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Hong-Li Wu,1 Bater Hurile,1 Zhi-Peng Li,1 Hong-Wei Zhao2 1Department of Cardiology, The Affiliated Hospital of Inner Mongolia Minzu University, Tongliao, People’s Republic of China; 2Department of Cardiology, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, People’s Republic of ChinaCorrespondence: Hong-Wei Zhao, Email zhaohongwei@sysush.comBackground: As a nutritional indicator, a lower level of geriatric nutritional risk index (GNRI) has been suggested as a predictor for poor prognosis in acute coronary syndrome (ACS). However, whether GNRI could improve the predictive value of the Global Registry of Acute Coronary Events (GRACE) score for the prognosis in elderly patients with non-ST segment elevation myocardial infarction (NSTEMI) after PCI remains unclear.Methods: A total of 446 elderly patients with NSTEMI after percutaneous coronary intervention (PCI) were consecutively enrolled. Patients were divided into major adverse cardiovascular and cerebrovascular events (MACCE) group and control group according to the occurrence of MACCE during one year follow up. The clinical parameters including GNRI were compared to investigate the predictors for MACCE. The performance after the addition of GNRI to the GRACE score for predicting MACCE was determined.Results: A total of 68 patients developed MACCE. In unadjusted analyses, the rate of MACCE was significantly higher in the 93.8

Xiao Xia Guo,1,* Hong Li Wu,2,* Hong Yun Shi,3 Lei Su,3 Xi Zhang3 1Department of Obstetrics and Gynecology, Sichuan Academy of Medical Sciences, Sichuan Provincial People’s Hospital, Chengdu, 2Department of Obstetrics and Gynecology, Hebei University Affiliated Hospital, 3Department of Radiation Oncology, Hebei University Affiliated Hospital, Baoding, China *These authors contributed equally to this work Purpose: PARP inhibition is an exciting new anticancer strategy. As the first PARP inhibitor approved for the treatment of advanced BRCA-mutated ovarian cancer, olaparib has proven to be effective in the treatment of several solid tumors. We performed a meta-analysis of published randomized controlled trials to evaluate the efficacy and safety of olaparib in cancer patients. Methods: PubMed, Embase, and oncology-conference proceedings were searched for relevant studies. End points were overall survival (OS), progression-free survival (PFS), overall response rate (ORR), and grade 3/4 adverse events. Pooled hazard ratio (HR)/risk ratio (RR) and 95% CI were calculated using random or fixed-effect models. Results: Eight trials involving 1,957 patients were ultimately identified. The pooled analysis demonstrated that olaparib treatment significantly improved PFS (HR 0.62, 95% CI 0.47–0.82; P=0.001), OS (HR 0.82, 95% CI 0.73–0.93; P=0.001), and ORR (RR 1.38, 95% CI 1.16–1.65; P

Fang Yang,1 Ka-Hing Wong,2 Yufeng Yang,3 Xiaoling Li,1 Jie Jiang,1 Wenjie Zheng,1 Hualian Wu,1 Tianfeng Chen1 1Department of Chemistry, Jinan University, Guangzhou, People’s Republic of China; 2Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hong Kong, People’s Republic of China; 3Institute of Hydrobiology, College of Life Science and Technology, Jinan University, Guangzhou, People’s Republic of China Abstract: Tellurium-containing phycocyanin (Te-PC) and allophycocyanin (Te-APC), two organic tellurium (Te) species, were purified from tellurium-enriched Spirulina platensis by a fast protein liquid chromatographic method. It was found that the incorporation of Te into the peptides enhanced the antioxidant activities of both phycobiliproteins. With fractionation by ammonium sulfate precipitation and hydroxylapatite chromatography, Te-PC and Te-APC could be effectively separated with high purity, and Te concentrations were 611.1 and 625.3 µg g-1 protein in Te-PC and Te-APC, respectively. The subunits in the proteins were identified by using MALDI-TOF-TOF mass spectrometry. Te incorporation enhanced the antioxidant activities of both phycobiliproteins, as examined by 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid assay. Moreover, Te-PC and Te-APC showed dose-dependent protection on erythrocytes against the water-soluble free radical initiator 2,2'-azo(2-asmidinopropane)dihydrochloride-induced hemolysis. In the hepatoprotective model, apoptotic cell death and nuclear condensation induced by tert-butyl hydroperoxide in HepG2 cells was significantly attenuated by Te-PC and Te-APC. Taken together, these results suggest that Te-PC and Te-APC are promising Te-containing proteins with application potential for treatment of diseases related to oxidative stress. Keywords: tellurium, phycocyanin, allophycocyanin, purification, antioxidant activity

Macroautophagy/autophagy activation in renal tubular epithelial cells protects against acute kidney injury (AKI). However, the role of immune cell autophagy, such as that involving macrophages, in AKI remains unclear. In this study, we discovered that macrophage autophagy was an adaptive response during AKI as mice with macrophage-specific autophagy deficiency ( atg5 -/- ) exhibited higher serum creatinine, more severe renal tubule injury, increased infiltration of ADGRE1/F4/80 + macrophages, and elevated expression of inflammatory factors compared to WT mice during AKI induced by either LPS or unilateral ischemia-reperfusion. This was further supported by adoptive transfer of atg5 -/- macrophages, but not WT macrophages, to cause more severe AKI in clodronate liposomes-induced macrophage depletion mice. Similar results were also obtained in vitro that bone marrow-derived macrophages (BMDMs) lacking Atg5 largely increased pro-inflammatory cytokine expression in response to LPS and IFNG. Mechanistically, we uncovered that atg5 deletion significantly upregulated the protein expression of TARM1 (T cell-interacting, activating receptor on myeloid cells 1), whereas inhibition of TARM1 suppressed LPS- and IFNG-induced inflammatory responses in atg5 -/- RAW 264.7 macrophages. The E3 ubiquitin ligases MARCHF1 and MARCHF8 ubiquitinated TARM1 and promoted its degradation in an autophagy-dependent manner, whereas silencing or mutation of the functional domains of MARCHF1 and MARCHF8 abolished TARM1 degradation. Furthermore, we found that ubiquitinated TARM1 was internalized from plasma membrane into endosomes, and then recruited by the ubiquitin-binding autophagy receptors TAX1BP1 and SQSTM1 into the autophagy-lysosome pathway for degradation. In conclusion, macrophage autophagy protects against AKI by inhibiting renal inflammation through the MARCHF1- and MARCHF8-mediated degradation of TARM1.

Background: To explore the most effective adjuvant chemotherapy regimen for malignant peritoneal mesothelioma (MPM) through patient derived tumor-like cell clusters (PTC) drug sensitivity test., Methods: PTC were cultured in vitro with intraoperative specimens, and drug sensitivity test was performed to calculate the most effective chemotherapy regimen for MPM. The patients were divided into conventional and individualized chemotherapy group according to whether they received PTC drug testing. Univariate and multivariate analyses were conducted to identify independent prognostic factors., Results: Among 186 MPM patients included, 63 underwent PTC culture and drug sensitivity test. The results showed that the most effective chemotherapy regimen was oxaliplatin + gemcitabine. After propensity score matching, a total of 64 patients were enrolled in the following study, including 32 patients receiving individualized chemotherapy guided by PTC drug results as group 1 and 32 patients receiving conventional chemotherapy as group 2. Survival analysis showed that the median OS of group 1 was not reached, significantly longer than that of group 2 (23.5 months) (p < 0.05)., Conclusions: Compared with conventional chemotherapy, individualized chemotherapy guided by PTC drug sensitivity tests can prolong patient survival, and oxaliplatin + gemcitabine + apatinib could be the optimal adjuvant treatment regimen for MPM., (© 2024 Wiley Periodicals LLC.)

Manipulating electronic polarizations such as ferroelectric or spin polarizations has recently emerged as an effective strategy for enhancing the efficiency of photocatalytic reactions. This study demonstrates the control of electronic polarizations modulated by ferroelectric and magnetic approaches within a two-dimensional (2D) layered crystal of copper indium thiophosphate (CuInP 2 S 6 ) to boost the photocatalytic reduction of CO 2 . We investigate the substantial influence of ferroelectric polarization on the photocatalytic CO 2 reduction efficiency, utilizing the ferroelectric-paraelectric phase transition and polarization alignment through electrical poling. Additionally, we explore enhancing the CO 2 reduction efficiency by harnessing spin electrons through the synergistic introduction of sulfur vacancies and applying a magnetic field. Several advanced characterization techniques, including piezoresponse force microscopy, ultrafast pump-probe spectroscopy, in situ X-ray absorption spectroscopy, and in situ diffuse reflectance infrared Fourier transformed spectroscopy, are performed to unveil the underlying mechanism of the enhanced photocatalytic CO 2 reduction. These findings pave the way for manipulating electronic polarizations regulated through ferroelectric or magnetic modulations in 2D layered materials to advance the efficiency of photocatalytic CO 2 reduction.

Objectives: To compare the success and complication rates of radial artery catheterization using ultrasound guidance versus the conventional palpation technique in obese patients by anesthesia residents with similar levels of experience in both methods, and to measure the skin-to-artery distance of radial, brachial, and dorsalis pedis arteries using ultrasound with standardized anatomic landmarks., Design: Prospective, randomized controlled trial SETTING: Single tertiary center PARTICIPANTS: Eighty adults with a body mass index (BMI) ≥30 kg/m 2 INTERVENTIONS: Ultrasound guidance or conventional palpation method MEASUREMENTS AND MAIN RESULTS: The primary outcome was the first-attempt success rate of arterial catheterization. The skin-to-artery distance of the radial artery was significantly greater in the BMI groups of 40 to 49 kg/m 2 and ≥50 kg/m 2 compared to the BMI group of 30 to 39 kg/m 2 (mean difference, 1.0 mm; 95% confidence interval [CI], 0.4-1.7; p = 0.0029) for BMI 40-49 kg/m 2 vs 30-39 kg/m 2 and 1.5 mm (95% CI, 0.6-2.4 mm; p = 0.0015) for ≥50 kg/m 2 vs 30-39 kg/m 2 . Similar findings were observed for the brachial artery. BMI was inversely associated with first-attempt success rates (p = 0.0145) and positively with time to successful catheterization (p = 0.0271). The first-attempt success and vascular complication rates of catheterization did not differ significantly between the ultrasound guidance group (65.0% and 52.5%, respectively) and the conventional palpation group (70.0% [p = 0.6331] and 57.5% [p = 0.6531], respectively)., Conclusion: The results of this study do not support the routine use of ultrasonography during radial arterial catheterizations for obese adults when junior practitioners perform the procedure., 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.)

Objective: Our aim is to explore the value of intraoperative facial motor evoked potentials (FMEP) for facial outcomes in cerebellopontine angle (CPA) tumor surgery to provide an evidence-based consensus standard for future clinical practice and prospective studies., Methods: Electronic databases were searched from inception to June 2023. Study quality was assessed with the QUADAS-2 tool. Bivariate and random-effects models for meta-analysis and meta-regression generated summary receiver operating characteristic curves (ROC) and forest plots for estimates of sensitivity and specificity., Results: We included 17 studies (1,206 participants). Sensitivity was lower in the immediate (IM) post-operative (0.76, 95% CI 0.65-0.84) compared to follow-up (FU) period (0.82, 95% CI 0.74-0.88) while specificity was similar in both groups (IM, 0.94, 95% CI 0.89-0.97; FU, 0.93, 95% CI 0.87-0.96). Data driven estimates improved FMEP performance but require confirmation from future studies. Amplitude cutoff criteria and studies that scored new deficits as worse than House-Brackmann (HB) grade 2 yielded best sensitivities., Conclusions: FMEP demonstrated statistically significant accuracy for facial function monitoring. Implementation of FMEPs varied widely across studies., Significance: Our study is the first systematic review with meta-analysis to demonstrate that intraoperative FMEP is valuable in CPA tumor surgery for facial outcomes. Meta-regression identified the methods that were most useful in the application of FMEPs., Competing Interests: Conflict of interest The authors declare that they have no conflict of interest., (Copyright © 2024. Published by Elsevier B.V.)

Malignant peritoneal mesothelioma (MPeM) is a rare primary malignant tumor originating from peritoneal mesothelial cells. Insufficient specificity of the symptoms and their frequent reappearance following surgery make it challenging to diagnose, creating a need for more efficient treatment options. Natural killer cells (NK cells) are part of the innate immune system and are classified as lymphoid cells. Under the regulation of activating and inhibiting receptors, NK cells secrete various cytokines to exert cytotoxic effects and participate in antiforeign body, antiviral, and antitumor activities. This review provides a comprehensive summary of the specific alterations observed in NK cells following MPeM treatment, including changes in cell number, subpopulation distribution, active receptors, and cytotoxicity. In addition, we summarize the impact of various therapeutic interventions, such as chemotherapy, immunotherapy, and targeted therapy, on NK cell function post-MPeM treatment.

Purpose: The prognostic value of lymphocyte infiltration score (LIS) and its nearest neighbor distance to tumor cells (NNDTC) in giant cell tumor of bone (GCTB) is currently not well established. This study aims to characterize LIS and NNDTC and examine their correlation with denosumab treatment responsiveness, clinicopathologic features, and patient prognosis., Methods: Using multiplexed quantitative immunofluorescence, LIS was evaluated in 253 tumor specimens, whereas NNDTC was computed using HALO software. Subsequently, we analyzed the association of these parameters with patient outcomes (progression-free survival [PFS] and overall survival [OS]), clinicopathologic features, and denosumab treatment responsiveness., Results: Low LIS was indicative of both poor PFS and OS (both P < .001). In addition, LIS was significantly associated with sex ( P = .046), Enneking staging ( P < .001), Ki-67 expression ( P = .007), and denosumab treatment responsiveness ( P = .005). Lower CD8 + (tumor interior [TI]) NNDTC, and CD3 + (TI) NNDTC were associated with worse PFS ( P = .003 and .038, respectively), whereas lower CD8 + (TI) NNDTC was associated with worse OS ( P = .001), but CD8 + (tumor infiltrating margin) NNDTC had the opposite effect ( P = .002). Moreover, NNDTC showed a correlation with several clinicopathologic features. Importantly, LIS outperformed Enneking and Campanacci staging systems in predicting the clinical outcomes of GCTB., Conclusion: These findings suggest that LIS is a reliable predictive tool for clinically relevant outcomes and response to denosumab therapy in patients with GCTB. These parameters may prove to be useful in guiding prognostic risk stratification and therapeutic optimization for patients.

The lack of intrinsic active sites for photocatalytic CO 2 reduction reaction (CO 2 RR) and fast recombination rate of charge carriers are the main obstacles to achieving high photocatalytic activity. In this work, a novel phosphorus and boron binary-doped graphitic carbon nitride, highly porous material that exhibits powerful photocatalytic CO 2 reduction activity, specifically toward selective CO generation, is disclosed. The coexistence of Lewis-acidic and Lewis-basic sites plays a key role in tuning the electronic structure, promoting charge distribution, extending light-harvesting ability, and promoting dissociation of excitons into active carriers. Porosity and dual dopants create local chemical environments that activate the pyridinic nitrogen atom between the phosphorus and boron atoms on the exposed surface, enabling it to function as an active site for CO 2 RR. The P-N-B triad is found to lower the activation barrier for reduction of CO 2 by stabilizing the COOH reaction intermediate and altering the rate-determining step. As a result, CO yield increased to 22.45 µmol g -1  h -1 under visible light irradiation, which is ≈12 times larger than that of pristine graphitic carbon nitride. This study provides insights into the mechanism of charge carrier dynamics and active site determination, contributing to the understanding of the photocatalytic CO 2 RR mechanism., (© 2024 Wiley‐VCH GmbH.)

Aim: To prospectively assess the value of a test bolus of diluted contrast medium (CM) combined with a personalized contrast protocol in craniocervical computed tomography angiography (cc-CTA) with low radiation and CM doses., Materials and Methods: Eighty-six consecutive subjects were divided into two groups at random (43 in each one): group A: 100/Sn140 kVp, filtered back-projection reconstruction, iopromide (370 mgI/ml) 50 ml; group B: 80/Sn140 kVp, iterative reconstruction, iodixanol (270 mgI/ml). In group B, the test bolus contained 27 ml of diluted CM, a personalized protocol with low-concentration CM was used for angiography, and the test bolus injection duration in angiography remained the same. Artery values over 200 Hounsfield units were considered significant., Results: Image quality for all cases was found to be diagnostic. No significant differences were found in the arterial densities of the ascending aorta or basilar artery between the groups. The values of the common carotid artery, internal carotid artery, and middle cerebral artery in group B were significantly lower. The effective dose and average iodine uptake were significantly lower in group B., Conclusion: With double-low-dose cc-CTA, test bolus scanning based on diluted CM combined with a personalized contrast protocol can yield diagnostic-quality images and significantly reduce the radiation and CM doses., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Malignant peritoneal mesothelioma (MPM) is a rare and invasive tumor, and some patients will develop paraneoplastic syndrome (PS) during the course of the disease. This review summarizes PS associated with MPM, focusing on the clinical characteristics and treatment progress in hematological, endocrine, rheumatic, neurological, urinary, and other systems to decrease missed diagnosis and misdiagnosis, help early diagnosis and prompt treatment, and provide guidance for the clinical decision-making of this kind of patients., (© 2024 Wiley Periodicals LLC.)

Persicae Semen (Taoren), the seed of mature peaches consumed as both food and medicine, is native to the temperate regions of China, distributed in the provinces of North and East China, and currently cultivated worldwide. The primary components of Persicae Semen include volatile oil, protein, amino acids, amygdalin, and prunasin, all of which have pharmacological properties, such as anti-inflammatory, antioxidant, and immune regulatory effects, and are clinically used in the treatment of gynecological, cardiovascular, cerebrovascular, orthopedic, and digestive system diseases. This review provides a comprehensive perspective on the resource status, ethnopharmacology, phytochemistry, pharmacology, and toxicology, as well as the trend of Persicae Semen patent, global distribution, and clinical applications. This review will help facilitate the development and utilization of Persicae Semen in clinical settings., (© 2024. The Chinese Journal of Integrated Traditional and Western Medicine Press and Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Currently, there is limited understanding regarding the clinical significance of the tumor-stroma ratio (TSR) in giant cell tumor of bone (GCTB). Hence, we aimed to investigate the distribution of TSR in GCTB and explore its correlation with various clinicopathologic factors, immune microenvironment, survival prognosis, and denosumab treatment responsiveness., Methods: We conducted a multicenter cohort study comprising 426 GCTB patients treated at four centers. TSR was evaluated on hematoxylin and eosin-stained and immunofluorescent sections of tumor specimens. Immunohistochemistry was performed to assess CD3+, CD4+, CD8+, CD20+, PD-1+, PD-L1+, and FoxP3+ TIL subtypes as well as Ki-67 expression levels in 426 tissue specimens. These parameters were then analyzed for their correlations with patient outcomes [local recurrence-free survival (LRFS) and overall survival (OS)], clinicopathological features, and denosumab treatment responsiveness., Results: Low TSR was significantly associated with poor LRFS and OS in both cohorts. Furthermore, TSR was also correlated with multiple clinicopathological features, TIL subtype expression, and denosumab treatment responsiveness. TSR demonstrated similar predictive capabilities as the conventional Campanacci staging system for predicting patients' LRFS and OS., Conclusion: The results of this study provide evidence supporting the use of TSR as a reliable prognostic tool in GCTB and as a predictor of denosumab treatment responsiveness. These findings may aid in developing individualized treatment strategies for GCTB patients in the future., (© 2024. The Author(s).)

The accurate construction of mono-, bi- and multi-layer networks has been an important challenge, especially for bi- and multi-layer networks. Monolayer, bilayer, sandwich bilayer, four-layer, and multi-layer two-dimensional pillararene-type metal-organic coordination networks have been constructed from functionalized pillar[5]arene and pillar[6]arene by utilizing the coordination interaction of cobalt and copper ions and combining with temperature control and guest induction. These two-dimensional coordination networks exhibit the excellent plasticity of pillararenes and structural variety, which are characterized by X-ray single crystal diffraction and PXRD, confirming that pillararenes units can function as excellent tunable scaffolds for structural regulation. Two-dimensional chiral double-layer structure products are also constructed from R - and S -pillar[6]arene, which are obtained by high-performance liquid chromatography. Atomic force microscopic imaging confirms the thicknesses of these networks. Moreover, these networks also exhibit high iodine adsorption capacity in aqueous environments at ambient temperature. The monolayer, bilayer, sandwich bilayer, four-layer and multi-layer structures of the pillararene-type networks represent a new facile supramolecular self-assembly strategy and platform for designing more mono-, bi- and multi-layer two-dimensional nanomaterials and chiral two-dimensional double-layer structures provide a new method for the construction of more two-dimensional chiral polymers., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Tumor endothelial marker 1 (TEM1), an activated mesenchymal cell marker, is implicated in tissue remodeling and repair. Herein, we investigated the role and therapeutic implications of TEM1 in abdominal aortic aneurysm (AAA), a potentially life-threatening aortic disease characterized by vascular inflammation and matrix turnover. Characterization of human AAA revealed increased TEM1 expression derived mainly from medial vascular smooth muscle cells (VSMCs) and adventitial fibroblasts. Bioinformatics analysis demonstrated the association between TEM1-expressing VSMCs and fibroblasts and collagen gene expression. Consistently, collagen content and TEM1 expressed by VSMCs and fibroblasts were increased during CaCl 2 -induced AAA formation in mice. TEM1 silencing in VSMCs and fibroblasts inhibited transforming growth factor-β1-induced phenotypic change, SMAD2 phosphorylation, and COL1A1 gene expression. Also, Tem1 deficiency reduced collagen synthesis and exacerbated CaCl 2 -induced AAA formation in mice without disturbing elastin destruction and inflammatory responses. In contrast, rTEM1 promoted phenotypic change and COL1A1 gene expression through SMAD2 phosphorylation in VSMCs and fibroblasts. Treatment with rTEM1 enhanced collagen synthesis, attenuated elastin fragmentation, and inhibited CaCl 2 -induced and angiotensin II-infused AAA formation. In summary, TEM1 in resident stromal cells regulates collagen synthesis to counteract aortic wall failure during AAA formation. Matrix integrity restored by rTEM1 treatment may hold therapeutic potential against AAA., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

A six-cyclic crown ether-type pillar[5]arene was synthesized, and the five ethylene oxide loops were located outside the cavity and not affected by temperature changes which was confirmed by variable-temperature NMR experiment in DMSO-d6 and CDCl 3 and 2D 1 H- 1 H NOESY experiment in CDCl 3 . The six-cyclic pillar[5]-crown also showed greater binding ability of host-guest with bis(pyridinium) derivatives than conventional alkoxy pillar[5]arenes that illustrated through 1 H NMR titration spectroscopic experiment in acetone-d6/CDCl 3 (1 : 1) and UV-vis titration experiments in CHCl 3 at room temperature. The five benzocrown ethers at the periphery were able to bind metal cations by 1 H NMR titration spectroscopic experiment in CD 2 Cl 2 /methanol-d4(9 : 1)., (© 2024 Wiley-VCH GmbH.)

Background: The present study aims to determine the impact of different cuff diameters on the cuff pressure of endotracheal tubes (ETTs) when the trachea is adequately sealed., Methods: In the present single-center clinical trial, adult patients who underwent cardiothoracic surgery were assigned to use ETTs from 2 brands (GME and GZW). The primary endpoint comprised of the following: cuff diameter, inner diameter of the ETT, manufacturer, and the number of subjects with tracheal leakage when the cuff pressure was 30 cm H2O., Results: A total of 298 patients were assigned into 2 groups, based on the 2 distinct brands of ETTs: experimental group (n = 122, GME brand) and control group (n = 176, GZW brand). There were no significant differences in baseline characteristics. However, the cuff diameter was significantly smaller in the control group, when compared to the experimental group (P = .001), and the incidence of tracheal leakage was significantly higher in the control group (P = .001). Furthermore, the GME brand ETT had a significantly larger cuff diameter, when compared to the GZW brand ETT., Conclusion: The cuff size would mismatch the tracheal area in clinical practice. Therefore, chest computed tomography is recommended to routinely evaluate the tracheal cross-sectional area during anesthesia, in order to ensure the appropriate cuff size selection., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Effective representation of molecules is a crucial factor affecting the performance of artificial intelligence models. This study introduces a flexible, fragment-based, multiscale molecular representation framework called t-SMILES (tree-based SMILES) with three code algorithms: TSSA (t-SMILES with shared atom), TSDY (t-SMILES with dummy atom but without ID) and TSID (t-SMILES with ID and dummy atom). It describes molecules using SMILES-type strings obtained by performing a breadth-first search on a full binary tree formed from a fragmented molecular graph. Systematic evaluations using JTVAE, BRICS, MMPA, and Scaffold show the feasibility of constructing a multi-code molecular description system, where various descriptions complement each other, enhancing the overall performance. In addition, it can avoid overfitting and achieve higher novelty scores while maintaining reasonable similarity on labeled low-resource datasets, regardless of whether the model is original, data-augmented, or pre-trained then fine-tuned. Furthermore, it significantly outperforms classical SMILES, DeepSMILES, SELFIES and baseline models in goal-directed tasks. And it surpasses state-of-the-art fragment, graph and SMILES based approaches on ChEMBL, Zinc, and QM9., (© 2024. The Author(s).)

Over the past two decades, metronomic chemotherapy has gained considerable attention and has demonstrated remarkable success in the treatment of cancer. Through chronic administration and low-dose regimens, metronomic chemotherapy is associated with fewer adverse events but still effectively induces disease control. The identification of its antiangiogenic properties, direct impact on cancer cells, immunomodulatory effects on the tumour microenvironment, and metabolic reprogramming ability has established the intrinsic multitargeted nature of this therapeutic approach. Recently, the utilization of metronomic chemotherapy has evolved from salvage treatment for metastatic disease to adjuvant maintenance therapy for high-risk cancer patients, which has been prompted by the success of several substantial phase III trials. In this review, we delve into the mechanisms underlying the antitumour effects of metronomic chemotherapy and provide insights into potential combinations with other therapies for the treatment of various malignancies. Additionally, we discuss health-economic advantages and candidates for the utilization of this treatment option., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Aim: The commonly recommended endotracheal tube cuff pressure is 20-30 cmH 2 O. However, some patients require a cuff pressure of >30 cmH 2 O to prevent air leakage. The study aims to determine the risk factors that contribute to the endotracheal tube cuff pressure of >30 cmH 2 O to prevent air leakage., Design: A multi-centre prospective observational study., Methods: Eligible patients undergoing mechanical ventilation in the intensive care unit of three hospitals between March 2020 and July 2022 were included. The endotracheal tube cuff pressure to prevent air leakage was determined using the minimal occlusive volume technique. The patient demographics and clinical information were collected., Results: A total of 284 patients were included. Among these patients, 55 (19.37%) patients required a cuff pressure of >30 cmH 2 O to prevent air leakage. The multivariate logistic regression results revealed that the surgical operation (odds ratio [OR]: 8.485, 95% confidence interval [CI]: 1.066-67.525, p = 0.043) was inversely associated with the endotracheal tube cuff pressure of >30 cmH 2 O, while the oral intubation route (OR: 0.127, 95% CI: 0.022-0.750, p = 0.023) and cuff inner diameter minus tracheal area (OR: 0.949, 95% CI: 0.933-0.966, p < 0.001) were negatively associated with the endotracheal tube cuff pressure of >30 cmH 2 O. Therefore, a significant number of patients require an endotracheal tube cuff pressure of ＞30 cmH 2 O to prevent air leakage. Several factors, including the surgical operation, intubation route, and difference between the cuff inner diameter and tracheal area at the T3 vertebra, should be considered when determining the appropriate cuff pressure during mechanical ventilation., (© 2024 The Author(s). Nursing Open published by John Wiley & Sons Ltd.)

Objective: To evaluate the short-term outcomes of all-inside endoscopic running locked stitch technique for acute Achilles tendon ruptures. Methods: This is a retrospective case series study. Forty-eight cases with acute Achilles tendon rupture were treated with the all-inside endoscopic running locked stitch technique from April 2020 to March 2022 at Department of Orthopaedics, General Hospital of Central Theater Command. There were 44 males and 4 females, aged (34.8±7.4) years (range: 24 to 50 years). Body mass index was (21.2±2.4)kg/m 2 (range: 18 to 26 kg/m 2 ); There were 29 cases (60.4%) on the left side and 19 cases (39.6%) on the right side. Under endoscopic control, the proximal tendon stumps were stitched with the running locked method using a semi-automatic flexible suture passer. The threads of the high-strength suture were grasped through the paratenon sub-space and then fixed into calcaneal insertion with a knotless anchor. MRI of Achilles tendon was performed to observe the regeneration of Achilles tendon during follow-up. Surgical time and complications were assessed. Achilles tendon total rupture score (ATRS), Achilles tendon resting angle, and heel rise height were utilized to evaluate final clinical outcomes. The differences of bilateral limbs were compared using the paired sample t test. Results: The follow-up time was (24.1±3.5)months (range:18 to 32 months). Appropriate tendon regeneration was observed on MRI at 12 months after operation. The median ATRS score ( M (IQR)) was 95.0 (4.7) points. Furthermore, there was no significant difference between the injured and contralateral side in the Achilles tendon resting angle ((17.1±2.4)° vs . (17.4±2.6)°, t =1.92, P =0.062) and heel rise height ((14.2±1.7)cm vs . (14.4±1.5)cm, t =1.71, P =0.094). No nerve injury, infection, deep vein thrombosis and re-rupture was encountered. Sports activity resumed six months postoperative in 46 patients. One patient had a slight anchor cut-out, due to an addition injury, which was removed after 5 months. Conclusions: All-inside endoscopic running locked stitch technique for acute Achilles tendon ruptures shows promising results. It provides stable connection of the tendon stumps with a low risk of complications.

Background & Aims: HBV expresses more than 10 spliced RNAs from the viral pregenomic RNA, but their functions remain elusive and controversial. To address the function of HBV spliced RNAs, we generated splicing-deficient HBV mutants and conducted experiments to assess the impact of these mutants on HBV infection., Methods: HepG2-NTCP cells, human hepatocyte chimeric FRG mice (hu-FRG mice), and serum from patients with chronic hepatitis B were used for experiments on HBV infection. Additionally, SHifter assays and cryo-electron microscopy were performed., Results: We found the infectivity of splicing-deficient HBV was decreased 100-1,000-fold compared with that of wild-type HBV in hu-FRG mice. Another mutant, A487C, which loses the most abundant spliced RNA (SP1), also exhibits severely impaired infectivity. SP1 hypothetically encodes a novel protein HBc SP1 (HBc -Cys ) that lacks the C-terminal cysteine from full-length HBc. In the SHifter assay, HBc SP1 was detected in wild-type viral particles at a ratio of about 20-100% vs. conventional HBc, as well as in the serum of patients with chronic hepatitis B, but not in A487C particles. When infection was conducted with a shorter incubation time of 4-8 h at lower PEG concentrations in HepG2-NTCP cells, the entry of the A487C mutant was significantly slower. SP1 cDNA complementation of the A487C mutant succeeded in rescuing its infectivity in hu-FRG mice and HepG2-NTCP cells. Moreover, cryo-electron microscopy revealed a disulfide bond between HBc cysteine 183 and 48 in the HBc intradimer of the A487C capsid, leading to a locked conformation that disfavored viral entry in contrast to the wild-type capsid., Conclusions: Prior studies unveiled the potential integration of the HBc -Cys protein into the HBV capsid. We confirmed the proposal and validated its identity and function during infection., Impact and Implications: HBV SP1 RNA encodes a novel HBc protein (HBc SP1 ) that lacks the C-terminal cysteine from conventional HBc (HBc -Cys ). HBc SP1 was detected in cell culture-derived HBV and confirmed in patients with chronic infection by both immunological and chemical modification assays at 10-50% of capsid. The splicing-deficient mutant HBV (A487C) impaired infectivity in human hepatocyte chimeric mice and viral entry in the HepG2-NTCP cell line. Furthermore, these deficiencies of the splicing-deficient mutant could be rescued by complementation with the SP1-encoded protein HBc SP1 . We confirmed and validated the identity and function of HBc SP1 during infection, building on the current model of HBV particles., (Copyright © 2024 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Translation is a crucial step in gene expression and plays a vital role in regulating various aspects of plant development and environmental responses. It is a dynamic and complex program that involves interactions between mRNAs, transfer RNAs, and the ribosome machinery through both cis- and trans-regulation while integrating internal and external signals. Translational control can act in a global (transcriptome-wide) or mRNA-specific manner. Recent advances in genome-wide techniques, particularly ribosome profiling and proteomics, have led to numerous exciting discoveries in both global and mRNA-specific translation. In this review, we aim to provide a "primer" that introduces readers to this fascinating yet complex cellular process and provide a big picture of how essential components connect within the network. We begin with an overview of mRNA translation, followed by a discussion of the experimental approaches and recent findings in the field, focusing on unannotated translation events and translational control through cis-regulatory elements on mRNAs and trans-acting factors, as well as signaling networks through 3 conserved translational regulators TOR, SnRK1, and GCN2. Finally, we briefly touch on the spatial regulation of mRNAs in translational control. Here, we focus on cytosolic mRNAs; translation in organelles and viruses is not covered in this review., Competing Interests: Conflict of interest statement: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of American Society of Plant Biologists.)

Cis -hydrobenzofurans, cis -hydroindoles, and cis -hydrindanes, privileged structural motifs found in numerous biologically active natural and synthetic compounds, are efficiently prepared by a Rh(I)-catalyzed cascade syn -arylation/1,4-addition protocol. This approach starts with the regioselective syn -arylation of the alkyne tethered to 2,5-hexadienone moieties, using a chiral Rh(I) catalyst generated in situ from a chiral bicyclo[2.2.1]hepatadiene ligand L4f . By forging two new carbon-carbon bonds and introducing two chiral centers, the resulting alkenylrhodium species undergoes desymmetrization via an intramolecular 1,4-addition reaction, delivering annulated products with high yields and enantioselectivities.

Respiratory syncytial virus (RSV) is one of the most important pathogens causing respiratory tract infection in humans, especially in infants and the elderly. The identification and structural resolution of the potent neutralizing epitopes on RSV fusion (F) protein enable an "epitope-focused" vaccine design. However, the display of RSV F epitope II on the surface of the widely-used human hepatitis B virus core antigen (HBcAg) has failed to induce neutralizing antibody response in mice. Here, we used the hepadnavirus core protein (HcAg) from different mammalian hosts as scaffolds to construct chimeric virus-like particles (VLPs) presenting the RSV F epitope II. Mouse immunization showed that different HcAg-based chimeric VLPs elicited significantly different neutralizing antibody responses, among which the HcAg derived from roundleaf bat (RBHcAg) is the most immunogenic. Furthermore, RBHcAg was used as the scaffold platform to present multiple RSV F epitopes, and the immunogenicity was further improved in comparison to that displaying a single epitope II. The designed RBHcAg-based multiple-epitope-presenting VLP formulated with MF59-like adjuvant elicited a potent and balanced Th1/Th2 immune response, and offered substantial protection in mice against the challenge of live RSV A2 virus. The designed chimeric VLPs may serve as the potential starting point for developing epitope-focused vaccines against RSV. Our study also demonstrated that RBHcAg is an effective VLP carrier for presenting foreign epitopes, providing a promising platform for epitope-focused vaccine design., (© 2024. The Author(s).)

Main Conclusion: The expression peak of VcAP1.4, VcAP1.6, VcAP3.1, VcAP3.2, VcAG3, VcFLC2, and VcSVP9 coincided with the endo-dormancy release of flower buds. Additionally, GA4 +7 not only increased the expression of these genes but also promoted flower bud endo-dormancy release. The MIKC C -type MADS-box gene family is involved in the regulation of flower development. A total of 109 members of the MIKC C -type MADS-box gene family were identified in blueberry. According to the phylogenetic tree, these 109 MIKC C -type MADS-box proteins were divided into 13 subfamilies, which were distributed across 40 Scaffolds. The results of the conserved motif analysis showed that among 20 motifs, motifs 1, 3, and 9 formed the MADS-box structural domain, while motifs 2, 4, and 6 formed the K-box structural domain. The presence of 66 pairs of fragment duplication events in blueberry suggested that gene duplication events contributed to gene expansion and functional differentiation. Additionally, the presence of cis-acting elements revealed that VcFLC2, VcAG3, and VcSVP9 might have significant roles in the endo-dormancy release of flower buds. Meanwhile, under chilling conditions, VcAP3.1 and VcAG7 might facilitate flower bud dormancy release. VcSEP11 might promote flowering following the release of endo-dormancy, while the elevated expression of VcAP1.7 (DAM) could impede the endo-dormancy release of flower buds. The effect of gibberellin (GA 4+7 ) treatment on the expression pattern of MIKC C -type MADS-box genes revealed that VcAP1.4, VcAP1.6, VcAP3.1, VcAG3, and VcFLC2 might promote flower bud endo-dormancy release, while VcAP3.2, VcSEP11, and VcSVP9 might inhibit its endo-dormancy release. These results indicated that VcAP1.4, VcAP1.6, VcAP1.7 (DAM), VcAP3.1, VcAG3, VcAG7, VcFLC2, and VcSVP9 could be selected as key regulatory promoting genes for controlling the endo-dormancy of blueberry flower buds., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The intricate interplay between biomechanical and biochemical pathways in modulating morphogenesis is an interesting research topic. How biomechanical force regulates epithelial cell tubulogenesis remains poorly understood. Here, we established a model of tubulogenesis by culturing renal proximal tubular epithelial cells on a collagen gel while manipulating contractile force. Epithelial cells were dynamically self-organized into tubule-like structures by augmentation of cell protrusions and cell-cell association. Reduction and asymmetric distribution of phosphorylated myosin light chain 2, the actomyosin contractility, in cells grown on soft matrix preceded tube connection. Notably, reducing matrix stiffness via sonication of collagen fibrils and inhibiting actomyosin contractility with blebbistatin promoted tubulogenesis, whereas inhibition of cytoskeleton polymerization suppressed it. CXC chemokine ligand 1 (CXCL1) expression was transcriptionally upregulated in cells undergoing tubulogenesis. Additionally, inhibiting actomyosin contractility facilitated CXCL1 polarization and cell protrusions preceding tube formation. Conversely, inhibiting the CXCL1-CXC receptor 1 pathway hindered cell protrusions and tubulogenesis. Mechanical property asymmetry with cell-collagen fibril interaction patterns at cell protrusions and along the tube structure supported the association of anisotropic contraction with tube formation. Furthermore, suppressing the mechanosensing machinery of integrin subunit beta 1 reduced CXCL1 expression, collagen remodeling, and impaired tubulogenesis. In summary, symmetry breaking of cell contractility on a soft collagen gel promotes CXCL1 polarization at cell protrusions which in turn facilitates cell-cell association and thus tubule connection., Competing Interests: Competing interests statement:The authors declare no competing interest.

A crucial step in functional genomics is identifying actively translated ORFs and linking them to biological functions. The challenge lies in identifying short ORFs, as their identification is greatly influenced by data quality and depth. Here, we improved the coverage of super-resolution Ribo-seq in Arabidopsis (Arabidopsis thaliana), revealing uncharacterized translation events for nuclear, chloroplastic, and mitochondrial genes. Assisted by a transcriptome assembly, we identified 7,751 unconventional translation events, comprising 6,996 upstream ORFs (uORFs) and 209 downstream ORFs on annotated protein-coding genes, as well as 546 ORFs in presumed noncoding RNAs. Proteomic data confirmed the production of stable proteins from some of these unannotated translation events. We present evidence of active translation from primary transcripts of trans-acting small interfering RNAs (TAS1-4) and microRNAs (pri-MIR163 and pri-MIR169) and periodic ribosome stalling supporting cotranslational decay. Additionally, we developed a method for identifying extremely short uORFs, including 370 minimum uORFs (AUG-stop), and 2,921 tiny uORFs (2 to 10 amino acids) and 681 uORFs that overlap with each other. Remarkably, these short uORFs exhibit strong translational repression as do longer uORFs. We also systematically discovered 594 uORFs regulated by alternative splicing, suggesting widespread isoform-specific translational control. Finally, these prevalent uORFs are associated with numerous important pathways. In summary, our improved Arabidopsis translational landscape provides valuable resources to study gene expression regulation., Competing Interests: Conflict of interest statement. None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of American Society of Plant Biologists.)

Broad-spectrum histone deacetylase inhibitors (HDACi) have excellent anti-tumor effects, such as abexinostat, which was a novel oral HDACi that was widely used in clinical treatment. The purpose of this study was to establish a rapid and reliable method for the detection of abexinostat concentrations in rat plasma using ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). The mobile phase we used was acetonitrile and 0.1% formic acid, and the internal standard (IS) was givinostat. Selective reaction monitoring (SRM) was used for detection with ion transitions at m/z 397.93 → 200.19 for abexinostat and m/z 422.01 → 186.11 for givinostat, respectively. The intra-day and inter-day precision of abexinostat were less than 11.5% and the intra-day and inter-day accuracy ranged from - 10.7% to 9.7% using this method. During the analysis process, the stability of the test sample was reliable. In addition, the recovery and matrix effects of this method were within acceptable limits. Finally, the method presented in this paper enabled accurate and quick determination of abexinostat levels in rat plasma from the pharmacokinetic study following gavage at a dose of 8.0 mg/kg abexinostat., (© 2024. The Author(s).)

Temozolomide (TMZ) resistance presents a significant challenge in the treatment of gliomas. Although lysine demethylase 4A (KDM4A) has been implicated in various cancer-related processes, its role in TMZ resistance remains unclear. This study aims to elucidate the contribution of KDM4A to TMZ resistance in glioma cells and its potential implications for glioma prognosis. We assessed the expression of KDM4A in glioma cells (T98G and U251MG) using qRT-PCR and Western blot assays. To explore the role of KDM4A in TMZ resistance, we transfected siRNA targeting KDM4A into drug-resistant glioma cells. Cell viability was assessed using the CCK-8 assay and the TMZ IC50 value was determined. ChIP assays were conducted to investigate KDM4A, H3K9me3, and H3K36me3 enrichment on the promoters of ROCK2 and HUWE1. Co-immunoprecipitation confirmed the interaction between HUWE1 and ROCK2, and we examined the levels of ROCK2 ubiquitination following MG132 treatment. Notably, T98G cells exhibited greater resistance to TMZ than U251MG cells, and KDM4A displayed high expression in T98G cells. Inhibiting KDM4A resulted in decreased cell viability and a reduction in the TMZ IC50 value. Mechanistically, KDM4A promoted ROCK2 transcription by modulating H3K9me3 levels. Moreover, disruption of the interaction between HUWE1 and ROCK2 led to reduced ROCK2 ubiquitination. Inhibition of HUWE1 or overexpression of ROCK2 counteracted the sensitization effect of si-KDM4A on TMZ responsiveness in T98G cells. Our findings highlight KDM4A's role in enhancing TMZ resistance in glioma cells by modulating ROCK2 and HUWE1 transcription and expression through H3K9me3 and H3K36me3 removal., (© 2023 The Authors. The Kaohsiung Journal of Medical Sciences published by John Wiley & Sons Australia, Ltd on behalf of Kaohsiung Medical University.)

Background: Saffron has gained people's attention and love for its unique flavor and valuable edible value, but the problem of saffron adulteration in the market is serious. It is urgent for us to find a simple and rapid identification and quantitative estimation of adulteration in saffron. Therefore, excitation-emission matrix (EEM) fluorescence combined with multi-way chemometrics was proposed for the detection and quantification of adulteration in saffron., Results: The fluorescence composition analysis of saffron and saffron adulterants (safflower, marigold and madder) were accomplished by alternating trilinear decomposition (ATLD) algorithm. ATLD and two-dimensional principal component analysis combined with k-nearest neighbor (ATLD-kNN and 2DPCA-kNN) and ATLD combined with data-driven soft independent modeling of class analogies (ATLD-DD-SIMCA) were applied to rapid detection of adulteration in saffron. 2DPCA-kNN and ATLD-DD-SIMCA methods were adopted for the classification of chemical EEM data, first with 100% correct classification rate. The content of adulteration of adulterated saffron was predicted by the N-way partial least squares regression (N-PLS) algorithm. In addition, new samples were correctly classified and the adulteration level in adulterated saffron was estimated semi-quantitatively, which verifies the reliability of these models., Conclusion: ATLD-DD-SIMCA and 2DPCA-kNN are recommended methods for the classification of pure saffron and adulterated saffron. The N-PLS algorithm shows potential in prediction of adulteration levels. These methods are expected to solve more complex problems in food authenticity. © 2023 Society of Chemical Industry., (© 2023 Society of Chemical Industry.)