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Introduction: Central nervous system leukemia (CNSL) remains a serious complication in patients with acute myeloid leukemia (AML) and an ambiguous prognostic factor for those receiving allo‐geneic hematopoiesis stem cell transplantation (allo‐HSCT). It is unknown whether using more sensitive tools, such as multiparameter flow cytometry (MFC), to detect blasts in the cerebrospinal fluid (CSF) would have an impact on outcome. Methods: We retrospectively analyzed the clinical outcomes of 1472 AML patients with or without cytology or MFC positivity in the CSF before transplantation. Abnormal CSF (CSF+) was detected via conventional cytology and MFC in 44 patients at any time after diagnosis. A control group of 175 CSF‐normal (CSF−) patients was generated via propensity score matching (PSM) analyses according to sex, age at transplant, and white blood cell count at diagnosis. Results: Compared to those in the CSF‐negative group, the conventional cytology positive and MFC+ groups had comparable 8‐year nonrelapse mortality (NRM) (4%, 4%, and 6%, p = 0.82), higher cumulative incidence of relapse (CIR) (14%, 31%, and 32%, p = 0.007), lower leukemia‐free survival (LFS) (79%, 63%, and 64%, p = 0.024), and overall survival (OS) (83%, 63%, and 68%, p = 0.021), with no significant differences between the conventional cytology positive and MFC+ groups. Furthermore, multivariate analysis confirmed that CSF involvement was an independent factor affecting OS and LFS. Conclusion: Our results indicate that pretransplant CSF abnormalities are adverse factors independently affecting OS and LFS after allotransplantation in AML patients. [ABSTRACT FROM AUTHOR]

Objective: In this study, we aimed to evaluate the combined diagnostic value of procalcitonin (PCT), C-reactive protein (CRP), and serum amyloid A (SAA) in sepsis caused by urinary tract infection. Method: A total of 80 patients with urosepsis who were hospitalized were included in the study group, and 80 patients with urinary tract infection without sepsis were included in the control group. We collected the PCT, SAA, and CRP levels of patients following admission. Subsequently, we conducted a comparative analysis to assess the specificity, accuracy, and sensitivity of combined diagnostic approaches in contrast to individual diagnostic methods for blood PCT, SAA, and CRP. Results: The levels of PCT, SAA, and CRP in the study group were significantly higher than those in the control group, and the differences were statistically significant (P < 0.01). Multi-factor logistic regression analysis revealed that the levels of PCT (P = 0.003) and SAA (P = 0.014) were associated with urosepsis. The sensitivity of PCT was 87.133% and the specificity was 93.066%, which were higher than that of SAA and CRP. The specificity of the combined detection of the three was 95.670%, which was higher than that of PCT, SAA, and CRP alone. Correlation analysis revealed that PCT had a significant positive correlation with CRP and SAA (P < 0.01), and a weak correlation with white blood cell count (WBC) and fibrinogen (FIB) (P = 0.03 for WBC, P = 0.04 for FIB). Conclusion: PCT, SAA, and CRP indicators in patients with urosepsis are significantly elevated, and all three are valuable in the diagnosis of urosepsis. PCT alone has good diagnostic efficiency for urosepsis, and a certain correlation with other inflammatory factors. The diagnostic efficacy of the three indicators in combination is better than that of any one of the three, and is worthy of widespread clinical application. [ABSTRACT FROM AUTHOR]

Objective: Chronological age (CAge), biological age (BAge), and accelerated age (AAge) are all important for aging‐related diseases. CAge is a known risk factor for benign prostatic hyperplasia (BPH); However, the evidence of association of BAge and AAge with BPH is limited. This study aimed to evaluate the association of CAge, Bage, and AAge with BPH in a large prospective cohort. Method: A total of 135,933 males without BPH at enrolment were extracted from the UK biobank. We calculated three BAge measures (Klemera–Doubal method, KDM; PhenoAge; homeostatic dysregulation, HD) based on 16 biomarkers. Additionally, we calculated KDM‐BAge and PhenoAge‐BAge measures based on the Levine method. The KDM‐AAge and PhenoAge‐AAge were assessed by the difference between CAge and BAge and were standardized (mean = 0 and standard deviation [SD] = 1). Cox proportional hazard models were applied to assess the associations of CAge, Bage, and AAge with incident BPH risk. Results: During a median follow‐up of 13.150 years, 11,811 (8.690%) incident BPH were identified. Advanced CAge and BAge measures were associated with an increased risk of BPH, showing threshold effects at a later age (all P for nonlinearity <0.001). Nonlinear relationships between AAge measures and risk of BPH were also found for KDM‐AAge (P = 0.041) and PhenoAge‐AAge (P = 0.020). Compared to the balance comparison group (−1 SD < AAge < 1 SD), the accelerated aging group (AAge > 2 SD) had a significantly elevated BPH risk with hazard ratio (HR) of 1.115 (95% CI, 1.000–1.223) for KDM‐AAge and 1.180 (95% CI, 1.068–1.303) for PhenoAge‐AAge, respectively. For PhenoAge‐AAge, subgroup analysis of the accelerated aging group showed an increased HR of 1.904 (95% CI, 1.374–2.639) in males with CAge <50 years and 1.233 (95% CI, 1.088–1.397) in those having testosterone levels <12 nmol/L. Moreover, AAge‐associated risk of BPH was independent of and additive to genetic risk. Conclusions: Biological aging is an independent and modifiable risk factor for BPH. We suggest performing active health interventions to slow biological aging, which will help mitigate the progression of prostate aging and further reduce the burden of BPH. [ABSTRACT FROM AUTHOR]

Background: Sporadic parathyroid adenoma (PA) is the most common cause of hyperparathyroidism, yet the mechanisms involved in its pathogenesis remain incompletely understood. Methods: Surgically removed PA samples, along with normal parathyroid gland (PG) tissues that were incidentally dissected during total thyroidectomy, were analysed using single‐cell RNA‐sequencing with the 10× Genomics Chromium Droplet platform and Cell Ranger software. Gene set variation analysis was conducted to characterise hallmark pathway gene signatures, and single‐cell regulatory network inference and clustering were utilised to analyse transcription factor regulons. Immunohistochemistry and immunofluorescence were performed to validate cellular components of PA tissues. siRNA knockdown and gene overexpression, alongside quantitative polymerase chain reaction, Western blotting and cell proliferation assays, were conducted for functional investigations. Results: There was a pervasive increase in gene transcription in PA cells (PACs) compared with PG cells. This is associated with high expression of histone‐lysine N‐methyltransferase 2A (KMT2A). High KMT2A levels potentially contribute to promoting PAC proliferation through upregulation of the proto‐oncogene CCND2, which is mediated by the transcription factors signal transducer and activator of transcription 3 (STAT3) and GATA binding protein 3 (GATA3). PA tissues are heavily infiltrated with myeloid cells, while fibroblasts, endothelial cells and macrophages in PA tissues are commonly enriched with proinflammatory gene signatures relative to their counterparts in PG tissues. Conclusions: We revealed the previously underappreciated involvement of the KMT2A‒STAT3/GATA3‒CCND2 axis and chronic inflammation in the pathogenesis of PA. These findings underscore the therapeutic promise of KMT2A inhibition and anti‐inflammatory strategies, highlighting the need for future investigations to translate these molecular insights into practical applications. Highlights: Single‐cell RNA‐sequencing reveals a transcriptome catalogue comparing sporadic parathyroid adenomas (PAs) with normal parathyroid glands.PA cells show a pervasive increase in gene expression linked to KMT2A upregulation.KMT2A‐mediated STAT3 and GATA3 upregulation is key to promoting PA cell proliferation via cyclin D2.PAs exhibit a proinflammatory microenvironment, suggesting a potential role of chronic inflammation in PA pathogenesis. [ABSTRACT FROM AUTHOR]

Background and Aims: Accurate preoperative prediction of microvascular invasion (MVI) and recurrence‐free survival (RFS) is vital for personalised hepatocellular carcinoma (HCC) management. We developed a multitask deep learning model to predict MVI and RFS using preoperative MRI scans. Methods: Utilising a retrospective dataset of 725 HCC patients from seven institutions, we developed and validated a multitask deep learning model focused on predicting MVI and RFS. The model employs a transformer architecture to extract critical features from preoperative MRI scans. It was trained on a set of 234 patients and internally validated on a set of 58 patients. External validation was performed using three independent sets (n = 212, 111, 110). Results: The multitask deep learning model yielded high MVI prediction accuracy, with AUC values of 0.918 for the training set and 0.800 for the internal test set. In external test sets, AUC values were 0.837, 0.815 and 0.800. Radiologists' sensitivity and inter‐rater agreement for MVI prediction improved significantly when integrated with the model. For RFS, the model achieved C‐index values of 0.763 in the training set and ranged between 0.628 and 0.728 in external test sets. Notably, PA‐TACE improved RFS only in patients predicted to have high MVI risk and low survival scores (p <.001). Conclusions: Our deep learning model allows accurate MVI and survival prediction in HCC patients. Prospective studies are warranted to assess the clinical utility of this model in guiding personalised treatment in conjunction with clinical criteria. [ABSTRACT FROM AUTHOR]

Numerous synaptic devices have been explored for the next generation of energy‐efficient computing techniques. Among them, optoelectronic synaptic devices based on semiconductor/ferroelectric heterostructures have received a lot of attention lately due to their amazing parallelism, efficiency, and fault tolerance properties. However, polarizing the ferroelectric layer or gating the dielectric layer is necessary to achieve tunable synaptic functions, which generally causes an increase in energy consumption and complex manufacturing processes. Here, a simple and efficient method is demonstrated to develop a tunable optoelectronic synaptic device based on a single ferroelectric semiconductor, BiFeO3‐BaTiO3 (BF‐BT). Multi‐essential synaptic functions including short‐term plasticity, paired‐pulse facilitation, and long‐term plasticity are all satisfactorily replicated by the memristor device. More significantly, light‐controllable synaptic behaviors are realized by altering the ferroelectric polarization state of BF‐BT. Synaptic devices' relaxation characteristics enable simulation of the effects of positive/negative emotions on learning and forgetting processes. This study highlights the potential of the ferroelectric semiconductor memristor in constructing the efficient optoelectronic synapses for future neuromorphic electronics with the ability to learn and sense optical information. [ABSTRACT FROM AUTHOR]

This work was designed to evaluate the effect of four enzyme-assisted extraction (EAE) combined hydrodistillation (HD) methods on the yield, microstructure and chemical composition of essential oil (EO) from leaves of Cinnamomum longepaniculatum (Gamble) N. Chao ex H. W. Li. The chemical composition of EO was analyzed using gas chromatography-mass spectrometry. Changes in the microstructure of leaf residues were observed by scanning electron microscopy. Response surface methodology was used to predict the best conditions for the EO extraction with the most effective enzyme pretreatment. Further, the anxiolytic effect and mechanism of the optimized EO were investigated by the open-field test (OFT), elevated plus-maze test (EPMT), hole-board test (HBT) and the assay of neurotransmitter concentrations (5-hydroxytryptamine, 5-HT; γ-aminobutyric acid, GABA; norepinephrine, NE). The results showed that different enzyme pretreatments increased the yield and quality of EO and disrupted the cell wall. The circumscribed-β-glucan/hemicellulose enzyme (1:1) pretreatment (4.33%) was the most effective compared to the enzyme-free group (2.82%). The optimum extraction process conditions were: pH:5, enzymolysis time: 67 min and digestion temperature: 48.5 °C. Under these conditions, the maximum yield of EO was 4.37%. After inhalation of EO, mice showed significant anxiolytic effects in EPMT, HBT, and OFT. In addition, EO significantly down-regulated 5-hydroxytryptamine and NE levels and up-regulated GABA levels. Cinnamomum longepaniculatum EO may be related to 5-HTergic, GABAergic and NEergic neurotransmitter systems for better anxiolytic effect. [ABSTRACT FROM AUTHOR]

Background and Aims: To assess patient comfort, wound healing, and scarring at the 6‐month follow‐up of split‐skin graft donor sites treated with Ba‐Hao burn ointment (BHBO) gauze, a compound preparation of traditional Chinese medicine since 1970s, compared with petrolatum gauze. Methods: Thirty patients admitted to the Department of Burns of the First Affiliated Hospital of Anhui Medical University between September 2021 and September 2022 participated in this randomized, prospective, self‐control clinical study. After harvesting the split skin, donor sites were divided into two parts along the midline. BHBO gauze was applied to half of the donor wounds, and petrolatum gauze was applied to the other half. The wound healing time, pain scores on the postoperative Days 3, 6, and 9, and Vancouver Scar Scale (VSS) score at the 6‐month follow‐up were assessed. Results: The wound healing time was significantly shorter in the BHBO group than in the control group (10.07 ± 1.48 days vs. 11.50 ± 1.74 days, p < 0.001). On postoperative Days 3 and 6, the pain scores quantified by visual analog scores were significantly lower in the BHBO group than in the control group (5.33 ± 1.54 and 4.17 ± 1.51, respectively vs. 7.57 ± 1.41 and 5.20 ± 1.47, respectively). The difference in the visual analog scale score on postoperative Day 9 between the groups was not significant (p > 0.05). Microbiological assessment revealed the absence of bacterial contamination in both groups. At the 6‐month follow up, the VSS score was significantly lower in the BHBO group (6.67 ± 1.92) than in the control group (9.57 ± 1.55). Conclusion: BHBO resulted in faster donor‐site healing, reduced postoperative pain, and improved scar quality at the 6‐month follow‐up than petrolatum gauze alone. Key points: Explore the different clinical effect of Ba‐Hao burn ointment (BHBO) and petrolatum gauzes in donor site.BHBO can shorten donor site wound healing time and dull pain.BHBO can improve scare quality. [ABSTRACT FROM AUTHOR]

Key message: Unreduced megagametophytes via second-division restitution were confirmed through heterozygosity analysis, and four candidate physical centromeres of rubber were located for the first time. The evaluation of maternal heterozygosity restitution (MHR) is vital in identifying the mechanism of 2n gametogenesis and assessing the utilization value of 2n gametes. In this study, three full-sib triploid populations were employed to evaluate the MHR of 2n female gametes of rubber tree clone GT1 and to confirm their genetic derivation. The 2n female gametes of GT1 were derived from second-division restitution (SDR) and transmitted more than half of the parental heterozygosity. In addition, low recombination frequency markers were developed, and four candidate physical centromeres of rubber tree were located for the first time. The confirmation that 2n female gametes of rubber tree clone GT1 are derived from SDR provides insights into the molecular mechanisms of 2n gametogenesis. In addition, the identified centromere location will aid in the development of centromeric markers for the rapid identification of the 2n gametogenesis mechanism. [ABSTRACT FROM AUTHOR]

Objectives: CD4+ T cell helper and regulatory function in human cancers has been well characterised. However, the definition of tumor‐infiltrating CD4+ T cell exhaustion and how it contributes to the immune response and disease progression in human gastric cancer (GC) remain largely unknown. Methods: A total of 128 GC patients were enrolled in the study. The expression of CD39 and PD‐1 on CD4+ T cells in the different samples was analysed by flow cytometry. GC‐infiltrating CD4+ T cell subpopulations based on CD39 expression were phenotypically and functionally assessed. The role of CD39 in the immune response of GC‐infiltrating T cells was investigated by inhibiting CD39 enzymatic activity. Results: In comparison with CD4+ T cells from the non‐tumor tissues, significantly more GC‐infiltrating CD4+ T cells expressed CD39. Most GC‐infiltrating CD39+CD4+ T cells exhibited CD45RA−CCR7− effector–memory phenotype expressing more exhaustion‐associated inhibitory molecules and transcription factors and produced less TNF‐α, IFN‐γ and cytolytic molecules than their CD39−CD4+ counterparts. Moreover, ex vivo inhibition of CD39 enzymatic activity enhanced their functional potential reflected by TNF‐α and IFN‐γ production. Finally, increased percentages of GC‐infiltrating CD39+CD4+ T cells were positively associated with disease progression and patients' poorer overall survival. Conclusion: Our study demonstrates that CD39 expression defines GC‐infiltrating CD4+ T cell exhaustion and their immunosuppressive function. Targeting CD39 may be a promising therapeutic strategy for treating GC patients. [ABSTRACT FROM AUTHOR]

Osteoporosis, a metabolic bone disease characterized by low bone mineral density and deterioration of bone microarchitecture, has led to a high risk of fatal osteoporotic fractures worldwide. Accumulating evidence has revealed that sexual dimorphism is a notable feature of osteoporosis, with sex-specific differences in epidemiology and pathogenesis. Specifically, females are more susceptible than males to osteoporosis, while males are more prone to disability or death from the disease. To date, sex chromosome abnormalities and steroid hormones have been proven to contribute greatly to sexual dimorphism in osteoporosis by regulating the functions of bone cells. Understanding the sex-specific differences in osteoporosis and its related complications is essential for improving treatment strategies tailored to women and men. This literature review focuses on the mechanisms underlying sexual dimorphism in osteoporosis, mainly in a population of aging patients, chronic glucocorticoid administration, and diabetes. Moreover, we highlight the implications of sexual dimorphism for developing therapeutics and preventive strategies and screening approaches tailored to women and men. Additionally, the challenges in translating bench research to bedside treatments and future directions to overcome these obstacles will be discussed. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the effectiveness and safety of perampanel (PER) monotherapy (MT) or add‐on therapy (AT) in Chinese children with epilepsy, as well as to evaluate the data from routine therapeutic drug monitoring (TDM) of PER for these pediatric patients. Methods: This retrospective and observational study was carried out on children with epilepsy (n = 340) from 2020 to 2022 at the Children's Hospital of Nanjing Medical University. Outcome measures were the responder rate (50% or greater seizure reduction), long‐term efficacy, and tolerability (number and types of adverse events) in MT and AT groups. Concentrations of plasma PER obtained from these patients, if available, were analyzed too. Results: A total of 279 patients achieved at least 3 months of therapy, and 58.1% responded to PER therapy. 53 of the responders were seizure‐free (32.7%). The retention rate dropped from 88.0% at 3 months to 40.6% at 12 months after treatment. Patients with MT achieved better seizure control than those with AT (P < 0.001). Intriguingly, PER exerted a very weak effect on patients who took more than 2 ASMs or were diagnosed with drug‐resistant epilepsy. There were no significant differences in tolerability between the two groups. In addition, 179 patients were routinely monitored for PER, and the trough concentrations (C0) for these patients ranged from 30.0 to 992.0 ng/mL. However, no significant difference in C0 was observed between responders and nonresponders (333 ng/mL vs 325.5 ng/mL, P = 0.264). Significance: This study provides effectiveness and safety data on Chinese children with epilepsy treated with PER either as MT or as AT. The efficacy of patients receiving MT was much better than cases administered with more than 2 ASMs or diagnosed with drug‐resistant epilepsy. In addition, no association was found between the plasma PER concentration and efficacy or safety. Plain Language Summary: The study reports the effects of perampanel on seizures and adverse effects in Chinese patients with epilepsy younger than 18 years. Seizures decreased in 58.1% of patients (responders); in a third of these responders, seizures stopped. After treatment was started, 88% of patients were still on perampanel at 3 months and 40.6% at 12 months. People who were treated with perampanel only were more likely to respond than those who received perampanel and other antiseizure treatments, although perampanel was tolerated equally well in these groups. Plasma perampanel concentration did not predict seizure response or adverse effects. [ABSTRACT FROM AUTHOR]

Objectives: Due to the urgent need to develop innovative, environmentally sustainable bactericides, we use the natural product isoquinoline as a lead compound to discover highly active bactericides from isoquinoline derivatives. Methods: In this paper, the antibacterial activity of 49 isoquinoline derivatives was evaluated against three plant bacteria in vitro. Results: Among all the derivatives, isoquinoline-3-carboxylic acid (IQ3CA) demonstrated significant antibacterial activity against Ralstonia solanacearum (Rs), Acidovorax citrulli (Ac), X. oryzae pv. oryzicola (Xoc), X. campestris pv. campestris (Xcc), P. carotovorum subsp. carotovorum (Pcc), and X. fragariae (Xf), with EC50 values ranging from 8.38 to 17.35 μg/mL. Furthermore, IQ3CA exhibited a potent protective effect against Ac, with an efficacy of 68.56% at 200 μg/mL, which was not significantly different from that of the positive control kasugamycin (72.48%) and was superior to that of the positive control thiosen copper (64.62%). The scanning electron microscopy observations revealed that treatment of Ac cells with IQ3CA at a concentration of 25 μg/mL resulted in a curved and sunken cell morphology, along with destroyed cell membrane integrity. Additionally, the motility and exopolysaccharides production of Ac were inhibited, and biofilm formation was prevented. Conclusion: These results suggest that IQ3CA holds promise as a lead compound with antibacterial properties against plant diseases. [ABSTRACT FROM AUTHOR]

Myelodysplastic syndromes (MDS) are a group of heterogeneous myeloid clonal disorders characterized by ineffective hematopoiesis. Accumulating evidence has shown that macrophages (MΦs) are important components in the regulation of tumor progression and hematopoietic stem cells (HSCs). However, the roles of bone marrow (BM) MΦs in regulating normal and malignant hematopoiesis in different clinical stages of MDS are largely unknown. Age‐paired patients with lower‐risk MDS (N = 15), higher‐risk MDS (N = 15), de novo acute myeloid leukemia (AML) (N = 15), and healthy donors (HDs) (N = 15) were enrolled. Flow cytometry analysis showed increased pro‐inflammatory monocyte subsets and a decreased classically activated (M1) MΦs/alternatively activated (M2) MΦs ratio in the BM of patients with higher‐risk MDS compared to lower‐risk MDS. BM MФs from patients with higher‐risk MDS and AML showed impaired phagocytosis activity but increased migration compared with lower‐risk MDS group. AML BM MΦs showed markedly higher S100A8/A9 levels than lower‐risk MDS BM MΦs. More importantly, coculture experiments suggested that the HSC supporting abilities of BM MΦs from patients with higher‐risk MDS decreased, whereas the malignant cell supporting abilities increased compared with lower‐risk MDS. Gene Ontology enrichment comparing BM MΦs from lower‐risk MDS and higher‐risk MDS for genes was involved in hematopoiesis‐ and immunity‐related pathways. Our results suggest that BM MΦs are involved in ineffective hematopoiesis in patients with MDS, which indicates that repairing aberrant BM MΦs may represent a promising therapeutic approach for patients with MDS. [ABSTRACT FROM AUTHOR]

This study investigates the influence of donor‐specific anti‐HLA antibodies (DSA) levels on primary poor graft function (PGF) and graft rejection (GR) after haploidentical stem cell transplantation (haplo‐SCT) with rituximab desensitization. A total of 155 DSA‐positive haplo‐SCT candidates with mean fluorescence intensity (MFI) between 2000 and 10,000 were enrolled in this prospective clinical trial. Receiver operating characteristic (ROC) curves determined the optimal DSA MFI cutoff for identifying high‐risk patients. Patients were categorized into two groups: DSA low‐level group (2000 ≤ DSA MFI < 5000, Group A) and high‐level group (5000 ≤ DSA MFI ≤ 10,000, Group B). The incidence of primary PGF was 6.5% (2.6%–10.3%), while GR incidence was 0.6% (0.0%–1.9%). Group A had significantly lower primary PGF rates than Group B (2.3% [0.0%–5.7%] vs. 12.9% [4.8%–21.0%], p = 0.017). Only one patient in Group B experienced GR. High DSA levels (5000 ≤ MFI ≤ 10,000) were identified as the sole independent risk factor for primary PGF and GR after haplo‐SCT with rituximab desensitization (HR = 7.282, 95% CI 1.517–34.953, p = 0.013). The 4‐year cumulative incidence of relapse, non‐relapse mortality, disease‐free survival, and overall survival were 14.7% (11.6%–17.8%), 16.3% (13.1%–19.4%), 69.0% (65.9%–76.2%), and 70.6% (66.4%–74.8%), respectively. DSA levels have an impact on efficiency of rituximab desensitization, and a DSA MFI threshold is provided for predicting primary PGF and GR. [ABSTRACT FROM AUTHOR]

Tormentic acid (TA), an effective triterpenoid isolated from Chaenomeles speciosa (Sweet) Nakai (Rosaceae) fruits, exerts an effective treatment for gastric damage. To investigate the gastroprotective effect of TA on indomethacin (IND) damaged GES-1 cells and rats, and explore potential mechanisms. TA concentrations of 1.563–25 µM were used. Cell proliferation, apoptosis and migration were performed using MTT, colony formation, wound healing, migration, Hoechst staining assays. SD rats were divided into control, IND, TA (1, 2 and 4 mg/kg) + IND groups, once a day for 21 continuous days. Twenty-four hours after the last administration, all groups except the control group were given IND (100 mg/kg) by gavage. Gastric juice parameters, gastric ulcer, gastric blood flow (GBF), blood biochemical parameters and cytokine analysis and gastric mucosal histopathology were detected for 2 h and 6 h after IND oral administration. The mRNA and protein expression of miR-139 and the CXCR4/CXCL12/PLC/PKC/Rho A/MLC pathway were analyzed in the IND-damaged GES-1 cells and gastric tissue of rats. TA might ameliorate the gastric mucosal injury by accelerating the IND-damaged GES-1 cell proliferation and migration, ameliorating GBF, ulcer area and pathologic changes, the redox system and cytokine levels, the gastric juice parameters, elevating the gastric pH in IND damaged rats; suppressed miR-139 mRNA expression, elevated CXCR4 and CXCL12 mRNA and protein expression, p-PLC, p-PKC, Rho A, MLCK and p-MLC protein expression. TA may have potential use as a clinical drug candidate for gastric mucosal lesion treatment. [ABSTRACT FROM AUTHOR]

Aplastic anemia (AA) is a life-threatening disease characterized by bone marrow (BM) failure and pancytopenia. As an important component of the BM microenvironment, endothelial cells (ECs) play a crucial role in supporting hematopoiesis and regulating immunity. However, whether impaired BM ECs are involved in the occurrence of AA and whether repairing BM ECs could improve hematopoiesis and immune status in AA remain unknown. In this study, a classical AA mouse model and VE-cadherin blocking antibody that could antagonize the function of ECs were used to validate the role of BM ECs in the occurrence of AA. N-acetyl-L-cysteine (NAC, a reactive oxygen species scavenger) or exogenous EC infusion was administered to AA mice. Furthermore, the frequency and functions of BM ECs from AA patients and healthy donors were evaluated. BM ECs from AA patients were treated with NAC in vitro, and then the functions of BM ECs were evaluated. We found that BM ECs were significantly decreased and damaged in AA mice. Hematopoietic failure and immune imbalance became more severe when the function of BM ECs was antagonized, whereas NAC or EC infusion improved hematopoietic and immunological status by repairing BM ECs in AA mice. Consistently, BM ECs in AA patients were decreased and dysfunctional. Furthermore, dysfunctional BM ECs in AA patients led to their impaired ability to support hematopoiesis and dysregulate T cell differentiation toward proinflammatory phenotypes, which could be repaired by NAC in vitro. The reactive oxygen species pathway was activated, and hematopoiesis- and immune-related signaling pathways were enriched in BM ECs of AA patients. In conclusion, our data indicate that dysfunctional BM ECs with impaired hematopoiesis-supporting and immunomodulatory abilities are involved in the occurrence of AA, suggesting that repairing dysfunctional BM ECs may be a potential therapeutic approach for AA patients. [ABSTRACT FROM AUTHOR]

As a novel nanomaterial, the TiN/Ti3C2 heterojunction has been demonstrated to possess exceptional optoelectronic properties, offering significant potential for applications in fields such as communication, optical sensors, and image processing. The rapid evolution of the internet demands higher communication capacity and information processing speed. In this context, all-optical wavelength conversion, a pivotal technique in all-optical signal processing, holds paramount importance in overcoming electronic bottlenecks, enhancing wavelength utilization, resolving wavelength competition, and mitigating network congestion. Utilizing the idle light generated through the four-wave mixing (FWM) process accurately mimics the bit patterns of signal channels. This process is inherently rapid and theoretically capable of surpassing electronic bottlenecks with ease. By placing an optical filter at the fiber output end to allow idle light passage while blocking pump and signal light, the output becomes a wavelength-converted replica of the original bitstream. It has been verified that TiN/Ti3C2 heterojunction-coated microfiber (THM) exhibits outstanding third-order nonlinear coefficients. Building upon this, we achieved a THM-enhanced FWM all-optical wavelength converter, resulting in a ~4.48 dB improvement in conversion efficiency. Compared to conventional high-nonlinear fibers, this compact device significantly reduces fiber length and can be easily integrated into current high-speed optical communication networks. It demonstrates broad prospects in the realms of all-optical signal processing, robotic applications, ultra-high-speed communication, and beyond. [ABSTRACT FROM AUTHOR]

Simple Summary: This study focuses on the Wuchang bream (Megalobrama amblycephala) as the research subject, aiming to investigate the effects of emodin on the total bacterial count of Aeromonas hydrophila and the immune response in various tissues of Wuchang bream following infection. The experimental diets were made by supplementing emodin at 0, 30, 100, and 150 mg kg−1 to a basal (control) diet, respectively, and fed to fish with an initial weight of 50.4 ± 2.35 g. All fish were divided into five experimental groups: uninfected fish fed with basal control diet (negative control, NC), infected fish fed with the diet supplemented with 0 (positive control group, PC), 30 (30), 100 (100), and 150 mg/kg (150) of emodin. Except for the negative control group, all other groups were injected with A. hydrophila at a concentration of 1 × 106 CFU/mL. The experiment was conducted over a period of 14 days, with sampling at various time points. The results of the experiment demonstrated that the total bacterial count of Aeromonas in the kidney, blood, and liver tissues of infected Wuchang bream was significantly affected by the dosage of added emodin and the feeding duration. Additionally, the immune response of Wuchang bream following intraperitoneal infection with A. hydrophila was also significantly influenced by emodin (p < 0.05). In conclusion, the addition of 100 mg/kg of emodin to the diet could enhance the Wuchang bream's resistance to A. hydrophila infection by reducing the total bacterial count of pathogenic bacteria in tissues, increasing the activity of relevant immune enzymes and promoting the secretion of cytokines. This study provides a theoretical basis for practical production. This experiment aimed to investigate the effects of emodin on the total bacterial count and immune response in various tissues of Wuchang bream infected with A. hydrophila. The experimental diets were made by supplementing emodin at 0, 30, 100, and 150 mg kg−1 to basal (control) diet, respectively, and fed to fish with an initial weight of 50.4 ± 2.35 g. All fish were divided into five experimental groups: uninfected fish fed with basal control diet (negative control, NC), infected fish fed with the diet supplemented with 0 (positive control group, PC), 30 (30), 100 (100), and 150 mg/kg (150) of emodin. The fish were reared for 14 days and sampled at different time points. The results showed that the total bacterial count in the kidney, blood, and liver tissues of Wuchang bream infected with A. hydrophila was significantly affected by the supplementation and feeding time of emodin. At the beginning of the experiment, the difference in total bacterial count among the groups was not significant. On day 1, the total bacterial count in all groups was significantly higher (p < 0.05) than that in the negative control group. On day 4, the total bacterial count in all the emodin groups was significantly reduced, and the best bactericidal effect was observed in the 100 mg kg−1 group. In addition, emodin had a significant effect on the immune response of Wuchang bream after infection with A. hydrophila (p < 0.05). Compared with the other groups, the respiratory burst activity, tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1) content, and white blood cell count (WBC) in the 100 and 150 mg kg−1 groups could be restored to normal levels in the shortest time (p < 0.05). Furthermore, this study also measured the complement alternative pathway activity (ACH50), plasma superoxide dismutase (SOD) activity, and malondialdehyde (MDA) content of the fish. The results showed that supplying 100 mg kg−1 emodin to the diet could significantly (p < 0.05) increase the ACH50 activity of the fish. Compared with the positive control (PC) group, the addition of emodin to the diet can inhibit the decrease in SOD activity and the increase in MDA content in the plasma of infected Wuchang bream. In conclusion, supplying 100 mg kg−1 emodin to the diet can enhance the ability of Wuchang bream to resist A. hydrophila infection by reducing the total bacterial count in tissues, increasing the activity of related immune enzymes, and promoting the secretion of cytokines. This provides a theoretical basis for production practice. [ABSTRACT FROM AUTHOR]

Oxidative stress-associated human diseases further include Parkinson's disease, Huntington's disease, inflammation (arthritis), ischemia-reperfusion injury, atherosclerosis, amyotrophic lateral sclerosis, stroke, red blood cell disorder, cancer and cataract, among others. The disruption of cellular redox homeostasis, viz., oxidative stress, results in the development of various human diseases/pathologies. The robust antioxidant system of I A. terreus i contributes to the resistance of this fungal pathogen to the oxidative stress drug amphotericin B. Therefore, disruption of the antioxidant systems of pathogens could serve as an effective strategy for the control of certain fungal pathogens including I A. terreus i . This Special Issue presented recent progress on natural products that serve as drug candidates for redox-related human diseases. [Extracted from the article]

The interleukin-1 family is a group of important cytokines that play a key regulatory role in the immune and inflammatory response (including infectious and non-bacterial injuries). Nowadays, the interleukin-1 family mainly includes 11 cytokines and has multiple roles in the pathology and physiology of inflammation. Moreover, accumulating number of research show that the interleukin-1 family and its receptors are involved in the occurrence and development of cardiovascular diseases. Therefore, we show here the review involving hotspots of the interleukin-1 family in the process of inflammation and its target therapy in cardiovascular diseases, including atherosclerosis, myocardial infarction and heart failure. [ABSTRACT FROM AUTHOR]

Background: Outbreaks of monkeypox have been ongoing in non-endemic countries since May 2022. A thorough assessment of its global zoonotic niche and potential transmission risk is lacking. Methods: We established an integrated database on global monkeypox virus (MPXV) occurrence during 1958 − 2022. Phylogenetic analysis was performed to examine the evolution of MPXV and effective reproductive number (Rt) was estimated over time to examine the dynamic of MPXV transmissibility. The potential ecological drivers of zoonotic transmission and inter-regional transmission risks of MPXV were examined. Results: As of 24 July 2022, a total of 49 432 human patients with MPXV infections have been reported in 78 countries. Based on 525 whole genome sequences, two main clades of MPXV were formed, of which Congo Basin clade has a higher transmissibility than West African clade before the 2022-monkeypox, estimated by the overall Rt (0.81 vs. 0.56), and the latter significantly increased in the recent decade. Rt of 2022-monkeypox varied from 1.14 to 4.24 among the 15 continuously epidemic countries outside Africa, with the top three as Peru (4.24, 95% CI: 2.89–6.71), Brazil (3.45, 95% CI: 1.62–7.00) and the United States (2.44, 95% CI: 1.62–3.60). The zoonotic niche of MPXV was associated with the distributions of Graphiurus lorraineus and Graphiurus crassicaudatus, the richness of Rodentia, and four ecoclimatic indicators. Besides endemic areas in Africa, more areas of South America, the Caribbean States, and Southeast and South Asia are ecologically suitable for the occurrence of MPXV once the virus has invaded. Most of Western Europe has a high-imported risk of monkeypox from Western Africa, whereas France and the United Kingdom have a potential imported risk of Congo Basin clade MPXV from Central Africa. Eleven of the top 15 countries with a high risk of MPXV importation from the main countries of 2022-monkeypox outbreaks are located at Europe with the highest risk in Italy, Ireland and Poland. Conclusions: The suitable ecological niche for MPXV is not limited to Africa, and the transmissibility of MPXV was significantly increased during the 2022-monkeypox outbreaks. The imported risk is higher in Europe, both from endemic areas and currently epidemic countries. Future surveillance and targeted intervention programs are needed in its high-risk areas informed by updated prediction. [ABSTRACT FROM AUTHOR]

Scedosporium apiospermum (S. apiospermum) is typically reported to be involved in superficial and subcutaneous fungal infections but overlooked in invasive infections, which is associated with a high mortality rate. It poses a diagnostic challenge due to its confusable characteristics to other hyaline hyphomycetes. Here, we reported a psoriasis patient with an invasive S. apiospermum infection. The patient presents an abscess at the intermuscular space of the left hip and an increased C-reactive protein level. Pus culture showed white-greyish, cottonlike colonies with aerial mycelium and terminal oval conidia, suggesting S. apiospermum. This rare fungus was rapidly confirmed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and RNA sequencing. The patient was successfully treated with voriconazole with no recurrence of the abscesses despite delayed treatment. This is the first such case infection report from China that described an unusual case of intermuscular space abscesses due to S. apiospermum. This report highlights the possibility of fungal infections in deeper tissue, as well as the necessity of thorough evaluation and microbiological diagnosis for invasive infections, particularly in immunocompromised patients. [ABSTRACT FROM AUTHOR]

Summary: Patients who receive allogeneic haematopoietic stem cell transplantation (allo‐HSCT) may develop sepsis, which result in a highly intensive care unit admission rate and mortality. Therefore, short‐term and long‐term prognostic models for sepsis after allo‐HSCT are urgently needed. We enrolled patients receiving allo‐HSCT who developed sepsis after allo‐HSCT at Peking University People's Hospital between 2012 and 2021, including 287 patients who received allo‐HSCT in 2018–2021 in the derivation cohort, and 337 patients in 2012–2017 in the validation cohort. Multivariate logistic regression analysis was used to identify prognostic factors, and these identified factors were incorporated into two scoring models. Seven independent factors (acute graft‐versus‐host disease (GVHD), chronic GVHD (cGVHD), total bilirubin, lactate dehydrogenase (LDH) and organ dysfunction [renal, lung and heart]) were included in the 6‐month prognostic model, and six factors (cGVHD, C‐reactive protein, LDH, organ dysfunction [lung, neurologic and coagulation]) were included in the 14‐day prognostic model. The area under the receiver operating characteristic curves, calibration plots and decision curve analysis demonstrated the robust predictive performance of the models, better than the Sequential Organ Failure Assessment score. Early identification of patients with high risk of 6‐month and 14‐day death may allow clinicians to provide timely treatments and improve the therapeutic effects. [ABSTRACT FROM AUTHOR]

Objective: The drug‐refractory epilepsy (DRE) in children is commonly observed but the underlying mechanisms remain elusive. We examined whether fatty acids (FAs) and lipids are potentially associated with the pharmacoresistance to valproic acid (VPA) therapy. Methods: This single‐center, retrospective cohort study was conducted using data from pediatric patients collected between May 2019 and December 2019 at the Children's Hospital of Nanjing Medical University. Ninety plasma samples from 53 responders with VPA monotherapy (RE group) and 37 non‐responders with VPA polytherapy (NR group) were collected. Non‐targeted metabolomics and lipidomics analysis for those plasma samples were performed to compare the potential differences of small metabolites and lipids between the two groups. Plasma metabolites and lipids passing the threshold of variable importance in projection value >1, fold change >1.2 or <0.8, and p‐value <0.05 were regarded as statistically different substances. Results: A total of 204 small metabolites and 433 lipids comprising 16 different lipid subclasses were identified. The well‐established partial least squares‐discriminant analysis (PLS‐DA) revealed a good separation of the RE from the NR group. The FAs and glycerophospholipids status were significantly decreased in the NR group, but their triglycerides (TG) levels were significantly increased. The trend of TG levels in routine laboratory tests was in line with the lipidomics analysis. Meanwhile, cases from the NR group were characterized by a decreased level of citric acid and L‐thyroxine, but with an increased level of glucose and 2‐oxoglutarate. The top two enriched metabolic pathways involved in the DRE condition were biosynthesis of unsaturated FAs and linoleic acid metabolism. Significance: The results of this study suggested an association between metabolism of FAs and the medically intractable epilepsy. Such novel findings might propose a potential mechanism linked to the energy metabolism. Ketogenic acid and FAs supplementation might therefore be high‐priority strategies for DRE management. [ABSTRACT FROM AUTHOR]

Background: Wild apple (Malus sieversii) is under second-class national protection in China and one of the lineal ancestors of cultivated apples worldwide. In recent decades, the natural habitation area of wild apple trees has been seriously declining, resulting in a lack of saplings and difficulty in population regeneration. Artificial near-natural breeding is crucial for protecting and restoring wild apple populations, and adding nitrogen (N) and phosphorous (P) is one of the important measures to improve the growth performance of saplings. In this study, field experiments using N (CK, N1, N2, and N3: 0, 10, 20, and 40 g m− 2 yr− 1, respectively), P (CK, P1, P2, and P3: 0, 2, 4, and 8 g m− 2 yr− 1, respectively), N20Px (CK, N2P1, N2P2, and N2P3: N20P2, N20P4 and N20P8 g m− 2 yr− 1, respectively), and NxP4 (CK, N1P2, N2P2, and N3P2: N10P4, N20P4, and N40P4 g m− 2 yr− 1, respectively) treatments (totaling 12 levels, including one CK) were conducted in four consecutive years. The twig traits (including four current-year stem, 10 leaf, and three ratio traits) and comprehensive growth performance of wild apple saplings were analyzed under different nutrient treatments. Results: N addition had a significantly positive effect on stem length, basal diameter, leaf area, and leaf dry mass, whereas P addition had a significantly positive effect on stem length and basal diameter only. The combination of N and P (NxP4 and N20Px) treatments evidently promoted stem growth at moderate concentrations; however, the N20Px treatment showed a markedly negative effect at low concentrations and a positive effect at moderate and high concentrations. The ratio traits (leaf intensity, leaf area ratio, and leaf to stem mass ratio) decreased with the increase in nutrient concentration under each treatment. In the plant trait network, basal diameter, stem mass, and twig mass were tightly connected to other traits after nutrient treatments, indicating that stem traits play an important role in twig growth. The membership function revealed that the greatest comprehensive growth performance of saplings was achieved after N addition alone, followed by that under the NxP4 treatment (except for N40P4). Conclusions: Consequently, artificial nutrient treatments for four years significantly but differentially altered the growth status of wild apple saplings, and the use of appropriate N fertilizer promoted sapling growth. These results can provide scientific basis for the conservation and management of wild apple populations. [ABSTRACT FROM AUTHOR]

During development, patterned neural activity instructs topographic map refinement. Axons with similar patterns of neural activity converge onto target neurons and stabilize their synapses with these postsynaptic partners, restricting exploratory branch elaboration (Hebbian structural plasticity). On the other hand, non-correlated firing in inputs leads to synapse weakening and increased exploratory growth of axons (Stentian structural plasticity). We used visual stimulation to control the correlation structure of neural activity in a few ipsilaterally projecting (ipsi) retinal ganglion cell (RGC) axons with respect to the majority contralateral eye inputs in the optic tectum of albino Xenopus laevis tadpoles. Multiphoton live imaging of ipsi axons, combined with specific targeted disruptions of brain-derived neurotrophic factor (BDNF) signaling, revealed that both presynaptic p75NTR and TrkB are required for Stentian axonal branch addition, whereas presumptive postsynaptic BDNF signaling is necessary for Hebbian axon stabilization. Additionally, we found that BDNF signaling mediates local suppression of branch elimination in response to correlated firing of inputs. Daily in vivo imaging of contralateral RGC axons demonstrated that p75NTR knockdown reduces axon branch elongation and arbor spanning field volume. What is the role of neurotrophic signaling in activity-dependent refinement of the retinotectal projection? Live imaging of knockdown of neurotrophin receptors reveals that exploratory axonal branching induced by asynchronous stimulation of the axon relative to other inputs required p75-NTR, while Hebbian stabilization of the arbor involved non-cell-autonomous activation of TrkB. [ABSTRACT FROM AUTHOR]

Background: Pain is a contributing factor to the low compliance rate for performing a colonoscopy on screening for colorectal cancer. Purpose: This meta-analysis aimed to evaluate the effect of visual distraction on adults undergoing colonoscopy. Methods: We searched PubMed, EMBASE, Web of Science, and Cochrane Library Database from their inception to February 2022. Randomized controlled trials comparing visual distraction with non-visual distraction were considered for inclusion. The fixed-effects and random-effects models were used to pool the data from individual studies and the Cochrane risk of bias assessment tool was used to determine the methodology quality. Results: This meta-analysis included four studies (N = 301) for pain level and total procedure time, three studies (N = 181) for satisfaction score, three studies (N = 196) for anxiety level, and four studie (N = 402) for willingness to repeat the procedure. The pooled analysis shown that significantly lower pain levels (SMD, − 0.25; 95% CI − 0.47 to − 0.02; P = 0.03), higher satisfaction score with the procedure (SMD, 0.63; 95% CI, 0.33 to 0.93; P < 0.0001), and higher willingness to repeat the procedure (OR, 2.66; 95% CI 1.70 to 4.17; P < 0.0001) in the visual distraction group than those in the non-visual distraction group, with no significant differences in total procedure time (SMD,− 0.07; 95% CI − 0.30 to 0.15; P = 0.53) or anxiety level (SMD,− 0.27; 95% CI − 0.55 to 0.01; P = 0.06). Conclusions: Visual distraction improved the patient's pain, satisfaction, and willingness to repeat the procedure. Thus, visual stimulation is an effective way to reduce pain during colonoscopy and should be recommended. [ABSTRACT FROM AUTHOR]

P53 inactivation occurs in about 50% of human cancers, where p53-driven p21 activity is devoid and p27 becomes essential for the establishment of the G1/S checkpoint upon DNA damage. Here, this work shows that the E2F1-responsive lncRNA LIMp27 selectively represses p27 expression and contributes to proliferation, tumorigenicity, and treatment resistance in p53-defective colon adenocarcinoma (COAD) cells. LIMp27 competes with p27 mRNA for binding to cytoplasmically localized hnRNA0, which otherwise stabilizes p27 mRNA leading to cell cycle arrest at the G0/G1 phase. In response to DNA damage, LIMp27 is upregulated in both wild-type and p53-mutant COAD cells, whereas cytoplasmic hnRNPA0 is only increased in p53-mutant COAD cells due to translocation from the nucleus. Moreover, high LIMp27 expression is associated with poor survival of p53-mutant but not wild-type p53 COAD patients. These results uncover an lncRNA mechanism that promotes p53-defective cancer pathogenesis and suggest that LIMp27 may constitute a target for the treatment of such cancers. [ABSTRACT FROM AUTHOR]

Objective: To compare the effectiveness of a six‐month home‐based telerehabilitation based on the Internet‐based rehabilitation management system coupled with conventional outpatient care in elderly patients with hip fractures following total hip replacement (THR). Methods: Elderly patients (aged over 65 years) with first hip fractures who underwent THR between March 2018 and September 2018 in Tianjin Hospital were enrolled in this study. Patients were divided into two groups: telerehabilitation group (n = 43) and telephone group (n = 42). A Internet‐based telerehabilitation management system was established and applied on patients in the telerehabilitation group. For patients in the telephone group, the rehabilitation intervention was administered through conventional outpatient care (telephone along with outpatient follow‐up). Data from the Harris hip scale (HHS), functional independence measure (FIM), self‐rating anxiety scale (SAS), and postoperative complications at 1, 3, and 6 months after surgery were collected and compared between the two groups. Results: A total of 85 elderly patients completed the 6‐month follow‐up assessment. Results showed that the HHS score was significantly higher in the telerehabilitation group than in the telephone group at 1 month (66.35 ± 4.63 vs 63.48 ± 4.49), 3 months (76.33 ± 4.52 vs 71.81 ± 3.84), and 6 months (84.23 ± 3.13 vs 77.29 ± 4.95) after surgery (P < 0.001). The FIM score was significantly higher in the telerehabilitation group than in the telephone group at 1 month (89.00 ± 5.63 vs 73.35 ± 8.70), 3 months (100.16 ± 4.56 vs 92.81 ± 5.17), and 6 months (111.70 ± 3.13 vs 98.64 ± 5.12) after surgery (P < 0.001). The SAS score was significantly lower in the telerehabilitation group than in the telephone group at 1 month (42.40 ± 3.07 vs 46.21 ± 3.53), 3 months (36.77 ± 2.26 vs 40.24 ± 1.66), and 6 months (29.26 ± 1.63 vs 33.81 ± 2.62) after surgery (P < 0.001). The overall complication rate was significantly lower in the telerehabilitation group than in the telephone group (14% vs 40.5%) (P < 0.05). Conclusion: Internet‐based rehabilitation management system can not only promote the physical rehabilitation of patients, but also play a positive role in psychological rehabilitation and the prevention of complications, which provides new ideas and methods for clinical rehabilitation. [ABSTRACT FROM AUTHOR]

This document is a correction notice for an article titled "Insights and implications of sexual dimorphism in osteoporosis" published in Bone Research. The authors reported an error in figure 1, where the terms "hematopoietic precursors" and "mesenchymal precursors" were wrongly reversed. The corrected figure 1 has been provided to ensure the accuracy of the article. The authors apologize for any inconvenience caused. [Extracted from the article]

Background: Although the prognosis of locally advanced cervical cancer has improved dramatically, survival for those with stage IIIB-IVA disease or lymph nodes metastasis remains poor. It is believed that the incorporation of intensity-modulated radiotherapy into the treatment of cervical cancer might yield an improved loco-regional control, whereas more cycles of more potent chemotherapy after the completion of concurrent chemotherapy was associated with a diminished distant metastasis. We therefore initiated a non-randomized prospective phaseII study to evaluate the feasibility of incorporating both these two treatment modality into the treatment of high risk locally advanced cervical cancer. Objectives: To determine whether the incorporation of intensity-modulated radiotherapy and the addition of adjuvant paclitaxel plus cisplatin regimen into the treatment policy for patients with high risk locally advanced cervical cancer might improve their oncologic outcomes. Study design: Patients were enrolled if they had biopsy proven stage IIIA-IVA squamous cervical cancer or stage IIB disease with metastatic regional nodes. Intensity-modulated radiotherapy was delivered with dynamic multi-leaf collimators using 6MV photon beams. Prescription for PTV ranged from 45.0 ~ 50.0 Gy at 1.8 Gy ~ 2.0 Gy/fraction in 25 fractions. Enlarged nodes were contoured separately and PTV-nodes were boosted simultaneously to a total dose of 50.0–65 Gy at 2.0- 2.6 Gy/fraction in 25 fractions. A total dose of 28 ~ 35 Gy high-dose- rate brachytherapy was prescribed to point A in 4 ~ 5 weekly fractions using an iridium- 192 source. Concurrent weekly intravenous cisplatin at 30 mg/m2 was initiated on the first day of radiotherapy for over 1-h during external-beam radiotherapy. Adjuvant chemotherapy was scheduled within 4 weeks after the completion of concurrent chemo-radiotherapy and repeated 3 weeks later. Paclitaxel 150 mg/m2 was given as a 3-h infusion on day1, followed by cisplatin 35 mg/m2 with 1-h infusion on day1-2 (70 mg/m2 in total). Results: Fifty patients achieved complete response 4 weeks after the completion of the treatment protocol, whereas 2 patients had persistent disease. After a median follow-up period of 66 months, loco-regional (including 2 persistent disease), distant, and synchronous treatment failure occurred in 4,5, and 1, respectively. The 5-year disease-free survival, loco-regional recurrence-free survival, distant-metastasis recurrence-free survival was 80.5%, 90.3%, and 88.0%, respectively. Four of the patients died of the disease, and the 5-year overall survival was 92.1%. Most of the toxicities reported during concurrent chemo-radiotherapy were mild and transient. The occurrence of hematological toxicities elevated mildly during adjuvant chemotherapy, as 32% (16/50) and 4% (2/50) patients experienced grade 3–4 leukopenia and thrombocytopenia, respectively. Grade 3–4 late toxicities were reported in 3 patients. Conclusions: The incorporation of intensity-modulated radiotherapy and adjuvant paclitaxel plus cisplatin chemotherapy were highly effective and well-tolerated in the treatment of high-risk locally advanced cervical cancer. The former yields an improved loco-regional control, whereas distant metastases could be effectively eradicated with mild toxicities when adjuvant regimen was prescribed. Highlights: 1. Incorporating IMRT and adjuvant chemotherapy into the treatment of locally advanced cervical cancer is highly effective. 2. IMRT is associated with a reduced loco-regional relapse. 3. Adding adjuvant TP chemotherapy could diminish tumor hematological spread. 4. Toxicity profiles were mild and manageable. [ABSTRACT FROM AUTHOR]

Oral antiseizure medications are the preferred option for the clinical treatment of epilepsy. Therapeutic drug monitoring has become an important means of achieving individualized treatment of epilepsy. A sensitive, accurate and rapid LC–ESI–MS/MS method was developed and validated for the simultaneous determination of 15 antiseizure medications in human plasma (carbamazepine, gabapentin, pregabalin, phenytoin, zonisamide, oxcarbazepine, tiagabine, lamotrigine, topiramate, phenobarbital, lacosamide, primidone, 10,11‐Dihydro‐10‐hydroxy carbamazepine, ethosuximide, and levetiracetam). The sample preparation procedure was an one‐step protein precipitation with methanol. Mass detection was performed in ionization polarity switching mode (positive–negative–positive) using multiple reaction monitoring mode. A "boot‐shaped" gradient elution program was applied to separate and concentrate those target analytes, resulting in symmetrical peak shapes within 10 min, without endogenous interference. The method showed great linearity over the concentration ranges with acceptable correlation coefficients (0.9966–0.9996). The precision and accuracy values for intra‐ and inter‐assays were within ±15%. Consequently, the method was successfully implemented on pediatric patients undergoing mono‐ or polytherapy for epilepsy and provided timely concentration results to ordering clinicians. [ABSTRACT FROM AUTHOR]

We synthesize a phosphor by combining trimethylammonium tetraphenyl porphyrin with palladium (II), obtaining Pd–TTAP, and investigate its interaction with graphene oxide (GO). Pd–TTAP and GO are found to be noncovalently bonded, according to high-resolution transmission electron microscopy (HR-TEM), ultraviolet-visible spectroscopy (UV-Vis), room temperature phosphorescence spectroscopy (RTP), Raman spectroscopy, and infrared spectroscopy (IR). The binding constant is 2.32 × 104 M−1, calculated using the Benesi–Hildebrand method, and a photoelectric response test finds that photo-induced electrons are transferred from the triplet excited state of Pd–TTAP to GO under visible light excitation. Our results demonstrate that Pd–TTAP can serve as an eff ective energy donor, with GO as an electron acceptor, in photoelectric conversion systems. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to investigate the efficacy and tolerability of perampanel (PER) therapy and to optimize a specific plasma reference range for PER in children. Another major aim was to evaluate the potential determinators of PER concentration. Methods: Concentrations obtained from 80 children were analyzed for routine therapeutic drug monitoring (TDM) between 2021 and 2022. We retrospectively reviewed the clinical data of these patients and assessed the efficacy at 3 months after treatment initiation. Trough concentration‐to‐dose ratio (C0/Dose ratio) of PER was compared among patients on various potential influencing factors. Results: A 3‐month PER therapy produced a ≥50% reduction in seizure frequency in 58.8% of patients. Twelve patients reported at least one adverse effect (AE), mainly dizziness. The monitoring data showed that the median C0 was 325.5 ng/mL. Under maintenance dosages, approximately 75% of the C0 values were 180.0‐610.0 ng/mL. The C0/Dose ratio in patients aged 1 to <4 was significantly lower by twofold than in those aged 4 to ≤12 years (P = 0.001). Enzyme‐inducing ASMs (EIASMs) decreased the C0/Dose ratio of PER by 25.9% (P = 0.165). In addition, seizure frequency reduction in responders was achieved at a median PER C0 value of 357 ng/mL, which was similar to the value of 314 ng/mL found in nonresponders (P = 0.288). No significant difference was found in PER C0 values between patients with and without AEs (P = 0.082). Significance: In this study, PER treatment showed acceptable efficacy and tolerance in Chinese children with epilepsy. Contributing factors like age to variable C0/Dose ratios were identified, and complex PER‐ASMs interactions were observed. Notably, the reference range, that is, 180.0‐610.0 ng/mL, for routine PER monitoring may be more applicable for them. Routine TDM should be considered a positive attempt to manage the effectiveness and safety of PER. [ABSTRACT FROM AUTHOR]

Octopamine (OA) is structurally and functionally similar to adrenaline/noradrenaline in vertebrates, and OA modulates diverse physiological and behavioral processes in invertebrates. OA exerts its actions by binding to specific octopamine receptors (OARs). Functional and pharmacological characterization of OARs have been investigated in several insects. However, the literature on OARs is scarce for parasitoids. Here we cloned three β-adrenergic-like OARs (CcOctβRs) from Cotesia chilonis. CcOctβRs share high similarity with their own orthologous receptors. The transcript levels of CcOctβRs were varied in different tissues. When heterologously expressed in CHO-K1 cells, CcOctβRs induced cAMP production, and were dose-dependently activated by OA, TA and putative octopaminergic agonists. Their activities were inhibited by potential antagonists and were most efficiently blocked by epinastine. Our study offers important information about the molecular and pharmacological properties of β-adrenergic-like OARs from C. chilonis that will provide the basis to reveal the contribution of individual receptors to the physiological processes and behaviors in parasitoids. [ABSTRACT FROM AUTHOR]

The importance of anti‐HLA antibodies in transplantation settings, such as HLA‐mismatched or haploidentical hematopoietic stem cell transplantation and platelet refractoriness, is widely recognized. In previous reports, it was mentioned that several cut‐off values of donor‐specific anti‐HLA antibodies mean fluorescence intensity (MFI) were related to graft rejection in the environment of HLA mismatched stem cell transplantation and the aim of this study was to investigate the prevalence and risk factors of anti‐HLA antibodies according to those cut‐off values of MFI. A total of 3805 patients with hematologic disease were prospectively enrolled and analyzed. When using MFI of anti‐HLA antibodies ≥500, ≥1000, ≥1500, ≥2000, ≥5000, and ≥ 10,000 as cut‐off values for positivity, the prevalence of class I or II anti‐HLA antibodies ranged from 4.6% to 20.2% in all cases. When the MFI cut‐off value was ≥500 for positivity, multivariate analysis indicated that platelet transfusion, underlying disease, and pregnancy were the most important risk factors for the presence of anti‐HLA antibodies for the total patients. Subgroup analysis according to age, gender, and underlying disease showed that pregnancy was the most important risk factor for the presence of anti‐HLA antibodies. For all patients (n = 3805), when anti‐HLA antibody positivity was defined according to different MFI cut‐off values, including ≥1000, ≥1500, ≥2000, ≥5000, and ≥ 10,000, an association of platelet transfusion and pregnancy with anti‐HLA antibodies was also demonstrated. Our results suggest that pregnancy and platelet transfusion are the main risk factors for the prevalence of anti‐HLA antibodies in haploid allograft candidates, providing evidence for guiding the evaluation of anti‐HLA antibodies and helping donor selection for HLA‐mismatched transplant candidates. [ABSTRACT FROM AUTHOR]

Acupuncture is an ancient therapeutic method based on the theory of Chinese medicine (CM). Traditional acupuncture has many limitations; it is subjective and relies more on the experience of an acupuncturist, and the efficacy is sometimes irreproducible. In contrast, electroacupuncture (EA) has special characteristics in terms of objectivity and stability, thereby gaining considerable attention. Parameter setting plays a crucial role in EA practice. The current paper summarizes the current situation and limitations of parameter setting in EA practice. Objectification is the tendency and future of CM as well as EA. With the development of computerized technologies, such as wearable sensors, vast data, and artificial intelligence, CM syndromes can be successfully objectified. We propose the development of a novel self-feedback-adjust EA system, which may improve the parameter setting in EA and be beneficial to both the patients and clinicians. [ABSTRACT FROM AUTHOR]

Oxidative coupling of 2-methylquinolines with quinoxalines via a TBHP (t -butyl hydroperoxide) and TFA (trifluoroacetic acid) mediated Minisci reaction affords quinolin-2-yl(quinoxalin-2-yl)methanone derivatives. This approach provides a simple and efficient method to construct various acyl derivatives in moderate to good yields (45%–92%) without any metal catalyst. Mechanistically, homolytic aromatic substitution (HAS) of acyl radicals mediated by TBHP is crucial for the construction of the quinolin-2-yl(quinoxalin-2-yl)methanone products. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effects of home‐based telerehabilitation based on the Internet‐based rehabilitation management system on hip function, activities of daily living and somatic integrative ability of elderly postoperative hip fracture patients. Methods: From June 2020 to November 2020, we recruited 58 elderly postoperative hip fracture patients and randomly assigned them to the telephone group (n = 29) and the telerehabilitation group (n = 29). Both groups received routine discharge instructions, and the former received telephone follow‐up after discharge, while the latter received remote rehabilitation based on the Internet‐based rehabilitation management system. The Harris hip score (HHS), functional independence measure (FIM), timed up‐and‐go test (TUG), and short physical performance battery (SPPB) were used to evaluate the patients' hip function, activities of daily living, and overall somatic ability. Results: There was no significant difference between the baseline data of the two groups before the intervention (P > 0.05); no matter after hip replacement or internal fixation, the HHS score and FIM score of both groups increased gradually with the postoperative time, and the scores in the telerehabilitation group were higher than those in the telephone group at 1 and 3 months after the intervention, and the difference was significant (P < 0.05); for patients after hip replacement, the TUG and SPPB scores in the telerehabilitation group were better than those in the telephone group at 3 months after the intervention, and the difference was significant (P < 0.05). Conclusions: The Internet‐based rehabilitation management system applied to postoperative home rehabilitation of elderly hip fracture patients can improve the functional recovery of the hip joint and enhance the ability to perform activities of daily living and somatic integration to a certain extent. This seems to provide an effective option for conducting home rehabilitation. [ABSTRACT FROM AUTHOR]