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This case report describes a rare occurrence of a 25-year-old female diagnosed with both systemic sclerosis (SSc) and ankylosing spondylitis (AS), two distinct autoimmune diseases. The patient presented with a combination of symptoms, including progressive skin tightening, lumbosacral pain, and Raynaud's phenomenon, which complicated the diagnosis. Despite the challenges posed by the coexistence of SSc and AS, a multidisciplinary treatment approach involving corticosteroids, immunosuppressants, and supportive therapies led to significant clinical improvement. Over the course of 3 weeks, the patient's Rodnan Skin Score improved from 18 to 11, and her pain and overall disease activity were markedly reduced. Although skin sclerosis showed substantial improvement, pulmonary involvement remains a concern that requires long-term monitoring. This case highlights the complexities in diagnosing and managing overlap syndromes, emphasizing the need for personalized treatment strategies and further investigation into the underlying genetic and immunological mechanisms., (© 2024 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

Behcet's disease is a rare, chronic inflammatory disorder that can affect various organs, with large vessel involvement being particularly uncommon. This case report discusses a 17-year-old male with Behcet's disease who presented with a rapidly enlarging, painful mass in the right groin region, later diagnosed as a femoral artery aneurysm. The patient underwent successful surgical intervention and was subsequently managed with immunosuppressive therapy to prevent relapse., (© 2024 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

One new isoflavone, 6'-dihydroxy-2-methyl-2'-methoxyl-3'-acetylisoflavone ( 1 ) and six known compounds ( 2 - 7 ) were isolated from the processed root barks of Paeonia suffruticosa . The structures of these compounds were elucidated using UV, IR, NMR, and HR-ESI-MS data. Compound 1 represents the first example of naturally occurring 2-substituted isoflavone. Compounds 2 - 7 were isolated from the processed root barks of P. suffruticosa for the first time. In addition, all of the compounds were screened for their procoagulant activity. As a result, compounds 4 , 6 , and 7 showed significantly in vitro procoagulant activity.

Objective: To evaluate the mid-and long-term clinical outcomes of percutaneous balloon mitral valvuloplasty (PBMV) guided solely by echocardiography. Methods: A total of 71 patients with moderate to severe mitral stenosis who underwent PBMV guided solely by echocardiography at Fuwai Hospital, Chinese Academy of Medical Sciences, from January 2016 to December 2022 were retrospectively included. The clinical data and follow-up information were collected and analyzed. Results: Finally, 71 patients (11 males and 60 females) aged (48.6±12.4) years, including 3 pregnant women were included. One patient required surgical intervention due to moderate to severe mitral regurgitation, resulting in a procedure success rate of 98.6% (70/71). The procedural duration was (84.1±40.2) minutes, with the balloon diameter of (26.5±1.1) mm and number of dilatations of 2.9±0.7. The mean mitral transvalvular pressure gradient decreased from (12.6±6.1) mmHg (1 mmHg=0.133 kPa) preoperatively to (5.4±2.4) mmHg postoperatively, while the mitral valve orifice area increased from (0.9±0.2) cm² to (1.7±0.3) cm² (both P <0.001). Before discharge, 16 patients developed new mild mitral regurgitation, five developed new moderate mitral regurgitation, and one patient had a small amount of pericardial effusion absorbed by herself. No severe complications such as death, pericardial tamponade, or thromboembolism occurred during the perioperative period. The average follow-up duration was 12-84 (49.7±21.4) months. At two years postoperatively, the mean mitral transvalvular pressure gradient was (6.2±2.5) mmHg, and the mitral valve orifice area was (1.6±0.3) cm². Eight patients underwent surgical mitral valve replacement at an median of [ M ( Q 1 , Q 3 )] 18 (5, 53) months postoperatively, and one patient died during the follow-up period due to non-cardiac reasons. Conclusion: The mid-and long-term outcomes of PBMV guided solely by echocardiography are favorable.

Grain weight, a key determinant of yield in rice (Oryza sativa L.), is governed primarily by genetic factors, whereas grain chalkiness, a detriment to grain quality, is intertwined with environmental factors such as mineral nutrients. Nitrogen (N) is recognized for its effect on grain chalkiness, but the underlying molecular mechanisms remain to be clarified. This study revealed the pivotal role of rice NODULE INCEPTION-LIKE PROTEIN 3 (OsNLP3) in simultaneously regulating grain weight and grain chalkiness. Our investigation showed that loss of OsNLP3 leads to a reduction in both grain weight and dimension, in contrast to the enhancement observed with OsNLP3 overexpression. OsNLP3 directly suppresses the expression of OsCEP6.1 and OsNF-YA8, which were identified as negative regulators associated with grain weight. Consequently, two novel regulatory modules, OsNLP3-OsCEP6.1 and OsNLP3-OsNF-YA8, were identified as key players in grain weight regulation. Notably, the OsNLP3-OsNF-YA8 module not only increases grain weight but also mitigates grain chalkiness in response to N. This research clarifies the molecular mechanisms that orchestrate grain weight through the OsNLP3-OsCEP6.1 and OsNLP3-OsNF-YA8 modules, highlighting the pivotal role of the OsNLP3-OsNF-YA8 module in alleviating grain chalkiness. These findings reveal potential targets for simultaneous enhancement of rice yield and quality., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Neuroimaging studies have revealed disturbances in brain functional connectivity (FC) after one night of sleep deprivation (SD). These researches explored the alterations of FC using classical regions of interest (ROI)-based analysis or functional connectivity density. However, these methods need for a priori information about the selected ROIs and a specific correlation threshold to define a connection between two ROIs or voxels, which may bring inconsistent results. In the present study, we adopted a data-driven, whole brain voxel-based graph-theoretical approach, intrinsic connectivity distribution (ICD) analysis, to examine changes of brain connectivity after SD in 52 normal young subjects without any prior knowledge. The cross-hemisphere ICD (ch-ICD) analysis was also performed to discover the effect of SD on cerebral lateralization. We found that sleep-deprived subjects showed significant reduced ICD in default mode network (DMN) and limbic network, and increased ICD in sensorimotor network. Furthermore, after SD, the ICD in the right precuneus showed significant correlation with psychomotor vigilance test (PVT) performance following the stepwise regression analysis after Bonferroni correction (ICD = 0.43 - 0.62∗10 % fast reaction time + 0.31∗the standard deviation of reaction time, p = 0.0012). Follow-up seed-based FC analyses in the right precuneus revealed decreased FC to regions in DMN, visual network, ventral attentional network and frontal-parietal network. Nevertheless, no striking difference of ch-ICD was found following SD. In conclusion, these findings suggested that DMN, especially precuneus may be hubs of FC disturbances associated with vigilance after SD, and may provide new insights into the intervention for SD., 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.)

Drought is one of the most severe environmental factors limiting plant growth and crop yield, necessitating the identification of genes that enhance drought resistance for crop improvement. Through screening an ethyl methyl sulfonate-mutagenized rice mutant library, we isolated the PEG tolerance mutant 97-1 (ptm97-1), which displays enhanced resistance to osmotic and drought stress, and increased yield under drought conditions. A point mutation in OsMATE6 was identified as being associated with the drought-resistant phenotype of ptm97-1. The role of OsMATE6 in conferring drought resistance was confirmed by additional OsMATE6 knockout mutants. OsMATE6 is expressed in guard cells, shoots and roots and the OsMATE6-GFP fusion protein predominantly localizes to the plasma membrane. Our ABA efflux assays suggest that OsMATE6 functions as an ABA efflux transporter; mutant protoplasts exhibited a slower ABA release rate compared to the wild type. We hypothesize that OsMATE6 regulates ABA levels in guard cells, influencing stomatal closure and enhancing drought resistance. Notably, OsMATE6 knockout mutants demonstrated greater yields under field drought conditions compared to wild-type plants, highlighting OsMATE6 as a promising candidate for improving crop drought resistance., (© 2024 John Wiley & Sons Ltd.)

Clinical Relevance: The morphological characteristics of the optic nerve head (ONH) in myopic eyes are a clinically significant issue, especially for high myopia in school-aged children, and this can be monitored using optical coherence tomography., Background: The purpose of this study is to investigate the morphological characteristics of ONH, and the factors associated with peripapillary choroidal thickness in Chinese school-aged high myopia children., Methods: A total of 48 patients, possessing 48 high myopia eyes and 48 contralateral low myopia eyes were enrolled. The ONH characteristic parameters, including peripapillary retinal nerve fibre layer thickness, peripapillary choroidal thickness, peripapillary choroidal blood flow density, Bruch's membrane opening (BMO) characteristic parameters were measured on optical coherence tomography scans., Results: Eyes with high myopia had a larger disc size, higher peripapillary atrophy area proportion, larger peripapillary atrophy area, larger BMO minimum rim width, lower peripapillary choroidal thickness compared with those contralateral low myopia eyes (all P  < 0.001). The BMO distance and border length were longer, and border tissue angle was smaller in the high myopia eyes. The multivariate regression analysis revealed that border length, axial length, and border tissue angle were independently associated with peripapillary choroidal thickness (all P  < 0.05); axial length was associated with peripapillary retinal nerve fibre layer thickness ( P  = 0.007)., Conclusion: The peripapillary atrophy area, BMO area, border length, BMO distance, and BMO minimum rim width increased, but peripapillary choroidal thickness, retinal nerve fibre layer thickness decreased with axial elongation of the globe in young myopia children. Longer axial length and border length were positively correlated with lower peripapillary choroidal thickness, and a smaller border tissue angle was positively correlated with lower peripapillary choroidal thickness were found in this study. Monitoring of border length and border tissue angle is essential in the early stages of myopia in children.

Eleven previously undescribed sesquiterpenoids (8-18), one undescribed jasmonic acid derivative (35) and 28 known compounds were isolated from the leaves of Artemisia stolonifera. Undescribed compounds with their absolute configurations were determined by extensive spectroscopic analysis, single-crystal X-ray diffraction and ECD calculation. Compound 8 was identified as a rare sesquiterpenoid featuring a rearranged 5/8 bicyclic ring system, whereas compound 17 was found to be an unprecedented monocyclic sesquiterpenoid with methyl rearrangement. Evaluation of biological activity showed that compounds 1-5 and 7 displayed cytotoxicity against six tumor cells. In the meantime, compounds 11, 12, 18 and 35 exhibited inhibitory effects against LPS-stimulated NO production in RAW 264.7 macrophage cells and reduced the transcription of IL-6 and IL-1β in a dose-dependent manner at 25, 50 and 100 μM. Moreover, the anti-inflammatory-based network pharmacology and molecular docking analyses revealed potential target proteins of 11, 12, 18 and 35., 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 Ltd. All rights reserved.)

One new flavonostilbene glycoside, polygonflavanol C ( 1 ), two new dimeric stilbene glycosides, multiflorumiside M and multiflorumiside N ( 2 - 3 ), one new diphenyl ethanol glycoside, ( R )-2,3,5,4'-tetrahydroxy-diphenylethanol 2- O - β -D-glucopyranoside ( 4 ), and one new deoxybenzoin glycoside, 2,4,3',5'-tetrahydroxy-6-methyl-deoxybenzoin 2- O - β -D-glucopyranoside ( 5 ), together with six known ones ( 6 - 11 ), were isolated from the roots of Polygonum multiflorum . Their structures were elucidated by the comprehensive spectroscopic analyses. In addition, compounds 1 and 7 showed significantly in vitro anti-inflammatory activity.

Background/purpose: Nano-hydroxyapatite (nHA)/ gel porous scaffolds loaded with WSM carriers are promising bone replacement materials that can improve osseointegration ability. This investigation aimed to evaluate the osteoinductive activity by implanting the composition of nano-hydroxyapatite (nHA)/ Gel porous scaffolds as a carrier of WSM via an animal model., Materials and Methods: WSM was extracted and nHA was added to the matrix to construct porous composite scaffolds. The dose-effect curve of WSM concentration and alkaline phosphatase (ALP) activity was made by culturing rat osteoblasts and examining the absorbance. Three different materials were implanted into critical size defects (CSD) in the skulls of rats, which were further divided into four groups: WSM nHA /Gel group, n-WSM nHA /Gel group, HA powder group, and control group., Results: WSM (150 μg/mL-250μg/mL) effectively improved the activity of ALP in rat osteoblasts. All rats in each group had normal healing. WSM-loaded nHA /Gel group showed better performance on newly-formed bone tissue of rat skull and back at 4th week and 8th week, respectively. At the 4th week, the network of woven bone formed in the WSM-loaded nHA/Gel scaffold material. At 8th week, the reticular trabecular bone in the WSM-loaded scaffold material became dense lamellar bone, and the defect was mature lamellar bone. In the subcutaneous implantation experiment, WSM-loaded nHA/Gel scaffold material showed a better performance of heterotopic ossification than the pure nHA/Gel scaffold material., Conclusion: WSM promotes osteoblast differentiation and bone mineralization. The results confirm that the nHA/ Gel Porous Scaffold with Nacre Water-Soluble Matrix has a significant bone promoting effect and can be used as a choice for tissue engineering to repair bone defects., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: To provide comprehensive evidence for the anti-cancer cachexia effect of Jianpi Decoction (JP) and to explore its mechanism of anti-cancer cachexia., Methods: A mouse model of colon cancer (CT26)-induced cancer cachexia (CC) was used to investigate the anti-CC effect of JP combined with medroxyprogesterone acetate (MPA). Thirty-six mice were equally divided into 6 groups: normal control, CC, MPA (100 mg•kg -1 •d -1 ), MPA + low-dose (20 mg•kg -1 •d -1 ) JP (L-JP), MPA + medium-dose (30 mg•kg -1 •d -1 ) JP (M-JP), and MPA + high-dose (40 mg•kg -1 •d -1 ) JP (H-JP) groups. After successful modeling, the mice were administered by gavage for 11 d. The body weight and tumor volume were measured and recorded every 2 d starting on the 8th day after implantation. The liver, heart, spleen, lung, kidney, tumor and gastrocnemius muscle of mice were collected and weighed. The pathological changes of the tumor was observed, and the cross-sectional area of the gastrocnemius muscle was calculated. The protein expressions of STAT3 and E3 ubiquitinase in the gastrocnemius muscle were measured by Western blot. In addition, an in vitro C2C12 myotube formation model was established to investigate the role of JP in hindering dexamethasone-induced muscle atrophy. In vitro experiments were divided into control, model, and JP serum groups. After 2-d administration, microscopic photographs were taken and myotube diameters were calculated. Western blot was performed to measure the protein expressions of STAT3 and E3 ubiquitinase., Results: JP combined with MPA restored tumor-induced weight loss (P<0.05, vs. CC) and muscle fiber size (P<0.01, vs. CC). Mechanistically, JP reduced the expression of atrophy-related proteins MuRF1 and MAFbx in tumor-induced muscle atrophy in vivo (P<0.05, vs. CC). In addition, JP reduced the expression of atrophy-related proteins MuRF1 and MAFbx and p-STAT3 phosphorylation (P<0.05 or P<0.01 vs. model group) in C2C12 myotubes treated with dexamethasone in vitro., Conclusions: Administration of JP combined with MPA restores tumor-induced cachexia conditions. In addition, the profound effect of JP combined with MPA on tumor-induced cachexia may be due to its inhibition of muscle proteolysis (E3 ubiquitinase system)., (© 2023. The Chinese Journal of Integrated Traditional and Western Medicine Press and Springer-Verlag GmbH Germany, part of Springer Nature.)

Solvent-switchable and site-selective phosphorylation of imidazoles at the C2 or C5 position of the imidazole ring was achieved via 1,4-palladium migration. P -Chiral tert -butyl(aryl)phosphine oxides were cross-coupled to 1-(2-bromophenyl)-1 H -imidazoles with high enantiospecificity, thereby leading to a novel class of chiral imidazole-based phosphine oxides. As proof of concept, reduction of an analogue yielded the corresponding P -chiral 2-phosphinyl imidazole ligand, which was shown to induce high enantioselectivity in the formation of axially chiral molecules synthesized via Pd-catalyzed Suzuki-Miyaura cross-coupling.

Background: Faecal incontinence is a common debilitating condition associated with poor quality of life that generates substantial economic strain on healthcare systems., Objectives: We aimed to evaluate, in a tertiary referral population presenting with faecal incontinence, the impact of suffering additional disorders of gut-brain interaction (DGBI) on symptom severity, anxiety, depression and quality of life., Methods: Design: Retrospective cohort study., Setting: Tertiary referral Neurogastroenterology centre., Patients: All patients presenting with faecal incontinence from 2007 to 2020 were included., Main Outcome Measures: The results from structured medical and surgical questionnaires including Rome III Integrative Questionnaire, Faecal Incontinence Severity Index, Hospital Anxiety and Depression Scale, SF-36, and anorectal physiology were analysed using Stata version 17. Patients were categorised into 3 groups: 0-1 additional DGBI, 2 DGBIs, and 3+ DGBI. Statistical significance was defined as p < 0.05 (two-tailed)., Key Results: Faecal incontinence patients (n = 249; mean age 63.4 ± 12.6 years; 93.6% female, 48.1% urge subtype) met diagnostic criteria for mean 2.2 additional DGBI each, mostly affecting bowel (n = 231, 42.4%) and anorectal (n = 150, 27.5%) regions. A greater number of DGBIs was associated with higher faecal incontinence symptom severity (p < 0.001), higher anxiety (p = 0.002) and depression (p = 0.003), and worse quality of life in areas of mental health (p = 0.037) and social effect (p < 0.001). Patients with a greater number of concurrent DGBI demonstrated a greater family history of gastrointestinal problems (p = 0.004). There were no associations found between a greater amount of DGBIs and anorectal physiology., Conclusions and Inferences: A greater number of additional DGBIs in faecal incontinence patients was associated with worse faecal incontinence symptoms, higher anxiety and depression scores, and worse quality of life but was unrelated to physiology. This highlights the need to proactively search for comorbid DGBI in patients presenting with faecal incontinence., (© 2024 The Authors. United European Gastroenterology Journal published by Wiley Periodicals LLC on behalf of United European Gastroenterology.)

Congenital radial head subluxation is relatively rare and may be overlooked due to mild symptoms. The diagnosis mainly relies on imaging and history. Observation is an option for those with insignificant symptoms, while surgical intervention, such as ulnar osteotomy or arthroscopy, is often required when dysfunction exists. A 30-year-old man was admitted with congenital radial head dislocation, which was treated with manipulative repositioning. During follow-up, the patient regained the original mobility of the elbow joint and had no recurrence of dislocation. In conclusion, in adults with congenital dislocation of the radial head, we recommend conservative treatment as a first step.

Neural tube defects (NTDs) are severe congenital neurodevelopmental disorders arising from incomplete neural tube closure. Although folate supplementation has been shown to mitigate the incidence of NTDs, some cases, often attributable to genetic factors, remain unpreventable. The SHROOM3 gene has been implicated in NTD cases that are unresponsive to folate supplementation; at present, however, the underlying mechanism remains unclear. Neural tube morphogenesis is a complex process involving the folding of the planar epithelium of the neural plate. To determine the role of SHROOM3 in early developmental morphogenesis, we established a neuroepithelial organoid culture system derived from cynomolgus monkeys to closely mimic the in vivo neural plate phase. Loss of SHROOM3 resulted in shorter neuroepithelial cells and smaller nuclei. These morphological changes were attributed to the insufficient recruitment of cytoskeletal proteins, namely fibrous actin (F-actin), myosin II, and phospho-myosin light chain (PMLC), to the apical side of the neuroepithelial cells. Notably, these defects were not rescued by folate supplementation. RNA sequencing revealed that differentially expressed genes were enriched in biological processes associated with cellular and organ morphogenesis. In summary, we established an authentic in vitro system to study NTDs and identified a novel mechanism for NTDs that are unresponsive to folate supplementation.

Background: Chlorantraniliprole (CAP) is a diamide insecticide with high efficacy against many pest insects, including the black cutworm, Agrotis ipsilon. Agrotis ipsilon is a serious pest causing significant yield losses in crops. Glutathione-S-transferases (GSTs) belong to a family of metabolic enzymes that can detoxify a wide range of pesticides. However, little is known about the functions of GSTs in CAP tolerance in A. ipsilon., Results: A cDNA sequence (designated AiGSTu1) encoding an unclassified GST was identified from A. ipsilon. AiGSTu1 is highly expressed during the 3 rd -instar larval and the pupal stages. Most of the mRNA transcripts were found in larval Malpighian tubules. Exposure to CAP strongly enhanced AiGSTu1 expression, GST activity, hydrogen peroxide (H 2 O 2 ) and malondialdehyde levels in larvae. H 2 O 2 treatment upregulated the transcription level of AiGSTu1, suggesting that CAP-induced oxidative stress may activate AiGSTu1 expression. The activity of recombinant AiGSTu1 was inhibited by CAP in a dose-dependent manner. Metabolism assay results demonstrated that AiGSTu1 is capable of depleting CAP. Overexpression of AiGSTu1 enhanced the tolerance of Escherichia coli cells to H 2 O 2 and the oxidative stress inducer, cumene hydroperoxide. Silencing of AiGSTu1 by RNA interference increased the susceptibility of A. ipsilon larvae to CAP., Conclusion: The findings of this study provide valuable insights into the potential role of AiGSTu1 in CAP detoxification and will improve our understanding of CAP tolerance in A. ipsilon. © 2023 Society of Chemical Industry., (© 2023 Society of Chemical Industry.)

Background: Solitary fibrous tumors (SFT) and meningiomas (MA) have similar clinical and radiographic presentations but require different treatment approaches and have different prognoses. This emphasizes the importance of a correct preoperative diagnosis of SFT versus MA., Objective: In this study, investigated the differences in imaging characteristics between SFT and MA to improve the accuracy of preoperative imaging diagnosis of SFT., Methods: The clinical and imaging data of 26 patients with SFT and 104 patients with MA who were pathologically diagnosed between August 2017 and December 2022, were retrospectively analyzed. The clinical and imaging differences between SFT and MA, as well as between the various pathological grades of SFT, were analyzed., Results: Age, gender, cystic change, flow void phenomenon, yin-yang sign, lobulation, narrow base, tumor/cortex signal ratio (TCSR) > 1.0 in T1-weighted imaging (T1WI), TCSR ≥ 1.1 in T2-weighted imaging (T2WI), peritumoral edema, and absence of dural tail sign varied between SFT and MA. As per the receiver operating characteristic (ROC) curve analysis, TCSR > 1 in T1WI has the maximum diagnostic accuracy for SFT. Cranial or venous sinus invasion had a positive effect on SFT (Grade III, World Health Organization (WHO) grading)., Conclusion: Among the many radiological and clinical distinctions between SFT and MA, TCSR ≥ 1 exhibits the highest predictive efficacy for SFT; while cranial or venous sinus invasion may be a predictor of WHO grade III SFT., (© 2024. The Author(s).)

Isodonxiaoluzhiensis , a new species of the tribe Ocimeae in family Lamiaceae, is described and illustrated. The new species is known only from the type locality, Xiaoluzhi village in Luzhijang dry-hot valley of Yimen County, central Yunnan, southwest China. It is characterized by having a procumbent habit, gracile stems and branches, relatively small leaves and flowers, and the phenology of flowering in winter. The morphological comparisons with its putative closest relatives ( I.adenanthus and I.hsiwenii ) are also presented., Competing Interests: The authors have declared that no competing interests exist., (Shi-Gang Li, Qiang-Chun Huang, Shao-Yun Liu, Chun-Lei Xiang, Huan-Chong Wang.)

Aims: This study aimed to characterize the first complete genome of Corynebacterium parakroppenstedtii and clarify the evolutionary relationship in the Corynebacterium kroppenstedtii complex (CKC) by using comparative genomics analysis., Methods and Results: The genome of isolate yu01 from a breast specimen was sequenced, and 35 CKC genomes were collected. Analysis of 16S rRNA, rpoB, and fusA suggested ambiguous identification, whereas ANI analysis assigned isolate yu01 as Coryne. parakroppenstedtii. The fourth genospecies "Corynebacterium aliikroppenstedtii" was identified in CKC. Comparative genomics analysis suggested that the genomic arrangement in CKC was highly conserved. A total of 43 potential virulence genes and 79 species-specific genes were detected. Most genome-based phylogenetic analysis were incapable of resolving the interspecific evolutionary relationships among CKCs. A total of 20 core genes were found to be distinguishable in CKC., Conclusions: This study suggested the limited divergence and unavailability of normal single gene-based identification in CKC and questioned the precise species of strains associated with mastitis, identified as Coryne. kroppenstedtii in previous studies. The 20 genes showed potential to enhance the methods for the identification and epidemiological investigation of CKC., (© The Author(s) 2023. Published by Oxford University Press on behalf of Applied Microbiology International.)

Prunella vulgaris has long been used in traditional medicine and is consumed as a tea in China. Here, the total phenolic and flavonoid concentrations of plants from different geographical regions were measured. It was found that the total phenolic acid concentration ranged from 4.15 to 8.82 g of gallic acid equivalent per 100 g of dry weight (DW), and the total flavonoid concentration was 4.67-7.33 g of rutin equivalent per 100 g DW. Antioxidant activities were measured using 2,2-diphenyl-1-picrylhydrazyl and 2,2'-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt, and the results ranged from 73.47% to 94.43% and 74.54% to 93.39%, respectively, whereas α-glucosidase inhibition was between 75.31% and 95.49%. Correlation analysis showed that the total flavonoids in P. vulgaris had superior antioxidant and anti-α-glucosidase activities compared to the total phenolic compounds. The active components of P. vulgaris were analyzed using high-performance liquid chromatography quadrupole time-of-flight mass spectrometry combined with both classical molecular networking and feature-based molecular networking on the Global Natural Products Social platform, identifying 32 compounds, namely 14 flavonoids, 12 phenolic compounds, and 6 other chemical components. These results could provide useful information on the use of P. vulgaris as a functional tea., (© 2023 John Wiley & Sons Ltd.)

Background: Hypertensive intracerebral hemorrhage (HICH) is a life-threatening disease and lacks effective treatments. Previous studies have confirmed that metabolic profiles altered after ischemic stroke, but how brain metabolism changes after HICH was unclear. This study aimed to explore the metabolic profiles after HICH and the therapeutic effects of soyasaponin I on HICH., Methods: HICH model was established first. Hematoxylin and eosin staining was used to estimate the pathological changes after HICH. Western blot and Evans blue extravasation assay were applied to determine the integrity of the blood-brain barrier (BBB). Enzyme-linked immunosorbent assay was used to detect the activation of the renin-angiotensin-aldosterone system (RAAS). Next, liquid chromatography-mass spectrometry-untargeted metabolomics was utilized to analyze the metabolic profiles of brain tissues after HICH. Finally, soyasaponin I was administered to HICH rats, and the severity of HICH and activation of the RAAS were further assessed., Results: We successfully constructed HICH model. HICH significantly impaired BBB integrity and activated RAAS. HICH increased PE(14:0/24:1(15Z)), arachidonoyl serinol, PS(18:0/22:6(4Z, 7Z, 10Z, 13Z, 16Z, and 19Z)), PS(20:1(11Z)/20:5(5Z, 8Z, 11Z, 14Z, and 17Z)), glucose 1-phosphate, etc., in the brain, whereas decreased creatine, tripamide, D-N-(carboxyacetyl)alanine, N-acetylaspartate, N-acetylaspartylglutamic acid, and so on in the hemorrhagic hemisphere. Cerebral soyasaponin I was found to be downregulated after HICH and supplementation of soyasaponin I inactivated the RAAS and alleviated HICH., Conclusion: The metabolic profiles of the brains changed after HICH. Soyasaponin I alleviated HICH via inhibiting the RAAS and may serve as an effective drug for the treatment of HICH in the future.

The black cutworm Agrotis ipsilon is a serious crop pest. Phoxim, an organophosphorus insecticide, has been widely used to control A. ipsilon . When phoxim is extensively applied, the susceptibility of A. ipsilon to insecticide is reduced. However, the mechanisms of tolerance of A. ipsilon to phoxim remain unclear. Herein, we report that an epsilon class glutathione S -transferase, AiGSTE1, confers phoxim tolerance in A. ipsilon . Exposure to a sublethal concentration (LC 50 ) of phoxim caused oxidative stress and activated the transcription of AiGSTe1 genes in A. ipsilon larvae. Recombinant AiGSTE1 expressed in Escherichia coli could metabolize phoxim. Furthermore, E. coli cells overexpressing AiGSTE1 displayed significant tolerance to oxidative stress. Knockdown of AiGSTe1 by RNA interference significantly increased the mortality of A. ipsilon larvae to phoxim. These results demonstrate that AiGSTE1 confers phoxim tolerance in A. ipsilon by metabolizing the insecticide and preventing phoxim-induced oxidative stress.

Background: Governments around the world have taken measures to limit adolescent drinking, however, rates are still alarmingly high. However, most of these measures ignore the peer effect of drinking among adolescents. Previous studies have not sufficiently considered the reciprocal relationship between adolescent alcohol consumption and peer alcohol consumption, which may lead to an overestimation of the peer effect and mask underlying issues. Good instrumental variables are powerful but rare tools to address these issues., Objective: This paper aims to correctly estimate the peer effect of drinking on adolescent drinking behavior in China., Methods: Owing to the detailed information of household background in the dataset of our survey, we were able to use the drinking behaviors of peers' fathers and their beliefs about the health risks of alcohol as instrumental variables, which are more powerful than school-average instrumental variables. We collected data from the 2017 Health and Nutrition Panel survey, which surveyed 10,772 primary school students from 59 urban migrant and 60 rural public schools., Results: The instrumental variable method estimation revealed that peer drinking significantly influences adolescent drinking behavior, with adolescents who have peers who drink alcohol being 10.5% points (2 stage least square, i.e., 2SLS, full sample estimation) more likely to engage in drinking compared to those without such peers. Furthermore, the effect differs significantly between migrant and rural adolescents., Conclusion: The study found that parental care plays a significant role in the degree of peer effect, with the absence of parental care being a key factor in the presence of the peer effect., 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 Liu, Zhao, Zhao, Wang and Li.)

The material basis and mechanism of Chaenomelis Fructus in the treatment of rheumatoid arthritis(RA) were explored by network pharmacology, and the potential anti-RA targets of Chaenomelis Fructus were verified by molecular docking and animal experiments. The active components and targets of Chaenomelis Fructus were searched against the Traditional Chinese Medicine System Pharmacology Database and Analysis Platform. GeneCards, DisGeNET, and OMIM were used to obtain RA-related targets. The common targets shared by Chaenomelis Fructus and RA were considered as the potential targets of Chaenomelis Fructus in the treatment of RA. Cytoscape 3.9.0 was employed to establish a &quot;traditional Chinese medicine-active component-common target-disease&quot; network. The protein-protein interaction(PPI) network was established by STRING, and the core genes were visualized by RStudio 4.1.0. DAVID was used for Gene Ontology(GO) annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment to predict and visualize the involved signaling pathways. Molecular docking was carried out with the active components screened out as ligands and RA core genes as the targets. Finally, the prediction results were verified by animal experiments. Four main active components of Chaenomelis Fructus were obtained, which corresponded to 137 targets. Chaenomelis Fructus and RA shared 37 common targets. GO annotation yielded 239 terms(P&lt;0.05), and KEGG pathway enrichment analysis screened out 94 signaling pathways(P&lt;0.05), mainly involving interleukin-17(IL-17), tumor necrosis factor, Toll-like receptor, and nuclear factor-kappa B(NF-κB) signaling pathways. Molecular docking results showed that the main active components of Chaenomelis Fructus bound well with the core targets of RA. The results of animal experiments proved that Chaenomelis Fructus can alleviate joint swelling in the mice with RA. The results of ELISA showed that Chaenomelis Fructus lowered the levels of interleukin-6(IL-6) and interleukin-1β(IL-1β). Western blot showed that Chaenomelis Fructus down-regulated the protein level of vascular endothelial growth factor A(VEGFA). Chaenomelis Fructus exerts anti-inflammatory effect and reduces pannus formation by regulating the core targets such as VEGFA, IL-1β, and IL6 in the treatment of RA. The findings of this study provide new ideas for the future treatment of RA with Chaenomelis Fructus.

This paper aims to compare the difference of growth and quality between wild and cultivated Artemisia stolonifera, thereby providing references for further development and utilization of A. stolonifera. The wild and cultivated A. stolonifera from different altitudes were collected, and the agronomic characters, moxa yield, volatile components, flavonoids, and phenolic acids were determined. The results showed that the cultivated species were taller and stronger, with more leaves and branches, than the wild species. The moxa yield and combustion quality of wild products were higher than those of cultivated products. The content of main volatile components in cultivated products was higher than that in wild products. The content of flavonoids and phenolic acids in wild products was higher than that in cultivated products. At high altitude, the ignition performance, combustion persistence, comprehensive combustion performance, and heat release during combustion of the wild and cultivated A. stolonifera. were optimal. At middle altitude, the content of main characteristic volatile components and flavone phenolic acids in the leaves of the cultivated and wild A. stolonifera were the highest. At low altitude, the combustion quality and the content of the above components of the cultivated A. stolonifera decrease significantly. Considering the combustion quality and the content of the internal components of the leaf lint, the middle and high altitude areas are suitable for the artificial cultivation of A. stolonifera.

The purpose of this study was to analyze the effects of shading intensity on the growth, yield, and quality of Artemisia stolonifera so as to provide references for the artificial cultivation of A. stolonifera. The seedlings of A. stolonifera with consistent growth underwent shading treatment at four shading intensity levels(0, 55%, 85%, and 95%) with different layers of black shading nets. The agronomic indexes, yield, moxa yield, total ash, quality characteristics of moxa during combustion and pyrolysis, main volatile components, flavonoids, and phenolic acids were measured. The results showed that under shading conditions, the stem diameter, leaf width, 5-leaf spacing, branch number, and yield of A. stolonifera decreased significantly, while the plant height, leaf length, leaf number, chlorophyll content, and moxa yield increased first and then decreased with the increase in shading intensity. The burning performance of moxa under natural light was better than that under moderate and severe shading conditions. The content of eucalyptol first increased and then decreased with the increase in shading intensity. The humulene content was negatively correlated with shading intensity. Other major volatile components showed no significant difference under various shading conditions. The content of neochlorogenic acid, cryptochlorogenic acid, isoschaftoside, and isochlorogenic acid B was positively correlated with shading intensity, while the content of chlorogenic acid, isochlorogenic acid A, and isochlorogenic acid C decreased first and then increased with the increase in shading intensity. To sum up, A. stolonifera is a light-loving plant, and shading can greatly reduce the yield, the content of internal components, and the burning performance of moxa. It is the main reason why A. stolonifera is mainly distributed in the forest edge, open forest, roadside, and wasteland grass in the middle and high mountains in the wild. For artificial domestication and cultivation of A. stolonifera, it is better to select plots with sufficient light.

Artemisia stolonifera is a relative of A. argyi. The two species are difficult to be distinguished due to the similarity in leaf shape and have even less distinctive features after processing. This study aims to establish a method to quickly distinguish between them. At the same time, we examined the reasonability and applicability of the specific polymerase chain reaction(PCR) method. The C/T single nucleotide polymorphism was detected at the position 202 of the sequence, based on which specific primers were designed to identify these two species. The PCR with the specific primer JNC-F and the universal primer ITS3R produced a specific band at 218 bp for A. argyi and no band for A. stolonifera, which can be used to detect at least 3% of A. argyi samples mixed in A. stolonifera samples. The PCR with the specific primer KY-F and the universal primer ITS3R produced a specific band at 218 bp for A. stolonifera and no band for A. argyi, which can be used to detect at least 5% of A. stolonifera samples mixed with A. argyi. The limit of detection of the established method was 5 ng DNA. The established PCR method can accurately distinguish between A. stolonifera and A. argyi, which provides an experimental basis for the quality control of A. stolonifera and determines whether the herbs are adulterated.

This study aimed to explore the anti-inflammatory material basis and molecular mechanism of Artemisia stolonifera based on the analysis of the chemical components in different extracted fractions of A. stolonifera and their antioxidant and anti-inflammatory effects in combination with network pharmacology and molecular docking. Thirty-two chemical components were identified from A. stolonifera by ultra-performance liquid chromatography coupled to tandem quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS). Among them, there were 7, 21 and 22 compounds in water, n-butanol and ethyl acetate fractions, respectively. The antio-xidant capacity of different extracted fractions was evaluated by measuring their scavenging ability against 1,1-diphenyl-2-picrylhydrazyl radical 2,2-diphenyl-1-(2,4,6-trinitrophenyl) hydrazyl(DPPH) and 2,2'-azinobis-(3-ethylbenzthiazoline-6-sulphonic acid)(ABTS) free radicals and total antioxidant capacity [ferric reducing antioxidant power(FRAP) assay]. The inflammatory model of RAW264.7 cells was induced by lipopolysaccharide(LPS), and the levels of nitrite oxide(NO), tumor necrosis factor-α(TNF-α), interleukin-6(IL-6) in the supernatant and the mRNA expression of related inflammatory factors in cells were used to evaluate the anti-inflammatory effects. The results revealed that ethyl acetate fraction of A. stolonifera was the optimal antioxidant and anti-inflammatory fraction. By network pharmacology, it was found that flavonoids such as rhamnazin, eupatilin, jaceosidin, luteolin and nepetin could act on key targets such as TNF, serine/threonine protein kinase 1(AKT1), tumor protein p53(TP53), caspase-3(CASP3) and epidermal growth factor receptor(EGFR), and regulate the phosphatidylinositol-3-kinase-protein kinase B(PI3K-AKT) and mitogen-activated protein kinase(MAPK) signaling pathways to exert the anti-inflammatory effects. Molecular docking further indicated excellent binding properties between the above core components and core targets. This study preliminarily clarified the anti-inflammatory material basis and mechanism of ethyl acetate fraction of A. stolonifera, providing a basis for the follow-up clinical application of A. stolonifera and drug development.

Background: The identification of protein-protein interactions is a great challenge. In this study, we fabricated a gold surface-modified biochip with activated sophorolipids (SLs) in combination with 16-amino-1-hexadecanethiol hydrochloride to detect serum proteins., Main Methods and Major Results: The on-chip immunoassay reported here included a forward assay, in which a ligand is immobilized on the biochip surface and allowed to interact with its free specific receptor in liquid phase, and a reverse assay, in which a receptor is loaded on the biochip surface and combined with its free specific ligand in solution. The specificity of the molecular interactions on the biochip was evaluated using immunological blocking assays and chemiluminescent immunoassays (CLIA). Hemophagocytic lymphohistiocytosis (HLH) serum was used to test the potential utilization of the biochip. Reverse receptor CD25-based interleukin (IL)-2 and forward ligand IL-2-based CD25 assays revealed that the limit of detection of the target proteins was as low as 156 and 78 pg/ml, respectively. Using receptor- or ligand-based platforms, we found that the positive rates of free IL-2 and soluble CD25 (sCD25) monomers in the sera of HLH patients were 14.3% and 71.4%, respectively. In addition, the biochip showed good compatibility with CLIA for the measurement of sCD25 (r = 0.77, p < 0.01)., Conclusions and Implications: Biochip platforms, such as on-chip immunoprecipitation (IP), can be used to evaluate the interactions between proteins, ligands, and receptors, or enzymes and substrates in serum., (© 2022 The Authors. Biotechnology Journal published by Wiley-VCH GmbH.)

Background: Mass screening and treatment (MSAT) for malaria elimination lacks an ideal diagnostic tool to allow sensitive and affordable test of the target population in the field. This study evaluated whether Capture and Ligation Probe-PCR (CLIP-PCR) could be used in a field MSAT in Laiza City, Myanmar., Methods: On day 0, two dried blood spots were collected from each participant. On day 1, all samples were screened for Plasmodium in a 20 m 2 laboratory with workbench, a biosafety cabinet, a refrigerator, a benchtop shaking incubator and a qPCR machine, by four technicians using CLIP-PCR with sample pooling, at a health clinic of the Chinese bordering town of Nabang. On day 2, all positives were followed up and treated., Results: Of 15,038 persons (65% of the total population) screened, 204 (1.36%) were CLIP-PCR positives. Among them, 188, 14, and 2 were infected with Plasmodium vivax, Plasmodium falciparum, and P. vivax/P. falciparum mix, respectively. The testing capacity was 538 persons/day, with a cost of US$0.92 /person. The proportion of submicroscopic infection was 64.7%. All positive individuals received treatment within 72 h after blood collection., Conclusion: Using CLIP-PCR in MSAT in low transmission settings can support the malaria elimination efforts in the China-Myanmar border region., (© 2023. The Author(s).)

Objective: To evaluate the predictive role of nodal skip metastasis (NSM) in the prognosis of lymph node-positive mid-thoracic esophageal squamous cell carcinoma, and to evaluate the significance of postoperative adjuvant treatment in patients with different sites of metastatic nodes., Methods: A retrospective analysis was performed on clinical data of 321 lymph node-positive mid-thoracic esophageal squamous cell carcinoma patients who underwent surgery in the Fourth Hospital of Hebei Medical University. Based on the site and condition of lymph node metastasis by postoperative pathology, the patients were divided into two groups: NSM group and non-NSM (NNSM) group. The propensity score matching (PSM) method was employed to match the two groups. The prognostic factors of patients before and after PSM as well as the effect of different adjuvant treatment modes on the prognosis of patients before and after PSM were analyzed. SPSS 29.0 statistical software was used for analysis., Results: PSM in a 1 : 1 matching ratio was performed, 103 patients were assigned to NSM group and NNSM group respectively. Significant differences were found in the 3- and 5-year OS and DFS between the two groups before PSM, the 3- and 5-year OS also showed a significant difference after PSM ( P  < 0.05). Multivariate analysis illustrated that gender, postoperative adjuvant treatment mode, N stage and lymph node metastasis were independent risk factors for OS and DFS after PSM ( P  < 0.05); for NSM patients, postoperative adjuvant chemotherapy and radiotherapy significantly prolonged OS and DFS before and after PSM ( P  < 0.05). But no significant difference was found in OS and DFS for NNSM patients after PSM ( P  > 0.05)., Conclusion: Postoperative NSM is a good prognostic factor for patients with mid-thoracic esophageal squamous cell carcinoma, postoperative adjuvant chemoradiotherapy was recommended for those group, thereby gaining survival benefits., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Gao, Zhao, Shen, li, Li and Zhu.)

We herein report two cases involving children who died of influenza A (H3N2) virus infection-associated encephalopathy/encephalitis (IAE). Both children developed convulsions and impaired consciousness within a relatively short period and eventually died of brainstem failure. Patient 1 presented with high fever, vomiting, and diarrhea. Laboratory tests indicated persistently high lactate, alanine aminotransferase, and urea nitrogen concentrations in the blood as well as a high protein concentration in the cerebrospinal fluid. Patient 2 presented with persistent hyperthermia and progressive disturbance of consciousness, but the cerebrospinal fluid remained normal during the disease course. Both patients were actively given oseltamivir antiviral treatment after diagnosis of influenza virus infection. However, the disease progressed and invasive mechanical ventilation was performed. Both children's condition quickly progressed to IAE, and they eventually died. IAE is a rare complication of influenza virus infection with high mortality, and its pathogenesis remains unclear. The purpose of this report is to draw attention to the serious central nervous system complications of influenza infection and raise awareness of the fatal consequences of this disease among pediatricians.

Chlorantraniliprole (CAP) is an insecticide widely used to control the small white butterfly (SWB), Pieris rapae. Exposure to CAP can cause oxidative injury in SWB; however, it is unclear if antioxidant enzymes are involved in the defense process. In this study, a thioredoxin peroxidase (PrTPX1) gene was identified from SWB by using a homology search method. The gene encoded a 195 amino-acid PrTPX1 protein. Sequence characteristics and phylogenetic analysis indicated that PrTPX1 was a typical "2-Cys" TPX, and the PrTPX1 gene consisted of four exons and three introns. Reverse transcription-quantitative polymerase chain reaction analysis indicated that the messenger RNA levels of PrTPX1 were highest in third-, fourth- and fifth-instar larval stages and in the larval midgut. Treatment with sublethal doses (LD 20 and LD 50 ) of CAP for 6, 12, 18, and 24 h resulted in increased H 2 O 2 concentration in SWB larvae, indicating insecticide-induced oxidative stress. The transcriptional levels of PrTPX1 were significantly enhanced in larvae exposed to CAP. Recombinant PrTPX1 protein was expressed in Escherichia coli. Enzymatic assay revealed that the protein displayed antioxidant activity and was able to protect against oxidative challenge. These results indicated that PrTPX1 plays an important role in oxidative stress responses and may contribute to the CAP tolerance in SWB., (© 2022 Wiley Periodicals LLC.)

Purpose: To investigate the influencing factors of abdominal lymph node metastasis in thoracic esophageal squamous cell carcinoma (TESCC), and to construct its predictive model, in order to analyze the targets for postoperative radiotherapy., Methods and Materials: From January 2008 to December 2014, the clinicopathological data of 479 patients who underwent radical resection for esophageal cancer in the Fourth Hospital of Hebei Medical University were collected and retrospectively analyzed. The influencing factors of postoperative abdominal lymph node metastasis were analyzed, and a predictive model was constructed based on their independent influencing factors. Receiver operating characteristic (ROC) curve was utilized to analyze the predictive value of this model; in the meantime, the postoperative locoregional recurrence (LRR) of this group was analyzed., Results: The postoperative pathology of all patients showed that the lymph node metastasis rate (LNR) was 39.7%, of which the abdominal lymph node metastasis rate was 22.0%. Logistic regression analysis revealed that the patient's lesion location, pN stage, vascular invasion, LND and mediastinal lymph node metastasis were independent risk factors for the positive rate of abdominal lymph nodes after surgery ( P  = 0.000, 0.000, 0.033, 0.000, 0.000). The probability of abdominal lymph node metastasis was Y = e x /(1 + e x ), and X = -5.502 + 1.569 × lesion location + 4.269 × pN stage + 1.890 × vascular invasion + 1.950 × LND-4.248 × mediastinal lymph node metastasis. The area under the ROC curve (AUC) of this model in predicting abdominal lymph node metastasis was 0.962 (95% CI, 0.946-0.977). This mathematical model had a high predictive value for the occurrence of abdominal lymph node metastasis ( P  = 0.000), and the sensitivity and specificity of prediction were 94.6% and 88.3% respectively. The overall survival rate was significantly higher (X 2  = 29.178, P  = 0.000), while abdominal lymph node recurrence rate was lower in patients with negative abdominal lymph nodes than in those with negative lymph nodes (1.4%&7.7%, X 2  = 12.254, P  = 0.000)., Conclusion: The lesion location, pN stage, vascular invasion, LND and mediastinal lymph node metastasis are independent influencing factors of abdominal lymph node metastasis in patients with TESCC. The mathematical model constructed by these indicators can accurately predict abdominal lymph node metastasis, which can help clinicians to choose the targets for postoperative radiotherapy., 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., (© 2022 Gao, Zhang, Shen, Xu, Li, Li and Zhu.)

Two pairs of unprecedented β-carboline-phenylpropanoid heterogeneous alkaloids, (±)-pheharmines A-B (1-4), characterized by a morpholino[4,3,2- hi ]β-carboline core with two chiral centers, were isolated from the roots of Peganum harmala . The structures, including their absolute configurations, were identified using spectroscopic analyses and electronic circular dichroism (ECD) calculations. The biosynthetic hypothesis for the formation of pheharmines A-B was proposed. Compounds 1-4 exhibited moderate cytotoxic activities against HL-60 cell lines.

Drug-resistant Neisseria gonorrhoeae is a serious global health concern. New drugs are needed that can overcome existing drug resistance and limit the development of new resistances. Here, we describe the small molecule tricyclic pyrimidoindole JSF-2414 [8-(6-fluoro-8-(methylamino)-2-((2-methylpyrimidin-5-yl)oxy)-9H-pyrimido[4,5-b]indol-4-yl)-2-oxa-8-azaspiro[4.5]decan-3-yl)methanol], which was developed to target both ATP-binding regions of DNA gyrase (GyrB) and topoisomerase (ParE). JSF-2414 displays potent activity against N. gonorrhoeae, including drug-resistant strains. A phosphate pro-drug, JSF-2659, was developed to facilitate oral dosing. In two different animal models of Neisseria gonorrhoeae vaginal infection, JSF-2659 was highly efficacious in reducing microbial burdens to the limit of detection. The parent molecule also showed potent in vitro activity against high-threat Gram-positive organisms, and JSF-2659 was shown in a deep tissue model of vancomycin-resistant Staphylococcus aureus (VRSA) and a model of Clostridioides difficile-induced colitis to be highly efficacious and protective. JSF-2659 is a novel preclinical drug candidate against high-threat multidrug resistant organisms with low potential to develop new resistance.

Objective: To investigate the dynamic change of the secundum atrial septal defect (ASD) throughout the cardiac cycle, and assess its impact on occluder selection. Methods: This study retrospectively analyzed 35 patients with ASD who received electrocardiogram-gated coronary CT angiography (CCTA) throughout the cardiac cycle as well as interventional closure therapy in Fuwai Hospital from December 2016 to December 2019. The raw data were reconstructed into 20 phasic images of RR intervals (RRI) ranging from 0 to 95% in an increment of 5% and transmitted to a workstation for postprocessing. For each phase image, CT virtual endoscopy reconstruction technique (CTVE) was used to provide views of ASD. Axial sequence assisted CT volumetric measurement (CTAS) was used to calculate the maximum dimensions in axial planes (D a ) and in superior-inferior direction (D b ). Using a formula for converting circumference to diameter, the equivalent circle dimensions were calculated (D e , D e =minor axis+2 (major axis-minor axis)/3). Taking the data of 75% RRI phase, the patients were divided into D a75%RRI ≥D b75%RRI group and D a75%RRI b75%RR group. According to the postoperative chest X-ray, the waist diameter of the occluder in the left anterior oblique plain film was measured, and its correction value (CR-POD laoc ) was calculated with the correction formula. Scatter plots of the changes of the mean values of D a , D b and D e with the cardiac cycle were presented. The change and ratio of measured values of D a and D e at 35% and 75% RRI was calculated. The ratio of D e change to D a change in D a75%RRI ≥D b75%RRI group and D a75%RRI b75%RR group was calculated, respectively, and compared between groups. Pearson correlation analysis was used to explore the correlation between CR-POD lao c and D e35%RRI and D e75%RRI. Results: A total of 35 patients, aged (42.7±15.0) years, including 10 males, were included. Among 35 patients, 8 cases were divided into group D a75%RRI ≥D b75%RRI and 27 cases into group D a75%RRI b75%RRI . Both D a and D b regularly changed at each phase throughout the cardiac cycle. The D a changed significantly, with a maximum at phase of 35%-45% of RRI, and a minimum between phases of 90% and 0 of RRI. While the D b showed insignificant changes during phases of 10%-90% RRI, and increased at 0-10% of RRI, then reduced in the remaining phases. The change of D a was (6.35±2.46) mm, and the ratio of D a values at 35% and 75% RRI was 0.77±0.08. The change of D e was (2.28±1.32) mm, and the ratio of D e at 35% and 75% RRI was 0.93±0.05. The ratio of D e change to D a change in the D a75%RRI ≥D b75%RRI group was 0.67±0.13; while the ratio was 0.34±0.05 in D a75%RRI b75%RR group, and there was significant difference between the two groups ( P =0.02). CR-POD lao c was positively correlated with D e35% RRI ( r =0.99, P <0.001) and D e75% RRI ( r =0.98, P <0.001). Conclusions: Most secundum ASDs show oval shape with D b >D a . D b is basically constant while D a changes significantly during cardiac cycle (10%-90% RRI). Nonetheless, both values peak and maintain the maximum status at end-systolic phase (35%-45% RRI). For patients with huge ASD, occluder selection should be based on the D e at 35% RRI phase, which is helpful for the successful intervention.