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Non-invasive determination of amyloid-β peptide (Aβ) and tau deposition are important for early diagnosis and therapeutic intervention for Alzheimer's disease (AD) and non-AD tauopathies. In the present study, we investigated the capacity of a novel radioiodinated compound AD-DRK ( 123/125 I-AD-DRK) with 50% inhibitory concentrations of 11 nM and 2 nM for Aβ and tau aggregates, respectively, as a single photon emission computed tomography (SPECT) ligand in living brains. In vitro and ex vivo autoradiography with 125 I-AD-DRK was performed in postmortem human and two transgenic (Tg) mice lines with either fibrillar Aβ or tau accumulation, APP23 and rTg4510 mice. SPECT imaging of 123 I-AD-DRK was performed in APP23 mice to investigate the ability of AD-DRK to visualize fibrillar protein deposition in the living brain. In-vitro autoradiogram of 125 I-AD-DRK showed high specific radioactivity accumulation in the temporal cortex and hippocampus of AD patients and the motor cortex of progressive supranuclear palsy (PSP) patients enriched by Aβ and/or tau aggregates. Ex-vivo autoradiographic images also demonstrated a significant increase in 125 I-AD-DRK binding in the forebrain of both APP23 and rTg450 mice compared to their corresponding non-Tg littermates. SPECT imaging successfully captured Aβ deposition in the living brain of aged APP23 mice. The present study developed a novel high-contrast SPECT agent for assisting the diagnosis of AD and non-AD tauopathies, likely benefiting from its affinity for both fibrillar Aβ and tau., Competing Interests: Declaration of competing interest Shanghai Fuji Medical Technology Co. LTD hold patents on compounds related to the present report (JP6831802/KR10–2,428,569). 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 © 2024. Published by Elsevier Inc.)

Amphiphilic magnetic-responsive mixed-shell nanoparticles (Mag-MSNPs) with tailorable compositions are synthesized by electrostatic-mediated cross-linking of core-forming blocks of two diblock copolymers, followed by in situ growth of magnetite in the cross-linked core. The Mag-MSNPs have a magnetic-responsive core and hydrophilic/lipophilic mixed shells, firmly anchoring at the oil-water interface of emulsified oil droplets due to their high interfacial activity (13.1 mN m -1 at a rather low emulsifier concentration of 1.2 mg mL -1 in the n-hexane/water system), outperforming most of Janus particles. Driven by the magnetic field, the emulsified oil droplets with Mag-MSNPs at the interface are drawn to one side for collection. The oil-water separation efficiency reaches 99.5%, manifesting their excellent ability to remove emulsified oil droplets from oily water. After five separation and regeneration cycles, the separation efficiency remains at 98.8%, showcasing their potential for recyclable oily water purification., (© 2024 Wiley‐VCH GmbH.)

The WNT5B ligand regulates the non-canonical wingless-related integration site (WNT)-planar cell polarity (PCP) pathway. However, the detailed mechanism underlying the activity of WNT5B in the WNT-PCP pathway in non-small cell lung cancer (NSCLC) is unclear. In this study, we assessed the clinicopathological significance of WNT5B expression in NSCLC specimens. WNT5B-overexpression and -knockdown NSCLC cell lines were generated in vivo and in vitro, respectively. WNT5B overexpression in NSCLC specimens correlates with advanced tumor node metastasis (TNM) stage, lymph node metastasis, and poor prognosis in patients with NSCLC. Additionally, WNT5B promotes the malignant phenotype of NSCLC cells in vivo and in vitro. Interactions were identified among WNT5B, frizzled3 (FZD3), and disheveled3 (DVL3) in NSCLC cells, leading to the activation of WNT-PCP signaling. The FZD3 receptor initiates DVL3 recruitment to the membrane for phosphorylation in a WNT5B ligand-dependent manner and activates c-Jun N-terminal kinase (JNK) signaling via the small GTPase RAC1. Furthermore, the deletion of the DEP domain of DVL3 abrogated these effects. Overall, we demonstrated a novel signal transduction pathway in which WNT5B recruits DVL3 to the membrane via its DEP domain through interaction with FZD3 to promote RAC1-PCP-JNK signaling, providing a potential target for clinical intervention in NSCLC treatment., Competing Interests: Declaration of competing interest None., (Copyright © 2024. Published by Elsevier Inc.)

Background: Endolysosomal compartments are acidic and contain low pH-dependent proteases, and these conditions are exploited by respiratory viruses, such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza virus, for escaping into the cytosol. Moreover, endolysosomes contain various pattern recognition receptors (PRRs), which respond to virus-derived pathogen-associated molecular patterns (PAMPs) by production of proinflammatory cytokines/chemokines. However, excessive proinflammatory responses can lead to a potentially lethal cytokine storm., Objectives: Here we investigated the endosomal PRR expression profile in primary human small airway epithelial cells (HSAECs), and whether blockade of endolysosomal acidification affects their cytokine/chemokine production after challenge with virus-derived stimulants., Methods: HSAECs were exposed to stimulants mimicking virus-derived PAMPs, either in the absence or presence of compounds causing blockade of endolysosomal acidification, followed by measurement of cytokine expression and release., Results: We show that Toll-like receptor 3 (TLR3) is the major endosomal PRR expressed by HSAECs, and that TLR3 expression is strongly induced by TLR3 agonists, but not by a range of other PRR agonists. We also demonstrate that TLR3 engagement with its agonists elicits a robust proinflammatory cytokine/chemokine response, which is profoundly suppressed through blockade of endolysosomal acidification, by bafilomycin A1, monensin, or niclosamide. Using TLR3 reporter cells, it was confirmed that TLR3 signaling is strongly induced by Poly(I:C) and that blockade of endolysosomal acidification efficiently blocked TLR3 signaling. Finally, we show that blockade of endolysosomal acidification causes a reduction in the levels of TLR3 mRNA and protein., Conclusions: These findings show that blockade of endolysosomal acidification suppresses TLR3-dependent cytokine and chemokine production in HSAECs., Competing Interests: Disclosure statement This study was funded by grants from the Swedish Society for Medical Research (SSMF; grant number PG-22-0423-H-01), Magnus Bergvall Foundation, the Swedish Research Council, the Swedish Cancer Foundation, the Swedish Heart and Lung Foundation, the Knut and Alice Wallenberg Foundation, the Erling-Persson Foundation, and the Consul Berg Foundation. Disclosure of potential conflict of interest: The authors declare that they have no relevant conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Developing red fluorescence emitters with simple structures via convenient synthetic routes is highly desirable yet challenging. Herein, two novel donor-acceptor-type red emitters, DCFOPV-TPA and SCFOPV-TPA, featuring the intramolecular charge transfer effect were designed by integrating triphenylamine and trifluoromethyl into a CN-substituted oligo( p -phenylene vinylene) backbone. Both chromophores exhibited aggregation-induced enhanced emission and solvatochromic behavior. Moreover, DCFOPV-TPA also displayed reversible mechanofluorochromic properties under external force.

Objectives: To investigate postoperative complications in patients who underwent alveolar bone graft surgery using mandibular cortical bone (MCB) with/without particulate artificial bone (PAB)., Design: Retrospective study., Setting: Department of Oral and Cranio-Maxillofacial Surgery in the hospital from August 2020 to August 2023., Patients: Patients who underwent alveolar bone graft using MCB were reviewed. They were diagnosed with unilateral or bilateral alveolar cleft, and some of them developed postoperative complications after MCB with/without PAB repair surgery., Interventions: No interventions., Main Outcome Measure(s): Complications., Results: Complications occurred in 12 of 149 patients who underwent surgery (8.05%). Among these evaluated patients, 10 had surgical site infection, 8 had mucosal dehiscence, 2 had discharge of resorbable plate debris, and 6 had grafted bone necrosis. Patients with bilateral alveolar clefts were more likely to experience complications (P = 0.033)., Conclusion: MCB with/without PAB grafting is effective enough for patients to undergo reconstruction of the alveolar process., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Numerous studies utilizing magnetic resonance imaging (MRI) have observed sex and interhemispheric disparities in sulcal morphology, which could potentially underpin certain functional disparities in the human brain. Most of the existing research examines the precentral sulcus comprehensively, with a rare focus on its subsections. To explore the morphology, asymmetry, and sex disparities within the inferior precentral sulcus (IPCS), we acquired 3.0T magnetic resonance images from 92 right-handed Chinese adolescents. Brainvisa was used to reconstruct the IPCS structure and calculate its mean depth (MD). Based on the morphological patterns of IPCS, it was categorized into five distinct types. Additionally, we analyzed four different types of spatial relationships between IPCS and inferior frontal sulcus (IFS). There was a statistically significant sex disparity in the MD of IPCS, primarily observed in the right hemisphere. Females exhibited significantly greater asymmetry in the MD of IPCS compared to males. No statistically significant sex or hemispheric variations were identified in sulcal patterns. Our findings expand the comprehension of inconsistencies in sulcal structure, while also delivering an anatomical foundation for the study of related regions' function., (© 2024. The Author(s).)

Chemoresistance is one of the major hindrances to many cancer therapies, including esophageal squamous cell carcinoma (ESCC). Ferroptosis, a new programmed cell death, plays an essential role in chemoresistance. IQ-domain GTPase activating protein 1 (IQGAP1) is a scaffold protein and functions as an oncogene in various human malignancies. However, the underlying effect and molecular mechanisms of IQGAP1 on paclitaxel (PTX) resistance and ferroptosis in ESCC remain to be elucidated. In this study, we found that IQGAP1 was highly expressed in ESCC tissues and could as a potential biomarker for diagnosis and predicting the prognosis of ESCC. Functional studies revealed that IQGAP1 overexpression reduced the sensitivity of ESCC cells to PTX by enhancing ESCC cell viability and proliferation and inhibiting cell death, and protected ESCC cells from ferroptosis, whereas IQGAP1 knockdown exhibited contrary effects. Importantly, reductions of chemosensitivity and ferroptosis caused by IQGAP1 overexpression were reversed with ferroptosis inducer RSL3, while the increases of chemosensitivity and ferroptosis caused by IQGAP1 knockdown were reversed with ferroptosis inhibitor ferrostatin-1 (Fer-1) in ESCC cells, indicating that IQGAP1 played a key role in resistance to PTX through regulating ferroptosis. Mechanistically, we demonstrated that IQGAP1 overexpression upregulated the expression of Yes-associated protein (YAP), the central mediator of the Hippo pathway. YAP inhibitor Verteporfin (VP) could reverse the effects of IQGAP1 overexpression on ESCC chemoresistance and ferroptosis. Taken together, our findings suggest that IQGAP1 promotes chemoresistance by blocking ferroptosis through targeting YAP. IQGAP1 may be a novel therapeutic target for overcoming chemoresistance in ESCC., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Quality of life, social support, and loneliness are common problems among older adults in China , but the relationships among these issues have not been clearly identified., Objectives: The present study aimed to determine the relationships among Quality of life, social support, and loneliness., Methods: A total of 560 older adults were randomly selected , the social support rating scale (SSRS), University of California at Los Angeles (UCLA) loneliness scale, and Short-Form 12 (SF-12) were employed to measure their degree of social support, level of loneliness, and quality of life., Results: The average physical component summary (PCS) score was 49.97±16.33, and the average mental component summary (MCS) score was 47.26±11.49. Loneliness plays a partial mediating role between social support and quality of life., Conclusion: Loneliness and a lack of social support will affect the quality of life of the older adults. Thus, we need to urgently strengthen the care and support for the older adults and alleviate the loneliness of the older adults in the community.

Here, a series of 3-(6-aminopyridin-3-yl) benzamide derivatives were designed and synthesized. Cell viability assay indicated that most compounds exhibited potent antiproliferative activity against all the tested cancer cells. Among them, compound 7l displayed the best antiproliferative activity particularly in A549 cells, with an IC 50 value of 0.04 ± 0.01 μM. RNA-seq analysis was employed to explore the potential pathways related to the antiproliferative activity of compound 7l. The data revealed that 7l exerted antiproliferative activity mainly by regulating cell cycle, DNA replication and p53 signaling pathway. Indeed, compound 7l induced G2/M phase arrest by AURKB transcription inhibition and resulted in cell apoptosis via p53 signaling pathway. Most importantly, compound 7l demonstrated potent antitumor activity in A549 xenograft tumor model. Collectively, 7l might be a promising lead compound for the development of new therapeutic agents for AURKB overexpressed or mutated cancers., 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 © 2024 Elsevier Inc. All rights reserved.)

Objective: This study is the first prospective within-patient self-controlled research seeking to investigate the safety and efficacy of 595 nm pulsed-dye laser (PDL) for the treatment of cleft-lip scars. Approach: This prospective, randomized, self-controlled study is based on the clinical records of the patients who received laser-assisted treatment due to bilateral cleft-lip scars. The bilateral scars were randomly assigned to the 595 nm PDL group with five consecutive sessions at 2-week intervals or control group in a blinded manner of evaluators, with subsequent follow-up for 6 months after the final treatment. Clinical efficacy and safety outcomes were evaluated by Vancouver Scar Scale (VSS), Patient Scar Assessment Questionnaire (PSAQ), and other objective evaluations. Results: A total of 18 patients were included. The 595 nm PDL-treated sides showed statistically significant improvement in VSS after treatment at follow-up compared with the baseline ( p  < 0.05). Interestingly, the 595 nm-PDL-treated side achieved significantly better improvement in scar pigmentation and pliability ( p  < 0.05). Though there was statistically significant difference between two groups ( p  < 0.05), the gap in overall PSAQ is not obvious. And comparison by area and coloring evaluation (E/M index) also suggests that the responses of scars to treatment by PDL were slightly improved ( p  < 0.05). Innovation and Conclusion: It is the first time to apply the 595nm PDL for cleft-lip scars. It would be a better choice for the early treatment of red scar with proliferative tendency after cleft-lip surgery.

Visual information is important for accurate spatial coding and memory-guided navigation. As a crucial area for spatial cognition, the medial entorhinal cortex (MEC) harbors diverse spatially tuned cells and functions as the major gateway relaying sensory inputs to the hippocampus containing place cells. However, how visual information enters the MEC has not been fully understood. Here, we identify a pathway originating in the secondary visual cortex (V2) and directly targeting MEC layer 5a (L5a). L5a neurons served as a network hub for visual processing in the MEC by routing visual inputs from multiple V2 areas to other local neurons and hippocampal CA1. Interrupting this pathway severely impaired visual stimulus-evoked neural activity in the MEC and performance of mice in navigation tasks. These observations reveal a visual cortical-entorhinal pathway highlighting the role of MEC L5a in sensory information transmission, a function typically attributed to MEC superficial layers before., (© 2024. The Author(s).)

Understanding the intrinsic mechanisms underpinning cancer metabolism and therapeutic resistance is of central importance for effective nutrition-starvation therapies. Here, we report that Interleukin 1A (IL1A) mRNA and IL-1α protein facilitate glutathione (GSH) synthesis to counteract oxidative stress and resistance against nutrition-starvation therapy in oral squamous cell carcinoma (OSCC). The expression of IL1A mRNA was elevated in the case of OSCC associated with unfavorable clinical outcomes. Both IL1A mRNA and IL-1α protein expression were increased under glucose-deprivation in vitro and in vivo. The transcription of IL1A mRNA was regulated in an NRF2-dependent manner in OSCC cell lines under glucose-deprivation. Moreover, the IL-1α conferred resistance to oxidative stress via GSH synthesis in OSCC cell lines. The intratumoral administration of siRNAs against IL1A mRNA markedly reversed GSH production and sensitized OSCC cells to Anlotinib in HN6 xenograft models. Overall, the current study demonstrates novel evidence that the autocrine IL-1α favors endogenous anti-oxidative process and confers therapeutic resistance to nutrition-starvation in OSCCs., 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 © 2024. Published by Elsevier B.V.)

Esophageal squamous cell carcinoma (ESCC) is a common malignancy with high morbidity and mortality. Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) serves as a reader of RNA m6A (N6 methyladenosine) modification to regulate gene expression at the post-transcriptional level. Emerging evidence suggests that IGF2BP2 plays critical roles in tumorigenesis and malignant development. However, the biological function and molecular mechanism of IGF2BP2 in ESCC are not well understood. Here, we found that IGF2BP2 expression was upregulated in esophageal cancer tissues and ESCC cells, and IGF2BP2 overexpression enhanced proliferation, migration, invasion, and stem cell-like properties of ESCC cells. Conversely, the knockdown of IGF2BP2 expression inhibited malignant phenotype of ESCC cells. Mechanistically, IGF2BP2 upregulated octomer-binding transcription factor 4 (OCT4) mRNA expression, and RNA immunoprecipitation (RIP) assay proved that IGF2BP2 could interact with OCT4 mRNA. Moreover, OCT4 was modified at m6A confirmed by methylated m6A RNA immunoprecipitation (Me-RIP)-qPCR assay, and IGF2BP2 knockdown reduced OCT4 mRNA stability. These results suggested that IGF2BP2 served as a reader for m6A-modified OCT4, thus increased OCT4 mRNA expression by regulating its stability. Furthermore, the knockdown of OCT4 could reverse the effects of IGF2BP2 on ESCC cells. In conclusion, these data indicate that IGF2BP2, as a reader for m6A, plays an oncogenic role by regulating OCT4 expression in ESCC, which provides new insights into targeting IGF2BP2/OCT4 axis for the therapy of ESCC., Competing Interests: The authors declare there are no competing interests.

Organic compounds have become an important electrode material for aqueous electrochemical energy storage. However, organic electrodes still face poor performance in aqueous batteries due to insufficient electrochemical activity. In this work, a novel conjugated quinone compound containing a rich carbonyl group was designed. The quinone compound was synthesized by a simple dehydration reaction of pyrene-4,5,9,10-tetrone (PTO) and 1,2-diaminoanthraquinone (1,2-AQ); it contains 4 pyrazines (CN) from AQ and 4 carbonyl groups (CO), as well as a large number of active sites and the excellent conductivity brought by its conjugated structure ensures the high theoretical capacity of PTO-AQ. In the context of aqueous sodium ion batteries (ASIBs), the electrode material known as PTO-AQ exhibits a notable reversible discharge capacity of 117.9 mAh/g when subjected to a current density of 1 A/g; impressively, it maintained a capacity retention rate of 74.3 % even after undergoing 500 charge and discharge cycles, a performance significantly surpassing that of pristine PTO and AQ. Notably, PTO-AQ exhibits a wide operating voltage range (-1.0-0.5 V) and a cycle life of up to 10,000 cycles. In situ Raman and ex situ measurements were used to analyze the structural changes of PTO-AQ during charge and discharge and the energy storage mechanism in NaAC. The effective promotion of Na + storage brought by a rich carbonyl group was obtained. The structural energy level and electrostatic potential of PTO-AQ were calculated, and the active center distribution of PTO-AQ was obtained. This work serves as a guide for designing high-performance aqueous organic electrode materials that operate across a wide voltage range while also explaining their energy storage mechanism., 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.)

One of the biggest obstacles to the development of aqueous proton batteries (APBs), despite numerous optimization techniques, is the preparation and use of high-performance electrode materials. In this work, to improve the high solubility, limited capacity and poor cycle life of small organic molecules in APBs, homogeneous dispersed quinone-amine polymer nanospheres (PQANS) (average diameter: 220 nm) were synthesized by a polymerization reaction based on 3,3'-diaminobenzidine (DAB) and benzoquinone (BQ), making them suitable for proton storage in aqueous systems. As an anode for APBs, the obtained PQANS exhibits an improved reversible capacity of 126.2 mAh/g at 1 A/g after 300 cycles. The durable stable measurement of PQANS at 10 A/g was also conducted with a specific capacity of 66.8 mAh/g after 12,000 cycles. A series of in situ or ex situ measurements were used to establish the superior H + storage mechanism of PQANS. A novel reaction mechanism of redox enhancement was revealed due to the existence of more carbonyl groups after the first cycle. Theoretical calculations were conducted to help illustrate the principle of binding protons with functional groups in PQANS. Finally, a PQANS anode-based aqueous proton full battery was constructed to demonstrate its potential application, which exhibits a specific capacity of 50.6 mAh/g at 1 A/g (600 cycles). This work provides a reference for preparing high-performance polymer-based electrode materials in aqueous batteries., 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.)

Layer 1 (L1) interneurons (INs) participate in various brain functions by gating information flow in the neocortex, but their role in the medial entorhinal cortex (MEC) is still unknown, largely due to scant knowledge of MEC L1 microcircuitry. Using simultaneous triple-octuple whole-cell recordings and morphological reconstructions, we comprehensively depict L1IN networks in the MEC. We identify three morphologically distinct types of L1INs with characteristic electrophysiological properties. We dissect intra- and inter-laminar cell-type-specific microcircuits of L1INs, showing connectivity patterns different from those in the neocortex. Remarkably, motif analysis reveals transitive and clustered features of L1 networks, as well as over-represented trans-laminar motifs. Finally, we demonstrate the dorsoventral gradient of L1IN microcircuits, with dorsal L1 neurogliaform cells receiving fewer intra-laminar inputs but exerting more inhibition on L2 principal neurons. These results thus present a more comprehensive picture of L1IN microcircuitry, which is indispensable for deciphering the function of L1INs in the MEC., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

The recent approvals for antibody-drug conjugates (ADCs) in multiple malignancies in the past few years have fueled the ongoing development of this class of drug. However, the limitation of ADCs is selectivity toward cancer cells especially overexpressing the antigen of interest. To broaden the anti-cancer spectrum of ADCs, combinatorial strategies of ADCs with chemotherapy have become a central focus of the current preclinical and clinical research. Here, we used the microtubule stabilizer paclitaxel and enfortumab vedotin-ejfv (EV), an ADC carrying the microtubule inhibitor payload monomethyl auristatin E (MMAE), for co-administration under the consideration of their mechanism of action associated with microtubules. We designed a sialic acid-cholesterol (SA-CH) conjugate-modified cationic liposome platform loaded with PTX (PTX-SAL) for efficiently targeting tumor-associated immune cells. Compared with monotherapy, PTX-SAL-mediated combination therapy with ADCs significantly inhibited S180 tumor growth in mice, with complete tumor regression occurring. The formation of a durable tumor-specific immunological memory response in mice that experienced complete tumor regression was assessed by secondary tumor cell rechallenge, and the production of memory T cells in the spleen was detected as related to the increased CD4 + T memory cells and the enhanced serum IFN-γ. All our preliminary results throw light on the tremendous application potential for the application of this combination therapy regimen capable of mounting a durable immune response and stimulating a robust T cell-mediated tumor-specific immunological memory.

Lithium-ion batteries (LIBs) have become the preferred battery system for portable electronic devices and transportation equipment due to their high specific energy, good cycling performance, low self-discharge, and absence of memory effect. However, excessively low ambient temperatures will seriously affect the performance of LIBs, which are almost incapable of discharging at -40~-60 °C. There are many factors affecting the low-temperature performance of LIBs, and one of the most important is the electrode material. Therefore, there is an urgent need to develop electrode materials or modify existing materials in order to obtain excellent low-temperature LIB performance. A carbon-based anode is one candidate for use in LIBs. In recent years, it has been found that the diffusion coefficient of lithium ion in graphite anodes decreases more obviously at low temperatures, which is an important factor limiting its low-temperature performance. However, the structure of amorphous carbon materials is complex; they have good ionic diffusion properties, and their grain size, specific surface area, layer spacing, structural defects, surface functional groups, and doping elements may have a greater impact on their low-temperature performance. In this work, the low-temperature performance of LIBs was achieved by modifying the carbon-based material from the perspectives of electronic modulation and structural engineering.

Objective: To determine the optimal time to apply a fractional CO 2 laser for the treatment of postsecondary repair scars in patients with cleft lip., Methods: Forty-two patients with linear scarring after cleft lip repair were recruited from November 2021 to October 2022. A single-blind, randomized, controlled cohort study was conducted to examine the impact of fractional CO 2 laser treatment compared with conventional conservative treatment. Thirty patients started laser treatment at 1 month ( n = 10), 3 months ( n = 10), and 6 months ( n = 10) postoperatively, and 12 patients were in the control group. Each patient was treated with high-energy low-density fractional CO 2 laser treatment 3 times at an interval of 1 month. The Vancouver Scar Scale (VSS) was used for scar evaluation to determine vascularity, pigmentation, pliability, and height., Results: The VSS scores decreased significantly after laser treatment ( p < .05), with the most significant improvement in scars in the group that started treatment 1 month after the surgery., Conclusion: Early postoperative fractional CO 2 laser treatment of cleft lip scars is more effective than later treatment., (Copyright © 2023 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved.)

This paper serves to enhance the current knowledge base of airborne microplastics which is significantly smaller than that of microplastics in marine, freshwater and terrestrial environments. It systematically presents the prevalence, sources, fate, risks and mitigations of airborne microplastics through the review of >140 scientific papers published mainly in the last 10 years. Unlike the extant review, it places an emphasis on the indoor microplastics, the risks of airborne microplastics on animals and plants and their mitigations. The outdoor microplastics are mostly generated by the wear and tear of tires, brake pads, waste incineration and industrial activities. They have been detected in many regions worldwide at concentrations ranging from 0.3 particles/m 3 to 154,000 particles/L of air even in the Pyrenees Mountains and the Arctic. As for indoor microplastics, the reported concentrations range from 1 piece/m 3 to 9900 pieces/m 2 /day, and are frequently higher than those of the outdoor microplastics. They come from the wear and tear of walls and ceilings, synthetic textiles and furniture finishings. Airborne microplastics could be suspended and resuspended, entrapped, settle under gravity as well as interact with chemicals, microorganisms and other microplastic particles. In the outdoors, they could also interact with sunlight and be carried by the wind over long distance. Airborne microplastics could adversely affect plants, animals and humans, leading to reduced photosynthetic rate, retarded growth, oxidative stress, inflammatory responses and increased cancer risks in humans. They could be mitigated indirectly through filters attached to air-conditioning system and directly through source reduction, regulation and biodegradable substitutes., 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 © 2022 Elsevier B.V. All rights reserved.)

Salicylic acid (SA) and ethylene (ET) are crucial fruit senescence hormones. SA inhibited ET biosynthesis. However, the mechanism of SA delaying fruit senescence is less known. ETHYLENE INSENSITIVE 3 (EIN3), a key positive switch in ET perception, functions as a transcriptional activator and binds to the primary ET response element that is present in the promoter of the ETHYLENE RESPONSE FACTOR1 gene. In this study, a gene encoding putative EIN3 protein was cloned from sand pear and designated as PpEIN3a . The deduced PpEIN3a contains a conserved EIN3 domain. The evolutionary analysis results indicated that PpEIN3a belonged to the EIN3 superfamily. Real-time quantitative PCR analysis revealed that the accumulation of PpEIN3a transcripts were detected in all tissues of this pear. Moreover, PpEIN3a expression was regulated during fruit development. Interestingly, the expression of PpEIN3a was downregulated by SA but upregulated by ET, auxin, and glucose. Additionally, the contents of free and conjugated SA were higher than those of the control after SA treatment. While the content of ET and auxin (indole-3-acetic acid, IAA) dramatically decreased after SA treatment compared with control during fruit senescence. The content of glucose increased when fruit were treated by SA for 12 h and then there were no differences between SA treatment and control fruit during the shelf life. SA also delayed the decrease in sand pear ( Pyrus pyrifolia Nakai. 'Whangkeumbae') fruit firmness. The soluble solid content remained relatively stable between the SA treated and control fruits. This study showed that SA plays an antagonistic role toward ET, auxin, and glucose in regulating the expression of PpEIN3a to delay fruit senescence., 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, Huo, Zhao, Li, Zhao, Wang, Wang and Shi.)

Background: Mast cells are implicated in the pathogenesis of asthma, but the underlying mechanisms are not fully elucidated. Under asthmatic conditions, mast cells can relocalize to the epithelial layer and may thereby affect the functional properties of the airway epithelial cells., Objectives: Activated mast cells release large quantities of proteases from their secretory granules, including chymase and tryptase. Here we investigated whether these proteases may affect airway epithelial cells., Methods: Primary small airway epithelial cells were treated with tryptase or chymase, and the effects on epithelial cell viability, proliferation, migration, cytokine output, and transcriptome were evaluated., Results: Airway epithelial cells were relatively refractory to tryptase. In contrast, chymase had extensive effects on multiple features of the epithelial cells, with a particular emphasis on processes related to extracellular matrix (ECM) remodeling. These included suppressed expression of ECM-related genes such as matrix metalloproteinases, which was confirmed at the protein level. Further, chymase suppressed the expression of the fibronectin gene and also caused degradation of fibronectin released by the epithelial cells. Chymase was also shown to suppress the migratory capacity of the airway epithelial cells and to degrade the cell-cell contact protein E-cadherin on the epithelial cell surface., Conclusion: Our findings suggest that chymase may affect the regulation of ECM remodeling events mediated by airway epithelial cells, with implications for the impact of mast cells in inflammatory lung diseases such as asthma., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

The obligate biotrophic fungus Puccinia striiformis f. sp. tritici , which causes yellow (stripe) rust disease, is among the leading biological agents resulting in tremendous yield losses on global wheat productions per annum. The combatting strategies include, but are not limited to, fungicide applications and the development of resistant cultivars. However, evolutionary pressure drives rapid changes, especially in its "effectorome" repertoire, thus allowing pathogens to evade and breach resistance. The extracellular and intracellular effectors, predominantly secreted proteins, are tactical arsenals aiming for many defense processes of plants. Hence, the identity of the effectors and the molecular mechanisms of the interactions between the effectors and the plant immune system have long been targeted in research. The obligate biotrophic nature of P. striiformis f. sp. tritici and the challenging nature of its host, the wheat, impede research on this topic. Next-generation sequencing and novel prediction algorithms in bioinformatics, which are accompanied by in vitro and in vivo validation approaches, offer a speedy pace for the discovery of new effectors and investigations of their biological functions. Here, we briefly review recent findings exploring the roles of P. striiformis f. sp. tritici effectors together with their cellular/subcellular localizations, host responses, and interactors. The current status and the challenges will be discussed. We hope that the overall work will provide a broader view of where we stand and a reference point to compare and evaluate new findings., 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 Wu, Ozketen, Cheng, Jiang, Zhou, Zhao, Guan, Xiang and Akkaya.)

Background: Health Technology Assessment (HTA) has been widely recognized as informing healthcare decision-making, and interest in HTA of medical devices has been steadily increasing. How does the assessment of medical devices differ from that of drug therapies, and what innovations can be adopted to overcome the inherent challenges in medical device HTA?, Method: HTA Accelerator Database was used to describe the landscape of HTA reports for medical devices from HTA bodies, and a literature search was conducted to understand the growth trend of relevant HTA publications in four case studies. Another literature review was conducted for a narrative synthesis of the characteristic differences and challenges of HTA in medical devices. We further conducted a focused Internet search of guidelines and a narrative review of methodologies specific to the HTA of medical devices., Main Body: The evidence of HTA reports and journal publications on medical devices around the world has been growing. The challenges in assessing medical devices include scarcity of well-designed randomized controlled trials, inconsistent real-world evidence data sources and methods, device-user interaction, short product lifecycles, inexplicit target population, and a lack of direct medical outcomes. Practical solutions in terms of methodological advancement of HTA for medical devices were also discussed in some HTA guidelines and literature., Conclusion: To better conduct HTA on medical devices, we recommend considering multi-source evidence such as real-world evidence; standardizing HTA processes, methodologies, and criteria; and integrating HTA into decision-making., (© 2022. The Author(s).)

Objectives: This study evaluates the cost-effectiveness of adding prolonged-release (PR)-fampridine to best supportive care (BSC) versus BSC alone in adult multiple sclerosis patients with walking disability in China. Materials & methods: A hybrid decision tree and Markov model from both the societal and healthcare perspectives were constructed. Parameters were derived from clinical trials of PR-fampridine, published sources and clinical expert interviews. Results: Over a 10-year time horizon, adding PR-fampridine to BSC led to 0.15 quality-adjusted life year (QALY) gain and lower costs, with incremental cost-effectiveness ratios of -238,806 Chinese Yuan/QALY and -113,488 Chinese Yuan/QALY from the societal and healthcare perspectives, respectively. Conclusion: Compared with BSC alone, PR-fampridine plus BSC is considered an economically dominant strategy for the treatment of multiple sclerosis-related walking disability in China.

The HIV/AIDS cases and proportion in older people are continuously and rapidly increasing in China, especially in males. However, the transmission mechanism is not well understood. This study aims to explore the transmission mechanism of HIV/AIDS and potential ways to prevent or control HIV/AIDS transmission in a city in southwestern China. Data from multiple sources, including HIV/AIDS case reports in 2010-2020, a survey of HIV/AIDS cases in 2020, and sentinel surveillance data of female sex workers (FSWs) in 2016-2020 were analyzed. We explored the transmission mechanism of HIV/AIDS cases aged 50 years and older. In this city, the number of newly reported HIV/AIDS cases aged 50 years and older increased from 2010 to 2019, and decreased in 2020. The number of male and female cases aged 50 years and older both increased rapidly in 2017-2019, though the number of male cases was larger than that of female. The survey data showed that 84.7% of older male cases reported commercial sexual behavior, among whom 87.7% reported never using condom and 37.6% reported more than 10 times of commercial sexual behaviors in 1 year. In terms of price of sexual behavior, 68.3% of older male cases sought low-tier FSWs among whom the HIV/AIDS positive rate was 5.4% from the sentinel surveillance data. These results suggested HIV transmission between older men and low-tier FSWs through commercial sexual behavior. Among female cases aged 50 years and older, most reported non-marital and non-commercial heterosexual (60.5%) or regular sexual partner (31.4%) transmission, suggesting that they were infected by their spouse/regular sexual partner. Data of matched couples showed that most male cases had both marital sexual behavior and commercial sexual behavior, or acquired HIV through commercial sexual behavior, while most female cases had only marital sexual behavior. Based on these findings, we proposed a transmission mode of that local older male people and FSWs are transmitting bilaterally through commercial sexual behavior, and local older male people are spreading to local older female people through spouse or regular sexual partner route. By studying data from multiple sources, we explored the HIV transmission mode among older people. In the meantime, we found that marital status had a different impact on male and female old people in their sex behaviors., (© 2022. The Author(s).)

NiCo 2 O 4 is a promising catalyst toward water splitting to hydrogen. However, low conductivity and limited active sites on the surfaces hinder the practical applications of NiCo 2 O 4 in water splitting. Herein, small sized NiCo 2 O 4 nanoparticles rich in oxygen vacancies were prepared by a simple salt-assisted method. Under the assistance of KCl, the formed NiCo 2 O 4 nanoparticles have abundant oxygen vacancies, which can increase surface active sites and improve charge transfer efficiency. In addition, KCl can effectively limit the growth of NiCo 2 O 4 , and thus reduces its size. In comparison with NiCo 2 O 4 without the assistance of KCl, both the richer oxygen vacancies and the reduced nanoparticle sizes are favorable for the optimal NiCo 2 O 4 -2KCl to expose more active sites and increase electrochemical active surface area. As a result, it needs only the overpotentials of 129 and 304 mV to drive hydrogen and oxygen evolution at 10 mA cm -2 in 1 M KOH, respectively. When NiCo 2 O 4 -2KCl is applied in a symmetrical water splitting cell, a voltage of ∼1.66 V is only required to achieve the current density of 10 mA cm -2 . This work shows that the salt-assisted method is an efficient method of developing highly active catalysts toward water splitting to hydrogen., 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 He, Dong, Yin, Li and Zhao.)

Dental caries is associated with caries-related streptococci and antimicrobial agents have been widely used for caries control, but troubled by antibiotic resistance. This study aimed to investigate the intrinsic and acquired resistance of caries-related streptococci to antimicrobial peptide GH12, which was proven promising for caries control, and preliminarily explore the phenotypic changes and whole genome of stable acquired resistant strains. In this study, susceptibility assays and resistance assays were performed, followed by stability assays of resistance, to evaluate the intrinsic resistance and the potential resistance of caries-related streptococci. Then, the phenotypic changes of the stable acquired resistant strain were explored. The whole genome of the resistant strain was sequenced and analyzed by second-generation and third-generation high-throughput sequencing technologies. Streptococcus gordonii and Streptococcus sanguinis were intrinsically resistant to GH12 compared to cariogenic Streptococcus mutans . Acquired GH12 resistance in one S. sanguinis and four S. mutans clinical strains was transient but stable in one S. mutans strain (COCC33-14). However, acquired resistance to daptomycin (DAP) and chlorhexidine in all strains was stable. Furthermore, the COCC33-14 showed cross-resistance to DAP and delayed growth rates and a lower population. However, no drug-resistant gene mutation was detected in this strain, but 6 new and 5 missing genes were found. Among them, annotation of one new gene (gene 1782|COCC33-14R) is related to the integral component of the membrane, and one missing gene rpsN is associated with the metabolism and growth of bacteria. The results indicate that stable resistant mutants of caries-related streptococci could hardly be selected by exposure to consecutive sublethal GH12, but the risk still existed. Resistance in COCC33-14R is mainly related to changes in the cell envelope., 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 Li, Wang, Jiang, Zeng, Zhao, Washio, Takahashi and Zhang.)

Mast cells have been linked to osteoporosis and bone fractures, and in a previous study we found that mice lacking a major mast cell protease, chymase, develop increased diaphyseal bone mass. These findings introduce the possibility that mast cell chymase can regulate bone formation, but the underlying mechanism(s) has not previously been investigated. Here we hypothesized that chymase might exert such effects through a direct negative impact on osteoblasts, i.e., the main bone-building cells. Indeed, we show that chymase has a distinct impact on human primary osteoblasts. Firstly, chymase was shown to have pronounced effects on the morphological features of osteoblasts, including extensive cell contraction and actin reorganization. Chymase also caused a profound reduction in the output of collagen from the osteoblasts, and was shown to degrade osteoblast-secreted fibronectin and to activate pro-matrix metallopeptidase-2 released by the osteoblasts. Further, chymase was shown to have a preferential impact on the gene expression, protein output and phosphorylation status of TGFβ-associated signaling molecules. A transcriptomic analysis was conducted and revealed a significant effect of chymase on several genes of importance for bone metabolism, including a reduction in the expression of osteoprotegerin, which was confirmed at the protein level. Finally, we show that chymase interacts with human osteoblasts and is taken up by the cells. Altogether, the present findings provide a functional link between mast cell chymase and osteoblast function, and can form the basis for a further evaluation of chymase as a potential target for intervention in metabolic bone diseases., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to declare., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Loving-kindness and compassion meditation (LKCM) was a promising intervention for improving life satisfaction, but previous findings have been inconsistent. The current study provides a systematic review and meta-analysis, including 23 empirical studies on LKCM with life satisfaction as an outcome variable. The primary meta-analysis indicated that LKCM significantly enhanced life satisfaction in pre-post design (g = 0.312, k = 15, n = 451), but the significance disappeared in the additional meta-analysis based on randomized controlled trials (g = 0.106, k = 6, n = 404). Moderator analyses found significant effects for type of control (i.e., the effects of LKCM were inferior to active control group, but superior to waitlist condition), but not for other moderators (i.e., participant type, previous meditation experience, specific protocol, components of LKCM, combination with mindfulness mediation, and intervention length). Narrative review identified self-compassion and positive emotions as important mediators. The practice time of LKCM had indirect but not direct association with life satisfaction. The findings supported that LKCM is promising in increasing life satisfaction, but more studies are needed to investigate the effects with more rigorous designs. Future studies should investigate other potential mechanisms and clarify whether LKCM change the reality or the perception of life., (© 2022 International Association of Applied Psychology.)

Objective: To verify the advantages and indications of 1-stage and 2-stage repair for asymmetric bilateral cleft lip (BCL)., Design: Retrospective study., Setting: From January 2004 to December 2016 in our department., Patients: Patients with BCL., Main Outcome Measure(s): Over 6 months after the operation, the surgery outcomes were evaluated and graded by 2 experienced surgeons., Results: The result of surgery was evaluated using the scoring method of Mortier et al and Anastassov and Chipkov. Among 133 patients with asymmetric BCL, 61 (45.9%) had 1-stage repair and 72 (54.1%) had 2-stage repair. Sixty-eight (51.1%) patients had complete-incomplete cleft lip (CL), and those who underwent 1-stage repair showed a trend of better outcome ( P = .028). Fifty (37.6%) patients with incomplete-microform CL showed no significant difference between the outcomes of 2 surgery plans ( P = .253). In 15 (11.3%) patients with complete-microform CL, only one had 1-stage repair with a score of 8.5. The other 14 patients with 2-stage repair were scored 3.68 ± 1.28. Two-stage repair was preferable when the deformity degree was very different on 2 sides, as it could reduce unnecessary scar tissue and extend the nasal columella. One-stage repair could help to achieve the anatomical reduction of the orbicularis oris and a better contour of the vermilion tubercle., Conclusion: One-stage repair is recommended for patients with complete-incomplete CL and incomplete-microform CL. Two-stage repair for patients with complete-microform CL is preferred in our center, but more studies are required to support this conclusion.

17β-estradiol (E2) plays a key role in endometriosis through regulation of angiogenesis. Smad1 has been reported to be up-regulated in patients with endometriosis. However, the role of Smad1 in E2-mediated angiogenesis during the development of endometriosis remains to be determined. This study aimed to explore the role of Smad1 in E2-mediated angiogenesis during endometriosis and its underlying mechanisms. Immunofluorescence staining and Western blotting were performed to examine the expression of p-Smad1 in ectopic and control endometrium. Western blotting was used to examine activation of Smad1 signaling in NMECs, EMECs and HUVECs. Tube formation assay was performed to examine the effect of E2 on angiogenesis. Cell proliferation and migration was determined using in real-time by xCELLigence RTCA DP instrument. We found that the expression of p-Smad1 was significantly up-regulated in ectopic endometrium and ectopic intima microvascular endothelial cells. E2 non-genomically stimulated phosphorylation of Smad1 in HUVECs. c-Src and p44/42 MAPK(ERK1/2) signaling pathways are required for E2's induction on Smad1 phosphorylation. Moreover, caveolae is involved in E2-induced Smad1 phosphorylation in vascular endothelial cells. E2 promoted tube formation of vascular endothelial cells through c-Src/ERK1/2/Smad1 signaling pathway. Knockdown of Smad1 expression attenuated E2-induced proliferation and migration of HUVECs. In conclusion, E2 promotes proliferation, migration and tube formation of HUVECs through c-Src/ERK1/2/Smad1 signaling pathway. Our data shed new lights on the mechanisms through which E2 contributes to endometriosis, and may provide novel strategies to treat endometriosis., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Mast cells (MCs) have a profound impact on allergic asthma. Under such conditions, MCs undergo degranulation, resulting in the release of exceptionally large amounts of MC-restricted proteases. However, the role of these proteases in asthma is only partially understood., Objectives: We sought to test our hypothesis that MC proteases can influence the functionality of human lung fibroblasts (HLFs)., Methods: Primary HLFs were treated with MC chymase or tryptase, followed by assessment of parameters related to fibroblast function., Results: HLFs underwent major morphologic changes in response to chymase, showing signs of cellular contraction, but were refractory to tryptase. However, no effects of chymase on HLF viability or proliferation were seen. Chymase, but not tryptase, had a major impact on the output of extracellular matrix-associated compounds from the HLFs, including degradation of fibronectin and collagen-1, and activation of pro-matrix metalloprotease 2. Further, chymase induced the release of various chemotactic factors from HLFs. In line with this, conditioned medium from chymase-treated HLFs showed chemotactic activity on neutrophils. Transcriptome analysis revealed that chymase induced a proinflammatory gene transcription profile in HLFs, whereas tryptase had minimal effects., Conclusions: Chymase, but not tryptase, has a major impact on the phenotype of primary airway fibroblasts by modifying their output of extracellular matrix components and by inducing a proinflammatory phenotype., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: To compare the cost-effectiveness of flash glucose monitoring versus self-monitoring of blood glucose/point of care testing (SMBG/POCT) in both patients with type 1 and patients with type 2 diabetes (T1D/T2D) receiving insulin therapy., Methods: The IQVIA CORE Diabetes Model (version 9.5) was used to project the lifetime costs and health outcomes of flash glucose monitoring and SMBG/POCT from a Chinese societal perspective. We considered both hospital and individual version flash glucose monitoring to reflect the clinical practice in China. The clinical inputs leveraged the outcomes from both clinical trials and real-world studies. Cohort characteristics, intervention costs, treatment-related disutility and mortality were extracted from the literature. We also conducted scenario analyses and probabilistic sensitivity analyses to test the robustness of results., Results: Compared with SMBG/POCT using efficacy results from clinical trial, flash glucose monitoring brought the incremental costs of Chinese yuan (CNY) 58,021 and CNY 90,997 and additional quality-adjusted life years (QALYs) of 1.22 and 0.65 for patients with T1D and patients with T2D, respectively. According to the "WHO-CHOICE threshold" of three times the gross domestic product per capita in China (CNY 217,341 in 2020) as cost-effectiveness threshold, flash glucose monitoring was cost-effective for both patients with T1D and patients with T2D with incremental cost-effectiveness ratios (ICER) of CNY 47,636 and CNY 140,297 per QALY gained, respectively. According to the real-world effectiveness data, flash glucose monitoring was dominant for patients with T1D (lower costs and better effectiveness) and cost-effective for patients with T2D with an ICER of CNY 124,169 per QALY gained compared with SMBG/POCT. Scenario analyses and probabilistic sensitivity analyses confirmed the robustness of the results., Conclusion: Flash glucose monitoring is likely to be considered as a cost-effective strategy compared to SMBG/POCT for Chinese patients with T1D and patients with T2D receiving insulin therapy., (© 2021. The Author(s).)

The complexity of the emotional presentation of users to Artificial Intelligence (AI) virtual assistants is mainly manifested in user motivation and social emotion, but the current research lacks an effective conversion path from emotion to acceptance. This paper innovatively cuts from the perspective of trust, establishes an AI virtual assistant acceptance model, conducts an empirical study based on the survey data from 240 questionnaires, and uses multilevel regression analysis and the bootstrap method to analyze the data. The results showed that functionality and social emotions had a significant effect on trust, where perceived humanity showed an inverted U relationship on trust, and trust mediated the relationship between both functionality and social emotions and acceptance. The findings explain the emotional complexity of users toward AI virtual assistants and extend the transformation path of technology acceptance from the trust perspective, which has implications for the development and design of AI applications., 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 Zhang, Meng, Chen, Yang and Zhao.)

Abstract: This study aimed to design and fabricate a customized distractor based on 3D printing technology and compare its mechanical properties with conventional distractor. The investigators designed and implemented a study composed of conventional and customized distractors. The design of customized distractor was based on the specification of conventional mandibular distractors and was fabricated using selective laser melting (SLM) technology. The same type of conventional distractors served as control group. Vickers-hardness test, three-point bending test and welding strength test were carried out for the conventional and customized distractor respectively and data was analyzed with t test using SPSS13.0 software package. The sample was composed of 18 distractors grouped as follows: customized distractor (n = 9) and conventional distractor (n = 9). The customized distractor showed better result than the conventional distractor in mechanical property tests, with statistically significant differences in Vickers-hardness and maximum load (P < 0.05), and no significant differences in yield strength and welding strength (P > 0.05). The results of this study suggest indicated that compared to the conventional distractor, the customized distractor had better mechanical properties and could be used in maxillofacial distraction osteogenesis., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2020 by Mutaz B. Habal, MD.)

Abstract: As Corona Virus Disease 2019 (COVID-19) has been gradually controlled domestically, various industries began to resume production in an orderly way. Attention should be paid to the disease and population characteristics of patients with cleft lip with/without palate during diagnosis and treatment. This article summarized and provided prevention and control recommendations on management strategies during hospitalization and protective measures of patients and healthcare workers, hoping to minimize the spread of disease and create a relatively safe environment for medical work., Competing Interests: The authors report no conflicts of interest., (Copyright © 2020 by Mutaz B. Habal, MD.)

Aim: To evaluate the cost-effectiveness of intravitreal aflibercept compared with macular laser photocoagulation and ranibizumab for diabetic macular edema (DME) in China. Methods: A Markov model was developed to reflect the vision changes in DME patients. Parameters were estimated from VIVID-EAST trial data, published literature and physician surveys. Results: In a 20-year horizon, intravitreal aflibercept was associated with 7.825 quality-adjusted life years (QALYs) and 217,841 Chinese Yuan Renminbi (CNY), laser photocoagulation was associated with 7.189 QALYs and 135,489 CNY, and ranibizumab was associated with 7.462 QALYs and 222,477 CNY. The incremental cost-effectiveness ratios were 129,397 CNY/QALY and -12,774 CNY/QALY for intravitreal aflibercept versus laser photocoagulation and ranibizumab, respectively. Conclusion: Intravitreal aflibercept was considered as a cost-effective strategy for DME when compared with laser photocoagulation; it was considered as a dominant strategy when compared with ranibizumab.

A novel bacterial strain, designated ZR32 T , was isolated from briquette warehouse soil in Ulsan (Korea). The strain was aerobic, showing pink-colored colonies on R2A agar. Phylogenetic analyses based on 16S rRNA gene sequences showed that strain ZR32 T was closely related to Mucilaginibacter soli R9-65 T (97.0%), Mucilaginibacter gynuensis YC7003 T (96.9%), and Mucilaginibacter lutimaris BR-3 T (96.8%). The values of DNA-DNA relatedness related two highest strains M. soli R9-65 T and M. gynuensis YC7003 T were 31.2 ± 6.9% and 19.7 ± 0.3%, respectively. Its genome size was 3.9 Mb, comprising 3402 predicted genes. The DNA G+C content of strain ZR32 T was 43.0 mol%. The major cellular fatty acids (> 5% of total) were summed feature 3 (C 16:1 ω6c and/or C 16:1 ω7c), C 16:0 , C 16:1 ω5c, iso-C 15:0 , iso-C 17:0 3-OH, and C 17:1 ω9c. The major respiratory quinine was menaquinone-7 (MK-7). The major polar lipids were phosphatidylethanolamine, two unidentified phospholipids, one unidentified sphingolipid, and one unidentified polar lipid. Strain ZR32 T showed distinctive characteristics such as the temperature and pH for growth ranges, being positive for β-glucosidase, salicin production, negative for N-acetyl-glucosamine assimilation, being resistant to carbenicillin and piperacillin to related species. On the basis of phenotypic, chemotaxonomic, and phylogenetic data, strain ZR32 T represents a novel species of the genus Mucilaginibacter, for which the name Mucilaginibacter hurinus sp. nov. is proposed. The type strain is ZR32 T (= KCTC 62193 = CCTCC AB 2017285).

Dendranthema morifolium cv. 'jinsidaju', cultivated only in Kaifeng, has been eaten for more than 1000 years. During the antioxidant-activity-guided studies on its chemistry and health care function, two new bisabolane-type sesquiterpenes, (6R,7R)-7-hydroxybisabol-2,9E,11-triene-4-one (jinsidajuol A, 1) and (6R,7R)-7-hydroxy-11-methoxybisabol-2,9E-diene-4-one (jinsidajuol B, 2), and thirteen known compounds (3-15) were isolated from the flowers. Their structures were elucidated by 1D and 2D NMR spectroscopy and HRMS. 1 and 2 are the first example of bisabolane-type sesquiterpenes isolated from the genus Dendranthema. Compounds 6-8, 12 and 13 exhibited strong scavenging activities on the ABTS radical cation with IC 50 3.33, 5.67, 2.00, 2.50, 5.33 μg/mL, respectively. The IC 50 values of all compounds on HepG2 human hepatoma tumor cell line were higher than 50 μM., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Both type 1 myotonic dystrophy (MD1) and Brugada syndrome (BrS) may be complicated by conduction disturbances and sudden death. Spontaneous BrS has been observed in MD1 patients, but the prevalence of drug-induced BrS in MD1 is unknown., Objective: The purpose of this study was to prospectively assess the prevalence of type 1 ST elevation as elicited during pharmacologic challenge with Class 1C drugs in a subgroup of MD1 patients and to further establish correlations with ECG and electrophysiologic variables and prognosis., Methods: From a group of unselected 270 MD1 patients, ajmaline or flecainide drug challenge was performed in a subgroup of 44 patients (27 men, median age 43 years) with minor depolarization/repolarization abnormalities suggestive of possible BrS. The presence of type 1 ST elevation after drug challenge was correlated to clinical, ECG, and electrophysiologic variables., Results: Eight of 44 patients (18%) presented with BrS after drug challenge. BrS was seen more often in men (26% vs 6%, P = .09) and was related to younger age (35 vs 48 years, P = .07). BrS was not correlated to symptoms, baseline ECG, HV interval, results of signal-averaged ECG, or abnormalities on ambulatory recordings. MD1 patients with BrS had longer corrected QT intervals, greater increase in PR interval after drug challenge, and higher rate of inducible ventricular arrhythmias (62% vs 21%, P = .03). Twelve patients were implanted with a pacemaker and 5 with an implantable cardioverter-defibrillator. Significant bradycardia did not occur in any patients, and malignant ventricular arrhythmia never occurred during median 7-year follow-up (except 1 hypokalemia-related ventricular fibrillation)., Conclusion: BrS is elicited by a Class 1 drug in 18% of MD1 patients presenting with minor depolarization/repolarization abnormalities at baseline, but the finding seems to be devoid of a prognostic role., (Copyright © 2014 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Several studies have showed that fragmented QRS complexes (f - QRS, defined as different RSR' patterns) on a routine 12 - lead electrocardiogram were associated with increased mortality and arrhythmic events in patients with coronary artery disease, but relatively little data were available regarding idiopathic dilated cardiomyopathy (IDCM)., Objective: The purpose of this study was to evaluate the relationship between fragmentation of QRS and the combined end point of all-cause mortality and ventricular arrhythmias in patients with IDCM., Methods: One hundred twenty-eight patients with IDCM and left ventricular dysfunction (ejection fraction, EF ≤ 40%) were analyzed, respectively. According to QRS duration and the existence of f - QRS on 12-lead electrocardiograph (ECG), the study populations were divided into three groups: (1) the f - QRS group (QRS <120 ms and with fragmented QRS, n = 51), (2) the wide QRS (wQRS) group (QRS ≥ 120 ms, n = 48), and (3) the nonfragmented QRS (non-fQRS) group (QRS < 120 ms and without f - QRS, n = 29)., Results: During a mean follow-up of 14 ± 5 months, 25 (19.5%) patients had deaths and ventricular arrhythmic events. The combined end point of all-cause mortality and ventricular tachyarrhythmias was significantly higher in the f - QRS and wQRS groups than the non-fQRS group (23.5%, 25%, and 3.4%, respectively; P < 0.05 for both). Event-free was significantly decreased in the f - QRS group versus the non-fQRS group (P = 0.02). Univaritae regression analysis revealed that f - QRS was a stronger predictor of mortality and arrhythmic events in IDCM patients., Conclusion: f - QRS on 12-lead ECG has a high predictive value for the combined end point of all-cause mortality and ventricular tachyarrhythmias in IDCM patients with left ventricular dysfunction., (©2011, Wiley Periodicals, Inc.)

Aims: This study was to evaluate perioperative anticoagulation therapy in patients with mechanic heart valve(s) undergoing pacemaker implantation., Methods and Results: A total of 109 patients with mechanical heart valve(s) undertaking pacemaker implantation were studied. Fifty-one patients with warfarin suspended 3 days before surgery were classified into Group 1 and 58 patients with warfarin suspended <3 days or not at all into Group 2. The perioperative incidence of complications was compared. Suspension of warfarin<3 days before surgery was associated with a higher incidence of excessive haemorrhage (16/51 vs. 5/58, P=0.003). Patients with pocket haematoma were more likely to have been treated with post-operation heparin (60% vs. 17.3%, P=0.032). In 42 patients treated with proposed protocol of perioperative anticoagulation, no pocket haematoma or embolism occurred., Conclusions: A minimum of 3 days cessation of warfarin prior to surgery is preferred. Low-molecular-weight heparin should not be used for at least 3 days post-surgery. We propose that the protocol of perioperative anticoagulation be a suspension of warfarin not <3 days with low-molecular-weight heparin bridging stopped 12 h before surgery, and warfarin rather than low-molecular-weight heparin initiated immediately after surgery.