Search

Organic scintillators are praised for their abundant element reserves, facile preparation procedures, and rich structures. However, the weak X-ray attenuation ability and low exciton utilization efficiency result in unsatisfactory scintillation performance. Herein, a new family of highly efficient organic phosphonium halide salts with thermally activated delayed fluorescence (TADF) are designed by innovatively adopting quaternary phosphonium as the electron acceptor, while dimethylamine group and halide anions (I - ) serve as the electron donor. The prepared butyl(2-[2-(dimethylamino)phenyl]phenyl)diphenylphosphonium iodide (C4-I) exhibits bright blue emission and an ultra-high photoluminescence quantum yield (PLQY) of 100 %. Efficient charge transfer is realized through the unique n-π and anion-π stacking in solid-state C4-I. Photophysical studies of C4-I suggest that the incorporation of I accounts for high intersystem crossing rate (k ISC ) and reverse intersystem crossing rate (k RISC ), suppressing the intrinsic prompt fluorescence and enabling near-pure TADF emission at room temperature. Benefitting from the large Stokes shift, high PLQY, efficient exciton utilization, and remarkable X-ray attenuation ability endowed by I, C4-I delivers an outstanding light yield of 80721 photons/MeV and a low limit of detection (LoD) of 22.79 nGy ⋅ s -1 . This work would provide a rational design concept and open up an appealing road for developing efficient organic scintillators with tunable emission, strong X-ray attenuation ability, and excellent scintillator performance., (© 2024 Wiley-VCH GmbH.)

Light-fueled dissipative self-assembly possesses enormous potential in the field of optical information due to controllable time-dependent optical signals, but remains a great challenge for constructing intelligent light-operated logic circuits due to the limited availability of optical signal inputs and outputs. Herein, a series of light-fueled dissipative self-assembly systems with variable optical signals are reported to realize diverse logic gates by modulating time-dependent fluorescence variations of the loaded fluorophores. Three kinds of alkyl trimethylammonium homologs are employed to co-assemble with a merocyanine-based photoinduced amphiphile separately to construct a series of dissipative self-assemblies, showing unexpectedly different fluorescence control behaviors of loaded fluorophores during light irradiation and thermal relaxation processes. The opposite monotonicity of time-dependent emission intensity is achieved just by changing the excitation wavelength. Furthermore, by varying the types of trimethylammoniums and excitation wavelengths, a robust logic system is accomplished, integrating AND, XNOR, and XOR functions, which provides an effective pathway for advancing information transmission applications., (© 2024 Wiley‐VCH GmbH.)

Histone modifications (HMs) play various roles in growth, development, and resistance to abiotic stress. However, HMs have been systematically identified in a few plants, and identification of HMs in medicinal plants is very rare. Aquilaria sinensis is a typical stress-induced medicinal plant, in which HMs remain unexplored. We conducted a comprehensive study to identify HMs and obtained 123 HMs. To conduct evolutionary analysis, we constructed phylogenetic trees and analyzed gene structures. To conduct functional analysis, we performed promoter, GO, and KEGG analyses and ortholog analyses against AtHMs. Based on the expression profiles of different tissues and different layers of Agar-Wit, some HMs of A. sinensis (AsHMs) were predicted to be involved in the formation of agarwood, and their response to MeJA and NaCl stress was tested by qRT-PCR analysis. By analyzing the enrichment of H3K4me3, H3K27me3, and H4K5ac in the promoter regions of two key sesquiterpene synthase genes, AsTPS13/18, we hypothesized that AsHMs play important roles in the synthesis of agarwood sesquiterpenes. We confirmed this hypothesis by conducting RNAi transgenic interference experiments. This study provided valuable information and important biological theories for studying epigenetic regulation in the formation of agarwood. It also provided a framework for conducting further studies on the biological functions of HMs., Competing Interests: Declaration of competing interest There are no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Objectives: To investigate how maternal MTR gene polymorphisms and their interactions with periconceptional folic acid supplementation are associated with the incidence of ventricular septal defects (VSD) in offspring., Methods: A case-control study was conducted, recruiting 426 mothers of infants with VSD under one year old and 740 mothers of age-matched healthy infants. A questionnaire survey collected data on maternal exposures, and blood samples were analyzed for genetic polymorphisms. Multivariable logistic regression analysis and inverse probability of treatment weighting were used to analyze the associations between genetic loci and VSD. Crossover analysis and logistic regression were utilized to examine the additive and multiplicative interactions between the loci and folic acid intake., Results: The CT and TT genotypes of the maternal MTR gene at rs6668344 increased the susceptibility of offspring to VSD ( P <0.05). The GC and CC genotypes at rs3768139, AG and GG at rs1050993, AT and TT at rs4659743, GG at rs3768142, and GT and TT at rs3820571 were associated with a decreased risk of VSD ( P <0.05). The variations at rs6668344 demonstrated an antagonistic multiplicative interaction with folic acid supplementation in relation to VSD ( P <0.05)., Conclusions: Maternal MTR gene polymorphisms significantly correlate with the incidence of VSD in offspring. Mothers with variations at rs6668344 can decrease the susceptibility to VSD in their offspring by supplementing with folic acid during the periconceptional period, suggesting the importance of periconceptional folic acid supplementation in genetically at-risk populations to prevent VSD in offspring.

Organic-inorganic metal halide (OIMH) glass offers the advantages of large-scale production, high transparency, and minimal light scattering. However, undesired crystallization in OIMH glass can occur, leading to deteriorated transparency. Herein, a series of bisphosphonium organic cations were designed to construct Mn-based metal halide crystals with a photoluminescence quantum yield (PLQY) near unity, alongside the development of highly thermally stable OIMH glasses. Two strategies were employed to lower the melting point of OIMH: alkyl chain elongation and fluorine substitution. The (Hex-3,4-2F)MnBr 4 ·MeOH (Hex-3,4-2F = hexane-1,6-diylbis((3,4-difluorobenzyl)diphenylphosphonium)) crystal delivers a glass transition temperature of 100 °C and the highest T g / T m ratio (0.82) among OIMHs. The resulting OIMH glass exhibits a PLQY of 47.6%, achieves an impressive resolution of 25 lp mm -1 in X-ray imaging, and remains transparent even after being heated at 90 °C for six weeks. These bisphosphonium-based OIMH glasses present a feasible design for the practical application of OIMH glasses in radiation detection., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

The LATERAL ORGAN BOUNDARIES DOMAIN (LBD) protein, named for its LATERAL ORGAN BOUNDARIES (LOB) domain, is a member of a class of specific transcription factors commonly found in plants and is absent from all other groups of organisms. LBD TFs have been systematically identified in about 35 plant species and are involved in regulating various aspects of plant growth and development. However, research on the signaling network and regulatory functions of LBD TFs is insufficient, and only a few members have been studied. Moreover, a comprehensive review of these existing studies is lacking. In this review, the structure, regulatory mechanism and function of LBD TFs in recent years were reviewed in order to better understand the role of LBD TFs in plant growth and development, and to provide a new perspective for the follow-up study of LBD TFs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Elevated serum corin concentrations in patients with cardiac diseases have been associated with adverse cardiovascular events and progressive renal dysfunction. This study aimed to determine the role of serum corin levels in predicting the incidence of acute kidney injury (AKI) and mortality in critically ill patients admitted to intensive care units (ICUs). We screened 323 patients admitted to the ICU in our institution from May 2018 through December 2019. After excluding patients receiving renal replacement therapy, 288 subjects were enrolled. Cases were divided equally into high (n = 144) and low (n = 144) corin groups according to median serum corin levels, using 910 pg/mL as the cut-off point. Patient characteristics and comorbidities were collected from medical records. The primary outcome was AKI within 48 h after ICU admission, while the secondary outcome was all-cause of mortality within 1 year. Compared with the low corin group, patients in the high corin group had higher prevalence rates of diabetes, cirrhosis, and nephrotoxic agent exposure; higher Sequential Organ Failure Assessment scores, white blood cell counts, proteinuria, and serum N-terminal pro-brain natriuretic peptide levels; but had lower initial estimated glomerular filtration rates. Furthermore, elevated serum corin was associated with higher risks of AKI within 48h of ICU admission (43.1% vs. 18.1%, p < 0.001) and all-cause mortality within one year (63.9% vs. 50.0%, p = 0.024). High corin level showed strongly positive results as an independent predictor of AKI (OR 2.15, 95% CI 1.11-4.19, p = 0.024) but not for the all-cause mortality after adjusting for confounding factors in multivariate analyses. Elevated circulating corin predicted AKI in critically ill patients, but did not predict all-cause mortality within 1 year. As a key enzyme in renin-angiotensin-aldosterone system, corin expression may be regulated through a feedback loop following natriuretic peptide resistance and desensitization of natriuretic peptide receptors in different critically ill status., (© 2024. The Author(s).)

BODIPY analogs are promising photosensitizers for molecular phototherapy; however, they exhibit high dark cytotoxicity and limited singlet oxygen generation capacity. In this study, we developed self-assembled core-shell nanophotosensitizers by linking a bipyridine group to BODIPY (Bpy-BODIPY) and promoting J-aggregation on gold nanourchins. This design enhances photostability and reduces the energy gap between the lowest singlet excited state and the lower triplet state, facilitating efficient singlet oxygen production. We characterized these nanophotosensitizers using UV-visible spectroscopy, transmission electron microscopy (TEM), surface-enhanced Raman spectroscopy (SERS) and dynamic light scattering (DLS), which confirmed the formation of the desired core-shell structure and J-aggregates. Notably, Bpy-BODIPY@Au significantly suppresses tau protein aggregation and enhances neuroprotective action, even in the presence of a phosphatase inhibitor. This work broadens the application of BODIPY chemistry to nanoagents for neuroprotective therapy., (© 2024 Wiley-VCH GmbH.)

Background: The GeneXpert MTB/RIF (Xpert) assay is a widely used technology for detecting Mycobacterium tuberculosis (MTB) in clinical samples. However, the study on the failure of the Xpert assay during routine implementation and its potential solutions is limited., Methods: We retrospectively analyzed the records of unsuccessful tests in the Xpert and the GeneXpert MTB/RIF Ultra (Ultra) assays between April 2017 and April 2021 at the Shanghai Public Health Clinical Center. To further investigate the effect of prolonged preprocessing on clinical sputum, an additional 120 sputum samples were collected for Xpert testing after 15 min, 3 h, and 6 h preprocessing. The analysis was performed by SPSS version 19.0 software., Results: A total of 11,314 test records were analyzed, of which 268 (2.37%) had unsuccessful test results. Among these, 221 (1.95%) were reported as "Error", 43 (0.38%) as "Invalid", and 4 (0.04%) as "No result". The most common clinical specimen for Xpert tests was sputum, accounting for 114 (2.17%) unsuccessful tests. The failure rate of urine specimens was lower than that of sputum (OR = 0.12, 95% CI: 0.02-0.88, χ 2  = 6.22, p = 0.021). In contrast, the failure rate of stool specimens was approximately twice as high as that of sputum (OR = 1.93, 95% CI: 1.09-3.40, χ 2  = 5.35, p = 0.014). In the prolonged preprocessing experiment, 102 cases (85%) yielded consistent results in Xpert tests. Furthermore, 7 cases (5.83%) detected an increase in MTB load, 8 cases (6.67%) detected a decrease in MTB load, and 3 cases (2.5%) yielded incongruent results in MTB and rifampicin resistance detection., Conclusions: The primary cause of unsuccessful tests in the Xpert assay was reported as "Error". Despite varying failure rates depending on the samples, the Xpert assay can be applied to extrapulmonary samples. For paucibacillary specimens, retesting the remaining preprocessed mixture should be carefully considered., (© 2024. The Author(s).)

Integrating genomics and histology for cancer prognosis demonstrates promise. Here, we develop a multi-classifier system integrating a lncRNA-based classifier, a deep learning whole-slide-image-based classifier, and a clinicopathological classifier to accurately predict post-surgery localized (stage I-III) papillary renal cell carcinoma (pRCC) recurrence. The multi-classifier system demonstrates significantly higher predictive accuracy for recurrence-free survival (RFS) compared to the three single classifiers alone in the training set and in both validation sets (C-index 0.831-0.858 vs. 0.642-0.777, p < 0.05). The RFS in our multi-classifier-defined high-risk stage I/II and grade 1/2 groups is significantly worse than in the low-risk stage III and grade 3/4 groups (p < 0.05). Our multi-classifier system is a practical and reliable predictor for recurrence of localized pRCC after surgery that can be used with the current staging system to more accurately predict disease course and inform strategies for individualized adjuvant therapy., (© 2024. The Author(s).)

Background: Intracerebral hemorrhage mainly occurs in middle-aged and elderly patients with hypertension, and surgery is currently the main treatment for hypertensive cerebral hemorrhage, but the bleeding caused by surgery will cause damage to the patient's nerve cells, resulting in cognitive and motor dysfunction, resulting in a decline in the patient's quality of life., Aim: To investigate associations between cerebral arterial blood flow and executive and cognitive functions in depressed patients after acute hypertensive cerebral hemorrhage., Methods: Eighty-nine patients with depression after acute hypertensive cerebral hemorrhage who were admitted to our hospital between January 2019 and July 2021 were selected as the observation group, while 100 patients without depression who had acute hypertensive cerebral hemorrhage were selected as the control group. The attention span of the patients was assessed using the Paddle Pin Test while executive function was assessed using the Wisconsin Card Sorting Test (WCST) and cognitive function was assessed using the Montreal Cognitive Assessment Scale (MoCA). The Hamilton Depression Rating Scale (HAMD-24) was used to evaluate the severity of depression of involved patients. Cerebral arterial blood flow was measured in both groups., Results: The MoCA score, net scores I, II, III, IV, and the total net score of the scratch test in the observation group were significantly lower than those in the control group ( P < 0.05). Concurrently, the total number of responses, number of incorrect responses, number of persistent errors, and number of completed responses of the first classification in the WCST test were significantly higher in the observation group than those in the control group ( P < 0.05). Blood flow in the basilar artery, left middle cerebral artery, right middle cerebral artery, left anterior cerebral artery, and right anterior cerebral artery was significantly lower in the observation group than in the control group ( P < 0.05). The basilar artery, left middle cerebral artery, right middle cerebral artery, left anterior cerebral artery, and right anterior cerebral artery were positively correlated with the net and total net scores of each part of the Paddle Pin test and the MoCA score ( P < 0.05), and negatively correlated with each part of the WCST test ( P < 0.05). In the observation group, the post-treatment improvement was more prominent in the Paddle Pin test, WCST test, HAMD-24 score, and MoCA score compared with those in the pre-treatment period ( P < 0.05). Blood flow in the basilar artery, left middle cerebral artery, right middle cerebral artery, left anterior cerebral artery, and right anterior cerebral artery significantly improved in the observation group after treatment ( P < 0.05)., Conclusion: Impaired attention, and executive and cognitive functions are correlated with cerebral artery blood flow in patients with depression after acute hypertensive cerebral hemorrhage and warrant further study., Competing Interests: Conflict-of-interest statement: There is no conflict of interest., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Heterotopic ossification (HO), the pathological formation of bone within soft tissues such as tendon and muscle, is a notable complication resulting from severe injury. While soft tissue injury is necessary for HO development, the specific molecular pathology responsible for trauma-induced HO remains a mystery. The previous study detected abnormal autophagy function in the early stages of tendon HO. Nevertheless, it remains to be determined whether autophagy governs the process of HO generation. Here, trauma-induced tendon HO model is used to investigate the relationship between autophagy and tendon calcification. In the early stages of tenotomy, it is observed that autophagic flux is significantly impaired and that blocking autophagic flux promoted the development of more rampant calcification. Moreover, Gt(ROSA)26sor transgenic mouse model experiments disclosed lysosomal acid dysfunction as chief reason behind impaired autophagic flux. Stimulating V-ATPase activity reinstated both lysosomal acid functioning and autophagic flux, thereby reversing tendon HO. This present study demonstrates that autophagy-lysosomal dysfunction triggers HO in the stages of tendon injury, with potential therapeutic targeting implications for HO., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Background: Existing studies have found that circular RNAs (circRNAs) act as sponges for micro RNAs (miRNAs) to control downstream genes. However, the specific functionalities and mechanisms of circRNAs in human clear cell renal cell carcinoma (ccRCC) have yet to be thoroughly investigated., Methods: Patient cohorts from online databases were used to screen candidate circRNAs, while another cohort from our hospital was obtained for validation. CircSOD2 was identified as a potential oncogenic target, and its relevant characteristics were investigated during ccRCC progression through various assays. A positive feedback loop containing downstream miRNA and its target gene were identified using bioinformatics and validated by luciferase reporter assays, RNA pull-down, and high-throughput sequencing., Results: CircSOD2 expression was elevated in tumor samples and significantly correlated with overall survival (OS) and the tumor stage of ccRCC patients, which appeared in the enhanced proliferation, invasion, and migration of tumor cells. Through competitive binding to circSOD2, miR-532-3p can promote the expression of PAX5 and the progression of ccRCC, and such regulation can be salvaged by miR-532-3p inhibitor., Conclusion: A novel positive feedback loop, PAX5/circSOD2/miR-532-3p/PAX5 was identified in the study, indicating that the loop may play an important role in the diagnosis and prognostic prediction in ccRCC patients., (© 2024. The Author(s).)

Objective: Pertussis cases have increased markedly since 2018 in Guangxi. The aim of this study was to evaluate antibody levels and the infection status of pertussis in the resident population., Method: A total of 10,215 serum samples from residents were collected from August-November 2018 and tested for anti-pertussis IgG and toxin IgG using the enzyme-linked immunosorbent assay (ELISA)., Results: Of the collected samples, 1,833 (17.94%) tested positive for anti-pertussis IgG, with the median concentration of 16.06 IU/mL. Antibody level < 10 IU/mL accounted for more than 60% in children under 4 years of age, but declined with age, whereas the percentages of the other three levels (10-40, 40-50, and ≥ 50 IU/mL) increased almost with age ( P < 0.001). Moreover, 7,924 samples were selected for anti-pertussis toxin IgG, of which 653 (8.24%) tested positive (≥ 40 IU/mL) with the median concentration of 5.89 IU/mL, and 204 participants (2.56%) had recent pertussis infection (≥ 100 IU/mL). Among the different age groups, the highest rates of positivity and recent infection were observed at 11-20 years of age, the lowest positivity rate at 5 years of age, and the lowest recent infection rate at 4 years of age ( P < 0.001, P = 0.005, respectively)., Conclusion: The survey results showed that all age groups in Guangxi lacked immunity against pertussis, which was one of the main factors contributing to the resurgence of pertussis in 2018. In addition, the prevalence of pertussis is relatively high in Guangxi, and its incidence is seriously underestimated, especially in adolescents and adults., (Copyright © 2024 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.)

Purpose: This study was designed to evaluate the effect of acupuncture on cough, expectoration, and shortness of breath in lung cancer patients., Methods: Between December 2021 and June 2022, a total of 130 lung cancer patients were recruited, and they were split into control and intervention groups at random. Routine nursing was provided to the control group, whereas routine nursing with acupuncture using LU7 (Lie Que), LU9 (Tai Yuan), BL13 (Fei Shu), and BL20 (Pi Shu) was administered to the intervention group for 7 days. The severity of cough, expectoration, and shortness of breath was assessed 1 day before and after the interventions using the lung cancer-specific module of the MDASI. A two-way ANOVA was performed for group comparisons., Results: Compared with the control group, the symptoms of cough in the intervention group were significantly improved (F = 5.095, MD = -0.32, 95% CI, -0.59 to 0.04, P = 0.025), while expectoration (F = 0.626, MD = -0.11, 95% CI, -0.38 to 0.16, P = 0.430) and shortness of breath (F = 0.165, MD = -0.05, 95% CI, -0.27 to 0.18, P = 0.685) had no significant change. Cough also identified an obvious interaction effect (P = 0.014), and the post-intervention simple main effect test demonstrated a tangible difference between the two groups (MD = -0.66, 95% CI, -0.99 to 0.33, P < 0.001) post-intervention., Conclusions: Acupuncture using LU7, LU9, BL13, and BL20 can relieve the cough of lung cancer patients, but not relieve expectoration and shortness of breath., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to disclose., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Introduction: Known to have pleiotropic functions, high-density lipoprotein (HDL) helps to regulate systemic inflammation during sepsis. As preserving HDL-C level is a promising therapeutic strategy for sepsis, the interaction between HDL and sepsis worth further investigation. This study aimed to determine the impact of sepsis on HDL's anti-inflammatory capacity and explore its correlations with disease severity and laboratory parameters., Methods and Materials: We enrolled 80 septic subjects admitted to the intensive care unit and 50 controls admitted for scheduled coronary angiography in this cross-sectional study. We used apolipoprotein-B depleted (apoB-depleted) plasma to measure the anti-inflammatory capacity of HDL-C. ApoB-depleted plasma's anti-inflammatory capacity is defined as its ability to suppress tumor necrosis factor-α-induced vascular cell adhesion molecule-1 (VCAM-1) expression in human umbilical-vein endothelial cells. A subgroup analysis was conducted to investigate in septic subjects according to disease severity., Results: ApoB-depleted plasma's anti-inflammatory capacity was reduced in septic subjects relative to controls (VCAM-1 mRNA fold change: 50.1% vs. 35.5%; p < 0.0001). The impairment was more pronounced in septic subjects with than in those without septic shock (55.8% vs. 45.3%, p = 0.0022). Both associations were rendered non-significant with the adjustment for the HDL-C level. In sepsis patients, VCAM-1 mRNA fold change correlated with the SOFA score (Spearman's r = 0.231, p = 0.039), lactate level (r = 0.297, p = 0.0074), HDL-C level (r = -0.370, p = 0.0007), and inflammatory markers (C-reactive protein level: r = 0.441, p <0.0001; white blood cell: r = 0.353, p = 0.0013)., Conclusion: ApoB-depleted plasma's anti-inflammatory capacity is reduced in sepsis patients and this association depends of HDL-C concentration. In sepsis patients, this capacity correlates with disease severity and inflammatory markers. These findings explain the prognostic role of the HDL-C level in sepsis and indirectly support the rationale for targeting HDL-C as sepsis treatment., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Chen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

A set of biotin-polyethylene glycol (PEG)-naphthalimide derivatives 4a-4h with dual targeting of ferroptosis and DNA were designed and optimized using docking simulation as antitumor agents. Docking simulation optimization results indicated that biotin-PEG4-piperazine-1,8-naphthalimide 4d should be the best candidate among these designed compounds 4a-4h, and therefore, we synthesized and evaluated it as a novel antitumor agent. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay and MGC-803 and U251 xenograft models identified 4d as a good candidate antitumor agent with potent efficacy and safety profiles, compared with amonafide and temozolomide. The findings of the docking simulations, fluorescence intercalator displacement (FID), western blot, comet, 5-ethynyl-2'-deoxyuridine (EdU), flow cytometry, transmission electron microscopy, and BODIPY-581/591-C11, FerroOrange, and dihydroethidium (DHE) fluorescent probe assays revealed that 4d could induce DNA damage, affect DNA synthesis, and cause cell cycle arrest in the S phase in MGC-803 cells. Also, it could induce lipid peroxidation and thus lead to ferroptosis in MGC-803 cells, indicating that it mainly exerted antitumor effects through dual targeting of ferroptosis and DNA. These results suggested that it was feasible to design, optimize using docking simulation, and evaluate the potency and safety of biotin-PEG-1,8-naphthalimide as a antitumor agent with dual targeting of ferroptosis and DNA, based on a multi-target drug strategy., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

The reproduction toxicity of pubertal exposure to Microcystin-LR (MC-LR) and the underlying mechanism needs to be further investigated. In the current study, pubertal male ICR mice were intraperitoneally injected with 2 μg/kg MC-LR for four weeks. Pubertal exposure to MC-LR decreased epididymal sperm concentration and blocked spermatogonia proliferation. In-vitro studies found MC-LR inhibited cell proliferation of GC-1 cells and arrested cell cycle in G2/M phase. Mechanistically, MC-LR exposure evoked excessive reactive oxygen species (ROS) and induced DNA double-strand break in GC-1 cells. Besides, MC-LR inhibited DNA repair by reducing PolyADP-ribosylation (PARylation) activity of PARP1. Further study found MC-LR caused proteasomal degradation of SIRT6, a monoADP-ribosylation enzyme which is essential for PARP1 PARylation activity, due to destruction of SIRT6-USP10 interaction. Additionally, MG132 pretreatment alleviated MC-LR-induced SIRT6 degradation and promoted DNA repair, leading to the restoration of cell proliferation inhibition. Correspondingly, N-Acetylcysteine (NAC) pre-treatment mitigated the disturbed SIRT6-USP10 interaction and SIRT6 degradation, causing recovered DNA repair and subsequently restoration of cell proliferation inhibition in MC-LR treated GC-1 cells. Together, pubertal exposure to MC-LR induced spermatogonia cell cycle arrest and sperm count reduction by oxidative DNA damage and simultaneous SIRT6-mediated DNA repair failing. This study reports the effect of pubertal exposure to MC-LR on spermatogenesis and complex mechanism how MC-LR induces spermatogonia cell proliferation inhibition., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper, (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: Understanding HPV vaccination willingness and its influencing factors among female sex workers (FSWs) in entertainment venues in an urban area of Guangxi, China., Methods: From 15 August to 15 October 2022, FSWs in entertainment venues with commercial sex trade in an urban area of Guangxi were selected as the study subjects for the questionnaire survey using the method of intentional sampling. The questionnaire based on the information-motivation-behavior (IMB) skills model was used to collect the basic characteristics, HPV and HPV vaccine-related information and cognition, motivation to vaccinate, behavioral skills and willingness to vaccinate from the research targets. A multifactor logistic regression model was used to analyze the factors influencing the research targets' willingness to receive HPV vaccination., Results: Of the 921 research targets, 712 (77.31%) were willing to receive HPV vaccination. The higher the level of knowledge regarding HPV and HPV vaccine-related information, the higher the motivation for HPV vaccination. In addition, the higher the behavioral skills score, the higher the willingness of FSWs in entertainment venues to receive HPV vaccination (P<0.001). FSWs in entertainment venues with lower venue grades [OR(95% CI)=0.693 (0.539, 0.891), P=0.004] were more reluctant to receive HPV vaccination. Those who favored the effectiveness of the vaccine in preventing the disease [OR(95% CI)=2.144 (1.449, 3.174), P<0.001] and those who had heard of HPV vaccine [OR(95% CI)=2.105 (1.451, 3.054), P<0.001], were able to perceive the benefits of HPV vaccination [OR(95% CI)=1.134 (1.045, 1.230), P=0.002]. These individuals acquired greater behavioral skills i.e., self-decision making for HPV vaccination [OR(95% CI)=1.130 (1.008, 1.267), P=0.036] and self-efficacy [OR(95% CI)=1.135 (1.081, 1.191), P<0.001] and they were more willing to receive HPV vaccine., Conclusions: There was a relatively high HPV vaccination willingness among FSWs in entertainment venues in an urban area of Guangxi, China. Attention should be focused on introducing the benefits of primary prevention measures such as the HPV vaccine for individuals and behavioral skills for HPV vaccination in order to increase their willingness to be vaccinated thus increasing their HPV vaccination rate., (© 2024. The Author(s).)

Objectives: Visceral leishmaniasis (VL) represents the most severe form of Leishmaniasis infection, often resulting in fatality without timely treatment. Previous studies have found that immunosuppression increases the risk of VL disease progression and mortality, and the total immunoglobulin G (IgG) levels in peripheral blood vary before and after treatment. However, the distinct levels and roles of IgG subclasses in VL have not been documented yet. This study aims to elucidate the characteristics and clinical significance of IgG subclasses in VL., Methods: A total of 43 cases newly-diagnosed with VL were enrolled in the cohort. We measured the levels of IgG subclasses before and after standard treatment and conducted assessments of bone marrow features. In addition, we analysed other haematological indices and examined the variations in IgG subclasses, as well as their correlation with clinical and laboratory factors., Results: The levels of total IgG, IgG1, and the ratios of both IgG1/IgG and IgG1/IgG2 decreased significantly after treatment, whereas the ratios of IgG2/ IgG showed an obvious increase. The VL patients without hyperglobulinemia displayed significant lower IgG1/IgG2 ratios, but higher IgG2/IgG ratios compared with those with hyperglobulinemia. In addition, VL patients with positive bone marrow amastigotes had significant higher IgG1/IgG and IgG1/IgG2 ratios, but lower IgG2/IgG ratios. IgG subclasses were correlated with abnormal blood test results, particularly immunological elements including IgM and Complement 4 (C4)., Conclusions: IgG1 and IgG2 exhibited contrasting changes after treatment in VL patients. The features of bone marrow and laboratory tests indicated that IgG1 and IgG2 serve different roles in the progression of VL. The ratios of IgG subclasses may be more precise indicators to evaluate immune reaction in VL than traditional total IgG., (© 2023 John Wiley & Sons Ltd.)

Introduction: Dalbergia odorifera T. Chen, known as fragrant rosewood, is a rare and endangered tree species. Studies have shown that plant growth regulators can effectively promote heartwood formation. This study aimed to investigate the effects of ethephon (ETH) on heartwood formation and the influence of ethephon and hydrogen peroxide (H 2 O 2 ) on the physiological characteristics in D. odorifera ., Methods: D. odorifera branches underwent treatment with 2.5% plant growth regulators, including ETH, jasmonic acid (JA), salicylic acid (SA), abscisic acid (ABA), H 2 O 2 , and inhibitors such as ascorbic acid (AsA) to inhibit H 2 O 2 synthesis, and (S) -trans 2-amino-4 - (2-aminoethoxy) -3-butene (AVG) to inhibit ethylene synthesis. After a 14-day period, we conducted an analysis to evaluate the impact of these plant growth regulators on elongation distance, vessel occlusion percentage, and trans-nerol content. Additionally, the effects of ETH and H 2 O 2 on endogenous plant hormones, H 2 O 2 content, soluble protein content, and enzyme activity were investigated within 0-48 h of treatment., Results: After treatment with ETH for 14 days, the extension distance of the heartwood material was 15 cm, while the trans-nerolol content was 15 times that of the ABA group. ETH and H 2 O 2 promoted endogenous ethylene synthesis; Ethylene content peaked at 6 and 18 h. The peak ethylene content in the ETH group was 68.07%, 12.89%, and 20.87% higher than the initial value of the H 2 O 2 group and ddH 2 O group, respectively, and 29.64% higher than that in the AVG group. The soluble protein content and activity of related enzymes were significantly increased following ETH treatment., Discussion: ETH exhibited the most impact on heartwood formation while not hindering tree growth. This treatment effectively triggered the production of endogenous ethylene in plants and enhanced the activity of essential enzymes involved in heartwood formation. These findings serve as a valuable reference for future investigations into heartwood formation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhu, Li, Meng, He, Yang and Wei.)

A series of 4-(N-dithiobenzyl piperazine)-1,8-naphthalimide derivatives 4-6 were designed, synthesized, and evaluated as novel multi-target antitumor agents. 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) results showed that compounds 5j, 5k, and 6j exhibited superior in vitro antiproliferative activity in MGC-803, HepG-2, SKOV-3, and T24 cancer cell lines and the cisplatin-resistant cell line A549/DDP. HepG-2, SKOV-3, and T24 xenograft assay results revealed that compounds 5j, 5k, and 6j exhibited good antitumor effects compared with amonafide. The pathology results indicated that compound 5j exhibited the least comprehensive toxicity among the three compounds, identifying compound 5j as a good candidate antitumor agent with good efficacy, limited toxicity, and low resistance. Compound 5j was thus chose for further antitumor mechanism investigation. Results from the omics research, confocal immunofluorescence, Western blot, transmission electron microscopy, and flow cytometry indicated that compound 5j exerted antitumor effects through multiple mechanisms, including ferroptosis, autophagy, apoptosis, and cell cycle arrest. These results suggest that screening novel 1,8-naphthalimide-based antitumor agents for good efficacy, limited toxicity, and low resistance based on a multi-target drug strategy is feasible., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Jian-Hua Wei, Ri-Zhen Huang, Ye Zhang reports financial support was provided by National Natural Science Foundation of China. Ye Zhang reports financial support was provided by Guangxi Natural Science Foundation. Jian-Hua Wei reports financial support was provided by State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

A new lignan, sonneralignan A ( 1 ), along with two known lignan compounds, (+)-lariciresinol-9- O - β -D-glucopyranoside ( 2 ) and (-)isolariciresinol-9- O - β -D-glucopyranoside ( 3 ) were isolated from the n-butanol extract of the mangrove Sonneratia apetala fruit. The structures of the compounds were elucidated on the basis of extensive spectral analysis. The evaluation of activity showed that compound 1 exhibited significant anti-aging activity, which extended the mean lifespan of Caenorhabditis elegans by up to 19.13% ( p  < 0.05) and 55.29% ( p  < 0.01) under normal and heat stress cultivation conditions, respectively. Molecular docking studies showed that compound 1 was bound to the DNA binding domain of DAF-16 and promoted the conformation of DAF-16, thus strengthening the interaction between the DAF-16 and related DNA. TRP-252, SER-250 and SER-249 of the binding region might be the key amino residues during the interaction.

Objectives: Perivascular adipose tissue (PVAT) surrounding human internal mammary artery (IMA) possesses anticontractile property. Its function under pathological conditions is barely studied. We previously reported that homocysteine impairs the vasodilator function of IMA through endothelium and smooth muscle-dependent mechanisms. This study investigated the effect of homocysteine on the function of PVAT and the associated mechanisms., Methods: Residual IMA tissues were collected from patients undergoing coronary artery bypass grafting. Vasoreactivity was studied using myograph. Adiponectin was measured by ELISA. Expressions of adiponectin receptors (AdipoRs), eNOS and p-eNOS were determined by RT-qPCR and Western blot., Results: Exposure to homocysteine augmented the contractile responses of PVAT-intact IMA to U46619 and potassium chloride, regardless with or without endothelium. Such augmentation was also observed in skeletonized IMA with transferred, homocysteine-exposed PVAT. Homocysteine attenuated the relaxant response of PVAT-intact while endothelium-denuded vessels to acetylcholine. Homocysteine lowered adiponectin content in the PVAT, downregulated the expression of AdipoR1 and AdipoR2 as well as eNOS and p-eNOS in skeletonized IMA. The relaxant response of skeletonized IMA to AdipoR agonist AdipoRon was blunted by homocysteine or eNOS inhibitor, and homocysteine significantly attenuated the inhibitory effect of eNOS inhibitor on AdipoRon-induced relaxation., Conclusions: Homocysteine impairs the anticontractile/vasorelaxing activity of PVAT surrounding the IMA through inhibiting adiponectin/AdipoR/eNOS/nitric oxide signalling pathway., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

This study aimed to investigate the chemical constituents of supercritical extract from Qi-nan Aquilariae Lignum Resinatum by silica gel column chromatography, thin-layer chromatography, and semi-preparative high-performance liquid chromatography. One new elemane-type and one new eudesmane-type sesquiterpene compounds were isolated from the extract, and their structures were identified by MS, UV, IR, NMR, and ECD spectroscopic techniques, and named aquqinanol C(1) and aquqinanol D(2). Both compounds are novel compounds. The neuroprotective effect of the compounds on CORT-induced PC12 cell damage was determined in vitro. The results showed that compounds 1 and 2 exhibited a certain protective effect against CORT-induced damage in PC12 cells.

Artemisia capillaris (Asteraceae) is an annual herb found in ˃10 provinces in China. It is cultivated on ˃670 ha, with annual production around 2,500 tons. Its shoot is used in traditional Chinese medicine (Liu et al. 2021). From April to May 2023, Sclerotinia rot symptoms were seen at the Institute of Medicinal Plant Development (40.04°N, 116.28°E), Beijing, China. Disease incidence was up to 10% in the field through investigation of 300 plants. Initial symptoms were irregular tan-brown lesions (0.5 to 5.0 mm) that expended to circumferential necrosis on the roots and basal stem, aerial mycelia and sclerotia were developed on them. The leaves and stem tips were withered and droopy in severe cases. Twelve symptomatic primary roots of 12 plants from two sites were cut into 5 × 5 mm pieces, surface sterilized with 75% ethanol for 30 s and 5% NaClO for 60 s, rinsed with distilled water for three times, dried with sterile filter paper, put on potato dextrose agar (PDA), and incubated at 25°C in the dark for 2 days. Two Sclerotinia-like isolates were obtained using the hyphaltip method. White aerial mycelia were sparse and appressed for isolate YC1-3 and dense for isolate YC1-7. After incubated at 25°C in the dark for 15 days, 10 to 25 sclerotia were developed near the colony margin. Sclerotia of isolate YC1-3 were 1.0 to 3.9 × 1.2 to 4.5 (mean 1.8 × 2.2) mm (n = 60), ovoid or arc-shaped. Sclerotia of isolate YC1-7 were 1.5 to 3.4 × 2.7 to 9.2 (mean 2.3 × 4.3) mm (n = 60), ovoid, dumbbell shaped or curved. The isolates were identified as Sclerotinia sclerotiorum based on morphology (Maas 1998). To further identify the pathogens, molecular identification was performed with isolates YC1-3 and YC1-7. DNA of the two isolates were extracted by the cetyltrimethylammonium bromide (CTAB) method. Polymerase chain reaction was performed with primers ITS1/ITS4 for the internal transcribed spacer (ITS) region (Choi et al. 2020; White et al. 1990) and primers G3PDHfor/G3PDHrev for the glyceraldehyde 3-phosphate dehydrogenase (G3PDH) gene (Garfinkel. 2021). BLAST search analysis revealed that the ITS sequence (GenBank OR229758 and OR229762) was ≥99% similar to S. sclerotiorum (MN099281, MZ379265, KX781301, etc.), and the G3PDH sequence (OR778388 and OR761975) was too (MZ493894, JQ036048, OQ790148, etc.). Phylogenetic trees were computed with ITS and G3PDH sequences using the Maximum Likelihood in MEGA 11. Nine two-month-old seedlings of A. capillaris were used to test pathogenicity. The epidermis layer of each primary root was slightly wounded (2 × 2 mm, 1 mm deep) using a sterile dissecting blade. Three plants were inoculated with mycelial plugs (5 mm in diameter) of YC1-3 and YC1-7 that cultured on PDA for 7 days. Control plants were inoculated with sterile PDA plugs. All seedlings were then incubated at 25oC and 90% relative humidity. After isolate YC1-7 inoculation 3 days and isolate YC1-3 inoculation 5 days, inoculated roots had symptoms like those in the field, controls had no symptoms. S. sclerotiorum was consistently re-isolated from diseased roots, fulfilling Koch's postulates. Diseases caused by S. sclerotiorum have been reported threatens several important economical crops (Marin and Peres 2020; Guan et al. 2022). To our knowledge, this is the first report of S. sclerotiorum causes Sclerotinia rot on A. capillaris. To avoid of significant economic losses, it is urgent to establish an effective disease-management strategy.

Aim: To assess the visual correction of patients with different degrees of astigmatism with toric soft contact lenses (TSC)., Methods: It was a real-world study with prospective and single-arm design. A total of 384 patients with astigmatism who came for TSC fitting and alignment from November 2022 to January 2023 were included. According to the difference in astigmatism, patients were divided into groups A (cylinder degree: -0.75 to -0.50 D), B (cylinder degree: -1.75 to -1.00 D) and C (cylinder degree ≤ -2.00 D), and followed up on the day of wear, 1wk, 1 and 3mo, mainly to observe visual acuity, refraction, lens fit, visual quality and comfort at 1wk after wear. The visual acuity success rate and the overall success rate of the fitting were evaluation indicators (taking into account the four dimensions of visual acuity, fitting, quality of vision and comfort). The visual acuity success rate was calculated by taking "corrected visual acuity with contact lenses is no less than 1 line or better than best spectacle-corrected visual acuity" ( i.e . corrected visual acuity with contact lenses is 1 line below, equal to, one line above or more than best spectacle-corrected visual acuity) as the criterion for visual success, and the the overall success rate of the fitting was calculated by using the comprehensive indicators (visual acuity, fit, visual quality, comfort) to meet certain conditions as the judgment criteria for successful fitting., Results: After 1wk of wearing TSC, the visual acuity success rates of patients were 100% (207/207), 98.58% (139/141) and 97.22% (35/36) in the three groups, respectively, with residual cylinder closed to 0. The acceptability of the lens fitting was over 95%; the incidence of adverse visual symptoms was within 10% and the comfort acceptability was over 97%. The overall success rate of fitting for patients with high, medium and low astigmatism was 93.72% (194/207), 90.78% (128/141) and 88.89% (32/36), respectively., Conclusion: TSC (model: G&G POP·CT) are effective in correcting astigmatism in patients with different degrees of astigmatism., (International Journal of Ophthalmology Press.)

Objectives: This study aimed to explore the relationship between social isolation and sleep in later life and the role of loneliness in this relationship., Methods: In Study 1, we conducted a cross-sectional analysis of the correlation between social isolation and sleep in community-dwelling older adults ( N  = 108). This relationship was assessed using subjective and objective measures. Moreover, we examined the mediating role of loneliness cross-sectionally (Study 1) and longitudinally (Study 2). Longitudinal study was based on three waves of data from the National Scale Life, Health, and Aging Project ( N  = 1, 554)., Results: The results showed that social isolation was robustly associated with sleep in the general population of older adults. Specifically, subjective social isolation was associated with subjective sleep, and objective social isolation was associated with objective sleep. The results of the longitudinal study showed that loneliness mediated the reciprocal link between social isolation and sleep across time after controlling for autoregressive effects and basic demographics., Conclusions: These findings address the gap in the literature on the link between social isolation and sleep in older adults, extending the understanding of improvement in older adults' social networks, sleep quality, and psychological well-being.

Objective: To investigate the effect of Notch2 gene knockout in Treg cells on head and neck squamous cell carcinoma (HNSCC) in mice., Methods: A mouse model of HNSCC was constructed. Flow cytometry and immunofluorescence were used to examine the numbers of related immune cells and programmed cell death in tumor cells in the spleen and tumor microenvironment of mice. Western blotting was used to measure the expression of related proteins in tumor tissues., Results: The tumor volume of regulatory T (Treg) cell-specific Notch2-knockout mice (experimental group) was significantly smaller than that of control mice (control group) (P < 0.05). Compared with those in the control group, the number of Treg cells and the expression of Ki67 in Treg cells in the spleen and tumor tissue were significantly decreased in the experimental group, while the numbers of CD45+ hematopoietic cells, CD4+ T cells, CD8+ T cells, T helper 1 (Th1) cells, CD11b+ cells (macrophages), and CD11b+CD11c+ cells (dendritic cells) and the expression of Ki67 in CD4+ T cells and CD8+ T cells were significantly increased (P < 0.05). There was no significant difference in the number of Th2 cells between the two groups (P > 0.05). Immunofluorescence analysis showed that the numbers of CD4+ T cells and CD8+ T cells in the tumor tissue in the experimental group were significantly higher than those in the control group (P < 0.05). Compared with that in the control group, programmed cell death in the experimental group was significantly increased (P < 0.05). Moreover, the expression levels of NLRP3, Caspase-1 and GSDMD in the tumor tissues of the experimental group were higher than those in the control group (P < 0.01), while the expression levels of BCL2, Bax, ATG5, LC3 and p62 were not significantly different (P > 0.05)., Conclusions: Specific knockout of the Notch2 gene in Treg cells significantly decreases the function of Treg cells, inhibits the growth of HNSCC and improves the immune microenvironment in mice, thus effectively treating HNSCC., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Dracaena cambodiana Pierre ex Gagnep is an important plant resource for producing dragon's blood and one of most popular ornamental trees in China. For a better understanding of the physiological function of the stem, the structural characteristics and main substance histological location of the stems of D. cambodiana were studied. The structural characteristics of the different developmental stages of stems of D. cambodiana were observed and described detailly. And then a schematic diagram of the mature stem was created. Histochemical staining showed that two kinds of polysaccharides distributed in parenchymal cells. Saponins distributed mainly in ground tissue and phenolic compounds distributed mainly in the thick cell walls. An abundant of calcium oxalate raphide bundles were identified in cortex and primary tissue. Finally, the role of the above results in the taxonomy of Dracaena species and in their strong adaptability was discussed., (© 2023 The Authors. Microscopy Research and Technique published by Wiley Periodicals LLC.)

Clear cell Renal Cell Carcinoma (ccRCC) is a highly heterogeneous disease, making it challenging to predict prognosis and therapy efficacy. In this study, we aimed to explore the role of 5-methylcytosine (m5C) RNA modification in ccRCC and its potential as a predictor for therapy response and overall survival (OS). We established a novel 5-methylcytosine RNA modification-related gene index (M5CRMRGI) and studied its effect on the tumor microenvironment (TME) using single-cell sequencing data for in-depth analysis, and verified it using spatial sequencing data. Our results showed that M5CRMRGI is an independent predictor of OS in multiple datasets and exhibited outstanding performance in predicting the OS of ccRCC. Distinct mutation profiles, hallmark pathways, and infiltration of immune cells in TME were observed between high- and low-M5CRMRGI groups. Single-cell/spatial transcriptomics revealed that M5CRMRGI could reprogram the distribution of tumor-infiltrating immune cells. Moreover, significant differences in tumor immunogenicity and tumor immune dysfunction and exclusion (TIDE) were observed between the two risk groups, suggesting a better response to immune checkpoint blockade therapy of the high-risk group. We also predicted six potential drugs binding to the core target of the M5CRMRGI signature via molecular docking. Real-world treatment cohort data proved once again that high-risk patients were appropriate for immune checkpoint blockade therapy, while low-risk patients were appropriate for Everolimus. Our study shows that the m5C modification landscape plays a role in TME distribution. The proposed M5CRMRGI-guided strategy for predicting survival and immunotherapy efficacy, we reported here, might also be applied to more cancers other than ccRCC., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Indoleamine-2,3-dioxygenase 1 (IDO1) and signal transducer and activator of transcription 3 (STAT3) have emerged as significant targets in the tumor microenvironment for cancer therapy. In this study, we synthesized three novel 2-amino-1,4-naphthoquinone amide-oxime derivatives and identified them as dual inhibitors of IDO1 and STAT3. The representative compound NK3 demonstrated effective binding to IDO1 and exhibited good inhibitory activity (hIDO1 IC 50 = 0.06 μM), leading to its selection for further investigation. The direct interactions between compound NK3 and IDO1 and STAT3 proteins were confirmed through surface plasmon resonance analysis. A molecular docking study of compound NK3 revealed key interactions between NK3 and IDO1, with the naphthoquinone-oxime moiety coordinating with the heme iron. In the in vitro anticancer assay, compound NK3 displayed potent antitumor activity against selected cancer cell lines and effectively suppressed nuclear translocation of STAT3. Moreover, in vivo assays conducted on CT26 tumor-bearing Balb/c mice and an athymic HepG2 xenograft model revealed that compound NK3 exhibited potent antitumor activity with low toxicity relative to 1-methyl-L-tryptophan (1-MT) and doxorubicin (DOX). Overall, these findings provided evidence that the dual inhibitors of IDO1 and STAT3 may offer a promising avenue for the development of highly effective drug candidates for cancer therapy.

We report that the core sequence of amyloid β (Aβ) peptide, KLVFF, when equipped with a C-terminal cysteine residue, exhibited an extremely low minimum hydrogelation concentration of 0.05 wt% in the presence of Ag + in pH 5 buffer, with this concentration 2 orders of magnitude lower than that of the pentapeptide itself. The CD signal of the Ag + -L-KLVFFC hydrogel was observed to be sensitive to the early-stage aggregation of amyloid β peptide.

Background: Improved markers for predicting recurrence are needed to stratify patients with localised (stage I-III) renal cell carcinoma after surgery for selection of adjuvant therapy. We developed a novel assay integrating three modalities-clinical, genomic, and histopathological-to improve the predictive accuracy for localised renal cell carcinoma recurrence., Methods: In this retrospective analysis and validation study, we developed a histopathological whole-slide image (WSI)-based score using deep learning allied to digital scanning of conventional haematoxylin and eosin-stained tumour tissue sections, to predict tumour recurrence in a development dataset of 651 patients with distinctly good or poor disease outcome. The six single nucleotide polymorphism-based score, which was detected in paraffin-embedded tumour tissue samples, and the Leibovich score, which was established using clinicopathological risk factors, were combined with the WSI-based score to construct a multimodal recurrence score in the training dataset of 1125 patients. The multimodal recurrence score was validated in 1625 patients from the independent validation dataset and 418 patients from The Cancer Genome Atlas set. The primary outcome measured was the recurrence-free interval (RFI)., Findings: The multimodal recurrence score had significantly higher predictive accuracy than the three single-modal scores and clinicopathological risk factors, and it precisely predicted the RFI of patients in the training and two validation datasets (areas under the curve at 5 years: 0·825-0·876 vs 0·608-0·793; p<0·05). The RFI of patients with low stage or grade is usually better than that of patients with high stage or grade; however, the RFI in the multimodal recurrence score-defined high-risk stage I and II group was shorter than in the low-risk stage III group (hazard ratio [HR] 4·57, 95% CI 2·49-8·40; p<0·0001), and the RFI of the high-risk grade 1 and 2 group was shorter than in the low-risk grade 3 and 4 group (HR 4·58, 3·19-6·59; p<0·0001)., Interpretation: Our multimodal recurrence score is a practical and reliable predictor that can add value to the current staging system for predicting localised renal cell carcinoma recurrence after surgery, and this combined approach more precisely informs treatment decisions about adjuvant therapy., Funding: National Natural Science Foundation of China, and National Key Research and Development Program of China., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

A series of chromone-oxime derivatives containing piperazine sulfonamide moieties were designed, synthesized and evaluated for their inhibitory activities against IDO1. These compounds displayed moderate to good inhibitory activity against IDO1 with IC 50 values in low micromolar range. Among them, compound 10m bound effectively to IDO1 with good inhibitory activities (hIDO1 IC 50  = 0.64 μM, HeLa IDO1 IC 50  = 1.04 μM) and were selected for further investigation. Surface plasmon resonance analysis confirmed the direct interaction between compound 10m and IDO1 protein. Molecular docking study of the most active compound 10m revealed key interactions between 10m and IDO1 in which the chromone-oxime moiety coordinated to the heme iron and formed several hydrogen bonds with the porphyrin ring of heme and ALA264, consistent with the observation by UV-visible spectra that 10m induced a Soret peak shift from 403 to 421 nm. Moreover, compound 10m exhibited no cytotoxicity at its effective concentration in MTT assay. Consistently, in vivo assays results demonstrated that 10m displayed potent antitumor activity with low toxicity in CT26 tumor-bearing Balb/c mice, in comparison with 1-methyl-l-tryptophan (1-MT) and 4-amino-N-(3-chloro-4-fluorophenyl)-N'-hydroxy-1,2,5-oxadiazole-3-carboximidamide (IDO5L). In brief, the results suggested that chromone-oxime derivatives containing sulfonamide moieties might serve as IDO1 inhibitors for the development of new antitumor agents., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Measurement-device-independent quantum key distribution (MDI-QKD) enables two legitimate users to generate shared information-theoretic secure keys with immunity to all detector side attacks. However, the original proposal using polarization encoding is sensitive to polarization rotations stemming from birefringence in fibers or misalignment. To overcome this problem, here we propose a robust QKD protocol without detector vulnerabilities based on decoherence-free subspaces using polarization-entangled photon pairs. A logical Bell state analyzer is designed specifically for such encoding. The protocol exploits common parametric down-conversion sources, for which we develop a MDI-decoy-state method, and requires neither complex measurements nor a shared reference frame. We have analyzed the practical security in detail and presented a numerical simulation under various parameter regimes, showing the feasibility of the logical Bell state analyzer along with the potential that double communication distance can be achieved without a shared reference frame.

Eukaryotes produce highly modified sterols, including cholesterol, essential to eukaryotic physiology. Although few bacterial species are known to produce sterols, de novo production of cholesterol or other complex sterols in bacteria has not been reported. Here, we show that the marine myxobacterium Enhygromyxa salina produces cholesterol and provide evidence for further downstream modifications. Through bioinformatic analysis we identify a putative cholesterol biosynthesis pathway in E. salina largely homologous to the eukaryotic pathway. However, experimental evidence indicates that complete demethylation at C-4 occurs through unique bacterial proteins, distinguishing bacterial and eukaryotic cholesterol biosynthesis. Additionally, proteins from the cyanobacterium Calothrix sp. NIES-4105 are also capable of fully demethylating sterols at the C-4 position, suggesting complex sterol biosynthesis may be found in other bacterial phyla. Our results reveal an unappreciated complexity in bacterial sterol production that rivals eukaryotes and highlight the complicated evolutionary relationship between sterol biosynthesis in the bacterial and eukaryotic domains., (© 2023. The Author(s).)

Parkinson's disease is a severe neurodegenerative disorder. Currently, deep brain electrical stimulation (DBS) is the first line of surgical treatment. However, serious neurological impairments such as speech disorders, disturbances of consciousness, and depression after surgery limit the efficacy of treatment. In this review, we summarize the recent experimental and clinical studies that have explored the possible causes of neurological deficits after DBS. Furthermore, we tried to identify clues from oxidative stress and pathological changes in patients that could lead to the activation of microglia and astrocytes in DBS surgical injury. Notably, reliable evidence supports the idea that neuroinflammation is caused by microglia and astrocytes, which may contribute to caspase-1 pathway-mediated neuronal pyroptosis. Finally, existing drugs and treatments may partially ameliorate the loss of neurological function in patients following DBS surgery by exerting neuroprotective effects.

LZTFL1 is a tumor suppressor located in chromosomal region 3p21.3 that is deleted frequently and early in various cancer types including the kidney cancer. However, its role in kidney tumorigenesis remains unknown. Here we hypothesized a tumor suppressive function of LZTFL1 in clear cell renal cell carcinoma (ccRCC) and its mechanism of action based on extensive bioinformatics analysis of patients' tumor data and validated it using both gain- and loss-functional studies in kidney tumor cell lines and patient-derive xenograft (PDX) model systems. Our studies indicated that LZTFL1 inhibits kidney tumor cell proliferation by destabilizing AKT through ZNRF1-mediated ubiquitin proteosome pathway and inducing cell cycle arrest at G1. Clinically, we found that LZTFL1 is frequently deleted in ccRCC. Downregulation of LZTFL1 is associated with a poor ccRCC outcome and may be used as prognostic maker. Furthermore, we show that overexpression of LZTFL1 in PDX via lentiviral delivery suppressed PDX growth, suggesting that re-expression of LZTFL1 may be a therapeutic strategy against ccRCC., (© 2023. The Author(s).)

A series of mono- and bisnaphthalimides derivatives containing 3-nitro and 4-morpholine moieties were designed, synthesized, and evaluated for their in vitro anticancer activities against four cancer cell lines. Some compounds exhibited relatively good antiproliferative activity on the cell lines tested, in comparison with mitonafide and amonafide. It is noteworthy that bisnaphthalimide A6 was identified as the most potent compound in anti-proliferation against MGC-803 cells, with an IC 50 lowered to 0.09 μM, a far greater potency than that of mono-naphthalimide A7, mitonafide, and amonafide. A gel electrophoresis assay revealed that DNA and Topo I were the potential targets of compounds A6 and A7. The treatment of CNE-2 cells with compounds A6 and A7 resulted in an S phase cell cycle arrest, accompanied by the upregulation of the expression levels of the antioncogene p27 and the down-regulation of the expression levels of CDK2 and cyclin E. In addition, compounds A6 and A7-induced apoptosis was further confirmed by flow cytometry, ROS generation assay, and Hoechst 33,258 staining. In particular, in vivo antitumor assay results revealed that bisnaphthalimide A6 exhibited potent anticancer efficiency in an MGC-803 xenograft tumor model, in comparison with mitonafide, and had lower toxicity than mono-naphthalimide A7. In brief, the results suggested that bisnaphthalimide derivatives containing 3-nitro and 4-morpholine moieties might serve as DNA binding agents for the development of new antitumor agents., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objectives: Studies in certain cardiac hypertrophy models suggested the individual role of soluble epoxide hydrolase (sEH) and canonical transient receptor potential 3 (TRPC3) channels, however, whether they jointly mediate hypertrophic process remains unexplored. Hyperhomocysteinemia promotes cardiac hypertrophy while the involvement of sEH and TRPC3 channels remains unknown. This study aimed to explore the role of, and interrelation between sEH and TRPC3 channels in homocysteine-induced cardiac hypertrophy., Methods: Rats were fed methionine-enriched diet to induce hyperhomocysteinemia. H9c2 cells and neonatal rat cardiomyocytes were incubated with homocysteine. Cardiac hypertrophy was evaluated by echocardiography, histological examination, immunofluorescence imaging, and expressions of hypertrophic markers. Epoxyeicosatrienoic acids (EETs) were determined by ELISA. TRPC3 current was recorded by patch-clamp. Gene promotor activity was measured using dual-luciferase reporter assay., Results: Inhibition of sEH by 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea (TPPU) reduced ventricular mass, lowered the expression of hypertrophic markers, decreased interstitial collagen deposition, and improved cardiac function in hyperhomocysteinemic rats, associated with restoration of EETs levels in myocardium. TPPU or knockdown of sEH suppressed TRPC3 transcription and translation as well as TRPC3 current that were enhanced by homocysteine. Exogenous 11,12-EET inhibited homocysteine-induced TRPC3 expression and cellular hypertrophy. Silencing C/EBPβ attenuated, while overexpressing C/EBPβ promoted homocysteine-induced hypertrophy and expressions of sEH and TRPC3, resulting respectively from inhibition or activation of sEH and TRPC3 gene promoters., Conclusions: sEH and TRPC3 channels jointly contribute to homocysteine-induced cardiac hypertrophy. Homocysteine transcriptionally activates sEH and TRPC3 genes through a common regulatory element C/EBPβ. sEH activation leads to an upregulation of TRPC3 channels via a 11,12-EET-dependent manner., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Background: Renal clear cell carcinoma (ccRCC) is one of the most prevailing type of malignancies, which is affected by chemokines. Chemokines can form a local network to regulate the movement of immune cells and are essential for tumor proliferation and metastasis as well as for the interaction between tumor cells and mesenchymal cells. Establishing a chemokine genes signature to assess prognosis and therapy responsiveness in ccRCC is the goal of this effort. Methods: mRNA sequencing data and clinicopathological data on 526 individuals with ccRCC were gathered from the The Cancer Genome Atlas database for this investigation (263 training group samples and 263 validation group samples). Utilizing the LASSO algorithm in conjunction with univariate Cox analysis, the gene signature was constructed. The Gene Expression Omnibus (GEO) database provided the single cell RNA sequencing (scRNA-seq) data, and the R package "Seurat" was applied to analyze the scRNA-seq data. In addition, the enrichment scores of 28 immune cells in the tumor microenvironment (TME) were calculated using the "ssGSEA" algorithm. In order to develop possible medications for patients with high-risk ccRCC, the "pRRophetic" package is employed. Results: High-risk patients had lower overall survival in this model for predicting prognosis, which was supported by the validation cohort. In both cohorts, it served as an independent prognostic factor. Annotation of the predicted signature's biological function revealed that it was correlated with immune-related pathways, and the riskscore was positively correlated with immune cell infiltration and several immune checkpoints (ICs), including CD47, PDCD1, TIGIT, and LAG-3, while it was negatively correlated with TNFRSF14. The CXCL2, CXCL12, and CX3CL1 genes of this signature were shown to be significantly expressed in monocytes and cancer cells, according to scRNA-seq analysis. Furthermore, the high expression of CD47 in cancer cells suggested us that this could be a promising immune checkpoint. For patients who had high riskscore, we predicted 12 potential medications. Conclusion: Overall, our findings show that a putative 7-chemokine-gene signature might predict a patient's prognosis for ccRCC and reflect the disease's complicated immunological environment. Additionally, it offers suggestions on how to treat ccRCC using precision treatment and focused risk assessment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Lin, Tang, Yao, Tan, Dai, Wang, Zhu, Xu, Mumin, Liang, Wang, Deng, Luo, Wei and Cao.)

Bariatric surgery reduces body weight, enhances metabolic and diabetic control, and improves outcomes on obesity-related comorbidities. However, the mechanisms mediating this protection against cardiovascular diseases remain unclear. We investigated the effect of sleeve gastrectomy (SG) on vascular protection in response to shear stress-induced atherosclerosis using an overweighted and carotid artery ligation mouse model. Eight-week-old male wild-type mice (C57BL/6J) were fed a high-fat diet (HFD) for two weeks to induce weight gain and dysmetabolism. SG was performed in HFD-fed mice. Two weeks after the SG procedure, partial carotid-artery ligation was performed to promote disturbed flow-induced atherosclerosis. Compared with the control mice, HFD-fed wild-type mice exhibited increased body weight, total cholesterol level, hemoglobin A1c, and enhanced insulin resistance; SG significantly reversed these adverse effects. As expected, HFD-fed mice exhibited greater neointimal hyperplasia and atherosclerotic plaques than the control group, and the SG procedure attenuated HFD-promoted ligation-induced neointimal hyperplasia and arterial elastin fragmentation. Besides, HFD promoted ligation-induced macrophage infiltration, matrix metalloproteinase-9 expression, upregulation of inflammatory cytokines, and increased vascular endothelial growth factor secretion. SG significantly reduced the above-mentioned effects. Moreover, HFD restriction partially reversed the intimal hyperplasia caused by carotid artery ligation; however, this protective effect was significantly lower than that observed in SG-operated mice. Our study demonstrated that HFD deteriorates shear stress-induced atherosclerosis and SG mitigates vascular remodeling, and this protective effect was not comparable in HFD restriction group. These findings provide a rationale for using bariatric surgery to counter atherosclerosis in morbid obesity.