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Jiun-Wen Guo,1 Yu-Hsuan Lee,2 Hsiau-Wen Huang,3 Mei-Chyun Tzou,3 Ying-Jan Wang,2 Jui-Chen Tsai1,4 1Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Chung Kung University, Tainan, Taiwan; 2Department of Environmental and Occupational Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 3Food and Drug Administration, Ministry of Health and Welfare, Taiwan; 4Center for Pharmaceutical Regulatory Science, National Cheng Kung University, Tainan, Taiwan Abstract: Nanotechnology offers potential in pharmaceuticals and biomedical developments for improving drug delivery systems, medical imaging, diagnosis, cancer therapy, and regenerative medicine. Although there is no international regulation or legislation specifically for nanomedicine, it is agreed worldwide that considerably more attention should be paid to the quality, safety, and efficacy of nanotechnology-based drugs. The US Food and Drug Administration and the European Medicines Agency have provided several draft regulatory guidance and reflection papers to assist the development of nanomedicines. To cope with the impact of nanotechnology and to foster its pharmaceutical applications and development in Taiwan, this article reviews the trends of regulating nanotechnology-based pharmaceuticals in the international community and proposes strategies for Taiwan’s regulation harmonized with international considerations. The draft regulatory measures include a chemistry, manufacturing, and controls (CMC) review checklist and guidance for CMC review of liposomal products. These have been submitted for discussion among an expert committee, with membership comprised of multidisciplinary academia, research institutions, the pharmaceutical industry, and regulators, and are currently approaching final consensus. Once a consensus is reached, these mechanisms will be recommended to the Taiwan Food and Drug Administration for jurisdiction and may be initiated as the starting point for regulating nanotechnology-based pharmaceuticals in Taiwan. Keywords: CMC review, nanomedicine, nanotechnology, pharmaceuticals, regulatory guidance

The development of superconducting ECR source with higher magnetic fields and higher microwave frequency is the most straight forward path to achieve higher beam intensity and higher charge state performance. SECRAL, a superconducting third generation ECR ion source, is designed for 24-28 GHz microwave frequency operation with an innovative magnet configuration of sextupole coils located outside the three solenoids. SECRAL at 24 GHz has already produced a number of record beam intensities, such as 40Ar12+ 1.4 emA, 129Xe26+ 1.1 emA, 129Xe30+ 0.36 emA, and 209Bi31+ 0.68 emA. SECRAL-II, an upgraded version of SECRAL, was built successfully in less than 3 years and has recently been commissioned at full power of a 28 GHz gyrotron and three-frequency heating (28 + 45 + 18 GHz). New record beam intensities for highly charged ion production have been achieved, such as 620 eμA 40Ar16+, 15 eμA 40Ar18+, 146 eμA 86Kr28+, 0.5 eμA 86Kr33+, 53 eμA 129Xe38+, and 17 eμA 129Xe42+. Recent beam test results at SECRAL and SECRAL II have demonstrated that the production of more intense highly charged heavy ion beams needs higher microwave power and higher frequency, as the scaling law predicted. A 45 GHz superconducting ECR ion source FECR (a first fourth generation ECR ion source) is being built at IMP. FECR will be the world's first Nb3Sn superconducting-magnet-based ECR ion source with 6.5 T axial mirror field, 3.5 T sextupole field on the plasma chamber inner wall, and 20 kW at a 45 GHz microwave coupling system. This paper will focus on SECRAL performance studies at 24-28 GHz and technical design of 45 GHz FECR, which demonstrates a technical path for highly charged ion beam production from 24 to 28 GHz SECRAL to 45 GHz FECR.

The superconducting electron cyclotron resonance ion source with advanced design in Lanzhou (SECRAL) is a superconducting-magnet-based electron cyclotron resonance ion source (ECRIS) for the production of intense highly charged heavy ion beams. It is one of the best performing ECRISs worldwide and the first superconducting ECRIS built with an innovative magnet to generate a high strength minimum-B field for operation with heating microwaves up to 24-28 GHz. Since its commissioning in 2005, SECRAL has so far produced a good number of continuous wave intensity records of highly charged ion beams, in which recently the beam intensities of Ar4012+ and Xe12926+ have, for the first time, exceeded 1 emA produced by an ion source. Routine operations commenced in 2007 with the Heavy Ion accelerator Research Facility in Lanzhou (HIRFL), China. Up to June 2017, SECRAL has been providing more than 28,000 hours of highly charged heavy ion beams to the accelerator demonstrating its great capability and reliability. The great achievement of SECRAL is accumulation of numerous technical advancements, such as an innovative magnetic system and an efficient double-frequency (24+18 GHz) heating with improved plasma stability. This article reviews the development of SECRAL and production of intense highly charged ion beams by SECRAL focusing on its unique magnet design, source commissioning, performance studies and enhancements, beam quality and long-term operation. SECRAL development and its performance studies representatively reflect the achievements and status of the present ECR ion source, as well as the ECRIS impacts on HIRFL.

This study examined the psychometric properties of the Pain Care Quality (PainCQ) survey, a new instrument to measure the quality of nursing and interdisciplinary care related to pain management. Hospitalized medical/surgical oncology patients with pain from 3 states completed the 44-item version of the PainCQ survey following completion of a nursing shift. Interdisciplinary items were evaluated over the entire hospital stay; nursing care was evaluated during the previous shift. The sample included 109 patients ranging in age from 20 to 84 (mean = 53.09). The sample was 58.7% female, 88% non-Hispanic white. Principal Axis Factoring with an oblimin rotation was used as factors were correlated. Two scales resulted. The PainCQ-Interdisciplinary scale included 11 items representing 2 constructs and explaining 47.1% of shared item variance: partnership with the health care team (k = 6 items; [alpha] = .85) and comprehensive interdisciplinary pain care (k = 5 items; [alpha] = .76). The PainCQ-Nursing scale measured three constructs and explained 60.8% of shared item variance: being treated right (k = 15 items; [alpha] = .95), comprehensive nursing pain care (k = 3 items; [alpha] = .77), and efficacy of pain management (k =4 items; [alpha] = .87). Results supported the internal consistency reliability and structural validity of the PainCQ survey with 33 items. PERSPECTIVE: This article presents the psychometric properties of a new tool to measure interdisciplinary and nursing care quality related to pain management from the patient's perspective. This tool can be used for research and as a clinical performance measure to monitor and improve quality of care and patient outcomes. [ABSTRACT FROM AUTHOR]

Background: The genus Amorphophallus (Araceae) contains approximately 250 species, most of which have high ecological and economic significance. The chloroplast genome data and the comprehensive analysis of the chloroplast genome structure of Amorphophallus is limited. In this study, four chloroplast genomes of Amorphophallus were sequenced and assembled. For the first time, comparative analyses of chloroplast genomes were conducted on the 13 Amorphophallus species in conjunction with nine published sequences., Results: The Amorphophallus chloroplast genomes exhibited typical quadripartite structures with lengths ranging from 164,417 to 177,076 bp. These structures consisted of a large single copy (LSC, 90,705 - 98,561 bp), a small single copy (SSC, 14,172 - 21,575 bp), and a pair of inverted repeats (IRs, 26,225 - 35,204 bp). The genomes contain 108 - 113 unique genes, including 76 - 79 protein-coding genes, 28 - 29 tRNA genes, and 4 rRNA genes. The molecular structure, gene order, content, codon usage, long repeats, and simple sequence repeats (SSRs) within Amorphophallus were generally conserved. However, several variations in intron loss and gene expansion on the IR-SSC boundary regions were found among these 13 genomes. Four mutational hotspot regions, including trnM-atpE, atpB, atpB-rbcL and ycf1 were identified. They could identify and phylogeny future species in the genus Amorphophallus. Positive selection was found for rpl36, ccsA, rpl16, rps4, rps8, rps11, rps12, rps14, clpP, rps3, ycf1, rpl20, rps2, rps18, rps19, atpA, atpF, rpl14, rpoA, rpoC1, rpoC2 and rps15 based on the analyses of Ka/Ks ratios. Phylogenetic inferences based on the complete chloroplast genomes revealed a sister relationship between Amorphophallus and Caladieae. All Amorphophallus species formed a monophyletic evolutionary clade and were divided into three groups, including CA-II, SEA, and CA-I. Amorphophallus albus, A. krausei, A. kachinensis and A. konjac were clustered into the CA-II clade, A. paeoniifolius and A. titanum were clustered into the SEA clade, A. muelleri 'zhuyajin1', Amorphophallus sp, A. coaetaneus, A. tonkinensis and A. yunnanensis were clustered into CA- I clade., Conclusions: The genome structure and gene content of Amorphophallus chloroplast genomes are consistent across various species. In this study, the structural variation and comparative genome of chloroplast genomes of Amorphophallus were comprehensively analyzed for the first time. The results provide important genetic information for species classification, identification, molecular breeding, and evolutionary exploration of the genus Amorphophallus., Competing Interests: Declarations. Ethics approval and consent to participate: The materials involved in the article does not an endangered or protected species; therefore, permission is not required to collect this species. Research on these species, including the collection of plant materials has been carried out in accordance with guidelines provided by Kunming University. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: The prognosis of lung metastasis in primary limb bone tumors represents a pivotal yet challenging aspect of oncological management. Despite advancements in diagnostic modalities, the predictive accuracy for metastatic spread remains suboptimal. This study aims to bridge this gap by leveraging the Surveillance, Epidemiology, and End Results (SEER) database to construct a nomogram that forecasts the risk of lung metastasis, thereby enhancing clinical decision-making processes., Methods: A retrospective cohort, including 1,822 patients with primary limb bony tumors from 2010 to 2015 in the SEER database, was extracted. Using precise inclusion and exclusion criteria, variables essential for predicting lung metastasis were identified through univariate and multivariate analyses, along with least absolute shrinkage and selection operator (LASSO) regression. These variables provided a solid basis for creating the multivariable nomogram, of which the discriminating power and utility were verified using receiver operating characteristic (ROC) curves, calibration plots, and decision curve analysis., Results: The model incorporated seven key predicting variables, including age, histological type, surgery, radiation, chemotherapy, T stage, and N stage. The nomogram emerged as a cohesive whole with good discriminative power. The area under the curve (AUC) was 0.806 in the training cohort and 0.767 in the validation cohort. The calibration curves demonstrated the model's validity by showing a good match between the actual outcomes and the model-predicted probabilities of lung metastasis., Conclusions: This study showed for the first time the reliability of the predictive model in translating the hard-to-interpret demographic, clinical, and pathologic data into a very usable predictive model. Thus, it represents a significant step toward demystifying the risk of lung metastasis in primary limb bone tumors. It is an invitation for a paradigm shift of oncology, to evidence-based, person-based oncology that is taking a new metric for cancer prognosis., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tcr.amegroups.com/article/view/10.21037/tcr-24-570/coif). The authors have no conflicts of interest to declare., (2024 AME Publishing Company. All rights reserved.)

Zhongfeng Xingnao Decoction(ZFXN) has been utilized for treating intracerebral hemorrhage(ICH) in China, while the pharmacological mechanism of ZFXN remains unclear. Exploring the pharmacological roles of ZFXN is critical for guiding the treatment of cerebrovascular diseases. In this study, a rat model of ICH was constructed by injection of Ⅶ collagenase in the right caudate nucleus. SD rats were randomly assigned into five groups, and the neurological function of rats was evaluated based on the Bederson score. Magnetic resonance imaging(MRI) was used to assess the volume of ICH. Hematoxylin-eosin(HE) staining and transmission electron microscopy(TEM) were employed to observe the pathological and ultrastructural changes in the brain tissue. The levels of reactive oxygen species(ROS) were measured by flow cytometry. The immunofluorescence assay was employed to detect the expression of glutathione peroxidase 4(GPX4) in neurons surrounding the hematoma. Finally, Western blot was employed to determine the expression of ferroptosis-related proteins upstream frameshift 1(UPF1), ferroportin(FPN), acyl-CoA ligase 4(ACSL4), cyclooxyge-nase-2(COX-2), GPX4, NADPH oxidase 1(NOX1), and solute carrier family 7 member 11(SLC7A11) after ICH. Compared with the model(ICH) group, ZFXN treatment for 5 days attenuated neurological dysfunction, reduced the hematoma volume, and alleviated the pathological changes induced by ICH. Meanwhile, ZFXN lowered the levels of Fe~(2+) and oxidative stress and up-regulated the expression of proteins inhibiting ferroptosis. ZFXN improved the prognosis of ICH in rats by inhibiting neuronal ferroptosis, which provided a valuable guide for the clinical application of ZFXN. ZFXN may inhibit ferroptosis by promoting the expression of SLC7A11 and FPN.

Rationale: An impairment of plasma membrane repair has been implicated in various diseases such as muscular dystrophy and ischemia/reperfusion injury. MOTS-c, a short peptide encoded by mitochondria, has been shown to pass through the plasma membrane into the bloodstream. This study determined whether this biological behavior was involved in membrane repair and its underlying mechanism. Methods and Results: In human participants, the level of MOTS-c was positively correlated with the abundance of mitochondria, and the membrane repair molecule TRIM72. In contrast to high-intensity eccentric exercise, moderate-intensity exercise improved sarcolemma integrity and physical performance, accompanied by an increase of mitochondria beneath the damaged sarcolemma and secretion of MOTS-c. Furthermore, moderate-intensity exercise increased the interaction between MOTS-c and TRIM72, and MOTS-c facilitated the trafficking of TRIM72 to the sarcolemma. In vitro studies demonstrated that MOTS-c attenuated membrane damage induced by hypotonic solution, which could be blocked by siRNA-TRIM72, but not AMPK inhibitor. Co-immunoprecipitation study showed that MOTS-c interacted with TRIM72 C-terminus, but not N-terminus. The dynamic membrane repair assay revealed that MOTS-c boosted the trafficking of TRIM72 to the injured membrane. However, MOTS-c itself had negligible effects on membrane repair, which was recapitulated in TRIM72 -/- mice. Unexpectedly, MOTS-c still increased the fusion of vesicles with the membrane in TRIM72 -/- mice, and dot blot analysis revealed an interaction between MOTS-c and phosphatidylinositol (4,5) bisphosphate [PtdIns (4,5) P 2 ]. Finally, MOTS-c blunted ischemia/reperfusion-induced membrane disruption, and preserved heart function. Conclusions: MOTS-c/TRIM72-mediated membrane integrity improvement participates in mitochondria-triggered membrane repair. An interaction between MOTS-c and plasma lipid contributes to the fusion of vesicles with membrane. Our data provide a novel therapeutic strategy for rescuing organ function by facilitating membrane repair with MOTS-c., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Background: Cardiovascular health (CVH) in young adulthood (YA) has been associated with cardiovascular outcomes in older age. However, little is known about the relationship between YA CVH and mid-life blood pressure (BP) trajectories., Methods: Baseline CVH (defined by 7 of the American Heart Association's [AHA] Life's Essential 8 [LE8] metrics, excluding BP) was measured in YA with individual metrics scored and averaged as a composite LE8 score. Categorical CVH status was defined as high, moderate, and low. Latent class analysis was used to identify trajectories of mid-BP (mean of systolic blood pressure [SBP] and diastolic blood pressure [DBP]) from average ages 35 to 55 years. Multinomial logistic regression was used to estimate the association of YA CVH status (continuously and categorically) with mid-life BP trajectory group membership., Results: There were 3,688 participants from the Coronary Artery Risk Development in Young Adults (CARDIA) study in YA with follow-up data for mid-life BP trajectories. We observed 3 BP trajectory groups, labeled as Persistently-Low, Middle, and High-Increasing. On average, each 10-points higher baseline LE8 score (mean [SD] of 73.5 [13.1]) in YA was associated with adjusted odds ratios of 0.78 (95% CI, 0.72-0.84) for membership in the Middle and 0.65 (0.57-0.73) for membership in the High-Increasing trajectory groups. Compared with categorical low CVH status at baseline, those with high CVH were significantly less likely to be in the Middle and High-Increasing BP trajectory groups., Conclusions: Moderate or low CVH status in YA is associated with elevated mid-life BP trajectory. These data suggest that young adult CVH promotion may be important for the primordial prevention of hypertension., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Journal of Hypertension, Ltd. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Spodoptera frugiperda poses a severe threat to crops, causing substantial economic losses. The increased use of chemical pesticides has led to resistance in S. frugiperda populations. Micro ribonucleic acids (MicroRNAs or miRNAs) are pivotal in insect growth and development. This study aims to identify miRNAs across different developmental stages of S. frugiperda to explore differential expression and predict target gene functions. High-throughput sequencing of miRNAs was conducted on eggs, 3rd instar larvae, pupae, and adults. Bioinformatics analyses identified differentially expressed miRNAs specifically in larvae, with candidate miRNAs screened to predict target genes, particularly those involved in detoxification pathways. A total of 184 known miRNAs and 209 novel miRNAs were identified across stages. Comparative analysis revealed 54, 15, and 18 miRNAs differentially expressed in larvae, compared to egg, pupa, and adult stages, respectively. Eight miRNAs showed significant differential expression across stages, validated by quantitative reverse transcription PCR (qRT-PCR). Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses predicted target genes' functions, identifying eight differentially expressed miRNAs targeting 10 gene families associated with detoxification metabolism, including P450s, glutathione S-transferase (GSTs), ATP-binding cassette (ABC) transporters, and sodium channels. These findings elucidate the species-specific miRNA profiles and regulatory mechanisms of detoxification-related genes in S. frugiperda larvae, offering insights and strategies for effectively managing this pest.

The cerebellum is heavily connected with other brain regions, sub-serving not only motor but also non-motor functions. Genetic mutations leading to cerebellar dysfunction are associated with mental diseases, but cerebellar outputs have not been systematically studied in this context. Here, we present three dimensional distributions of 50,168 target neurons of cerebellar nuclei (CN) from wild-type mice and Nlgn3R451C mutant mice, a mouse model for autism. Our results derived from 36 target nuclei show that the projections from CN to thalamus, midbrain and brainstem are differentially affected by Nlgn3R451C mutation. Importantly, Nlgn3R451C mutation altered the innervation power of CN→zona incerta (ZI) pathway, and chemogenetic inhibition of a neuronal subpopulation in the ZI that receives inputs from the CN rescues social defects in Nlgn3R451C mice. Our study highlights potential role of cerebellar outputs in the pathogenesis of autism and provides potential new therapeutic strategy for this disease., (© The Author(s) 2024. Published by Oxford University Press on behalf of Higher Education Press.)

Introduction: Understanding patterns and processes of microbial biogeography in soils is important for monitoring ecological responses to human activities, particularly in ecologically vulnerable areas such as the Qinghai-Xizang Plateau. Highland barley is the staple food of local people and has mainly been cultivated along the Yarlung Zangbo River valley in Xizang., Methods: Here we investigated soil bacterial communities from 33 sampling sites of highland barley farmland in this region and compared them to those from wild ecosystems including alpine tundra, meadow, forest, and swamp. Additionally, the effects of environmental factors on bacterial communities, as well as the relative importance of stochastic and deterministic processes in shaping the beta diversity of soil bacterial communities in alpine ecosystems were assessed., Results: In contrast to soils of wild ecosystems, these farmland samples harbored a highly homogeneous bacterial community without significant correlations with geographic, elevation, and edaphic distances. Discriminant bacterial taxa identified for farmland samples belong to Acidobacteria , with Acidobacteria Gp4 as the dominant clade. Although Acidobacteria were the most abundant members in all ecosystems, characterized bacterial taxa of meadow and forest were members of other phyla such as Proteobacteria and Verrucomicrobia . pH and organic matter were major edaphic attributes shaping these observed patterns across ecosystems. Null model analyses revealed that the deterministic assembly was dominant in bacterial communities in highland barley farmland and tundra soils, whereas stochastic assembly also contributed a large fraction to the assembly of bacterial communities in forest, meadow and swamp soils., Discussion: These findings provide an insight into the consequences of human activities and agricultural intensification on taxonomic homogenization of soil bacterial communities in the Qinghai-Xizang Plateau., 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 Wang, Yang, Nan, Guo, Tan, Shao and Tian.)

Globally, hepatitis B virus (HBV) affects over 250 million people, whereas hepatitis C virus (HCV) affects approximately 70 million people, posing major public health challenges. Despite the availability of vaccines and treatments, a lack of comprehensive diagnostic coverage has left many cases undiagnosed and untreated. To address the need for sensitive, specific, and accessible diagnostics, this study introduced a multiplex loop-mediated isothermal amplification assay with lateral flow detection for simultaneous HBV and HCV testing. This assay achieved exceptional sensitivity and was capable of detecting HBV and HCV concurrently in a single tube and on a single strip within 25 min, achieving the required clinical sensitivity (10 and 10 3  genomic copies/reaction for HBV and HCV, respectively). The method was validated in clinical samples of various viral genotypes, achieving an equivalent limit of detection. Additionally, a custom portable heating device was developed for field use. The assay developed here, capable of direct viral detection on the strip, shows promise in supplanting current methods that solely identify antibodies and necessitate additional qPCR for viral activity assessment. This economical and rapid assay aligns with point-of-care testing needs, offering significant advancements in enhancing viral hepatitis diagnostics in settings with limited resources., (© 2024 Wiley Periodicals LLC.)

Objective: To review the effectiveness of different physical therapies for acute and sub-acute low back pain supported by evidence, and create clinical recommendations and expert consensus for physiotherapists on clinical prescriptions., Data Sources: A systematic search was conducted in PubMed and the Cochrane Library for studies published within the previous 15 years., Review Methods: Systematic review and meta-analysis, randomized controlled trials assessing patients with acute and sub-acute low back pain were included. Two reviewers independently screened relevant studies using the same inclusion criteria. The Physiotherapy Evidence Database and the Assessment of Multiple Systematic Reviews tool were used to grade the quality assessment of randomized controlled trials and systematic reviews, respectively. The final recommendation grades were based on the consensus discussion results of the Delphi of 22 international experts., Results: Twenty-one systematic reviews and 21 randomized controlled trials were included. Spinal manipulative therapy and low-level laser therapy are recommended for acute low back pain. Core stability exercise/motor control, spinal manipulative therapy, and massage can be used to treat sub-acute low back pain., Conclusions: The consensus statements provided medical staff with appliable recommendations of physical therapy for acute and sub-acute low back pain. This consensus statement will require regular updates after 5-10 years., Competing Interests: Declaration of conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Amorphophallus muelleri is an Araceae plant with perennial tuber, widely used in food, pharmaceutical and chemical industry due to its richness in glucomannan. In April 2022, an outbreak of a target spot on A. muelleri plantlets was observed in a nursery in Ruili, Yunnan, China. The leafstalks of the diseased plantlets in the nursery turned brown and decayed (Fig.1 A-B), then gradually some water-soaked spots on the true leaves developed along the veins (Fig.1 A). Subquencely, the spots on the true leaves turned dark green to white-grayish in the center, which formed light to dark brown concentric rings with a target-like appearance surrounded by a yellow halo (Fig.1 C). When the temperature was 20-34℃ and the relatively humidity was 25-80%, dark-green to black sporodochia with white hypha appeared on the lower and upper leaf surfaces. Finally, 5-8% of the plants surveyed on 800 m2 of one-year-old plantlets in the nursery showed the symptoms and some plants with infected leafstalks would be death. Similar symptoms were also observed on about 10% of the transplanted plants surveyed on 12000 m2 (1.2 ha) of two-year-old plantlets in the field. Five diseased leaves from five distinct plantlets in the nursery were collected for pathogen isolation. Leaf pieces(5 x 5 mm) were cut from the edge of necrotic lesions, and surface-sterilized with 2.5% sodium hypochlorite for 1 min, 75% ethanol for 30 s, then rinsed 5 times by sterilized distilled water, finally put the leaf pieces on sterilized filter paper for 3-5 minutes to dry them and transferred onto potato dextrose agar (PDA) in petri dishes at 25℃ for three days. Five pure cultures identical to colony and conidial characteristics were isolated from five individual plants. The representative pure culture (M1) was grayish-white and circular colonies were 7.50 cm in diamter after 15 days at 25℃, with dark green concentric rings of sporodochia, the dorsal view of the colonies were yellowish. Conidia were aseptate, smooth, cylindrical, 5.00-6.25 (5.71) x 1.25-1.67 (1.63) µm (n = 20) rounded at both ends. A spore suspension (1 x 106 spores/ml) was prepared by harvesting spores from 15-day-old cultures grown in the dark at 25℃, then a thirty-ml of spore suspension was sprayed on the healthy leaves of 10 two-year-old plantlets. Thirty-ml of sterile water was sprayed on the healthy leaves of another 10 seedlings and used as the control. All seedlings were placed in a nursery at 20 to 34℃ and a relative humidity of 25 to 80%. Similar symptoms (Fig.1 D-F) to those observed in the nursery and field developed on all the 10 seedlings inoculated with M1 after two days, but not on the control leaves. The pathogenicity tests were repeated for three times. Fungal cultures reisolated from the infected leaves were identical to the original colonies and conidia, completing Koch's postulates. The internal transcribed spacer (ITS, primers ITS1 and ITS4) region of ribosomal DNA (OQ553785), calmodulin (cmdA, primers CAL-228F and CAL2Rd)(OQ559103), RNA polymerase II second largest subunit (rpb2, primers RPB2-5F2 and RPB2-7cR) (OQ559104) and β-tubulin (tub2, primers Bt2a and Bt2b) (OQ559105) of M1 had 100%, 98.52%, 98.98% and 98.98% identity with the sequences of Paramyrothecium breviseta CBS544.75 (KU846289 for ITS, KU846262 for cmdA, KU846351 for rpb2, and KU846406 for tub2), respectively. In the phylogenic tree based on ITS, cmdA, rpb2 and tub2 gene sequences, the pure culture M1 clustered with P. breviseta CBS544.75, SDBR-CMU387, DRL4 and DRL3, which has been reported as the pathogen of leaf spot of Coffea arabica in China, C. canephora in China and Thailand (Wu et al. 2021; Withee et al. 2022). Molecular and morphological observations showed the pure culture M1 were P. breviseta (Withee et al. 2022), in addition the disease was named as target spot dueing to the typical target symptom on the leaves. To our knowledge, this is the first report of P. breviseta on A. muelleri from Yunnan, China, as well as worldwide. This disease can caused serious economic losses of A. muelleri dueing to that it can result 5-8% death of the plants in the nursery.

Purpose: Use of artificial intelligence (AI) in cancer care is increasing. What remains unclear is how best to design patient-facing systems that communicate AI output. With oncologist input, we designed an interface that presents patient-specific, machine learning-based 6-month survival prognosis information designed to aid oncology providers in preparing for and discussing prognosis with patients with advanced solid tumors and their caregivers. The primary purpose of this study was to assess patient and caregiver perceptions and identify enhancements of the interface for communicating 6-month survival and other prognosis information when making treatment decisions concerning anticancer and supportive therapy., Methods: This qualitative study included interviews and focus groups conducted between November and December 2022. Purposive sampling was used to recruit former patients with cancer and/or former caregivers of patients with cancer who had participated in cancer treatment decisions from Utah or elsewhere in the United States. Categories and themes related to perceptions of the interface were identified., Results: We received feedback from 20 participants during eight individual interviews and two focus groups, including four cancer survivors, 13 caregivers, and three representing both. Overall, most participants expressed positive perceptions about the tool and identified its value for supporting decision making, feeling less alone, and supporting communication among oncologists, patients, and their caregivers. Participants identified areas for improvement and implementation considerations, particularly that oncologists should share the tool and guide discussions about prognosis with patients who want to receive the information., Conclusion: This study revealed important patient and caregiver perceptions of and enhancements for the proposed interface. Originally designed with input from oncology providers, patient and caregiver participants identified additional interface design recommendations and implementation considerations to support communication about prognosis.

Objectives: To describe cancer survivors' and care partners' perceived stress and social support during the COVID-19 pandemic and assess the feasibility of audio diaries for assessing role-related needs and resources., Methods: Participants (N = 51; n = 28 survivors, n = 23 care partners) recorded three monthly audio diaries reporting stress and support experiences. Diaries were transcribed and content-analyzed using a hybrid approach. Stress-related content was inductively coded, and social support content was deductively coded by type (instrumental, information, emotional, companionship, appraisal; κ = 0.75) then inductively coded. Descriptive statistics summarized sociodemographic data and compared coding frequencies by role. We developed narrative summaries of stress and support categories and selected quotes for contextual detail., Results: Cancer-related stressors were most prevalent (28.8%), followed by work (26.8%), family (23.1%), social isolation (13.4%), and finances (8.0%). While no significant difference in reporting frequency was observed between roles, cancer-related stress was more prevalent for survivors while work-related stress was mentioned more by care partners. Emotional support was the most prevalent support type (32.1%), followed by companionship (25.3%), appraisal (17.9%), instrumental (16.67%), and informational support (8%). Survivors reported more appraisal support than care partners (χ 2  = 6.48, df = 1, P = .011) and more support for self-care, while care partners expressed more other-oriented concerns and focused more on managing responsibilities and interactions outside the household., Conclusions: The pandemic complicated and intensified role-based stressors already present in the survivorship context. Our findings highlight the importance of informal social support networks, particularly when access to formal services is limited, and suggest that audio diaries can be an effective tool for assessing support needs and resources., Implications for Nursing Practice: Nurses and healthcare providers should tailor social support assessments to address the distinct support needs and individual resources of cancer survivors and their care partners. This is especially critical in contexts that limit access to care and formal services., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Sarah Wawrzynski reports financial support was provided by National Institute of Nursing Research. Jacqueline Kent-Marvick reports financial support was provided by National Institute of Nursing Research., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The outbreak of coronavirus disease 2019 (COVID-19) has become a major threat to the global healthcare system. As an airborne disease, COVID-19 posed a great challenge to the management of sleep medicine. Given the increased risk of adverse events in obstructive sleep apnea patients infected with COVID-19, strategies have been proposed worldwide. These include standard treatment procedure, use of self-protect equipment, telemedicine services, development of machine learning and portable monitoring, and in-home sleep monitoring and titration. This review aims to introduce the impact of COVID-19 on the operation of sleep medicine landscape and provide advice on public health care emergency.

The violent goods vibration during curve negotiation is a huge threat to the vehicle running safety. Qualified load restraint assemblies that can significantly suppress the cargo vibration are necessary. This study proposes a novel method for evaluating the essential restraint strength, focusing on the relative motion between cargo and wagon. In the beginning, as a comparison, current methods are used to calculate the necessary stiffness of lashings, which are adopted to restrain the cargo vibration on the wagon. Based on the data of the field test, the accuracy of the established wagon-cargo coupled dynamics model is validated. The loaded wagon model negotiates the curve under different running and loading conditions. The simulation results and analysis demonstrate effective strategies for suppressing the vibration of the cargo and reveal the necessary lashing stiffness. The comparison among the results of different evaluation methods shows that the stability of the cargo can be improved by optimizing the lashing stiffness with the method of dynamics simulations. We hope this study will make a positive contribution to the safety of railway freight transportation., (© 2024. The Author(s).)

Background: With the continuous growth of the modern elderly population, the risk of fracture increases. Hip fracture is a common type of fracture in older people. Total hip arthroplasty (THA) has significant advantages in relieving chronic pain and promoting the recovery of hip joint function., Aim: To investigate the effect of ulinastatin combined with dexmedetomidine (Dex) on the incidences of postoperative cognitive dysfunction (POCD) and emergence agitation in elderly patients who underwent THA., Methods: A total of 397 patients who underwent THA from February 2019 to August 2022. We conducted a three-year retrospective cohort study in Shaanxi Provincial People's Hospital. Comprehensive demographic data were obtained from the electronic medical record system. We collected preoperative, intraoperative, and postoperative data. One hundred twenty-nine patients who were administered Dex during the operation were included in the Dex group. One hundred fifty patients who were intravenously injected with ulinastatin 15 min before anesthesia induction were included in the ulinastatin group. One hundred eighteen patients who were administered ulinastatin combined with Dex during the operation were included in the Dex + ulinastatin group. The patients' perioperative conditions, hemodynamic indexes, postoperative Mini-Mental State Examination (MMSE) scores, Ramsay score, incidence of POCD, and serum inflammatory cytokines were evaluated., Results: There was a significant difference in the 24 h visual analogue scale score among the three groups, and the score in the Dex + ulinastatin group was the lowest ( P < 0.05). Compared with the Dex and ulinastatin group, the MMSE scores of the Dex + ulinastatin group were significantly increased at 1 and 7 d after the operation (all P < 0.05). Compared with those in the Dex and ulinastatin groups, incidence of POCD, levels of serum inflammatory cytokines in the Dex + ulinastatin group were significantly decreased at 1 and 7 d after the operation (all P < 0.05). The observer's assessment of the alertness/sedation score and Ramsay score of the Dex + ulinastatin group were significantly different from those of the Dex and ulinastatin groups on the first day after the operation (all P < 0.05)., Conclusion: Ulinastatin combined with Dex can prevent the occurrence of POCD and emergence agitation in elderly patients undergoing THA., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Introduction: Although health systems increasingly integrate social needs screening and referrals into routine care, the effectiveness of these interventions and for whom they work remains unclear., Methods: Patients (N=4,608) seen in the emergency department were screened for social needs (e.g., transportation, housing, food) and offered an opportunity to receive outreach from community service specialists., Results: Among 453 patients with 1 or more social needs who requested assistance, outreach specialists connected with 95 (21.0%). Patients preferred to be contacted through their telephone ( n =21, 60.2%), email ( n =126, 28.0%), someone else's telephone ( n =30, 6.7%), or first by telephone followed by email ( n =23, 5.1%). Preferred contact method varied by patient age; endorsement of unmet transportation, housing, and utility needs; receipt of service outreach; and differences in emergency department utilization from the 6 months before the index visit to the 6 months after., Conclusions: Because limited access to a stable telephone or internet connection may prevent patients from connecting with resource referrals, social needs interventions may not benefit the most underserved populations who are at the highest risk of negative health outcomes. Future research should investigate whether communication preferences are an important indicator of needs and how to adapt social needs screening and referral processes so that they are more accessible to populations who may experience more frequent disruptions in methods utilized for digital communication., (© 2024 The Author(s).)

Objective: Suicide is of primary public concern for adolescents and young adults (AYAs) who commonly use social media platforms to express their suicidal thoughts and behaviors. Understanding how AYAs communicate their suicide-related thoughts and behaviors in texts can support early detection of suicide risk from their social media posts. Therefore, this study sought to identify themes relevant to suicide risk in AYAs and explore words or terms used by AYAs when they described suicidal thoughts and behaviors., Method: This secondary data analysis utilized an existing data set collected from 255 AYAs between 12 and 25 years of age, who provided brief descriptions of how they and their peers expressed their experiences of self-harm, suicidal thinking, and attempts. Text analysis was conducted using KH Coder software. Three-step theory of suicide was used to guide a content analysis to explore the key themes from the narratives., Results: A word co-occurrence network with 24 clusters of words was generated from the text analysis. These word clusters were further grouped into pain or hopelessness , connectedness , and capacity to attempt suicide in the content analysis. Six subthemes corresponding to these three themes were identified to provide detailed information: psychological or physical pain , hopelessness , relationship , help seeking , methods , and outcomes . Moreover, several slang terms and acronyms (e.g., Kermit Sewage Slide, KMS ) were also identified., Conclusions: The findings of this study, including themes and slang terms and acronyms, are valuable to facilitate the use of terms or phrases within social media texts to identify suicide risk in AYAs., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Macrophage-derived foam cells are a hallmark of atherosclerosis. Scavenger receptors, including lectin-like oxidized low-density lipoprotein (LDL) receptor-1 (OLR-1), are the principal receptors responsible for the uptake and modification of LDL, facilitating macrophage lipid load and the uptake of oxidized LDL by arterial wall cells. Krüppel-like factor 15 (KLF15) is a transcription factor that regulates the expression of genes by binding to the promoter during transcription. Therefore, this study aimed to investigate the precise role of macrophage KLF15 in atherogenesis., Methods: We used two murine models of atherosclerosis: mice injected with an adeno-associated virus (AAV) encoding the Asp374-to-Tyr mutant version of human PCSK9, followed by 12 weeks on a high-fat diet (HFD), and ApoE -/-- mice on a HFD. We subsequently injected mice with AAV-KLF15 and AAV-LacZ to assess the role of KLF15 in the development of atherosclerosis in vivo. Oil Red O, H&E, and Masson's trichome staining were used to evaluate atherosclerotic lesions. Western blots and RT-qPCR were used to assess protein and mRNA levels, respectively., Results: We determined that KLF15 expression was downregulated during atherosclerosis formation, and KLF15 overexpression prevented atherosclerosis progression. KLF15 expression levels did not affect body weight or serum lipid levels in mice. However, KLF15 overexpression in macrophages prevented foam cell formation by reducing OLR-1-meditated lipid uptake. KLF15 directly targeted and transcriptionally downregulated OLR-1 levels. Restoration of OLR-1 reversed the beneficial effects of KLF15 in atherosclerosis., Conclusion: Macrophage KLF15 transcriptionally downregulated OLR-1 expression to reduce lipid uptake, thereby preventing foam cell formation and atherosclerosis. Thus, our results suggest that KLF15 is a potential therapeutic target for atherosclerosis., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023. Published by Elsevier Ltd.)

Ginseng is rich of polysaccharides, however, the evidence supporting polysaccharides to distinguish various ginseng species is rarely reported. Focusing on six root ginseng (e.g., Panax ginseng-PG, P. quinquefolius-PQ, P. notoginseng-PN, red ginseng-RG, P. japonicus-PJ, and P. japonicus var. major-PJM), the contained non-starch polysaccharides (NPs) were structurally characterized and compared by both the chemical and biological evaluation. Holistic fingerprinting at three levels (the NPs and the acid hydrolysates involving oligosaccharides and monosaccharides) utilized various chromatography methods, and the treatment of H9c2 cells with the NPs by OGD and H 2 O 2 -induced injury models was used to assess the protective effect. NPs from six Panax herbal medicines occupied about 20 % of the total polysaccharides, which were of the highest content in RG and the lowest in PN. NPs from six ginseng exhibited weak differentiations in the molecular weight distribution, while marker oligosaccharides were found to distinguish PN and RG from the others. Glc and GalA were more abundant in the NPs for PG and RG, respectively. NPs from PQ (100/200 μg/mL) showed significant cardiomyocyte protection effect by regulating the mitochondrial functions. This work further testifies the role of polysaccharides in quality control of herbal medicine, with new markers discovered beneficial to distinguish the ginseng., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Patients with Rett syndrome suffer from a loss-of-function mutation of the Mecp2 gene, which results in various symptoms including autistic traits and motor deficits. Deletion of Mecp2 in the brain mimics part of these symptoms, but the specific function of methyl-CpG-binding protein 2 (MeCP2) in the cerebellum remains to be elucidated. Here, we demonstrate that Mecp2 deletion in Purkinje cells (PCs) reduces their intrinsic excitability through a signaling pathway comprising the small-conductance calcium-activated potassium channel PTP1B and TrkB, the receptor of brain-derived neurotrophic factor. Aberration of this cascade, in turn, leads to autistic-like behaviors as well as reduced vestibulocerebellar motor learning. Interestingly, increasing activity of TrkB in PCs is sufficient to rescue PC dysfunction and abnormal motor and non-motor behaviors caused by Mecp2 deficiency. Our findings highlight how PC dysfunction may contribute to Rett syndrome, providing insight into the underlying mechanism and paving the way for rational therapeutic designs., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: To design an interface to support communication of machine learning (ML)-based prognosis for patients with advanced solid tumors, incorporating oncologists' needs and feedback throughout design., Materials and Methods: Using an interdisciplinary user-centered design approach, we performed 5 rounds of iterative design to refine an interface, involving expert review based on usability heuristics, input from a color-blind adult, and 13 individual semi-structured interviews with oncologists. Individual interviews included patient vignettes and a series of interfaces populated with representative patient data and predicted survival for each treatment decision point when a new line of therapy (LoT) was being considered. Ongoing feedback informed design decisions, and directed qualitative content analysis of interview transcripts was used to evaluate usability and identify enhancement requirements., Results: Design processes resulted in an interface with 7 sections, each addressing user-focused questions, supporting oncologists to "tell a story" as they discuss prognosis during a clinical encounter. The iteratively enhanced interface both triggered and reflected design decisions relevant when attempting to communicate ML-based prognosis, and exposed misassumptions. Clinicians requested enhancements that emphasized interpretability over explainability. Qualitative findings confirmed that previously identified issues were resolved and clarified necessary enhancements (eg, use months not days) and concerns about usability and trust (eg, address LoT received elsewhere). Appropriate use should be in the context of a conversation with an oncologist., Conclusion: User-centered design, ongoing clinical input, and a visualization to communicate ML-related outcomes are important elements for designing any decision support tool enabled by artificial intelligence, particularly when communicating prognosis risk., (© The Author(s) 2023. Published by Oxford University Press on behalf of the American Medical Informatics Association.)

Background: Pediatric cancer disrupts the lives of siblings in many ways, including physical separations from family and friends that increase risk for distress. Research suggests that siblings use technology and social media to connect with friends and family and seek social support and interaction. However, this may expose siblings to negative online experiences that can erode self-esteem, reducing resilience., Objective: This study explored the relationship between online experiences, internet-fostered connection, resilience, and psychosocial health among siblings of children with cancer., Methods: Participants included adolescent siblings (N = 81; aged 12-17 years) of children with cancer. Most were female (56.8%), and 50.6% represented racially or ethnically minoritized groups. Online experiences, social media use, resilience, and psychosocial health were self-reported and analyzed using structural equation modeling., Results: A majority of siblings reported moderate to severe posttraumatic stress symptoms (PTSSs) (59%) and elevated emotional and behavioral difficulties (EBDs) (53%). Experiencing more positive online experiences was associated with greater perceived connection to family and friends online, but not resilience, PTSSs, or EBDs. In contrast, higher negative online experience scores were significantly associated with more PTSSs and EBDs. In addition, the association between negative online experiences and EBDs was significantly mediated by a negative association between negative online experiences and resilience., Conclusions: Although social media may be a valuable tool for helping siblings of children with cancer garner social support, negative online experiences may be detrimental to their adjustment., Implications for Practice: Efforts should be made to preserve and foster resilience among siblings who use social media for support., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: A diagnosis of pediatric cancer can leave healthy siblings with limited access to support. Technology-mediated interpersonal interactions have been noted among adolescent and young adults with cancer and may be an effective source of support for adolescent siblings of children with cancer. In this study, we understand how adolescent siblings use technology to connect with their support network and how their technology use changes after their sibling's cancer diagnosis. Methods: Participants included a national sample ( N  = 24) of adolescents aged 12-17 who had a sibling diagnosed with cancer in the last 2 years (up to 3 years if still receiving curative-focused treatment). Ecomaps were cocreated with participants to identify sources of social support and modality of interactions. Interviews were transcribed, coded, content analyzed, and descriptively summarized. Results: Adolescent siblings (mean = 14.2 years) perceived technology as a tool to maintain support from their established personal network, rather than a way to expand sources of social support. Most did not seek support or information about cancer outside their known network, preferring information to come from parents or trusted network members. Siblings identified video calls as an important resource for connecting with parents, their sick brother or sister, and others to receive emotional support and companionship. Conclusions: Findings suggest that adolescent siblings of children use technology to connect with their established network for support, an important finding for designing assessments and interventions for this population. Future inquiry should explore these differences, identify unmet needs, and inform acceptable, effective interventions to augment support.

Purpose: The purpose of this mixed-methods psychometric study was to translate and adapt the Arabic Pain Care Quality (APainCQ) Survey to Arabic and to measure the quality of pain care provided to Arab patients., Patients and Methods: This study used an iterative, mixed-methods approach that employed cognitive interviews, expert content analysis, and factor analysis to develop the APainCQ Survey. The study was conducted at Dubai Hospital, Dubai Health Authority, United Arab Emirates. Arabic-speaking patients admitted to the oncology/hematology inpatient units with a minimum 24-hour stay were eligible for the study., Results: The sample consisted of 155 patients. The iterative exploratory factor analysis process resulted in the sequential removal of three items. The results of the significant Bartlett test ( P < .001) of sphericity and Kaiser-Meyer-Olkin test of 0.93 for both the health care team scale and the nurse scale. The total variance explained was 76.17% for the health care team scale and 60.91% for the nurse scale, which explained 56.51% for factor 1 with 14 items and 4.40% for factor 2. Regarding internal consistency reliability, Cronbach's alpha and McDonald's omega for the health care team scale and nurse scale were high; both values were .95. Internal consistency reliability of pain assessment and pain management subscales of nurse scales were also high, with values of 0.96 and 0.79, respectively. Moreover, there was a moderate correlation ( r = 0.66; P < .001) between the two subscales in the nurse scale., Conclusion: This study provides evidence that the APainCQ is a reliable and valid measure of pain dimensions, including pain management and monitoring. This APainCQ scale can potentially expand research and clinical assessment in the Arab world.

More than 30% of fruits of Chinese Quince (Chaenomeles speciosa) and peach (Prunus persica) showed circular, water-soaked and brown spots in July 2022 in Kunming, Yunnan, China. The center of these spots was covered by a large number of earthy brown and oblate sporogeneous mycelium containing conidiophore and conidia, which were one-celled, limoniform, hyaline (13.73 to 22.77 x 8.17 to 12.84 µm, n=50). By September 2022, almost 100% of fruits showed symptoms. Later, most of them fell or a few stiff, black and mummified fruits were left on the trees. Fungal isolates were isolated by single-spore technique on Potato Dextrose agar (PDA) from the diseased fruits, and incubated at room temperature (20-28 °C) in darkness for 14 days. The colony was gray, smooth at margins, 7.6-8.0 cm in diameter. To fullfill Koch's postulates, mycelial plugs of one representative isolate YHD611 from Chinese Quince and another YHD610 from peach were used to inoculate three wounded and three non-wounded surface-disinfected fruits of both hosts at room temperature (19-27 °C), respectively. Three wounded and three non-wounded fruits inoculated with sterile PDA plugs served as the control. The wounded peaches appeared water-soaked and had brown lesions after three days of inoculation, then completely decayed after nine days, while non-wounded fruits showed symptoms after five days. The wounded fruits of Chinese Quince developed similar symptoms after eight days of inoculation, and completely decayed after 13 days, while non-wounded fruits showed obvious symptoms after 15 days. In a subsequent study, isolate YHD611 was inoculated to peach while isolate YHD610 was inoculated to Chinese Quince to understand host specificity of the isolates. The results showed that when peaches were infected with YHD611, symptoms were observed on wounded fruits after three days while on non-wounded fruits after five days. When Chinese Quince was infected with YHD610, symptoms were observed on wounded fruits after 14 days while on non-wounded fruits after 21 days. Fungal isolates from symptomatic fruits were identical to the original isolates. There were no symptoms on the control fruits of both hosts. Molecular identification was confirmed based on the sequences of internal transcribed spacer (ITS, primers ITS1 and ITS4) and β-tubulin (TUB2, primers Bt2a and Bt2b) genes (Niu et al. 2016). BLASTn analysis of the ITS (OQ15519and OQ155196) and TUB2 (OQ185202 and OQ185201) of YHD611 and YHD610 revealed a 100% sequence identity, respectively, to Monilia yunnanensis AH7-2 (KT735924.1 for ITS, KT736008.1 for TUB2). In the phylogenetic analyses based on ITS and TUB2 sequence data, the isolates YHD611 and YHD610 belonged to the M. yunnanensis clade. Based on morphological and molecular identification, both isolates were identified as M. yunnanensis, which was reported as the pathogen causing brown rot of plum, peach, apple and pear in Yunnan, China (Hu et al. 2011; Yin et al. 2015). To our knowledge, this is the first report of M. yunnanensis causing brown rot on the fruits of Chinese Quince in Yunnan, China. This study also reports that M. yunnanensis from Chinese Quince can infect peach, and the pathogen from peach can infect Chinese Quince. These findings suggest that M. yunnanensis can transfer from one host to another and causing serious economic losses in multiple fruit crops in Yunnan, China. References: Hu, M. J., et al. 2011. PLoS One. 6:e24990. Niu, C. W., et al. 2016. Mycosystema, 35(10):1. Yin, L. F., et al. 2015. Plant Dis. 99:1775.

(1) Background: Human keratinocytes and murine skin express various cytochrome P450 enzymes. These include cytochrome P450 3A4, which may participate in the metabolism of cytochrome P450 3A4 substrate drugs. Desoximetasone, a topical corticosteroid and cytochrome P450 3A4 substrate, is used to treat skin conditions such as skin allergies, atopic dermatitis, and psoriasis. In this study, we aimed to investigate the anti-psoriatic effect of a low dose of desoximetasone by inhibiting cytochrome P450 3A4 metabolism in the epidermis. (2) Methods: Psoriasis-like skin was induced in BALB/c mice via the topical administration of imiquimod. The mice were then topically treated with 0.01-0.05% desoximetasone loaded into a cytochrome P450 3A4 enzyme inhibitor excipient base emollient microemulsion, 0.25% commercial desoximetasone ointment, or 0.5 mg/gm clobetasol ointment. (3) Results: The topical application of 0.05% desoximetasone loaded into a cytochrome P450 3A4 enzyme inhibitor excipient base emollient formulation restored the imiquimod-induced skin barrier disruption and resulted in fewer severe clinical and pathological features compared with the treatments with 0.25% commercial desoximetasone ointment and 0.5 mg/gm clobetasol ointment. (4) Conclusions: The cytochrome P450 3A4 enzyme inhibitor excipient base emollient formulation improved and prolonged the therapeutic effect of cytochrome P450 3A4 substrate drugs and may be a promising approach for psoriasis treatment.

Scaling up superconducting nanowire single-photon detectors (SNSPDs) into a large array for imaging applications is the current pursuit. Although various readout architectures have been proposed, they cannot resolve multiple-photon detections (MPDs) currently, which limits the operation of the SNSPD arrays at high photon flux. In this study, we focused on the readout ambiguity of a superconducting nanowire single-photon imager applying time-of-flight multiplexing readout. The results showed that image distortion depended on both the incident photon flux and the imaging object. By extracting multiple-photon detections on idle pixels, which were virtual because of the incorrect mapping from the ambiguous readout, a correction method was proposed. An improvement factor of 1.3~9.3 at a photon flux of µ = 5 photon/pulse was obtained, which indicated that joint development of the pixel design and restoration algorithm could compensate for the readout ambiguity and increase the dynamic range.

Objective: We evaluated nursing-related free-text communication orders to identify potential safety hazards and describe patterns and scope of care domains addressed that may reveal preventable workarounds and potential gaps in electronic health record (EHR) functionality., Materials and Methods: A retrospective analysis of free-text EHR-based communication orders sent to or by nurses providing inpatient care at a major academic health system. Using built-in EHR tools and selection criteria, 13 193 orders were extracted, including 1373 unique orders. Using the Clinical Care Classification system standardized framework, we classified content by care domain and identified unique requests within each order. We reviewed each order for error-prone textual features based on standard patient safety guidance. We describe the distribution of domains, co-occurrence when 2 domains were present, and common patterns., Results: The 1373 unique orders included a single request (65.3%), 2 requests related to 1 or 2 domains (19%), or 3 or more requests (15.7%). No orders included terms on the Joint Commission's "Do Not Use" list. However, 13.6% of unique orders, and 16.7% of those related to medications, included error-prone symbols or abbreviations according to Institute for Safe Medication Practices guidance. Order content spanned 20 different care components but physical regulation, fluid volume, nutritional, safety, and medication were most frequently identified as single or co-occurring topics. Patterns were heterogenous., Discussion: Free-text communication orders reveal workarounds, responses to upstream workarounds, and design constraints that should be further investigated. Remediation strategies are needed to reduce safety hazards and workflow impediments., Conclusions: Analysis of free-text communication orders revealed opportunities for improvement., (© The Author(s) 2023. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Inflammatory mechanisms play important roles in intracerebral hemorrhage (ICH) and have been linked to the development of stroke-associated pneumonia (SAP). The neutrophil-to-lymphocyte ratio (NLR), systemic immune-inflammation index (SII), platelet-to-lymphocyte ratio (PLR) and systemic inflammation response index (SIRI) are inflammatory indexes that influence systemic inflammatory responses after stroke. In this study, we aimed to compare the predictive value of the NLR, SII, SIRI and PLR for SAP in patients with ICH to determine their application potential in the early identification of the severity of pneumonia., Methods: Patients with ICH in four hospitals were prospectively enrolled. SAP was defined according to the modified Centers for Disease Control and Prevention criteria. Data on the NLR, SII, SIRI and PLR were collected at admission, and the correlation between these factors and the clinical pulmonary infection score (CPIS) was assessed through Spearman's analysis., Results: A total of 320 patients were enrolled in this study, among whom 126 (39.4%) developed SAP. The results of the receiver operating characteristic (ROC) analysis revealed that the NLR had the best predictive value for SAP (AUC: 0.748, 95% CI: 0.695-0.801), and this outcome remained significant after adjusting for other confounders in multivariable analysis (RR=1.090, 95% CI: 1.029-1.155). Among the four indexes, Spearman's analysis showed that the NLR was the most highly correlated with the CPIS (r=0.537, 95% CI: 0.395-0.654). The NLR could effectively predict ICU admission (AUC: 0.732, 95% CI: 0.671-0.786), and this finding remained significant in the multivariable analysis (RR=1.049, 95% CI: 1.009-1.089, P=0.036). Nomograms were created to predict the probability of SAP occurrence and ICU admission. Furthermore, the NLR could predict a good outcome at discharge (AUC: 0.761, 95% CI: 0.707-0.8147)., Conclusions: Among the four indexes, the NLR was the best predictor for SAP occurrence and a poor outcome at discharge in ICH patients. It can therefore be used for the early identification of severe SAP and to predict ICU admission., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Wang, Wen, Jiang, Du, Ma, Lu, Li, Yuan, Wu, Guo, Cai, Huang, Wang and Lu.)

Objective: Anti-Ro60 and anti-Ro52 antibodies are associated with different connective tissue diseases (CTDs). However, the clinical significance of anti-Ro antibodies is not always consistent among different global regions. The aim of this study was to investigate the clinical characteristics of patients with anti-Ro antibodies., Methods: A total of 1596 inpatients with anti-Ro antibodies were included in the study. Demographic, clinical, and serological data were compared between individuals with different profiles of anti-Ro antibodies: patients with anti-Ro52 antibodies alone, patients with anti-Ro60 antibodies alone, and patients with combined anti-Ro52 and anti-Ro60 antibodies., Results: Of the 1596 patients, 1362 (85.3%) were female, the mean age was 45.5 years, and systemic lupus erythematosus (SLE) (46.0%) and Sjogren's syndrome (SS) (19.0%) were the most common CTD diagnoses. Among the patients with anti-Ro52 antibodies alone, idiopathic inflammatory myopathy (18.8%) and SLE (17.6%) were the most common CTD diagnoses. The coexistent autoantibodies of this group were significantly lower compared with those of the other two groups, while the presence of anti-Jo1 antibodies were significantly higher compared with those of the other two groups (3.7% vs. 0.6% vs. 1.9%, p = 0.029). In addition, the patients with isolated anti-Ro52 antibodies were more likely to suffer from interstitial lung disease (35.5% vs. 11.3% vs. 13.7%, p < 10 -4 ) and pulmonary arterial hypertension (10.1% vs. 5.3% vs. 3.6%, p = 0.001) compared with the other two groups of patients. Compared with patients with isolated anti-Ro52 or anti-Ro60 antibodies, the patients with combined anti-Ro52 and anti-Ro60 antibodies were more likely to suffer from xerophthalmia and xerostomia. Furthermore, hypocomplementemia, hyperglobulinemia, and proteinuria were particularly prevalent in patients with anti-Ro60 antibodies., Conclusion: Different profiles of anti-Ro antibodies were significantly associated with clinical phenotypic features in CTDs, indicating the potential diagnostic and prognostic value of these antibodies in clinical practice., Competing Interests: The authors have declared that they have no competing interests., (Copyright © 2023 Hai-Tao Yang et al.)

Background: Polymyositis (PM) and dermatomyositis (DM) are non-suppurative and autoimmune inflammatory diseases of striated muscle. Interstitial lung disease (ILD) is a group of heterogeneous diseases that mainly involve the pulmonary interstitium, alveoli, and/or bronchioles, also known as diffuse parenchymal lung disease (DPLD). A significant cause of death in persons with polymyositis (PM) and dermatomyositis (DM) is concurrent interstitial lung disease (ILD). However, research on the clinical characteristics and associated influencing factors of PM/DM combined with ILD (PM/DM-ILD) is currently scarce in China., Objective: The study aimed to probe the clinical features and risk factors of PM/DM-ILD., Methods: The data of 130 patients with PM/DM were gathered. General medical status, clinical symptoms, laboratory parameters, high-resolution CT, therapeutic outcomes, and prognoses were retrospectively reviewed in patients with PM/DM with (ILD group) and without (NILD) ILD., Results: The age of the ILD group (n=65) was more than the NILD group (n=65), and the difference was statistically significant; there were no significant between-group variations in the PM/DM ratio, sex, or duration of the disease. The initial symptoms were arthritis and respiratory symptoms in the ILD group, and myasthenia symptoms in the NILD group. Incidences of Raynaud's phenomenon, dry cough, expectoration, dyspnea on exertion, arthritis, fever, total globulin (GLOB), erythrocyte sedimentation rate (ESR), and anti-Jo-1 antibody rate were higher for ILD; however, albumin (ALB), creatine kinase aspartate aminotransferase activity ratio (CK/AST) and CK levels were significantly lower in the ILD group. Bivariate logistic regression analysis showed age, dry cough, arthritis, dyspnea on exertion, anti-Jo-1 antibody, and elevated GLOB to be independent risk factors for ILD among patients with PM/DM., Conclusion: Advanced age, dry cough, arthritis, dyspnea on exertion, anti-Jo-1 antibody positivity, and elevated GLOB level are risk factors for PM/DM-ILD. This information could be utilized to carefully monitor changing lung function in these patients., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: One of the most serious complications of sepsis is sepsis-associated encephalopathy (SAE), which impairs the cognition ability of survivors. Environmental enrichment (EE) has been demonstrated to alleviate cognition deficits under many kinds of brain injury conditions. However, EE's effects on SAE remain unknown. Therefore, this study aimed to determine EE's effect on cognition disorders under SAE conditions and the underlying mechanism., Materials and Methods: Adult male rats, subject to SAE or not, were housed under a standard environment (SE) or EE for 30 days. Subsequently, the rats were subjected to cognitive tests, such as the novel object recognition (NOR) test, the Morris water maze (MWM) test, an Open Field (OF) test, the elevated plus maze (EPM) test, and a sensory neglect (SN) test. Neuroinflammation, apoptosis, and oxidative stress changes in the brain were also detected., Results: The results revealed that SAE impaired somatesthesia, recognition memory, spatial learning and memory, and exploratory activity, which were significantly improved by EE housing. EE also prevented SAE-induced anxiety-like behavior. In addition, EE housing capable induced a decrease in pro-inflammatory cytokines, and an increase in anti-inflammatory cytokines and antioxidant properties in the brain. Moreover, EE housing exerted an anti-apoptosis function by upregulating the level of B-cell lymphoma/leukemia-2 (Bcl-2) level and downregulating the level of p53 level in the hippocampus., Conclusions: The results of the present study indicated that EE exerts a neuroprotective function on cognitive ability in SAE rats. The effect is achieved by increasing antioxidants, and anti-inflammatory and antiapoptotic capacities. EE can effectively rescue SAE-induced cognitive deficits., Competing Interests: The authors declare no conflict of interest., (© 2022 The Author(s). Published by IMR Press.)

Since 1999, the "Grain for Green" Program has been extensively implemented in the Loess Plateau region. This measure has largely been of concern not only for its contribution to soil erosion reduction but also for its effects on carbon sequestration. The aim of this study was to assess the carbon sequestration characteristics of different restored vegetation types in areas with severe soil erosion on the Loess Plateau and to compare the effects of restoration age and slope direction on the vegetation carbon sequestration. To evaluate the carbon density and composition characteristics of different ecosystem types, six typical vegetation types (including farmland, grassland, Hippophae rhamnoides Linn., Caragana korshinskii Kom., Robinia pseudoacacia L., and Populus davidiana Dode.) were selected in the Loess Hilly Region, i.e., Wuqi County and Zhidan County in Northern Shaanxi province, which is a typical area for the implementation of artificial vegetation restoration. The results showed that:① vegetation restoration in the semi-arid loess region had a profound impact on carbon sequestration. The carbon density of different vegetations, as well as different vegetation components including above-ground vegetation, below-ground roots, and litter, shared the same pattern as tree>scrub>grassland>farmland. The 0-40 cm soil layer of the farmland showed the lowest soil organic carbon density (1355.5 g·m -2 ), compared to which those of grassland, H. rhamnoides Linn., C. korshinskii Kom., R. pseudoacacia L., and P. davidiana Dode. were higher by 91.4%, 125.2%, 144.0%, 124.5%, and 232.6%, respectively. ② It was common in grassland, H. rhamnoides Linn., C. korshinskii Kom., and P. davidiana Dode. for the carbon density of different vegetation components as well as soil organic carbon density of different soil layers (0-5, 5-20, and 20-40 cm) to generally show an increasing trend with increased restoration age. ③ Slope direction had a significant impact on the vegetation carbon density only for H. rhamnoides Linn., C. korshinskii Kom., R. pseudoacacia L., and P. davidiana Dode., while showing the contrary for farmland and grassland. Soil organic carbon densities for sunny slopes were significantly lower than those for shaded slopes by 22.9%, 34.3%, 75.8%, 49.1%, 22.4%, and 69.4%, respectively, for farmland, grassland, H. rhamnoides Linn., C. korshinskii Kom., R. pseudoacacia L., and P. davidiana Dode. ④ Ecosystem carbon density varied significantly for different ecosystem types, among which farmland showed the lowest (2022.1 g·m -2 ), and grassland, H. rhamnoides Linn., C. korshinskii Kom., R. pseudoacacia L., and P. davidiana Dode. showed values higher by 48.7%, 152.8%, 125.1%, 166.3%, and 530.7%, respectively. The carbon density of each ecosystem component showed a pattern as follows:soil layer>above-ground vegetation layer>root layer>litter layer. Soil organic carbon constituted the main part of the ecosystem carbon density and accounted for 67.0%, 86.3%, 59.7%, 72.7%, and 56.5%, respectively, for farmland, grassland, H. rhamnoides Linn., C. korshinskii Kom., and R. pseudoacacia L. These results can provide an essential basis for scientific management of ecosystem carbon pools and promote ecological environment management on the Loess Plateau.

Food insecurity is a complex problem affected by a number of factors from individual to societal. While individual-level demographic information and population-level social determinants of health (SDoH) are commonly used to identify patients at risk of food insecurity and to direct resources, a more comprehensive understanding of food insecurity requires integrating multi-level data. Our goal is to identify factors associated with food insecurity using patient, health system, and population level data. Between January 2019 and April 2020, we screened adult patients visiting an academic health sciences emergency department in Utah using a 10-item social needs screener. Patients' demographic data were linked to their screener responses. ZIP Code-level food-related SDoH such as accessibility to food providers, measured by geographic information systems methods, were assigned to patients. We then applied multilevel logistic regression modeling to identify factors associated with unmet food needs at two different levels-individual and ZIP Code. Unmet food needs were identified by asking patients if they felt there was not enough money for food in the last month, which grossly represents food insecurity. On a sample of 2,290 patients, 21.61% reported unmet food needs. Patient-reported housing, medical care, and utility needs along with Supplemental Nutrition Assistance Program participation and primary care provider utilization were highly associated with unmet food needs. Our efforts to identify the population at risk of food insecurity should be centered around patient-reported social needs. Our results suggest that addressing food insecurity in health care settings should include assessing social needs in primary care., Competing Interests: 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., (© 2022 The Author(s).)

This study examined the psychometric properties of the Screener for Intensifying Community Referrals for Health (SINCERE), a 10-item, low literacy screening tool developed to elicit social needs (e.g., transportation, housing) impacting patients' ability to engage in health-related activities. Patients seeking care in a tertiary care emergency department (ED) were invited to complete the SINCERE as part of registration processes, and were asked about their desire for follow-up by a partnering service provider offering low- and no-cost community resource referrals. A total of 5,081 patients completed screenings were included in this sample. Exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) identified and verified one-factor structure, suggesting that the SINCERE's 10-items are homogenous and measure one construct. The reliability of Cronbach's α and McDonald's ω were 0.89. Item Response Theory (IRT) suggested the SINCERE can effectively identify patients wishing referrals, or who have social needs. Moreover, patients who had two or more social needs were those willing to receive referrals after discharge. The SINCERE is a valid and reliable tool for measuring social needs for health, and should be considered as a screening option for practice interventions seeking to address social needs.

Purpose: The purpose of this study was to test the feasibility, usability, and acceptability of implementing a web-based method for collecting social network and longitudinal daily interaction data from cancer survivors and their caregivers., Methods: Young adult and sexual/gender minority cancer survivors and their informal caregivers were recruited as dyads. Feasibility data, including enrollment and retention, were captured. Individual social network data were collected at baseline and used to individualize daily electronically delivered surveys assessing characteristics of daily social support-related interactions with identified network members for 14 days. Follow-up questionnaires assessing usability and exit interviews assessing acceptability were completed at the end of the 2-week study period., Results: Fourteen survivor-caregiver dyads (28 individual participants) were enrolled and completed all baseline and final measures. Participants completed 85.2% of daily diary reports and reported excellent usability ratings. Acceptability was also high. In qualitative interviews, participants reported enjoying the daily reflection on social support facilitated by our methods., Conclusions: Our method has been shown to be highly feasible, usable, and acceptable., Implications for Cancer Survivors: Developing better data collection tools can lead to better understanding of the social support cancer survivors and their caregivers receive, and how the social network structure facilitates or creates barriers to accessing this support., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

A superconducting nanowire single-photon imager (SNSPI) uses a time-multiplexing method to reduce the readout complexity. However, due to the serial connection, the nanowire should be uniform so that a common bias can set all segments of the nanowire to their maximum detection efficiency, which becomes more challenging as the scalability (i.e., the length of the nanowire) increases. Here, we have developed a 64-pixel SNSPI based on amorphous Mo 80 Si 20 film, which yielded a uniform nanowire and slow transmission line. Adjacent detectors were separated by delay lines, giving an imaging field of 270 µm × 240 µm. Benefiting from the high kinetic inductance of Mo 80 Si 20 films, the delay line gave a phase velocity as low as 4.6 µm/ps. The positions of all pixels can be read out with a negligible electrical cross talk of 0.02% by using cryogenic amplifiers. The timing jitter was 100.8 ps. Saturated internal quantum efficiency was observed at a wavelength of 1550 nm. These results demonstrate that amorphous film is a promising material for achieving SNSPIs with large scalability and high efficiency.

(1) Background: Psoriasis is a T helper 1/T helper 17 cells-involved immune-mediated genetic disease. Lithospermic acid, one of the major phenolic acid compounds of Danshen, has antioxidation and anti-inflammation abilities. Due to the inappropriate molecular weight for topical penetration through the stratum corneum, lithospermic acid was loaded into the well-developed microemulsion delivery system for IMQ-induced psoriasis-like dermatitis treatment. (2) Methods: BALB/c mice were administered with topical imiquimod to induce psoriasis-like dermatitis. Skin barrier function, disease severity, histology assessment, autophagy-related protein expression, and skin and spleen cytokine expression were evaluated. (3) Results: The morphology, histopathology, and skin barrier function results showed that 0.1% lithospermic acid treatment ameliorated the IMQ-induced psoriasis-like dermatitis and restored the skin barrier function. The cytokines array results confirmed that 0.1% lithospermic acid treatment inhibited the cutaneous T helper-17/Interleukin-23 axis related cytokines cascades. (4) Conclusions: The results implied that lithospermic acid might represent a possible new therapeutic agent for psoriasis treatment.

Introduction: Acute appendicitis is one of the most common causes of intra-abdominal emergency surgery worldwide. This study was conducted to contribute to global databases by presenting data from our institution, which consist of multi-racial population. We aimed to evaluate the presentation, diagnosis, and management of acute appendicitis and post-operative outcome in our institution and evaluate the risks factors associated with severe complications and prolonged length of stay (LOS)., Materials and Methods: We performed a retrospective analysis using multivariate regression analysis of all patients who underwent appendectomy (2009-2014) in our institution. The primary outcomes included demographics, presentation, and perioperative management, and the secondary outcomes included risk factors associated with prolonged LOS., Results: Of the 1185 patients, the mean age was 36.4 years, and 940 (79.3%) were male. Majority (98.1%) of patients were ASA (American Society of Anaesthesiologists) 1 or 2. Most of them (83.9%) were from the four racial subgroups (Chinese, Malay, Bangladeshi, and Indian). There was no racial variation in the diagnosis and presentation of disease. The mean duration of symptoms was 1.8 days. The history was commonly a localised or migratory abdominal pain associated with anorexia, nausea, vomiting, and fever. The commonest physical findings were right-sided abdominal tenderness associated with rebound and guarding. About 42.9% of the patients underwent pre-operative CT scan to establish the diagnosis of appendicitis prior to surgery, whilst 57.1% underwent surgery on clinical diagnosis and blood investigation (NWR and CRP). An open appendectomy was performed in 13.2% of the patients. The conversion rate of laparoscopic appendectomy was 4.9% (n = 50). The mean length of hospital stay was 3.6 days. On multivariate Cox regression, patients of Burmese and Thai descent were independently associated with a prolonged LOS. The postoperative morbidity was 5.5%. The 30-day readmission rate was 2.4%. There was no mortality in our study., Discussion: Our study showed that pre-operative diagnosis of acute appendicitis can be made accurately by classical clinical presentation or by imaging. Independent risk factors associated with increased LOS included increased age, male gender, prolonged duration of symptoms pre-admission, fever, generalised tenderness, and prolonged operative time. The effect of race on LOS has been observed in the literature for other surgical procedures. The prolonged LOS found in Burmese and Thai patients contribute to the possibility of intrinsic racial differences in the post-surgery recovery. However, the numbers are small and therefore prone to type I error. Compared to the open approach, the use of laparoscopic appendectomy was associated with shorter LOS. This has similar outcomes to those reported in the literature., Conclusion: The identification of risks factors could help surgical team to predict the clinical outcomes and develop risk reduction strategy in post-operative care of these patients.

Osteoarthritis (OA) is the most common arthritis with a rapidly increasing prevalence. Disease progression is irreversible, and there is no curative therapy available. During OA onset, abnormal mechanical loading leads to excessive osteoclastogenesis and bone resorption in subchondral bone, causing a rapid subchondral bone turnover, cyst formation, sclerosis, and finally, articular cartilage degeneration. Moreover, osteoclast-mediated angiogenesis and sensory innervation in subchondral bone result in abnormal vascularization and OA pain. The traditional Chinese medicine Panax notoginseng (PN; Sanqi) has long been used in treatment of bone diseases including osteoporosis, bone fracture, and OA. In this study we established two-dimensional/bone marrow mononuclear cell/cell membrane chromatography/time of flight mass spectrometry (2D/BMMC/CMC/TOFMS) technique and discovered that diterbutyl phthalate (DP) was the active constituent in PN inhibiting osteoclastogenesis. Then we explored the therapeutic effect of DP in an OA mouse model with anterior cruciate ligament transaction (ACLT). After ACLT was conducted, the mice received DP (5 mg·kg -1 ·d -1 , ip) for 8 weeks. Whole knee joint tissues of the right limb were harvested at weeks 2, 4, and 8 for analysis. We showed that DP administration impeded overactivated osteoclastogenesis in subchondral bone and ameliorated articular cartilage deterioration. DP administration blunted aberrant H-type vessel formation in subchondral bone marrow and alleviated OA pain assessed in Von Frey test and thermal plantar test. In RANKL-induced RAW264.7 cells in vitro, DP (20 μM) retarded osteoclastogenesis by suppressing osteoclast fusion through inhibition of the ERK/c-fos/NFATc1 pathway. DP treatment also downregulated the expression of dendritic cell-specific transmembrane protein (DC-STAMP) and d2 isoform of the vacuolar (H+) ATPase V0 domain (Atp6v0d2) in the cells. In conclusion, we demonstrate that DP prevents OA progression by inhibiting abnormal osteoclastogenesis and associated angiogenesis and neurogenesis in subchondral bone., (© 2021. The Author(s), under exclusive licence to CPS and SIMM.)