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Ling-Xia Ha,1 Wei-Xia Li,2 Yu-Dong Du,3 Ying-Ying Yuan,1 Xiao-Xiao Qu3 1Reproductive Medicine Center, General Hospital of Ningxia Medical University, Yinchuan, 750004, Ningxia, People’s Republic of China; 2Reproductive Center, Maternal and Child Health Care Hospital of Yinchuan City, Yinchuan, Ningxia, 750000, People’s Republic of China; 3Ningxia Medical University, General Hospital of Ningxia Medical University, Yinchuan, Ningxia, 750004, People’s Republic of ChinaCorrespondence: Ling-Xia Ha, Reproductive Medicine Center, General Hospital of Ningxia Medical University, No. 804 of Shengli Road, Xingqing District, Yinchuan, Ningxia, 750004, People’s Republic of China, Tel +86 951 6744033 ; +86 13629500990, Fax +86 951 6743891, Email halingxia@126.comObjective: This study aimed to analyze tumor necrosis factor alpha (TNF-α) level in the uterine fluid of patients with polycystic ovary syndrome (PCOS) and its correlation with the clinical parameters of PCOS.Methods: A total of 162 patients treated in the Reproductive Medicine Center of the General Hospital of Ningxia Medical University between December 2019 and November 2021 were enrolled as research subjects, including 80 patients with PCOS and 82 patients with other gynecological disease, who were used as the controls. The patients’ general data, along with blood glucose, blood lipid, insulin, and sex hormone levels and other data, were collected. The TNF-α levels in the patients’ serum and uterine fluid were detected using enzyme-linked immunosorbent assay.Results: Compared with the patients in the control group, the body mass index (BMI), anti-Müllerian hormone, luteinizing hormone, testosterone (T), fasting insulin (FINS), homeostasis model assessment insulin resistance (HOMA-IR), triglyceride (TG), and low-density lipoprotein (LDL) of patients with PCOS were higher, and high-density lipoprotein was lower (P < 0.05). The TNF-α levels in the serum and uterine fluid of patients with PCOS were higher than those in the control group (P < 0.01), and the TNF-α levels in the uterine fluid of these patients was significantly correlated with BMI, T, FINS, HOMA-IR, serum TNF-α, TG, and LDL (P < 0.05).Conclusion: There is local inflammation in the uterine cavity of patients with PCOS, and the detection of cytokines in uterine secretions may be a simple and feasible method of understanding the uterine microenvironment of patients with PCOS.Keywords: polycystic ovary syndrome, uterine fluid, TNF-α, insulin resistance, lipid metabolism

Ruifeng Zhang, Xuhong Dang, Zhongxin Zhang, Yayi Yuan, Yue Ren, Zhikai Duan, Yahui Zuo China Institute for Radiation Protection, Taiyuan, Shanxi 030006, China Objective: Heavy ions have contributed to tumor site-specific radiotherapy and are a major health risk for astronauts. The purpose of this study was to investigate the changes in gene expression in peripheral lymphocytes of cancer patients and astronauts exposed to 12C ions, and identify suitable molecular biomarkers for health monitoring. We also aimed to observe the effects of treatment and the level of damage, by comparing the transcriptional profiles of human lymphocyte cell lines exposed to 12C ion beams at doses of 0–2.0 Gy.Materials and methods: A human lymphocyte cell line was irradiated with 12C ion beams at 0, 0.1, 0.5, and 2.0 Gy and transcriptional profiles were evaluated using the Agilent human gene expression microarray at 24 hours after irradiation. Differentially expressed genes were identified using a fold change of ≥2.0. Representative genes were further validated by RT-PCR. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed to determine the roles of differentially expressed mRNAs. Results: Based on the microarray assays, 1,113 genes were upregulated and 853 genes were downregulated in human lymphocyte cells irradiated with 0.1 Gy 12C ion beams compared with the control group, 1,095 genes were upregulated and 1,220 genes were downregulated in cells irradiated with 0.5 Gy 12C ion beams, and 1,055 genes were upregulated and 1,356 genes were downregulated in cells irradiated with 2.0 Gy. A total of 504 genes were differentially expressed in all irradiated groups, of which 88 genes were upregulated and 416 genes downregulated. Most of these altered genes were related to the cell cycle, apoptosis, signal transduction, DNA transcription, repair, and replication. The expression differences were further confirmed by RT-PCR for a subset of differentially expressed genes. Conclusion: Differentially expressed genes between treatment and control groups at 24 hours post-irradiation increased as the radiation dose increased; upregulated genes gradually decreased and downregulated genes increased. Our data indicated that 12C ion beams could repress a number of genes in a dose-dependent manner, which might lead to the failure of multiple cellular biological functions. Keywords: 12C ion beams, human lymphocyte cell line, microarray assay, gene expression

To investigate the structural characteristics of cell wall pectic polysaccharides from wampee, water soluble pectin (WSP), chelator-soluble pectin (CSP) and sodium carbonate-soluble pectin (SSP) were purified. And the inhibitory effects of wampee polyphenol (WPP) on pectinase when these cell wall pectic polysaccharides were used as substrates were also explored. Purified WSP (namely PWSP) had the lowest molecular weight (8.47 × 10 5  Da) and the highest GalA content (33.43%). While purified CSP (called PCSP) and SSP contained more abundant rhamnogalacturonan I side chains. All of them were low-methoxy pectin (DE < 50%). Enzyme activity and kinetics analysis showed that the inhibition of pectinase by wampee polyphenol was reversible and mixed type. When SSP was used as the substrate, WPP had the strongest inhibition (IC 50  = 1.96 ± 0.06 mg/mL) on pectinase. Fluorescence quenching results indicated that WPP inhibited enzyme activity by interacting with substrates and enzymes. Therefore, WPP has the application potential in controlling softening of fruits and vegetables., 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.)

Background and Objectives: A quarter of ischemic strokes are of lacunar clinical subtype and have an underlying recent small subcortical infarct (RSSI), but their long-term outcomes remain poorly characterized. Hemosiderin deposits (HDs) have been noted in RSSIs at chronic stages and might mimic primary hemorrhage. We characterized HDs' morphology, frequency, and clinical relevance., Methods: Participants with RSSIs were identified from a prospective longitudinal study and evaluated on 3T MRI including susceptibility-weighted imaging (SWI) from stroke diagnosis to 12 months. We categorized HDs in RSSIs on SWI at all available time points into 4 types (spots, smudge, rim, cluster) and assessed their associations with demographic factors, stroke-related factors, and image markers with adjusted logistic regression., Results: HDs were observed in 43 (55.0%) of 108 participants within 3 months and 83 (76.9%) of 108 within 12 months after stroke onset. The mean time to first detection of HDs was 87 (interquartile range 53-164) days. A "rim" pattern (similar to late appearance of primary hemorrhage) occurred in at least 26.5% of RSSIs at all follow-up time points, mainly those located in the lentiform/internal capsule (50.0%) or thalamus (36.4%). Infarct volume (odds ratio [OR] 1.003, 95% CI 1.001-1.006; p = 0.004) and the total small vessel disease (SVD) score at baseline (OR 2.50, 95% CI 1.28-4.86, p = 0.007) independently predicted HDs at 12 months. HDs were positively associated with more lacunes (OR 1.60, 95% CI 1.13-2.26, p < 0.01), but not the Fazekas score, number of microbleeds, basal ganglia mineral deposit score, or clinical outcomes., Discussion: HDs occur commonly in RSSIs and may be associated with infarct volume and SVD score. Hemosiderin "rim" is common in RSSIs, urging caution to avoid mistaking ischemic RSSI for primary hemorrhage in subacute and chronic stages.

Herein, a cobalt-catalyzed intramolecular enantioselective reductive Heck reaction is disclosed. Starting from N - ortho -iodoaryl-2-(trifluoromethyl)acrylamides, a plethora of chiral oxindoles bearing trifluoromethylated quaternary stereogenic centers at the C3-position are achieved in moderate to good yields (up to 88% yield) and good to excellent enantioselectivities (up to 94% ee) by employing zinc/silane as reducing agent. Other than the trifluoromethyl group, a number of chiral oxindoles bearing alkyl, aryl, and ester groups at C3-position were also obtained albeit in relatively lower enantioselectivities (68-78% ee).

We report a novel large α-globin gene cluster deletion in a Chinese family from the Guangxi Zhuang Autonomous Regionfor the first time. The proband was a 20-year-old male who presented with microcytic hypochromatosis. Routine genetic analysis showed none of the common mutations in theα-globin and β-globin genes. Multiplex ligation-dependent probe amplification (MLPA) of the α-globin chain revealed there was a large deletion, which removed the entire HBA2 and HBA1 genes, HBQ gene, HBZ gene, and major regulatory element HS-40, eliminating more than 134 kb from the α-globin chain. Subsequently, pedigree analysis revealed that the proband inherited the novel deletion from his father. By consultation of literature and databases, it was confirmed as a hitherto undescribed chain deletion and named Laibin deletion (- LB ) for the origin of the proband.

Background: Recent advances in ultrasound technology have led to widespread adoption of ultrasonic energy devices in liver resections. While various studies have assessed the comparative advantages of ultrasonic devices and traditional clamp-crushing, their findings vary. Moreover, a specific systematic review on this topic has not yet been conducted., Objectives: This study aims to present a comprehensive, up-to-date analysis comparing outcomes between ultrasonic devices and conventional clamp-crushing methods in liver resection, based on currently available literature., Patients and Methods: We conducted a systematic literature search in databases such as PubMed, Embase, Web of Science, and CNKI up to November 2023. Studies that compared the efficacy or safety of ultrasonic devices against traditional clamp-crushing methods in hepatectomy were included. The analysis covered intraoperative outcomes like operating time, blood loss, and transfusion rate, as well as postoperative outcomes such as complication rate, mortality, postoperative bleeding, and bile leakage. Review Manager version 5.3 (Cochrane Collaboration, Oxford, UK) and Stata 17.0 (Stata Corp, College Station, TX, USA) were used for data analysis., Results: Thirteen studies, involving a total of 1,417 patients (630 using ultrasonic devices and 787 using clamp-crushing methods), were included. The clamp-crush method resulted in a shorter operation time. Contrarily, the ultrasonic device group experienced reduced blood loss and lower transfusion rates. Postoperatively, there was no significant difference in mortality or postoperative bleeding between the groups. However, the ultrasonic group had a lower overall complication rate, particularly a reduced incidence of bile leakage. Overall, the ultrasonic devices were associated with improved perioperative outcomes., Conclusions: The findings suggest that ultrasonic devices provide better outcomes in hepatectomy compared to traditional clamp-crushing techniques. Nonetheless, large-scale randomized controlled trials are needed to confirm these results due to potential heterogeneity and biases. The choice of using ultrasonic devices should consider the surgeon's experience and individual patient circumstances., Competing Interests: Declarations Ethics approval and consent to participate Ethical review and approval were not required for the study of human participants in accordance with the local legislation and institutional requirements. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Background: Acidosis is the most common complication that seriously affects the prognosis of acute respiratory distress syndrome (ARDS). Acid-sensitive ion channel 1a (ASIC1a) is activated in acidic environments to regulate inflammatory process. However, the role of ASIC1a in ARDS is unclear., Methods: In this study, we examined the expression of ASIC1a in airway epithelial cells in an acidic environment. We then investigated whether blocking ASIC1a could inhibit pyroptosis of airway epithelial cells and the molecular mechanism. In the mouse acute lung injury (ALI) model, we observed the changes of lung histopathology, arterial blood gas and pyroptosis related indexes after ASIC1a inhibition. Bronchoalveolar lavage fluid (BALF) from patients with ARDS were collected to explore the expression level of ASIC1a in ARDS patients., Results: Inhibiting ASIC1a can reduce the airway epithelial cell pyroptosis induced by an extracellular acidic environment. ASIC1a can bind to PRKACA, and silencing ASIC1a and PRKACA can inhibit the occurrence of pyroptosis in airway epithelial cells. Compared with control group, arterial blood pH and PaO 2 in ALI group were significantly reduced. The inflammation in the lungs is more intense, and the mRNA and protein of NLRP3, Caspase1 and GSDMD were increased, while ASIC1a specific blocker psalmotoxin-1 alleviated this phenomenon. The expression of ASIC1a in BALF of ARDS patients was significantly increased, especially in non-survival group., Conclusion: Acidic micro-environment can induce the increased expression of ASIC1a, and inhibition of ASIC1a can alleviate the inflammation and airway epithelial cell pyroptosis in ARDS. ASIC1a may be a new target for the treatment of ARDS., 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 Author(s). Published by Elsevier B.V. All rights reserved.)

Geminal and vicinal borosilanes have unique applications in functional materials and synthetic transformations. Herein, a convenient method for the synthesis of geminal and vicinal borosilanes is developed via photoredox metal-free hydrosilylation of vinylboronic esters. This strategy features the advantages of high atom economy, environmental friendliness, and excellent functional group compatibility. The mechanism studies reveal that the catalytic reaction goes through photoredox HAT catalysis and a radical addition pathway.

Soil salinization poses a significant global challenge, exerting adverse effects on both agriculture and ecosystems. Planting halophytes has the potential ability to improve saline-alkali land and enhance ecosystem multifunctionality (EMF). However, it remains unclear which halophytes are effective in improving saline-alkali land and what impact they have on the rhizosphere microbial communities and EMF. In this study, we evaluated the Na + absorption capability of five halophytes (Grubovia dasyphylla, Halogeton glomeratus, Suaeda salsa, Bassia scoparia, and Reaumuria songarica) and assessed their rhizosphere microbial communities and EMF. The results showed that S. salsa possessed the highest shoot (3.13 mmol g -1 ) and root (0.92 mmol g -1 ) Na + content, and its soil Na + absorption, along with B. scoparia, was significantly higher than that of other plants. The soil pH, salinity, and Na + content of the halophyte rhizospheres decreased by 6.21%, 23.49%, and 64.29%, respectively, when compared to the bulk soil. Extracellular enzymes in the halophyte rhizosphere soil, including α-glucosidase, β-glucosidase, β-1,4-N-acetyl-glucosaminidase, neutral phosphatase, and alkaline phosphatase, increased by 70.1%, 78.4%, 38.5%, 79.1%, and 64.9%, respectively. Furthermore, the halophyte rhizosphere exhibited higher network complexity of bacteria and fungi and EMF than bulk soil. The relative abundance of the dominant phyla Proteobacteria, Firmicutes, and Ascomycota in the halophyte rhizosphere soil increased by 9.4%, 8.3%, and 22.25%, respectively, and showed higher microbial network complexity compared to the bulk soil. Additionally, keystone taxa, including Muricauda, Nocardioides, and Pontibacter, were identified with notable effects on EMF. This study confirmed that euhalophytes are the best choice for saline-alkali land restoration. These findings provided a theoretical basis for the sustainable use of saline-alkali cultivated land., 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.)

Ethnopharmacological Relevance: Cordyceps cicadae (C.cicadae), named "Chan Hua", an anamorph of Isaria cicadae Miquel, is an entomogenous complex formed by fungi parasitizing on the larvae of cicadas and belongs to the Claviciptaceae family and the genus Codyceps, which traditionally holds a significant place in Chinese ethnopharmacology, specifically for eye clarity and as a remedy for age-related ocular conditions. The underlying mechanisms contributing to its eyesight enhancement and potential effectiveness against Age-related macular degeneration (AMD) remain unexplored., Aim of the Study: This study aims to elucidate the protective role of C.cicadae and its active ingredient, Myriocin (Myr), against AMD., Materials and Methods: A chemical inducer was employed to make retinal pigment epithelium (RPE) damage in vitro and in vivo. The key ingredients of C.cicadae and their related mechanisms for anti-AMD were studied through bioinformatic analysis and molecular biological approaches., Results: Myr was identified through high-performance liquid chromatography (HPLC) as an active ingredient in C.cicadae, and demonstrated a protective effect on RPE cells, reducing the structural damage and cell death induced by sodium iodate (SI). Further, Myr reduced eyelid secretions in AMD mice and restored their retinal structure and function. The differentially expressed genes (DEGs) in Myr treatment are primarily associated with TNF and Necroptosis signaling pathways. Molecular docking indicated a strong affinity between TNF and Myr. Myr inhibited the TNF signaling pathway thereby reducing the expression of inflammatory factors in ARPE-19 cells. Additionally, Myr had consistent action with the necroptosis inhibitor Necrostatin-1 (Nec-1), inhibited the RIPK1/RIPK3/MLKL pathway thereby protecting ARPE-19 cells., Conclusion: The findings present Myr, as a potent protector against SI-induced AMD, predominantly through modulation of the TNF-RIPK1/RIPK3/MLKL signaling pathway, offering the insights of therapeutic C.cicadae as viable candidates for AMD 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 B.V. All rights reserved.)

Itaconic acid and its metabolites have demonstrated significant therapeutic potential in various immune diseases. Originating from the tricarboxylic acid cycle in immune cells, itaconic acid can modulate immune responses, diminish inflammation, and combat oxidative stress. Recent research has uncovered multiple mechanisms through which itaconic acid exerts its effects, including the inhibition of inflammatory cytokine production, activation of anti-inflammatory pathways, and modulation of immune cell function by regulating cellular metabolism. Cellular actions are influenced by the modulation of metabolic pathways, such as inhibiting succinate dehydrogenase (SDH) activity or glycolysis, activation of nuclear-factor-E2-related factor 2 (Nrf2), boosting cellular defences against oxidative stress, and suppression of immune cell inflammation through the NF-κB pathway. This comprehensive review discusses the initiation, progression, and mechanisms of action of itaconic acid and its metabolites, highlighting their modulatory effects on various immune cell types. Additionally, it examines their involvement in immune disease like rheumatoid arthritis, multiple sclerosis, type 1 diabetes mellitus, and autoimmune hepatitis, offering greater understanding for creating new therapies for these ailments., (© 2024 John Wiley & Sons Ltd.)

Liver fibrosis (LF) is a common sequela to diverse chronic liver injuries, leading to rising rates of cirrhosis and hepatocellular carcinoma (HCC). As the medicinal and edible homologous material, traditional teas have exhibited promising applications in the clinical management of liver fibrosis. Here, we generated a liver fibrosis mouse model to explore the potent therapeutic ability of Ampelopsis grossedentata (AG) tea on this condition by multi-omics analysis. The biochemistry results pointed towards mitigated increases of ALT, AST, TBIL, and ALP triggered by BDL in the AG-treated group. Examination using H&E and Sirius Red staining revealed severe liver injuries, inflammation infiltration, amplified fibrosed regions, and the creation of bile ducts, all of which were fallout from BDL. Immunohistochemistry findings also implicated a noteworthy upregulation of the HSC activation marker α-smooth muscle actin (α-SMA) and the fibrosis marker collagen I in the BDL group. However, these symptoms demonstrated a significant improvement in the group treated with 100 mg/kg AG. Findings from the Western Blot test corroborated the prominent elevation of TNF-α, col1a1, α-SMA, and TGF-β, instigated by BDL, while AG treatment meaningfully modulated these proteins. Furthermore, our study underscored the potential involvement of several microbiota, such as Ruminococcaceae UCG-014, Eubacterium Ruminantium, Ruminococcus 1, Christensenellaceae R-7, Acetatifactor, Dubosiella, Parasutterella, Faecalibaculum, and Defluviitaleaceae UCG-011, in the progression of liver fibrosis and the therapeutic efficacy of AG. This investigation shows that during the process of AG ameliorating BDL-induced liver fibrosis, bile acid derivatives such as CDCA, TCDCA, 3-DHC, UCA, DCA, among others, play significant roles. In this study, we identified that several non-bile acid metabolites, such as Deltarasin, Thr-Ile-Arg, etc., are entailed in the process of AG improving liver fibrosis., Competing Interests: Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Photonic heterostructures with codable properties have shown great values as versatile information carriers at the micro- and nanoscale. These heterostructures are typically prepared by a step-by-step growth or post-functionalization method to achieve varied emission colors with different building blocks. In order to realize high-throughput and multivariate information loading, we report here a strategy to integrate polarization signals into photonic heterojunctions. A U-shaped di-Pt(II) complex has been assembled into highly polarized yellow-phosphorescent crystalline microrods (Y-rod) by strong intermolecular Pt⋅⋅⋅Pt interaction. Upon end-initiated desorption of the incorporated CH 2 Cl 2 solvents, the Y-rod is transformed in a domino fashion into tri-block polarized photonic heterojunctions (PPHs) with alternate red-yellow-red emissions or red-phosphorescent microrods (R-rods). The red emissions of these structures are also highly polarized; however, their polarization directions are just orthogonal to those of the yellow phosphorescence of the Y-rod. With the aid of a patterned mask, the R-rod can be further programmed into multi-block PPHs with precisely controlled block sizes by side-allowed adsorption of CH 2 Cl 2 vapor. X-ray diffraction analysis and theoretical calculations suggest that the solvent-regulated modulation of the crystal packing and excited-state property is critical for the construction of these PPHs., (© 2024 Wiley-VCH GmbH.)

Objective: Epilepsy is one of the most prevalent brain diseases. Approximately one third of patients consistently experience drug-resistant epilepsy (DRE), a condition where seizures persist despite the use of antiseizure medications. Exploration of new therapies for DRE is urgently needed. In this single-center, randomized, sham-controlled, crossover clinical trial (NCT05042726), we aimed to investigate the effectiveness and safety of transcranial magnetic continuous theta burst stimulation (cTBS) targeting the cerebellum to treat DRE., Methods: Patients with DRE for ≥2 years and a seizure frequency of ≥2 seizures per month were enrolled and randomized 1:1 to receive active stimulation followed by sham stimulation or vice versa. The bilateral cerebellum was targeted by navigated cTBS focusing on the cerebellar dentate nucleus, once daily on workdays for 2 weeks. The primary outcomes were the percentage of seizure reduction and 50% responder rate in the per-protocol population within 2 months after treatment., Results: Forty-four patients were enrolled and randomized; 18 patients in the active stimulation-first group and 20 in the sham stimulation-first group were included in the final analysis. Active cTBS significantly reduced seizures compared to sham stimulation (difference in percentage of seizure reduction between treatments = 25%, 95% confidence interval [CI] = 5%-46%, p = .018). The 50% responder rate after active stimulation was significantly higher than that after sham stimulation (difference in 50% responder rate between treatments = 24%, 95% CI = 11%-40%, p = .029). Adverse events occasionally occurred during active stimulation (moderate headache in 5% of patients, tinnitus in 3% of patients, dizziness in 3% of patients) but resolved spontaneously within days after treatment completion., Significance: This trial suggested that cTBS targeting the cerebellum was effective and well tolerated in the treatment of DRE. Further studies are warranted to confirm its effectiveness and mechanism., (© 2024 International League Against Epilepsy.)

Owning to the hydrophobic characteristics of microporous organic networks (MONs), their utilizations still largely limited in non- and weak-polar analytes. To expend their applications, here we reported the synthesis of a novel hollowed H-MON-PEI 1800 -2 composite via sacrifice template method and subsequent modification with polyethyleneimine (PEI) for efficient solid phase extraction of polar and ionic phenolic acid (PAs) from fruit juice samples. H-MON-PEI 1800 -2 exhibits large surface area, rapid extraction kinetics, remarkable chemical and thermal stabilities, and provides synergistic electrostatic, π-π, hydrogen bonding, and hydrophobic interaction sites for PAs. The developed method owns low limit of detection, wide linear range, large enrichment factors, and good reusability. The recoveries of H-MON-PEI 1800 -2 for PAs are 1-3 orders of magnitude higher than those of commercial adsorbents like activated carbon, C18 and Oasis HLB. This work highlights the prospects of functional H-MONs for enriching polar and ionic targets from complex sample matrices., 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 and Purpose: To investigate the impact of radiotherapy (RT) on the risk of secondary pelvic neoplasms (SPN) and the survival outcomes of patients following a diagnosis of female patients with genital neoplasm(FGN)., Materials and Methods: Utilizing SEER databases, this study involved 102,895 patients from nine oncology centers, spanning 1990 to 2015. We employed the Fine-Gray competing risks regression methodology to chart the trajectory of SPN development and used the Kaplan-Meier method to calculate the 10-year overall survival rates., Results: This study included 25,774 patients in the RT group and 77,121 in the non-radiotherapy (NRT) group. The cumulative incidence rate of SPN was 5.10 % in the RT group and 3.42 % in the NRT group. The RT group showed a significantly higher incidence of bladder cancer (adjusted hazard ratio [HR]: 1.75; 95 % confidence interval [CI]: 1.43-2.14; P < 0.05), colon cancer (adjusted HR: 1.32; 95 % CI: 1.16-1.49; P < 0.05), and rectal cancer (adjusted HR: 1.34; 95 % CI: 1.10-1.65; P < 0.05) compared to the NRT group. After propensity score matching, patients in the RT group who developed bladder cancer had significantly reduced 10-year survival rates compared to patients with primary pelvic tumors (P = 0.01)., Conclusion: RT is identified as an independent risk factor for the development of SPN in patients with FGN. Patients with FGN who undergo RT demonstrate a significant increase in the risk of developing secondary neoplasms, specifically bladder cancers, and experience a reduction in 10-year survival rates., 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 Author(s). Published by Elsevier B.V. All rights reserved.)

Objective: This study investigates the sleep-modulating effects of ginsenoside Rg1 (Rg1, C 42 H 72 O 14 ), a key bioactive component of ginseng, and elucidates its underlying mechanisms., Methods: C57BL/6J mice were intraperitoneally administered doses of Rg1 ranging from 12.5 to 100 mg/kg. Sleep parameters were assessed to determine the average duration of each sleep stage by monitoring the electrical activity of the brain and muscles. Further, orexin neurons in the lateral hypothalamus (LH) and corticotropin-releasing hormone (CRH) neurons in the paraventricular hypothalamic nucleus (PVH) were ablated using viral vector surgery and electrode embedding. The excitability of LH orexin and PVH CRH neurons was evaluated through the measurement of cellular Finkel-Biskis-Jinkins murine osteosarcoma viral oncogene homolog (c-Fos) expression., Results: Rg1 (12.5-100 mg/kg) augmented the duration of non-rapid eye movement (NREM) sleep phases, while reducing the duration of wakefulness, in a dose dependent manner. The reduced latency from wakefulness to NREM sleep indicates an accelerated sleep initiation time. We found that these sleep-promoting effects were weakened in the LH orexin and PVH CRH neuron ablation groups, and disappeared in the orexin and CRH double-ablation group. Decreased c-Fos protein expression in the LH and PVH confirmed that Rg1 promoted NREM sleep by inhibiting orexin and CRH neurons., Conclusion: Rg1 increases the duration of NREM sleep, underscoring the essential roles of LH orexin and PVH CRH neurons in facilitating the sleep-promoting effects of Rg1. Please cite this article as: Wang YY, Wu Y, Yu KW, Xie HY, Gui Y, Chen CR, Wang NH. Ginsenoside Rg1 promotes non-rapid eye movement sleep via inhibition of orexin neurons of the lateral hypothalamus and corticotropin-releasing hormone neurons of the paraventricular hypothalamic nucleus. J Integr Med . 2024; Epub ahead of print., 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 Shanghai Yueyang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine. Published by Elsevier B.V. All rights reserved.)

Meditation is a family of ancient and contemporary contemplative mind-body practices that can modulate psychological processes, awareness, and mental states. Over the last 40 years, clinical science has manualised meditation practices and designed various meditation interventions (MIs), that have shown therapeutic efficacy for disorders including depression, pain, addiction, and anxiety. Over the past decade, neuroimaging has examined the neuroscientific basis of meditation practices, effects, states, and outcomes for clinical and non-clinical populations. However, the generalizability and replicability of current neuroscientific models of meditation are yet to be established, as they are largely based on small datasets entrenched with heterogeneity along several domains of meditation (e.g., practice types, meditation experience, clinical disorder targeted), experimental design, and neuroimaging methods (e.g., preprocessing, analysis, task-based, resting-state, structural MRI). These limitations have precluded a nuanced and rigorous neuroscientific phenotyping of meditation practices and their potential benefits. Here, we present ENIGMA-Meditation, the first worldwide collaborative consortium for neuroscientific investigations of meditation practices. ENIGMA-Meditation will enable systematic meta- and mega-analyses of globally distributed neuroimaging datasets of meditation using shared, standardized neuroimaging methods and tools to improve statistical power and generalizability. Through this powerful collaborative framework, existing neuroscientific accounts of meditation practices can be extended to generate novel and rigorous neuroscientific insights, accounting for multi-domain heterogeneity. ENIGMA-Meditation will inform neuroscientific mechanisms underlying therapeutic action of meditation practices on psychological and cognitive attributes, advancing the field of meditation and contemplative neuroscience., (Copyright © 2024. Published by Elsevier Inc.)

Background: Miller fisher syndrome (MFS) is a variant of Guillain-Barré syndrome, an acute immune-mediated peripheral neuropathy that is often secondary to viral infections. Anti-ganglioside antibodies play crucial roles in the development of MFS. The positive rate of ganglioside antibodies is exceptionally high in MFS patients, particularly for anti-GQ1b antibodies. However, the presence of other ganglioside antibodies does not exclude MFS., Case Summary: We present a 56-year-old female patient who suddenly developed right blepharoptosis and progressively worsening vision in both eyes. There were flu symptoms prior to onset, and a coronavirus disease 2019 test was positive. On physical examination, the patient exhibited bilateral extraocular muscle paralysis, weakened reflexes in both limbs, and impaired coordination. The cerebrospinal fluid examination results showed no obvious abnormalities. Bilateral peroneal nerve F-waves were not extracted. Serum anti-GD1b IgG and anti-GT1a IgG antibodies were positive. The patient received intravenous methylprednisolone (1000 mg/day), with the dosage gradually decreased. Additionally, intravenous high-dose immunoglobulin treatment was administered for 5 days (0.4 g/kg/day) from day 2 to day 6 of hospitalization. The patient's symptoms improved after treatment with immunoglobulins and hormones., Conclusion: Positive ganglioside antibodies may be used as supporting evidence for the diagnosis; however, the diagnosis of MFS is more reliant on clinical symptoms., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflict of interest., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

In field of electrochemistry, there has been a growing interest in the potential applications of proton-conducting metal-organic frameworks (MOFs). Therefore, how to design and synthesize MOFs with high proton conductivity is considered crucial. In this study, two examples of nitro-containing Cd-based MOFs, MOF-1 {[Cd3(TIPE)1.5(NO3)5Cl(H2O)2]·17H2O}n and MOF-2 {[Cd(TIPE)0.5(nip)]·10H2O}n (TIPE=1,1,2,2-tetrakis(4-(1H-imidazole-1-yl)phenyl)ethene, H2nip=5-Nitroisophthalic Acid), had been successfully designed and synthesized, and their proton-conducting properties were thoroughly investigated. Notably, both materials displayed peak proton conductivity at 98% RH and 90 °C, exhibiting values of 9.13 × 10-3 and 3.00 × 10-3 S∙cm-1 for MOF-1 and MOF-2, respectively. The plausible proton conduction pathways and mechanisms were elucidated through structural analyses, water vapor adsorption studies, and the determination of activation energy (Ea) values. It was found that the difference in proton conductivity between MOF-1 and MOF-2 was mainly associated with the different water absorption rates of the samples. The uniqueness of this study was that for the first time conducted an in-depth study of the role of nitrate in proton conduction, providing new ideas for designing materials with excellent proton conductivity., (© 2024 Wiley‐VCH GmbH.)

Background: Urolithiasis is a prevalent urological ailment characterized by increasing prevalence and recurrence rates, resulting in substantial social and economic burden. While men exhibit an incidence rate nearly twice that of women, this gender disparity is gradually diminishing. Nevertheless, the mechanisms underlying this condition remain incompletely elucidated. The identification of the urinary microbiome (urobiome) has provided a fresh perspective on urolithiasis. This study aimed to analyze the urobiome of unilateral stone formers in the renal pelvis and evaluate the variations in microbial diversity and community composition between males and females., Methods: Renal pelvis urine samples were obtained from a cohort of 21 male and 9 female patients and subsequently subjected to taxonomic and functional analysis using 2bRAD sequencing for Microbiome (2bRAD-M). The collected samples were categorized into four distinct groups, namely the stone side of males (SM), stone side of females (SF), non-stone side of males (NSM), and non-stone side of females (NSF)., Results: Through the application of beta diversity analysis, dissimilarity was observed between NSM and NSF. Additionally, NSF exhibited a higher abundance of microbial populations, and a total of 29 distinct species were identified as differentially present between NSM and NSF using LEfSe. Lactobacillus iners, Atopobium deltae, Lawsonella clevelandensis, and Meyerozyma guilliermondii exhibited enrichment in the SF group compared to the SM group. Furthermore, we identified distinct species that differed between the SM and NSM groups, as well as the SF and NSF groups. Besides, we conducted COG annotation and KEGG pathway predictions, revealing significant differences in urobiome function across the different groups., Conclusion: Variations in microbial community composition and predicted functions were observed among the various groups. Future research could potentially leverage the urobiome to personalize urolithiasis treatment based on individual microbial characteristics, taking into account gender-specific differences., (© 2024. The Author(s).)

Precise synthesis of carboxylic acids via catalytic carboxylation with CO 2 is highly appealing. Although considerable advancements have been achieved in difunctionalizing carboxylation of unsaturated hydrocarbons, the asymmetric variants are conspicuously underdeveloped, particularly in addressing axially chiral alkenes. Herein, we report the first catalytic atroposelective carboxylation of alkynes with CO 2 . A variety of valuable axially chiral carboxylic acids are obtained with good yields and high chemo-, regio-, Z/E and enantio-selectivities. Notably, an unexpected anti-selective carbo-carboxylation is observed in the sp 2 -hybrid carbo-electrophile-initiated reductive carboxylation of alkynes. Mechanistic studies including DFT calculation elucidate the origin of chiral induction and anti-selectivity in vinyl-carboxylation of alkynes., (© 2024 Wiley-VCH GmbH.)

Objectives: Elizabethkingia spp. are resistant to multiple antibiotics. This study aimed to determine in vitro and in vivo activities of cefiderocol against Elizabethkingia spp. and to investigate resistance mechanisms., Methods: Bloodstream isolates were collected from four hospitals. In vitro and in vivo activities were determined using broth microdilution and the wax moth model, respectively. Genome comparison and gene editing were used to confirm the contribution of target genes. Conjugation experiments and serial passage were used to determine transferability and stability, respectively. A MIC of ≤ 4 mg/L was designated as the susceptibility breakpoint., Results: Among 228 non-duplicated isolates, 226 exhibited a MIC of ≤ 4 mg/L with MIC 50/90 of 1/2 mg/L. Two isolates had a MIC of 128 mg/L; both source patients had multiple comorbidities, were ventilator-dependent, and had not received cefiderocol previously. Resistance was attributable to acquisition of bla CfxA-3 , carried by a conjugative transposon from Prevotella jejuni, and duplication of intrinsic bla CME-3 , which led to its overexpression. tetQ coexisted with bla CfxA-3 in this conjugative transposon and minocycline facilitated its transfer among E. anophelis. Antibiotics prescribed for source patients did not induce bla CME-3 duplication. The stabilities of bla CfxA-3 and double bla CME-3 were 100% and > 90%, respectively, after 10-day serial passage. Cefiderocol failed to rescue moth larvae infected with resistant strains, but removal of resistance mechanisms restored in vivo efficacy., Conclusions: Cefiderocol was in vitro and in vivo active against Elizabethkingia spp. but resistance may emerge due to the availability, transferability, and/or stability of resistance mechanisms., Competing Interests: Competing Interests All authors declare that they have no competing interests., (Copyright © 2024. Published by Elsevier Ltd.)

We report two organic-inorganic hybrid thermochromic crystals, [(2A5MP) 2 CuCl 4 ] (2A5MP = 2-amino-5-methylpyridine) (1) and [(2A4MP) 2 CuCl 4 ] (2A4MP = 2-amino-4-methylpyridine) (2). Through hydrogen bond engineering optimization, the ferroelastic material 2 undergoes an isomorphic phase transition with a large thermal hysteresis of 36 K at 397 K/361 K.

This study aimed to analyze the clinical phenotype of the HBA2 : c.95G>A mutation in the Chinese population and to provide guidance for clinical diagnosis and genetic counseling. Peripheral blood samples were collected from 16 patients, including 6 newborns, 2 children, and 8 adults. Hematological parameters and hemoglobin electrophoresis were analyzed, and genotypes were identified using methods such as PCR combined with reverse dot blot (RDB), nested PCR, gap polymerase chain reaction (Gap-PCR), and DNA sequencing. The results showed that 10 patients had mild anemia, 2 had moderate anemia, and 12 exhibited microcytic hypochromic features with MCV values ranging from 53 to 74.7 fl and MCH values from 16.2 to 25.4 pg. Additionally, 3 cases displayed obvious HbH + HbBarts bands (>15%). Among the 16 cases, various combinations of the HBA2 : c.95G>A mutation were observed: one case had -α 3.7 combined with HBA2 : c.95G>A, another had -α 4.2 combined with HBA2 : c.95G>A, and five had - SEA combined with HBA2 : c.95G>A, while the remaining cases were HBA2 : c.95G>A heterozygotes. The study concludes that the HBA2 : c.95G>A mutation in the α2 globin gene causes α+ thalassemia. When this mutation is combined with the Southeast Asian deletion (- SEA ), it results in HbH disease, characterized by moderate microcytic hypochromic anemia and the presence of HbH + HbBarts bands.

Lupus nephritis (LN) is a prevalent and severe manifestation of systemic lupus erythematosus (SLE), leading to significant morbidity and mortality. OTUB1, a deubiquitinating enzyme, has emerged as a potential therapeutic target due to its role in cellular protection and regulation of ferroptosis, a form of cell death linked to LN. Our study revealed significantly reduced OTUB1 expression in the glomeruli of LN patients and podocytes, correlated with disease severity. CRISPR/Cas9-mediated OTUB1 knockout in podocytes resulted in pronounced injury, indicated by decreased levels of nephrin and podocin. Ferrostatin-1 treatment effectively mitigated this injury, restoring SLC7A11 expression and significantly reducing MDA levels, Fe 2+ levels, BODIPY C11 expression, and normalized cysteine and glutathione expression. In the MRL/lpr mouse model, Ferrostatin-1 significantly improved renal function decreased proteinuria, and ameliorated renal histopathological changes, including reduced glomerular endothelial swelling, mesangial cell proliferation, and leukocyte infiltration. These results underscore the protective role of Ferrostatin-1 in modulating the pathogenesis of LN. OTUB1 plays a crucial protective role against podocyte injury in LN by regulating ferroptosis. Ferrostatin-1 effectively mitigates podocyte damage induced by OTUB1 deficiency, suggesting that targeting ferroptosis could be a promising therapeutic strategy for LN., (© 2024. The Author(s).)

Dearomative functionalization of heteroarenes offers an attractive and sustainable approach for the rapid construction of complex 3D heterocyclic scaffolds from planar structures. Despite progress in this field, dearomative amination of heteroarenes via a radical anion intermediate remains a challenge. Here, we report a photoredox-catalyzed dearomative hydroamination of heteroarenes with hydrazodiformates under mild and transition-metal-free reaction conditions. Various benzofurans and benzothiophenes can efficiently participate in this transformation. A series of mechanistic experiments revealed that heteroaryl radical anions are the crucial intermediates, generated through photo-induced electron transfer between the excited phenolate photocatalyst and heteroarenes.

Objective: This study aimed to compare the effectiveness and safety of high-dose dual therapy (HDDT) using esomeprazole and amoxicillin to furazolidone-based quadruple therapy (FBQT) in treating nonresponsive patients with Helicobacter pylori (H. pylori) infection., Materials and Methods: A total of 209 patients with H. pylori infection, who had previously received ineffective treatment and visited an outpatient clinic, were randomly assigned to either the HDDT or FBQT groups. All patients underwent a 14-day treatment regimen, and the success rates of H. pylori eradication and safety of the treatment regimens were assessed 4 weeks posttreatment., Results: Following the 14-day treatment period, the intention-to-treat (ITT) analysis revealed eradication rates of 93.6% for HDDT and 86.9% for FBQT. In the per-protocol (PP) analysis, eradication rates were 94.5% for HDDT and 88.7% for FBQT. No significant difference in eradication rates was observed between the two groups. HDDT exhibited significantly lower rates of adverse reactions (9.1% in ITT and 9.2% in PP) compared with FBQT (58.6% in ITT and 59.8% in PP). Multivariate analysis identified interval time, alkaline phosphatase, and serum creatinine level as factors influencing the eradication rate. The area under the receiver operating curve of the interval time between the FBQT group and the HDDT group and the success of H. pylori eradication were 0.622 and 0.578, respectively. The optimal salvage treatment intervals were determined as 6 months for FBQT and 1 year for HDDT., Conclusion: HDDT using high-dose esomeprazole and amoxicillin demonstrated efficacy in treating H. pylori infection, with the added benefits of reduced side effects and improved medication compliance compared with FBQT. HDDT can be considered a rescue treatment option when other methods fail, with treatment intervals optimized accordingly., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Multiple instance learning (MIL) has become a cornerstone in whole slide image (WSI) analysis. In this paradigm, a WSI is conceptualized as a bag of instances. Instance features are extracted by a feature extractor, and then a feature aggregator fuses these instance features into a bag representation. In this paper, we advocate that both feature extraction and aggregation can be enhanced by considering the context or correlation between instances. We learn contextual features between instances, and then fuse contextual features with instance features to enhance instance representations. For feature aggregation, we observe performance instability particularly when disease-positive instances are only a minor fraction of the WSI. We introduce a self-attention mechanism to discover correlation among instances and foster more effective bag representations. Through comprehensive testing, we have demonstrated that the proposed method outperforms existing WSI classification methods by 1 to 4% classification accuracy, based on the Camelyon16 and the TCGA-NSCLC datasets. The proposed method also outperforms the most recent weakly supervised WSI segmentation method by 0.6 in terms of the Dice coefficient, based on the Camelyon16 dataset., (© 2024. The Author(s) under exclusive licence to Society for Imaging Informatics in Medicine.)

Objective: To study the incidence of congenital posterior arch defects of the atlas and in combination with other congenital variations in the Chinese population., Methods: We retrospectively reviewed 1405 images of cervical 3-dimensional computed tomography (3D CT) and 1284 images of head and cervical 3-dimensional computed tomography angiography (3D CTA), including images of 1539 male and 1150 female individuals. These images of cervical 3D CT and head and cervical 3D CTA were obtained in the Department of Radiology of 2 hospitals, Second and Third People's Hospital of Jingzhou, China, from January 2020 to October 2023. Congenital posterior arch defects of the atlas were classified according to the criteria of Currarino and colleagues. Congenital posterior arch defects of the atlas combined with other congenital variations including occipitalization of the atlas, the ponticulus posticus variation of the vertebral artery groove of the atlas, cervical fusion, and the transversal foramen of the atlas variant were also observed., Results: A total of 2689 patients were included in this study. The overall prevalence of congenital posterior arch defects of the atlas was 0.74% (20 of 2689). There was no statistically significant difference in incidence between male (0.78%, 12 of 1539) and female patients (0.70%, 8 of 1150) (P > 0.05). Among all posterior defects, type A and B defects were found in 0.6% (16 of 2689) and 0.15% (4 of 2689) cases, respectively. There were no type C, D, and E defects and no anterior arch defects. However, in 20 cases of congenital posterior arch defects of atlas, 40% (8 of 20) combined with other congenital variations including occipitalization of atlas in 4 type A cases, bilateral complete ponticulus posticus variation of atlas vertebral groove in 1 type A case, C2-C3 fusion in 1 type A case, coexistence of unilateral complete ponticulus posticus variation of the vertebral artery groove of the atlas and unilateral unclosed transverse foramen in 1 type B case, and coexistence of unilateral unclosed transverse foramen in 1 type A case., Conclusions: The incidence of congenital posterior arch defects of the atlas was low in a Chinese population. There was no difference between male and female individuals. Types A and B were the 2 major defects in this Chinese population, and the prevalence of type A and B combined with other congenital cervical variations were higher than those of types C, D, and E., (Copyright © 2024. Published by Elsevier Inc.)

Background: Although improvement of cognitive function after liver transplantation has been demonstrated in several neuropsychological studies, there is limited research on longitudinal changes in the cirrhotic patients' brain structure before and after transplantation., Purpose: To investigate longitudinal changes of brain microstructure in cirrhotic patients using diffusion kurtosis imaging (DKI)., Study Type: Prospective., Subjects: A total of 153 cirrhosis patients, comprising 60 hepatic encephalopathy (HE) patients (16 females/44 males) and 93 no-HE patients (35 females/58 males), along with 93 healthy controls (HCs) (53 females/40 males) were enrolled. Subsequently, 58 recipients completed 1-month postoperative follow-up, 29 patients completed 1-, 3-months, and 17 patients completed 1-, 3-, 6-month follow-up., Sequence: Spin-echo single-shot echo-planar sequence using a 3.0 T scanner., Assessment: Diffusion kurtosis estimator software was used to estimate the DKI parameter maps by a MR imaging physicist (Y.-Y.C. with 12 years of experience)., Statistical Tests: The diffusion metrics (eg, radial kurtosis [RK], mean kurtosis, fractional anisotropy, mean diffusivity) of the patients before transplantation were compared with those of the HCs using voxel-wise analysis of variance (ANOVA), along with t tests for post hoc analysis. Linear mixed-effects models were applied to the longitudinal data. We imposed a cluster level Family Wise Error (FWE) correction rate of P FWE  = 0.05 with voxel-wise cutoff of P = 0.001 together with a cluster-size cutoff of N ≥ 56, and generated smoothness estimates from the preprocessed data using the mixed-model autocorrelation function., Results: The RK metrics of the patients decreased significantly in the anterior cingulate cortex (HE/no-HE < HC, ANOVA-F = 21.91). After transplantation, the RK of the pallidum showed a continuous upward trend (time effect T = 11.26); whereas the RK of the right postcentral gyrus showed a continuous downward trend (time effect T = -9.56). In addition, the RK in superior longitudinal fasciculus showed new-onset decrease after transplantation., Data Conclusion: Longitudinal changes in DKI metrics reveal the course of brain microstructural changes before and after transplantation in cirrhotic patients, potentially associated with cognitive alterations after surgery., Level of Evidence: 1 TECHNICAL EFFICACY: Stage 4., (© 2024 International Society for Magnetic Resonance in Medicine.)

Background: SLC7A9 is responsible for the exchange of dibasic amino acids and cystine (influx) for neutral amino acids (efflux). Cystine/cysteine transport is related to ferroptosis., Methods: Sanger sequencing detected TP53 status of cancer cells. Transcriptomic sequencing and untargeted metabolome profiling were used to identify differentially expressed genes and metabolites, respectively, upon SLC7A9 overexpression. CCK8, cell clonality, and EdU assays were used to observe cell proliferation. Cystine probes, glutathione (GSH) probes, and lipid ROS probes were used to examine cystine, GSH, and lipid ROS levels. 13 C metabolic flow assays were used to monitor cellular cystine and GSH metabolism. Patient-derived organoids (PDO), immunocompetent MFC mice allograft models and patient-derived xenograft (PDX) models were used to evaluate SLC7A9 impact on chemotherapeutic response and to observe therapeutic effect of SLC7A9 knockdown., Findings: Elevated SLC7A9 expression levels in gastric cancer cells were attributed to p53 loss. SLC7A9 knockdown suppressed the proliferation and increased the chemotherapy sensitivity of the cells. Chemotherapy was more effective in PDX and immunocompetent mice models upon SLC7A9 knockdown. Differentially expressed genes and metabolites between the SLC7A9 overexpression and control groups were associated with ferroptosis and GSH metabolism. SLC7A9 knockdown reduced cystine transport into cells, hampered intracellular cystine and GSH metabolic flow, decreased GSH synthesis, and increased lipid ROS levels in gastric cancer cells. Erastin was more effective at inducing ferroptosis in PDO and PDX models upon SLC7A9 knockdown., Interpretation: SLC7A9 promotes gastric cancer progression by acting as a suppressor of ferroptosis, independent of SLC7A11, which is negatively regulated by p53., Funding: This work was supported by National Natural Science Foundation of China, Innovation Promotion Program of NHC and Shanghai Key Labs SIBPT, and Shanghai Academy of Science & Technology., Competing Interests: Declaration of interests The authors declare that they have no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Remarkable progress has been made in the radical cascade cyclization of heteroaryl- or aryl-tethered alkenes to construct benzene-fused frameworks via the cracking of aryl C-H bonds. In contrast, the radical cascade cyclization of linear dienes through the cracking of vinyl C-H bonds to construct nonbenzene-fused ring frameworks with endocyclic double bonds has significantly lagged behind, and major advances have largely been restricted to the generation of 5-membered heterocycles, such as pyrrolinones. Herein, we report the silver-mediated regioselective sulfonylation-cyclization of linear dienes with sodium sulfinates to form sulfonylated 6- and 7-membered cyclic enamines.

Background: Patients with head and neck cancer (HNC) have to cope with a multitude of treatment-related adverse effects that impact their quality of life (QoL) post-treatment completion. The presence of family resilience could potentially foster individual resilience and might contribute to patients' QoL. However, this interconnection has not been confirmed., Objective: To explore the relationships between family resilience, individual resilience, and QoL in patients with HNC and to determine whether individual resilience in HNC patients functions as a mediator between family resilience and QoL., Methods: From September 2022 to June 2023, a cross-sectional survey was conducted among 185 patients with HNC recruited through convenience sampling from a tertiary care hospital in Jiangsu Province, China. Self-report measures of family resilience, individual resilience, and QoL were assessed. Relationships were examined by Pearson's correlations. Structural equation models were used to assess whether individual resilience played a mediating role between family resilience and QoL., Results: There were significant positive correlations between QoL and both family resilience ( r  = 0.43, P  < .01) and individual resilience ( r  = 0.59, P  < .01). Moreover, family resilience had an indirect influence on QoL through its effect on individual resilience (β = 0.319, 95% CI: 0.336-0.815)., Conclusion: Family resilience emerges as a significant positive factor capable of enhancing QoL for patients with HNC by bolstering their resilience. To mitigate the detrimental effects of inadequate individual resilience on QoL of patients with HNC, it is advised to implement interventions focused on enhancing family resilience., China Clinical Trials Registry Number: ChiCTR2300067612., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Patients with relapsed/refractory acute myeloid leukaemia (R/R AML), especially those who failed in novel target agents are related to dismal survival. We developed a multi-institutional, single-arm, prospective phase II trial, to investigate intensified conditioning with 'Mega-Dose' decitabine (MegaDAC) following allogeneic haematopoietic cell transplantation (allo-HCT) for R/R AML. From 2019 to 2023, 70 heavily treated R/R AML patients in active disease were consecutively enrolled. Significantly, every patient (n = 18) harbouring specific mutations exhibited no response to their best available target agents (BATs). Moreover, 74.3% of the enrolled patients did not reach remission following venetoclax-based regimens. All patients underwent intravenous decitabine (400 mg/m 2 ) along with busulfan and cyclophosphamide. Median follow-up was 26 months (8-65) after HCT. All engrafted patients achieved MRD negativity post-HCT, with a median 3.3-log reduction in recurrent genetic abnormalities. The regimen was well tolerated, without irreversible grades III-IV toxicity peri-engraftment. The estimated 2-year CIR was 29.6% (18.4%-41.7%) and the est-2-year NRM was 15.5% (7.8%-25.5%). The est-2-year LFS, OS, and GRFS were 55.0% (43.5%-69.4%), 58.6% (47.0%-73.0%), and 42.9% (31.9%-57.6%), respectively. Multivariate analysis showed that pre-HCT drug exposures had no significant impact on primary outcomes. MegaDAC is highlighted as an effective and safe option for R/R AML in the new era of targeted therapies., (© 2024 British Society for Haematology and John Wiley & Sons Ltd.)

Introduction: Anemia may contribute significantly to the onset of Parkinson's disease (PD). Current research on the association between anemia and PD risk is inconclusive, and the relationships between anemia-related blood cell indices and PD incidence require further clarification. This study aims to investigate the relationships between anemia, blood cell indicators, and PD risk using a thorough prospective cohort study., Methods: We used data from the UK Biobank, a prospective cohort study of 502,649 participants, and ultimately, 365,982 participants were included in the analysis. Cox proportional hazards models were utilized to adjust for confounding factors, aiming to thoroughly explore the associations between anemia and blood cell indices with the risk of incident PD. The interaction between anemia and Polygenic Risk Score (PRS) for PD was also examined. Linear regression and mediation analyses assessed potential mechanisms driven by brain structures, including grey matter volume., Results: During a median follow-up of 14.24 years, 2513 participants were diagnosed with PD. Anemia considerably increased PD risk (hazard ratio [HR] 1.98, 95 % confidence interval [CI]: 1.81-2.18, P < 0.001) after adjustments. Those with high PRS for anemia had an 83 % higher PD incidence compared to low PRS participants. Sensitivity analyses confirmed result robustness. Linear regression showed that anemia correlated with grey matter volumes and most white matter tracts. Furthermore, mediation analyses identified that the volume of grey matter in Thalamus mediates the relationship between anemia and PD risk., Conclusion: In summary, we consider there to be a substantial correlation between anemia and increased PD risk., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Background: Several population pharmacokinetic (PopPK) models of caffeine in preterm infants have been published, but the extrapolation of these models to facilitate model-informed precision dosing (MIPD) in clinical practice is uncertain. This study aimed to comprehensively evaluate their predictive performance using an external, independent dataset., Methods: Data used for external evaluation were based on an independent cohort of preterm infants. Currently available PopPK models for caffeine in preterm infants were identified and re-established. Prediction- and simulation-based diagnostics were used to assess model predictability. The influence of prior information was assessed using Bayesian forecasting., Results: 120 plasma samples from 76 preterm infants were included in the evaluation dataset. Twelve PopPK models of caffeine in preterm infants were re-established based on our previously published study. Although two models showed superior predictive performance, none of the 12 PopPK models met all the clinical acceptance criteria of these external evaluation items. Besides, the external predictive performances of most models were unsatisfactory in prediction- and simulation-based diagnostics. Nevertheless, the application of Bayesian forecasting significantly improved the predictive performance, even with only one prior observation., Conclusions: Two models that included the most covariates had the best predictive performance across all external assessments. Inclusion of different covariates, heterogeneity of preterm infant characteristics, and different study designs influenced predictive performance. Thorough evaluation is needed before these PopPK models can be implemented in clinical practice. The implementation of MIPD for caffeine in preterm infants could benefit from the combination of PopPK models and Bayesian forecasting as a helpful tool., 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.)

Adipocyte-secreted factors intricately regulate adipose tissue function, and the underlying molecular mechanisms are only partially understood. However, the function of PRELP, which is a key component of the extracellular matrix (ECM) in adipocytes, remains largely unknown. In this study, we demonstrate that PRELP was upregulated in both obese humans and mice, which exhibited a positive correlation with metabolic disorders. PRELP knockout could resist HFD-induced obesity and inhibit adipocyte differentiation. PRELP knockout improved glucose tolerance, insulin sensitivity and alleviated adipose tissue fibrosis. Mechanistically, PRELP was secreted into the ECM and bound to the extracellular domain of its receptor p75 NTR in adipocytes, which further activated the FAK/MAPK (JNK, p38 MAPK, ERK1/2) signaling pathway, promoting adipocyte differentiation and exacerbating adipocyte fibrosis. Adipocyte PRELP plays a pivotal role in regulating obesity and adipose tissue fibrosis through an autocrine manner, and PRELP may be a therapeutic target for obesity and its related metabolic disorders., Competing Interests: Declaration of competing interest All the authors declare no competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: Research into the effectiveness and applicability of deep learning, radiomics, and their integrated models based on Magnetic Resonance Imaging (MRI) for preoperative differentiation between Primary Central Nervous System Lymphoma (PCNSL) and Glioblastoma (GBM), along with an exploration of the interpretability of these models., Materials and Methods: A retrospective analysis was performed on MRI images and clinical data from 261 patients across two medical centers. The data were split into a training set (n = 153, medical center 1) and an external test set (n = 108, medical center 2). Radiomic features were extracted using Pyradiomics to build the Radiomics Model. Deep learning networks, including the transformer-based MobileVIT Model and Convolutional Neural Networks (CNN) based ConvNeXt Model, were trained separately. By applying the "late fusion" theory, the radiomics model and deep learning model were fused to produce the optimal Max-Fusion Model. Additionally, Shapley Additive exPlanations (SHAP) and Grad-CAM were employed for interpretability analysis., Results: In the external test set, the Radiomics Model achieved an Area under the receiver operating characteristic curve (AUC) of 0.86, the MobileVIT Model had an AUC of 0.91, the ConvNeXt Model demonstrated an AUC of 0.89, and the Max-Fusion Model showed an AUC of 0.92. The Delong test revealed a significant difference in AUC between the Max-Fusion Model and the Radiomics Model (P = 0.02)., Conclusion: The Max-Fusion Model, combining different models, presents superior performance in distinguishing PCNSL and GBM, highlighting the effectiveness of model fusion for enhanced decision-making in medical applications., Clinical Relevance Statement: The preoperative non-invasive differentiation between PCNSL and GBM assists clinicians in selecting appropriate treatment regimens and clinical management strategies., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: To observe the protective effect and mechanism of hydroxyl safflower yellow A (HSYA) from myocardial ischemia-reperfusion injury on human umbilical vein endothelial cells (HUVECs)., Methods: HUVECs were treated with oxygen-glucose deprivation reperfusion (OGD/R) to simulate the ischemia reperfusion model, and cell counting kit-8 was used to detect the protective effect of different concentrations (1.25-160 µ mol/L) of HSYA on HUVECs after OGD/R. HSYA 80 µ mol/L was used for follow-up experiments. The contents of inflammatory cytokines interleukin (IL)-18, IL-1 β, monocyte chemotactic protein 1 (MCP-1), tumor necrosis factor α (TNF-α) and IL-6 before and after administration were measured by enzyme-linked immunosorbent assay. The protein expressions of toll-like receptor, NOD-like receptor containing pyrin domain 3 (NLRP3), gasdermin D (GSDMD) and GSDMD-N-terminal domain (GSDMD-N) before and after administration were detected by Western blot. NLRP3 inflammasome inhibitor cytokine release inhibitory drug 3 sodium salt (CRID3 sodium salt, also known as MCC950) and agonist were added, and the changes of NLRP3, cysteine-aspartic acid protease 1 (Caspase-1), GSDMD and GSDMD-N protein expressions were detected by Western blot., Results: HSYA inhibited OGD/R-induced inflammation and significantly decreased the contents of inflammatory cytokines IL-18, IL-1 β, MCP-1, TNF-α and IL-6 (P<0.01 or P<0.05). At the same time, by inhibiting NLRP3/Caspase-1/GSDMD pathway, HSYA can reduce the occurrence of pyroptosis after OGD/R and reduce the expression of NLRP3, Caspase-1, GSDMD and GSDMD-N proteins (P<0.01)., Conclusions: The protective effect of HSYA on HUVECs after OGD/R is related to down-regulating the expression of NLRP3 inflammasome and inhibiting pyroptosis., (© 2023. The Chinese Journal of Integrated Traditional and Western Medicine Press and Springer-Verlag GmbH Germany, part of Springer Nature.)

Graft-versus-host disease (GVHD), an immunological disorder that arises from donor T cell activation through recognition of host alloantigens, is the major limitation in the application of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Traditional immunosuppressive agents can relieve GVHD, but they induce serious side effects. It is highly required to explore alternative therapeutic strategy. Human amniotic epithelial stem cells (hAESCs) were recently considered as an ideal source for cell therapy with special immune regulatory property. In this study, we evaluated the therapeutic role of hAESCs in the treatment of GVHD, based on our previous developed cGMP-grade hAESCs product. Humanized mouse model of acute GVHD (aGVHD) was established by injection of huPBMCs via the tail vein. For prevention or treatment of aGVHD, hAESCs were injected to the mice on day -1 or on day 7 post-PBMC infusion, respectively. We showed that hAESCs infusion significantly alleviated the disease phenotype, increased the survival rate of aGVHD mice, and ameliorated pathological injuries in aGVHD target organs. We demonstrated that hAESCs directly induced CD4 + T cell polarization, in which Th1 and Th17 subsets were downregulated, and Treg subset was elevated. Correspondingly, the levels of a series of pro-inflammatory cytokines were reduced while the levels of the anti-inflammatory cytokines were upregulated in the presence of hAESCs. We found that hAESCs regulated CD4 + subset polarization in a paracrine mode, in which TGFβ and PGE2 were selectively secreted to mediate Treg elevation and Th1/Th17 inhibition, respectively. In addition, transplanted hAESCs preserved the graft-versus-leukemia (GVL) effect by inhibiting leukemia cell growth. More intriguingly, hAESCs infusion in HSCT patients displayed potential anti-GVHD effect with no safety concerns and confirmed the immunoregulatory mechanisms in the preclinical study. We conclude that hAESCs infusion is a promising therapeutic strategy for post-HSCT GVHD without compromising the GVL effect. The clinical trial was registered at www.clinicaltrials.gov as #NCT03764228., (© 2024. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Background and Aims: Despite the benefits of artificial intelligence in small-bowel (SB) capsule endoscopy (CE) image reading, information on its application in the stomach and SB CE is lacking., Methods: In this multicenter, retrospective diagnostic study, gastric imaging data were added to the deep learning-based SmartScan (SS), which has been described previously. A total of 1069 magnetically controlled GI CE examinations (comprising 2,672,542 gastric images) were used in the training phase for recognizing gastric pathologies, producing a new artificial intelligence algorithm named SS Plus. A total of 342 fully automated, magnetically controlled CE examinations were included in the validation phase. The performance of both senior and junior endoscopists with both the SS Plus-assisted reading (SSP-AR) and conventional reading (CR) modes was assessed., Results: SS Plus was designed to recognize 5 types of gastric lesions and 17 types of SB lesions. SS Plus reduced the number of CE images required for review to 873.90 (median, 1000; interquartile range [IQR], 814.50-1000) versus 44,322.73 (median, 42,393; IQR, 31,722.75-54,971.25) for CR. Furthermore, with SSP-AR, endoscopists took 9.54 minutes (median, 8.51; IQR, 6.05-13.13) to complete the CE video reading. In the 342 CE videos, SS Plus identified 411 gastric and 422 SB lesions, whereas 400 gastric and 368 intestinal lesions were detected with CR. Moreover, junior endoscopists remarkably improved their CE image reading ability with SSP-AR., Conclusions: Our study shows that the newly upgraded deep learning-based algorithm SS Plus can detect GI lesions and help improve the diagnostic performance of junior endoscopists in interpreting CE videos., Competing Interests: Disclosure The following authors disclosed financial relationships: A. Koulaouzidis: Consultant for Jinshan Science & Technology LTD, and lecture honoraria from Medtronic. All other authors disclosed no financial relationships., (Copyright © 2024 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Conductive hydrogels, characterized by their unique features of flexibility, biocompatibility, electrical conductivity, and responsiveness to environmental stimuli, have emerged as promising materials for sensitive strain sensors. In this study, a facile strategy to prepare highly conductive hydrogels is reported. Through rational structural and synthetic design, silver nanowires (AgNWs) are incorporated into poly(N-acryloyl glycinamide) (PNAGA) hydrogels, achieving high electrical conductivity (up to 0.88 S m -1 ), significantly enhanced mechanical properties, and elevated deformative sensitivity. Furthermore, surface modification with polyhexafluoropropylene oxide (PHFPO) has substantially improved the water retention capacity and dressing comfort of this hydrogel material. Based on the above merits, these hydrogels are employed to fabricate highly sensitive wearable strain sensors which can detect and interpret subtle hand and finger movements and enable precise control of machine interfaces. The AgNWs/PNAGA based strain sensors can effectively sense finger motion, enabling the control of robotic fingers to replicate the human hand's gestures. In addition, the high deformative sensitivity and elevated water retention performance of the hydrogels makes them suitable for flow sensing. These conceptual applications demonstrate the potential of this conductive hydrogel in high-performance strain sensors in the future., (© 2024 Wiley‐VCH GmbH.)

Cuproptosis is characterized by the aggregation of lipoylated enzymes of the tricarboxylic acid cycle and subsequent loss of iron-sulfur cluster proteins as a unique copper-dependent form of regulated cell death. As dysregulation of copper homeostasis can induce cuproptosis, there is emerging interest in exploiting cuproptosis for cancer therapy. However, the molecular drivers of cancer cell evasion of cuproptosis were previously undefined. Here, we found that cuproptosis activates the Wnt/β-catenin pathway. Mechanistically, copper binds PDK1 and promotes its interaction with AKT, resulting in activation of the Wnt/β-catenin pathway and cancer stem cell (CSC) properties. Notably, aberrant activation of Wnt/β-catenin signaling conferred resistance of CSCs to cuproptosis. Further studies showed the β-catenin/TCF4 transcriptional complex directly binds the ATP7B promoter, inducing its expression. ATP7B effluxes copper ions, reducing intracellular copper and inhibiting cuproptosis. Knockdown of TCF4 or pharmacological Wnt/β-catenin blockade increased the sensitivity of CSCs to elesclomol-Cu-induced cuproptosis. These findings reveal a link between copper homeostasis regulated by the Wnt/β-catenin pathway and cuproptosis sensitivity, and suggest a precision medicine strategy for cancer treatment through selective cuproptosis induction., (© 2024. The Author(s), under exclusive licence to ADMC Associazione Differenziamento e Morte Cellulare.)

Background: Sepsis has the characteristics of high morbidity and high mortality in intensive care unit (ICU) patients. Chronic obstructive pulmonary disease (COPD) is an important cause of death. Studies have shown the value of aspirin on COPD and sepsis, separately, but its role in the combined COPD and sepsis patients is unclear. This study aimed to analyze the association of aspirin use after ICU admission with the mortality risk in COPD patients with sepsis., Methods: We conducted a retrospective study using the Medical Information Mart for Intensive Care (MIMIC)-IV database, enrolling 2,964 COPD patients with sepsis admitted to ICU. They were divided into aspirin users (n=1,642) and non-users (n=1,322). We evaluated the association of aspirin use with in-hospital and 28-day mortality using logistic regression, Kaplan-Meier survival analysis, and Cox proportional-hazards models. The role of aspirin dose and the association of aspirin use with 90-day and 1-year mortality were also assessed., Results: Aspirin use was associated with lower in-hospital death (13.642% vs. 23.676%) and 28-day mortality (17.296% vs. 30.257%) (P<0.001). Adjusted models confirmed reduced mortality odds ratio (OR) with aspirin use: OR for in-hospital mortality was 0.574 [95% confidence interval (CI): 0.456, 0.721] and 28-day mortality was 0.539 (95% CI: 0.437, 0.665) in model 3. Survival analyses showed higher survival probabilities for aspirin users. Subgroup analyses supported consistent aspirin benefits across various clinical parameters. Additionally, aspirin users had lower 90-day (21.498% vs. 34.191%) and 1-year mortality (27.649% vs. 41.982%) (P<0.001)., Conclusions: Aspirin use is significantly related to in-hospital and 28-day mortality risk in COPD patients with sepsis. This highlighted the clinical relevance of aspirin in COPD patients with sepsis., Competing Interests: Conflicts of Interest: Both authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-24-952/coif). The authors have no conflicts of interest to declare., (2024 AME Publishing Company. All rights reserved.)