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Naphthylimides play a pivotal role as aromatic heterocyclic compounds, serving as the foundational structures for numerous pharmacologically significant drugs. These drugs encompass antibacterial, antifungal, anticancer, antimalarial, antiviral, anti-inflammatory, antithrombotic, and antiprotozoal agents. The planar and heteroaromatic characteristics of naphthylimides grant them a strong ability to intercalate into DNA. This intercalation property renders naphthylimide derivatives highly valuable for various biological activities. The advantageous pharmacological activity and ease of synthesis associated with naphthylimides and their derivatives provide significant benefits in the design and development of new compounds within this class. Currently, only a few such molecules are undergoing preclinical and clinical evaluations. In this paper, we have compiled the literature on naphthylimides reported by researchers from 2006 to 2024. Our focus lies on exploring the pharmacological activities of their analogues from a drug development and discovery perspective, while examining their structure-activity relationship and mechanisms of action., Competing Interests: The authors declare no conflicts of interest.

Metabolic imbalance leading to inflammatory hypoxia and stabilization of hypoxia-inducible transcription factors (HIFs) is a hallmark of inflammatory bowel diseases. We hypothesize that HIF could be stabilized in CD4 + T cells during intestinal inflammation and alter the functional responses of T cells via regulation of microRNAs. Our assays reveal markedly increased T cell-intrinsic hypoxia and stabilization of HIF protein during experimental colitis. microRNA screen in primary CD4 + T cells points us towards miR-29a and our subsequent studies identify a selective role for HIF-2α in CD4-cell-intrinsic induction of miR-29a during hypoxia. Mice with T cell-intrinsic HIF-2α deletion display elevated T-bet (target of miR-29a) levels and exacerbated intestinal inflammation. Mice with miR-29a deficiency in T cells show enhanced intestinal inflammation. T cell-intrinsic overexpression of HIF-2α or delivery of miR-29a mimetic dampen T H 1-driven colitis. In this work, we show a previously unrecognized function for hypoxia-dependent induction of miR-29a in attenuating T H 1-mediated inflammation., (© 2024. The Author(s).)

This research paper utilizes a fused-in-silico approach alongside bioactivity evaluation to identify active FtsZ inhibitors for drug discovery. Initially, ROC-guided machine learning was employed to obtain almost 13182 compounds from three libraries. After conducting virtual screening to assess the affinity of 2621 acquired compounds, cluster analysis and bonding model analysis led to the discovery of five hit compounds. Additionally, antibacterial activity assays and time-killing kinetics revealed that T3995 could eliminate Staphylococcus aureus ATCC6538 and Bacillus subtilis ATCC9732, with MIC values of 32 and 2 μg/mL. Further morphology and FtsZ polymerization assays indicated that T3995 could be an antimicrobial inhibitor by targeting FtsZ protein. Moreover, hemolytic toxicity evaluation demonstrated that T3995 is safe at or below 16 ug/mL concentration. Additionally, bonding model analysis explained how the compound T3995 can display antimicrobial activity by targeting the FtsZ protein. In conclusion, this study presents a promising FtsZ inhibitor that was discovered through a fused computer method and bioactivity evaluation., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Tunability of interfacial effects between two-dimensional (2D) crystals is crucial not only for understanding the intrinsic properties of each system, but also for designing electronic devices based on ultra-thin heterostructures. A prerequisite of such heterostructure engineering is the availability of 2D crystals with different degrees of interfacial interactions. In this work, we report a controlled epitaxial growth of monolayer TaSe 2 with different structural phases, 1H and 1 T, on a bilayer graphene (BLG) substrate using molecular beam epitaxy, and its impact on the electronic properties of the heterostructures using angle-resolved photoemission spectroscopy. 1H-TaSe 2 exhibits significant charge transfer and band hybridization at the interface, whereas 1 T-TaSe 2 shows weak interactions with the substrate. The distinct interfacial interactions are attributed to the dual effects from the differences of the work functions as well as the relative interlayer distance between TaSe 2 films and BLG substrate. The method demonstrated here provides a viable route towards interface engineering in a variety of transition-metal dichalcogenides that can be applied to future nano-devices with designed electronic properties., (© 2024. The Author(s).)

Charge density wave (CDW is one of the most ubiquitous electronic orders in quantum materials. While the essential ingredients of CDW order have been extensively studied, a comprehensive microscopic understanding is yet to be reached. Recent research efforts on the CDW phenomena in two-dimensional (2D) materials provide a new pathway toward a deeper understanding of its complexity. This review provides an overview of the CDW orders in 2D with atomically thin transition metal dichalcogenides (TMDCs) as the materials platform. We mainly focus on the electronic structure investigations on the epitaxially grown TMDC samples with angle-resolved photoemission spectroscopy and scanning tunneling microscopy/spectroscopy as complementary experimental tools. We discuss the possible origins of the 2D CDW, novel quantum states coexisting with them, and exotic types of charge orders that can only be realized in the 2D limit., (© 2024 IOP Publishing Ltd.)

Two-dimensional materials have emerged as an important research frontier for overcoming the challenges in nanoelectronics and for exploring new physics. Among them, black phosphorus, with a combination of a tunable bandgap and high mobility, is one of the most promising systems. In particular, black phosphorus nanoribbons show excellent electrostatic gate control, which can mitigate short-channel effects in nanoscale transistors. Controlled synthesis of black phosphorus nanoribbons, however, has remained an outstanding problem. Here we report large-area growth of black phosphorus nanoribbons directly on insulating substrates. We seed the chemical vapour transport growth with black phosphorus nanoparticles and obtain uniform, single-crystal nanoribbons oriented exclusively along the [100] crystal direction. With comprehensive structural calculations, we discover that self-passivation at the zigzag edges holds the key to the preferential one-dimensional growth. Field-effect transistors based on individual nanoribbons exhibit on/off ratios up to ~10 4 , confirming the good semiconducting behaviour of the nanoribbons. These results demonstrate the potential of black phosphorus nanoribbons for nanoelectronic devices and also provide a platform for investigating the exotic physics in black phosphorus., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Hypoxia-inducible factors (HIFs) are highly conserved transcription factors that are crucial for adaptation of metazoans to limited oxygen availability. Recently, HIF activation and inhibition have emerged as therapeutic targets in various human diseases. Pharmacologically desirable effects of HIF activation include erythropoiesis stimulation, cellular metabolism optimization during hypoxia and adaptive responses during ischaemia and inflammation. By contrast, HIF inhibition has been explored as a therapy for various cancers, retinal neovascularization and pulmonary hypertension. This Review discusses the biochemical mechanisms that control HIF stabilization and the molecular strategies that can be exploited pharmacologically to activate or inhibit HIFs. In addition, we examine medical conditions that benefit from targeting HIFs, the potential side effects of HIF activation or inhibition and future challenges in this field., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Research on the comprehensive utilization of sour jujube and its beneficial properties to human health has attracted extensive attention. This study aims to conduct a bibliometric analysis of the bioactive profile of sour jujube and future trends in applications. The research advancements within this field from 2000 to 2023 were addressed using the Web of Science database and VOSviewer. Among the 322 results, the most frequent keywords of bioactivity are flavonoids, antioxidants, saponins, insomnia, polyphenols, terpenoids and anti-inflammatory; the most studied parts of sour jujube are seeds, fruits and leaves; the published articles with high citations mainly focus on identification, biological effects and different parts distribution of bioactive compounds. The bioactivity of various parts of sour jujube was reviewed considering their application potential. The seeds, rich in flavonoids, saponins and alkaloids, exhibit strong effects on central nervous system diseases and have been well-developed in pharmacology, healthcare products and functional foods. The pulp has antioxidant properties and is used to develop added-value foods (e.g., juice, vinegar, wine). The leaves can be used to make tea and flowers are good sources of honey; their extracts are rich sources of flavonoids and saponins, which show promising medicinal effects. The branches, roots and bark have healing properties in traditional folk medicine. Overall, this study provides a reference for future applications of sour jujube in food and medicine fields.

Due to antibiotic overuse, many bacteria have developed resistance, creating an urgent need for novel antimicrobial agents. It has been established that the filamentous temperature-sensitive mutant Z (FtsZ) of the bacterial cell division protein is an effective and promising antibacterial target. In this study, the optimal proteins were assessed by early recognition ability and the processed compound libraries were virtually screened using Vina. This effort resulted in the identification of 14 potentially active antimicrobial compounds. Among them, the compound T5S1607 demonstrated remarkable antibacterial efficacy against Bacillus subtilis ATCC9732 (MIC = 1 μg/mL) and Staphylococcus aureus ATC5C6538 (MIC = 4 μg/mL). Furthermore, in vitro experiments demonstrated that the selected compound T5S1607 rapidly killed bacteria and induced FtsZ protein aggregation, preventing bacterial division and leading to bacterial death. Additionally, cell toxicity and hemolysis experiments indicate that compound T5S1607 exhibits minimal toxicity to LO2 cells and shows no significant hemolytic effects on mammalian cells in vitro at the MIC concentration range. All the results indicate that compound T5S1607 is a promising antibacterial agent and a potential FtsZ inhibitor. In conclusion, this work successfully discovered FtsZ inhibitors with good activity through the virtual screening drug discovery process., 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 © 2023 Elsevier Ltd. All rights reserved.)

The human respiratory and circulatory systems collaborate intricately to ensure oxygen delivery to all cells, which is vital for ATP production and maintaining physiological functions and structures. During limited oxygen availability, hypoxia-inducible factors (HIFs) are stabilized and play a fundamental role in maintaining cellular processes for hypoxia adaptation. First discovered during investigations of erythropoietin production regulation, HIFs influence physiological and pathological processes, including development, inflammation, wound healing, and cancer. HIFs promote extracellular adenosine signaling by enhancing adenosine generation and receptor signaling, representing an endogenous feedback mechanism that curbs excessive inflammation, supports injury resolution, and enhances hypoxia tolerance. This is especially important for conditions that involve tissue hypoxia, such as acute respiratory distress syndrome (ARDS), which globally poses significant health challenges without specific treatment options. Consequently, pharmacological strategies to amplify HIF-mediated adenosine production and receptor signaling are of great importance., Competing Interests: HE and XY received research funding through a contract between Akebia Therapeutics and UTHealth to support a clinical trial on the effect of vadadustat in hospitalized COVID-19 patients NCT04478071. The remaining 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. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Figarella, Kim, Ruan, Mills, Eltzschig and Yuan.)

Acquired resistance to EGFR is a major impediment in lung cancer treatment, highlighting the urgent need to discover novel compounds to overcome EGFR drug resistance. In this study, we utilized in silico methods and bioactivity evaluation for drug discovery to identify novel active anticancer agents targeting EGFR T790M/L858R and EGFR T790M/C797S/L858R . Firstly, we employed ROC-guided machine learning to retrieve nearly 7,765 compounds from a collection of three libraries (comprising over 220,000 compounds). Next, virtual screening, cluster analysis, and binding model analysis were employed to identify six potential compounds. Additionally, the kinase assay revealed that these six compounds demonstrated higher sensitivity to EGFR than c-Met. Among these compounds, T6496 inhibited both EGFR T790M/L858R and EGFR T790M/C797S/L858R kinases, with an IC 50 of 3.30 and 8.72 μM. Furthermore, we evaluated the antitumor effects of the six selected compounds, and compound T6496 exhibited the strongest anticancer activity against H1975 cell lines, with an IC 50 value of 2.7 μM. These results suggest that T6496 may mitigate EGFR resistance caused by T790M or C797S mutations. Moreover, the AO staining assay, JC-1 staining, ROS experiment and hemolytic toxicity evaluation revealed that T6496 could induce apoptosis in H1975 cell lines in a time-dependent and concentration-dependent manner, and is a potential compound for further structural optimization.Communicated by Ramaswamy H. Sarma.

In recent years, the overuse of antibiotics has resulted in the emergence of antibiotic resistance, which is a serious global health problem. Methicillin-resistant Staphylococcus aureus (MRSA) is a common and virulent bacterium in clinical practice. Numerous researchers have focused on developing new candidate drugs that are effective, less toxic, and can overcome MRSA resistance. Thiazole derivatives have been found to exhibit antibacterial activity against drug-sensitive and drug-resistant pathogens. By hybridizing thiazole with other antibacterial pharmacophores, it is possible to obtain more effective antibacterial candidate drugs. Thiazole derivatives have shown potential in developing new drugs that can overcome drug resistance, reduce toxicity, and improve pharmacokinetic characteristics. This article reviews the recent progress of thiazole compounds as potential antibacterial compounds and examines the structure-activity relationship (SAR) in various directions. It covers articles published from 2018 to 2023, providing a comprehensive platform to plan and develop new thiazole-based small MRSA growth inhibitors with minimal side effects., 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 © 2023. Published by Elsevier Masson SAS.)

Mammals have evolved to adapt to differences in oxygen availability. Although systemic oxygen homeostasis relies on respiratory and circulatory responses, cellular adaptation to hypoxia involves the transcription factor hypoxia-inducible factor (HIF). Given that many cardiovascular diseases involve some degree of systemic or local tissue hypoxia, oxygen therapy has been used liberally over many decades for the treatment of cardiovascular disorders. However, preclinical research has revealed the detrimental effects of excessive use of oxygen therapy, including the generation of toxic oxygen radicals or attenuation of endogenous protection by HIFs. In addition, investigators in clinical trials conducted in the past decade have questioned the excessive use of oxygen therapy and have identified specific cardiovascular diseases in which a more conservative approach to oxygen therapy could be beneficial compared with a more liberal approach. In this Review, we provide numerous perspectives on systemic and molecular oxygen homeostasis and the pathophysiological consequences of excessive oxygen use. In addition, we provide an overview of findings from clinical studies on oxygen therapy for myocardial ischaemia, cardiac arrest, heart failure and cardiac surgery. These clinical studies have prompted a shift from liberal oxygen supplementation to a more conservative and vigilant approach to oxygen therapy. Furthermore, we discuss the alternative therapeutic strategies that target oxygen-sensing pathways, including various preconditioning approaches and pharmacological HIF activators, that can be used regardless of the level of oxygen therapy that a patient is already receiving., (© 2023. Springer Nature Limited.)

Introduction: The provincial malaria diagnosis reference laboratories review and assess malaria cases diagnosed in health facilities for supporting the malaria elimination efforts and preventing re-transmission of imported malaria. The study aimed to evaluate the detection capability of malaria diagnosis in China from 2014 to 2021., Methods: Data on malaria cases reported in the provincial-level administrative divisions (PLADs) of Anhui, Henan, Hubei, Guangxi, and Zhejiang from 2014 to 2021 were collected and analyzed., Results: In total, 5,770 malaria cases were reported from 2014 to 2021, and 99.05% (5,715/5,770) were submitted to the provincial malaria diagnosis reference laboratories. The median time between malaria cases being reported and the samples being received by reference laboratories was 6 days (Interquartile range, IQR:3-12 days) from 2017 to 2021. Diagnosis of 5,680 samples in the laboratory were confirmed by provincial reference laboratories, including 3,970 cases of Plasmodium falciparum , 414 of P. vivax , 1,055 of P. ovale , 158 of P. malariae , 1 of P. knowlesi , and 82 of mixed infections. Plasmodium species of 5,141 confirmed cases were consistent with the initial diagnosis, with a species accuracy rate of 90.53% (5,141/5,679). The accuracy of P. falciparum diagnosis in health facilities was higher than that of non-falciparum species. The inconsistency between microscopy and nested polymerase chain reaction (nPCR) results of confirmatory diagnosis was mainly in malaria-positive versus malaria-negative cases, as well as in mixed versus single infection cases., Conclusion: The provincial malaria diagnosis reference laboratories have played an important role in ensuring the accuracy and reliability of Plasmodium diagnosis in health facilities. However, the results of this study imply that capacity training for the identification of Plasmodium species in health facilities is warranted., 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 Zhang, Jiang, Sui, Yan, Xia, Liu, Sun, Wang, Marfurt, Lu, Li, Ruan and Wang.)

Objectives: The widespread occurrence of anti-malarial drug resistance threatens the current efforts to control malaria in African regions. Molecular marker surveillance helps to track the emergence and spread of drug-resistant malaria cases., Methods: A total of 237 Plasmodium falciparum infections imported from central Africa to Zhejiang Province, China, between 2016 and 2021, were investigated. Genomic DNA was extracted from blood samples of each patient and nested PCRs was used to detect molecular markers in k13 , Pfcrt , and Pfmdr1 genes. The spatial and temporal distributions of the molecular markers were analyzed., Results: A limited polymorphism of k13 was observed, including two nonsynonymous (D464E and K503E) and five synonymous mutations. Wild-type CVMNK of Pfcrt predominated (78.5%), whereas 19.5% of the samples harbored the mutant haplotype, CVIET. The point mutation Y184F and the single mutant haplotype NF of Pfmdr1 were the most frequently observed. The geographical distributions of the Pfcrt and Pfmdr1 haplotypes displayed distinct patterns, with the mutant haplotype of Pfcrt more common in Gabon (53.9%) and Congo (50.0%), and wild haplotypes of Pfmdr1 more frequently found in Cameroon, Angola, and Congo. The prevalence of wild-type CVMNK of Pfcrt increased from 68.5-74.6% in 2016-2017 to 81.8-87.5% in 2018-2021. The proportion of wild-type Pfmdr1 also increased from 27.1% in 2016 to 38.5% in 2019., Conclusion: The geographical and temporal distribution of k13 , Pfcrt , and Pfmdr1 polymorphisms in P. falciparum parasites imported from central Africa between 2016 and 2021 are demonstrated. Our data provide updated evidence that can be used to adjust anti-malarial drug policies in central Africa and China., 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 Xu, Zhang, Chen, Zhang, Lu, Ruan and Wang.)

Background: Intracranial hemorrhage after spinal surgery is a rare and devastating complication., Aim: To investigate the economic burden, clinical characteristics, risk factors, and mechanisms of intracranial hemorrhage after spinal surgery., Methods: A retrospective cohort study was conducted from January 1, 2015, to December 31, 2022. Patients aged ≥ 18 years, who had undergone spinal surgery were included. Intracranial hemorrhage patients were selected after spinal surgery during hospitalization. Based on the type of spinal surgery, patients with intracranial hemorrhage were randomly matched in a 1:5 ratio with control patients without intracranial hemorrhage. The patients' pre-, intra-, and post-operative data and clinical manifestations were recorded., Results: A total of 24472 patients underwent spinal surgery. Six patients (3 males and 3 females, average age 71.3 years) developed intracranial hemorrhage after posterior spinal fusion procedures, with an incidence of 0.025% (6/24472). The prevailing type of intracranial hemorrhage was cerebellar hemorrhage. Two patients had a poor clinical outcome. Based on the type of surgery, 30 control patients were randomly matched in 1:5 ratio. The intracranial hemorrhage group showed significant differences compared with the control group with regard to age (71.33 ± 7.45 years vs 58.39 ± 8.07 years, P = 0.001), previous history of cerebrovascular disease (50% vs 6.7%, P = 0.024), spinal dura mater injury (50% vs 3.3%, P = 0.010), hospital expenses (RMB 242119.1 ± 87610.0 vs RMB 96290.7 ± 32029.9, P = 0.009), and discharge activity daily living score (40.00 ± 25.88 vs 75.40 ± 18.29, P = 0.019)., Conclusion: The incidence of intracranial hemorrhage after spinal surgery was extremely low, with poor clinical outcomes. Patient age, previous stroke history, and dura mater damage were possible risk factors. It is suggested that spinal dura mater injury should be avoided during surgery in high-risk patients., Competing Interests: Conflict-of-interest statement: All study participants or their legal guardians provided informed written consent regarding personal and medical data collection before study enrolment., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: The global battle against malaria is facing formidable challenges, particularly in controlling Plasmodium vivax and Plasmodium ovale, whose cases have not been reduced as effectively as Plasmodium falciparum because of their relapse. This study investigates the current situation and underlying factors contributing to relapse or recrudescence of imported cases of P. vivax and P. ovale, and seeks to provide a reference for reducing relapse or recrudescence in malaria-free areas and offers a scientific basis for designing strategies to prevent imported re-transmission., Methods: This study analysed imported P. vivax and P. ovale in Anhui, Zhejiang, Henan, Hubei, and Guangxi provinces during 2014-2021 by retrospective analysis. A case-control study was conducted on patients who experienced relapse or recrudescence., Results: From 2014 to 2021, 306 cases of P.vivax and 896 cases of P.ovale were included in the study, while 75 cases had relapse or recrudescence, including 49 cases of P. ovale (65.33%) and 26 cases of P. vivax (34.67%). Within less than 5 weeks after returning to the country, 122 cases of P. vivax (39.87%, 122/306) and 265 cases of P. ovale (29.58%, 265/896) occurred. Within less than 53 weeks, the ratio of P. vivax was 94.77% (290/306), and that of P. ovale was 89.96% (806/896). Among the cases experiencing relapse or recrudescence, only 1 case of P. vivax (1/26 3.85%) and 3 cases of P. ovale (3/49 6.12%) occurred within less than 5 weeks after the first onset, whereas 21 cases of P. vivax (21/26 80.77%) and 42 cases of P. ovale (42/49 85.71%) occurred within less than 53 weeks after the first onset. The difference in relapse or recrudescence due to different drugs and medication regimens and medical activities at various levels of medical institutions was statistically significant., Conclusion: In areas where malaria has been eliminated, routine health screening in a scientific time frame for people returning from at-risk areas can effectively improve the efficiency of preventing re-transmission, thereby reducing prevention costs and disease burden. Preventing patients from self-treating and strengthening medication regulations in health facilities are key measures to reduce relapse or recrudescence., (© 2023. The Author(s).)

Background: This study aimed at exploring the epidemiological pattern of imported malaria in China before malaria elimination in 2021, to provide evidence-based data for preventing malaria re-establishment in China., Methods: Nine-year surveillance data on imported malaria in four provincial-level administrative divisions (PLADs) (Anhui, Chongqing, Guangxi, and Zhejiang) between 2011 and 2019 were thoroughly collected and analyzed., Results: A quite stable trend in imported malaria cases between 2011 and 2019 was observed. In total, 6,064 imported patients were included. Plasmodium falciparum was the most frequently reported species (4,575, 75.6%). Cases of malaria were most frequently imported from Western Africa (54.4%). We identified an increasing trend in P. ovale and a persistence of P. vivax infections among the cases of malaria imported from Western Africa. Most patients (97.5%) were 20-50 years old. Among imported malaria infections, the main purposes for traveling abroad were labor export (4,914/6,064, 81.0%) and business trips (649, 10.7%). Most patients (2,008/6,064, 33.1%) first visited county-level medical institutions when they sought medical help in China. More patients were diagnosed within 3 days after visiting Centers for Disease Control and Prevention (CDCs) or entry-exit quarantine facilities (EQFs) (1,147/1609, 71.3%) than after visiting medical institutions (2,182/3993, 54.6%)., Conclusion: Imported malaria still poses a threat to the malaria-free status of China. County-level institutions are the primary targets in China to improve the sensitivity of the surveillance system and prevent the re-establishment of malaria. Health education should focus on exported labors, especially to Western and Central Africa. Increasing trend in P. ovale and persistence of P. vivax infections indicated their underestimations in Western Africa. Efficient diagnostic tools and sensitive monitoring systems are required to identify Plasmodium species in Africa., 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, Xu, Luo, Lin, Zhang, Yao, Zhang, Zhang, Auburn, Wang and Ruan.)

Previous studies implicate extracellular adenosine signaling in attenuating myocardial ischemia and reperfusion injury (IRI). This extracellular adenosine signaling is terminated by its uptake into cells by equilibrative nucleoside transporters (ENTs). Thus, we hypothesized that targeting ENTs would function to increase cardiac adenosine signaling and concomitant cardioprotection against IRI. Mice were exposed to myocardial ischemia and reperfusion injury. Myocardial injury was attenuated in mice treated with the nonspecific ENT inhibitor dipyridamole. A comparison of mice with global Ent1 or Ent2 deletion showed cardioprotection only in Ent1-/- mice. Moreover, studies with tissue-specific Ent deletion revealed that mice with myocyte-specific Ent1 deletion (Ent1loxP/loxP Myosin Cre+ mice) experienced smaller infarct sizes. Measurements of cardiac adenosine levels demonstrated that postischemic elevations of adenosine persisted during reperfusion after targeting ENTs. Finally, studies in mice with global or myeloid-specific deletion of the Adora2b adenosine receptor (Adora2bloxP/loxP LysM Cre+ mice) implied that Adora2b signaling on myeloid-inflammatory cells in cardioprotection provided by ENT inhibition. These studies reveal a previously unrecognized role for myocyte-specific ENT1 in cardioprotection by enhancing myeloid-dependent Adora2b signaling during reperfusion. Extension of these findings implicates adenosine transporter inhibitors in cardioprotection against ischemia and reperfusion injury.

Background: Parasternal intercostal nerve block has been increasingly used for postoperative analgesia and has shown that this technique can provide effective postoperative analgesia. This study aimed to investigate the effect of preemptive parasternal intercostal nerve block on the opioid and vasoactive drug dose required for intraoperative hemodynamic stability and postoperative analgesia in patients undergoing off-pump coronary artery bypass grafting., Methods: In this prospective, randomized controlled study, 64 participants aged 45-75 years scheduled for off-pump coronary artery bypass grafting at The Second Xiangya Hospital of Central South University. Patients were randomized into two groups and preoperatively administered ropivacaine (group R) and saline (group S), in the parasternal intercostal spaces with ultrasound-guided bilateral nerve block., Results: The primary outcome was intraoperative sufentanil and vasopressor dosage. The secondary outcomes were intraoperative hemodynamics, postoperative pain scores, and anesthesia recovery, postoperative use of rescue dezocine, stay in intensive care unit, and length of hospital stay. The consumption of intraoperative sufentanil and vasopressor was significantly lower in group R than in group S. The visual analog score in group R was significantly lower than that in group S up to 12 h postoperatively. The time to anesthesia recovery was significantly less in group R than in group S. Most patients in group S required rescue dezocine, whereas most patients in group R did not. The hemodynamic variables were stable in all patients., Conclusions: A preemptive parasternal intercostal nerve block effectively reduced the required intraoperative sufentanil and norepinephrine dose and provided adequate analgesia for the first 12 h after surgery. Therefore, a preemptive parasternal intercostal nerve block is a good option for patients undergoing off-pump coronary artery bypass grafting., Clinical Trial Registration: chictr.org.cn, identifier ChiCTR1800017210., 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., (© 2023 Zou, Ruan, Liu and Xu.)

Pancreatic ductal adenocarcinoma (PDAC) is characterized by a dense desmoplastic stroma that impedes drug delivery, reduces parenchymal blood flow, and suppresses the anti-tumor immune response. The extracellular matrix and abundance of stromal cells result in severe hypoxia within the tumor microenvironment (TME), and emerging publications evaluating PDAC tumorigenesis have shown the adenosine signaling pathway promotes an immunosuppressive TME and contributes to the overall low survival rate. Hypoxia increases many elements of the adenosine signaling pathway, resulting in higher adenosine levels in the TME, further contributing to immune suppression. Extracellular adenosine signals through 4 adenosine receptors (Adora1, Adora2a, Adora2b, Adora3). Of the 4 receptors, Adora2b has the lowest affinity for adenosine and thus, has important consequences when stimulated by adenosine binding in the hypoxic TME. We and others have shown that Adora2b is present in normal pancreas tissue, and in injured or diseased pancreatic tissue, Adora2b levels are significantly elevated. The Adora2b receptor is present on many immune cells, including macrophages, dendritic cells, natural killer cells, natural killer T cells, γδ T cells, B cells, T cells, CD4 + T cells, and CD8 + T cells. In these immune cell types, adenosine signaling through Adora2b can reduce the adaptive anti-tumor response, augmenting immune suppression, or may contribute to transformation and changes in fibrosis, perineural invasion, or the vasculature by binding the Adora2b receptor on neoplastic epithelial cells, cancer-associated fibroblasts, blood vessels, lymphatic vessels, and nerves. In this review, we discuss the mechanistic consequences of Adora2b activation on cell types in the tumor microenvironment. As the cell-autonomous role of adenosine signaling through Adora2b has not been comprehensively studied in pancreatic cancer cells, we will also discuss published data from other malignancies to infer emerging therapeutic considerations for targeting the Adora2b adenosine receptor to reduce the proliferative, invasive, and metastatic potential of PDAC cells., 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 Strickland, Faraoni, Ruan, Yuan, Eltzschig and Bailey-Lundberg.)

The remediation of heavy metal deserves to be on the agenda, with the adsorbent design bearing the brunt of it. In this study, the molecule (4, 6-diamino-2-mercaptopyrimidine, DMP) containing thiol (-SH) and amino (-NH 2 ) functional groups was grafted onto Uio-66-NH 2 , and a composite metal-organic framework nanomaterial (Zr(NH 2 )-DMP) was synthesized via a facile post-modification scheme. The morphological characteristics and structural features of the modified adsorbent were characterized by XRD, FT-IR, FE-SEM, EDS, BET, and XPS. The characterization results verified that the post-modification scheme was successfully achieved. The adsorption experiments were carried out to investigate the removal performance of the Zr(NH 2 )-DMP towards Hg 2+ under different influencing parameters. The maximum adsorption capacity of 389.4 mg/g was obtained, and the adsorption equilibrium was achieved within 30 min at pH 6 at room temperature. Adsorption thermodynamic study indicated that the adsorption process was exothermic and spontaneous. The Zr(NH 2 )-DMP exhibited excellent selectivity for Hg 2+ , and also has the potential to remove Cu 2+ , Fe 2+ , and Zn 2+ ions. The introduction of Cl - inhibited the removal of Hg 2+ due to the formation of mercuric chlorides (removal efficiency reduced from 97.8 to 95.6%). The removal efficiency of up to 86.7% was obtained after four cycles. The Langmuir isotherm and Pseudo-second kinetic were more suitable for fitting the adsorption process of Hg 2+ by Zr(NH 2 )-DMP. The main removal mechanism could be attributed to the chelation between Hg 2+ (soft acid) and nitrogen/sulfur (soft base) elements. These findings convinced that the successful synthesis of Zr(NH 2 )-DMP provides an option for Hg 2+ removal from wastewater., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

High mobility electron gases confined at material interfaces have been a venue for major discoveries in condensed matter physics. Ultra-high vacuum (UHV) technologies played a key role in creating such high-quality interfaces. The advent of two-dimensional (2D) materials brought new opportunities to explore exotic physics in flat lands. UHV technologies may once again revolutionize research in low dimensions by facilitating the construction of ultra-clean interfaces with a wide variety of 2D materials. Here, we describe the design and operation of a UHV 2D material device fabrication system, in which the entire fabrication process is performed under pressure lower than 5 × 10 -10 mbar. Specifically, the UHV system enables the exfoliation of atomically clean 2D materials. Subsequent in situ assembly of van der Waals heterostructures produces high-quality interfaces that are free of contamination. We demonstrate functionalities of this system through exemplary fabrication of various 2D materials and their heterostructures.

Background: In areas where malaria has been eliminated, delayed care-seeking and diagnosis of imported malaria are constant threats. This study aimed to describe the profile and determinants of delayed care-seeking and diagnosis among patients with imported malaria in China., Methods: This retrospective study assessed surveillance data obtained from 2014 to 2021 in the Chinese provincial-level administrative divisions (PLADs) of Anhui, Henan, Hubei, and Zhejiang, and Guangxi. Epidemiological characteristics were analyzed using descriptive statistics. Furthermore, factors associated with delayed care-seeking and diagnosis among imported malaria cases were identified using multivariate logistic regression., Results: Overall, 11.81% and 30.08% of imported malaria cases had delays in seeking care and diagnosis, respectively. During the study period, there was a decreasing trend in the proportion of imported malaria cases with delayed care-seeking (χ 2  = 36.099, P < 0.001) and diagnosis (χ 2  = 11.395, P = 0.001). In multivariate analysis, independent risk factors associated with delayed care-seeking include PLADs (Guangxi as reference), consultations in high-level facilities for the first medical visit, infections with non-Plasmodium falciparum species, and older age. However, PLADs (Guangxi as reference), the purpose of traveling (labour as reference), and infections with non-P. falciparum species increased the risk of delayed diagnosis. Delayed care-seeking (adjusted odds ratio: 1.79, P = 0.001) and diagnosis (adjusted odds ratio: 1.62, P = 0.004) were risk factors for severe disease development., Conclusions: Based on this study's findings, we strongly advocate for improved access to quality healthcare to reduce the rate of misdiagnosis at the first visit. Infections caused by non-P. falciparum species should be highlighted, and more sensitive and specific point-of-care detection methods for non-P. falciparum species should be developed and implemented. In addition, education programs should be enhanced to reach target populations at risk of malaria infection. All these factors may reduce delayed care-seeking and diagnosis of imported malaria., (© 2022. The Author(s).)

Sulfadoxine-pyrimethamine (SP) resistance impairs the efficacy of antimalarial drugs. Monitoring molecular markers in exported malaria infections provides an efficient way to trace the emergence of drug resistance in countries where malaria is endemic. Molecular markers in Pfdhfr and Pfdhps of 237 Plasmodium falciparum infections imported from central Africa between 2016 and 2021 were detected. The spatial and temporal distributions of Pfdhfr and Pfdhps mutations were analyzed. A high prevalence of Pfdhfr single-nucleotide polymorphisms (SNPs) (~92.34% to 99.10%) and a high frequency of the triple mutation haplotype I 51 R 59 N 108 were observed. Cameroon, Equatorial Guinea, and Gabon showed a higher frequency (~96.61% to 100.00%) of I 51 R 59 N 108 than other countries (~71.11% to 88.10%). The prevalence of C59R and I 51 R 59 N 108 increased while that of other SNPs or haplotypes did not fluctuate greatly from 2016 to 2021. Large proportions of Pfdhps SNPs (A437G and K540E) were demonstrated. The SNP distribution of Pfdhps differed between countries, with S436A dominating in northern countries and A437G dominating in others. The proportions of I431V, A437G, and the triple mutant haplotype declined between 2016 and 2021, whereas the prevalence of the single mutant haplotype rose from 61.60% to 73.68%. Combinations of Pfdhfr - Pfdhps alleles conferring partial resistance, full resistance, and superresistance to SP, as defined in the text, were detected in 63.64%, 8.64%, and 0.91% of the samples, respectively. The octuple Pfdhfr - Pfdhps allele ( I 51 R 59 N 108 - V 431 A 436 G 437 K 540 G 581 S 613 ) was seen in 5.00% of the samples. We demonstrated the wide geographic spread and increasing trends in highly SP-resistant Pfdhfr genes and varying spatial patterns of Pfdhps mutants across countries in central Africa. The high prevalences of partially resistant, fully resistant, and superresistant Pfdhfr-Pfdhps combinations observed here indicated impaired SP efficacy. Increased molecular surveillance is required to monitor the changing status of the Pfdhfr and Pfdhps genes. IMPORTANCE Monitoring drug resistance is important for malaria control because its early detection enables timely action to prevent its spread and mitigate its impact. The wide geographic spread and the increasing trend of highly resistant Pfdhfr genes between 2016 and 2021 found in our study are worrisome and emphasize the urgency to monitor their updated status in central Africa. This study also illustrated the wide spread of the novel mutant Pfdhps I431V as well as the high prevalence of "partially resistant," "fully resistant," and "superresistant" Pfdhfr - Pfdhps combinations, indicating the urgent concern for SP efficacy in central Africa. These findings are alarming in central African countries where malaria is endemic, where SP was is widely used for the intermittent preventive treatment of malaria in pregnancy (IPTp) and the intermittent preventive treatment of malaria in infants below 5 years of age (IPTi), and urge enhanced molecular surveillance and responses to the threat of drug resistance.

Malaria poses public health threats worldwide. Nigeria accounted for the highest numbers of cases (26.8%) and deaths (31.9%) among countries where malaria is endemic in 2020. Currently, monitoring molecular markers in imported malaria cases provides an efficient means to screen for emerging drug resistance in countries where malaria is endemic, particularly in those where field surveillance is challenging. Here, we investigated 165 Plasmodium falciparum infections imported from Nigeria to Zhejiang Province, China, between 2016 and 2020. Multiple molecular markers in k13 , Pfcrt , Pfmdr1 , Pfdhfr , and Pfdhps were detected. The prevalences and patterns of mutations were analyzed. Polymorphism of k13 was limited to 5 of 156 (3.21%) isolates. The wild-type CVMNK allele of Pfcrt became predominant (65.36%) compared with the triple mutation CVIET. A low frequency (4.73%) of double mutations (N86Y and Y184F) in Pfmdr1 was observed. The dominant haplotypes of Pfdhfr and Pfdhps were IRN DI (92.41%) and IS G KAA (36.84%), respectively. The newly discovered mutant I431V was identified in 21.71% of isolates. A "fully resistant" combination of Pfdhfr-Pfdhps , IRN-GE, was found in eight (5.67%) samples, which was hardly seen in Nigeria. The current study demonstrated a high frequency of wild-type Pfcrt . Limited polymorphism of Pfmdr1 but a high prevalence of Pfdhfr and Pfdhps mutations was illustrated. Our data so far serve as comprehensive surveillance of molecular markers of the k13 , Pfcrt , Pfmdr1 , Pfdhfr , and Pfdhps genes. Based on our findings, it has become crucial to evaluate the impact of the emerging fully resistant type of Pfdhfr - Pfdhps as well as its combination with I431V on the efficacy of sulfadoxine-pyrimethamine (SP) in Nigeria. IMPORTANCE Monitoring the current resistance to antimalarial drugs is critical to enable timely action to prevent its spread and limit its impact. The high prevalence of wild-type Pfcrt found in our study is an optimistic signal to reevaluate chloroquine (CQ) sensitivity in Nigeria, which is cost-effective and once played a crucial role in the fight against malaria. Based on the continued emergence of fully resistant Pfdhfr - Pfdhps alleles illustrated in the current investigation, actions are needed in Nigeria, such as national systemic surveillance to monitor their updated epidemiology as well as assessments of their influence on SP efficacy to minimize any public health impact. These findings urge a response to the threat of drug resistance to facilitate appropriate drug policies in the study area.

Jujube pulp separated from Ziziphus jujube is often discarded after processing, resulting in a serious waste of resources and environmental pollution. Herein, Ziziphus jujube pulp was used as a raw material for vinegar fermentation. To investigate the dynamic distribution of microorganisms and flavor substances in ZJV, correlations between environmental variables (e.g., total acid, reducing sugar, temperature) and flavor substances (organic acids, amino acids, volatile substances) and microorganisms were analyzed. Physicochemical indicators (temperature, total acid, alcohol) were the main factors affecting ZJV fermentation. The middle and later stages of ZJV fermentation were the periods showing the largest accumulation of flavor substances. Organic acids (acetic acid, malic acid, citric acid, lactic acid), amino acids (Asp, Glu, Arg) and volatile substances (ethyl phenylacetate, phenethyl alcohol) were important odor-presenting substances in ZJV. In the bacterial community, the Operational Taxonomic Units (OTUs) with an average relative abundance of more than 10% in at least one fermentation stage were mainly Acetobacter , Lactobacillus and Saccharopolyspora , while it was Thermomyces in the fungal community. Pearson correlation coefficients showed that Penicillium , Lactobacillus and Acetobacter were the core microorganisms, implying that these microorganisms contributed to the flavor formation greatly in ZJV fermentation. This study reveals the correlation between physicochemical indexes and flavor substances and microorganisms in ZJV fermentation. The results of the study can provide a theoretical basis for the development of the ZJV industry.

The transcription factor hypoxia-inducible factor HIF1A induces cardioprotection from ischemia and reperfusion injury. Here, we investigate tissue-specific pathways that are critical for HIF1A-elicited tissue protection. Initial studies showed that mice with induced global Hif1a deletion ( Hif1a loxP/loxP UbiquitinCre+) have exaggerated myocardial injury during in situ ischemia and reperfusion. Surprisingly, this phenotype was mirrored only in mice with myeloid-specific Hif1a deletion (Hif1a loxP/loxP LysM Cre+). In contrast, mice with myocardial specific ( Hif1a loxP/loxP Myosin Cre+), or vascular Hif1a deletion ( Hif1a loxP/loxP VEcadherin Cre+) experienced similar levels of injury as controls. Subsequent studies using adoptive transfer of Hif1a- deficient polymorphonuclear neutrophils (PMNs) prior to myocardial injury demonstrated increased reperfusion injury. On the contrary, the adoptive transfer of PMNs treated ex vivo with the hypoxia inducible factor (HIF) stabilizer dimethyloxalylglycine (DMOG) was associated with attenuated myocardial injury. Furthermore, DMOG-mediated cardioprotection was abolished in Hif1a loxP/loxP LysM Cre+ mice, but not in Hif2a loxP/loxP LysM Cre+ mice. Finally, studies of PMN-dependent HIF1A target genes implicated the neuronal guidance molecule netrin-1 in mediating the cardioprotective effects of myeloid HIF1A. Taken together, the present studies identified a functional role for myeloid-expressed HIF1A in providing cardioprotection during ischemia and reperfusion injury, which is mediated, at least in part, by the induction of the netrin-1 neuronal guidance molecule in neutrophils., 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 Heck-Swain, Li, Ruan, Yuan, Wang, Koeppen and Eltzschig.)

The spontaneous formation of electronic orders is a crucial element for understanding complex quantum states and engineering heterostructures in 2D materials. A novel 19 $\sqrt {19} $ × 19 $\sqrt {19} $ charge order in few-layer-thick 1T-TaTe 2 transition metal dichalcogenide films grown by molecular beam epitaxy, which has not been realized, is report. The photoemission and scanning probe measurements demonstrate that monolayer 1T-TaTe 2 exhibits a variety of metastable charge density wave orders, including the 19 $\sqrt {19} $ × 19 $\sqrt {19} $ superstructure, which can be selectively stabilized by controlling the post-growth annealing temperature. Moreover, it is found that only the 19 $\sqrt {19} $ × 19 $\sqrt {19} $ order persists in 1T-TaTe 2 films thicker than a monolayer, up to 8 layers. The findings identify the previously unrealized novel electronic order in a much-studied transition metal dichalcogenide and provide a viable route to control it within the epitaxial growth process., (© 2022 Wiley-VCH GmbH.)

Despite increasing availability and more successful interventional approaches to restore coronary reperfusion, myocardial ischemia-reperfusion injury is a substantial cause of morbidity and mortality worldwide. During myocardial ischemia, the myocardium becomes profoundly hypoxic, thus causing stabilization of hypoxia-inducible transcription factors (HIF). Stabilization of HIF leads to a transcriptional program that promotes adaptation to hypoxia and cellular survival. Transcriptional consequences of HIF stabilization include increases in extracellular production and signaling effects of adenosine. Extracellular adenosine functions as a signaling molecule via the activation of adenosine receptors. Several studies implicated adenosine signaling in cardioprotection, particularly through the activation of the Adora2a and Adora2b receptors. Adenosine receptor activation can lead to metabolic adaptation to enhance ischemia tolerance or dampen myocardial reperfusion injury via signaling events on immune cells. Many studies highlight that clinical strategies to target the hypoxia-adenosine link could be considered for clinical trials. This could be achieved by using pharmacologic HIF activators or by directly enhancing extracellular adenosine production or signaling as a therapy for patients with acute myocardial infarction, or undergoing cardiac surgery.

Since December 2019, the Coronavirus Disease 2019 (COVID-19) pandemic has become a non-neglectable context for the whole healthcare system. Under the background of COVID-19, the detection and diagnosis of malaria cases are under challenge. Here, we reported a COVID-19 and malaria co-infection traveler who has a long living history in Cameroon. The case was administered with dihydroartemisinin and piperaquine tablets for malaria, Lopinavir and Ritonavir tablets, Arbidol, recombinant human interferon α-2b and Compound Maxing Yifei mixture for COVID-19, and Zolpidem Tartrate tablets, Diazepam, Paroxetine Hydrochloride tablets, Thymosin α1, and Lianhua Qinwen Jiaonang during the second hospitalization of the patient since the patient has a certain level of anxiety and insomnia with no evidence of inflammatory reactions. After being tested negative two times for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 48 h, the patient met China's COVID-19 discharge standards and was discharged with stable vital signs and mental state. Since most countries in the sub-Saharan region have a fragile health system, co-infection for both Plasmodium and SARS-CoV-2 may not be uncommon, and raise a challenge in diagnosis, treatment, and prevention for both diseases. We add to the literature on co-infection of P. falciparum malaria and COVID-19 and offer operational advice on diagnosis, prevention, and treatment for the co-infection., 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 Huang, Xu, Wang, Zhang, Pan, Zhang, Chen, Ruan and Yao.)

One-dimensional electron systems exhibit fundamentally different properties than higher-dimensional systems. For example, electron-electron interactions in one-dimensional electron systems have been predicted to induce Tomonaga-Luttinger liquid behaviour. Naturally occurring grain boundaries in single-layer transition metal dichalcogenides exhibit one-dimensional conducting channels that have been proposed to host Tomonaga-Luttinger liquids, but charge density wave physics has also been suggested to explain their behaviour. Clear identification of the electronic ground state of this system has been hampered by an inability to electrostatically gate such boundaries and tune their charge carrier concentration. Here we present a scanning tunnelling microscopy and spectroscopy study of gate-tunable mirror twin boundaries in single-layer 1H-MoSe 2 devices. Gating enables scanning tunnelling microscopy and spectroscopy for different mirror twin boundary electron densities, thus allowing precise characterization of electron-electron interaction effects. Visualization of the resulting mirror twin boundary electronic structure allows unambiguous identification of collective density wave excitations having two velocities, in quantitative agreement with the spin-charge separation predicted by finite-length Tomonaga-Luttinger liquid theory., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Extensive parasitic diseases epidemiology in Zhejiang province has not been carried out since the second national survey in 2004. Therefore, dynamics in prevalence and infection pattern of the major intestinal parasites should be explored., Methods: The distribution of three parasites including soil-transmitted helminths (STH), intestinal protozoa and C. sinensis in Zhejiang from 2014 to 2015 were explored. Kato-Katz technique was used for STH and C. sinensis detection, whereas transparent adhesive paper anal swab was used for pinworm detection, and iodine smear was used for protozoa detection. A questionnaire survey on alimentary habits and sanitary behaviors was conducted in half of the studied counties., Results: This study recruited 23,552 participants: 19,935 from rural and 3617 from urban area. Overall prevalence of intestinal helminth infections was 1.80%. In this study, seven helminth species were identified including A. duodenale, N. americanus, Trichuris trichiura, Ascaris lumbricoides, C. sinensis, Fasciolopsis buski and pinworm. The average prevalence of STH infection was 1.71%: 1.94% in rural and 0.44% in urban area. Hookworm was the most prevalent infection at 1.58%: 1.79% in rural and 0.44% in urban area. Prevalence varied considerably in the studied counties. Prevalence was highest in Yongkang county at 10.25%. Only 2.79% of children from rural area were infected with pinworm. A proportion of 0.40% of rural participants were infected with protozoa, whereas Endolimax nana was the most prevalent at 0.23%. C. sinensis showed infection only in one man. Awareness on C. sinensis was 24.47% in rural and 45.96% in urban area, respectively., Conclusions: Prevalence of STH and protozoa infections declined considerably whereas C. sinensis infections remained few in Zhejiang province compared with the prevalence reported in previous large scale surveys (19.56% for national STH infection in 2004, 18.66% and 4.57% for provincial STH and protozoa infection, respectively in 1999). The findings of this study showed that hookworm, mainly N. americanus remained a parasitic threat to population health, mainly in the central and western Zhejiang. Therefore, more health education regarding fertilization and farming habits is necessary in rural areas. The awareness concerning hookworm infection should be reinforced., (© 2021. The Author(s).)

Foamed polypropylene (PP) composites containing inorganic particles were prepared using a combined in-mold decoration and microcellular injection molding (IMD/MIM) method, and supercritical fluid-nitrogen was used as the physical blowing agent. Calcium carbonate (CaCO 3 ) and montmorillonite (MMT) with particle size that varied from nanometer to micron were selected as reinforcement particles. The effect of inorganic particle type and size on the crystallization, mechanical properties, and cellular structure of the parts were investigated. The results showed that the polymer chains were not well inserted into the MMT layer, and there was almost no increase in the interlayer spacing. As the particle size decreased, the relative amount of β-crystal and mechanical properties increased. The addition of CaCO 3 was more effective than MMT at increasing the volume fraction of the β-crystal form when the particle size was reduced to the nanometer level. In the vertical and parallel section, the average cell diameter of the composites decreased and the cell density increased as the particle size decreased. As the particle size of the inorganic filler decreased, the deformation degree of cells gradually increased., Competing Interests: The authors declare no conflict of interest., (This journal is © The Royal Society of Chemistry.)

Objective: To observe the effect of acupuncture combined with rehabilitation training on cognitive function and amino acid metabolism in children with cerebral palsy., Methods: Twenty children with cerebral palsy (cerebral palsy group) were randomly divided into an acupuncture and rehabilitation group (11 cases) and a rehabilitation group (9 cases), and 10 healthy children were included as the normal group. The rehabilitation group was treated with rehabilitation training, 30 min each time; on the basis of rehabilitation training, the acupuncture and rehabilitation group was treated with acupuncture at Sishenzhen, Zhisanzhen, Naosanzhen, Niesanzhen, Dazhui (GV 14), Shenzhu (GV 12), Mingmen (GV 4), etc. The Sishenzhen (left and right points) and the ipsilateral Niesanzhen were respectively connected with a group of electrodes, intermittent wave, frequency of 2 Hz for 30 min. Both groups were treated once every other day, three times a week, totaling for 3 months. The Gesell developmental diagnostic scale (GESELL) was used to evaluate the developmental quotient (DQ) scores before and after treatment, and the blood samples of children with cerebral palsy before and after treatment and normal children were collected for amino acid metabolomics., Results: Compared before treatment, the DQ scores of adaptation, fine motor and social in the acupuncture and rehabilitation group was increased after treatment ( P <0.05), and the DQ score of fine motor in the rehabilitation group was increased after treatment ( P <0.05). Compared with the normal group, the serum L-glutamate, L-ornithine, L-tyrosine, L-methionine and L-arginine in the cerebral palsy group were down-regulated, and L-histidine, L-citrulline, 5-hydroxylysine and L-glutamine were up-regulated before treatment. The functional pathways mapped by different metabolites between the cerebral palsy group and the normal group included arginine biosynthesis, arginine and proline metabolism, etc. Compared with the cerebral palsy group, the serum L-histidine was decreased, and L-citrulline showed decreasing trend in the acupuncture and rehabilitation group after treatment., Conclusion: Acupuncture combined with rehabilitation training could improve cognitive function in children with cerebral palsy, and the effect may be related to the down-regulation of L-histidine and L-citrulline metabolism.

Background: Perioperative complications of transcatheter aortic valve replacement (TAVR) are decreasing but can be catastrophic when they occur. Systematic reports of the nature of these events are lacking in the contemporary era. Our study aimed to report the incidence, outcomes, and perioperative management of catastrophic cardiac events in patients undergoing TAVR and to propose a working strategy to address these complications., Methods: This is a retrospective cohort study of patients who developed catastrophic cardiac events during or immediately after TAVR between 2015 and 2019 at a single academic centre., Results: Of 2102 patients who underwent TAVR, 51 (2.5%) developed catastrophic cardiac events. The causes included cardiac perforation and tamponade (n = 19, 37.3%), acute left- ventricular failure (n = 10, 19.6%), coronary artery obstruction (n = 10, 19.6%), aortic-root disruption (n = 7, 13.7%), and device embolization (n = 5, 9.8%). Twenty-four patients (47.0%) with catastrophic cardiac events required stabilization by either intra-aortic balloon counter-pulsation or extracorporeal membrane oxygenation. The in-hospital mortality rate increased by 11.7-fold for patients with catastrophic cardiac events compared with those without (25.5% vs 2.0%, P < 0.001). Patients who developed aortic root disruption had the highest mortality rate (42.8%) compared with the others. The incidence of catastrophic cardiac events remained stable over a 5-year period, but the associated mortality decreased from 38.5% in 2015 to 9.1% in 2019., Conclusions: Catastrophic cardiac events during TAVR are rare, but they account for a dramatic increase in perioperative mortality. Early recognition and development of a standardized perioperative team approach can help manage patients experiencing these complications., (Copyright © 2021 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Background: Malaria causes major public health problems globally and drug resistance hinders its control and elimination. Molecular markers associated with drug resistance are considered as a beneficial tool to monitor the disease trends, evolution and distribution so as to help improve drug policy., Methods: We collected 148 Plasmodium falciparum and 20 Plasmodium vivax isolates imported into Hangzhou city, China between 2014 and 2019. k13 gene of P. falciparum and k12 of P. vivax were sequenced. Polymorphisms and prevalence of k13 and k12 were analyzed., Results: Most (98.65%, 146/148) P. falciparum infections were imported from Africa, and half P. vivax cases came from Africa and the other half from Asia. Nucleotide mutation prevalence was 2.03% (3/148) and the proportion of amino acid mutations was 0.68% (1/148). The amino acid mutation, A676S, was observed in an isolate from Nigeria. No mutation of k12 was observed from the parasites from African and Asian countries., Conclusions: Limited polymorphism in k13 gene of P. falciparum isolates imported from African countries, but no evidence for the polymorphism of k12 in P. vivax samples from African and Asian countries was found. These results provide information for drug policy update in study region., (© 2021. The Author(s).)

Background: An organ donation coordinator plays an important role in the process of organ donation and transplant. Therefore, investigating and analyzing the current situation in organ donation and examining the correlation between professional identity and psychological resilience of human organ donation coordinator, provides a reference for promoting stable development of organ donation. Methods: A total of 48 coordinators of organ donation in Zhejiang Province were recruited for the study by using the method of convenience sampling. The psychological resilience scale and professional identity questionnaire were used to collect data. Results: The results revealed that the total average score of the professional identity of organ donation coordinators was 34.92 ± 8.57. Compared with the median professional identity score of 34.50, the professional identity of the coordinator in this survey was at a moderate level. The total average score of psychological resilience was 64.44 ± 11.91. There was a significant positive correlation between the professional identity of the coordinator and the total score of psychological resilience ( r = 0.641, P < 0.01). Conclusion: The professional identity and psychological resilience of the coordinators in Zhejiang Province were found to be in the middle level and the higher the psychological resilience score, the stronger the professional identity of the coordinators. It is important to improve the level of psychological resilience among organ donation coordinators to enhance their professional identity., 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 Shu, Xing, Ruan, Gao and Miao.)

Previous studies implicated the neuronal guidance molecule netrin-1 in attenuating myocardial ischemia-reperfusion injury. However, the tissue-specific sources and receptor signaling events remain elusive. Neutrophils are among the first cells responding to an ischemic insult and can be associated with tissue injury or rescue. We found netrin-1 levels were elevated in the blood of patients with myocardial infarction, as well as in mice exposed to myocardial ischemia-reperfusion. Selectively increased infarct sizes and troponin levels were found in Ntn1loxP/loxP Lyz2 Cre+ mice, but not in mice with conditional netrin-1 deletion in other tissue compartments. In vivo studies using neutrophil depletion identified neutrophils as the main source for elevated blood netrin-1 during myocardial injury. Finally, pharmacologic studies using treatment with recombinant netrin-1 revealed a functional role for purinergic signaling events through the myeloid adenosine A2b receptor in mediating netrin-1-elicited cardioprotection. These findings suggest an autocrine signaling loop with a functional role for neutrophil-derived netrin-1 in attenuating myocardial ischemia-reperfusion injury through myeloid adenosine A2b signaling., Competing Interests: Disclosures: The authors declare no competing interests exist., (© 2021 Li et al.)

Sepsis and sepsis-associated lung inflammation significantly contribute to the morbidity and mortality of critical illness. Here, we examined the hypothesis that neuronal guidance proteins could orchestrate inflammatory events during endotoxin-induced lung injury. Through a targeted array, we identified netrin-1 as the top upregulated neuronal guidance protein in macrophages treated with lipopolysaccharide (LPS). Furthermore, we found that netrin-1 is highly enriched in infiltrating myeloid cells, particularly in macrophages during LPS-induced lung injury. Transcriptional studies implicate hypoxia-inducible factor HIF-1α in the transcriptional induction of netrin-1 during LPS treatment. Subsequently, the deletion of netrin-1 in the myeloid compartment (Ntn1 loxp/loxp LysM Cre) resulted in exaggerated mortality and lung inflammation. Surprisingly, further studies revealed enhanced natural killer cells (NK cells) infiltration in Ntn1 loxp/loxp LysM Cre mice, and neutralization of NK cell chemoattractant chemokine (C-C motif) ligand 2 (CCL2) reversed the exaggerated lung inflammation. Together, these studies provide functional insight into myeloid cell-derived netrin-1 in controlling lung inflammation through the modulation of CCL2-dependent infiltration of NK cells., (© 2021 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.)

Cadmium is known as an environmental pollutant that contributes to pancreatic damage and the pathogenesis of diabetes. However, less attention has been devoted to elucidating the mechanisms underlying Cd-induced pancreatic β-cell dysfunction and the role of Cd toxicity in the development of diabetes. In this study, we demonstrated that exposure to Cd caused remarkable pancreatic β-cell dysfunction and death, both in vitro and in vivo. Lipidomic analysis of Cd-exposed pancreatic β-cells using high-resolution mass spectrometry revealed that Cd exposure altered the profile and abundance of lipids. Cd exposure induced intracellular lipid accumulation, promoted lipid biogenesis, elevated pro-inflammatory lipid contents and inhibited lipid degradation. Furthermore, Cd exposure upregulated the expression levels of TNF-α, IL-1β and IL-6 in pancreatic β-cells and elevated the TNF-α, IL1-β and IL-6 levels in the serum and pancreas. Taken together, the results of our study demonstrated that environmental relevant Cd exposure causes pro-inflammatory lipids elevation and insulin secretion dysfunction in β-cells and hence exaggerates diabetes development. Combined exposure to environmental hazardous chemicals might markedly increase the probability of developing diabetes in humans. This study provides new metabolic and pharmacological targets for antagonizing Cd toxicity., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

The circadian clock evolved in diverse organisms to integrate external environmental changes and internal physiology. The clock endows the host with temporal precision and robust adaptation to the surrounding environment. When circadian rhythms are perturbed or misaligned, as a result of jet lag, shiftwork or other lifestyle factors, adverse health consequences arise, and the risks of diseases such as cancer, cardiovascular diseases or metabolic disorders increase. Although the negative impact of circadian rhythm disruption is now well established, it remains underappreciated how to take advantage of biological timing, or correct it, for health benefits. In this Review, we provide an updated account of the circadian system and highlight several key disease areas with altered circadian signalling. We discuss environmental and lifestyle modifications of circadian rhythm and clock-based therapeutic strategies, including chronotherapy, in which dosing time is deliberately optimized for maximum therapeutic index, and pharmacological agents that target core clock components and proximal regulators. Promising progress in research, disease models and clinical applications should encourage a concerted effort towards a new era of circadian medicine.

Three types of Co-xZr (x = 5, 7.5, and 10 wt.%) were treated with hydroxyapatite (HA) and used as an object to investigate the effect of HA coating on the surface and biocompatibility of Co-xZr alloys. And the protein adsorption and the subsequent biological behaviour of osteoblast, fibroblast and macrophages were also investigated. The surface microstructure and wettability were assessed by scanning electron microscopy (SEM) and static angle profilometer. To evaluate the biocompatibility of Co-xZr and Co-xZr-HA, we quantified plasma proteins adsorption by bicinchoninic acid assay (BCA), cytotoxicity and cell proliferation by cell counting kit-8 (CCK-8) and scanning electron microscopy (SEM). The results indicated that Co-xZr-HA alloy surfaces were more hydrophilic and had higher affinity to plasma proteins. Higher protein concentrations were found adsorbed onto Co-7.5Zr-HA and Co-10Zr-HA alloys. Cytotoxicity analysis indicated that HA coating improved the biocompatibility of Co-xZr alloys. Furthermore, the comparable results of co-incubation of Co-xZr-HA alloys with cells reveal cellular attachments to HA surfaces. HA was successfully formed on Co-xZr alloys and modified the surface structure and biocompatibility of the alloys. Co-10Zr-HA and Co-7.5Zr-HA had the most favourable properties and cytocompatibility, and therefore can be potentially used for dental implants.

In this paper, a radial basis neural network adaptive sliding mode controller (RBF-NN ASMC) for nonlinear electromechanical actuator systems is proposed. The radial basis function neural network (RBF-NN) control algorithm is used to compensate for the friction disturbance torque in the electromechanical actuator system. An adaptive law was used to adjust the weights of the neural network to achieve real-time compensation of friction. The sliding mode controller is designed to suppress the model uncertainty and external disturbance effects of the electromechanical actuator system. The stability of the RBF-NN ASMC is analyzed by Lyapunov's stability theory, and the effectiveness of this method is verified by simulation. The results show that the control strategy not only has a better compensation effect on friction but also has better anti-interference ability, which makes the electromechanical actuator system have better steady-state and dynamic performance.

The fertilization capacity of sex-sorted sperms is seriously decreased, which inhibits its wide application. However, little information is still available about the effect of vitamin C (VC) and lycopene (Lyc) on the fertilization capacity of sex-sorted bull sperm. In this study, the washing medium and fertilization medium of sex-sorted sperm from three bull individuals were supplemented with different concentrations of VC (0, 1 × 10 -3 , 1 × 10 -4 , 1 × 10 -5 , 1 × 10 -6  M) or Lyc (0, 1 × 10 -4 , 1 × 10 -5 , 1 × 10 -6 , 1 × 10 -7 ). After washing twice and incubation for 1.5 hr, the malondialdehyde (MDA) level, phosphatidylserine (PS) translocation, membrane potential (Δψm) and IVF (in vitro fertilization) ability of sex-sorted sperm were investigated. For the sex-sorted sperm of bulls A, B and C, 1 × 10 -3  M VC or 1 × 10 -4  M Lyc treatment significantly decreased their MDA levels and PS translocation and increased their Δψm levels and cleavage rates after IVF. When blastocysts were concerned, 1 × 10 -4  M Lyc significantly improved the blastocyst rates and their IFN-tau expression of bulls A and C. In conclusion, supplementation of 1 × 10 -3  M VC or 1 × 10 -4  M Lyc in washing and fertilization medium contributed greatly to improving the fertilization capacity of sex-sorted bull sperm during IVF procedure., (© 2020 Blackwell Verlag GmbH.)

Background: Myeloid derived suppressor cells (MDSCs) have been reported to keep elevating during sepsis. The current study was performed to investigate the immunosuppressive effect of MDSCs and their subsets with the underlying mechanisms. Methods: The immunosuppressive status was manifested by the apoptosis of splenocytes, quantity of T cells and PD-1 expression. The dynamics of quantity and PD-L1 level of MDSCs and the subsets were determined over time. The subset of MDSCs with high PD-L1 level was co-cultured with T cells to observe the suppressive effect. Results: Abdominal abscess was observed after 7 days post-sepsis. Five biomarkers related to organ functions were all significantly higher in the CLP group. The survival rate was consistent with the middle grade severity of sepsis model. Apoptosis of splenocytes increased over time during sepsis; CD4 + T cell decreased from day 1 post-sepsis; CD8+ T cells significantly reduced at day 7. The PD-1 expression in spleen was upregulated from an early stage of sepsis, and negatively related with the quantity of T cells. MDSCs were low at day 1 post-sepsis, but increased to a high level later; the dynamics of PMN-MDSC was similar to MDSCs. PD-L1 on MDSCs was highest at day 1 post-sepsis; PMN-MDSC was the main subset expressing PD-L1. The PMN-MDSC with high PD-L1 expression level extracted on day 1 after surgery from CLP mice significantly inhibited the proliferation of T cells. Conclusions: Sepsis-induced immunosuppression is initiated from a very early stage, a high expression level of PD-L1 on MDSCs and the main subset, PMN-MDSC might play a critical role suppressive role on T cells through PD-L1/PD-1 axis., (Copyright © 2020 Ruan, Feng, Xu, Xu, Song, Lin, Li and Lu.)