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Ting Yang,1– 4,* Han-Rui Wang,1– 4,* Ya-Kui Mou,1– 4,* Wan-Chen Liu,1– 4 Yao Wang,1– 4 Xiao-Yu Song,1– 4 Chao Ren,1– 5 Xi-Cheng Song1– 4 1Department of Otorhinolaryngology, Head and Neck Surgery, Yantai Yuhuangding Hospital, Qingdao University, Yantai, People’s Republic of China; 2Shandong Provincial Key Laboratory of Neuroimmune Interaction and Regulation, Yantai Yuhuangding Hospital, Yantai, People’s Republic of China; 3Shandong Provincial Clinical Research Center for Otorhinolaryngologic Diseases, Yantai Yuhuangding Hospital, Yantai, People’s Republic of China; 4Yantai Key Laboratory of Otorhinolaryngologic Diseases, Yantai Yuhuangding Hospital, Qingdao University, Yantai, People’s Republic of China; 5Department of Neurology, Yantai Yuhuangding Hospital, Qingdao University, Yantai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xi-Cheng Song, Department of Otolaryngology, Head and Neck Surgery, Yantai Yuhuangding Hospital, Qingdao University, No. 20, East Road, Zhifu District, Yantai, 264000, People’s Republic of China, Tel +86535 6691999, Fax +865356240341, Email drxchsong@163.com Chao Ren, Department of Neurology, Yantai Yuhuangding Hospital, Qingdao University, No. 20, East Road, Zhifu District, Yantai, 264000, People’s Republic of China, Tel +865356691999, Fax +86535 6240341, Email renchaotg@126.comAbstract: Patients with allergic rhinitis (AR) have a high incidence of sleep disorders, such as insomnia, which can easily exacerbate nasal symptoms. The aggravation of nasal symptoms further promotes the deterioration of sleep disorders, forming a vicious cycle. Severe cases may even trigger psychological and neurological issues, such as anxiety, depression, and cognitive impairment, causing significant distress to patients, making clinical diagnosis and treatment difficult, and increasing costs. Furthermore, satisfactory therapeutics remain lacking. As the pathogenesis of AR-associated sleep disorders is not clear and research is still insufficient, paying attention to and understanding AR-related sleep disorders is crucial in clinical practice. Multiple studies have shown that the most crucial issues in current research on AR and sleep are analyzing the relationship between AR and sleep disorders, searching for the influencing factors, and investigating potential targets for diagnosis and treatment. This review aimed to identify and summarize the results of relevant studies using “AR” and “sleep disorders” as search terms. In addition, we evaluated the correlation between AR and sleep disorders and examined their interaction and potential mechanisms, offering a foundation for additional screening of potential diagnostic biomarkers and therapeutic targets.Keywords: allergic rhinitis, biological rhythm, immune inflammatory, neurological regulation, sleep disorders

Wen-Cai Liu,1,2 Ming-Xuan Li,2 Wen-Xing Qian,3 Zhi-Wen Luo,1,4 Wei-Jie Liao,1,4 Zhi-Li Liu,1,4 Jia-Ming Liu1,4 1Department of Orthopaedic Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, People’s Republic of China; 2The First Clinical Medical College of Nanchang University, Nanchang, 330006, People’s Republic of China; 3School of Computer and Information Technology, Beijing Jiaotong University, Beijing, 100044, People’s Republic of China; 4Institute of Spine and Spinal Cord, Nanchang University, Nanchang, 330006, People’s Republic of ChinaCorrespondence: Jia-Ming LiuDepartment of Orthopaedic Surgery, The First Affiliated Hospital of Nanchang University, No. 17 Yongwaizheng Street, Donghu District, Nanchang, Jiangxi Province, People’s Republic of ChinaTel/Fax +86-791-86319815Email liujiamingdr@hotmail.comObjective: This study aimed to develop and validate a machine learning model for predicting bone metastases (BM) in prostate cancer (PCa) patients.Methods: Demographic and clinicopathologic variables of PCa patients in the Surveillance, Epidemiology and End Results (SEER) database from 2010 to 2017 were retrospectively analyzed. We used six different machine learning algorithms, including Decision tree (DT), Random forest (RF), Multilayer Perceptron (MLP), Logistic regression (LR), Naive Bayes classifiers (NBC), and eXtreme gradient boosting (XGB), to build prediction models. External validation using data from 644 PCa patients of the First Affiliated Hospital of Nanchang University from 2010 to 2016. The performance of the models was evaluated using the area under receiver operating characteristic curve (AUC), accuracy score, sensitivity (recall rate) and specificity. A web predictor was developed based on the best performance model.Results: A total of 207,137 PCa patients from SEER were included in this study. Of whom, 6725 (3.25%) developed BM. Gleason score, Prostate-specific antigen (PSA) value, T, N stage and age were found to be the risk factors of BM. The XGB model offered the best predictive performance among these 6 models (AUC: 0.962, accuracy: 0.884, sensitivity (recall rate): 0.906, and specificity: 0.879). An XGB model-based web predictor was developed to predict BM in PCa patients.Conclusion: This study developed a machine learning model and a web predictor for predicting the risk of BM in PCa patients, which may help physicians make personalized clinical decisions and treatment strategy for patients.Keywords: prostate cancer, bone metastasis, machine learning, prediction model, SEER

Yun-Qian Li,1,* Meng Xu,2,* Udesh Dhawan,3,4 Wai-Ching Liu,5 Kou-Ting Wu,5 Xin-Rui Liu,1 Chingpo Lin,1 Gang Zhao,1 Yu-Chuan Wu,3,6,7 Ren-Jei Chung5 1Department of Neurosurgical Oncology, First Hospital, Jilin University, Changchun, People’s Republic of China; 2School of Materials Science and Engineering, Beijing Institute of Technology, Beijing, People’s Republic of China; 3Department of Materials and Mineral Resources Engineering, National Taipei University of Technology (Taipei Tech), Taipei, Taiwan, Republic of China; 4Institute of Chemistry, Academia Sinica, Taipei, Taiwan, Republic of China; 5Department of Chemical Engineering and Biotechnology, National Taipei University of Technology (Taipei Tech), Taipei, Taiwan, Republic of China; 6Institute of Materials Science and Engineering, National Taipei University of Technology (Taipei Tech), Taipei, Taiwan, Republic of China; 7Department of Chemical and Materials Engineering, Chinese Culture University, Taipei, Taiwan, Republic of China *These authors contributed equally to this work Introduction: The efficacy of a chemotherapy drug in cancer therapy is highly determined by the ability to control the rate and extent of its release in vivo. However, the lack of techniques to accurately control drug release drastically limits the potency of a chemotherapy drug.Materials and methods: Here, we present a novel strategy to precisely monitor drug release under magnetic stimulation. Methotrexate (MTX), an anticancer drug, was covalently functionalized onto iron–gold alloy magnetic nanoparticles (Fe–Au alloy nanoparticles or NFAs) through 2-aminoethanethiol grafting and the ability of this drug–nanoparticle conjugate (NFA–MTX) in limiting HepG2 (liver carcinoma) cell growth was studied. Well-dispersed NFAs were prepared through pyrolysis.Results and discussion: Transmission electron microscopy revealed the average nanoparticle size to be 7.22±2.6 nm, while X-ray diffraction showed distinct 2θ peaks for iron and gold, confirming the presence of iron and gold nanoparticles. Inductively coupled plasma mass spectrometry revealed that the amount of NFA–MTX conjugate ingested by HepG2 cancer cells was 1.5 times higher than that ingested by L929 fibroblasts, thereby proving a higher selective ingestion by cancer cells compared to normal cells. Fourier-transform infrared spectroscopy revealed the breakage of Au-S bonds by the heat generated under magnetic field stimulation to release MTX from the NFA–MTX conjugate, triggering a 95% decrease in cellular viability at 100 µg/mL.Conclusion: The ability of NFA–MTX to dissociate under the influence of an applied magnetic field provides a new strategy to induce cancer cell death via hyperthermia. Applications in drug delivery, drug development, and cancer research are expected. Keywords: iron–gold nanoparticles, methotrexate, hyperthermia, superparamagnetic, controlled drug release

Ya Feng, Wuchao Liu, Lizhen Pan, Cong Jiang, Chengxi Zhang, Yuxuan Lu, Zhiyu Nie, Lingjing Jin Department of Neurology, Shanghai Tongji Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China Abstract: Four botulinumtoxin type A (BoNT/A) products, onabotulinumtoxinA (A/Ona), incobotulinumtoxinA (A/Inco), lanbotulinumtoxinA (A/Lan) and chinbotulinumtoxinA (A/Chin), are applied in the present study, among which A/Chin is newly produced. We aimed to compare the neurotoxic potency of these toxins by the gauge of muscle strength reduction. Furthermore, potential molecular and cellular mechanisms were also explored. According to our data, muscle strengths in the four toxin groups were all significantly decreased after injection for 1 week. A/Chin achieved the most obvious reduction in muscle strength as compared to the other three products at the dose of 0.5 U. However, there was no difference between the four toxins when increased to 2 U. As the toxins wore off, muscle strength recovered to basal level 12 weeks postinjection. We further measured the expression levels of key factors involved in neuromuscular junction stabilization and muscle genesis. Our results showed that nicotinic acetylcholine receptor, myogenic regulatory factors and muscle-specific receptor tyrosine kinase were all significantly upregulated upon BoNT/A treatment. Consistent with the result of muscle strength, A/Chin had the most obvious induction of gene expression. Moreover, we also found local inflammation response following BoNT/A injection. Owing to lack of complexing proteins, both A/Inco and A/Chin stimulated relatively lighter inflammation compared to that of A/Ona and A/Lan groups. In conclusion, our study provided evidence for the efficacy of the novel A/Chin and its similar functional mode to that of A/Ona, A/Inco and A/Lan. In addition, A/Chin has superiority in inducing muscle paralysis and inflammation stimulation, which may indicate faster onset and longer duration of this novel A/Chin. Keywords: A/Chin, A/Lan, A/Ona, A/Inco, neurotoxic potency

Wen-Chao Liu, Liang Wen, Hao Wang, Jiang-Biao Gong, Tian-Xiang Zhan, Yuan-Yuan Meng, Xiao-Feng Yang Department of Neurosurgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China Abstract: In the present study, we evaluated the changes in autophagy after hyperbaric oxygen (HBO) treatment for traumatic brain injury (TBI) and investigated whether autophagy takes part in the neuroprotection after HBO treatment. Male Sprague Dawley rats were assigned to four groups randomly: sham injury, sham injury and HBO, TBI, and TBI and HBO. The HBO rats received HBO treatment for 100 min immediately after injury. Rats were sacrificed at 24 h after the brain injury and the levels of cleaved caspase-3 and the number of terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling-positive cells in the injured cortex were measured to determine cell death. The expression levels of autophagy-associated proteins were measured by immunohistochemistry and Western blotting to assess changes in autophagy. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling-positive cell density and cleaved caspase-3 expression were increased 24 h after TBI. These increases were suppressed by post-TBI HBO treatment. Immunohistochemistry and Western blotting of autophagy-associated proteins showed that TBI can induce autophagy and that HBO treatment can further upregulate the expression of autophagy makers, as shown by an increase in LC3, ATG-5, and Beclin-1 expression and reduction in P62 expression. In conclusion, HBO treatment can reduce apoptosis and further upregulate autophagy in the injured cortex after brain injury, and the autophagy pathway may take part in the neuroprotection provided by HBO treatment for TBI. Keywords: autophagy, hyperbaric oxygen treatment, traumatic brain injury, apoptosis, neuroprotective effect

YuKun Huang,1 Wenchao Liu,1 Feng Gao,1 Xiaoling Fang,2 Yanzuo Chen1 1Department of Pharmaceutics, School of Pharmacy, East China University of Science and Technology, 2Key Laboratory of Smart Drug Delivery, Ministry of Education & PLA, School of Pharmacy, Fudan University, Shanghai, People’s Republic of China Abstract: Brain glioma therapy is an important challenge in oncology. Here, doxorubicin (DOX) and paclitaxel (PTX)-loaded cyclic arginine-glycine-aspartic acid peptide (c(RGDyK))-decorated Pluronic micelles (cyclic arginine-glycine-aspartic acid peptide-decorated Pluronic micelles loaded with doxorubicin and paclitaxel [RGD-PF-DP]) were designed as a potential targeted delivery system to enhance blood–brain barrier penetration and improve drug accumulation via integrin-mediated transcytosis/endocytosis and based on integrin overexpression in blood–brain barrier and glioma cells. The physicochemical characterization of RGD-PF-DP revealed a satisfactory size of 28.5±0.12 nm with uniform distribution and core-shell structure. The transport rates across the in vitro blood–brain barrier model, cellular uptake, cytotoxicity, and apoptosis of U87 malignant glioblastoma cells of RGD-PF-DP were significantly greater than those of non-c(RGDyK)-decorated Pluronic micelles. In vivo fluorescence imaging demonstrated the specificity and efficacy of intracranial tumor accumulation of RGD-PF-DP. RGD-PF-DP displayed an extended median survival time of 39 days, with no serious body weight loss during the regimen. No acute toxicity to major organs was observed in mice receiving treatment doses via intravenous administration. In conclusion, RGD-PF-DP could be a promising vehicle for enhanced doxorubicin and paclitaxel delivery in patients with brain glioma. Keywords: Pluronic micelles, integrin, blood–brain barrier, brain glioma, targeted delivery

Background/purpose: Men who have sex with men (MSM) are at increased risk for hepatitis A virus (HAV), hepatitis B virus (HBV), and hepatitis C virus (HCV) infections than the general population. Comparisons of the seroprevalence rates of these hepatitis viruses between HIV-positive and HIV-negative MSM are rarely performed in Taiwan.Methods: Between January 2009 and June 2010, data on the serologies for HAV, HBV, and HCV were collected from two groups of patients: HIV-negative MSM, aged 18-40 years, who sought voluntary counseling and testing (VCT) for HIV infection, and HIV-positive MSM of the same age group who sought HIV care at the National Taiwan University Hospital. Both groups of patients were also tested for syphilis.Results: During the 18-month study period, 690 HIV-negative MSM and 438 HIV-positive MSM were enrolled and tested for anti-HAV antibody, HBV surface antigen (HBsAg), hepatitis B core antibody (anti-HBc antibody), and anti-HCV antibody. HIV-positive MSM were older than HIV-negative MSM (30.5 ± 5.4 vs. 25.8 ± 4.7 years, p < 0.01). For HIV-positive MSM, the mean CD4 lymphocyte count was 477.6 ± 230.0 cells/μL and 46% of them had undetectable plasma HIV RNA load (< 40 copies/mL by reverse transcription-polymerase chain reaction assay). The overall seroprevalence rates of HAV, HBsAg, and HCV in HIV-positive MSM were 15.1%, 16.4%, and 5.5%, respectively, while in HIV-negative MSM, they were 7.4%, 6.2%, and 0.4%, respectively. In the multivariate analysis, age was significantly associated with seropositivity for HAV (OR [per one age group increase]: 1.96; 95% CI: 1.6-2.5), HBsAg (OR: 2.02; 95% CI: 1.6-2.6), anti-HBc (OR: 2.68; 95% CI: 2.3-3.2), anti-HCV (OR: 1.67; 95% CI: 1.0-2.7), and anti-HBs (OR: 1.25; 95% CI: 1.0-1.5). HIV infection was associated with seropositivity for HBsAg (OR: 1.73; 95% CI: 1.1-2.7), anti-HBc (OR: 2.44; 95% CI: 1.8-3.3), HCV (OR: 8.91; 95% CI: 2.5-31.4), and syphilis (OR: 11.21; 95% CI: 6.7-18.9).Conclusion: HIV-positive MSM have a higher seroprevalence rate of HBV and HCV infection than HIV-negative MSM in Taiwan. Vaccination and safe-sex counseling should be provided to prevent the transmission of hepatitis viruses among MSM who may be engaged in high-risk behaviors. [ABSTRACT FROM AUTHOR]

This study evaluates the effectiveness of CT and MR imaging in differentiating intradural extramedullary spinal schwannomas and meningiomas in a large group of patients. In addition, the study correlates tumour location, morphologic characteristics and enhancement pattern. From January 2000 to June 2007, we retrospectively reviewed 128 consecutive patients (51 male, 77 female; mean age at admission 53.8 years; range 17-83 years) with spinal intradural extramedullary tumours (92 schwannomas, 36 meningiomas) at our institution. Fifty-one of ninety-two schwannomas (55.4%) showed fluid signal intensity on T2-weighted MR images. Twenty-two of thirty-six meningiomas (61.1%) showed hyperintense signal intensity and thirteen of thirty-six meningiomas (36.1%) showed isointense signal on T2-weighted MR images. Fifty-four schwannomas (58.7%) showed rim enhancement and thirty-three meningiomas (91.7%) showed diffuse enhancement on contrast-enhanced T1-weighted MR imaging. Twenty-one meningiomas (58.3%) showed dural tail sign in contrast-enhanced T1-weighted MR imaging. Twenty-one meningiomas (58.3%) showed calcification on CT images. MR and CT imaging results are therefore useful for the differentiation of schwannomas from meningiomas of the spine. [ABSTRACT FROM AUTHOR]

Objective: In patients with large middle cerebral artery (MCA) infarction, space-occupying brain edema may lead to a malignant course with up to 80% mortality, under conservative treatment. As interventional treatment strategies must be started before the deterioration occurs, predictors of a malignant course are necessary.Material and Methods: This study reports on the results of evoked potentials (brainstem auditory evoked potentials [BAEP] and median-nerve somatosensory evoked potentials [SEP]) within 24 h after onset of stroke in 30 patients suffering a large MCA infarct (14 patients with a malignant and 16 with a non-malignant course).Results: Our findings indicate that pathological BAEP indicate a malignant course (P < 0.05).Conclusion: This study shows that in patients suffering from large MCA infarction early assessment of EP within 24 h after onset of stroke may deliver useful information to select those patients who develop malignant edema. [ABSTRACT FROM AUTHOR]

Mathematical models are constructed to investigate the population dynamics of Verocytotoxin-producing Escherichia coli (VTEC) serogroups O26 and O103 in two different calf cohorts. We compare the epidemiological characteristics of these two serogroups within the same calf cohort as well as the same serogroups between the two calf cohorts. The sources of infection are quantified for both calf cohort studies. VTEC serogroups O26 and O103 mainly differ in the rate at which calves acquire infection from sources other than infected calves, while infected calves typically remain infectious for less than 1 week regardless of the serogroups. Fewer than 20% of VTEC-positive samples are the result of calf-to-calf transmission. PFGE typing data are available for VTEC-positive samples to further subdivide the serogroup data in one of the two calf cohort studies. For serogroup O26 but not O103, there is evidence for unequal environmental exposure to infection with different PFGE types. [ABSTRACT FROM AUTHOR]

Background: Alpha-s1 casein hydrolysate (ACH; Lactium®) is recognized as a supplementary treatment to enhance sleep quality. However, limited studies utilizing objective sleep assessment tools have resulted in a lack of substantial validation. This study aimed to assess the effects of ACH on both subjective sleep assessments and objective polysomnography (PSG) recordings in a hospital-based cohort of Taiwanese individuals with chronic insomnia., Methods: In this 4-week randomized, double-blind, placebo-controlled trial, 36 participants diagnosed with chronic insomnia were enrolled and randomly assigned to either the ACH or placebo groups. Initially, participants in the ACH group received 600 mg of ACH daily, which was reduced to 300 mg for the latter two weeks; the placebo group received maltodextrin capsules throughout the study. The study utilized polysomnography (PSG), along with detailed sleep questionnaires including the Insomnia Severity Index (ISI), Global Sleep Disorders Score (GSDS), Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), and Hospital Anxiety and Depression Scale (HADS), to assess improvements in sleep quality and related health markers. The efficacy of the intervention was assessed through measures of sleep efficiency, stage distribution, and psychological well-being, comparing results from before to after the treatment phase., Results: The study demonstrated that ACH treatment notably enhanced sleep quality, evidenced by significant improvements in ISI, GSDS, PSQI, ESS, and HADS scores at both week 2 and 4 (all p-values <0.05) compared with baseline scores. When compared to the placebo group, the ACH group experienced a marked reduction in GSDS scores over time (p = 0.045). Furthermore, PSG data revealed a significant decrease in sleep onset latency from baseline in the ACH group compared to the placebo group (p = 0.012; -7.7 ± 16.0 min vs. 6.1 ± 17.7 min for ACH and placebo groups, respectively). These results indicate that ACH treatment effectively improved sleep initiation and overall sleep quality., Conclusion: ACH Supplementation significantly improved sleep quality, particularly by reducing GSDS scores and sleep onset latency, demonstrating its potential as an effective intervention for chronic insomnia. Future studies with larger samples and exploration of long-term effects are needed to confirm these results., Competing Interests: Conflict of interest All authors listed on the manuscript have contributed sufficiently to the paper, have approved the paper, and declare that they have no conflicts of interest to declare., (Copyright © 2024 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Introduction/aims: Neuromas come in different shapes and sizes; yet the correlation between neuroma morphology and symptomatology is unknown. Therefore, we aim to investigate macroscopic traits of excised human neuromas and assess the validity of a morphological classification system and its potential clinical implications., Methods: End-neuroma specimens were collected from prospectively enrolled patients undergoing symptomatic neuroma surgery. Protocolized images of the specimens were obtained intraoperatively. Pain data (Numeric rating scale, 0-10) were prospectively collected during preoperative interview, patient demographic and comorbidity factors were collected from chart review. A morphological classification is proposed, and the inter-rater reliability (IRR) was assessed. Distribution of neuroma morphology with patient factors, was described., Results: Forty-five terminal neuroma specimens from 27 patients were included. Residual limb patients comprised 93% of the population, of which 2 were upper (8.0%) and 23 (92.0%) were lower extremity residual limb patients. The proposed morphological classification, consisting of three groups (bulbous, fusiform, atypical), demonstrated a strong IRR (Cohen's kappa = 0.8). Atypical neuromas demonstrated higher preoperative pain, compared with bulbous and fusiform. Atypical morphology was more prevalent in patients with diabetes and peripheral vascular disease., Discussion: A validated morphological classification of neuroma is introduced. These findings may assist surgeons and researchers with better understanding of symptomatic neuroma development and their clinical implications. The potential relationship of neuroma morphology with the vascular and metabolic microenvironment requires further investigation., (© 2024 Wiley Periodicals LLC.)

The plasma membrane (PM)-localized Na+/H+ antiporter Salt Overly Sensitive1 (SOS1) is essential for plant salt tolerance through facilitating Na+ efflux; however, how SOS1 localization and protein accumulation is regulated in plants remains elusive. Here, we report that Sorting Nexin 1 (SNX1) is required for plant salt stress tolerance through affecting endosomal trafficking of SOS1 in Arabidopsis (Arabidopsis thaliana). Disruption of SNX1 caused salt hypersensitivity with increased Na+ accumulation and decreased Na+ efflux in Arabidopsis when challenged with high salinity stress. SNX1 co-localized and interacted with SOS1 in endosomes, promoting its PM localization and protein stability in plants under saline conditions. SOS1 overexpression promoted salt tolerance in the wild-type, whereas such effect was greatly compromised in the snx1-2 mutant. Pharmaceutical results showed that SOS1 recycling from the cytosol to the PM was largely blocked while its vacuolar degradation was accelerated in the snx1-2 mutant. Furthermore, salt-induced SOS1 phosphorylation enhanced its interaction and co-localization with SNX1, which is required for SOS1 PM localization in plants. Our study elucidates that SNX1 facilitates SOS1 PM localization and protein accumulation through endosomal trafficking, thereby enhancing salt tolerance in plants., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Society of Plant Biologists. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Postamputation pain (PAP) is underexplored in East Asian populations, with most data originating from Western countries. This study aimed to investigate the prevalence and risk factors of PAP in East Asian individuals who underwent surgical amputation, particularly those requiring subsequent analgesia or nerve interventions., Materials and Methods: The study used data from the Longitudinal Health Insurance Database, encompassing claims from 2 million randomly selected individuals out of 23.5 million enrolled in Taiwan's National Health Insurance Research Database from 2000 to 2019. The risk factors for PAP were analyzed using multivariable regression, considering criteria such as chronic postamputation pain, symptomatic neuroma treatment, chronic analgesia use, and nerve interventions., Results: Among the 7287 amputees (mean age 59.5 years; 65.1% male), 18.1% (95% CI 17.2%, 19.0%) (1318 patients) experienced PAP requiring intervention. Significant risk factors included cancer (OR 2.20 (95% CI 1.27, 3.68)), peripheral artery disease (OR 2.11 (95% CI 1.66, 2.69)), infection (OR 1.93 (95% CI 1.55, 2.40)), diabetes mellitus (OR 1.85 (95% CI 1.45, 2.37)), and a higher Elixhauser Comorbidity Index (OR 1.04 (95% CI 1.02, 1.06)). Prior radiculopathy (OR 1.30 (95% CI 1.13, 1.51)) and myelopathy (OR 1.33 (95% CI 1.14, 1.55)) also increased pain odds, while age showed a slight inverse association (OR 0.99 (95% CI 0.98, 0.99))., Conclusion: The prevalence of PAP requiring subsequent analgesia or nerve interventions in this East Asian population is 18.1%. Identified risk factors include multiple medical comorbidities and pre-existing radiculopathy or myelopathy. These findings highlight the important considerations for both clinical practice and future research directions., Competing Interests: Competing interests: KRE is a consultant for AxoGen Inc., Checkpoint Surgical Inc., Integra Lifesciences Inc., Tulavi Therapeutics Inc., and Biocircuit. Other coauthors have nothing to disclose., (© American Society of Regional Anesthesia & Pain Medicine 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: An increasing number of studies have demonstrated that dynamic changes in lipid species can affect allergic diseases; however, the causal relationship and mediating role of immune cells remain unclear., Methods: We conducted a bidirectional two-sample mendelian randomization (MR) analysis using genome-wide association study (GWAS) data on 179 lipid species (n = 7,174) and three types of allergic diseases including allergic rhinitis (AR) (n = 370,158), allergic asthma (n = 219,753), and allergic conjunctivitis (n = 377,277). The principal model used was the inverse variance-weighted approach, and a series of sensitivity analyses were conducted to ensure the robustness of the results. We used a two-step MR approach to assess whether the causal effect was mediated by immune cells (n = 3,757)., Results: Sterol ester and sphingomyelin played pathogenic roles in allergic asthma, AR, and allergic conjunctivitis; however, the effective subtypes differed. Among them, CD45RA- CD4+ mature T cells and CCR2 on CD14+ CD16+ monocytes affected the promoting impact of sterol ester's metabolism on allergic asthma and AR with different mediating proportions, while the role of sphingomyelin may not involve the immune cells. Moreover, we observed that HLA-DR on CD33- HLA DR+ myeloid cells, CD11b on CD66b++ myeloid cells, and IgD+ CD38- B cells played the most mediating effect of phosphatidylethanolamine (O-18:2&#95;20:4) in allergic asthma, phosphatidylinositol (16:0&#95;18:1) in AR, and phosphatidylethanolamine (18:0&#95;18:2) in allergic conjunctivitis., Conclusion: This MR study provides evidence for specific lipid species associated with the risk of allergic diseases, especially sterol esters, and identifies the immune cells that mediate this causal relationship., (© 2024 S. Karger AG, Basel.)

The Chinese Mars rover Zhurong successfully landed in southern Utopia Planitia on Mars in May 2021. Previous research suggested a Hesperian ocean may have existed in the northern lowland on Mars. Recent research observed water-related features at the Zhurong landing site from in situ data. In this study, we conducted a comprehensive geomorphological analysis of the landing area using remote sensing data, supplemented by in situ observations, and unveiled features consistent with the existence of a nearshore zone in southern Utopia. Different types of water-related geomorphological features were separated by specific topographic contours, suggesting different types of marine environments. The area was subdivided into a foreshore highland-lowland transition unit, a shallow marine unit and a deep marine unit. In situ observations including sedimentary deposit rocks, water-related lamination features, and subsurface sedimentary layers, also indicate past water activities. Results suggested an evolution scenario of the nearshore zone in southern Utopia: (1) Flooding of the Utopia Planitia in Late Noachian around 3.65-3.68 Ga reached the foreshore unit; (2) formation of the shallow and deep marine units after the flooding was completed by about 3.5 Ga and 3.42 Ga in Early Hesperian, respectively; (3) gradual loss of subsurface volatiles during the Amazonian epoch., (© 2024. The Author(s).)

The nose-brain axis (NBA), a critical component of the body-brain axis, not only serves as a drug transport route for the treatment of brain diseases but also mediates changes such as neuroimmune disorders, which may be an important mechanism in the occurrence and development of some nasal or brain diseases. Despite its importance, there are substantial gaps that remain in our understanding of the characteristics of NBA-mediated diseases and of the cellular and molecular mechanisms underlying the bidirectional NBA crosstalk. These gaps have limited the translational application of NBA-related research findings to some extent. Therefore, this review aims to address the conceptual framework of NBA and highlight its values in representative diseases by combining existing literature with new research results from our group. We hope that this paper will provide a basis for further in-depth research in this field, and facilitate the clinical translation of NBA., 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 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: Omega-3 polyunsaturated fatty acids ( n -3 PUFAs) have demonstrated protective effects in major depressive disorder (MDD) patients receiving antidepressant treatment. However, there have been a few double-blind randomized controlled trials focused on n -3 PUFAs as monotherapy in MDD, and the outcomes have been mixed. This study aimed to assess the clinical effects of n -3 PUFAs monotherapy in patients with MDD., Methods: A total of 60 patients with MDD participated in this 12-week double-blind randomized controlled trial. They were randomized to either the n -3 PUFAs group (n = 30; 3.2 g of eicosapentaenoic acid, EPA and docosahexaenoic acid, DHA per day) or the placebo group (n = 30; 3.2 g of soybean oil per day). The severity of depression was evaluated using the Hamilton Rating Scale for Depression (HRSD)., Results: The n -3 PUFAs group had a significantly lower HRSD score compared with the placebo group at week 4 ( p = 0.004), week 6 ( p = 0.006), week 8 ( p = 0.004), and week 12 ( p = 0.01). The n -3 PUFAs group showed slightly higher rates for both remission (26.7% vs. 10%, p = 0.095) and response (23.3% vs. 6.7%, p = 0.145) compared with the placebo group at week 12, but these differences did not reach statistical significance., Conclusions: These findings suggested that monotherapy of n -3 PUFAs could improve depression and potentially serve as an alternative option for MDD patients.

Introduction: Patients with advanced-stage or intermediate-stage hepatocellular carcinoma (HCC) unsuitable for transarterial chemoembolization (TACE) had poor prognoses. Recent advancements in hepatic arterial infusion chemotherapy (HAIC) and immune checkpoint inhibitors (ICIs) have demonstrated higher tumor response rates, which improved overall survival (OS). HAIC achieves an OS rate of approximately 14.5-15.3 months with a 39.1-42.5% tumor response rate. In comparison, ICIs have a 12-14 month OS rate with a 26-33% tumor response rate. Given these promising responses, this study evaluates the efficacy of conversion therapy with curative intent following HAIC or ICIs, focusing on survival outcomes., Methods: We retrospectively analyzed 80 patients with advanced or TACE-unsuitable intermediate HCC. Patients completed two HAIC or four ICI cycles, followed by Response Evaluation Criteria in Solid Tumors (RECIST) criteria imaging. Based on demographics, cirrhosis status, Barcelona Clinic Liver Cancer classification (BCLC) stage, treatment responses, and treatment modality, survival impacts were analyzed. OS was compared between HAIC and immunotherapy groups. The effect of conversion therapy with curative intent on survival outcomes was analyzed using a Cox regression model., Results: Among the 80 patients, 26 achieved positive response (CR/PR) with HAIC or ICIs, and 9 of them subsequently underwent conversion therapy with curative intent. Key prognostic factors included Child-Pugh stage B vs. A (HR=2.21, p=0.041), BCLC stage C vs. B (HR=4.38, p=0.011), and elevated AFP levels (HR=5.02, p&lt;0.001). Positive responders saw substantial survival benefits (HR=0.26, p=0.001). Patients undergoing conversion therapy exhibited significantly enhanced survival. Median OS was 13.58 months with standard therapy, while the curative intent surgery group did not reach the median OS (p=0.002). For CR/PR patients, 48-month survival was 75.0% for the curative surgery group versus 38.0% for standard treatment., Conclusion: Conversion therapy with curative intent following HAIC or ICIs might enhances survival in patients with advanced or TACE-unsuitable intermediate-stage HCC., (S. Karger AG, Basel.)

The comorbidity of obesity and depression has major public health impacts, highlighting the need to understand their shared mechanisms. This study explored the connection between obesity and depression through the transient receptor potential V1 (TRPV1) signaling pathway, using obese/depressed murine models and clinical data. Mice fed a high-fat diet showed altered TRPV1 pathway expression in brain regions of the mice: downregulated in the medial prefrontal cortex (mPFC) and hippocampus, and upregulated in the hypothalamus and amygdala, influencing depression-like behaviors and inflammation. Treatments like eicosapentaenoic acid (EPA) and acupoint catgut embedding (ACE) reversed these effects, similar to observations in Trpv1 -/- mice. Furthermore, chemogenetic activation in the ventral mPFC also alleviated depression via TRPV1. In our clinical validation, single nucleotide polymorphisms (SNPs) in TRPV1-related genes (PIK3C2A and PRKCA) were linked to interferon-induced depression. These findings underscore the potential of targeting TRPV1 as a therapeutic approach for obesity-related depression., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 2019 led to the coronavirus infection diseases 2019 (COVID-19) pandemic, significantly impacting global public health and the economy. Numerous COVID-19 vaccines based on the receptor binding domain (RBD) of SARS-CoV-2 spike protein have been developed, utilizing various protein expression platforms and adjuvant systems. In a previous study, we reported using the direct fusion of the A subunit of type IIb E. coli heat-labile enterotoxin with the SARS-CoV-2 RBD protein (RBD-LTA) as an intranasal vaccine candidate (Hsieh et al., 2023). In this study, we investigated the effects of an intranasal booster of RBD-LTA/RBD mixture proteins after one or two doses of intramuscular bivalent BA.4/5 mRNA vaccination over 17 and 35 weeks. Our results indicate that the intranasal RBD-LTA/RBD mixture proteins booster maintains high levels of anti-RBD IgG and neutralizing antibodies, comparable to those elicited by a two-dose mRNA vaccination regimen. An additional RBD-LTA/RBD mixture proteins booster significantly increased antibody titers, demonstrating the potential of this approach for long-term immunity against SARS-CoV-2. Our findings suggest that combining primary mRNA vaccination with an intranasal RBD-LTA/RBD mixture proteins booster can effectively sustain antibody levels over extended periods, providing a promising strategy for long-term protection against SARS-CoV-2 and its variants., Competing Interests: Declaration of competing interest The National Tsing Hua University has filed a patent application on the RBD-based COVID-19 mucosal vaccine candidates., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objective: This meta-analysis aimed to compare videolaryngoscope (VL)-assisted transesophageal echocardiography (TEE) probe insertion with conventional methods in terms of efficacy and safety., Methods: Several major databases such as Medline and Embase were systematically searched to identified relevant studies from inception to June 2024. The primary outcome was complication rate, defined as the proportion of patients experiencing complications related to TEE probe insertion. Injuries at specific sites (e.g., posterior hypopharyngeal wall) from both groups were also analyzed. The secondary outcomes included the first-attempt success rate and total insertion time of VL and conventional methods., Results: Seven trials involving 716 participants were identified. The use of VL was found to significantly reduce the complication rate (risk ratio[RR]:0.28, 95% confidence interval[CI]:0.17-0.46, P < 0.00001) and increased the first-attempt success rate [FASR] (RR:1.33, 95%CI: 1.10-1.60, P = 0.003) compared with conventional methods. These findings were confirmed by trial sequential analysis. No significant difference was found in the TEE insertion time among the two techniques (mean difference: -2.94s, 95%CI: -10.28-4.4, P = 0.43). VL significantly reduced the risk of trauma to the hypopharyngeal wall but showed no significant benefits in other areas (e.g., pyriform sinus). The certainty of evidence was moderate for the complication rate, very low for the FAS rate, and low for the TEE insertion time., Conclusion: The use of VL for TEE probe insertion is associated with a significantly lower complication rate and higher FAS rate than conventional methods. These findings suggest that VL enhances patient safety and improves the efficiency of TEE probe insertion., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Hung et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Object: Osteosarcoma is a malignant tumor originating from the bones, commonly found in children and adolescents, especially in rapidly growing bone areas such as the knees and upper arms. In this study, we aim to delineate the evolution and convergence of research themes in osteosarcoma metabolomics over the past decade, identify major contributors, and forecast emerging trends that could direct future research efforts., Method: The bibliometric method has been applied to systematically analyze the literature in the field of osteosarcoma metabolomics. The relevant literatures were collected from the Web of Science Core Collection, spanning from January 1, 2014, to December 31, 2023. Tools such as CiteSpace, Bibliometrix, and VOSviewer were used for the visual analysis of the collected literatures. The focused information includes institutions, journals, countries, authors, keywords, and citations., Result: Various aspects in the field of osteosarcoma metabolism were analyzed. Shanghai Jiao Tong University has published the most papers in the past ten years, followed by Central South University and Zhejiang University. Among the sources, the international journal of molecular sciences publishes the most articles, and oncotarget is the journal with the highest H index. According to Bradford's law, there are 34 core journals identified. A total of 5501 authors participated in the creation of papers in this field. The distribution of authors follows Lotka`s Law, and 85.3% of authors have only one article. 46% of the corresponding authors are from China, but most of these corresponding authors are not good at international cooperation. China also has the largest number of publications, followed by the United States. It can be confirmed that China dominates this field. Among the keywords, "expression" is the keyword that has received the most attention in the past ten years. All keywords can be divided into 9 clusters. Based on the explosive words and hot topics each year, we speculate that future research will focus on the tumor microenvironment, molecular mechanisms and autophagy, targeted therapies and inhibitors., Conclusion: In summary, this study comprehensively analyzed the current state of research in the field of osteosarcoma metabolism through bibliometric methods. The findings revealed the development trends and research hotspots in this field, which may provide valuable references for future research directions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Tu, Liu, Li, Long, Wang, Liu and Gao.)

The biosynthesis of novel nanoparticles with varied morphologies, which has good implications for their biological capabilities, has attracted increasing attention in the field of nanotechnology. Bioactive compounds present in the extract of fungi, bacteria, plants and algae are responsible for nanoparticle synthesis. In comparison to other biological resources, brown seaweeds can also be useful to convert metal ions to metal nanoparticles because of the presence of richer bioactive chemicals. Carbohydrates, proteins, polysaccharides, vitamins, enzymes, pigments, and secondary metabolites in brown seaweeds act as natural reducing, capping, and stabilizing agents in the nanoparticle's synthesis. There are around 2000 species of seaweed that dominate marine resources, but only a few have been reported for nanoparticle synthesis. The presence of bioactive chemicals in the biosynthesized metal nanoparticles confers biological activity. The biosynthesized metal and non-metal nanoparticles from brown seaweeds possess different biological activities because of their different physiochemical properties. Compared with terrestrial resources, marine resources are not much explored for nanoparticle synthesis. To confirm their morphology, characterization methods are used, such as absorption spectrophotometer, X-ray diffraction, Fourier transforms infrared spectroscopy, scanning electron microscope, and transmission electron microscopy. This review attempts to include the vital role of brown seaweed in the synthesis of metal and non-metal nanoparticles, as well as the method of synthesis and biological applications such as anticancer, antibacterial, antioxidant, anti-diabetic, and other functions., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Male hypogonadism is not uncommon in people with HIV (PWH), with estimated prevalence ranging from 9% to 16%. Existing data are limited on the serum testosterone levels in PWH in Asian populations., Methods: We enrolled HIV-positive men who have sex with men (MSM) and had been on stable antiretroviral therapy and MSM without HIV between February 2021 and November 2022. Serum free testosterone levels, sex hormone-binding globulins and other associated hormones were measured. Multiple linear regression analysis was performed to assess the association between serum free testosterone levels and clinical variables collected., Results: A total of 447 MSM with HIV and 124 MSM without HIV were enrolled. Compared with MSM without HIV, MSM with HIV had a higher age (median, 41 versus 29.5 years) and prevalence of symptomatic hypogonadism (8.3% versus 1.6%). Among MSM who were aged <35 years, there were no significant differences in the serum free testosterone levels and prevalences of hypogonadism between the two groups. In multiple linear regression analysis, serum free testosterone level significantly decreased with advanced age (a decrease of 1.14 pg/mL per 1-year increase) and a higher body-mass index (BMI) (a decrease of 1.07 pg/mL per 1-kg/m 2 increase), but was not associated with HIV serostatus., Conclusion: We found that MSM with HIV had a higher prevalence of symptomatic hypogonadism than MSM without HIV in Taiwan, which could be attributed to age difference. Serum free testosterone levels were negatively correlated with age and BMI, but did not show a significant correlation with HIV serostatus., Competing Interests: Declaration of competing interest CCH has received honoraria for speaking at educational events or consulting from Gilead Sciences, and research funding from Gilead Sciences. HYS has received research funding from Gilead Sciences. The remaining authors declare no conflict of interest., (Copyright © 2024. Published by Elsevier B.V.)

Introduction: Targeted muscle reinnervation (TMR) is an established modality for the surgical management of neuropathic pain. Although the preventive effect of primary (acute) TMR at the time of amputation has been demonstrated previously, it remains unclear how many and which patients benefit most. Therefore, this study investigated the proportion of patients achieving sustained pain prophylaxis following amputation, as well as factors associated with its efficacy., Methods: Primary patients who underwent TMR with a minimum follow-up of 6 months between 2018 and 2023 were enrolled. Pain outcomes (numeric rating scale [NRS], 0-10), comorbidities, and surgical factors were collected from chart review. Patients achieving sustained pain prophylaxis (NRS of ≤3 for ≥3 months until final follow-up) were identified. Multilevel mixed-effect models and multivariable regression were used to visualize pain courses and identify associated factors., Results: Seventy-five patients who underwent primary TMR were included (median follow-up: 2.0 years), of whom 57.3% achieved sustained pain prophylaxis whereas 26.7% reported pain disappearance. Distal amputation levels (p = 0.036), a lower Elixhauser Comorbidity Index (p = 0.001), and the absence of psychiatric comorbidities (p = 0.039) were associated with pain prophylaxis., Conclusion: This study demonstrates that more than half of all patients undergoing primary TMR achieved sustained pain prophylaxis, and approximately a quarter of patients achieved sustained pain disappearance. Several factors associated with these favorable outcomes are described. These results will aid in preoperative counseling, managing patient expectations, and selecting patients who may benefit most from primary TMR surgery., Level of Evidence: IV - Therapeutic., (Copyright © 2024 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

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.

Major depressive disorder (MDD), affecting over 264 million individuals globally, is associated with immune system dysregulation and chronic neuroinflammation, potentially linked to neurodegenerative processes. This review examines blood-brain barrier (BBB) dysfunction in MDD, focusing on key regulators like matrix metalloproteinase 9 (MMP9), aquaporin-4 (AQP4), and ATP-binding cassette subfamily B member 1 (ABCB1). We explore potential mechanisms by which compromised BBB integrity in MDD may contribute to neuroinflammation and discuss the therapeutic potential of omega-3 polyunsaturated fatty acids (n-3 PUFAs). n-3 PUFAs have demonstrated anti-inflammatory and neuroprotective effects, and potential ability to modulate MMP9, AQP4, and ABCB1, thereby restoring BBB integrity in MDD. This review aims to elucidate these potential mechanisms and evaluate the evidence for n-3 PUFAs as a strategy to mitigate BBB dysfunction and neuroinflammation in MDD., (Copyright ©2024, Yale Journal of Biology and Medicine.)

The killer-cell immunoglobulin-like receptor (KIR) gene complex, a highly polymorphic region of the human genome that encodes proteins involved in immune responses, poses strong challenges in genotyping owing to its remarkable genetic diversity and structural intricacy. Accurate analysis of KIR alleles, including their structural variations, is crucial for understanding their roles in various immune responses. Leveraging the high-quality genome assemblies from the Human Pangenome Reference Consortium (HPRC), we present a novel bioinformatic tool, the structural KIR annoTator (SKIRT), to investigate gene diversity and facilitate precise KIR allele analysis. In 47 HPRC-phased assemblies, SKIRT identifies a recurrent novel KIR2DS4/3DL1 fusion gene in the paternal haplotype of HG02630 and maternal haplotype of NA19240. Additionally, SKIRT accurately identifies eight structural variants and 15 novel nonsynonymous alleles, all of which are independently validated using short-read data or quantitative polymerase chain reaction. Our study has discovered a total of 570 novel alleles, among which eight haplotypes harbor at least one KIR gene duplication, six haplotypes have lost at least one framework gene, and 75 out of 94 haplotypes (79.8%) carry at least five novel alleles, thus confirming KIR genetic diversity. These findings are pivotal in providing insights into KIR gene diversity and serve as a solid foundation for understanding the functional consequences of KIR structural variations. High-resolution genome assemblies offer unprecedented opportunities to explore polymorphic regions that are challenging to investigate using short-read sequencing methods. The SKIRT pipeline emerges as a highly efficient tool, enabling the comprehensive detection of the complete spectrum of KIR alleles within human genome assemblies., (© 2024 Hung et al.; Published by Cold Spring Harbor Laboratory Press.)

Background: Remimazolam is a novel ultra-short-acting benzodiazepine that has been recently introduced as an alternative to propofol for general anesthesia. While both agents have been compared in terms of safety and efficacy, their relative effects on postoperative quality of recovery (QoR) remain unclear. Therefore, this meta-analysis aimed to compare the effects of remimazolam and propofol on subjective QoR in surgical patients who underwent general anesthesia., Methods: Medline, Embase, Google Scholar, and the Cochrane Central Register of Controlled Trials were searched from inception to May 28, 2024 to identify randomized controlled trials comparing remimazolam and propofol in terms of postoperative QoR. The Cochrane risk-of-bias tool (RoB 2) was used to assess study quality. QoR score on postoperative day (POD) 1 (primary outcome), QoR scores on PODs 2-3, QoR dimensions, time to loss of consciousness, other recovery characteristics, and rescue analgesia requirement were evaluated using random-effects meta-analyses., Results: This meta-analysis included 13 studies published between 2022 and 2024 involving 1,418 patients. QoR was evaluated using either the QoR-15 (10 studies) or QoR-40 (3 studies) questionnaire. The pooled results indicated no significant difference in the QoR scores on POD 1 (standardized mean difference: 0.02, 95% confidence interval [CI]: - 0.20, 0.23, P = 0.88, I 2  = 73%) and PODs 2-3 between remimazolam and propofol. Furthermore, no significant differences were observed in QoR dimensions, length of postanesthesia care unit (PACU) stay, and time to extubation as well as in the risks of agitation and postoperative nausea and vomiting. Patients administered remimazolam exhibited slower anesthetic induction (mean difference (MD): 32.27 s) but faster recovery of consciousness (MD: - 1.60 min) than those administered propofol. Moreover, remimazolam was associated with a lower risk of rescue analgesia requirement in the PACU (risk ratio: 0.62, 95% CI: 0.43, 0.89, P = 0.009, I 2  = 0%) but not in the ward., Conclusion: Remimazolam is a potential alternative to propofol for general anesthesia as it offers similar QoR to the latter and has advantages in terms of consciousness recovery and immediate postoperative analgesia requirement., (© 2024. The Author(s).)

The entrance channel of bimolecular reactions sometimes involves the formation of outer complexes as weakly bound, fleeting intermediates. Here, we characterize such an outer complex in a system that models the bimolecular, C-O bond-forming reaction of a phosphine oxide Lewis base with a carbenium Lewis acid. Crystallographic studies show that the C-O distance in the outer form exceeds that of the final or inner adduct by 1.1 angstroms. As the system samples the two forms of the complex, which correspond to minima on the corresponding potential energy surface, the C-O linkage switches from a secondary interaction in the outer complex to a dative bond in the inner complex. This phenomenon is harnessed as a functional feature to stabilize xanthylium-based photoredox catalysts.

Objective: The impact of time on neuroma growth and morphology on pain intensity is unknown. This study aims to assess magnetic resonance imaging (MRI) differences between symptomatic and non-symptomatic neuromas in oncological amputees, and whether time influences MRI-detected neuroma dimensions and their association with pain., Material and Methods: Oncological patients who underwent traditional extremity amputation were included. Post-amputation MRIs were assessed before decision for neuroma surgery. Chart review was performed for residual limb pain (numeric rating scale, 0-10) and the presence of neuropathic symptoms. Neuromas were classified as symptomatic or non-symptomatic, with neuroma size expressed as radiological neuroma-to-nerve-ratio (NNR)., Results: Among 78 neuromas in 60 patients, the median NNR was 2.0, and 56 neuromas (71.8%) were symptomatic with a median pain score of 3.5. NNR showed no association with symptomatology or pain intensity but correlated with a longer time-to-neuroma-excision interval and a smaller nerve caliber. Symptomatic neuromas were associated with lower extremity amputation, T2 heterogeneity, and the presence of heterotopic ossification. Lower extremity amputation, T2 heterogeneity, perineural edema, and presence of heterotopic ossification were associated with more painful neuromas., Conclusion: MRI features associated with symptomatic neuromas and pain intensity were identified. Awareness of the potential clinical significance of these imaging features may help in the interpretation of MRI exams and may aid clinicians in patient selection for neuroma surgery in oncological amputees., (© 2024. The Author(s), under exclusive licence to International Skeletal Society (ISS).)

Background and Objectives: Anatomic features of neuromas have been explored in imaging studies. However, there has been limited research into these features using resected, ex vivo human neuroma specimens. The aim of this study was to investigate the influence that time may have on neuroma growth and size, and the clinical significance of these parameters., Methods: Patients who underwent neuroma excision between 2022 through 2023 were prospectively included in this study. Neuroma specimens were obtained after operative resection. Standardized neuroma size measurements, expressed as a neuroma-to-nerve ratio (NNR), were conducted with ImageJ software. Pain data (numeric rating scale, 0-10) were prospectively recorded during preoperative evaluation, and patient factors were collected from chart reviews., Results: Fifty terminal neuroma specimens from 31 patients were included, with 94.0% of the neuromas obtained from individuals with amputations. Most neuromas were excised from the lower extremities (n = 44, 88.0%). The neuromas had a median NNR of 2.45, and the median injury to neuroma excision interval was 6.3 years. Larger NNRs were associated with a longer injury to neuroma excision interval and with a smaller native nerve diameter. In addition, sensory nerves were associated with a larger NNR compared with mixed nerves. NNR was not associated with preoperative pain or with anatomical nerve distribution., Conclusion: This study suggests that neuromas seem to continue to grow over time and that smaller nerves may form relatively larger neuromas. In addition, sensory nerves develop relatively larger neuromas compared with mixed nerves. Neuroma size does not appear to correlate with pain severity. These findings may stimulate future research efforts and contribute to a better understanding of symptomatic neuroma development., (Copyright © Congress of Neurological Surgeons 2024. All rights reserved.)

Arabidopsis (Arabidopsis thaliana) H+-ATPase1 (AHA1), a plasma membrane (PM)-localized H+-ATPase, plays a key role in plant alkali stress tolerance by pumping protons from the cytoplasm to the apoplast. However, its molecular dynamics are poorly understood. We report that many C2-domain ABA-related (CAR) protein family members interact with AHA1 in Arabidopsis. Single or double mutants of CAR1, CAR6, and CAR10 had no obvious phenotype of alkali stress tolerance, while their triple mutants showed significantly higher tolerance to this stress. The disruption of AHA1 largely compromised the increased alkali stress tolerance of the car1car6car10 mutant, revealing a key role of CARs in AHA1 regulation during the plant's response to a high alkali pH. Furthermore, variable angle total internal reflection fluorescence microscopy was used to observe AHA1-mGFP5 in intact Arabidopsis seedlings, revealing the presence of heterogeneous diffusion coefficients and oligomerization states in the AHA1 spots. In the aha1 complementation lines, alkali stress curtailed the residence time of AHA1 at the PM and increased the diffusion coefficient and particle velocity of AHA1. In contrast, the absence of CAR proteins decreased the restriction of the dynamic behavior of AHA1. Our results suggest that CARs play a negative role in plant alkali stress tolerance by interacting with AHA1 and provide a perspective to investigate the regulatory mechanism of PM H+-ATPase activity at the single-particle level., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Society of Plant Biologists. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Carboxylesterase 1 (CES1), a member of the serine hydrolase superfamily, is involved in a wide range of xenobiotic and endogenous substances metabolic reactions in mammals. The inhibition of CES1 could not only alter the metabolism and disposition of related drugs, but also be benefit for treatment of metabolic disorders, such as obesity and fatty liver disease. In the present study, we aim to develop potential inhibitors of CES1 and reveal the preferred inhibitor structure from a series of synthetic pyrazolones (compounds 1-27). By in vitro high-throughput screening method, we found compounds 25 and 27 had non-competitive inhibition on CES1-mediated N-alkylated d-luciferin methyl ester (NLMe) hydrolysis, while compound 26 competitively inhibited CES1-mediated NLMe hydrolysis. Additionally, Compounds 25, 26 and 27 can inhibit CES1-mediated fluorescent probe hydrolysis in live HepG2 cells with effect. Besides, compounds 25, 26 and 27 could effectively inhibit the accumulation of lipid droplets in mouse adipocytes cells. These data not only provided study basis for the design of newly CES1 inhibitors. The present study not only provided the basis for the development of lead compounds for novel CES1 inhibitors with better performance, but also offered a new direction for the explore of candidate compounds for the treatment of hyperlipidemia and related diseases., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Heat stress (HS) poses a great challenge to the poultry industry by inducing oxidative damage to the liver, endangering the health and production of broilers. As an important type of seaweed polyphenols, phlorotannin has been shown to have antioxidant properties. The present study evaluated the protective effects of dietary phlorotannin on HS-induced liver injury in broilers based on oxidative damage parameters. A total of 108 twenty-one days old male Arbor Acres plus (AA+) broilers were randomly divided into three groups: TN group (thermoneutral, 24 ± 1 °C, fed with basal diet), HS group (HS, 33 ± 1 °C for 8 h/day, fed with basal diet), and HS + phlorotannin group (HS + 600 mg/kg phlorotannin). Each group has six replicate cages with six birds per cage. The feeding experiment lasted 21 days. At the termination of the feeding experiment (42 days old), samples were collected for analysis of morphological and biochemical features. The results showed that HS decreased the liver index, serum albumin (ALB) content, hepatic antioxidant enzymes activities of catalase (CAT), total superoxide dismutase (T-SOD), glutathione S-transferase (GST), and glutathione peroxidase (GSH-Px) ( p < 0.05), while increasing the hepatic histopathology score, apoptosis rate, and malondialdehyde (MDA) content ( p < 0.05) in 42-day-old broilers. Compared with the HS group, dietary phlorotannin improved the activities of antioxidant enzymes (GST and GSH-Px) but decreased the histopathology score and apoptosis rate in the liver ( p < 0.05). Moreover, HS down-regulated hepatic mRNA expression of CAT1 , NQO1 , HO-1 , and SLC7A11 ( p < 0.05), while up-regulated hepatic mRNA expression of Keap1 , MafG , IκBα , NF-κB P65 , IFN-γ , TFR1 , ACSL4 , Bax, and Caspase-9 ( p < 0.05). Compared with HS group, dietary phlorotannin up-regulated hepatic mRNA expression of Nrf2 , CAT1 , MafF , GSTT1 , NQO1 , HO-1 , GCLC , GPX1 , TNF-α , Fpn1, and SLC7A11 ( p < 0.05), while down-regulated hepatic mRNA expression of IκBα , Bax , Caspase-9, and TFR1 ( p < 0.05). In conclusion, dietary supplementation of 600 mg/kg phlorotannin could alleviate HS-induced liver injury via regulating oxidative status, apoptosis, and ferroptosis in broilers; these roles of phlorotannin might be associated with the regulation of the Nrf2 signaling pathway.

Macrophages played an important role in the progression and treatment of head and neck squamous cell carcinoma (HNSCC). We employed weighted gene co-expression network analysis (WGCNA) to identify macrophage-related genes (MRGs) and classify patients with HNSCC into two distinct subtypes. A macrophage-related risk signature (MRS) model, comprising nine genes: IGF2BP2, PPP1R14C, SLC7A5, KRT9, RAC2, NTN4, CTLA4, APOC1, and CYP27A1, was formulated by integrating 101 machine learning algorithm combinations. We observed lower overall survival (OS) in the high-risk group and the high-risk group showed elevated expression levels in most of the immune checkpoint and human leukocyte antigen (HLA) genes, suggesting a strong immune evasion capacity. Correspondingly, TIDE score positively correlated with risk score, implying that high-risk tumors may resist immunotherapy more effectively. At the single-cell level, we noted macrophages in the tumor microenvironment (TME) predominantly stalled in the G2/M phase, potentially hindering epithelial-mesenchymal transition and playing a crucial role in the inhibition of tumor progression. Finally, the proliferation and migration abilities of HNSCC cells significantly decreased after the expression of IGF2BP2 and SLC7A5 reduced. It also decreased migration ability of macrophages and facilitated their polarization towards the M1 direction. Our study constructed a novel MRS for HNSCC, which could serve as an indicator for predicting the prognosis, immune infiltration and immunotherapy for HNSCC patients., (© 2024. The Author(s).)

In recent decades, orthopedic implants have been widely used as materials to replace human bone tissue functions. Among these, metal implants play a crucial role. Metals with better chemical stability, such as stainless steel, titanium alloys, and cobalt-chromium-molybdenum (CoCrMo) alloy, are commonly used for long-term applications. However, good chemical stability can result in poor tissue integration between the tissue and the implant, leading to potential inflammation risks. This study creates hydrogenated CoCrMo (H-CoCrMo) surfaces, which have shown promise as anti-inflammatory orthopedic implants. Using the electrochemical cathodic hydrogen-charging method, the surface of the CoCrMo alloy was hydrogenated, resulting in improved biocompatibility, reduced free radicals, and an anti-inflammatory response. Hydrogen diffusion to a depth of approximately 106 ± 27 nm on the surface facilitated these effects. This hydrogen-rich surface demonstrated a reduction of 85.2% in free radicals, enhanced hydrophilicity as evidenced by a decrease in a contact angle from 83.5 ± 1.9° to 52.4 ± 2.2°, and an increase of 11.4% in hydroxyapatite deposition surface coverage. The cell study results revealed a suppression of osteosarcoma cell activity to 50.8 ± 2.9%. Finally, the in vivo test suggested the promotion of new bone formation and a reduced inflammatory response. These findings suggest that electrochemical hydrogen charging can effectively modify CoCrMo surfaces, offering a potential solution for improving orthopedic implant outcomes through anti-inflammatory mechanisms.