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Sheng-fa Li,1,2,* Jia-jun Tang,1,2,* Jian Chen,1–3,* Pei Zhang,4,* Ting Wang,5 Tian-yu Chen,1,2 Bo Yan,1,2 Bin Huang,1,2 Liang Wang,1,2 Min-jun Huang,1,2 Zhong-min Zhang,1,2 Da-di Jin1,21Academy of Orthopedics of Guangdong Province, Guangzhou, People’s Republic of China; 2Department of Orthopedics, The Third Affiliated Hospital, Southern Medical University, Guangzhou, Guangdong, People’s Republic of China; 3Three Gorges Central Hospital of Chongqing, Chongqing, People’s Republic of China; 4School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong, People’s Republic of China; 5Department of Cell Biology, School of Basic Medical Science, Southern Medical University, Guangzhou, Guangdong, People’s Republic of China*These authors contributed equally to this workAbstract: Osteoporosis is a systemic skeletal disease that is characterized by low bone density and microarchitectural deterioration of bone tissue. The increasing prevalence of osteoporosis has attracted much attention. In this study, MC3T3-E1 pre-osteoblasts were treated with the natural compound, baicalein (0.1 µmol/L, 1 µmol/L, 10 µmol/L), to stimulate differentiation over a 14-day period. In addition, a canonical ovariectomized (OVX) mouse model was used to investigate the effect of 3-month baicalein treatment (10 mg/kg per day) in preventing postmenopausal osteoporosis. In vitro, we found that baicalein induced activation of alkaline phosphatase, stimulated the mammalian target of rapamycin complex 1 (mTORC1) signaling pathway, and induced expression of osteoblast differentiation markers, ie, osteocalcin, osterix, collagen Iα1, and runt-related transcription factor 2 (RUNX2), in osteoblasts. In vivo, several bone parameters, including trabecular thickness, trabecular bone mineral density, and trabecular number, in the distal femoral metaphysis were significantly increased in OVX mice treated intragastrically with baicalein for 3 months compared with OVX mice that were not treated with baicalein. We also found that expression of osteocalcin and RUNX2 was decreased in primary ossified tissue from the OVX group, and baicalein increased the levels of osteocalcin and RUNX2 in OVX mice. These data suggest that baicalein can stimulate MC3T3-E1 cells to differentiate into osteoblasts via activation of the mTORC1 signaling pathway, which includes protein kinases and transcription factors such as P-4E/BP1 and P-S6K1.Keywords: osteoblast, osteoporosis, menopause, mTOR

Alzheimer's disease (AD, also known as dementia) has become a serious global health problem along with population aging, and neuroinflammation is the underlying cause of cognitive impairment in the brain. Nowadays, the development of multitarget anti-AD drugs is considered to be one effective approach. Imidazolylacetophenone oxime ethers or esters (IOEs) were multifunctional agents with neuroinflammation inhibition, metal chelation, antioxidant and neuroprotection properties against Alzheimer's disease. In this study, IOEs derivatives 1-8 were obtained by structural modifications of the oxime and imidazole groups, and the SARs showed that (Z)-oxime ether (derivative 2) had stronger anti-neuroinflammatory and neuroprotective ability than (E)-congener. Then, IOEs derivatives 9-30 were synthesized based on target-directed ligands and activity-based groups hybridization strategy. In vitro anti-AD activity screening revealed that some derivatives exhibited potentially multifunctional effects, among which derivative 28 exhibited the strongest inhibitory activity on NO production with EC 50 value of 0.49 μM, and had neuroprotective effects on 6-OHDA-induced cell damage and RSL3-induced ferroptosis. The anti-neuroinflammatory mechanism showed that 28 could inhibit the release of pro-inflammatory factors PGE 2 and TNF-α, down-regulate the expression of iNOS and COX-2 proteins, and promote the polarization of BV-2 cells from pro-inflammatory M1 phenotype to anti-inflammatory M2 phenotype. In addition, 28 can dose-dependently inhibit acetylcholinesterase (AChE) and Aβ 42 aggregation. Moreover, the selected nuclide [ 18 F]-labeled 28 was synthesized to explore its biodistribution by micro-PET/CT, of which 28 can penetrate the blood-brain barrier (BBB). These results shed light on the potential of 28 as a new multifunctional candidate for AD treatment., 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 Masson SAS. All rights reserved.)

Background: Sick sinus syndrome (SSS) is a common condition resulting in reduced quality of life, syncope, and permanent pacemaker (PPM) implantation, but predictors have not been elucidated. Whereas atrial arrhythmias are frequently associated with SSS, we hypothesized that atrial flutter (AFL) would strongly predict SSS, given shared relationships with right atrial and particularly crista terminalis fibrosis., Objective: The study aimed to assess the impact of AFL on the occurrence of SSS and associated syncope and PPM implantation., Methods: Health care databases were used to identify adults aged ≥18 years receiving hospital-based care in California in 2005-2019. International Classification of Diseases codes were used to identify diagnoses and procedures. Patients were classified on the basis of the presence of AFL and atrial fibrillation (AF). Cox proportional hazards models adjusting for demographics and comorbidities were employed., Results: We included 29,357,609 individuals (54% female; mean age, 46 years), 101,243 with AFL alone, 1,674,680 with AF alone, and 284,547 with AF and AFL. After adjustment for age, sex, race and ethnicity, and comorbidities, AF, AFL, and both arrhythmias were each associated with increased risk of SSS and associated syncope and PPM implantation (all P < .001). In the population with AF, an additional AFL diagnosis conferred a higher risk for development of SSS (hazard ratio [HR],1.62; 95% confidence interval, 1.59-1.64), syncope (HR, 1.63; 1.54-1.72), and PPM implantation (HR, 1.74; 1.70-1.79)., Conclusion: AFL is associated with an increased risk of incident SSS and its adverse consequences, especially in patients with coexisting AF. AFL may be useful for risk stratification strategies to predict, to prevent, and to treat SSS., Competing Interests: Disclosures Dr Marcus reports receiving funding from the NIH, PCORI, and the California Department of Cannabis Control; he is a consultant for and equity holder in InCarda., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Purpose: To determine how low inorganic phosphate stress (LIPS) induced by sevelamer transartieral embolization (S-TAE) affects immune regulation and angiogenesis in hepatocellular carcinoma (HCC)., Material and Methods: Transcatheter arterial embolization (TAE) using conventional lipiodol plus Poly (vinyl alcohol) (PVA) microsphere and S-TAE were conducted on a McA-RH7777 orthotopic liver tumor model in rats, followed by the assessment of alterations in immunity- and angiogenesis-related factors. The cells were cultured under hypoxic conditions and stimulated with LIPS to analyze the modulation of programmed cell death 1 ligand 1 (PD-L1), vascular endothelial growth factor (VEGFα), and transforming growth factor-β1 (TGF-β1) expression through Western blotting, qRT‒PCR, and immunofluorescence assays. Cell migratory capacity and angiogenesis were also evaluated., Results: TAE increased the expression of neoplastic PD-L1 and VEGFα, and S-TAE, which depletes intratumoral Pi, downregulated the expression of PD-L1, VEGFα and TGF-β1, and augmented the infiltration of CD8+ T-cells, thereby inhibited angiogenesis and activated anticancer immunity. In vitro, the study demonstrated that LIPS inhibits hypoxia-induced upregulation of PD-L1 expression and the HIF-1α/VEGFα axis. Moreover, LIPS inhibited the tube formation ability of Human Umbilical Vein Endothelial Cells (HUVECs) and the migration ability and epithelial-mesenchymal transition (EMT) process of cancer cells under hypoxic conditions., Conclusions: S-TAE inhibited the expression of PD-L1 and VEGFα, thereby activated anti-tumor immunity and suppressing tumor angiogenesis. All the findings reveal the biology of tumors under low Pi stress and suggest the potential therapeutic value of S-TAE., (Copyright © 2024. Published by Elsevier Inc.)

Background: Prevalence estimates of atrial fibrillation (AF) from large populations have not been updated for >2 decades. Using data from 1996 to 1997, a previous study projected that there would be 3.3 million adults with AF in the United States in 2020., Objectives: The purpose of this study was to determine the contemporary age-, sex-, and race-standardized prevalence and the number of adults with diagnosed AF in the United States., Methods: We merged California's state-wide health care databases to assemble a cohort of adults aged ≥20 years who received hospital-based care in California from 2005 to 2019. International Classification of Diseases codes were used to identify AF and other comorbidities. After accounting for deaths, we utilized the U.S. Census to calculate the national age-, sex-, and race-standardized estimates of diagnosed AF., Results: Of 29,250,310 patients (mean age 50.6 ± 19.8 years, 53.8% women, 50.1% White), 2,003,867 (6.8%) had an AF diagnosis. The proportion of patients with diagnosed AF increased from 4.49% in 2005 to 2009 to 6.82% in 2015 to 2019. Over time, AF patients became relatively younger, were less likely to be female or White, and were more likely to have hypertension and diabetes. Standardizing based on age-, sex-, race-, and ethnicity-based proportions to the U.S. population, we estimate that the current national prevalence of diagnosed AF is at least 10.55 million (95% CI: 10.48-10.62 million), comprising 4.48% (95% CI: 4.47%-4.49%) of the adult population., Conclusions: The prevalence of diagnosed AF in the United States is higher than previously estimated. More efficient prevention and treatment strategies are needed to curb the burden of AF in the United States., Competing Interests: Funding Support and Author Disclosures This study was supported by the National Institutes of Health/National Heart, Lung, and Blood Institute, Grant R01HL158825-01 (to Dr Marcus). Dr Marcus has received funding from the National Institutes of Health, PCORI, and the California Department of Cannabis Control; and is a consultant for and equity holder in InCarda. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Although smoking heightens the risk of AF, it remains unknown if that risk is amenable to modification after smoking cessation., Objectives: This study sought to evaluate the association between smoking cessation and atrial fibrillation (AF) risk in a large longitudinal cohort., Methods: After excluding those with prevalent AF and no history of smoking at baseline, we evaluated 146,772 UK Biobank participants with serial smoking assessments. We compared AF risk between former smokers at baseline and those who quit smoking during the study to current smokers. Incident AF was ascertained from outpatient and inpatient encounters and identified using International Classification of Diseases codes. Cox models were used to compare the risk of incident AF among current and former smokers as well as those who quit smoking during the study while controlling for age, sex, race, body mass index, education, cardiovascular comorbidities, alcohol use, and pack-years., Results: Among the 146,772 participants (48.3% female; age: 57.3 ± 7.9 years), 37,377 (25.5%) currently smoked; 105,429 (72.0%) were former smokers; and 3,966 (2.7%) quit smoking during the study. Over a mean 12.7 ± 2.0 years of follow-up, 11,214 (7.6%) participants developed AF. Compared to current smokers, the adjusted risk of AF was 13% lower in former smokers (HR: 0.87; 95% CI: 0.83-0.91) and 18% lower in those who quit smoking during the study (HR: 0.82; 95% CI: 0.70-0.95)., Conclusions: Compared to those who continue to smoke, smoking cessation was associated with a lower risk of AF., Competing Interests: Funding Support and Author Disclosures This research was conducted using the UK Biobank resource. UK Biobank is supported by its founding funders the Wellcome Trust and UK Medical Research Council, as well as the British Heart Foundation, Cancer Research UK, Department of Health, Northwest Regional Development Agency, and Scottish Government. Dr Marcus receives funding from the National Institutes of Health, Patient-Centered Outcomes Research Institute, and California Tobacco-Related Disease Research Program and is a consultant for and owns equity in InCarda. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

As one of the main pathmechanisms of Alzheimer's disease (AD), amyloid-β (Aβ) is widely considered to be the prime target for the development of AD therapy. Recently, imidazolylacetophenone oxime ethers or esters (IOEs) have shown neuroprotective effects against neuronal cells damage, suggesting their potential use in the prevention and treatment of AD. Thirty IOEs compounds from our lab in-house library were constructed and screened for the inhibitory effects on Aβ 42 -induced cytotoxicity. Among them, TJ1, as a new IOEs hit, preliminarily showed the effect on inhibiting Aβ 42 -induced cytotoxicity. Furthermore, the inhibitory effects of TJ1 on Aβ 42 aggregation were tested by ThT assays and TEM. The neuroprotective effects of TJ1 were evaluated in Aβ 42 -stimulated SH-SY5Y cells, LPS-stimulated BV-2 cells, and H 2 O 2 - and RSL3-stimulated PC12 cells. The cognitive improvement of TJ1 was assessed in 5xFAD (C57BL/6J) transgenic mouse. These results showed that TJ1 had strong neuroprotective effects and high blood-brain barrier (BBB) permeability without obvious cytotoxicity. TJ1 impeded the self-accumulation process of Aβ 42 by acting on Aβ oligomerization and fibrilization. Besides, TJ1 reversed Aβ-, H 2 O 2 - and RSL3-induced neuronal cell damage and decreased neuroinflammation. In 5xFAD mice, TJ1 improved cognitive impairment, increased GSH level, reduced the level of Aβ 42 and Aβ plaques, and attenuated the glia reactivation and inflammatory response in the brain,. Taken together, our results demonstrate that TJ1 improves cognitive impairments as a new neuroprotective candidate via targeting amyloidogenesis, which suggests the potential of TJ1 as a treatment for AD., 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 B.V. All rights reserved.)

Background: The epidemiology of atrial fibrillation (AF)-associated thromboembolic complications outside of ischemic strokes has not been thoroughly elucidated., Objective: The aim of this study was to describe the epidemiology of AF-associated systemic infarcts and relevant interactions by sex and race/ethnicity., Methods: Using the Office of Statewide Health Planning and Development, we performed a longitudinal analysis of patients aged ≥18 years who received ambulatory surgery, emergency, or inpatient medical care in California between 2005 and 2015. We determined the distribution of infarct locations and risks of systemic infarcts for patients with AF. Interaction analyses by sex and race/ethnicity were conducted., Results: Of 1,321,694 patients with AF, the average annual rate of systemic infarct was 2.1% ± 0.18% compared with 0.56% ± 0.06% in the 22,944,488 patients without AF. The increased frequency of these infarcts was observed for every body area investigated. After adjustment for potential confounders and mediators, patients with AF experienced a 45% increased risk of a systemic infarct (hazard ratio, 1.45; 95% confidence interval, 1.44-1.47; P < .001). Women, Asians, Blacks, and Hispanics each exhibited a statistically significant heightened relative risk of systemic infarcts in the presence of AF., Conclusion: AF increases the risk of infarcts throughout the body. Susceptibility to these systemic infarcts varies by sex and race/ethnicity in patterns similar to differential risks for stroke. The presence of a systemic infarct in the absence of a clear cause should raise suspicion for AF, and the potential benefits of AF prevention and anticoagulation should be considered beyond only infarcts to the brain., Competing Interests: Disclosures Dr Marcus receives research funding from the National Institutes of Health and PCORI and is a consultant for and holds equity in InCarda. The remaining authors have nothing to disclose., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Artemisinin (ART) analogs, such as dihydroartemisinin, arteether, artemether, and artesunate, all featuring an endoperoxide bridge, have demonstrated efficacy against schistosomiasis. Artemisitene (ATT), which contains an additional α, β-unsaturated carbonyl structure, has shown enhanced biological activities. This study aims to evaluate the anti-schistosomaiasis japonica activity of ATT and compare it with ART., Methods: We assessed liver inflammation and fibrosis in mice using hematoxylin and eosin staining and Sirius red staining, respectively. RNA sequencing analyzed transcriptomics in female and male Schistosoma japonicum (S. japonicum) adult worms and mice livers, with cytokine profiling and flow cytometry to study immune responses under ART or ATT treatment., Results: ATT exhibits a marked reduction in female S. japonicum adult worms and egg numbers, damaging the adult worms' surface. It also influences the transcription of genes related to cellular anatomical structures. Notably, ATT treatment resulted in significant reductions in liver granuloma size and collagen area, alongside lowering serum levels of glutamic pyruvic and glutamic oxaloacetic transaminase more effectively than ART. Both ART and ATT markedly decreased neutrophil frequency in the liver and elevated eosinophil counts. However, only ATT treatment significantly reduced the M1/M2 and Th1/Th2 indices, indicating a pronounced shift in immune response profiles. ATT-affected host immunity correlated with the extent of liver fibrosis and the count of single males more strongly than ART., Conclusion: ATT, as a novel preventive strategy for schistosomiasis japonica in mice, significantly outperforms ART., (© 2024. The Author(s).)

Inhibition of oxidative stress and ferroptosis is currently considered to be a promising therapeutic approach for neurodegenerative diseases. Herpotrichones, a class of compounds derived from insect symbionts, have shown potential for neuroprotective activity with low toxicity. However, the specific mechanisms through which herpotrichones exert their neuroprotective effects remain to be fully elucidated. In this study, the natural [4 + 2] adducts herpotrichone A ( He-A ) and its new analogues were isolated from the isopod-associated fungus Herpotrichia sp. SF09 and exhibited significantly protective effects in H 2 O 2 -, 6-OHDA-, and RSL3-stimulated PC12 cells and LPS-stimulated BV-2 cells. Moreover, He-A was able to relieve ferroptotic cell death in RSL3-stimulated PC12 cells and 6-OHDA-induced zebrafish larvae. Interestingly, He-A can activate antioxidant elements and modulate the SLC7A11 pathway without capturing oxidic free radical and chelating iron. These findings highlight He-A as a novel hit that protects against ferroptosis-like neuronal damage in the treatment of neurodegenerative diseases.

Colorectal cancer (CRC) is the third most common type of cancer in the world. It is characterized by complex crosstalk between various signaling pathways, as a result of which it is highly challenging to identify optimal therapeutic targets and design treatment strategies. In this study, we tested the effect of 700 compounds on the CRC cell line HT-29 by using the sulforhodamine B assay and screened out 17 compounds that exhibited high toxicity (indicated by an inhibition rate of ≥75 % when applied at a concentration of 10 µM) against the HT-29 cell line. Next, we investigated the mechanisms underlying the effects of these 17 highly toxic compounds. The results of ferroptosis analysis and electron microscopy showed that compounds 575 and 578 were able to significantly reverse RSL3-induced increase in ferroptosis, while compound 580 had a less pronounced ferroptosis-regulating effect. In subsequent experiments, western blotting showed that compounds 575, 578, and 580, which belong to a class of meroterpene-like compounds that affect ferroptosis, do not induce autophagy or apoptosis in the CRC cell line. Instead, Fe 2+ chelation experiments showed that these three compounds can serve as iron chelators by chelating Fe 2+ at a 1:1 (chelator: Fe 2+ ) ratio. Specifically, the aldehyde and hydroxyl groups of the benzene ring in these compounds may chelate Fe 2+ , thus reducing Fe 2+ levels in cells and inhibiting ferroptosis. These results indicate that these novel meroterpene-like compounds are potential therapeutic small-molecule candidates for targeting ferroptosis in tumors., 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.)

LiFePO 4 is widely used because of its high safety and cycle stability, but its inefficient electronic conductivity combined with sluggish Li + diffusivity restricts its performance. To overcome this obstacle, applying a layer of conductive carbon onto the surface of LiFePO 4 has the greatest improvement in electronic conductivity and Li + diffusivity. However, the rate performance of carbon-coated LiFePO 4 makes it difficult to meet the application requirements. Although nitrogen doping improves electrochemical performance by providing active sites and electronic conductivity, the N-doped carbon coating is prone to agglomeration, which causes a sharp decrease in capacity when the current rate increases. In this work, a synergistic N, Mn codoping strategy is implemented to overcome the aforementioned drawbacks by disrupting the large agglomeration of C-N bonds, improving the uniformity of the surface coating layer to enhance the completeness of the conductive network and increasing the number of Li + diffusion channels, and thus accelerating the mass transfer rate under high-rate current. Consequently, this strategy effectively improves the rate capability (119 mA h g -1 at 10 C) while maintaining excellent cycling performance (88% capacity retention over 600 cycles at 5 C). This work improves the rate of ion diffusion and the rate capability of micrometer-sized LiFePO 4 , thus, enabling its wider application.

Alzheimer's disease (AD) is a complex neurodegenerative condition. 5α-epoxyalantolactone (5α-EAL), a eudesmane-type sesquiterpene isolated from the herb of Inula macrophylla, has various pharmacological effects. This work supposed to investigate the improved impact of 5α-EAL on cognitive impairment. 5α-EAL inhibited the generation of nitric oxide (NO) in BV-2 cells stimulated with lipopolysaccharide (LPS) with an EC 50 of 6.2 μM. 5α-EAL significantly reduced the production of prostaglandin E2 (PGE 2 ) and tumor necrosis factor-α (TNF-α), while also inhibiting the production of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) proteins. The ability of 5α-EAL to penetrate the blood-brain barrier (BBB) was confirmed via a parallel artificial membrane permeation assay. Scopolamine (SCOP)-induced AD mice model was employed to assess the improved impacts of 5α-EAL on cognitive impairment in vivo. After the mice were pretreated with 5α-EAL (10 and 30 mg/kg per day, i.p.) for 21 days, the behavioral experiments indicated that the administration of the 5α-EAL could alleviate the cognitive and memory impairments. 5α-EAL significantly reduced the AChE activity in the brain of SCOP-induced AD mice. In summary, these findings highlight the beneficial effects of the natural product 5α-EAL as a potential bioactive compound for attenuating cognitive deficits in AD due to its pharmacological profile., (© 2024. The Author(s).)

Objective: To investigate the clinical efficacy of simultaneous arthroscopic repair of anterior talofibular ligament (ATFL) and calcaneofibular ligament (CFL) for treating chronic lateral ankle instability (CLAI) in conjunction with subtalar instability (STI). Methods: This is a retrospective case series study. The clinical data of 15 patients with ankle arthroscopic in the Department of Hand and Foot Surgery, the Second Affiliated Hospital of Soochow University from January 2019 to December 2022 were analyzed retrospectively. There were 11 male cases and 4 female cases, aged (28.6±1.5) years (range: 19 to 39 years). All the patients were evaluated by manual inversion stress X-ray and MRI before operation. Arthroscopically observing and then repairing the ATFL and CFL separately after further diagnostic confirmation. One year after operation, MRI was performed, and pain visual analogue score(VAS), American Orthopedic Foot and Ankle Society ankle hindfoot scale (AOFAS-AH) and Karlsson ankle functional scale(KAFS) were evaluated. Data were compared using paired sample t test. Results: The follow-up period was (23.6±2.3) months (range: 12 to 30 months). At last follow-up,the VAS decreased from 6.1±1.4 preoperatively to 1.4±1.2( t =9.482, P <0.01).The AOFAS-AH improved from 50.5±11.7 preoperatively to 94.2±6.1( t =-13.132, P <0.01), and the KAFS improved from preoperatively 44.3±10.8 to 90.8±6.4 ( t =-12.510, P <0.01). There was no complication such as recurred instability or joint stiffness. Conclusions: Arthroscopically repairing the ATFL and CFL separately can effectively restore the stability of the ankle and subtalar joint with small trauma. Patients can recover quickly after surgery. It provides a new idea for the clinical treatment of CLAI combined with STI.

A simple, efficient, and practical method for the synthesis of S-quinolyl xanthates was developed via Ts 2 O-promoted deoxygenative C-H dithiocarbonation of quinoline N-oxides with various potassium O-alkyl xanthates. The reaction performed well under transition-metal-free, base-free, and room-temperature conditions with wide substrate tolerance. Employing potassium O - tert -butyl xanthate ( t BuOCS 2 K) as a nucleophile, some valuable quinoline-2-thiones were unexpectedly obtained in a one-pot reaction without any additional base.

Background: The prognosis for atrial fibrillation (AF) patients is based on data that is decades old. Given evolving standards of clinical practice, we sought to evaluate temporal trends in clinically important outcomes among patients with AF., Methods: California's Department of Health Care Access and Information databases were used to identify adults aged ≥ 18 years with AF receiving hospital-based care in California. We compared 3 time-periods: 2005-2009, 2010-2014, and 2015-2019. ICD codes were used to identify chronic diseases and acute events. The outcomes were incident ischemic stroke, intracranial hemorrhage, and overall mortality., Results: We included 2 009 832 patients with AF (52.7% males, 70.7% Whites, and mean age of 75.0 years), divided in 3 cohorts: 2005-2009 (n = 738 954), 2010-2014 (n = 609 447), and 2015-2019 (n = 661 431). Each outcome became substantially less common with time: compared to 2005-2009, AF patients diagnosed in 2015-2019 experienced a 34% (adjusted hazard ratio [HR] 0.66, 95% CI 0.64-0.69), 22% (HR 0.78, 0.75-0.82), and 24% (HR 0.76, 0.75-0.77) reduction in risk of incident ischemic stroke, intracranial hemorrhage, and mortality, respectively. Between 2005-2009 and 2015-2019, patients aged ≥ 65 years experienced more reductions in each outcome compared to younger patients (p < 0.001 for all), and declines in each outcome were significantly lower for Hispanics and Blacks compared to white patients., Conclusion: The risks of stroke, intracranial hemorrhage, and death have significantly declined among AF patients, although differences in the magnitude of improvement of these outcomes by demographic groups were observed. Commonly described estimates of the prognosis for AF patients should be updated to reflect contemporary care., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Inubritantrimer A ( 1 ), a trace trimerized sesquiterpenoid [4 + 2] adduct featuring an unusual exo - exo type spiro-polycyclic scaffold, together with three new endo - exo [4 + 2] adducts, inubritantrimers B-D ( 2 - 4 ), were discovered from the flowers of Inula britannica . Their structures were elucidated using 1D/2D NMR, X-ray diffraction, and ECD approaches. 1 is characterized as a novel exo - exo trimer, synthesized biogenetically from three sesquiterpenoid monomers, featuring a unique linkage of C-11/C-1', C-13/C-3' and C-13'/C-3″, C-11'/C-1″ through a two-step exo [4 + 2] cycloaddition process. Compounds 1 - 4 exhibited modest cytotoxicity against breast cancer cells with IC 50 values in the range of 5.84-12.01 μM.

Background: Cannabis use is increasing worldwide. While prior studies have reported an association between cannabis use and a higher risk of atrial fibrillation (AF), most were cross-sectional and generally relied on diagnostic coding to identify cannabis users, which may not be representative of the typical recreational cannabis user., Objective: The purpose of this study was to examine the association between recreational cannabis use and lifetime AF risk., Methods: We evaluated the AF risk of participants of the UK Biobank cohort who completed the cannabis use lifestyle questionnaire. Cannabis exposure was categorized as "Occasional Use" for less than 100 times used, "Frequent Use" for more than 100 times used, and "Never" users. AF events were identified using International Classification of Diseases codes. Cox models were used to estimate the hazard ratios (HRs) between cannabis use and incident AF and were subsequently adjusted for age, sex, race, alcohol, coffee, smoking, education, and baseline cardiovascular comorbidities., Results: A total of 150,554 participants (mean age 63.4 ± 7.7 years; 86,487 (57.4%) female; and 33,442 (22.2%) using cannabis at least once) were followed for a mean period of 6.1 ± 0.6 years. After multivariable adjustment, there were no statistically significant differences in incident AF among occasional users (HR 0.98; 95% confidence interval 0.89-1.08) nor frequent users (HR 1.03; 95% confidence interval 0.81-1.32) as compared with never users., Conclusion: In a large prospective cohort study, there was no evidence that cannabis use was associated with a higher risk of incident AF. An evaluation of cannabis ingestion methods and quantification was not possible using the current data set., Competing Interests: Disclosures Dr Marcus is a consultant for Johnson & Johnson and InCarda and owns equity in InCarda. The rest of the authors report no conflicts of interest., (Copyright © 2023 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Antibiotic-resistant Serratia marcescens (Sm) is known to cause bloodstream infections, pneumonia, etc. The nod-like receptor family, pyrin domain-containing 3 (NLRP3), has been implicated in various lung infections. Yet, its role in Sm-induced pneumonia was not well understood. In our study, we discovered that deletion of Nlrp3 in mice significantly improved Sm-induced survival rates, reduced bacterial loads in the lungs, bronchoalveolar lavage fluid (BALF), and bloodstream, and mitigated the severity of acute lung injury (ALI) compared to wild-type (WT) mice. Mechanistically, we observed that 24 h post-Sm infection, NLRP3 inflammasome activation occurred, leading to gasdermin D NH2-terminal (GSDMD-NT)-induced pyroptosis in macrophages and IL-1β secretion. The NLRP3 or NLRP3 inflammasome influenced the expression PD-L1 and PD-1, as well as the count of PD-L1 or PD-1-expressing macrophages, alveolar macrophages, interstitial macrophages, PD-L1-expressing neutrophils, and the count of macrophage receptors with collagenous structure (MARCO)-expressing macrophages, particularly MARCO + alveolar macrophages. The frequency of MARCO + alveolar macrophages, PD-1 expression, particularly PD-1 + interstitial macrophages were negatively or positively correlated with the Sm load, respectively. Additionally, IL-1β levels in BALF correlated with three features of acute lung injury: histologic score, protein concentration and neutrophil count in BALF. Consequently, our findings suggest that Nlrp3 deletion offers protection agaisnt acute Sm pneumonia in mice by inhibiting inflammasome activation and reducing Sm infection-induced PD-L1/PD-1 or MARCO expression, particularly in macrophages. This highlights potential therapeutic targets for Sm and other gram-negative bacteria-induced acute pneumonia., 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 B.V. All rights reserved.)

The incorporation of amide groups into biologically active molecules has been proven to be an efficient strategy for drug design and discovery. In this study, we present a simple and practical method for the synthesis of amide-containing quinazolin-4(3 H )-ones under transition-metal-free conditions. This is achieved through a carbamoyl-radical-triggered cascade cyclization of N3-alkenyl-tethered quinazolinones. Notably, the carbamoyl radical is generated in situ from the oxidative decarboxylative process of oxamic acids in the presence of (NH 4 ) 2 S 2 O 8 .

Inubritanolides C and D (1 and 2), two exo sesquiterpenoid [4 + 2] adducts with unprecedented interconverting conformations of twist-chair and chair, together with two previously undescribed endo [4 + 2] dimers (3 and 4) were discovered from Inula britannica flowers. Dimers 1 and 2 have an undescribed carbon skeleton comprising of eudesmanolide and guaianolide units with the linkage mode of C-11/C-1' and C-13/C-3' via a Diels-Alder cycloaddition reaction. Their structures were elucidated using 1D/2D NMR, X-ray diffraction, ECD, and variable-temperature NMR experiments. Dimer 2 displayed a strong inhibitory effect on breast cancer cells by promoting lipid ROS production, showing its potential as ferroptosis inducer., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

A visible-light-driven iron-catalyzed C(sp 3 )-H amination of diphenylmethane derivatives with 1,2,3,4-tetrazoles under mild conditions has been developed. The reaction proceeds with photosensitizer-free conditions and features satisfactory to good yields. Mechanistic studies revealed that the reaction proceeded via an iron-nitrene intermediate, and H atom abstraction was the rate-determining step. Computational studies showed that the denitrogenation of 1,2,3,4-tetrazole depends on the conversion of the sextet ground state of 1,2,3,4-tetrazole-bounding iron species to the quartet spin state under visible-light irradiation.

Background: Occult breast cancer (OBC) has traditionally been considered to be a carcinoma of unknown primary origin with a favorable prognosis and can be treated as stage II-III breast cancer. Due to the small number of cases and limited clinical ex-perience, treatments vary greatly around the world and no standardized treat-ment has yet been established., Aim: To investigate the clinicopathological features, psychological status and prog-nostic features of patients with OBC., Methods: The clinicopathological data of 33 OBC patients diagnosed and treated in the Affiliated Hospital of Xuzhou Medical University and Xuzhou Central Hospital from November 2015 to November 2022 were retrospectively analyzed. The psychological status of OBC patients was evaluated by the Self-rating Anxiety Scale and Self-rating Depression Scale. Patients' emotions, stress perception and psychological resilience were evaluated by the Positive and Negative Affect Schedule, the Chinese Perceived Stress Scale, and the Connor-Davidson Resilience Scale (CD-RISC), respectively. Patient survival was calculated using the Kaplan-Meier method, and survival curves were plotted for analysis with the log-rank test. Univariate and multivariate survival analyses were performed using the Cox regression model., Results: The 33 OBC patients included 32 females and 1 male. Of the 33 patients, 30 (91%) had axillary tumors, 3 (9%) had a neck mass as the primary symptom; 18 (54.5%) had estrogen receptor-positive tumors, 17 (51.5%) had progesterone receptor-positive tumors, and 18 (54.5%) had Her-2-positive tumors; 24 (72.7%) received surgical treatment, including 18 patients who underwent modified radical mastectomy, 1 patient who underwent breast-conserving surgery plus axillary lymph node dissection (ALND), and 5 patients who underwent ALND alone; 12 patients received preoperative neoadjuvant therapy. All 30 patients developed anxiety and depression, with low positive affect scores and high negative affect scores, accompanied by a high stress level and poor psychological resilience. There were no differences in the psychological status of patients according to age, body mass index, or menopausal status. The overall survival and disease-free survival (DFS) of all the patients were 83.3% and 55.7%, respectively. Univariate analysis demonstrated that the initial tumor site ( P = 0.021) and node stage ( P = 0.020) were factors that may affect patient prognosis. The 5-year DFS rate of OBC patients who received radiotherapy was greater ( P < 0.001), while the use of different surgical methods ( P = 0.687) had no statistically significant effect on patient outcomes. Multivariate analysis revealed that radiotherapy ( P = 0.031) was an independent prognostic factor. Receiving radiotherapy had a significant effect on the CD-RISC score ( P = 0.02)., Conclusion: OBC is a rare breast disease whose diagnosis and treatment are currently controversial. There was no significant difference in the efficacy of other less invasive surgical procedures compared to those of modified radical mastectomy. In addition, radiotherapy can significantly improve patient outcomes. We should pay attention to the psychological state of patients while they receive antitumor therapy., Competing Interests: Conflict-of-interest statement: There is no conflict of interest., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Aqueous zinc-ion batteries (AZIBs) have caused significant research attention due to their low redox potential of 0.76 V, high theoretical capacity of 820 mAh g -1 . However, the dendrite growth of zinc anode and the side reactions caused by water seriously affect the cycle life of AZIBs. To solve the above problems, a new method of etching zinc anodes with CuCl 2 salt solution was designed, which the zinc anode was named CZn. The process resulted to a uniformly distributed micro gully morphology on the zinc surface, and providing an increased number of nucleation sites for zinc deposition and reducing local current density. The calculation results of exchange current density and activation energy show that CZn has stronger Zn/Zn 2+ kinetic effect. At a current density of 5 mA cm -2 and an area capacity of 5 mAh cm -2 , cycle life of the CZn symmetrical cell can reach 500 h, which is more than seven times that of the raw Zn symmetrical cell. This work proposes a simple method of zinc anode protection, which provides a new idea for zinc metal anode protection., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Chronic sleep disruption is associated with incident atrial fibrillation (AF), but it is unclear whether poor sleep quality acutely triggers AF., Objectives: The aim of this study was to characterize the relationship between a given night's sleep quality and the risk of a discrete AF episode., Methods: Patients with symptomatic paroxysmal AF in the I-STOP-AFIB (Individualized Studies of Triggers of Paroxysmal Atrial Fibrillation) trial reported sleep quality on a daily basis. Participants were also queried daily regarding AF episodes and were provided smartphone-based mobile electrocardiograms (ECGs) (KardiaMobile, AliveCor)., Results: Using 15,755 days of data from 419 patients, worse sleep quality on any given night was associated with a 15% greater odds of a self-reported AF episode the next day (OR: 1.15; 95% CI: 1.10-1.20; P < 0.0001) after adjustment for the day of the week. No statistically significant associations between worsening sleep quality and mobile ECG-confirmed AF events were observed (OR: 1.04; 95% CI: 0.95-1.13; P = 0.43), although substantially fewer of these mobile ECG-confirmed events may have limited statistical power. Poor sleep was also associated with longer self-reported AF episodes, with each progressive category of worsening sleep associated with 16 (95% CI: 12-21; P < 0.001) more minutes of AF the next day., Conclusions: Poor sleep was associated with an immediately heightened risk for self-reported AF episodes, and a dose-response relationship existed such that progressively worse sleep was associated with longer episodes of AF the next day. These data suggest that sleep quality may be a potentially modifiable trigger relevant to the near-term risk of a discrete AF episode., Competing Interests: Funding Support and Author Disclosures This study was funded by a Patient-Powered Research Network Demonstration Project award from the Patient-Centered Outcomes Research Institute and the National Institutes of Health/National Institute of Biomedical Imaging and Bioengineering (grant IU2CEB021881-01). Dr Wong’s institution has received, on his behalf, lecture, travel, and/or research funding from Abbott Medical, Bayer, Boehringer Ingelheim, Medtronic, MicroPort, Novartis, Servier, St. Jude Medical, and Vifor Pharma. Dr Marcus has received personal fees and equity interest from InCarda; personal fees from Johnson & Johnson; and grants from Baylis Medical, Medtronic, the National Institutes of Health, the Patient-Centered Outcomes Research Institute, and the California Tobacco-Related Disease Research Program during the conduct of the study. Drs Modrow and Pletcher have received grants from the Patient-Centered Outcomes Research Institute during the conduct of the study. Dr Olgin has received personal fees from AliveCor during the conduct of the study; personal fees from VivaLNK outside the submitted work; and grants from Samsung outside the submitted work. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Chemobrain is a condition that negatively affects cognition in cancer patients undergoing active chemotherapy, as well as following chemotherapy cessation. Chemobrain is also known as chemotherapy-induced cognitive impairment (CICI) and has emerged as a significant medical contingency. There is no therapy to ameliorate this condition, hence identification of novel therapeutic strategies to prevent CICI is of great interest to cancer survivors. Utilizing the platinum-based chemotherapy cisplatin in an investigative approach for CICI, we identified increased expression of cyclooxygenase-2 (COX-2) and prostaglandin E 2 (PGE 2 ) in the adult mouse hippocampus, and in human cortical neuron cultures derived from induced pluripotent stem cells (iPSCs). Notably, administration of NS398, a selective COX-2 inhibitor, prevented CICI in vivo without negatively affecting the antitumor efficacy of cisplatin or potentiating tumor growth. Given that dysfunctional mitochondrial bioenergetics plays a prominent role in CICI, we explored the effects of NS398 in cisplatin-induced defects in human cortical mitochondria. We found that cisplatin significantly reduces mitochondrial membrane potential (MMP), increases matrix swelling, causes loss of cristae membrane integrity, impairs ATP production, as well as decreases cell viability and dendrite outgrowth. Pretreatment with NS398 in human cortical neurons attenuated mitochondrial dysfunction caused by cisplatin, while improving cell survival and neurite morphogenesis. These results suggest that aberrant COX-2 inflammatory pathways may contribute in cisplatin-induced mitochondrial damage and cognitive impairments. Therefore, COX-2 signaling may represent a viable therapeutic approach to improve the quality of life for cancer survivors experiencing CICI., 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. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2023 Rashid, Tang, Yoo, Corujo-Ramirez, Oliveros, Kim, Ullah, Altawell, Hawse, Cole and Jang.)

An environmentally benign protocol that provides various S -quinolyl xanthates via a ball milling enabled cross coupling reaction of haloquinolines and readily available potassium O -alkyl xanthates is first reported. The reaction proceeded well under mild, transition metal- and solvent-free conditions, making it an attractive method for the introduction of xanthates into the quinoline scaffold.

Plant functional traits have an essential role in community formation and ecosystem function. Unlike natu-ral ecosystems, agroecosystems are affected by natural conditions and human management. Plant ( i.e ., crop)functional traits in the agroecosystems are thus shaped by natural and human selection. We reviewed the development of functional trait research, focusing on crop functional traits, research methods of agroecosystems based on traits, and the application of functional traits in agriculture. We then elaborated on the effect of domestication on crop trait trade-offs, the relationship between community functional structure and agroecosystem services, and the application of functional traits in weed management, cover cropping, and intercropping systems. Future research directions of crop functional traits include enriching the types of agroecosystems and crop species in studies, buil-ding up a crop functional trait database, and focusing on agroecosystem multifunctionality.

Objective: To explore the clinical effects of pedicled omental flap transplantation in repairing secondary rejection wounds after brain pacemaker implantation. Methods: A retrospective observational study was conducted. From January to August 2021, 5 patients with secondary rejection wounds after brain pacemaker implantation who met the inclusion criteria were admitted to the Wound Repair Center of Ruijin Hospital of Shanghai Jiao Tong University School of Medicine, including 3 males and 2 females, aged 56-69 years, with the wound developed at the pulse generator implantation site in the chest in 2 cases, at the connection site of the wire and electrode behind the ear in 2 cases, and at both the chest and the back of the ear in 1 case. All the wounds were repaired by pedicled omental flap transplantation. The wound area after debridement was 2-15 cm 2 . After operation, the wound healing and related complications (pain, infection, incisional hernia, omental flap necrosis, etc.) were observed. During follow-up, the recurrence of the wound was observed. Results: The wounds of all 5 patients healed within 2 weeks after operation, without related complications. During follow up of 12-18 months, 1 patient got a recurrence of rejection wound behind the left ear 4 months after surgery and eventually had the brain pacemaker removed; the other 4 patients had no recurrence of wounds. Conclusions: Pedicled omental flap transplantation can repair the secondary rejection wounds after brain pacemaker implantation safely and effectively, with few postoperative complications.

Diosgenin, a steroidal sapogenin, obtained from Trigonella foenum-graecum, Dioscorea, and Rhizoma polgonati, has shown high potential and interest in the treatment of various cancers such as oral squamous cell carcinoma, laryngeal cancer, esophageal cancer, liver cancer, gastric cancer, lung cancer, cervical cancer, prostate cancer, glioma, and leukemia. This article aims to provide an overview of the in vivo, in vitro, and clinical studies reporting the diosgenin's anticancer effects. Preclinical studies have shown promising effects of diosgenin on inhibiting tumor cell proliferation and growth, promoting apoptosis, inducing differentiation and autophagy, inhibiting tumor cell metastasis and invasion, blocking cell cycle, regulating immunity and improving gut microbiome. Clinical investigations have revealed clinical dosage and safety property of diosgenin. Furthermore, in order to improve the biological activity and bioavailability of diosgenin, this review focuses on the development of diosgenin nano drug carriers, combined drugs and the diosgenin derivatives. However, further designed trials are needed to unravel the diosgenin's deficiencies in clinical application., (© 2023. The Chinese Journal of Integrated Traditional and Western Medicine Press and Springer-Verlag GmbH Germany, part of Springer Nature.)

A visible-light-driven Mn-catalyzed C(sp 3 )-H amidation of diphenylmethane derivatives with dioxazolones was described. These reactions occur with an external photosensitizer-free process and feature satisfactory to good yields (up to 81%) under mild conditions. Mechanistic investigations revealed that the reaction proceeded via a Mn-acyl nitrene intermediate and that H-atom abstraction was the rate-determining step. Computational studies showed that the decarboxylation of dioxazolone depends on the conversion of ground sextet state dioxazolone-bounding Mn species to quartet spin state via visible-light irradiation.

Temperature is a key environmental factor in ectotherms and influences many life history traits. In the present study, the nymphal development time, sex ratio and wing dimorphism of the small brown planthopper Laodelphax striatellus were examined under the conditions of constant temperatures, naturally varying temperatures (or different generations), and different temperatures combined with different photoperiod. The results showed that from 18 to 28 °C, the developmental time of nymphs was gradually shortened with the increase of temperature, whereas the high temperatures of 30 and 32 °C in the third to fifth instar nymphal stages and high summer temperature of 28.8 and 29.7 °C significantly delayed developmental time and resulted in higher mortality of nymphs. In all treatments, the developmental time was longer in females than males. The nymphs took significantly longer time to develop in the short daylength of 12 h than in longer daylengths of 13, 14, 15 and 16. Differences in developmental time were also found between wing morph, with long-winged individuals being significantly longer than the short-winged individuals at lower temperatures and significantly shorter than the short-winged individuals at higher temperatures. In all treatments, the sex ratio was stable, approaching 1:1, without being affected by temperature, generations and photoperiod. Photoperiod and temperature had significantly influence on the wing dimorphism. Long daylength combined with different temperatures resulted in significantly higher proportions of long-winged morph, whereas the low temperatures combined with the short daylengths in autumn and winter resulted in significantly high proportion of short-winged morph. This study broadens our understanding of the life-history traits of this planthopper and provides basic data for analyzing the effects of climate change on the planthopper reproduction., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objective To investigate the influencing factors and establish a model predicting the performance of needle visualization in fine-needle aspiration (FNA) of thyroid nodules. Methods This study prospectively included 175 patients who underwent FNA of thyroid nodules in the Department of Ultrasound in China-Japan Friendship Hospital and compared the display of the needle tips in the examination of 199 thyroid nodules before and after the application of needle visualization.We recorded the location,the positional relationship with thyroid capsule,ultrasonic characteristics,and the distribution of the soft tissue strip structure at the puncture site of the nodules with unclear needle tips display before using needle visualization.Furthermore,according to the thyroid imaging reporting and data system proposed by the American College of Radiology,we graded the risk of the nodules.Lasso-Logistic regression was employed to screen out the factors influencing the performance of needle visualization and establish a nomogram for prediction. Results The needle tips were not clearly displayed in the examination of 135 (67.8%) and 53 (26.6%) nodules before and after the application of needle visualization,respectively,which showed a significant difference ( P <0.001).Based on the positional relationship between the nodule and capsule,anteroposterior/transverse diameter (A/T) ratio,blood supply,and the distribution of subcutaneous strip structure at the puncture site,a nomogram was established to predict the probability of unclear display of the needle tips after application of needle visualization.The C-index of the prediction model was 0.75 (95% CI =0.67-0.84) and the area under the receiver operating characteristic curve was 0.72.The calibration curve confirmed the appreciable reliability of the prediction model,with the C-index of 0.70 in internal validation. Conclusions Needle visualization can improve the display of the needle tip in ultrasound-guided FNA of thyroid nodules.The nomogram established based on ultrasound features such as the positional relationship between the nodule and capsule,A/T ratio,blood supply,and the distribution of subcutaneous strip structure at the puncture site can predict whether needle visualization is suitable for the examination of nodules.

Objective To establish a nomogram for predicting the risk of cervical lymph node metastasis in differentiated thyroid carcinoma (DTC). Methods The patients with complete clinical data of DTC and cervical lymph node ultrasound and diagnosed based on pathological evidence from January 2019 to December 2021 were assigned into a training group ( n =444) and a validation group ( n =125).Lasso regression was performed to screen the data with differences between groups,and multivariate Logistic regression to establish a prediction model with the factors screened out by Lasso regression.C-index and calibration chart were employed to evaluate the prediction performance of the established model. Results The predictive factors for establishing the model were lymph node short diameter≥0.5 cm,long-to-short-axis ratio<2,disappearance of lymph node hilum,cystic transformation,hyperechogenicity,calcification,and abnormal blood flow (all P <0.001).The established model demonstrated a good discriminative ability,with the C index of 0.938 (95% CI =0.926-0.961) in the training group. Conclusion The nomogram established based on the ultrasound image features of cervical lymph nodes in DTC can accurately predict the risk of cervical lymph node metastasis in DTC.

Objective: To describe the clinical characteristics, management and quality of life of psoriasis patients with and without coexistent lupus erythematosus (LE)., Methods: This retrospective cross-sectional study uses data from the Malaysian Psoriasis Registry (MPR) from January 2007 to December 2018., Results: Of 21 735 psoriasis patients, 34 (0.16%) had coexistent LE. The male to female ratio among psoriasis patients with coexistent LE was 1:5.8 versus 1.3:1 in patients with psoriasis but without LE. Nearly 70% presented with LE preceding psoriasis. Psoriasis patients with LE had an earlier age of psoriasis onset (27.56 ± 11.51 versus 33.31 ± 16.94 years, P = 0.006), a higher rate of psoriatic arthropathy (26.5% versus 13.0%, P = 0.02), and a significantly greater impairment of quality of life (Dermatology Quality of Life Index >10; 57.6% versus 40.3%, P = 0.04) compared with psoriasis patients without LE. The majority (87.5%) had systemic LE. The incidences of lupus nephritis (72.7% versus 40%) and hematological abnormalities (50% versus 20%) were higher among patients with LE preceding psoriasis compared with those with psoriasis preceding LE. Antinuclear antibody and double-stranded DNA were positive in 59.4% and 28.1% of psoriasis patients with LE, respectively. Hydroxychloroquine triggered the onset of psoriasis in 7 (24.1%) patients. Patients with LE were more likely to receive systemic treatment for psoriasis compared with those without LE (30.3% versus 14.2%, P = 0.008)., Conclusions: Psoriasis patients with coexistent LE were uncommon, displayed a female preponderance, were more likely to have joint involvement, and had greater quality of life impairment than those without LE. LE preceded psoriasis in most of these patients, and systemic LE was the most common subtype., (© 2022 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

Case: A 20-year-old man with a Tile C1.2 pelvic fracture was treated with skeletal traction. After 3 months, the patient was unable to stand and walk, and the right lower limb was shortened by 7 cm. Radiographs showed that the sacroiliac joint dislocation was not reduced. Gradual traction reduction with the Ilizarov method was used to correct sacroiliac joint dislocation, and open internal fixation was performed. Postoperatively, the old pelvic fracture was successfully reduced without sacral plexus injury., Conclusion: Gradual traction reduction with the Ilizarov method can reduce the risk of sacral plexus injury and achieve satisfactory reduction of Tile C1.2 old pelvic fractures., Competing Interests: Disclosure: The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article (http://links.lww.com/JBJSCC/C3)., (Copyright © 2023 The Authors. Published by The Journal of Bone and Joint Surgery, Incorporated. All Rights Reserved.)

A series of novel trienomycin A (TA)-mimetic compounds (5a-p) have been designed, synthesized, and evaluated for their in vitro anti-neuroinflammatory and neuroprotective activities. Among them, compounds 5h, 5n, and 5o exhibits relatively strong NO inhibitory activity in LPS-activated BV-2 cells with the EC 50 values of 12.4, 17.3, and 8.9 μM, respectively. Moreover, 5h showed evidently neuroprotective effect against H 2 O 2 -induced PC-12 cells without cytotoxicity at 20 μM. Overall, these compounds can provide a better understanding of the structure-activity relationship of TA and furnish research ideas for anti-neuroinflammatory and neuroprotective agents., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Arterial remodeling is a common pathological basis of cardiovascular diseases such as atherosclerosis, vascular restenosis, hypertension, pulmonary hypertension, aortic dissection, and aneurysm. Vascular smooth muscle cells (VSMCs) are not only the main cellular components in the middle layer of the arterial wall but also the main cells involved in arterial remodeling. Dedifferentiated VSMCs lose their contractile properties and are converted to a synthetic, secretory, proliferative, and migratory phenotype, playing key roles in the pathogenesis of arterial remodeling. As mitochondria are the main site of biological oxidation and energy transformation in eukaryotic cells, mitochondrial numbers and function are very important in maintaining the metabolic processes in VSMCs. Mitochondrial dysfunction and oxidative stress are novel triggers of the phenotypic transformation of VSMCs, leading to the onset and development of arterial remodeling. Therefore, pharmacological measures that alleviate mitochondrial dysfunction reverse arterial remodeling by ameliorating VSMCs metabolic dysfunction and phenotypic transformation, providing new options for the treatment of cardiovascular diseases related to arterial remodeling. This review summarizes the relationship between mitochondrial dysfunction and cardiovascular diseases associated with arterial remodeling and then discusses the potential mechanism by which mitochondrial dysfunction participates in pathological arterial remodeling. Furthermore, maintaining or improving mitochondrial function may be a new intervention strategy to prevent the progression of arterial remodeling.

Aims: Atrial fibrillation (AF) is now regarded as a preventable disease, requiring a search for modifiable risk factors. With legalization of cannabis and more lenient laws regarding the use of other illicit substances, investigation into the potential effects of methamphetamine, cocaine, opiate, and cannabis exposure on incident AF is needed., Methods and Results: Using Office of Statewide Health Planning and Development databases, a longitudinal analysis was performed of adult Californians ≥18 years of age who received care in an emergency department, outpatient surgery facility, or hospital from 1 January 2005 to 31 December 2015. Associations between healthcare coding for the use of each substance and a new AF diagnosis were assessed. Among 23,561,884 patients, 98 271 used methamphetamine, 48 701 used cocaine, 10 032 used opiates, and 132 834 used cannabis. Of the total population, 998 747 patients (4.2%) developed incident AF during the study period. After adjusting for potential confounders and mediators, use of methamphetamines, cocaine, opiates, and cannabis was each associated with increased incidence of AF: hazard ratios 1.86 [95% confidence interval (CI) 1.81-1.92], 1.61 (95% CI 1.55-1.68), 1.74 (95% CI 1.62-1.87), and 1.35 (95% CI 1.30-1.40), respectively. Negative control analyses in the same cohort failed to reveal similarly consistent positive relationships., Conclusion: Methamphetamine, cocaine, opiate, and cannabis uses were each associated with increased risk of developing incident AF. Efforts to mitigate the use of these substances may represent a novel approach to AF prevention., Competing Interests: Conflict of interest: T.A.D. reports consulting for Adagio Medical and Farapulse. G.M.M. reports grants from the NIH (NHLBI, NIBIB), PCORI, California TRDRP, and Baylis Medical; consulting for Johnson and Johnson and InCarda; and stock in InCarda. All other authors declare that there are no conflicts of interest to disclose., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Polarized structured nitride semiconductors are attractive due to their unique and environment-friendly electronic properties. The stability, ferroelectricity and photocatalytic and photovoltaic properties of super-wurtzite Mg 2 XN 3 (X = Bi, Mo, Nb, Sb, Ta, Tc and W) were determined based on first principles calculations in this study. The calculated results indicate that Mg 2 XN 3 (X = Sb, Ta, Bi and Nb) are stable polar nitrides by phonon frequencies, elastic coefficients and ferroelectric analysis. Mg 2 XN 3 (X = Sb, Ta and Nb) with large ferroelectric polarization strength could absorb ultraviolet light to promote photocatalytic water splitting for hydrogen production. Mg 2 BiN 3 is a new excellent photovoltaic candidate due to its ideal energy band, high electron mobility, high absorption coefficient and large ferroelectric polarization strength.

As the most efficient method to treat hepatocellular carcinoma in the immediate or advanced stage, transarterial chemoembolization (TACE) is coming into the era of microsphere (MP). Drug-eluting beads have shown their huge potential as an embolic agent and drug carrier for chemoembolization, but their sizes are strictly limited to be above 40 μm, which was considered to occlude vessels in a safe mode. microsphere smaller than 40 µm is easy to be washed out and transported to the normal liver lobe or other organs, causing severe adverse events and failed embolization. To determine whether sevelamer ultrafine particle (0.2-0.5 µm) is qualified as a safe and efficient embolic agent, we investigated the safety and therapeutic efficiency of transarterial sevelamer embolization (TASE) in the VX2 rabbit liver cancer model, aiming to challenge the "40 µm" rule on the selection criteria of the MP. In a four-arm study, blank bead (Callisphere, 100-300 µm), luminescent polystyrene microsphere (10, 100 µm), and sevelamer particle were transarterially administered to evaluate the threshold size of the MP size for intrahepatic or extrahepatic permeability. Another four-arm study was designed to clarify the safety and efficiency of preclinical transarterial sevelamer embolizationTASE tests over other techniques. Sham (saline), TASE, C-TACE, and D-TACE ( n = 6) were compared in terms of serum chemistry, histopathology, and tumor necrosis ratio. In the first trials, the "40 µm" rule was detectable on the VX2 cancer model, but the regulation has no application to the new embolic agent as sevelamer ultrafine particles have not been found to leak out from the VX2 lesions, only found in the embolized vessels. Pathology proves that less viable tumor residue was found 2 weeks after the procedure, evidencing a better therapeutic outcome. No adverse events were found except for a short stress response. These results indicate that sevelamer is a safe and efficient embolic as an alternative to the current MP-based embolization therapy techniques., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Chen, Xie, Li, Deng, Lv, Bi, Tang, Luo and Tang.)

Aberrant DNA methylation of genes is closely linked to many aspects of tumor development. This study focuses on the effect of DNA hypermethylation of von Willebrand factor C domain containing 2 (VWC2) on colorectal cancer (CRC) progression and the underpinning mechanism. According to data in the bioinformatic systems, VWC2 had the highest degree of DNA methylation in colonic adenocarcinoma, and it showed DNA hypermethylation in rectal adenocarcinoma as well. CRC and the para-tumorous tissues were collected from 86 patients. VWC2 was expressed at low levels in CRC samples and inversely correlated with tumor stage and tumor biomarker expression. DNA hypermethylation and reduced expression of VWC2 were also detected in CRC cell lines HCT-116 and HT29. VWC2 overexpression suppressed the malignant growth of cells in vitro and in vivo. Co-immunoprecipitation and western blot assays showed that small ubiquitin-like modifier 1 (SUMO1) mediated SUMOylation of DNA methyltransferase 1 (DNMT1) and strengthened its protein stability, which promoted DNA methylation and suppression of the VWC2 gene. In summary, this study demonstrates that SUMO1-mediated activation of DNMT1 induces DNA methylation and downregulation of VWC2 in CRC to augment cancer development.

It is a decade-long controversy that transarterial chemoembolization (TACE) has definite priority over transarterial embolization (TAE) in treating patients with hepatocellular carcinoma (HCC), since HCC cells are regularly resistant to chemotherapy by enhanced expression of proteins that confer drug resistance, and ABC transporters pump the intracellular drug out of the cell. We addressed this issue by modulating the chemo-environment. In an animal model, sevelamer, a polymeric phosphate binder, was introduced as an embolic agent to induce intratumoral inorganic phosphate (Pi) starvation, and trans-arterially co-delivered with doxorubicin (DOX). The new type of TACE was named as DOX-TASE. This Pi-starved environment enhanced DOX tumoral accumulation and retention, and DOX-TASE thereby induced more severe tumor necrosis than that induced by conventional TACE (C-TACE) and drug-eluting bead TACE (D-TACE) at the same dose. In vitro tests showed that Pi starvation increased the cellular accumulation of DOX in an irreversible manner and enhanced cytotoxicity and cell apoptosis by suppressing the expression of ABC transporters (P-glycoprotein (P-gp), BCRP, and MRP1) and the production of intracellular ATP. Our results are indicative of an alternative interventional therapy combining chemotherapy with embolization more effectively.

Arsenic trioxide (As 2 O 3 , ATO) has limited therapeutic benefit to treat solid tumors, whether used alone or in combination. Nanoscale drug delivery vehicles have great potential to overcome the limitation of the utility of ATO by rapid renal clearance and dose-limiting toxicity. Polymeric materials ranging from gelatin foam to synthetic polymers such as poly(vinyl alcohol) were developed for vascular embolic or chemoembolic applications. Recently, we have introduced sevelamer, an oral phosphate binder, as a new polymeric embolic for vascular interventional therapy. In this paper, sevelamer arsenite nanoparticle with a polygonal shape and a size of 50-300 nm, synthesized by anionic exchange from sevelamer chloride, was developed as a Pi-responsive bifunctional drug carrier and embolic agent for chemoembolization therapy. At the same arsenic dosage, sevelamer arsenite-induced severer tumor necrosis than ATO on the VX2 cancer model. In vitro tests evidenced that Pi deprivation by sevelamer could enhance ATO's anticancer effect. The results showed that ATO in Pi starvation reduced cell viability, induced more apoptosis, and diminished the mitochondrial membrane potential (Δψm) of cells since Pi starvation helps ATO to further down-regulate Bcl-2 expression, up-regulate Bax expression, enhance the activation of caspase-3 and increase the release of cytochrome c, and the production of excessive reactive oxygen species (ROS). Sevelamer arsenite not only plays a Pi-activated nano-drug delivery system but also integrated anticancer drug with embolic for interventional therapy. Therefore, our results presented a new administration route of ATO as well as an alternative chemoembolization therapy.