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Bacterial cellulose (BC), a natural biomaterial synthesized by bacteria, has a unique structure of a cellulose nanofiber-weaved three-dimensional reticulated network. BC films can be ultrasoft with sufficient mechanical strength, strong water absorption and moisture retention and have been widely used in facial masks. These films have the potential to be applied to implantable neural interfaces due to their conformality and moisture, which are two critical issues for traditional polymer or silicone electrodes. In this work, we propose a micro-electrocorticography (micro-ECoG) electrode named "Brainmask", which comprises a BC film as the substrate and separated multichannel parylene-C microelectrodes bonded on the top surface. Brainmask can not only guarantee the precise position of microelectrode sites attached to any nonplanar epidural surface but also improve the long-lasting signal quality during acute implantation with an exposed cranial window for at least one hour, as well as the in vivo recording validated for one week. This novel ultrasoft and moist device stands as a next-generation neural interface regardless of complex surface or time of duration., Competing Interests: Conflict of interestThe authors declare no competing interests., (© Aerospace Information Research Institute, Chinese Academy of Sciences 2023.)

Background: The Appraisal of Guidelines for Research and Evaluation II (AGREE II) instrument was developed to improve the methodological quality of clinical practice guidelines (CPGs). High-quality guidelines can provide reliable recommendations for different clinical issues. Currently, there is no quality appraisal of CPGs for urolithiasis. This study evaluated the quality of evidence-based CPGs for urolithiasis and provided new insights into improving guideline quality on urolithiasis., Methods: Systematic reviews were conducted to identify urolithiasis CPGs in PubMed, electronic databases, and websites of medical associations from January 2009 to July 2022. The quality of included CPGs was evaluated by four reviewers using the AGREE II instrument. Subsequently, the scores of all domains in the AGREE II instrument were calculated., Results: A total of 19 urolithiasis CPGs were identified for review: seven from Europe, six from USA, three from international union, two from Canada, and one from Asia. The agreement among reviewers was rated good [intraclass correlation coefficient (ICC), 0.806; 95% CI: 0.779-0.831]. The domains with the highest scores were scope and purpose (69.7%, 54.2-86.1%) and clarity of presentation (76.8%, 59.7-90.3%). The domains of stakeholder involvement (44.9%, 19.4-84.7%) and applicability (48.5%, 30.2-72.9%) gained the lowest score. Only five guidelines (26.3%) were considered "strongly recommended"., Conclusions: The overall quality of the eligible CPGs was relatively high; however, future work is still needed in the domains of rigor of development, editorial independence, applicability, and stakeholder involvement., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tau.amegroups.com/article/view/10.21037/tau-22-846/coif). The authors have no conflicts of interest to declare., (2023 Translational Andrology and Urology. All rights reserved.)

Potassium plays important roles in most plant physiological processes. Arbuscular mycorrhizal (AM) fungi promote plant water and mineral nutrient acquisition to promote plant growth. However, few studies have focused on the effect of AM colonization on potassium uptake by the host plant. In this study, the effects of an AM fungus ( Rhizophagus irregularis ) and potassium concentration (0, 3, or 10 mM K + ) on Lycium barbarum were evaluated. A split-root test with L. barbarum seedlings was conducted, and the potassium uptake capacity of LbKAT3 was verified in yeast. A tobacco line overexpressing LbKAT3 was generated and mycorrhizal functions under two potassium concentrations (0.2 and 2 mM K + ) were studied. Inoculation of R. irregularis and application of potassium increased the dry weight, and potassium and phosphorus contents of L. barbarum , and increased the colonization rate and arbuscule abundance of R. irregularis . In addition, the expression of LbKAT3 and AQP genes in L. barbarum was upregulated. Inoculation of R. irregularis induced LbPT4 , Rir-AQP1 , and Rir-AQP2 expression, and application of potassium upregulated the expression of these genes. Inoculation with the AM fungus locally regulated the expression of LbKAT3 . Inoculation of R. irregularis improved the growth, and potassium and phosphorus contents, and induced NtPT4 , Rir-AQP1 , and Rir-AQP2 expression in tobacco overexpressing LbKAT3 under both potassium concentrations. Overexpression of LbKAT3 in tobacco improved the growth, potassium accumulation, and AM colonization, and upregulated the expression of NtPT4 and Rir-AQP1 in mycorrhizal tobacco. The results suggest that LbKAT3 may assist in mycorrhizal potassium uptake, and overexpression of LbKAT3 may promote potassium, phosphorus, and water transport from the AM fungus to tobacco., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Han, Zhou, Li, Ren, Liu, Zhang, Zhang and Tang.)

As a highly conserved, multifunctional protein with multiple domains, p62/SQSTM1 plays a crucial role in several essential cellular activities, particularly selective autophagy. Recent research has shown that p62 is crucial in eradicating intracellular bacteria by xenophagy, a selective autophagic process that identifies and eliminates such microorganisms. This review highlights the various roles of p62 in intracellular bacterial infections, including both direct and indirect, antibacterial and infection-promoting aspects, and xenophagy-dependent and independent functions, as documented in published literature. Additionally, the potential applications of synthetic drugs targeting the p62-mediated xenophagy mechanism and unresolved questions about p62's roles in bacterial infections are also discussed., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhou, Hua and Song.)

We developed a mechanism model which allows for simulating the novel coronavirus (COVID-19) transmission dynamics with the combined effects of human adaptive behaviours and vaccination, aiming at predicting the end time of COVID-19 infection in global scale. Based on the surveillance information (reported cases and vaccination data) between 22 January 2020 and 18 July 2022, we validated the model by Markov Chain Monte Carlo (MCMC) fitting method. We found that (1) if without adaptive behaviours, the epidemic could sweep the world in 2022 and 2023, causing 3.098 billion of human infections, which is 5.39 times of current number; (2) 645 million people could be avoided from infection due to vaccination; and (3) in current scenarios of protective behaviours and vaccination, infection cases would increase slowly, levelling off around 2023, and it would end completely in June 2025, causing 1.024 billion infections, with 12.5 million death. Our findings suggest that vaccination and the collective protection behaviour remain the key determinants against the global process of COVID-19 transmission.

Introduction: COVID-19 (SARS-CoV-2) has been linked to organ damage in humans since its worldwide outbreak. It can also induce severe sperm damage, according to research conducted at numerous clinical institutions. However, the exact mechanism of damage is still unknown. Methods: In this study, testicular bulk-RNA-seq Data were downloaded from three COVID-19 patients and three uninfected controls from GEO to evaluate the effect of COVID-19 infection on spermatogenesis. Relative expression of each pathway and the correlation between genes or pathways were analyzed by bioinformatic methods. Results: By detecting the relative expression of each pathway and the correlation between genes or pathways, we found that COVID-19 could induce testicular cell senescence through MAPK signaling pathway. Cellular senescence was synergistic with MAPK pathway, which further affected the normal synthesis of cholesterol and androgen, inhibited the normal synthesis of lactate and pyruvate, and ultimately affected spermatogenesis. The medications targeting MAPK signaling pathway, especially MAPK1 and MAPK14, are expected to be effective therapeutic medications for reducing COVID-19 damage to spermatogenesis. Conclusion: These results give us a new understanding of how COVID-19 inhibits spermatogenesis and provide a possible solution to alleviate this damage., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Wang, Ma, Chen, Yang, Liu, Pan, Wang, Liu, Zhou, Zhang, Zhou, Yang, Zou, Lin, Cai, Jiang, Zhou and Zhao.)

To break the stereotype that silica can only be reduced via a magnesiothermic and aluminothermic method at low-temperature condition, the novel strategy for converting silica to SiO x using disproportionation effect of SnO generated via low-temperature pyrolysis coreduction reaction between SnO 2 and rice husk is proposed, without any raw materials waste and environmental hazards. After the low-temperature pyrolysis reaction, SnO y @C/SiO x composites with unique structure (Sn/SnO 2 dispersed on the surface and within pores of biochar as well as SiO x residing in the interior) are obtained due to the exclusive biological properties of rice husk. Such unique structural features render SnO y @C/SiO x composites with an excellent talent for repairing the damaged structure and the highly electrochemical storage ability (530.8 mAh g -1 at 10 A g -1 after 7500 cycles). Furthermore, assembled LiFePO 4 ||SnO y -50@C/SiO x full cell displays a high discharge capacity of 463.7 mAh g -1 after 100 cycles at 0.2 A g -1 . The Li + transport mechanism is revealed by density functional theory calculations. This work provides references and ideas for green, efficient, and high-value to reduce SiO 2 , especially in biomass, which also avoids the waste of raw materials in the production process, and becomes an essential step in sustainable development., (© 2022 Wiley-VCH GmbH.)

Platycladus orientalis is a significant woody plant for phytoremediation in heavy metals contaminated soils. The growth and tolerance of host plants under the lead (Pb) stress were enhanced by arbuscular mycorrhizal fungi (AMF). To evaluate the adjustment by AMF on growth and activity of antioxidant system of P. orientalis under Pb stress. The two-factor pot experiment was conducted with three AM fungal treatments (noninoculated, Rhizophagus irregularis , and Funneliformis mosseae ) and four Pb levels (0, 500, 1000, and 2000 mg kg -1 ). AMF increased dry weight, phosphorus uptake, root vitality, and total chlorophyll content of P. orientalis in spite of Pb stress. Compared with nonmycorrhizal treatments, mycorrhizal P. orientalis had lower H 2 O 2 and malondialdehyde (MDA) contents under Pb stress. AMF increased Pb uptake in roots and decreased the Pb translating to the shoots yet under Pb stress. Total glutathione and ascorbate in roots of P. orientalis were decreased by AMF inoculation. Mycorrhizal P. orientalis had higher superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), and glutathione S-transferase (GST) activities in shoots and roots than nonmycorrhizal counterparts. Mycorrhizal P. orientalis under Pb stress showed higher expression of PoGST1 and PoGST2 in roots than that in CK treatments. Future studies will explore the function of induced tolerance genes by AMF of P. orientalis under Pb stress.

Background: Nonalcoholic fatty liver disease (NAFLD) poses a substantial socioeconomic burden and is becoming the fastest growing driver of chronic liver disease, potentially accompanied by a poor prognosis., Objective: We aim to elucidate the global and regional epidemiologic changes in NAFLD during the past 30 years and explore the interconnected diseases., Methods: Data on NAFLD incidence, prevalence, death, and disability-adjusted life-years (DALYs) were extracted from the Global Burden of Disease Study 2019. The age-standardized incident rate (ASIR), age-standardized prevalent rate (ASPR), age-standardized death rate (ASDR), and age-standardized DALYs were calculated to eliminate the confounding effects of age when comparing the epidemiologic changes between different geographical regions. In addition, we also investigated the correlation between the NAFLD burden and the sociodemographic index (SDI). Finally, the associations of the 3 common comorbidities with NAFLD were determined., Results: Globally, the incidence and prevalence of NAFLD both increased drastically during the past 3 decades (incidence: from 88,180 in 1990 to 172,330 in 2019, prevalence: from 561,370,000 in 1990 to 1,235,700,000 in 2019), mainly affecting young adults who were aged from 15 to 49 years. The ASIR increased slightly from 1.94 per 100,000 population in 1990 to 2.08 per 100,000 population in 2019, while ASPR increased from 12,070 per 100,000 population in 1990 to 15,020 per 100,000 population in 2019. In addition, the number of deaths and DALYs attributable to NAFLD increased significantly as well from 93,760 in 1990 to 168,970 in 2019 and from 2,711,270 in 1990 to 4,417,280 in 2019, respectively. However, the ASDR and age-standardized DALYs presented decreasing trends with values of estimated annual percentage change equaling to -0.67 and -0.82, respectively (ASDR: from 2.39 per 100,000 population in 1990 to 2.09 per 100,000 population in 2019; age-standardized DALYs: from 63.28 per 100,000 population in 1990 to 53.33 per 100,000 population in 2019). Thereinto, the burden of death and DALYs dominated the patients with NAFLD who are older than 50 years. Moreover, SDI appeared to have obvious negative associations with ASPR, ASDR, and age-standardized DALYs among 21 regions and 204 countries, although there is no marked association with ASIR. Finally, we found that the incidence and prevalence of NAFLD were positively related to those of diabetes mellitus type 2, stroke, and ischemic heart disease., Conclusions: NAFLD is leading to increasingly serious health challenges worldwide. The morbidity presented a clear shift toward the young populations, while the heavier burden of death and DALYs in NAFLD was observed in the aged populations and in regions with relatively low SDI. Comprehensive acquisition of the epidemiologic pattern for NAFLD and the identification of high-risk comorbidities may help policy makers and clinical physicians develop cost-effective prevention and control strategies, especially in countries with a high NAFLD burden., (©Huilong Chen, Yuan Zhan, Jinxiang Zhang, Sheng Cheng, Yuhao Zhou, Liyuan Chen, Zhilin Zeng. Originally published in JMIR Public Health and Surveillance (https://publichealth.jmir.org), 12.12.2022.)

Developing a bottom-water reservoir with rupturable interlayers is a significant challenge. This paper used a 2D visualization model to study the seepage characteristics of gas-water in two phases during noncondensable gas antiwater invasion. On this basis, the mechanisms of antiwater invasion and enhanced oil recovery (EOR) were summarized. The results show that bottom water advances from the crack of the interlayer to the oil layer, leading to a profile of radial flow. The major swept area occupies the scope near the horizontal well and the oil layer's middle part. Therefore, a lot of remaining oil distributes beside the crack of the interlayer. Noncondensable gas preferentially flows into the water-swept area due to a lower seepage resistance. Under gravity differentiation, the dispersed gas displaces the invaded bottom water downward, inhibiting water from invading and increasing the oil production rate. These studies provide practical guidance for analyzing bottom-water invading processes and designing suitable measures to develop such reservoirs., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

Since the effects of mono-unsaturated fatty acids (MUFA) on lipid profile are still controversial, a meta-analysis of randomized controlled trials was conducted in the present study to assess the effect of MUFA-rich food on lipid profiles. The study was designed, conducted, and reported according to the guidelines of the 2020 preferred reporting items for systematic reviews and meta-analysis (PRISMA) statement. A systematic and comprehensive search was performed in several databases from inception up to 30 January 2022. The results showed that the intake of edible oil-derived MUFA (EDM) could increase the blood HDL-C level (mean difference = 0.08; 95%CI: -0.01, 0.17, p = 0.03), but did not affect the level of TC, TG, or LDL-C. Moreover, the consumption of other food-derived MUFA (ODM) significantly decreased TG concentration (mean difference = -0.35; 95%CI: -0.61, -0.09, p = 0.01)), but did not affect the level of TC, LDL-C, or HDL-C. Findings from this study suggest that MUFA-rich food might be beneficial to modulate the blood lipid profile.

A multi-objective optimization based on the non-dominated sorting genetic algorithm (NSGA-II) is carried out in the present work for the basic organic Rankine cycle (BORC) and regenerative ORC (RORC) systems. The selection of working fluids is integrated into multi-objective optimization by parameterizing the pure working fluids into a two-dimensional array. Two sets of decision indicators, exergy efficiency vs. thermal efficiency and exergy efficiency vs. levelized energy cost (LEC), are adopted and examined. Five decision variables including the turbine inlet temperature, vapor superheat degree, the evaporator and condenser pinch temperature differences, and the mass fraction of the mixture are optimized. It is found that the turbine inlet temperature is the most effective factor for both the BORC and RORC systems. Compared to the reverse variation of exergy efficiency and thermal efficiency, only a weak conflict exists between the exergy efficiency and LEC which tends to make the binary objective optimization be a single objective optimization. The RORC provides higher thermal efficiency than BORC at the same exergy efficiency while the LEC of RORC also becomes higher because the bare module cost of buying one more heat exchange is higher than the cost reduction due to the reduced heat transfer area. Under the heat source temperature of 423.15 K, the final obtained exergy and thermal efficiencies are 45.6% and 16.6% for BORC, and 38.6% and 20.7% for RORC, respectively.

Hypertension is the most common chronic disease and the primary risk factor for cardiovascular diseases. Prehypertension is closely related to a variety of cardiovascular disease risk factors during the development of hypertension. The objective of this study was to explore the relationship between dietary patterns and hypertension in Jiangsu Province. Specifically, we included the participants from 2007 and then followed up in 2014 in the Jiangsu Province of China and collected information from food frequency questionnaires, anthropometric measurements, and disease self-reports. A total of 1762 women and men were included in the final analysis. We extracted four dietary patterns using factor analysis, calculated the pattern-specific factor scores, and divided the scores into quartiles, which increased from Q1 to Q4. Compared with participants in Q1, an increased risk of high diastolic blood pressure was found in Q4 of the snack dietary pattern. Additionally, participants in Q2-Q4 of the frugal dietary pattern were found to have a positive association with abnormal blood pressure. However, the results found in the frugal dietary pattern vanished after adjusting more confounders in Q4 of high systolic blood pressure. We found that some food items were associated with hypertension and prehypertension. The overconsumption of salt and alcohol are risk factors for both prehypertension and hypertension. Added sugar and saturated fatty acids are risk factors for hypertension, which may provide suggestions for the residents in China to change dietary habits to prevent prehypertension and hypertension.

As key regulators of gene function, long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs) are generally accepted to be involved in lung cancer pathogenesis and progression. Recent research has clarified the phenomenon of metabolic reprogramming in lung cancer because of its significant role in tumor proliferation, migration, invasion, metastasis, and other malignant biological behaviors. Emerging evidence has also shown a relationship between the aberrant expression of lncRNAs and circRNAs and metabolic reprogramming in lung cancer tumorigenesis. This review provides insight regarding the roles of different lncRNAs and circRNAs in lung cancer metabolic reprogramming, by how they target transporter proteins and key enzymes in glucose, lipid, and glutamine metabolic signaling pathways. The clinical potential of lncRNAs and circRNAs as early diagnostic biomarkers and components of therapeutic strategies in lung cancer is further discussed, including current challenges in their utilization from the bench to the bedside and how to adopt a proper delivery system for their therapeutic use., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 Yuhao Zhou et al.)

The standard potential of a lithium metal electrode versus the standard hydrogen electrode was calculated by constructing the thermodynamic cycle in a hypothetical electrochemical cell with a dual-phase electrolyte. It is demonstrated that the standard potential of the lithium metal electrode can fluctuate over 0.5 V in different organic solvents, and is correlated to the modified donor number by the entropy of fusion of the solvents.

Lung cancer is one of the main cancer types due to its persistently high incidence and mortality, yet a simple and effective prognostic model is still lacking. This study aimed to identify independent prognostic genes related to the heterogeneity of lung adenocarcinoma (LUAD), generate a prognostic risk score model, and construct a nomogram in combination with other pathological characteristics to predict patients' overall survival (OS). A significant amount of data pertaining to single-cell RNA sequencing (scRNA-seq), RNA sequencing (RNA-seq), and somatic mutation were used for data mining. After statistical analyses, a risk scoring model was established based on eight independent prognostic genes, and the OS of high-risk patients was significantly lower than that of low-risk patients. Interestingly, high-risk patients were more sensitive and effective to immune checkpoint blocking therapy. In addition, it was noteworthy that CCL20 not only affected prognosis and differentiation of LUAD but also led to poor histologic grade of tumor cells. Ultimately, combining risk score, clinicopathological information, and CCL20 mutation status, a nomogram with good predictive performance and high accuracy was established. In short, our research established a prognostic model that could be used to guide clinical practice based on the constantly updated big multi-omics data. Finally, this analysis revealed that CCL20 may become a potential therapeutic target for LUAD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zheng, Zhang, Jiang, Wang, Liu, Zhou, Zhou and Liu.)

The acoustic signal in the operation of a power transformer contains a lot of transformer operation state information, which is of great significance to the detection of DC bias state. In this paper, three typical parameters used for DC bias state detection are selected by comparing the acoustic variation of a 500 kV Jingting transformer substation No. 2 transformer with that of the core model built in the laboratory; then, acoustic samples of the 162 EHV normal state transformers are collected, and the distribution regularity of three typical parameters in normal state is given. Finally, according to the distribution regularity, clear warning threshold of typical parameters are given, and the DC bias cases from the 500 kV Jingting transformer substation are used to verify the effectiveness of the threshold.

Eucommia ulmoides Oliver has been used extensively in many fields. To satisfy increasing demand, great efforts must be made to further improve its traits. However, limited information is available on these traits, which is a factor that restricts their improvement. To improve traits directionally, nine clones were assigned to six sites to analyze the effect of different variation sources (the genotype, site, and genotype × environment interaction) on the phenotypic trait. In addition, a mixed linear model was used to assess the contribution of variations. In general, for most traits, the site effect accounted for a larger proportion of the variance, followed by the genotype and genotype × environment interaction effects. All the studied genotypes and sites had a significant effect, indicating that they could be improved by selecting preferable genotypes or cultivation areas, respectively. Interestingly, growth traits or economic traits could be improved simultaneously. Trait performance and stability are necessary when selecting genotypes. Moreover, the discriminating ability of genotypes should be considered in selecting cultivation areas. Annual mean temperature and annual sunshine duration proved to be crucial factors that affected the traits. They were correlated positively with economic traits and leaf yield and correlated negatively with growth traits. These findings contributed to selecting a wider range of cultivation areas. Regarding the genotype × environment interaction effect, there were significant differences only in the gutta-percha content, the total number of leaves, and the chlorogenic acid content. These traits could also be improved by choosing appropriate genotypes for the local environment. The research has provided preliminary data on the main factors that affect the traits of E. ulmoides and offered solutions for trait improvement. This information could be a reference for the trait improvement of other plants., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Deng, Wang, Hu, Yu, Liang, Zhang, Wang, Zhou and Li.)

This paper investigates the problem of adaptive tracking control for a class of nonlinear multi-input and multi-output (MIMO) state-constrained systems with input delay and saturation. During the process of the control scheme, neural network is employed to approximate the unknown nonlinear uncertainties and the appropriate barrier Lyapunov function is introduced to prevent violation of the constraint. In addition, for the issue of input saturation with time delay, a smooth non-affine approximate function and a novel auxiliary system are utilized, respectively. Moreover, adaptive neural tracking control is developed by combining the command filtering backstepping approach, which effectively avoids the explosion of differentiation and reduces the computation burden. The introduced filtering error compensating system brings a significant improvement for the system tracking performance. Finally, the simulation result is presented to verify the feasibility of the proposed strategy., 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 Ltd. All rights reserved.)

Polypeptide-based injectable hydrogels have attracted the attention of biomedical researchers due to their unique biocompatibility and biodegradability, tunable residue chirality, and secondary conformation of polypeptide chains. In the present study, four types of poly(ethylene glycol)- block -poly(glutamic acid)s with different topological structures and residue chirality of polypeptide segments were developed, which were grafted with tyramine side groups for further cross-linking. The results demonstrated that the covalent conjugation between the tyramine groups in the presence of horseradish peroxidase and hydrogen peroxide could form porous hydrogels rapidly. Additionally, the gelation time and mechanical strength of the hydrogels were measured. All the polymer precursors and hydrogels exhibited good cytocompatibility in vitro. Further assessment of the enzymatic degradability of the hydrogels and copolymers in vitro revealed that the degradation rate was influenced by the adjustment of polymer topology or residue chirality of polypeptide copolymers. Subsequently, the effect of copolymer topology and polypeptide chirality on in vivo biodegradability and biocompatibility was assessed. This study will provide insights into the relationship between copolymer structures and hydrogel properties and benefit future polypeptide-based hydrogel studies in biomedical applications.

Hearing loss is one of the most common disabilities affecting both children and adults worldwide. However, traditional treatment of hearing loss has some limitations, particularly in terms of drug delivery system as well as diagnosis of ear imaging. The blood-labyrinth barrier (BLB), the barrier between the vasculature and fluids of the inner ear, restricts entry of most blood-borne compounds into inner ear tissues. Nanoparticles (NPs) have been demonstrated to have high biocompatibility, good degradation, and simple synthesis in the process of diagnosis and treatment, which are promising for medical applications in hearing loss. Although previous studies have shown that NPs have promising applications in the field of inner ear diseases, there is still a gap between biological research and clinical application. In this paper, we aim to summarize developments and challenges of NPs in diagnostics and treatment of hearing loss in recent years. This review may be useful to raise otology researchers' awareness of effect of NPs on hearing diagnosis and treatment., 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 Huang, Xie, Li, Zhou, He, Lin, Yang, Song and Chen.)

In the past decades, apoptosis has been the most well-studied regulated cell death (RCD) that has essential functions in tissue homeostasis throughout life. However, a novel form of RCD called necroptosis, which requires receptor-interacting protein kinase-3 (RIPK3) and mixed-lineage kinase domain-like pseudokinase (MLKL), has recently been receiving increasing scientific attention. The phosphorylation of RIPK3 enables the recruitment and phosphorylation of MLKL, which oligomerizes and translocates to the plasma membranes, ultimately leading to plasma membrane rupture and cell death. Although apoptosis elicits no inflammatory responses, necroptosis triggers inflammation or causes an innate immune response to protect the body through the release of damage-associated molecular patterns (DAMPs). Increasing evidence now suggests that necroptosis is implicated in the pathogenesis of several human diseases such as systemic inflammation, respiratory diseases, cardiovascular diseases, neurodegenerative diseases, neurological diseases, and cancer. This review summarizes the emerging insights of necroptosis and its contribution toward the pathogenesis of lung diseases., 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, Zhou, Zhou, Liu, Jiang, Zhang and Liu.)

Objective: To evaluate epidemiological characteristics and transmission dynamics of COVID-19 outbreak resurged in Beijing and to assess the effects of three non-pharmaceutical interventions., Design: Descriptive and modelling study based on surveillance data of COVID-19 in Beijing., Setting: Outbreak in Beijing., Participants: The database included 335 confirmed cases of COVID-19., Methods: To conduct spatiotemporal analyses of the outbreak, we collected individual records on laboratory-confirmed cases of COVID-19 from 11 June 2020 to 5 July 2020 in Beijing, and visitor flow and products transportation data of Xinfadi Wholesale Market. We also built a modified susceptible-exposed-infected-removed model to investigate the effect of interventions deployed in Beijing., Results: We found that the staff working in the market (52.2%) and the people around 10 km to this epicentre (72.5%) were most affected, and the population mobility entering-exiting Xinfadi Wholesale Market significantly contributed to the spread of COVID-19 (p=0.021), but goods flow of the market had little impact on the virus spread (p=0.184). The prompt identification of Xinfadi Wholesale Market as the infection source could have avoided a total of 25 708 (95% CI 13 657 to 40 625) cases if unnoticed transmission lasted for a month. Based on the model, we found that active screening on targeted population by nucleic acid testing alone had the most significant effect., Conclusions: The non-pharmaceutical interventions deployed in Beijing, including localised lockdown, close-contact tracing and community-based testing, were proved to be effective enough to contain the outbreak. Beijing has achieved an optimal balance between epidemic containment and economic protection., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Oral peptide or protein delivery is considered a revolutionary alternative to daily subcutaneous injection; however, major challenges remain in terms of impediments of the gastrointestinal environment and the intestinal epithelium consisting of mucus and the epithelial cell layer, leading to low bioavailability. To protect against gastrointestinal degradation and promote penetration across the intestinal mucosa, a pH-triggered self-unpacking capsule encapsulating zwitterionic hydrogel-coated metal-organic framework (MOF) nanoparticles is engineered. The MOF nanoparticles possess a high exendin-4 loading capacity, and the zwitterionic hydrogel layer imparts unique capability of permeation across the mucus layer and effective internalization by epithelial cells to the nano-vehicles. In addition to the gastro-resistant feature, the pH-responsive capsules are dissociated drastically in the intestinal environment due to the rapid generation of abundant CO 2 bubbles, which triggers a sudden release of the nanoparticles. After oral administration of the capsules containing exendin-4-loaded nanoparticles into a diabetes rat model, markedly enhanced plasma exendin-4 levels are achieved for over 8 h, leading to significantly increased endogenous insulin secretion and a remarkable hypoglycemic effect with a relative pharmacological availability of 17.3%. Owing to the low risk of hypoglycemia, this oral exendin-4 strategy will provide a vast potential for daily and facile diabetes treatment., (© 2021 Wiley-VCH GmbH.)

Objective: Von Hippel-Lindau (VHL) syndrome is a rare disease that occurs in an autosomal-dominant genetic pattern. Due to the high genetic variability of VHL diseases, current studies have limited clinical value. Moreover, casual genetic variations in patients with VHL syndrome are still unclear., Methods: Here, we performed whole-exome sequencing of 25 individuals to identify reliable disease-related variations. Systemic computational analysis was performed for variant detection, and Sanger sequencing was used to validate detected mutations., Results: Most of the known mutations in the VHL gene were observed in the studied population. In addition, a large fragment deletion in VHL exon 2 in the immediate family members of the last family was detected. This had not been reported earlier. Moreover, we identified 3 novel mutation sites in the MAP2K3 gene that may be involved in the occurrence and development of the VHL disease., Conclusions: These results demonstrated that the heterogeneous nature of VHL syndrome and novel mutational signatures may help to improve the diagnostic ability of VHL syndrome., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Haemaphysalis longicornis, a vector of various pathogens with medical and veterinary importance, is native to eastern Asia, and recently reached the USA as an emerging disease threat. In this study, we aimed to identify the geographical distribution, hosts, and associated pathogens of H longicornis., Methods: Data were collected from multiple sources, including a field survey, reference book, literature review, and related websites. The thematic maps showing geographical distribution of H longicornis and associated pathogens were produced by ArcGIS. Hosts of H longicornis and positive rates for H longicornis-associated pathogens were estimated by meta-analysis. Ecological niche modelling was used to predict potential global distribution of H longicornis., Findings: H longicornis was found to be present in ten countries, predominantly in eastern Asia, the USA, Australia, and New Zealand. The tick was known to feed on a variety of domestic and wild animals, and humans. At least 30 human pathogens were associated with H longicornis, including seven species of spotted fever group rickettsiae, seven species in the family of Anaplasmataceae, four genospecies in the complex Borrelia burgdorferi sensu lato, two Babesia species, six species of virus, and Francisella, Bartonella, Coxiella, and Toxoplasma, which were mainly reported in eastern Asia. The predictive modelling revealed that H longicornis might affect more extensive regions, including Europe, South America, and Africa, where the tick has never been recorded before., Interpretation: H longicornis is relatively common in the world, and is associated with various human and animal pathogens. Authorities and health-care workers should be aware of the threat of the tick species to public health and veterinary medicine. Surveillance and further investigations should be enhanced globally., Funding: National Natural Science Foundation of China and National Key Research and Development Program of China., (Copyright © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Objective: To investigate the effects of lycopene on metabolism of glycolipid and inflammation in rats with non-alcoholic fatty liver disease., Methods: According to body weight, sixty male Sprague-Dawley rats were randomly divided into control group, non-alcoholic fatty liver model group, 20, 60 mg/kg lycopene intervention groups, with 15 rats in each group. The control group was fed normal diet, and the other 3 groups were fed high-fat and high-fructose diet for 4 weeks to establish the model of non-alcoholic fatty liver disease. After modeling, the intervention groups were fed lycopene of different doses by gavage. After 8 weeks of continuous feeding, the rats were sacrificed, the body weight and liver weight were weighed, and the liver index was calculated. Hematoxylin-eosin staining was used to observe the morphological changes of liver tissue. Serum was collected, fasting blood glucose(FBG), fasting insulin(INS), and insulin resistance index(HOMA-IR) were calculated; Liver function indicators alanine aminotransferase(ALT), aspartate aminotransferase(AST) were measured; Serum triglycerides(TG), total cholesterol(TC), high density lipoprotein-cholesterol(HDL-C), low density lipoprotein-cholesterol(LDL-C) and levels of inflammatory cytokines interleukin-6(IL-6), interleukin-18(IL-18) and interleukin-1β(IL-1β) were measured., Results: Compared with the control group, the liver weight and liver index in the model group increased by 27% and 24%, respectively; And steatosis occurred in the liver tissue; The levels of serum ALT, TG, TC, LDL-C, IL-6, IL-1β were significantly increased, the level of serum HDL-C was significantly decreased(P<0. 05). Compared with the model group, liver weight, liver index, levels of serum ALT, TG, FBG, IL-6 and IL-1β were significantly lower in the 20, 60 mg/kg lycopene intervention groups(P<0. 05), the INS and HOMA-IR index showed a downward trend; Liver tissue lesions were reduced to different degrees, and the effect was more significant in the 60 mg/kg lycopene group., Conclusion: Lycopene can improve non-alcoholic fatty liver disease by regulating glycolipid metabolism and reducing levels of inflammatory cytokines in rats.