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A Norrish-Yang photocyclization reaction has been applied to regio- and stereoselective construction of the ABCDE pentacyclic motif of natural product phainanoids. The observed substrate conformation control implicates this powerful reaction could be applied to the construction of structurally diverse natural product scaffolds.

Ca 2+ -binding proteins (CaBPs; CaBP1-5) are a subfamily of neuronal Ca 2+ sensors with high homology to calmodulin. Notably, CaBP4, which is exclusively expressed in rod and cone photoreceptors, is crucial for maintaining normal retinal functions. However, the functional roles of CaBP1, CaBP2, and CaBP5 in the retina remain elusive, primarily due to limited understanding of their expression patterns within inner retinal neurons. In this study, we conducted a comprehensive transcript analysis using single-cell RNA sequencing datasets to investigate the gene expression profiles of CaBPs in mouse and human retinal neurons. Our findings revealed notable similarities in the overall expression patterns of CaBPs across both species. Specifically, nearly all amacrine cell, ganglion cell, and horizontal cell types exclusively expressed CaBP1. In contrast, the majority of bipolar cell types, including rod bipolar (RB) cells, expressed distinct combinations of CaBP1, CaBP2, and CaBP5, rather than a single CaBP as previously hypothesized. Remarkably, mouse rods and human cones exclusively expressed CaBP4, whereas mouse cones and human rods coexpressed both CaBP4 and CaBP5. Our single-cell reverse transcription polymerase chain reaction analysis confirmed the coexpression CaBP1 and CaBP5 in individual RBs from mice of either sex. Additionally, all three splice variants of CaBP1, primarily L-CaBP1, were detected in mouse RBs. Taken together, our study offers a comprehensive overview of the distribution of CaBPs in mouse and human retinal neurons, providing valuable insights into their roles in visual functions., Competing Interests: The authors declare no competing financial interests., (Copyright © 2024 Liu et al.)

Background: Heart failure (HF) with improved ejection fraction (EF, HFimpEF) is a distinct HF subtype, characterized by left ventricular (LV) reverse remodeling and myocardial functional recovery. Multiple cardiometabolic factors are implicated in this process. Epicardial adipose tissue (EAT), emerging as an endocrine and paracrine organ, contributes to the onset and progression of HF. However, the relation between EAT and the incidence of HFimpEF is still unclear., Methods: A total of 203 hospitalized HF patients with reduced EF (HFrEF, LVEF ≤ 40%) who underwent coronary CT angiography (CCTA) during index hospitalization were consecutively enrolled between November 2011 and December 2022. Routine follow-up and repeat echocardiograms were performed. The incidence of HFimpEF was defined as (1) an absolute LVEF improvement ≥ 10% and (2) a second LVEF > 40% (at least 3 months apart). EAT volume and density were semiautomatically quantified on non-enhanced series of CCTA scans., Results: During a median follow-up of 8.6 (4.9 ~ 13.3) months, 104 (51.2%) patients developed HFimpEF. Compared with HFrEF patients, HFimpEF patients had lower EAT volume (115.36 [IQR 87.08 ~ 154.78] mL vs. 169.67 [IQR 137.22 ~ 218.89] mL, P < 0.001) and higher EAT density (-74.92 ± 6.84 HU vs. -78.76 ± 6.28 HU, P < 0.001). Multivariate analysis showed lower EAT volume (OR: 0.885 [95%CI 0.822 ~ 0.947]) and higher density (OR: 1.845 [95%CI 1.023 ~ 3.437]) were both independently associated with the incidence of HFimpEF. Subgroup analysis revealed that the association between EAT properties and HFimpEF was not modified by HF etiology., Conclusions: This study reveals that lower EAT volume and higher EAT density are associated with development of HFimpEF. Therapies targeted at reducing EAT quantity and improving its quality might provide favorable effects on myocardial recovery in HF patients., (© 2024. The Author(s).)

MicroRNA is regarded as a significant biomarker for cancer diagnosis, disease process evaluation and therapeutic guidance, and dual-parameter measurement may contribute to a more accurate and realistic assessment. To meet the urgent need for simultaneous detection of multiple biomarkers, we combined three-dimensional DNAzyme motors with single molecule imaging technique to construct a convenient, intuitive, and sensitive approach for the simultaneous detection of dual miRNAs in the free state or in extracellular vesicles. Quantification of target miRNAs can be realized through the detection of amplified fluorescence signals generated by the target miRNA-initiated cleavage of fluorescent substrate strands by the DNAzyme motors. The practicability was systematically validated with microRNA-21-5p and microRNA-10b-5p as targets, acquiring a satisfactory sensitivity sufficient to detect low abundance targets at 0.5 or 1 pM to 100 pM. Besides, the extracellular vesicular miRNAs can be conveniently detected without extraction. The clinical applicability was verified with a series of extracellular vesicles from clinical samples, which exhibited good distinguishability between colorectal cancer patients and healthy donors. In addition to the advantages of good specificity and high sensitivity, the system has potential to be easily adapted by minor alteration of the DNA sequences and fluorophore sets for detection of multiple miRNAs and even other types of biomarkers such as proteins. Therefore, it shows promise to be widely applied in various fields such as early diagnosis of cancer and its prognostic assessment.

Aging is the main cause of many degenerative diseases. The skin is the largest and the most intuitive organ that reflects the aging of the body. Under the interaction of endogenous and exogenous factors, there are cumulative changes in the structure, function, and appearance of the skin, which are characterized by decreased synthesis of collagen and elastin, increased wrinkles, relaxation, pigmentation, and other aging characteristics. skin aging is inevitable, but it can be delayed. The successful isolation of mesenchymal stromal cells (MSC) in 1991 has greatly promoted the progress of cell therapy in human diseases. The International Society for Cellular Therapy (ISCT) points out that the MSC is a kind of pluripotent progenitor cells that have self-renewal ability (limited) in vitro and the potential for mesenchymal cell differentiation. This review mainly introduces the role of perinatal umbilical cord-derived MSC(UC-MSC) in the field of skin rejuvenation. An in-depth and systematic understanding of the mechanism of UC-MSCs against skin aging is of great significance for the early realization of the clinical transformation of UC-MSCs. This paper summarized the characteristics of skin aging and summarized the mechanism of UC-MSCs in skin rejuvenation reported in recent years. In order to provide a reference for further research of UC-MSCs to delay skin aging., (© 2024. The Author(s).)

This study proposes a novel robust optimization approach for an integrated water supply system, wherein the decision-makers attempt to improve failure safety of system under various uncertainty strategies. To cope with uncertainty, the ellipsoid uncertainty set is assumed to evaluate the best feasible solution in the direction of water supply under various strategies. We assessed the case of Hamoun watershed, a water-stressed watershed in southeastern of Iran, to evaluate the developed robust optimization model. In the following, the comparative feasibility under uncertainty levels is conducted to analyze the impacts of simulation strategies on the status of robust model. Based on the final results, the reliability of the model's objective functions experienced an increasing trend ( 58.3 % ), and the objective function values under the uncertainty strategies is greatly improved. The findings of the analysis show that the robust strategies in response to the failure safety achieve outstanding optimal objectives under uncertainty., (© 2024. The Author(s).)

Introduction: Uremic pruritus (UP) is a prevalent symptom in patients suffering from uremia, yet its underlying etiology and mechanisms remain incompletely elucidated. Given the significant incidence of UP, identifying specific alterations in proteins present in the blood of UP patients could offer insights into the potential biological pathways associated with UP and facilitate the exploration of biomarkers. Methods: In this study, we employed LC-MS/MS-based data-independent acquisition (DIA) mode to analyze serum samples obtained from 54 UP patients categorized as DKD-UP, HN-UP, and GN-UP (n = 18 for each subgroup), along with 18 uremic patients without pruritus (Negative) and 18 CKD patients without pruritus (CKD). Through DIA mode analysis, a total of 7075 peptides and 959 proteins were quantified. Within these, we identified four upregulated and 13 downregulated Differentially Expressed Proteins (DEPs) in DKD-UP versus Negative, five upregulated and 22 downregulated DEPs in HN-UP versus Negative, and three upregulated and 23 downregulated DEPs in GN-UP versus Negative. Furthermore, we conducted an intersection analysis of the DEPs across these three comparison groups to derive a set of common DEPs (COMP). Subsequently, a total of 67 common DEPs were identified in the three UP groups when compared to the CKD group, with 40 DEPs showing upregulation and 27 DEPs displaying downregulation. Results: Following Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Protein-Protein Interaction (PPI) analyses, we observed that the DEPs distinguishing UP from CKD were primarily associated with mitochondrial function (MT-CYB, PRDX2, TOMM22), inflammation (CD59, CSF1), renal injury (WFDC2), and neural function (CAP1, VGF). Discussion: Our findings contribute to a potential molecular comprehension of UP pathogenesis, shedding light on the identification of these DEPs as plausible biomarkers for UP., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wen-Jing, Rui-Zhi, Si-Yuan, Xiao-Mei, Qiong-Dan, Xiao-Qian, Wen-Hua, Hong-Wei, Jian, Qiong and Li.)

The Diels-Alder reaction stands as one of the most pivotal transformations in organic chemistry. Its efficiency, marked by the formation of two carbon-carbon bonds and up to four new stereocenters in a single step, underscores its versatility and indispensability in synthesizing natural products and pharmaceuticals. The most significant stereoselectivity feature is the "endo rule". While this rule underpins the predictability of the stereochemical outcomes, it also underscores the challenges in achieving the opposite diastereoselectivity, making the exo-Diels-Alder reactions often considered outliers. This review delves into recent examples of exo-Diels-Alder reactions, shedding light on the factors inverting the intrinsic tendency. We explore the roles of steric, electrostatic, and orbital interactions, as well as thermodynamic equilibriums in influencing exo/endo selectivity. Furthermore, we illustrate strategies to manipulate these factors, employing approaches such as bulky substituents, s-cis conformations, transient structural constraints, and innovative control physics. Through these analyses, our aim is to provide a comprehensive understanding of how to predict and design exo-Diels-Alder reactions, paving the way for new diastereoselective catalyst systems and expanding the chemical scope of Diels-Alder reactions., (© 2024 Wiley‐VCH GmbH.)

Background: Currently, in the field of total joint arthroplasty (TJA), there are no studies that have demonstrated the value of the sequential application of hydrogen peroxide, povidone-iodine, and physiological saline during the surgical procedure in decreasing postoperative infections in total knee arthroplasty (TKA), and in decreasing the incidence of periprosthetic joint infections (PJI) in particular. This study aimed to assess the efficacy of the sequential application of hydrogen peroxide, povidone-iodine, and physiological saline in reducing postoperative infections in TKA., Methods: The study prospectively included 4743 patients, with Group A (2371, 49.9%) receiving sequential intraoperative application of hydrogen peroxide, povidone-iodine, and physiological saline irrigation of the incision, and Group B (2372, 50.1%) receiving intraoperative application of physiological saline irrigation of the incision only, to collect the patients' baseline data and clinical characteristics, and to statistically assess the incidence of superficial infections and the PJI during the follow up period to evaluate the clinical value of the study., Results: The baseline levels of patients in Groups A and B were comparable. There were 132 (2.8%) lost visits during the study period. The incidence of superficial infections within 30 days after surgery was 0.22% in Group A and 1.17% in Group B, the difference between the two groups was statistically significant (P = 0.007). The incidence of PJI was 0.17% in Group A and 1.26% in Group B, the difference between the two groups was statistically significant (P = 0.0121)., Conclusion: Sequential application of hydrogen peroxide, povidone-iodine, and physiological saline to irrigate incision in TKA can significantly reduce the incidence of postoperative superficial infections and PJI. The scientific and rational application of this therapy intraoperatively greatly reduces the incidence of PJI and postoperative superficial infections, which is of great benefit to the patient's prognosis., 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 B.V. All rights reserved.)

Humans have long been combating chronic pain. In clinical practice, opioids are firstchoice analgesics, but long-term use of these drugs can lead to serious adverse reactions. Finding new, safe and effective pain relievers that are useful treatments for chronic pain is an urgent medical need. Based on accumulating evidence from numerous studies, excess reactive oxygen species (ROS) contribute to the development and maintenance of chronic pain. Some antioxidants are potentially beneficial analgesics in the clinic, but ROS-dependent pathways are completely inhibited only by scavenging ROS directly targeting cellular or subcellular sites. Unfortunately, current antioxidant treatments do not achieve this effect. Furthermore, some antioxidants interfere with physiological redox signaling pathways and fail to reverse oxidative damage. Therefore, the key upstream processes and mechanisms of ROS production that lead to chronic pain in vivo must be identified to discover potential therapeutic targets related to the pathways that control ROS production in vivo . In this review, we summarize the sites and pathways involved in analgesia based on the three main mechanisms by which ROS are generated in vivo, discuss the preclinical evidence for the therapeutic potential of targeting these pathways in chronic pain, note the shortcomings of current research and highlight possible future research directions to provide new targets and evidence for the development of clinical analgesics., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Lead-free double perovskites (DPs) are emerging highly stable emitters with efficient broadband self-trapped exciton (STE) photoluminescence (PL), but their low electroluminescent (EL) efficiency is a critical shortcoming. This work promotes the external quantum efficiency (EQE) and luminance of DP-based white light-emitting diode (wLED) with a normal device structure to 0.76% and 2793 cd m -2 via two modifications: This work prevents the formation of adverse metallic silver, spatially confined STE, and lowers local site symmetry in Cs 2 Na 0.4 Ag 0.6 In 0.97 Bi 0.03 Cl 6 DP by terbium doping; and this work develops a guest-host strategy to improve film morphology, reduce defect density, and increase carrier mobility. These alterations cause substantial increase in STE radiative recombination and charge injection efficiency of perovskite layer. Finally, pure white EL with ideal color coordinates of (0.328, 0.329) and a record-breaking optoelectronic performance is achieved by introducing additional green carbon dots in LED to fill the deficient green component., (© 2023 Wiley-VCH GmbH.)

Aim: This retrospective clinical study was designed to examine the predictive value of thromboelastography (TEG) combined with coagulation function for venous thromboembolism (VTE) in hospitalized patients with cancer. Materials & methods: Among 215 patients admitted between May 2020 and January 2022, 39 (18.14%) were diagnosed with VTE during hospitalization. Results: Significant differences were found in D-dimer, ATIII and TEG parameters (maximum amplitude and coagulation index) between VTE-positive and VTE-negative patients (p < 0.05). Multivariate analysis revealed tumor node metastasis stage, concomitant infection, smoking history and D-dimer as independently associated with VTE. The constructed model and D-dimer areas under the curve were 0.809 and 0.764, respectively. Conclusion: TEG parameters were not significantly predictive indicators for VTE, with D-dimer remaining a key predictor.

Despite the widespread use in industrial production, benzene derivatives are harmful to both human beings and the environment. The control of these substances has become an important subject of scientific research. This study introduces a new approach for adsorption and separation of benzene derivatives utilizing pagoda[n]arene based supramolecular materials. Density functional theory calculations were employed to investigate the molecular recognition mechanism of benzene derivatives by pagoda[4]arenes and pagoda[5]arenes (Pa[4]As and Pa[5]As). Results indicate that Pa[4]As and Pa[5]As can effectively accommodate benzene derivatives through non-covalent interactions, leading to the formation of stable host-guest complexes. Additionally, molecular dynamics simulations revealed that both crystalline and non-crystalline supramolecular aggregates of Pa[4]As and Pa[5]As possess the ability to adsorb benzene derivatives and maintain the stability of the adsorption. Moreover, increasing the temperature causes benzene derivatives to desorb from the adsorbing aggregates, and thus the material can be reutilized., (© 2023 Wiley-VCH GmbH.)

In general, the sustainability of the water supply system is indicative of an adaptive operational approach, wherein the decision-maker adjusts the system's performance based on the availability of water resources in a given time frame. In light of this, a novel framework is proposed in this study to evaluate sustainability, including three key indicators: resilience, reliability, and vulnerability. To address stressors that may lead to system failure, a multisectoral water allocation optimization is undertaken. In order to account for the future implications of climate change on the hydrological cycle, a simulation step, is incorporated, utilizing the Soil and Water Assessment Tool (SWAT) under various emission scenarios (RCP4.5 and RCP8.5), prior to integrating the streamflow data into our proposed optimal framework. To calibrate and validate historical data (2014-2019) and simulate future streamflow patterns (2025-2085), the Sistan Basin, located in an arid region of Iran, is analyzed as a case study. In light of the anticipated adverse impacts on the water supply system, certain adaptation measures, such as demand shrinkage scenarios, are considered to further appraise the proposed framework. Based on the final output, it is evident that the agricultural and industrial sectors, being the primary water consumers, are more susceptible to negative impacts resulting from the reduction in system sustainability. This susceptibility is primarily attributed to their highest vulnerability and comparatively lower reliability., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Moudi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

With the rapid development of society and the economy, population aging has become a common challenge faced by many countries in the world today. Structural and functional changes in the cardiovascular system can occur with age, increasing the incidence and severity of cardiovascular diseases in older adults. Due to the limited regenerative capacity of myocardial cells, myocardial infarction and its resulting heart failure and congenital heart disease have become the number one killer of human health. At present, the treatment of cardiovascular diseases includes drug therapy and nondrug therapy. Nondrug therapy mainly includes minimally invasive interventional therapy, surgical diagnosis and treatment, and cell therapy. Long-term drug treatment may cause headache due to vasodilation, lower blood pressure, digestive system dysfunction and other side effects. Surgical treatment is traumatic, difficult to treat, and expensive. In recent years, stem cell therapy has exhibited broad application prospects in basic and clinical research on cardiovascular disease because of its plasticity, self-renewal and multidirectional differentiation potential. Therefore, this paper looks at stem cell therapy for diseases, reviews recent advances in the mechanism and clinical transformation of cardiovascular aging and related diseases in China, and briefly discusses the development trend and future prospects of cardiovascular aging research., Competing Interests: This paper has not been published elsewhere in whole or in part. All authors have read and approved the content, and agree to submit for consideration for publication in the journal. There are no any ethical/legal conflicts involved in the article. Your consideration for this manuscript is highly appreciated., (© 2023 The Japanese Society for Regenerative Medicine. Production and hosting by Elsevier B.V.)

The yellow peach moth, Conogethes punctiferalis, is a highly polyphagous pest widespread in eastern and southern Asia. It demonstrates a unique ability to adapt to rotten host fruits and displays resistance to pathogenic microorganisms, including fungi. However, the lack of available genomic resources presents a challenge in comprehensively understanding the evolution of its innate immune genes. Here, we report a high-quality chromosome-level reference genome for C. punctiferalis utilizing PacBio HiFi sequencing and Hi-C technology. The genome assembly was 494 Mb in length with a contig N50 of 3.25 Mb. We successfully anchored 1,226 contigs to 31 pseudochromosomes. Our BUSCO analysis further demonstrated a gene coverage completeness of 96.3% in the genome assembly. Approximately 43% repeat sequences and 21,663 protein-coding genes were identified. In addition, we resequenced 110 C. punctiferalis individuals from east China, achieving an average coverage of 18.4 × and identifying 5.8 million high-quality SNPs. This work provides a crucial resource for understanding the evolutionary mechanism of C. punctiferalis' innate immune system and will help in developing new antibacterial drugs., (© 2023. The Author(s).)

In this paper, we report an efficient strategy for synthesizing the DEFGH rings of phainanoid F. The key to the construction of the 13,30-cyclodammarane skeleton of the molecule was a photo-induced 6π-electrocyclization and a homoallylic elimination. Notably, this is a rare example of using electrocyclization reaction to simultaneously construct two vicinal quaternary carbons in total synthesis. The strategy outlined here forms the basis of our total synthesis of Phainanoid F, and it could also serve as a generally applicable approach for synthesizing other natural products containing similar 13,30-cyclodammarane skeletons., (© 2023 Wiley-VCH GmbH.)

Due to the uncertainty of rainfall and water demand, the water supply of various participants has been challenged in such a way that this challenge has accelerated the failure of water supply system. Thus, this study proposes a multi-stage Adjustable Robust Optimization integrated to the multi-objective programming framework to drive water supply system to the failure safety zone and thereby improve robustness of system under different scenarios. Indeed, Adjustable Robust Optimization framework is applied to investigate the two uncertain factors of rainfall and water demand. A real arid area of Sistan basin in southeastern Iran is considered to analyze the proposed multi-objective programming model. Next, various comparative feasibilities under different levels of uncertainty are carried out to examine the robustness status in more detail. In the following, due to the deterioration of climatic patterns in the coming years, some managerial insights are highlighted. According to the final outputs, the domestic sector has reached more optimal value compared to that of the agricultural and industrial participants in all objectives due to less water intake, and as a result, it has a significant impact on the robustness of water supply system., 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 Inc. All rights reserved.)

A highly enantioselective catalytic system for exo-Diels-Alder reactions was developed based on the newly discovered bispyrrolidine diboronates (BPDB). Activated by various Lewis or Brønsted acids, BPDB can catalyze highly stereoselective asymmetric exo-Diels-Alder reactions of monocarbonyl-based dienophiles. When 1,2-dicarbonyl-based dienophiles are used, the catalyst can sterically distinguish between the two binding sites, which leads to highly regioselective asymmetric Diels-Alder reactions. BPDB can be prepared as crystalline solids on a large scale and are stable under ambient condition. Single-crystal X-ray analysis of the structure for acid-activated BPDB indicated that its activation involves cleavage of a labile B←N bond., (© 2023 Wiley-VCH GmbH.)

Objective: This study aimed to investigate the role of computed tomography angiography (CTA) and three-dimensional (3D) reconstruction of renal arteries in the evaluation of bleeding after mini- percutaneous nephrolithotomy (PCNL)., Methods: Thirty-one consecutive patients with continuous renal hemorrhage after mini-PCNL were enrolled from January 2015 to January 2022. Demographic and clinical data were retrospectively recorded and analyzed. All patients had received CTA evaluation and subsequently digital subtraction angiography (DSA) embolization to manage renal bleeding. CTA and 3D reconstruction of renal arteries were performed using the 320 multi-detector computed tomography technique and the images were evaluated by experienced radiologists. DSA embolization were performed by an interventional radiologist with more than 10 years of experiences., Results: CTA and 3D construction of renal arteries showed 28 cases of vascular lesions (28/31, 90.3%), including 15 cases of pseudoaneurysm (15/28, 53.6%), 9 cases of arteriovenous fistula (9/28, 32.1%), and 4 cases of suspicious bleeding spot (4/28, 14.3%). While DSA revealed 31 cases of vascular lesions (100%), including 15 cases of pseudoaneurysm (15/31, 48.4%), 10 cases of arteriovenous fistula (10/31, 32.3%), 6 cases of bleeding spot and (6/31, 19.4%). The serum creatinine level was elevated slightly before mini-PCNL and after DSA embolization (73.1±18.1 vs 92.1±33.6, P <.01). 15 patients (15/31, 48.4%) required blood transfusion, with mean blood transfusion volume of 700 ml ±660 ml (range, 400 ml-1800 ml). The bleeding was controlled without any further severe complications., Conclusion: CTA and 3D reconstruction of renal arteries were safe and effective in diagnosing renal arterial bleedings after mini-PCNL, with a sensitivity of 90.3% and a specificity of 100%., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Purpose: To observe the effect of gellan gum loaded with nano-hydroxyapatite (GG/nHA) on repairing mandibular defect in rats., Methods: Critical bone defects with 5 mm in diameter on the mandible of 16 SD rats were created and randomly divided into two groups. The bone defects in the experimental group were injected with GG/nHA and the control group were filled with absorbable gelatin sponge. The rats were sacrificed at 4 and 8 weeks after operation. The bone tissue healing was evaluated by Micro-CT. Bone tissue repairing effect was evaluated by hematoxylin-eosin (H-E) staining and Masson staining. GraphPad Prism 8.0 software package was used for statistical analysis., Results: The prepared GG/nHA had a good injectability and could be delivered to the bone defect area with a syringe. Four and 8 weeks after operation, the newly formed bone and bone volume fraction (BV/TV) in the experimental group were higher than those in the control group, and the difference was statistically significant (P<0.05). Larger number of new bone were observed in the experimental group than the control group by H-E staining and Masson staining., Conclusions: GG/nHA can be injected into the mandibular defect area to promote its healing, and it is expected to be used as a novel bio-material for minimally invasive repair of oral and maxillofacial bone defects.

(-)-Anisomelic acid, isolated from Anisomeles indica (L.) Kuntze (Labiatae) leaves, is a macrocyclic cembranolide with a trans -fused α-methylene-γ-lactone motif. Anisomelic acid effectively inhibits SARS-CoV-2 replication and viral-induced cytopathic effects with an EC 50 of 1.1 and 4.3 μM, respectively. Challenge studies of SARS-CoV-2-infected K18-hACE2 mice showed that oral administration of anisomelic acid and subcutaneous dosing of remdesivir can both reduce the viral titers in the lung tissue at the same level. To facilitate drug discovery, we used a semisynthetic approach to shorten the project timelines. The enantioselective semisynthesis of anisomelic acid from the naturally enriched and commercially available starting material (+)-costunolide was achieved in five steps with a 27% overall yield. The developed chemistry provides opportunities for developing anisomelic-acid-based novel ligands for selectively targeting proteins involved in viral infections., (© The Author(s) 2022. Published by Oxford University Press on behalf of China Science Publishing & Media Ltd.)

Retinal bipolar cells (BCs) compose the canonical vertical excitatory pathway that conveys photoreceptor output to inner retinal neurons. Although synaptic transmission from BC terminals is thought to rely almost exclusively on Ca 2+ influx through voltage-gated Ca 2+ (Ca V ) channels mediating L-type currents, the molecular identity of Ca V channels in BCs is uncertain. Therefore, we combined molecular and functional analyses to determine the expression profiles of Ca V α 1 , β, and α 2 δ subunits in mouse rod bipolar (RB) cells, BCs from which the dynamics of synaptic transmission are relatively well-characterized. We found significant heterogeneity in Ca V subunit expression within the RB population from mice of either sex, and significantly, we discovered that transmission from RB synapses was mediated by Ca 2+ influx through P/Q-type (Ca V 2.1) and N-type (Ca V 2.2) conductances as well as the previously-described L-type (Ca V 1) and T-type (Ca V 3) conductances. Furthermore, we found both Ca V 1.3 and Ca V 1.4 proteins located near presynaptic ribbon-type active zones in RB axon terminals, indicating that the L-type conductance is mediated by multiple Ca V 1 subtypes. Similarly, Ca V 3 α 1 , β, and α 2 δ subunits also appear to obey a "multisubtype" rule, i.e., we observed a combination of multiple subtypes, rather than a single subtype as previously thought, for each Ca V subunit in individual cells. SIGNIFICANCE STATEMENT Bipolar cells (BCs) transmit photoreceptor output to inner retinal neurons. Although synaptic transmission from BC terminals is thought to rely almost exclusively on Ca 2+ influx through L-type voltage-gated Ca 2+ (Ca V ) channels, the molecular identity of Ca V channels in BCs is uncertain. Here, we report unexpectedly high molecular diversity of Ca V subunits in BCs. Transmission from rod bipolar (RB) cell synapses can be mediated by Ca 2+ influx through P/Q-type (Ca V 2.1) and N-type (Ca V 2.2) conductances as well as the previously-described L-type (Ca V 1) and T-type (Ca V 3) conductances. Furthermore, Ca V 1, Ca V 3, β, and α 2 δ subunits appear to obey a "multisubtype" rule, i.e., a combination of multiple subtypes for each subunit in individual cells, rather than a single subtype as previously thought., (Copyright © 2022 the authors.)

Background: Hoverflies (Diptera: Syrphidae) including Eupeodes corollae are important insects worldwide that provide dual ecosystem services including pest control and pollination. The larvae are dominant predators of aphids and can be used as biological control agents, and the adults are efficient pollinators. The different feeding habits of larvae and adults make hoverflies a valuable genetic resource for understanding the mechanisms underlying the evolution and adaptation to predation and pollination in insects., Results: Here, we present a 595-Mb high-quality reference genome of the hoverfly E. corollae, which is typical of an aphid predator and a pollinator. Comparative genomic analyses of E. corollae and Coccinellidae (ladybugs, aphid predators) shed light on takeout genes (3), which are involved in circadian rhythms and feeding behavior and might regulate the feeding behavior of E. corollae in a circadian manner. Genes for sugar symporter (12) and lipid transport (7) related to energy production in E. corollae had homologs in pollinator honeybees and were absent in predatory ladybugs. A number of classical cytochrome P450 detoxification genes, mainly CYP6 subfamily members, were greatly expanded in E. corollae. Notably, comparative genomic analyses of E. corollae and other aphidophagous hoverflies highlighted three homologous trypsins (Ecor12299, Ecor12301, Ecor2966). Transcriptome analysis showed that nine trypsins, including Ecor12299, Ecor12301, and Ecor2966, are strongly expressed at the larval stage, and 10 opsin genes, which are involved in visual perception, are significantly upregulated at the adult stage of E. corollae., Conclusions: The high-quality genome assembly provided new insights into the genetic basis of predation and pollination by E. corollae and is a valuable resource for advancing studies on genetic adaptations and evolution of hoverflies and other natural enemies., (© 2022. The Author(s).)

Excitatory amino acid transporters (EAATs) control visual signal transmission in the retina by rapidly removing glutamate released from photoreceptors and bipolar cells (BCs). Although it has been reported that EAAT2 and EAAT5 are expressed at presynaptic terminals of photoreceptors and some BCs in mammals, the distinct functions of these two glutamate transporters in retinal synaptic transmission, especially at a single synapse, remain elusive. In this study, we found that EAAT2 was expressed in all BC types while coexisting with EAAT5 in rod bipolar (RB) cells and several types of cone BCs from mice of either sex. Our immunohistochemical study, together with a recently published literature (Gehlen et al., 2021), showed that EAAT2 and EAAT5 were both located in RB axon terminals near release sites. Optogenetic, electrophysiological and pharmacological analyses, however, demonstrated that EAAT2 and EAAT5 regulated neurotransmission at RB→AII amacrine cell synapses in significantly different ways: EAAT5 dramatically affected both the peak amplitude and kinetics of postsynaptic responses in AIIs, whereas EAAT2 had either relatively small or opposite effects. By contrast, blockade of EAAT1/GLAST, which was exclusively expressed in Müller cells, showed no obvious effect on AII responses, indicating that glutamate uptake by Müller cells did not influence synaptic transmission from RB terminals. Furthermore, we found that temporal resolution at RB→AII synapses was reduced substantially by blockade of EAAT5 but not EAAT2. Taken together, our work reveals the distinct functions of EAAT2 and EAAT5 in signal transmission at RB ribbon synapses., (Copyright © 2022 Tang et al.)

Background: The general principle of using microbes from one species to manage a different pest species has a clear precedent in the large-scale release of mosquitoes carrying a Wolbachia bacterium derived from Drosophila flies. New technologies will facilitate the discovery of microbes that can be used in a similar way. Previously, we found three novel partiti-like viruses in the African armyworm (Spodoptera exempta). To investigate further the utility and consistency of host shift of insect viruses as a potential pest management tool, we tested the interaction between the partiti-like viruses and another novel host, the Egyptian cotton leafworm (Spodoptera littoralis)., Result: We found that all three partiti-like viruses appeared to be harmful to the novel host S. littoralis, by causing increased larval and pupal mortality. No effect was observed on host fecundity, and partiti-like virus infection did not impact host susceptibility when challenged with another pathogen, the baculovirus SpliNPV. Transcriptome analysis of partiti-like virus-infected and noninfected S. littoralis indicated that the viruses could impact host gene-expression profiles of S. littoralis, but they impact different pathways to the two other Spodoptera species through effects on pathways related to immunity (Jak-STAT/Toll and Imd) and reproduction (insulin signaling/insect hormones)., Conclusion: Taken together with the previous findings in the novel host S. frugiperda, these results indicate a parasitic relationship between the partiti-like viruses and novel insect hosts, suggesting a possible use and novel pest management strategy through the artificial host shift of novel viruses. © 2021 Society of Chemical Industry., (© 2021 Society of Chemical Industry.)

Background: Acute pulmonary embolism and severe renal bleeding are two lethal postoperative complications, but there has been no report that involves both of them after mini-percutaneous nephrolithotomy., Case Presentation: A 62-year-old woman was admitted to our hospital with extremely severe hydronephrosis and multiple right renal calculi. After thorough examination, she received prone-position mini-percutaneous nephrolithotomy under spinal anaesthesia. Three days postoperatively, the patient complained of chest pain and dyspnea. Computed tomography pulmonary angiogram (CTPA) showed multiple embolisms in the left pulmonary artery and its branches. Symptoms were relieved after anticoagulant and thrombolysis therapy. On the 6th postoperative day, the patient developed shortness of breath, computed tomography angiography (CTA) showed massive hemorrhage in the right kidney, diffused contrast medium in the middle and lower part of the right kidney was seen during digital substraction angiography (DSA). Superselective right renal artery embolization (SRAE) was then applied using coil to occlude the responsible artery. The patient generally recovered under conscientious care and was approved to be discharged 26 days postoperatively., Conclusions: This is the first case that involved both acute pulmonary embolism and severe post thrombolysis renal bleeding. The importance of D-dimer in the prediction and early detection of pulmonary embolism should be noted. For post thrombolysis renal bleeding, SRAE is considered as a reliable treatment., (© 2022. The Author(s).)

Background: Repair of peripheral nerve defect presents a considerable challenge for reconstructive surgeons. The aim of this study is to develop a brain-derived neurotrophic factor (BDNF) from poly(D,L-lactide-co-glycolide) (PLGA) microspheres for the treatment of the peripheral nerve defect., Method: BDNF microspheres were prepared by using an oil-in-water emulsification-solvent evaporation method. The morphology, particle size, encapsulation efficiency, drug loading and sustained release performance of microspheres was observed and calculated. Adipose mesenchymal stem cells (ADSCs) were isolated and expanded. ADSCs were divided into four groups: control, BDNF, blank microsphere and BDNF microsphere groups. Cell count kit-8 (CCK-8) assays were used to assess cell proliferation. Cell migration was determined by Transwell assays. Twenty-eight male Sprague-Dawley rats underwent transection damage model on the right sciatic nerve. The wet weight ratio of the gastrocnemius muscle was calculated by comparing the weight of the gastrocnemius muscle from the operated side to that of the normal side. Neuroelectrophysiological testing was performed to assess nerve function recovery. Nerve regeneration was evaluated by histological analysis and immunohistochemical staining., Results: The microspheres were spherical and had uniform size (46.38 ± 1.00 μm), high encapsulation efficiency and high loading capacity. In vitro release studies showed that BDNF-loaded microspheres had good sustained release characteristics. The duration of BDNF release was extended to more than 50 days. BDNF or BDNF microsphere promote the proliferation and migration of ADSCs than control group (P < 0.05). Compared with control group, BDNF significantly decreased the nerve conduction velocity (NCV) and compound amplitude (AMP) (P < 0.05). The nerve fibers in the BDNF microsphere group were closely arranged and uniformly distributed than control group., Conclusion: BDNF/PLGA sustained-release microsphere could promote the migration of ADSCs and promoted neural differentiation of ADSCs. Moreover, BDNF/PLGA sustained-release microsphere ameliorated nerve conduction velocity and prevented neuralgic amyotrophy., (© 2022. The Author(s).)

Based on the brushless DC motor system with DC-link small capacitance powered by a single-phase AC power source, a boosting DC-link voltage strategy to reduce the commutation torque ripple of brushless DC motors is proposed in this paper. The control strategy utilizes the special topology of the motor system to boost the DC-link capacitor voltage in a specific zone during the non-commutation period. During the commutation period, the high voltage of the DC-link capacitor is released to meet the voltage requirement of the brushless DC motor during commutation. In order to reduce the commutation torque ripple and ensure the normal operation of the brushless DC motor, each rectifier cycle is divided into three zones according to the characteristics of the periodic change of the rectifier output voltage. Different operation modes are proposed for different zones. In DC-link capacitor boost voltage mode, the DC-link capacitor boosts the voltage to meet the voltage of the motor demand during the commutation period for achieving the purpose of reducing the commutation torque ripple. In this paper, the controller of the brushless DC motor system is designed and the experimental platform is built. The experimental results verified the correctness of the theoretical analysis and the feasibility of the proposed method.

The treatment of infected bone defects in complex anatomical structures, such as oral and maxillofacial structures, remains an intractable clinical challenge. Therefore, advanced biomaterials that have excellent anti-infection activity and allow convenient delivery are needed. We fabricated an innovative injectable gellan gum (GG)-based hydrogel loaded with nanohydroxyapatite particles and chlorhexidine (nHA/CHX). The hydrogel has a porous morphology, suitable swelling ratio, and good biocompatibility. It exerts strong antibacterial activity against Staphylococcus aureus growth and biofilm formation in vitro . We successfully established an infected calvarial defect rat model. Bacterial colony numbers were significantly lower in tissues surrounding the bone in rats of the GG/nHA/CHX group after debride surgery and hydrogel implantation in the defect regions than in rats of the blank group. Rats in the GG/nHA/CHX group exhibited significantly increased new bone formation compared to those in the blank group at 4 and 8 weeks. These findings indicate that gellan gum-based hydrogel with nHA/CHX can accelerate the repair of infected bone defects.

Diastereoselective syntheses of syn - and anti -vicinal dihalides were achieved via an aza-Belluš-Claisen rearrangement, which involved the reaction of an α-chloro carboxylic acid chloride with halogen-substituted trans -allyl morpholines in the presence of Lewis acids. The developed method was used for the total synthesis of a group of monoterpene natural products bearing vicinal dichloride subunits.

Malignant hyperthermia (MH) is characterized by a rapid rise in body temperature after using inhalational anesthetics and depolarizing muscle relaxants. A 19-year-old female had a rapidly developing fever up to 43.0 °C, after rhinoplasty surgery. Inhalational anesthetics and depolarizing muscle relaxants were used in general anesthesia. It was suspected that the patient died of MH. The medico-legal autopsy findings showed classical MH histopathological changes in the skeletal muscles, cardiac muscles, as well as lungs. Additionally, postmortem blood biochemical results indicated rhabdomyolysis. A combination of clinical records and autopsy revealed that MH might have caused the death. A diagnostic genetic testing was performed to confirm the existence of MH, and an MH diagnostic variant RYR1 c.7048G >A (p. A2350T) was detected. Eventually, the cause of death was determined as MH based on clinical records, autopsy, and genetic analysis. This case highlights that diagnostic genetic analysis plays a vital role in postmortem diagnosis of MH in routine medico-legal contexts., (Copyright © 2021 Elsevier B.V. All rights reserved.)

A field manipulative experiment was carried out during 2015 and 2016 to examine the changes and influencing factors of root production, turnover rate, and standing crop under different nitrogen (N) addition levels, i.e ., 0, 1, 2, 4, 8 and 16 g N·m -2 ·a -1 , in a Tibetan alpine steppe. The results showed that root production and standing crop decreased linearly or exponentially with increasing N addition rates. Compared with control, 16 g N·m -2 ·a -1 significantly reduced the two-year average root production and standing crop by 43.0% and 45.7%, respectively. Root turnover rate increased first and then decreased along the N addition gradient, with the maximum appearing under 2 and 4 g N·m -2 ·a -1 treatments for 2015 and 2016, respectively. Results from linear mixed-effects models showed that root starch content was the main factor modulating the N-induced changes in root production and turnover rate, explaining 21.7% and 25.4% of their variations. Root protein content mainly contributed to the variations in standing crop, with an explanation of 20.8% of its variance. Overall, N addition had negative effect on root production and standing crop, and low N promoted while high N inhibited root turnover rate. Root metabolic parameters were the main factors modulating the N-induced changes in root dynamics.

Water scarcity poses a real crisis for decision makers of water supply system because satisfying growing demand and, as a result, achieving full consumer satisfaction in different sectors of the system remains a major problem. Therefore, this study develops a dynamic multi-objective model of water supply optimization under different scenarios to improve multisectoral consumer satisfaction. To diminish the negative effects of the water crisis on long-term consumer satisfaction, the performance of the dynamic water supply system is evaluated and optimized, which can change the situation from a state of dissatisfaction to satisfaction. In this regard, to analyze the developed model, a real case study of the Hamoun wetland in southeastern Iran is considered. According to the proposed model, various strategies are performed along with the analysis of two scenarios related to runoff uncertainty in order to investigate the consumer satisfaction status in detail. However, given to the final results, which show the greater impact of the two sensitive factors of reliability and vulnerability on consumer satisfaction, the highest level of dissatisfaction is related to the agricultural sector because it has less reliability and higher vulnerability compared to other sectors. In this regard, by proposing policies such as weight scenarios and demand reduction scheme, the situation of consumer satisfaction has improved much more desirable., (Copyright © 2021. Published by Elsevier Ltd.)

This study describes a morphology-based unilateral cervical facet interlocking classification in an attempt to clarify the injury mechanism, instability, neurological deficits, radiological features, and determine optimum management strategies for these injuries. A total of 55 patients with unilateral cervical locked facet (UCLF) involving C3 to C7 were identified between January 1, 2012 and December 1, 2019. The injuries were classified into three types, and they were further divided into six subtypes using three-dimensional computed tomography. The injury mechanism, clinical features, neurological deficits, and imaging characteristics were analyzed, and the appropriate treatment strategies for UCLF were discussed. UCLFs were divided into the following six subtypes: UCLF without lateral mass-facet fracture (type I) in nine cases, with superior articular process fracture (type II A) in 22, with inferior articular process fracture (type II B) in seven, both superior and inferior articular process fractures (type II C) in four, with lateral mass splitting fracture (type III A) in three, and with lateral mass comminution fractures (type III B) in ten. A total of 22 (40.0%) of the 55 patients presented with radiculopathy, and 23 patients (41.8%) had spinal cord injuries. The subtype analyses showed high rates of radiculopathy in types II A (68.2%) and II C (75.0%), as well as significant spinal cord injury in types I (77.8%) and III (61.5%). Destruction of the facet capsule was observed in all patients, but the injury of disc, ligamentous complex, and vertebra had a significant difference among the types or subtypes. The instability parameters of the axial rotation angle, segmental kyphosis, and sagittal displacement showed significant differences in various types of UCLF. Closed reduction by preoperative and intraoperative general anesthesia traction was achieved in 27 patients (49.1%), and successful rate of closed reduction in type I (22.2%) was significantly lower than that in type II (51.5%) and type III (61.5%). A total of 35 of 55 patients underwent a single anterior fixation and fusion, 10 patients were treated with posterior pedicle and (or) lateral mass fixation, and combined surgery was performed in ten patients. Ten patients (18.2%) with a poor outcome were observed after first surgery. Among them, 3 patients treated with a single anterior surgery had persistent or aggravated radiculopathy and posterior approach surgery with ipsilateral facet resection, foramen enlargement, and pedicle and (or) lateral mass screw fixation was performed immediately, 5 patients treated with a short-segment posterior surgery showed mild late kyphosis deformity, and 2 patients with vertebral malalignment were encountered after anterior single-level fusion during the follow-up. This retrospective study indicated that UCLF is a rotationally unstable cervical spine injury. The classification proposed in this study will contribute to understanding the injury mechanism, radiological characteristics, and neurological deficits in various types of UCLF, which will help the surgeons to evaluate the preoperative closed reduction and guide the selection of surgical approach and fusion segment., (© 2021. The Author(s).)

Bacillus thuringiensis (Bt) crops have been widely planted and the effects of Bt-crops on populations of the target and non-target insect pests have been well studied. However, the effects of Bt-crops exposure on microorganisms that interact with crop pests have not previously been quantified. Here, we use laboratory and field data to show that infection of Helicoverpa armigera with a densovirus (HaDV2) is associated with its enhanced growth and tolerance to Bt-cotton. Moreover, field monitoring showed a much higher incidence of cotton bollworm infection with HaDV2 in regions cultivated with Bt-cotton than in regions without it, with the rate of densovirus infection increasing with increasing use of Bt-cotton. RNA-seq suggested tolerance to both baculovirus and Cry1Ac were enhanced via the immune-related pathways. These findings suggest that exposure to Bt-crops has selected for beneficial interactions between the target pest and a mutualistic microorganism that enhances its performance on Bt-crops under field conditions., Competing Interests: YX, WL, XY, PX, MJ, HY, WZ, KW, KW No competing interests declared, MS, AB coauthor of a patent on modified Bt toxins, "Suppression of Resistance in Insects to Bacillus thuringiensis Cry Toxins, Using Toxins that do not Require the Cadherin Receptor" (patent numbers: CA2690188A1, CN101730712A, EP2184293A2, EP2184293A4, EP2184293B1, WO2008150150A2, WO2008150150A3)., (© 2021, Xiao et al.)

Objective: Common venous malformations (VMs) are a frequent sporadic subtype of vascular malformations. Given the TEK and PIK3CA mutations identified, this study aims to investigate the genetic landscape of VMs in the head and neck., Methods: Patients from published sequencing studies related to common VMs were reviewed. Detailed data regarding clinical characteristics, sequencing strategies, and mutation frequency were synthesized. Lesion distribution of common VMs in the head and neck were further retrospectively analyzed by the pathologic database of the Department of Oral and Maxillofacial-Head and Neck Oncology, Shanghai Ninth People's Hospital. For the frequently affected sites in the head and neck, patients were selected for targeted sequencing with a designed vascular malformation-related gene panel or whole exome sequencing. Detected variants were analyzed by classical bioinformatic algorithms (SIFT23, PolyPhen-2 HDIV, LRT, MutationTaster, Mutation Assessor, and GERP++). To confirm the expression pattern of particular candidate gene, specimens were examined histochemically. Gene ontology enrichment analysis and a protein-protein interaction network were also constructed., Results: Three hundred patients from eight sequencing studies related to common VMs were reviewed. The total prevalence rates of TEK and PIK3CA mutations were 41.3% and 26.7%, respectively. The most frequent TEK/PIK3CA mutations were TEK-L914F/PIK3CA-H1047R. TEK/PIK3CA mutations existed in 70.3% and 2.7% of VMs in the head and neck. In retrospective data from 649 patients carrying cervicofacial VMs at Shanghai Ninth Hospital, the most frequent sites were the maxillofacial region (lips, cheek, parotid-masseteric region, submandibular region) and the oral and oropharyngeal region (buccal mucosa, tongue). Targeted sequencing for 14 frequent lesions detected TEK variants in three patients (21.4%), but no PIK3CA mutations. On whole exome sequencing of two patients without TEK/PIK3CA mutations, CDH11 was the only shared deleteriously mutated gene. Bioinformatic analyses of CDH11 implied that genes involved in cellular adhesion and junctions formed a significant portion., Conclusions: Common VMs of the head and neck have a unique genetic landscape. Novel CDH11 and TEK variants imply that pathogenesis is mediated by the regulatory relationship between endothelial cells and extracellular components., (Copyright © 2020 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

A novel method for the concise synthesis of cyclohepta[b]indoles in high yields was developed. The method involves a visible-light-induced, photocatalyzed [2+2]-cycloaddition/ retro-Mannich-type reaction of enaminones. Experimental and computational studies suggested that the reaction is a photoredox process initiated by single-electron oxidation of an enaminone moiety, which undergoes subsequent cyclobutane formation and rapidly fragmentation in a radical-cation state to form cyclohepta[b]indoles., (© 2021 Wiley-VCH GmbH.)

Macrophages play an important role in the immune microenvironment during bone healing, and sequential macrophage phenotypic transition could achieve superior osteogenic outcomes. Microcrystalline bioactive glasses (MCBGs) with osteoimmunomodulatory effects show potential in bone tissue regeneration. Zinc (Zn) has been approved to coordinate innate and adaptive immunity. Therefore, in this study, different amounts of ZnO were incorporated into microcrystalline bioactive glass to improve its immunomodulatory ability. The effect of Zn-MCBG ionic extracts on macrophage transition was studied, and the 5Zn-MCBG extracts could orchestrate sequential M1-to-M2 macrophage transition and promote the expression of proinflammatory and anti-inflammatory genes and cytokine expression to induce human bone marrow stromal cells (hBMSCs) osteogenic differentiation in vitro. Macroporous Zn-MCBG scaffolds containing mesopores were fabricated and showed good cell adhesion and feasible apatite formation when immersed in SBF in vitro. Furthermore, a rat calvarial defect model was used to confirm that the Zn-MCBG scaffold could modulate macrophage phenotypic transition and create a desirable osteogenic microenvironment to promote osteogenesis in vivo.

Plexiform neurofibroma (pNF) in the head and neck is a characteristic feature in patients with neurofibromatosis type 1 (NF1) and is associated with significant disfigurement and psychological distress. Yes-associated protein (YAP), the key molecule involved in the Hippo pathway, is a vital transductor that regulates the proliferation and remyelinating of Schwann cells. The functional status of YAP and its feasibility as a potential target are still unknown in pNF. A total of 17 pNF tumor tissue specimens from the head and neck were collected at the Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine. Histologically, diagnosis of the Schwann cell region in pNF was achieved with hematoxylin-eosin staining, positive reactions for S100, SOX10, ERK and p-ERK, and low identification of Ki67 and SMA. Compared with normal nerve tissue, obviously increased nuclear YAP was detected in the Schwann cell region of pNF, with a mean nuclear staining rate of 67.11%. Based on the shNF1 Schwann cell model (the RSC96 cell line), with upregulated expression of RAS, ERK and p-ERK, p-YAP (Ser127) and p-YAP (Ser397) were significantly decreased and total YAP and nuclear YAP were increased. According to a confocal assay, the interference of shNF1 substantially promoted YAP nuclear translocation. Compared with control Schwann cells, the YAP inhibitor CA3 might have a more sensitive effect (IC 50 : NC=0.96±0.04, shNF1=0.71±0.02, P <0.05) on the shNF1 Schwann cell model than the classic MEK1/2 inhibitor selumetinib (IC 50 : NC=14.36±0.95, shNF1=24.83±0.98, P >0.05). For in vivo inhibition, the CA3 group and the selumetinib group displayed a similar inhibition effect with no significant difference. Increased nuclear translation and the functional state of YAP implies that the YAP-Hippo pathway might play an important role in the formation and remyelination of pNF. Compared with selumetinib, the YAP inhibitor can exhibit a similar but more sensitive effect on NF1 -/- Schwann cells. These observations imply that YAP as a novel or adjuvant therapy target in the treatment of pNF., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

The final phase of the total synthesis of (-)-spirochensilide A is described. A tungsten-mediated cyclopropene-based Pauson-Khand reaction was developed to form the spiral CD ring system with desired stereochemistry at the C13 quaternary center. Other important steps enabling completion of this synthesis included an intermolecular aldol condensation to link the ABCD core with the EF fragment and a Cu-mediated 1,4-addition to stereoselectively install the C21 stereogenic center. The chemistry developed for this total synthesis of (-)-spirochensilide A ( 1 ) will aid the synthesis of polycyclic natural products bearing this unique spiral ring system.

A concise and diastereoselective construction of the ABCD ring system of spirochensilide A is described. The key steps of this synthesis are a semipinacol rearrangement reaction to stereoselectively construct the AB ring system bearing two vicinal quaternary chiral centers and a Co-mediated Pauson-Khand reaction to form the spiro-based bicyclic CD ring system. This chemistry leads to the stereoselective synthesis of 13( R )-demethyl spirochensilide A, paving the way for the first asymmetric total synthesis of (-)-spirochensilide A.

Infections are the leading cause of failure of osteogenic material implantation. Antibiotic treatment, treatment with bone cement, or collagen sponge placement can result in drug resistance and difficulties in operation. To address this, gellan gum (GG) was selected in this study and prepared as an injectable hydrogel containing chlorhexidine (CHX) and nanohydroxyapatite (nHA) that overcomes these intractable problems. Scanning electron microscopy and micro-computed tomography revealed a three-dimensional polymeric network of the hydrogel. The hydrogel had excellent biocompatibility, as detected by cell counting kit-8 and Live/Dead assay. Bone marrow mesenchymal stem cells could be encapsulated into the network, showing that the structure was suitable for cell growth. Additionally, loading the hydrogel with nHA improved its mechanical, biodegradable, and osteogenic properties. Quantitative alkaline phosphatase and Alizarin Red S staining validated its osteogenic ability. Furthermore, antibacterial activity assessment showed that the hydrogel loaded with 50 μg/mL CHX inhibited Enterococcus faecalis in a concentration-dependent manner. Thus, we report an injectable GG-based hydrogel with superior antibacterial effect against E. faecalis and osteogenesis, which holds promise for treating infectious bone defects caused by refractory periradicular periodontitis., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The idea of combining a flexible fiber bundle with the microscopic imaging system provides the possibility of the cross-scale detection of defects and textures on large-scale complex components. However, the pixelization artifacts caused by the inter-core spacing of the fibers degrade the image quality and make it difficult to identify the micro-features. A high-resolution reconstruction strategy is proposed based on dictionary learning. By training the high- and low-resolution image pairs after image registration, a coupled dictionary is obtained. Then high-quality images are obtained from the trained dictionary. Experimental results demonstrate that the pixelization artifacts can be effectively addressed, and the resolution of the reconstructed images can be promoted by 1.8 times.

Objectives: Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a severe complication of systemic nitrogen-containing bisphosphonate (N-BP) administration, which leads to osteonecrosis, pain, and infection. Despite much effort, effective remedies are yet to be established. This study aimed to investigate potential recovery effect of borate bioactive glass (BBG) in vitro and in vivo., Methods: The effect of BBG on zoledronate-treated bone marrow mesenchymal cells (BMSCs) and human umbilical vein endothelial cells (HUVECs) was explored by cell counting kit-8, EdU assay, flow cytometry, alkaline phosphatase staining, alizarin red staining, angiogenesis experiment, and real-time quantitative polymerase chain reaction. The preventive effect of BBG on zoledronate-induced osteonecrosis of the jaw in rat model was examined by micro-CT, HE staining, and immunohistochemistry., Results: Exposure of BBG to BMSCs and HUVECs increased cell proliferation and restored their osteogenesis and angiogenesis potential in vitro. The BRONJ lesions were satisfactorily repaired and bone mineral density, bone volume/tissue volume, trabecula number, OCN-positive cells, and CD31-positive cells were increased in the BBG-treated groups compared with saline-treated groups., Conclusions: Exposure of BMSCs and HUVECs to BBG restores osteogenesis and angiogenesis inhibited by zoledronate. BBG successfully restores extraction socket healing of BRONJ in rat model., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. All rights reserved.)

Background: Colorectal cancer (CRC) is one of the most common malignant tumors in China, and the liver is the most common metastatic site in patients with advanced CRC. Hepatectomy is the gold standard treatment for colorectal liver metastases. For patients who cannot undergo radical resection of liver metastases for various reasons, ablation therapy, interventional therapy, and systemic chemotherapy can be used to improve their quality of life and prolong their survival time., Aim: To explore the prognostic factors and treatments of liver metastases of CRC., Methods: A retrospective analysis was conducted on 87 patients with liver metastases from CRC treated at the Liaoning Cancer Hospital and Institute between January 2005 and March 2011. According to different treatments, the patients were divided into the following four groups: Surgical resection group (36 patients); ablation group (23 patients); intervention group (15 patients); and drug group (13 patients). The clinicopathological data and postoperative survival of the four groups were analyzed. The Kaplan-Meier method was used for survival analysis, and the Cox proportional hazards regression model was used for multivariate analysis., Results: The median survival time of the 87 patients was 38.747 ± 3.062 mo, and the 1- and 3-year survival rates were 87.5% and 53.1%, respectively. The Cox proportional hazards model showed that the following factors were independent factors affecting prognosis: The degree of tumor differentiation, the number of metastases, the size of metastases, and whether the metastases are close to great vessels. The results of treatment factor analysis showed that the effect of surgical treatment was better than that of drugs, intervention, or ablation alone, and the median survival time was 48.83 ± 4.36 mo. The drug group had the worst prognosis, with a median survival time of only 13.5 ± 0.7 mo ( P < 0.05). For patients with liver metastases of CRC near the great vessels, the median survival time (27.3 mo) of patients undergoing surgical resection was better than that of patients using other treatments (20.6 mo) ( P < 0.05)., Conclusion: Patients with a low degree of primary tumor differentiation, multiple liver metastases (number of tumors > 4), and maximum diameter of liver metastases > 5 cm have a poor prognosis. Among drug therapy, intervention, ablation, and surgical treatment options, surgical treatment is the first choice for liver metastases. When liver metastases are close to great vessels, surgical treatment is significantly better than drug therapy, intervention, and ablation alone., Competing Interests: Conflict-of-interest statement: The authors declare no potential financial interests., (©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.)

Previously, we reported a novel iflavirus in Helicoverpa armigera (helicoverpa armigera iflavirus, HaIV) and here we report the effects of HaIV on its host. In a laboratory bioassay, HaIV-positive larvae and pupae developed more slowly and had higher mortality than HaIV-negative larvae, suggesting that the virus is pathogenic. The relative fitness of H. armigera decreased with HaIV infection by a ratio of 0.65. Transcriptional analysis indicated that infection significantly changed the expression levels of host genes, with more genes affected at 72 h after inoculation than at 48 h (138 up- and 229 downregulated at 48 h; 185 up- and 299 downregulated at 72 h). Interestingly, pathways related to digestion and absorption were significantly enriched, e.g., protein digestion and absorption, suggesting developmental regulation of the host by HaIV via these pathways. HaIV-infected H. armigera showed significantly downregulated expression of genes encoding cuticular proteins (CPs), essential for structural and protective functions, at 48 h and 72 h, suggesting that HaIV increased larval mortality by downregulating CP gene expression., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: The need for a transfusion is one of the adverse events following total knee arthroplasty (TKA), and accurately predicting this need remains challenging for arthroplasty surgeons. The purpose of the present research is to study the preoperative predictors of transfusion risk in patients following TKA and develop a nomogram., Methods: The nomogram was developed based on a training set of 5402 patients who underwent TKA at the Affiliated Hospital of Qingdao University between September 2013 and November 2018. The independent predictors of transfusion were identified by univariate, LASSO, and binary logistic regression analyses. Then, a nomogram was established based on these independent predictors. The area under the curve (AUC), calibration curve, and decision curve analysis (DCA) were selected to evaluate the nomogram. The results were validated using an independent set of 1116 patients who underwent TKA between December 2018 and September 2019. In addition, we also carried out subgroup analyses in the training and testing sets based on the independent predictors., Results: Five independent predictors were identified by multivariate analysis and were used to establish the nomogram. The AUCs of the nomogram were 0.884 (95% CI: 0.865-0.903) and 0.839 (95% CI, 0.773-0.905) in the training and testing sets, respectively. In both the training and testing sets, the calibration curve indicated that the prediction by the nomogram was highly consistent with the actual observation, and the DCA indicated that the nomogram had a favorable level of clinical usefulness. In addition, the AUC of the nomogram was significantly higher than the AUC of any independent predictor for predicting transfusion risk following TKA, and the subgroup analysis showed good performance in 20 subgroups., Conclusion: Lower preoperative Hb levels, simultaneous bilateral TKA, lower BMI, older age, and coronary heart disease were identified as independent predictors of postoperative transfusion in patients following TKA. A nomogram incorporating the above five predictors could accurately predict the transfusion risk.

Objective: Disruption of the demineralization-remineralization balance could trigger the development of dental caries, making it challenging for enamel to "self-heal". Thus, extrinsic assistance is needed to restore enamel lesions and stop undermining progression. The aim of this study was to investigate enamel remineralization in a simulated oral environment via poly (amino amine) (PAMAM) dendrimers quantitatively., Methods: Bovine enamel specimens were shaken in demineralization solution (pH 4.5, 37°C, 50rpm/min) for 72h to create initial enamel carious lesions. The subsurface-demineralized specimens were then divided into four groups: enamel treated with PAMAM-NH 2 , enamel treated with PAMAM-COOH, enamel treated with PAMAM-OH, and enamel treated with deionized water. The treated specimens underwent subsequent 12-day pH cycling. Enamel blocks were analyzed by transverse microradiography (TMR), surface microhardness testing and scanning electron microscopy (SEM) before and after demineralization and pH cycling., Results: Groups treated with PAMAM dendrimers showed lower lesion depth and less mineral loss, attained more vertical-section surface microhardness recovery, and adsorbed more mineral deposits (p<0.05). The enamel lesion remineralization values of PAMAM-NH 2 , PAMAM-COOH, and PAMAM-OH groups were 76.42±3.32%, 60.07±5.92% and 54.52±7.81%, respectively., Significance: In conclusion, PAMAM with different terminal groups could induce enamel remineralization, among which PAMAM-NH 2 showed the most prominent competence, followed by PAMAM-COOH and PAMAM-OH, in that order., (Copyright © 2019 The Academy of Dental Materials. Published by Elsevier Inc. All rights reserved.)