyte subsets have been reported to be useful as prognostic and/or diagnostic markers for patients with cancer. However, the clinical value of peripheral blood lymphocyte subsets in gastric cancer (GC) has remained elusive. In the present study, peripheral CD3 + , CD4 + and CD8 + T lymphocytes, B cells (CD19 + ), regulatory T cells (Tregs; CD4 + CD25 + CD127 - ) and natural killer (NK) cells (CD3 - CDl6 + CD56 + ) were detected by flow cytometry in 122 patients with GC, 80 healthy donors (HDs) and 80 patients with gastric ulcer (GU). NK cells (CD56 + ) were detected by immunohistochemical (IHC) analysis in 20 GC and three GU tissue samples. A receiver-operating characteristic (ROC) curve was used to determine the threshold of the peripheral NK cell level and survival analysis was performed to assess its prognostic value in patients with GC. The results indicated that the peripheral NK cell proportion in patients with GC (18.77%) was significantly higher than that in the HD (12.19%) and GU (12.74%) groups. IHC analysis suggested that the NK level in GC tumor samples was correlated with that in paired serum samples. ROC curve analysis indicated that the peripheral NK cell level (15.16%) was able to effectively identify patients with GC, a diagnostic sensitivity of 75.41% and a specificity of 77.45% were determined. Multivariate logistic regression analysis revealed that the peripheral NK cell level was independently associated with the T stage and survival analysis demonstrated that high levels of peripheral NK cells were associated with poor prognosis of patients with GC. In conclusion, the peripheral NK cell level may be a diagnostic and prognostic marker for patients with GC., (Copyright: © Chen et al.)

The human proteome is a major source of therapeutic targets. Recent genetic association analyses of the plasma proteome enable systematic evaluation of the causal consequences of variation in plasma protein levels. Here we estimated the effects of 1,002 proteins on 225 phenotypes using two-sample Mendelian randomization (MR) and colocalization. Of 413 associations supported by evidence from MR, 130 (31.5%) were not supported by results of colocalization analyses, suggesting that genetic confounding due to linkage disequilibrium is widespread in naïve phenome-wide association studies of proteins. Combining MR and colocalization evidence in cis-only analyses, we identified 111 putatively causal effects between 65 proteins and 52 disease-related phenotypes ( https://www.epigraphdb.org/pqtl/ ). Evaluation of data from historic drug development programs showed that target-indication pairs with MR and colocalization support were more likely to be approved, evidencing the value of this approach in identifying and prioritizing potential therapeutic targets.

Importance: Genetic studies of Alzheimer disease have focused on the clinical or pathologic diagnosis as the primary outcome, but little is known about the genetic basis of the preclinical phase of the disease., Objective: To examine the underlying genetic basis for brain amyloidosis in the preclinical phase of Alzheimer disease., Design, Setting, and Participants: In the first stage of this genetic association study, a meta-analysis was conducted using genetic and imaging data acquired from 6 multicenter cohort studies of healthy older individuals between 1994 and 2019: the Anti-Amyloid Treatment in Asymptomatic Alzheimer Disease Study, the Berkeley Aging Cohort Study, the Wisconsin Registry for Alzheimer's Prevention, the Biomarkers of Cognitive Decline Among Normal Individuals cohort, the Baltimore Longitudinal Study of Aging, and the Alzheimer Disease Neuroimaging Initiative, which included Alzheimer disease and mild cognitive impairment. The second stage was designed to validate genetic observations using pathologic and clinical data from the Religious Orders Study and Rush Memory and Aging Project. Participants older than 50 years with amyloid positron emission tomographic (PET) imaging data and DNA from the 6 cohorts were included. The largest cohort, the Anti-Amyloid Treatment in Asymptomatic Alzheimer Disease Study (n = 3154), was the PET screening cohort used for a secondary prevention trial designed to slow cognitive decline associated with brain amyloidosis. Six smaller, longitudinal cohort studies (n = 1160) provided additional amyloid PET imaging data with existing genetic data. The present study was conducted from March 29, 2019, to February 19, 2020., Main Outcomes and Measures: A genome-wide association study of PET imaging amyloid levels., Results: From the 4314 analyzed participants (age, 52-96 years; 2478 participants [57%] were women), a novel locus for amyloidosis was noted within RBFOX1 (β = 0.61, P = 3 × 10-9) in addition to APOE. The RBFOX1 protein localized around plaques, and reduced expression of RBFOX1 was correlated with higher amyloid-β burden (β = -0.008, P = .002) and worse cognition (β = 0.007, P = .006) during life in the Religious Orders Study and Rush Memory and Aging Project cohort., Conclusions and Relevance: RBFOX1 encodes a neuronal RNA-binding protein known to be expressed in neuronal tissues and may play a role in neuronal development. The findings of this study suggest that RBFOX1 is a novel locus that may be involved in the pathogenesis of Alzheimer disease.

Among arthropod vectors, ticks transmit the most diverse human and animal pathogens, leading to an increasing number of new challenges worldwide. Here we sequenced and assembled high-quality genomes of six ixodid tick species and further resequenced 678 tick specimens to understand three key aspects of ticks: genetic diversity, population structure, and pathogen distribution. We explored the genetic basis common to ticks, including heme and hemoglobin digestion, iron metabolism, and reactive oxygen species, and unveiled for the first time that genetic structure and pathogen composition in different tick species are mainly shaped by ecological and geographic factors. We further identified species-specific determinants associated with different host ranges, life cycles, and distributions. The findings of this study are an invaluable resource for research and control of ticks and tick-borne diseases., Competing Interests: Declaration of Interests The authors declare no competing interests., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Autophagy is a conserved recycling system required for cellular homeostasis. Identifications of diverse selective receptors/adaptors that recruit appropriate autophagic cargoes have revealed critical roles of selective autophagy in different biological processes in plants. In this review, we summarize the emerging roles of selective autophagy in both biotic and abiotic stress tolerance and highlight the new features of selective receptors/adaptors and their interactions with both the cargoes and Autophagy-related gene 8s (ATG8s). In addition, we review how the two major degradation systems, namely the ubiquitin-proteasome system (UPS) and selective autophagy, are coordinated to cope with stress in plants. We especially emphasize how plants develop the selective autophagy as a weapon to fight against pathogens and how adapted pathogens have evolved the strategies to counter and/or subvert the immunity mediated by selective autophagy.

Single-atom catalysts (SACs) have attracted widespread interest for many catalytic applications because of their distinguishing properties. However, general and scalable synthesis of efficient SACs remains significantly challenging, which limits their applications. Here we report an efficient and universal approach to fabricating a series of high-content metal atoms anchored into hollow nitrogen-doped graphene frameworks (M-N-Grs; M represents Fe, Co, Ni, Cu, etc.) at gram-scale. The highly compatible doped ZnO templates, acting as the dispersants of targeted metal heteroatoms, can react with the incoming gaseous organic ligands to form doped metal-organic framework thin shells, whose composition determines the heteroatom species and contents in M-N-Grs. We achieved over 1.2 atom % (5.85 wt %) metal loading content, superior oxygen reduction activity over commercial Pt/C catalyst, and a very high diffusion-limiting current (6.82 mA cm -2 ). Both experimental analyses and theoretical calculations reveal the oxygen reduction activity sequence of M-N-Grs. Additionally, the superior performance in Fe-N-Gr is mainly attributed to its unique electron structure, rich exposed active sites, and robust hollow framework. This synthesis strategy will stimulate the rapid development of SACs for diverse energy-related fields., Competing Interests: The authors declare no competing financial interest., (Copyright © 2020 American Chemical Society.)

In this paper, we study two less-touched challenging problems in single image dehazing neural networks, namely, how to remove haze from a given image in an unsupervised and zeroshot manner. To the ends, we propose a novel method based on the idea of layer disentanglement by viewing a hazy image as the entanglement of several "simpler" layers, i.e., a hazy-free image layer, transmission map layer, and atmospheric light layer. The major advantages of the proposed ZID are two-fold. First, it is an unsupervised method that does not use any clean images including hazy-clean pairs as the ground-truth. Second, ZID is a "zero-shot" method, which just uses the observed single hazy image to perform learning and inference. In other words, it does not follow the conventional paradigm of training deep model on a large scale dataset. These two advantages enable our method to avoid the labor-intensive data collection and the domain shift issue of using the synthetic hazy images to address the real-world images. Extensive comparisons show the promising performance of our method compared with 15 approaches in the qualitative and quantitive evaluations. The source code could be found at www.pengxi.me.

Dermacentor everestianus is an important vector for several pathogens endemic in the Qinghai-Tibet Plateau. However, knowledge of its seasonal activity and abundance is limited. Hence, the seasonal dynamics of questing and host-feeding D. everestianus were investigated from March 2014 to February 2016 in Damxung County, north of Lhasa City in Tibet. During the 2-year period, questing ticks were collected weekly from two habitats (grassland and shrubs) by flag-dragging. Host-feeding ticks were removed weekly from sheep and their attachment sites were recorded. Plateau pikas (Ochotona curzoniae) captured by traps were examined for immature ticks from May to September 2014. Results revealed that questing D. everestianus were primarily distributed in grassland, whereas host-feeding adults and nymphs were mainly found on sheep, and larvae usually were on plateau pikas. Dermacentor everestianus can complete one generation per year with population overlap between the larvae and nymphs. Adults were mainly observed from February to April with the major peak occurring in late March. Additionally, unfed adults were detected on sheep from August to next February. Nymphs were found from late May to July and reached their peak in late June. Larvae collected during May and June reached peak numbers in late May.

To investigate the effect of microRNA-487b (miR-487b) as well as the underlying mechanism in osteosarcoma (OS). Data downloaded from the Gene Expression Omnibus (GEO) database were used to analyze the expression and prognostic value of miR-487b/TRAK2. Cell counting kit-8, colony formation, and transwell assays were performed to investigate the biological functions of miR-487b and TRAK2. Luciferase reporter assay was applied to confirm the interactions between miR-487b and TRAK2. miR-487b was overexpressed in OS tissues and was inversely associated with the prognosis of OS patients. We discovered that miR-487b could contribute to the proliferative, clonogenic, invasive, and migratory capabilities of OS cells. Through target prediction using miRWalk and differential expression analysis based on the GEO data set, trafficking kinesin protein 2 (TRAK2) was recognized as a potential target of miR-487b, which was further verified by luciferase reporter assay. The expression of TRAK2 was decreased in OS tissues compared with normal tissues and was positively correlated with the prognosis of OS patients. A negative relevance was presented between the expression of miR-487b and TRAK2 in OS cells. Of note, further mechanistic analyses indicated that TRAK2 was implicated in the regulatory effect of miR-487b on the cell malignant behaviors in OS. To sum up, these results demonstrated that miR-487b played an oncogenic role in OS progression via directly targeting TRAK2, which could advance the development of cancer treatment., (© 2020 Wiley Periodicals, Inc.)

Vascular calcification (VC) is an inducement of many cardiovascular diseases. Clinic evidences have confirmed that diabetes was the independent risk factor for VC, and the mechanism has not been well explored. Apelin as a ligand molecule is widely found in the cardiovascular system and showed potential in inhibiting VC, but the inhibitory effect and mechanism of apelin-13 against high glucose-induced VC have not been investigated yet. Herein, apelin-13 was employed to inhibit high glucose-induced VC in mouse aortic vascular smooth muscle cells (MOVAS), and the underlying mechanism was explored. The results showed that apelin-13 significantly inhibited high glucose-induced cells proliferation, migration and invasion of MOVAS cells. Apelin-13 also effectively attenuated high glucose-induced calcification by inhibiting alkaline phosphatase (ALP) activity and expression. Further investigation revealed that apelin-13 dramatically suppressed high glucose-induced DNA damage through inhibiting reactive oxide species (ROS) generation. Moreover, apelin-13 also effectively improved high glucose-induced dysfunction of MAPKs and PI3K/AKT. Inhibition of ERK by inhibitor (U0126) significantly blocked high glucose-induced calcification, which further confirmed the significance of MAPKs. Taken together, these results suggested that apelin-13 had the potential to attenuate high glucose-induced calcification of MOVAS cells by inhibiting ROS-mediated DNA damage and regulating MAPKs and PI3K/AKT pathways. Our findings validated the strategy of using apelin-13 maybe a novel way in treating high glucose-mediated VC., Competing Interests: Declaration of Competing Interest The authors declare that there is no conflict of interest for all the authors., (Copyright © 2020 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Biological ion channels have remarkable ion selectivity, permeability and rectification properties, but it is challenging to develop artificial analogues. Here, we report a metal-organic framework-based subnanochannel (MOFSNC) with heterogeneous structure and surface chemistry to achieve these properties. The asymmetrically structured MOFSNC can rapidly conduct K + , Na + and Li + in the subnanometre-to-nanometre channel direction, with conductivities up to three orders of magnitude higher than those of Ca 2+ and Mg 2+ , equivalent to a mono/divalent ion selectivity of 10 3 . Moreover, by varying the pH from 3 to 8 the ion selectivity can be tuned further by a factor of 10 2 to 10 4 . Theoretical simulations indicate that ion-carboxyl interactions substantially reduce the energy barrier for monovalent cations to pass through the MOFSNC, and thus lead to ultrahigh ion selectivity. These findings suggest ways to develop ion selective devices for efficient ion separation, energy reservation and power generation.

The mechanism by which miR-605-3p regulates hepatocellular carcinoma (HCC) metastasis has not been clarified. In this study, we found that miR-605-3p was down-regulated in HCC and that low miR-605-3p expression was associated with tumour thrombus and tumour satellites. HCC patients with low miR-605-3p expression showed shorter overall survival and disease-free survival after surgery. Overexpression of miR-605-3p inhibited epithelial-mesenchymal transition and metastasis of HCC through NF-κB signalling by directly inhibiting expression of TRAF6, while silencing of miR-605-3p had the opposite effect. We also found that SNHG16 directly bound to miR-605-3p as a competing endogenous RNA. Mechanistically, high expression of SNHG16 promoted binding to miR-605-3p and inhibited its activity, which led to up-regulation of TRAF6 and sustained activation of the NF-κB pathway, which in turn promoted epithelial-mesenchymal transition and metastasis of HCC. TRAF6 increased SNHG16 promoter activity by activating NF-κB, thereby promoting the transcriptional expression of SNHG16 and forming a positive feedback loop that aggravated HCC malignancy. Our findings reveal a mechanism for the sustained activation of the SNHG16/miR-605-3p/TRAF6/NF-κB feedback loop in HCC and provide a potential target for a new HCC treatment strategy., (© 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Background: 3-Hydroxy butyrate dehydrogenase 2 (BDH2) is a short-chain dehydrogenase/reductase family member that plays a key role in the development and pathogenesis of human cancers. However, the role of BDH2 in gastric cancer (GC) remains largely unclear. Our study aimed to ascertain the regulatory mechanisms of BDH2 in GC, which could be used to develop new therapeutic strategies., Methods: Western blotting, immunohistochemistry, and RT-PCR were used to investigate the expression of BDH2 in GC specimens and cell lines. Its correlation with the clinicopathological characteristics and prognosis of GC patients was analysed. Functional assays, such as CCK-8 and TUNEL assays, transmission electron microscopy, and an in vivo tumour growth assay, were performed to examine the proliferation, apoptosis, and autophagy of GC cells. Related molecular mechanisms were clarified by luciferase reporter, coimmunoprecipitation, and ubiquitination assays., Results: BDH2 was markedly downregulated in GC tissues and cells, and the low expression of BDH2 was associated with poor survival of GC patients. Functionally, BDH2 overexpression significantly induced apoptosis and autophagy in vitro and in vivo. Mechanistically, BDH2 promoted Keap1 interaction with Nrf2 to increase the ubiquitination level of Nrf2. Ubiquitination/degradation of Nrf2 inhibited the activity of ARE to increase accumulation of reactive oxygen species (ROS), thereby inhibiting the phosphorylation levels of Akt Ser473 and mTOR Ser2448 ., Conclusions: Our study indicates that BDH2 is an important tumour suppressor in GC. BDH2 regulates intracellular ROS levels to mediate the PI3K/Akt/mTOR pathway through Keap1/Nrf2/ARE signalling, thereby inhibiting the growth of GC.

The 1T' phase of transition metal dichalcogenides (TMDs) is a low symmetry charge density wave (CDW) phase, which can be viewed as a periodically distorted structure (Peierls distortion) of the high symmetry 1T phase. In this paper, using density functional theory (DFT) calculations, we report that the positive charge (hole) injection is an effective method to modulate the Peierls distortion of MoS2 1T' for a new CDW phase and superior electromechanical properties. A new stable CDW phase is discovered at a hole doping level of 0.10 h+ per atom, named 1T't. Hole charging and discharging can induce a reversible phase transition of MoS2 among the three phases, 1T, 1T' and 1T't. Such a reversible phase transition leads to superior electromechanical properties including a strain output as high as -5.8% with a small hysteresis loop, multi-step super-elasticity, and multi-shape memory effect, which are valuable in active electromechanical device designs at the nanoscale. In-depth analysis of the change of the electronic structure under hole doping was performed to understand the new CDW phase and the observed phase transition. Using charge doping to modulate the Peierls distortion in two-dimensional materials can serve as a general concept for nano-active material designs.