Search

To investigate the association of attention-deficit/hyperactivity disorder (ADHD) with the 48-base pair (bp) variable number of tandem repeats (VNTR) in exon 3 of the dopamine receptor D4 (DRD4) gene, we genotyped 240 ADHD patients and their parents from Hong Kong. The 4R allele was most common, followed by 2R. We examined association between the 2R allele (relative to 4R) and ADHD by Transmission Disequilibrium Test (TDT). The odds ratio (OR) (95% confidence interval) was 0.90 (0.64-1.3). The p-value was 0.6. Examining subgroups revealed nominally significant association of 2R with inattentive ADHD: OR = 0.33 (0.12-0.92) and p = 0.03. Because our study used TDT analysis, we meta-analyzed the association of 2R with ADHD in Asians (1329 patient alleles), revealing results similar to ours: OR = 0.97 (0.80-1.2) and p = 0.8. To examine the association of 2R with inattentive ADHD, we meta-analyzed all studies (regardless of analysis type or ethnicity, in order to increase statistical power): 702 patient alleles, 1420 control alleles, OR = 0.81 (0.57-1.1) and p = 0.2. Overall, there is no evidence of association between ADHD and the 2R allele, but the suggestive association with the inattentive type warrants further investigation., (© 2024 The Authors. Annals of Human Genetics published by University College London (UCL) and John Wiley & Sons Ltd.)

Harnessing the inexhaustible solar energy for water splitting is regarded one of the most promising strategies for hydrogen production. However, sluggish kinetics of oxygen evolution reaction (OER) and expensive photovoltaics have hindered commercial viability. Here, an adhesive-free electrodeposition process is developed for in-situ preparation of earth-abundant electrocatalysts on super-flat indium tin oxide (ITO) substrate. NiFe hydroxide exhibited prominent OER performance, achieving an ultra-low overpotential of 236 mV at 10 mA/cm 2 in alkaline solution. With the superior OER activity, we achieved an unassisted solar water splitting by series connected perovskite solar cells (PSCs) of 2 cm 2 aperture area with NiFe/ITO//Pt electrodes, yielding overall solar to hydrogen (STH) efficiency of 13.75 %. Furthermore, we upscaled the monolithic facility to utilize perovskite solar module for large-scale hydrogen production and maintained an approximate operating current of 20 mA. This creative strategy contributes to the decrease of industrial manufacturing expenses for perovskite-based photovoltaic-electrochemical (PV-EC) hydrogen production, further accelerating the conversion and utilization of carbon-free energy., 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.)

This paper investigates the impact of regulatory distance on corporate environmental performance using data from Chinese A-share listed companies. The results demonstrate that staying away from regulatory agencies significantly improves corporate environmental performance. The potential impact mechanism is that the increase in regulatory distance significantly suppresses rent-seeking activities. The above impacts are particularly pronounced in companies with weak CEO political and financial connections, state-owned enterprises, and firms in regions with low levels of marketization, owing to the fact that these company characteristics influence firms' ability or inclination to participate in rent-seeking. Further evidence indicates that the effect of regulatory distance on environmental performance will be significantly enhanced by strengthening media regulation and anti-corruption efforts., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The development of architecturally unique molecular nanocarbons by bottom-up organic synthesis is essential for accessing functional organic materials awaiting technological developments in fields such as energy, electronics, and biomedicine. Herein, we describe the design and synthesis of a triptycene-based three-dimensional (3D) nanocarbon, GFN-1 , with geometrical flexibility on account of its three peripheral π-panels being capable of interconverting between two curved conformations. An effective through-space electronic communication among the three π-panels of GFN-1 has been observed in its monocationic radical form, which exhibits an extensively delocalized spin density over the entire 3D π-system as revealed by electron paramagnetic resonance and UV-vis-NIR spectroscopies. The flexible 3D molecular architecture of GFN-1 , along with its densely packed superstructures in the presence of fullerenes, is revealed by microcrystal electron diffraction and single-crystal X-ray diffraction, which establish the coexistence of both propeller and tweezer conformations in the solid state. GFN-1 exhibits strong binding affinities for fullerenes, leading to host-guest complexes that display rapid photoinduced electron transfer within a picosecond. The outcomes of this research could pave the way for the utilization of shape and electronically complementary nanocarbons in the construction of functional coassemblies.

Mechanical thrombectomy has emerged as a promising treatment for acute ischemic stroke caused by large vessel occlusion. However, cases involving cancerous emboli retrieved during endovascular embolectomy are rare. We present a case of a 65-year-old man with a history of heavily treated rectal cancer, who developed a middle cerebral artery (MCA) infarction due to metastatic adenocarcinoma. The patient presented with sudden onset right-side weakness, right facial palsy, global aphasia, and left gaze deviation, with a National Institutes of Health Stroke Scale (NIHSS) score of 16. Following intravenous thrombolysis, endovascular thrombectomy was performed, achieving nearly complete recanalization. Pathological examination of the retrieved thrombus revealed metastatic adenocarcinoma of rectal origin. The patient's neurological deficits gradually improved, and he was successfully discharged to undergo further palliative therapy. This case underscores the importance of considering mechanical thrombectomy for patients with advanced solid organ malignancy presenting with acute ischemic stroke, even when the etiology could be a tumor embolus. Our findings highlight the potential for mechanical thrombectomy to restore neurological function in such cases, allowing patients to proceed to the next level of care with a reasonably good post-stroke quality of life., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Ko et al.)

While photo-cross-linking (PXL) with alkyl diazirines can provide stringent distance restraints and offer insights into protein structures, unambiguous identification of cross-linked residues hinders data interpretation to the same level that has been achieved with chemical cross-linking (CXL). We address this challenge by developing an in-line system with systematic modulation of light intensity and irradiation time, which allows for a quantitative evaluation of diazirine photolysis and photo-reaction mechanism. Our results reveal a two-step pathway with mainly sequential generation of diazo and carbene intermediates. Diazo intermediate preferentially targets buried polar residues, many of which are inaccessible with known CXL probes for their limited reactivity. Moreover, we demonstrate that tuning light intensity and duration enhances selectivity towards polar residues by biasing diazo-mediated cross-linking reactions over carbene ones. This mechanistic dissection unlocks the full potential of PXL, paving the way for accurate distance mapping against protein structures and ultimately, unveiling protein dynamic behaviors., (© 2024. The Author(s).)

Objective: NK cells play a vital role in tumor immune resistance. Various factors affect NK cell activity. While NK cell dysfunction has been observed in numerous malignancies, the underlying mechanisms in gastric cancer remain unclear., Method: Flow cytometry was used to identify the phenotypic distribution and expression of activated receptors on NK cells. ELISA was used to determine the expression of cytokines. We examined the expression of NK cell-related genes and explored their association with survival and prognosis. Additionally, we conducted PCR detection of miR-552-5p expression levels in plasma exosomes of patients and investigated its correlation with phenotypic distribution and activated receptors. We used flow cytometry and ELISA to verify the role of miR-552-5p in NK cell dysfunction. Furthermore, we investigated the potential role of PD-1/PD-L1 in regulating NK cell dysfunction in patients' cells., Results: We observed a significant decrease in the percentage of NKG2D and NKp30 and IFN-γ and TNF-α in patients than in healthy volunteers. Patients with low levels of CD56, CD16, NKG2D, and NKP46 exhibited poorer survival prognoses. Moreover, increased expression levels of plasma exosomal miR-552-5p in patients were negatively associated with NK cell phenotypic distribution and activated receptor expression. MiR-552-5p downregulated the secretion of perforin, granzyme, and IFN-γ as well as the expression of NKp30, NKp46, and NKG2D. Additionally, it suppressed the cytotoxicity of NK cells. The inhibitory effect of miR-552-5p, on NK cell function was reversed when anti-PD-L1 antibodies were used., Conclusion: Exosomal miR-552-5p targets the PD-1/PD-L1 axis, leading to impaired NK cell function., (© 2024. The Author(s).)

A mounting body of evidences suggests that patients with chronic heart failure (HF) frequently experience cognitive impairments, but the neuroanatomical mechanism underlying these impairments remains elusive. In this retrospective study, 49 chronic HF patients and 49 healthy controls (HCs) underwent brain structural MRI scans and cognitive assessments. Cortical morphology index (cortical thickness, complexity, sulcal depth and gyrification) were evaluated. Correlations between cortical morphology and cognitive scores and clinical variables were explored. Logistic regression analysis was employed to identify risk factors for predicting 3-year major adverse cardiovascular events. Compared with HCs, patients with chronic HF exhibited decreased cognitive scores (p < .001) and decreased cortical thickness, sulcal depth and gyrification in brain regions involved cognition, sensorimotor, autonomic nervous system (family-wise error correction, all p values <.05). Notably, HF duration and New York Heart Association (NYHA) demonstrated negative correlations with abnormal cortex morphology, particularly HF duration and thickness in left precentral gyrus (r = -.387, p = .006). Cortical morphology characteristics exhibited positive associations with global cognition, particularly cortical thickness in left pars opercularis (r = .476, p < .001). NYHA class is an independent risk factor for adverse outcome (p = .001). The observed correlation between abnormal cortical morphology and global cognition suggested that cortical morphology may serve as a promising imaging biomarker and provide insights into neuroanatomical underpinnings of cognitive impairment in patients with chronic HF., (© 2024 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Background: Frozen shoulder (FS) is characterized by restricted active and passive shoulder mobility and pain., Purpose: Compare the effect of muscle-biased manual therapy (MM) and regular physical therapy (RPT) in patients with FS., Study Design: Pretest-post-test control group study design., Methods: We recruited 34 patients with FS and compared the effect of 12-session MM and RPT. The outcome measures were scapular kinematics and muscle activation, scapular alignment, shoulder range of motion, and pain intensity. Two-way analysis of variance was used to examine the intervention effect with α = 0.05., Results: Both programs resulted in similar improvements in pain and shoulder function. Compared to the RPT, MM resulted in increased posterior tilt (MM: 7.04°-16.09°, RPT: -2.50° to -4.37°; p = 0.002; ES = 0.261) and lower trapezius activation (MM: 260.61%-470.90%, RPT: 322.64%-313.33%; p = 0.033; ES = 0.134) during scaption, and increased posterior tilt (MM: 0.70°-15.16°, RPT: -9.66° to -6.44°; p = 0.007; ES = 0.205) during the hand-to-neck task. The MM group also showed increased GH backward elevation (MM: 37.18°-42.79°, RPT: 43.64°-40.83°; p = 0.004, ES = 0.237) and scapular downward rotation (MM: -2.48° to 6.80°, RPT: 1.93°-1.44°; p < 0.001; ES = 0.404) during the thumb-to-waist task, enhanced shoulder abduction (MM: 84.6°-102.3°, RPT: 85.1°-92.9°; p = 0.02; ES = 0.153), and improved scapular alignment (MM: 10.4-9.65 cm, RPT: 9.41-9.56 cm; p = 0.02; ES = 0.114)., Conclusions: MM was superior to the RPT regarding scapular neuromuscular performance. Clinicians should consider adding muscle-biased treatment when treating FS., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Colorectal cancer (CRC) has a high incidence and mortality. Recent studies have shown that indole derivatives involved in gut microbiota metabolism can impact the tumorigenesis, progression, and metastasis of CRC., Aim: To investigate the effect of indole-3-acetaldehyde (IAAD) on CRC., Methods: The effect of IAAD was evaluated in a syngeneic mouse model of CRC and CRC cell lines (HCT116 and DLD-1). Cell proliferation was assessed by Ki-67 fluorescence staining and cytotoxicity tests. Cell apoptosis was analysed by flow cytometry after staining with Annexin V-fluorescein isothiocyanate and propidium iodide. Invasiveness was investigated using the transwell assay. Western blotting and real-time fluorescence quantitative polymerase chain reaction were performed to evaluate the expression of epithelial-mesenchymal transition related genes and aryl hydrocarbon receptor (AhR) downstream genes. The PharmMapper, SEA, and SWISS databases were used to screen for potential target proteins of IAAD, and the core proteins were identified through the String database., Results: IAAD reduced tumorigenesis in a syngeneic mouse model. In CRC cell lines HCT116 and DLD1, IAAD exhibited cytotoxicity starting at 24 h of treatment, while it reduced Ki67 expression in the nucleus. The results of flow cytometry showed that IAAD induced apoptosis in HCT116 cells but had no effect on DLD1 cells, which may be related to the activation of AhR. IAAD can also increase the invasiveness and epithelial-mesenchymal transition of HCT116 and DLD1 cells. At low concentrations (< 12.5 μmol/L), IAAD only exhibited cytotoxic effects without promoting cell invasion. In addition, predictions based on online databases, protein-protein interaction analysis, and molecular docking showed that IAAD can bind to matrix metalloproteinase-9 (MMP9), angiotensin converting enzyme (ACE), poly(ADP-ribose) polymerase-1 (PARP1), matrix metalloproteinase-2 (MMP2), and myeloperoxidase (MPO)., Conclusion: Indole-3-aldehyde can induce cell apoptosis and inhibit cell proliferation to prevent the occurrence of CRC; however, at high concentrations (≥ 25 μmol/L), it can also promote epithelial-mesenchymal transition and invasion in CRC cells. IAAD activates AhR and directly binds MMP9, ACE, PARP1, MMP2, and MPO, which partly reveals why it has a bidirectional effect., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflict of interest to disclose., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

A high average power re-frequency operation Fe:ZnSe laser using laser diode side-pumped free-running Er:YAG lasers as activating sources is presented. Two pieces of subsurface layer doped Fe:ZnSe polycrystal are adoptive in a reflective resonator configuration and face-cooled by liquid nitrogen. A maximal Fe:ZnSe laser power of 105 W at a wavelength of 4.1 μm is achieved upon pumping by ten home-made Er:YAG lasers with fiber coupled output working at a frequency of 250 Hz and a pulse duration of ∼420 μs. Corresponding to the maximum Fe:ZnSe laser power, the optical-optical efficiency and slope efficiency with respect to the absorbed pump power are 43% and 44% respectively. The beam quality factor M 2 is measured to be 3.4. To the best of our knowledge, it is the highest output average power of an Fe:ZnSe laser reported.

Diamond is considered the most promising next-generation semiconductor material due to its excellent physical characteristics. It has been more than three decades since the discovery of a special structure named n-diamond. However, despite extensive efforts, its crystallographic structure and properties are still unclear. Here, we show that subdisordered structures in diamond provide an explanation for the structural feature of n-diamond. Monocrystalline diamond with subdisordered structures is synthesized via the chemical vapor deposition method. Atomic-resolution scanning transmission electron microscopy characterizations combined with the picometer-precision peak finder technology and diffraction simulations reveal that picometer-scale shifts of atoms within cells of diamond govern the subdisordered structures. First-principles calculations indicate that the bandgap of diamond decreases rapidly with increasing shifting distance, in accordance with experimental results. These findings clarify the crystallographic structure and electronic properties of n-diamond and provide new insights into the bandgap adjustment in diamond.

Objective: Disruption of the protective stratum corneum barrier increases the skin's vulnerability to microorganisms and facilitates conditions such as dandruff. Dandruff is a disorder of the scalp that causes increased scaling of the SC and is associated with Malassezia fungus. Consequently, many anti-dandruff commercial products use anti-fungal active ingredients such as piroctone olamine also known as Octopirox (OPX). OPX is an active ingredient used in a number of topical preparations for the management of dandruff. The characterization of the physicochemical properties of OPX was previously reported. The aim of the present work was to investigate a range of solvent systems for their effects on OPX interaction with human skin., Methods: The solvents used in this study were propylene glycol (PG), diethylene glycol monoethyl ether or Transcutol® (TC), PG monolaurate (PGML), isopropyl myristate (IPM), caprylic/capric triglyceride or Labrafac™ Lipophile WL 1349 (LAB), PG caprylate or Capryol® 90 (CAP), isostearyl isostearate (ISIS) and Plurol® Oleique CC 497 (PIOI). The single solvent systems evaluated were PG, TC, PGML, IPM, ISIS and CAP. For the binary solvent systems, PG and TC were examined. Ternary solvent systems consisted of: PG, TC and LAB; PG, PGML and LAB; and PG, TC and IPM. The concentration of OPX used was 1% (w/v). Heat-separated human epidermis was used for 24 h permeation experiments performed under finite dose conditions; mass balance studies were also conducted., Results: For the six single solvents examined no permeation was evident. Skin permeation of OPX was observed for binary and ternary solvent systems. The highest permeation for all PG:TC binary solvent system ratios tested was from the PG:TC (75:25) system. For the ternary solvent systems investigated, highest cumulative permeation of OPX was observed for PG:PGML:LAB (60:30:10). Considering all systems, PG:TC (75:25) delivered the greatest amount of OPX through the skin. Although OPX is deposited in the skin following the application of neat solvents, higher skin retention values were generally observed for binary and ternary systems., Conclusion: To our knowledge, this is the first study to examine the permeation behaviour of OPX for a range of single, binary and ternary solvent systems., (© 2023 The Authors. International Journal of Cosmetic Science published by John Wiley & Sons Ltd on behalf of Society of Cosmetic Scientists and Societe Francaise de Cosmetologie.)

Background: Cardiac cycle morphological changes can accelerate plaque growth proximal to myocardial bridging (MB) in the left anterior descending artery (LAD)., Objective: To assess coronary CT angiography (CCTA)-based vascular radiomics for predicting proximal plaque development in LAD MB., Methods: Patients with repeated CCTA scans showing LAD MB without proximal plaque in index CCTA were included from Jinling Hospital as development set. They were divided into training and internal testing in an 8:2 ratio. Patients from 4 other tertiary hospitals were set as external validation set. The endpoint was proximal plaque development of LAD MB in follow-up CCTA. Four vascular radiomics models were built: MB centerline (MB CL), proximal MB CL (pMB CL), MB cross section (MB CS), and proximal MB CS (pMB CS), whose performances were evaluated using area under the curve (AUC), integrated discrimination improvement (IDI) and net reclassification improvement (NRI)., Results: 295 patients were included in the development (n=192; median age, 54±11 years; 137 men) and external validation sets (n=103; median age, 57±9 years; 57 men). The pMB CS vascular radiomics model exhibited higher AUCs in training, internal test, and external sets (AUC=0.78, 0.75, 0.75) than the clinical and anatomical model (all p<0.05). Integration of the pMB CS vascular radiomics model significantly raised the AUC of the clinical and anatomical model from 0.56 to 0.75 (p=0.002), along with enhanced NRI (0.76 [0.37-1.14], p<0.001) and IDI (0.17 [0.07-0.26], p<0.001) in the external validation set., Conclusion: The CCTA-based pMB CS vascular radiomics model can predict plaque development in LAD MB., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Immune cells are key players in acute tissue injury and inflammation, including acute kidney injury (AKI). Their development, differentiation, activation status, and functions are mediated by a variety of transcription factors, such as interferon regulatory factor 8 (IRF8) and IRF4. We speculated that IRF8 has a pathophysiologic impact on renal immune cells in AKI and found that IRF8 is highly expressed in blood type 1 conventional dendritic cells (cDC1s), monocytes, monocyte-derived dendritic cells (moDCs) and kidney biopsies from patients with AKI. In a mouse model of ischemia‒reperfusion injury (IRI)-induced AKI, Irf8 -/- mice displayed increased tubular cell necrosis and worsened kidney dysfunction associated with the recruitment of a substantial amount of monocytes and neutrophils but defective renal infiltration of cDC1s and moDCs. Mechanistically, global Irf8 deficiency impaired moDC and cDC1 maturation and activation, as well as cDC1 proliferation, antigen uptake, and trafficking to lymphoid organs for T-cell priming in ischemic AKI. Moreover, compared with Irf8 +/+ mice, Irf8 -/- mice exhibited increased neutrophil recruitment and neutrophil extracellular trap (NET) formation following AKI. IRF8 primarily regulates cDC1 and indirectly neutrophil functions, and thereby protects mice from kidney injury and inflammation following IRI. Our results demonstrate that IRF8 plays a predominant immunoregulatory role in cDC1 function and therefore represents a potential therapeutic target in AKI., Competing Interests: 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., (© 2024 The Authors. Published by Elsevier Ltd.)

The sequence-controlled assembly of nucleic acids and amino acids into well-defined superstructures constitutes one of the most revolutionary technologies in modern science. The elaboration of such superstructures from carbohydrates, however, remains elusive and largely unexplored on account of their intrinsic constitutional and configurational complexity, not to mention their inherent conformational flexibility. Here, we report the bottom-up assembly of two classes of hierarchical superstructures that are formed from a highly flexible cyclo-oligosaccharide─namely, cyclofructan-6 (CF-6). The formation of coordinative bonds between the oxygen atoms of CF-6 and alkali metal cations (i) locks a myriad of flexible conformations of CF-6 into a few rigid conformations, (ii) bridges adjacent CF-6 ligands, and (iii) gives rise to the multiple-level assembly of three extended frameworks. The hierarchical superstructures present in these frameworks have been shown to modulate their nanomechanical properties. This research highlights the unique opportunities of constructing convoluted superstructures from carbohydrates and should encourage future endeavors in this underinvestigated field of science.

Dandruff, or pityriasis capitis simplex, is a common scalp condition associated with excessive flaking and scaling of the epidermal tissue. Other features include irregular corneocyte turnover, irritation, itching and an impaired skin barrier function. Previously we reported the characterization of climbazole (CBZ), an antifungal agent used in the management of dandruff. Skin permeation of CBZ from neat solvents was also investigated. In the present work we evaluated CBZ permeation in human skin in vitro from more complex formulations that better represent products used by consumers. The various systems studied were composed of propylene glycol (PG), Transcutol®P (TC), octyl salicylate (OSal) and isopropyl alcohol (IPA). As well as measurement of skin uptake and penetration of CBZ, where possible, the skin retention and permeation of the various solvents was also determined. All vehicles promoted skin permeation of CBZ but no significant differences in amount permeated were evident between the binary vehicles (PG:TC, TC:OSal) and the ternary vehicle studied (PG:IPA:OSal). The binary vehicles generally promoted more skin uptake of CBZ compared with the neat solvents (PG, TC, OSal) studied previously. Permeation and skin extraction of CBZ from the PG:TC vehicles increased with increasing PG content; a similar trend was evident for the PG:IPA:OSal systems. New methods were developed and validated for measurement of PG, TC and OSal. Analysis of the individual solvents indicated that PG permeation was also independent of the amounts of other solvents in the binary or ternary systems. Consistent with previous findings higher proportions of TC permeated compared with PG for the PG:TC binary systems; TC also permeated the skin more rapidly than PG from these vehicles. For OSal, skin extraction was generally higher for TC:OSal compared with the PG:IPA:OSal vehicle. However, increasing the content of OSal did not appear to influence CBZ skin uptake nor permeation. Interestingly, the effects of the various PG:TC vehicles on CBZ skin delivery contrast with results we previous reported for the same systems for a different active. This confirms that with reference to skin permeation, formulation effects and/or skin penetration enhancement should be expected to vary and may not be predicted for specific vehicles., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Purpose: The purpose of this study was to investigate the effect of integrated evaluation of resting static computed tomography perfusion (CTP) and coronary computed tomography angiography (CCTA)-derived fractional flow reserve (FFR CT ) on therapeutic decision-making and predicting major adverse cardiovascular events (MACEs) in patients with suspected coronary artery disease., Materials and Methods: In this post hoc analysis of a prospective trial of CCTA in patients assigned to either CCTA or CCTA plus FFR CT arms, 500 patients in the CCTA plus FFR CT arm were analyzed. Both resting static CTP and FFR CT were evaluated by using the conventional CCTA. Perfusion defects in the myocardial segments with ≥50% degree of stenosis in the supplying vessels were defined as resting static CTP positive, and any vessel with an FFR CT value of ≤0.80 was considered positive. Patients were divided into 3 groups: (1) negative CTP-FFR CT match group (resting static CTP-negative and FFR CT -negative group); (2) mismatch CTP-FFR CT group (resting static CTP-positive and FFR CT -negative or resting static CTP-negative and FFR CT -positive group); and (3) positive CTP-FFR CT match group (resting static CTP-positive and FFR CT -positive group). We compared the revascularization-to-invasive coronary angiography ratio and the MACE rate among 3 subgroups at 1- and 3-year follow-ups. The adjusted Cox hazard proportional model was used to assess the prognostic value of FFR CT and resting static CTP to determine patients at risk of MACE., Results: Patients in the positive CTP-FFR CT match group were more likely to undergo revascularization at the time of invasive coronary angiography compared with those in the mismatch CTP-FFR CT group (81.4% vs 57.7%, P =0.033) and the negative CTP-FFR CT match group (81.4% vs 33.3%, P= 0.001). At 1- and 3-year follow-ups, patients in the positive CTP-FFR CT match group were more likely to have MACE than those in the mismatch CTP-FFR CT group (10.5% vs 4.2%, P= 0.046; 35.6% vs 9.4%, P <0.001) and the negative CTP-FFR CT match group (10.5% vs 0.9%, P <0.001; 35.6% vs 5.4%, P <0.001). A positive CTP-FFR CT match was strongly related to MACE at 1-year (hazard ratio=8.06, P= 0.003) and 3-year (hazard ratio=6.23, P <0.001) follow-ups., Conclusion: In patients with suspected coronary artery disease, the combination of FFR CT with resting static CTP could guide therapeutic decisions and have a better prognosis with fewer MACE in a real-world scenario., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

The influence of distance restraints from chemical cross-link mass spectroscopy (XL-MS) on the quality of protein structures modeled with the coarse-grained UNRES force field was assessed by using a protocol based on multiplexed replica exchange molecular dynamics, in which both simulated and experimental cross-link restraints were employed, for 23 small proteins. Six cross-links with upper distance boundaries from 4 Å to 12 Å (azido benzoic acid succinimide (ABAS), triazidotriazine (TATA), succinimidyldiazirine (SDA), disuccinimidyl adipate (DSA), disuccinimidyl glutarate (DSG), and disuccinimidyl suberate (BS 3 )) and two types of restraining potentials ((i) simple flat-bottom Lorentz-like potentials dependent on side chain distance (all cross-links) and (ii) distance- and orientation-dependent potentials determined based on molecular dynamics simulations of model systems (DSA, DSG, BS 3 , and SDA)) were considered. The Lorentz-like potentials with properly set parameters were found to produce a greater number of higher-quality models compared to unrestrained simulations than the MD-based potentials, because the latter can force too long distances between side chains. Therefore, the flat-bottom Lorentz-like potentials are recommended to represent cross-link restraints. It was also found that significant improvement of model quality upon the introduction of cross-link restraints is obtained when the sum of differences of indices of cross-linked residues exceeds 150.

A high-power all-fiber radially polarized laser system is demonstrated, in which an integrated nanograting mode convertor (S-wave plate) is used for the generation of radially polarized beam. Experimentally, a 1-W radially polarized beam was used as the seed laser, whose mode purity and mode extinction ratio (MER) were 96.5% and 98.3%, respectively. A single-stage few-mode fiber amplifier was employed to boost the 1-W seed laser to an average power of 113.2 W, when the pump power was 160 W. The corresponding slope efficiency and beam quality factor (M 2 ) were approximately 72% and 2.3%, respectively. Moreover, the mode purity and MER of the amplified radially polarized laser were measured to be 95.7% and 97%, respectively. To the best of our knowledge, this is the highest output power from an all-fiber radially polarized laser system without obvious degradations of the mode purity and MER.

The study of immune regulation mechanisms induced by parasites may help develop new treatment methods for inflammatory diseases including type 1 diabetes, which is related to type 1 immune responses. The negative correlation between schistosomiasis infection and type 1 diabetes has been confirmed, and the mechanism of Schistosoma-mediated prevention of type 1 diabetes may be related to the adaptive and innate immune systems. Schistosoma-related molecules affect immune cell composition and macrophage polarization and stimulate an increase in natural killer T cells. Furthermore, Schistosoma-related molecules can regulate the adaptive immune responses related to the prevention of type 1 diabetes and change the Th1/Th2 and Th17/Treg axis. Our previous review showed the role of regulatory T cells in the protective of type 1 diabetes mediated by Schistosoma. Here, we aim to review the other mechanisms of schistosomiasis infection and Schistosoma-related products in regulating the immune response associated with the treatment of type 1 diabetes., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023. Published by Elsevier B.V.)

Saccharomyces cerevisiae ( S. cerevisiae ) and Kluyveromyces marxianus ( K. marxianus ) are often used as fermenters in yogurt and alcohol, and have been less studied within meat products. The yeasts were added to sauce meat, and the uninoculated group served as a control in this study to examine and compare the changing patterns of physicochemical and flavor characteristics of S. cerevisiae and K. marxianus on sauce meat during storage. The changes in moisture content, aw, pH, thiobarbituric acid reactive substances (TBARS), and other flavor characteristics were measured in sauce meat during the first, second, fourth, and sixth months after production. The following factors were examined: moisture content, aw, pH, TBARS, peroxide value (POV), acid value (AV), soluble protein (SP), free amino acid (FAA), and volatile flavoring compounds. With VIP > 1 and p < 0.05 as the screening conditions, the partial least squares model (PLS-DA) was used to assess the distinctive flavor components in the sausages. The findings demonstrated that the three groups' changes in sauce meat were comparable during the first two months of storage but differed significantly between the 4th and 6th months. The moisture content, water activity, and pH of the sauce meat decreased gradually with the storage time; TBARS, AV, and FAA increased significantly; SP decreased significantly from 2.61 to 1.72, while POV increased to 0.03 and then decreased to 0.02. The POV and TBARS values of the yeast-infected meat were substantially lower than those of the control group, and the POV and TBARS values of the meat inoculated with S. cerevisiae were particularly decreased ( p < 0.05). The POV and TBARS values of SC ( S. cerevisiae group) decreased by 49.09% and 40.15%, respectively, compared to CK (the control group) at the time of storage until June. The experimental group (KM: K. marxianus group) significantly increased the SP and FAA values of the sauce meat ( p < 0.05) by 32.4% and 29.84% compared to the CK group, respectively. Esters and olefins as well as alcohols and esters were much greater in meat that had been supplemented with S. cerevisiae and K. marxianus than in meat from the control group. In conclusion, inoculating sauce meat with S. cerevisiae can significantly enhance the quality and flavor of sauce meat while it is being stored.

Purpose: Alzheimer's disease (AD) is the most common neurodegenerative disease, and its multifactorial nature increases the difficulty of medical research. To explore an effective treatment for AD, a series of novel tacrine-selegiline hybrids with ChEs and MAOs inhibitory activities were designed and synthesized as multifunctional drugs., Methods: All designed compounds were evaluated in vitro for their inhibition of cholinesterases (AChE/BuChE) and monoamine oxidases (MAO-A/B) along with their blood-brain barrier permeability. Then, further biological activities of the optimizing compound 7d were determined, including molecular model analysis, in vitro cytotoxicity, acute toxicity studies in vivo, and pharmacokinetic and pharmacodynamic property studies in vivo., Results: Most synthesized compounds demonstrated potent inhibitory activity against ChEs/MAOs. Particularly, compound 7d exhibited good and well-balanced activity against ChEs ( h AChE: IC 50 = 1.57 μM, h BuChE: IC 50 = 0.43 μM) and MAOs ( h MAO-A: IC 50 = 2.30 μM, h MAO-B: IC 50 = 4.75 μM). Molecular modeling analysis demonstrated that 7d could interact simultaneously with both the catalytic active site (CAS) and peripheral anionic site (PAS) of AChE in a mixed-type manner and also exhibits binding affinity towards BuChE and MAO-B. Additionally, 7d displayed excellent permeability of the blood-brain barrier, and under the experimental conditions, it elicited low or no toxicity toward PC12 and BV-2 cells. Furthermore, 7d was not acutely toxic in mice at doses up to 2500 mg/kg and could improve the cognitive function of mice with scopolamine-induced memory impairment. Lastly, 7d possessed well pharmacokinetic characteristics., Conclusion: In light of these results, it is clear that 7d could potentially serve as a promising multi-functional drug for the treatment of AD., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Huang et al.)

Coronary artery disease is a leading cause of death worldwide. Major adverse cardiac events are associated not only with coronary luminal stenosis but also with atherosclerotic plaque components. Coronary computed tomography angiography (CCTA) enables non-invasive evaluation of atherosclerotic plaque along the entire coronary tree. However, precise and efficient assessment of plaque features on CCTA is still a challenge for physicians in daily practice. Artificial intelligence (AI) refers to algorithms that can simulate intelligent human behavior to improve clinical work efficiency. Recently, cardiovascular imaging has seen remarkable advancements with the use of AI. AI-assisted CCTA has the potential to facilitate the clinical workflow, offer objective and repeatable quantitative results, accelerate the interpretation of reports, and guide subsequent treatment. Several AI algorithms have been developed to provide a comprehensive assessment of atherosclerotic plaques. This review serves to highlight the cutting-edge applications of AI-assisted CCTA in atherosclerosis plaque characterization, including detecting obstructive plaques, assessing plaque volumes and vulnerability, monitoring plaque progression, and providing risk assessment. Finally, this paper discusses the current problems and future directions for implementing AI in real-world clinical settings., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2024 The Author(s). Published by IMR Press.)

Hyperglycaemia causes impairment of osteogenic differentiation and accelerates stem cell senescence, resulting in weakened osteogenesis and disordered bone metabolism. Phytic acid (PA) is an antioxidant that is reportedly beneficial to bone homeostasis. The present study aims to clarify how PA affects the osteogenic capacity and cellular senescence of bone marrow mesenchymal stem cells (BMSCs) exposed to high-glucose environments, as well as the potential molecular mechanisms. Our results indicate that osteogenic differentiation in BMSCs cultivated in high-glucose conditions is enhanced by PA, as evidenced by increased alkaline phosphatase activity and staining, Alizarin Red S staining, osteogenic marker in in vitro studies, and increased osteogenesis in animal experiments. PA also prevented high-glucose-induced senescence of BMSCs, as evidenced by the repression of reactive oxygen species production, senescence-associated β-galactosidase staining, and P21 and P53 expression. Furthermore, it was found that PA rescued the high-glucose-inhibited expression of phosphorylated extracellular regulated protein kinases (p-ERK). The inhibition of ERK pathway by the specific inhibitor PD98059 blocked the PA-enhanced osteogenesis of BMSCs and promoted cell senescence. Our results revealed that PA enhances osteogenic differentiation and inhibits BMSC senescence in a high-glucose environment. In addition, the activation of the ERK pathway seems to mediate the beneficial effects of PA. The findings provide novel insights that could facilitate bone regeneration in patients with diabetes., 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.)

Objectives: To evaluate the prognostic value of radiomics features based on late gadolinium enhancement (LGE) cardiac magnetic resonance (CMR) images in patients with cardiac amyloidosis (CA)., Methods: This retrospective study included 120 CA patients undergoing CMR at three institutions. Radiomics features were extracted from global and three different segments (base, mid-ventricular, and apex) of left ventricular (LV) on short-axis LGE images. Primary endpoint was all-cause mortality. The predictive performance of the radiomics features and semi-quantitative and quantitative LGE parameters were compared by ROC. The AUC was used to observe whether Rad-score had an incremental value for clinical stage. The Kaplan-Meier curve was used to further stratify the risk of CA patients., Results: During a median follow-up of 12.9 months, 30% (40/120) patients died. There was no significant difference in the predictive performance of the radiomics model in different LV sections in the validation set (AUCs of the global, basal, middle, and apical radiomics model were 0.75, 0.77, 0.76, and 0.77, respectively; all p > 0.05). The predictive performance of the Rad-score of the base-LV was better than that of the LGE total enhancement mass (AUC:0.77 vs. 0.54, p < 0.001) and LGE extent (AUC: 0.77 vs. 0.53, p = 0.004). Rad-score combined with Mayo stage had better predictive performance than Mayo stage alone (AUC: 0.86 vs. 0.81, p = 0.03). Rad-score (≥ 0.66) contributed to the risk stratification of all-cause mortality in CA., Conclusions: Compared to quantitative LGE parameters, radiomics can better predict all-cause mortality in CA, while the combination of radiomics and Mayo stage could provide higher predictive accuracy., Clinical Relevance Statement: Radiomics analysis provides incremental value and improved risk stratification for all-cause mortality in patients with cardiac amyloidosis., Key Points: • Radiomics in LV-base was superior to LGE semi-quantitative and quantitative parameters for predicting all-cause mortality in CA. • Rad-score combined with Mayo stage had better predictive performance than Mayo stage alone or radiomics alone. • Rad-score ≥ 0.66 was associated with a significantly increased risk of all-cause mortality in CA patients., (© 2023. The Author(s), under exclusive licence to European Society of Radiology.)

Type 1 diabetes mellitus is a chronic disease caused by the destruction of pancreatic beta cells. Based on the hygiene hypothesis, a growing body of evidence suggests a negative association between parasitic infections and diabetes in humans and animal models. The mechanism of parasite-mediated prevention of type 1 diabetes mellitus may be related to the adaptive and innate immune systems. Macrophage polarization is a new paradigm for the treatment of type 1 diabetes mellitus, and different host macrophage subsets play various roles during parasite infection. Proinflammatory cytokines are released by M1 macrophages, which are important in the development of type 1 diabetes mellitus. Parasite-activated M2 macrophages prevent the development of type 1 diabetes mellitus and can influence the development of adaptive immune responses through several mechanisms, including Th2 cells and regulatory T cells. Here, we review the role and mechanism of macrophage polarization in parasitic protection against type 1 diabetes mellitus., Competing Interests: Declaration of competing interest No., (Copyright © 2023. Published by Elsevier Inc.)

Accurately distinguishing between enantiomeric molecules is a fundamental challenge in the field of chemistry. However, there is still significant room for improvement in both the enantiomeric selectivity (K R(S) /K S(R) ) and binding strength of most reported macrocyclic chiral receptors to meet the demands of practical application scenarios. Herein, we synthesized a water-soluble conjugated tubular host-namely, corral[4]BINOL-using a chiral 1,1'-bi-2-naphthol (BINOL) derivative as the repeating unit. The conjugated chiral backbone endows corral[4]BINOL with good fluorescent emission (QY=34 % ) and circularly polarized luminescence (|g lum | up to 1.4×10 -3 ) in water. Notably, corral[4]BINOL exhibits high recognition affinity up to 8.6×10 10  M -1 towards achiral guests in water, and manifested excellent enantioselectivity up to 18.7 towards chiral substrates, both of which represent the highest values observed among chiral macrocycles in aqueous solution. The ultrastrong binding strength, outstanding enantioselectivity, and facile accessibility, together with the superior fluorescent and chiroptical properties, endow corral[4]BINOL with great potential for a wide range of applications., (© 2023 Wiley-VCH GmbH.)

Background: Endosseous implants are widely used as a treatment for tooth loss, but gaps in the implant-abutment interface, and the cavity inside the implant, can cause inflammation of the tissue surrounding the implant. Currently available filling materials, however, cannot solve these problems. Therefore, the development of new antibacterial materials is key. In this study, we synthesized Ag nanoparticle-coated polytetrafluoroethylene (PTFE), analyzed the effect of Ag ion concentration, and estimated the antibacterial effects against oral pathogens in vitro. Method: The Ag nanoparticles (AgNPs)-modified PTFE was achieved using self-polymerized dopamine in an alkaline solution (2 mg/mL) and reduction reaction of Ag ions (0.01 mol/L and 0.05 mol/L). The surface features, chemical components, and wettability were characterized by scanning electron microscopy (SEM), energy-dispersive spectroscopy (EDS), X-ray photoelectron spectroscopy (XPS) and contact angle measurement. The antibacterial effect against Streptococcus mutans and Porphyromonas gingivalis was evaluated by counting colony-forming units on agar media and the visualization of bacteria present on the specimens by SEM and confocal laser scanning microscope (CLSM)., Results: The surface characterization results indicated that a polydopamine film was successfully formed on the PTFE membrane, and spherical AgNPs were successfully reduced. With increasing concentration of the Ag precursor, the contents of the AgNPs increased ( p < 0.05). The antibacterial ratio of AgNP-coated PTFE against Streptococcus mutans and Porphyromonas gingivalis reached 94.2% and 80.6%, respectively. The results of antibacterial testing analyzed via SEM and CLSM also demonstrated the robust antibacterial ability of AgNPs-modified PTFE ( p < 0.05)., Conclusions: AgNPs-modified PTFE has great potential to function as an implant filling material with enhanced antibacterial properties, and has the potential to be a novel antimicrobial material for the prevention of peri-implantitis in the clinic.

Purpose: Methyltransferase like 1 (METTL1) regulates epitranscriptomes via the m7G modification in mammalian mRNA and microRNA. Systemic lupus erythematosus (SLE) is caused by abnormal immune reactivity and has diverse clinical manifestations. RNA methylation as a mechanism to regulate gene expression is widely implicated in immune regulation. However, the role of m7G in immune response of SLE has not been extensively studied., Patients and Methods: Expression of METTL1 was identified in the public dataset GSE122459 and validated in an independent cohort of SLE patients. We investigated the association between METTL1-expression and clinical manifestations of SLE. Subsequently, differentially expressed genes (DEG) that were correlated with METTL1-expression in GSE122459 were used for functional enrichment analysis. The correlation between infiltrating immune cells and METTL1, as well as candidate biomarkers identified to be correlated with either METTL1 or immune cell infiltration were assessed by single-sample GSEA. Potential mechanisms were explored with Gene ontology and KEGG pathway enrichment. Diagnostic performances of candidate biomarkers in SLE were analyzed., Results: The mRNA and protein expression of METTL1 in SLE patients were significantly decreased in both datasets. METTL1-coexpressed DEGs were enriched in several key immune-related pathways. Activated CD8 T cells, activated CD4 T cells, memory B cells and type 2 helper T cells were different between patients with high and low METTL1 expression. Further, activated CD8 T-cells, activated CD4 T-cells, memory B-cells were correlated with METTL1. The genes of LAMP3, CD83, PDCD1LG2, IGKVD3D-20, IGKV5-2, IGKV2D-30, IGLV3-19 and IGLV4-60 were identified as candidate targets that were correlated with immune cell proportion. Moreover, LAMP3, CD83, and PDCD1LG2 expression were of diagnostic value in SLE as indicated by ROC analysis., Conclusion: Our findings suggested that METTL1 and its candidate targets LAMP3, CD83, PDCD1LG2 may be used for diagnosing SLE and could be explored for developing targeted molecular therapy for SLE., Competing Interests: The authors report no conflicts of interest in this work., (© 2023 Liu et al.)

Polymer properties can be altered via lithium ion doping, whereby adsorbed Li + binds with H 2 O within the polymer chain. However, direct spectroscopic evidence of the tightness of Li + /H 2 O binding in the solid state is limited, and the impact of Li + on polymer sidechain packing is rarely reported. Here, we investigate a polystyrene/H 2 O/LiCl system using solid-state NMR, from which we determined a dipolar coupling of 11.4 kHz between adsorbed Li + and H 2 O protons. This coupling corroborates a model whereby Li + interacts with the oxygen atom in H 2 O via charge affinity, which we believe is the main driving force of Li + binding. We demonstrated the impact of hydrated Li + on sidechain packing and dynamics in polystyrene using proton-detected solid-state NMR. Experimental data and density functional theory (DFT) simulations revealed that the addition of Li + and the increase in the hydration levels of Li + , coupled with aromatic ring binding, change the energy barrier of sidechain packing and dynamics and, consequently, changes the glass transition temperature of polystyrene.

Green power trading is an institutional innovation proposed by China to promote green and sustainable development. This policy aims to relieve the serious debt pressure of renewable energy generation enterprises, thus laying the foundation for achieving carbon reduction targets. This paper empirically examines the role of green power trading by constructing the difference-in-differences (DID) model. Our findings indicate that green power trading significantly reduces the debt levels of policy-covered generation enterprises. This effect is more pronounced for state-owned enterprises, companies with better ESG performance, companies in regions with higher degree of marketization and companies specializing in renewable energy power generation. Further research discusses the impact mechanism of green power trading in terms of external and internal environmental channels. We find that a strong green development atmosphere, especially the external atmosphere, will significantly reinforce the weakening effect of green power trading on corporate debt. Our research provides empirical evidence for the success of green power trading policy in its pilot phase., 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.)

Anti-phospholipid autoantibodies are a group of antibodies that can specifically bind to anionic phospholipids and phospholipid protein complexes. Recent studies have reported elevated serum anti-phospholipid autoantibody levels in patients with antiphospholipid syndrome, systemic lupus erythematosus, rheumatoid arthritis, metabolic disorders, malaria, SARS-CoV-2 infection, obstetric diseases and cardiovascular diseases. However, the underlying mechanisms of anti-phospholipid autoantibodies in disease pathogenesis remain largely unclear. Emerging evidence indicate that anti-phospholipid autoantibodies modulate NETs formation, monocyte activation, blockade of apoptotic cell phagocytosis in macrophages, complement activation, dendritic cell activation and vascular endothelial cell activation. Herein, we provide an update on recent advances in elucidating the effector mechanisms of anti-phospholipid autoantibodies in the pathogenesis of various diseases, which may facilitate the development of potential therapeutic targets for the treatment of anti-phospholipid autoantibody-related disorders., Competing Interests: Declaration of Competing Interest The authors have declared that no competing interest exists., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objectives: To evaluate the performance of coronary computed tomography angiography (CCTA) derived characteristics including CT derived fractional flow reserve (CT-FFR) with FFR as a reference standard in identifying the lesion-specific ischemia by machine learning (ML) algorithms., Methods: The retrospective analysis enrolled 596 vessels in 462 patients (mean age, 61 years ± 11 [SD]; 71.4 % men) with suspected coronary artery disease who underwent CCTA and invasive FFR. The data were divided into training cohort, internal validation cohort, external validation cohorts 1 and 2 according to participating centers. All CCTA-derived parameters, which contained 10 qualitative and 33 quantitative plaque parameters, were collected to establish ML model. The Boruta and unsupervised clustering algorithm were implemented to select important and non-redundant parameters. Finally, the eight features with the highest mean importance were included for further ML model establishment and decision tree building. Five models were built to predict lesion-specific ischemia: stenosis degree from CCTA, CT-FFR, ΔCT-FFR, ML model and nested model., Results: Low-attenuation plaque, bend and lesion length were the main predictors of ischemia-specific lesions. Of 5 models, the ML model showed favorable discrimination for ischemia-specific lesions in the training and three validation sets (area under the curve [95 % confidence interval], 0.93 [0.90-0.96], 0.86 [0.79-0.94], 0.88 [0.83-0.94], and 0.90 [0.84-0.96], respectively). The nested model which combined the ML model and CT-FFR showed better diagnostic efficacy (AUC [95 %CI], 0.96 [0.94-0.99], 0.92 [0.86-0.99], 0.92 [0.86-0.99] and 0.94 [0.91-0.98], respectively; all P < 0.05), and net reclassification improvement (NRI) and integrated discrimination improvement (IDI) were significantly higher than CT-FFR alone., Conclusions: Comprehensive CCTA-derived multiparameter model could better predict the ischemia-specific lesions by ML algorithms compared to stenosis degree from CTA, CT-FFR and ΔCT-FFR. Decision tree can be used to predict myocardial ischemia effectively., 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. This work was supported by the Jiangsu Province Key Project of Comprehensive Prevention and Control of Chronic Diseases (grant BE2020699)., (Copyright © 2023. Published by Elsevier B.V.)

A high beam quality diode-pumped Nd:YAG master oscillator power-amplifier (MOPA) laser with three end-pumped slab amplifiers is developed. The Q -swtiched side-pumped rod oscillator presented a pulse energy 3.1 mJ with beam quality factors of M x 2=1.17 and M y 2=1.15 at a repetition of 1 kHz. The MOPA system delivered a pulse energy of 1.36 J with a pulse width of 48.2 ns and an extraction efficiency of 44.8%. The beam quality factors of M x 2=1.72 and M y 2=3.85 are measured without any phase-conjugators or adaptive optics.

Coherent beam combining (CBC) of cylindrical vector beams (CVBs) based on an active phase controller is proposed and demonstrated. Experimentally, two pieces of spatially variant wave plates (S-wave plate) were employed as vector mode convertors for two individual 1064-nm fiber amplifier channels. When the system was in a closed loop, a combined output power of 10 W and a CBC efficiency of higher than 94% were achieved, for both TM 01 (radially polarized) mode and TE 01 (azimuthally polarized) mode cases. Moreover, the laser system showed a high vector mode purity, which was measured to be ∼97.4% (TM 01 ) and ∼97.3% (TE 01 ). To the best of knowledge, this could possibly be the first demonstration of CBC of CVBs, which paves the way for power scaling of CVBs.

Background: Endobronchial ultrasonography-guided transbronchial needle aspiration biopsy (EBUS-TBNA) has been used for more than 10 years in China. Its clinical application and diagnostic value in different diseases with large sample was lack of report., Methods: A retrospective analysis was performed about the application and diagnostic value of EBUS-TBNA in different disease of patients in Respiratory Intervention Center of Guangzhou Institute of Respiratory Health from January 2012 to July 2020., Results: A total 5758 patients were included with 182 patients excluded for lack of information. Finally, data of 5576 patients (3798 males and 1778 females) were analyzed. For anesthetize, most patients were undergoing general anesthesia of intravenous with spontaneous breathing (69.4%), followed by general anesthesia of intravenous and inhalation with tracheal intubation and mechanical ventilation (17.9%) and conscious sedation and analgesia (12.8%). Lymph nodes were the main sites of biopsy obtained (76.4%). Tumors accounted for the highest proportion of disease (66.4%), followed by infection diseases (9.9%), sarcoidosis (3.9%), lymphoma (1.1%), and others (18.7%). The sensitivity of EBUS-TBNA for diagnosis of tumor was 89.7%, and 40.8% for infection diseases. There were significant differences in the puncture site and proportions of diseases between male and females (both p < 0.05). Higher diagnostic value was found in male patients (p < 0.05)., Conclusion: EBUS-TBNA has good diagnostic value for different mediastinal and central pulmonary space-occupying lesions diseases, with highest sensitivity for tumors. Higher diagnostic value was found in male patients., (© 2023. BioMed Central Ltd., part of Springer Nature.)

As one of the famous karst springs in Shanxi Province, the Gudui spring is the only medium-low temperature hot spring, with a long history of development and a rich cultural accumulation. The karst groundwater in the Gudui spring catchment was taken as the research object. Through systematic sample collection and isotope analysis, hydrochemistry (Durov map, ion ratio, Gibbs map, and hydrogen and oxygen isotope) methods were comprehensively used to analyze groundwater hydrochemistry and groundwater system runoff characteristics. The 87 Sr/ 86 Sr value of karst groundwater in the Gudui spring catchment was 0.709 to 0.717, and the Mg/(Mg+Ca) value was 0.27 to 0.74. By analyzing the Sr isotope composition and Mg/(Mg+Ca) and 1/Sr variation characteristics, it was concluded that the karst groundwater in the Gudui spring catchment was a mixture of deep hot water and shallow cold water. The karst water subsystem of Nanliang spring presented the characteristics of carbonate stratum runoff. The karst water subsystem of Fuling Mountain Gaoxian Haitou spring and the deep circulation subsystem of Houma Basin exhibited the runoff characteristics of carbonate rock and igneous rock strata. The karst water subsystem of Taiershan Jiuyuanshan Gudui spring presented the runoff characteristics of carbonate rock and ancient silicoaluminate strata. The δ 18 O value in karst groundwater of Guodui spring area ranged from -11.46‰ to -7.81‰, and the average value was -10.08‰. The range of the δ D value was -83.7‰ to -60.8‰, and the average value was -73.6‰. This showed that karst groundwater in the spring area was the result of mixing of various types of water. Through comparative analysis of hydrogen and oxygen isotopes of 2014 and 2021 sampling points at the same location, it was concluded that the change in water samples at the Guduiquan resulted from the gradual accumulation of water supplied by Sanquan Reservoir. The change in Sanquan Reservoir was due to the influence of Yellow River diversion. The karst groundwater in the spring area were characterized by large calcium ion, magnesium ion, and sodium ion values; a small potassium ion value; a large sulfate value; and a small chloride value. The hydrochemical types of karst groundwater in Gudui spring catchment could be divided into SO 4 -Na, SO 4 -Ca, HCO 3 -Na, HCO 3 -Mg, HCO 3 -Ca, and Cl-Na. The hydrochemical types of karst groundwater showed evident hydrochemical composition zoning from HCO 3 -Ca·Mg→HCO 3 ·SO 4 -Ca·Mg→SO 4 ·HCO 3 -Na·Ca→SO 4 ·Cl-Na·Ca. According to the comprehensive analysis of hydrochemical isotope and hydrogeological conditions, the karst water subsystem of Nanliang spring was primarily recharged by rainfall infiltration in the exposed limestone area and river infiltration, and its karst groundwater was recharged by runoff from south to north to the karst water subsystem of Fuling Mountain Gaoxian Haitou spring and the deep circulation subsystem of Houma Basin. The karst water subsystem of Taier Jiuyuan Mountain Gudui spring received rainfall infiltration supplement and upstream runoff supplement from the exposed limestone area. Its karst groundwater flowed from north to south and received the supply of Sanquan Reservoir from Yellow River water in the natural discharge area of Gudui spring.

The conventional approach toward molecules with large two-photon absorption (TPA) involves donor-acceptor conjugation. Herein we show a new strategy involving the use of hexa-branched nanographenes. We synthesized two hexa-branched nanographenes, one with six benzoaceanthrylene arms fused to the coronene core and the other with six pyrenyl arms fused to the coronene core. Neither of these hexa-branched nanographenes has a donor-acceptor structure, yet they exhibited high TPA values of 3.6 × 10 3 and 1.9 × 10 4 GM, respectively, which are the highest values recorded for heteroatom-free hydrocarbon molecules. Theoretical analysis suggests that the fused branched structures are responsible for the large TPA cross-section. These findings illustrate the importance of the topology of the fused conjugated skeleton in TPA and provide an alternative structural design toward large TPA.

Background: Rapid plaque progression (RPP) is associated with a higher risk of acute coronary syndromes compared with gradual plaque progression. We aimed to develop and validate a coronary computed tomography angiography (CCTA)-based radiomics signature (RS) of plaques for predicting RPP., Methods: A total of 214 patients who underwent serial CCTA examinations from 2 tertiary hospitals (development group, 137 patients with 164 lesions; validation group, 77 patients with 101 lesions) were retrospectively enrolled. Conventional CCTA-defined morphological parameters (eg, high-risk plaque characteristics and plaque burden) and radiomics features of plaques were analyzed. RPP was defined as an annual progression of plaque burden ≥1.0% on lesion-level at follow-up CCTA. RS was built to predict RPP using XGBoost method., Results: RS significantly outperformed morphological parameters for predicting RPP in both the development group (area under the receiver operating characteristic curve, 0.82 versus 0.74; P =0.04) and validation group (area under the receiver operating characteristic curve, 0.81 versus 0.69; P =0.04). Multivariable analysis identified RS (odds ratio, 2.35 [95% CI, 1.32-4.46]; P =0.005) as an independent predictor of subsequent RPP in the validation group after adjustment of morphological confounders. Unlike unchanged RS in the non-RPP group, RS increased significantly in the RPP group at follow-up in the whole dataset ( P <0.001)., Conclusions: The proposed CCTA-based RS had a better discriminative value to identify plaques at risk of rapid progression compared with conventional morphological plaque parameters. These data suggest the promising utility of radiomics for predicting RPP in a low-risk group on CCTA., Competing Interests: Disclosures None.

Voltage-gated sodium channel 1.7 (Nav1.7) remains one of the most promising drug targets for pain relief. In the current study, we conducted a high-throughput screening of natural products in our in-house compound library to discover novel Nav1.7 inhibitors, then characterized their pharmacological properties. We identified 25 naphthylisoquinoline alkaloids (NIQs) from Ancistrocladus tectorius to be a novel type of Nav1.7 channel inhibitors. Their stereostructures including the linkage modes of the naphthalene group at the isoquinoline core were revealed by a comprehensive analysis of HRESIMS, 1D, and 2D NMR spectra as well as ECD spectra and single-crystal X-ray diffraction analysis with Cu Kα radiation. All the NIQs showed inhibitory activities against the Nav1.7 channel stably expressed in HEK293 cells, and the naphthalene ring in the C-7 position displayed a more important role in the inhibitory activity than that in the C-5 site. Among the NIQs tested, compound 2 was the most potent with an IC 50 of 0.73 ± 0.03 µM. We demonstrated that compound 2 (3 µM) caused dramatical shift of steady-state slow inactivation toward the hyperpolarizing direction (V 1/2 values were changed from -39.54 ± 2.77 mV to -65.53 ± 4.39 mV, which might contribute to the inhibition of compound 2 against the Nav1.7 channel. In acutely isolated dorsal root ganglion (DRG) neurons, compound 2 (10 μM) dramatically suppressed native sodium currents and action potential firing. In the formalin-induced mouse inflammatory pain model, local intraplantar administration of compound 2 (2, 20, 200 nmol) dose-dependently attenuated the nociceptive behaviors. In summary, NIQs represent a new type of Nav1.7 channel inhibitors and may act as structural templates for the following analgesic drug development., (© 2023. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Bioaccessible fractions of particle-bound hydrophobic organic compounds (HOCs) are critical to evaluating human inhalation exposure risk. However, the key factors for controlling the release of HOCs into the lung fluid are not adequately examined. To address this issue, eight particle size fractions (0.056-18 μm) from different particle emission sources (barbecue and smoking) were collected and incubated with an in vitro method for determining inhalation bioaccessibilities of polycyclic aromatic hydrocarbons (PAHs). The bioaccessible fractions of particle-bound PAHs were 35-65% for smoke-type charcoal, 24-62% for smokeless-type charcoal, and 44-96% for cigarette. The size distributions of bioaccessible fractions of 3-4 ring PAHs were symmetric with the patterns of their masses, characterized as a unimodal distribution with both the trough and peak at 0.56-1.0 μm. Analysis from machine learning showed that chemical hydrophobicity appeared to be the most significant factor affecting inhalation bioaccessibility of PAHs, followed by organic carbon and elemental carbon contents. Particle size seemed to have little effect on the bioaccessibility of PAHs. A compositional analysis of human inhalation exposure risk from total concentration, deposition concentration, and bioaccessible deposition concentration in alveolar region showed a shift in the key particle size from 0.56-1.0 μm to 1.0-1.8 μm and an increasing in the contributions of 2-3 ring PAHs to risk for cigarette due to the high bioaccessible fractions. These results suggested the significance of particle deposition efficiency and bioaccessible fractions of HOCs in risk assessment., 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.)

Organic trisradicals featuring threefold symmetry have attracted significant interest because of their unique magnetic properties associated with spin frustration. Herein, we describe the synthesis and characterization of a triangular prism-shaped organic cage for which we have coined the name PrismCage 6+ and its trisradical trication─ TR 3(•+) . PrismCage 6+ is composed of three 4,4'-bipyridinium dications and two 1,3,5-phenylene units bridged by six methylene groups. In the solid state, PrismCage 6+ adopts a highly twisted conformation with close to C 3 symmetry as a result of encapsulating one PF 6 - anion as a guest. PrismCage 6+ undergoes stepwise reduction to its mono-, di-, and trisradical cations in MeCN on account of strong electronic communication between its 4,4'-bipyridinium units. TR 3(•+) , which is obtained by the reduction of PrismCage 6+ employing CoCp 2 , adopts a triangular prism-shaped conformation with close to C 2 v symmetry in the solid state. Temperature-dependent continuous-wave and nutation-frequency-selective electron paramagnetic resonance spectra of TR 3(•+) in frozen N , N -dimethylformamide indicate its doublet ground state. The doublet-quartet energy gap of TR 3(•+) is estimated to be -0.08 kcal mol -1 , and the critical temperature of spin-state conversion is found to be ca. 50 K, suggesting that it displays pronounced spin frustration at the molecular level. To the best of our knowledge, this example is the first organic radical cage to exhibit spin frustration. The trisradical trication of PrismCage 6+ opens up new possibilities for fundamental investigations and potential applications in the fields of both organic cages and spin chemistry.

Background: Cisplatin is effective against various types of cancers. However, its clinical application is limited owing to its adverse effects, especially acute kidney injury (AKI). Dihydromyricetin (DHM), a flavonoid derived from Ampelopsis grossedentata, has varied pharmacological activities. This research aimed to determine the molecular mechanism for cisplatin-induced AKI., Methods: A murine model of cisplatin-induced AKI (22 mg/kg, I.P.) and a HK-2 cell model of cisplatin-induced damage (30 μM) were established to evaluate the protective function of DHM. Renal dysfunction markers, renal morphology and potential signaling pathways were investigated., Results: DHM decreased the levels of renal function biomarkers (blood urea nitrogen and serum creatinine), mitigated renal morphological damage, and downregulated the protein levels of kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin. It upregulated the expression levels of antioxidant enzymes (superoxide dismutase and catalase expression), nuclear factor-erythroid-2-related factor 2 (Nrf2) and its downstream proteins, including heme oxygenase-1 (HO-1), glutamate-cysteine ligase catalytic (GCLC) and modulatory (GCLM) subunits, thus eventually reducing cisplatin-induced reactive oxygen species (ROS) production. Moreover, DHM partially inhibited the phosphorylation of the active fragments of caspase-8 and -3 and mitogen-activated protein kinase and restored glutathione peroxidase 4 expression, which attenuated renal apoptosis and ferroptosis in cisplatin-treated animals. DHM also mitigated the activation of NLRP3 inflammasome and nuclear factor (NF)-κB, attenuating the inflammatory response. In addition, it reduced cisplatin-induced HK-2 cell apoptosis and ROS production, both of which were blocked by the Nrf2 inhibitor ML385., Conclusions: DHM suppressed cisplatin-induced oxidative stress, inflammation and ferroptosis probably through regulating of Nrf2/HO-1, MAPK and NF-κB signaling pathways., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2023. Published by Elsevier Inc.)

In this paper, we propose a method for narrowing the spectrum in high-power narrow-linewidth polarization-maintaining (PM) fiber amplifiers and investigate its potential for suppressing the stimulated Brillouin scattering (SBS). In this method, in addition to common phase modulation to suppress SBS, precisely designed amplitude modulation is induced to generate self-phase modulation in a high-power PM fiber amplifier. In this co-modulation way, the spectrum can be gradually compressed along the fiber. Compared to phase modulation alone or fiber-Bragg-gratings (FBGs) based narrow-linewidth fiber oscillator schemes, in which the spectrum remains the same or broadens, this scheme can achieve a higher SBS threshold for the same output spectral linewidth. Experiments on a ∼ 3 kW peak power quasi-continuous wave (QCW) fiber amplifier show that the co-modulation scheme can compress the spectrum from 0.25 nm to 0.084 nm as output peak power increases from 13 W to 3.2 kW and enhances the SBS threshold by ∼1.7 times compared to traditional FBGs-based fiber oscillator schemes, and by ∼1.4 times compared to common phase modulation schemes. This co-modulation scheme has the potential for mitigating SBS in high-power fiber amplifiers.

Introduction: The management of paediatric femoral shaft fractures is expensive and is guided by age and fracture characteristics. The primary aim of this study was to perform a cost evaluation for managing paediatric femoral shaft fractures. The secondary aim of this study was to perform and compare costs of the different techniques of managing paediatric femoral shaft fractures., Methods: Ninety-eight femoral shaft fractures in children aged ≤16 were identified between 01/06/2014-30/06/2019. Retrospective data of clinical complications were obtained on infection, malunion and non-union. Data on additional intervention, reoperations for complications and routine removal of metal work were obtained. Costing analysis was performed by a bottom-up calculation, and gathering Patient Level Information and Costing System (PLICS) data., Results: There were 41 hip spica casting (HSC), 21 flexible intramedullary nailing (FIN), 14 submuscular plating (SMP), 19 rigid intramedullary nailing (RIN) and 3 external fixation (EF). Complications observed were HSC 3(7%); FIN 8(38%); SMP 2(14%); RIN 1(5%); EF 2(67%). The total costs for managing femoral shaft fractures were £8,955pp the costs for the different managements were; HSC £3,442pp; FIN £7,739pp; SMP £6,953pp; RIN £8,925pp; EF £19,116pp. The additional costs incurred for managing complications and routine removal of metal work for the internal fixation methods were: HSC 0.7%, FIN 23.7%, SMP 16.3%, RIN 10.9%, EF 28.1%., Conclusion: The operative management of paediatric femoral shaft fractures is associated with a high cost burden and this study demonstrates how financial data can be used to influence clinical management strategy. RIN carry a high initial implant cost however when considering the additional costs, such as treating complications it remains comparable to other modes of fixation. Our cost analysis did not demonstrate a significant difference between FIN, SMP and RIN. Due to the clinical complications observed and associated additional costs, we have discontinued the routine use of FIN for femoral shaft fractures at our centre. We recognise other centres may have a different complication and cost profile for each technique, but recommend they evaluate their practice given the potential economic benefit it has on the service provider., Competing Interests: Declaration of Competing Interest None., (Crown Copyright © 2023. Published by Elsevier Ltd. All rights reserved.)