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Purpose: To evaluate the effectiveness of both synthetic magnetic resonance imaging (SyMRI) and conventional diffusion-weighted imaging (DWI) for identifying the human epidermal growth factor receptor 2 (HER2) status in breast cancer (BC) patients., Method: In this retrospective study, 114 women with DWI and SyMRI were pathologically classified into three groups: HER2-overexpressing (n = 40), HER2-low-expressing (n = 53), and HER2-zero-expressing (n = 21). T1 and T2 relaxation times and proton density (PD) were assessed before and after enhancement, and the resulting quantitative parameters produced by SyMRI were recorded as T1, T2, and PD and T1e, T2e, and PDe. Logistic regression was used to identify the best indicators for classifying patients based on HER2 expression. The discriminative performance of the models was evaluated using receiver operating characteristic (ROC) curves., Results: Our preliminary study revealed significant differences in progesterone receptor (PR) status, Ki-67 index, and axillary lymph node (ALN) count among the HER2-zero, -low, and -overexpressing groups (p < 0.001 to p = 0.03). SyMRI quantitative indices showed significant differences among BCs in the three HER2 subgroups, except for ΔT2 (p < 0.05). our results indicate that PDe achieved an area under the curve（AUC）of 0.849 (95 % CI: 0.760-0.915) for distinguishing HER2-low and -overexpressing BCs. Further investigation revealed that both the PDe and ADC were indicators for predicting differences among patients with HER2-zero and HER2-low-expressing BC, with AUCs of 0.765(95 % CI: 0.652-0.855) and 0.684(95 % CI: 0.565-0.787), respectively. The addition of the PDe to the ADC improved the AUC to 0.825(95 % CI: 0.719-0.903)., Conclusions: SyMRI could noninvasively and robustly predict the HER2 expression status of patients with BC., 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.)

The Alexandrine parakeet (Palaeornis eupatria), also known as the Alexandrine parrot, is a critically endangered species in the world and a national second class protected animal. Current knowledge on gut microbiome and metabolome of captive Alexandrine parrots is limited. In the current study, we characterized the effect of dietary change with pellet feeding on the gut microbiome and metaboliome in Alexandrine parrots using 16S gene sequencing and liquid chromatography with tandem mass spectrometry (LC-MS/MS). Total of 12 Alexandrine parrots were used in a cross-over study with each period for 10 days. The results showed that dietary change with pellet feeding did not affect alpha indices of gut microbiota. Cyanobacteria, Firmicutes and Proteobacteria were the predominant bacterial phyla in the gut of Alexandrine parrot with Cynobacteria being the highest. Change of diet significantly increased the relative abundance of Actinobacteria and decreased Spirochaetota. The relative abundance of Fusobacteriota tended to increase with pellet feeding. No treatment effects were observed between the control and pellet feeding groups at the genus level. Based on the annotation results from Clusters of Orthologous Genes (COG) database, dietary change with pellet feeding significantly increased the relative abundance of genes coding for extracellular structures and lipid transport and metabolism. Metabolomics analysis combined with enrichment analysis revealed that dietary change altered the concentrations of gut metabolites as well as the metabolic pattern, and significantly affected the concentrations of fecal metabolites involved in isoflavonoid biosynthesis, flavonoid biosynthesis, nucleotide metabolism etc. In summary, dietary changes with pellet feeding affected the gut microbial composition and metabolites to some extent. The relevance of current findings to Alexandrine parrots' health and potential zoonosis need further exploring., Competing Interests: Declaration of competing interest 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 Elsevier Inc. All rights reserved.)

Background: Dysregulation of vascular smooth muscle cell (VSMC) function leads to a variety of diseases such as atherosclerosis and hyperplasia after injury. However, antiproliferative drug targeting VSMC exhibits poor specificity. Therefore, there is an urgent to develop highly specific antiproliferative drugs to prevention and treatment VSMC dedifferentiation associated arteriosclerosis. Kanglexin (KLX), a new anthraquinone compound designed by our team, has potential to regulate VSMC phenotype according to the physicochemical properties., Purpose: This project aims to evaluate the therapeutic role of KLX in VSMC dedifferentiation and atherosclerosis, neointimal formation and illustrates the underlying molecular mechanism., Methods: In vivo, the ApoE -/- mice were fed with high-fat diet (HFD) for a duration of 13 weeks to establish the atherosclerotic model. And rat carotid artery injury model was performed to establish the neointimal formation model. In vitro, PDGF-BB was used to induce VSMC dedifferentiation., Results: We found that KLX ameliorated the atherosclerotic progression including atherosclerotic lesion formation, lipid deposition and collagen deposition in aorta and aortic sinus in atherosclerotic mouse model. In addition, The administration of KLX effectively ameliorated neointimal formation in the carotid artery following balloon injury in SD rats. The findings derived from molecular docking and surface plasmon resonance (SPR) experiments unequivocally demonstrate that KLX had potential to bind PDGFR-β. Mechanism research work proved that KLX prevented VSMC proliferation, migration and dedifferentiation via activating the PDGFR-β-MEK -ERK-ELK-1/KLF4 signaling pathway., Conclusion: Collectively, we demonstrated that KLX effectively attenuated the progression of atherosclerosis in ApoE-/- mice and carotid arterial neointimal formation in SD rats by inhibiting VSMC phenotypic conversion via PDGFR-β-MEK-ERK-ELK-1/KLF4 signaling. KLX exhibits promising potential as a viable therapeutic agent for the treatment of VSMC phenotype conversion associated arteriosclerosis., Competing Interests: Declaration of competing interest All authors disclosed no relevant relationships., (Copyright © 2024. Published by Elsevier GmbH.)

Background: Identical bursts on electroencephalography (EEG) are considered a specific predictor of poor outcomes in cardiac arrest, but its relationship with structural brain injury severity on magnetic resonance imaging (MRI) is not known., Methods: This was a retrospective analysis of clinical, EEG, and MRI data from adult comatose patients after cardiac arrest. Burst similarity in first 72 h from the time of return of spontaneous circulation were calculated using dynamic time-warping (DTW) for bursts of equal (i.e., 500 ms) and varying (i.e., 100-500 ms) lengths and cross-correlation for bursts of equal lengths. Structural brain injury severity was measured using whole brain mean apparent diffusion coefficient (ADC) on MRI. Pearson's correlation coefficients were calculated between mean burst similarity across consecutive 12-24-h time blocks and mean whole brain ADC values. Good outcome was defined as Cerebral Performance Category of 1-2 (i.e., independence for activities of daily living) at the time of hospital discharge., Results: Of 113 patients with cardiac arrest, 45 patients had burst suppression (mean cardiac arrest to MRI time 4.3 days). Three study participants with burst suppression had a good outcome. Burst similarity calculated using DTW with bursts of varying lengths was correlated with mean ADC value in the first 36 h after cardiac arrest: Pearson's r: 0-12 h: - 0.69 (p = 0.039), 12-24 h: - 0.54 (p = 0.002), 24-36 h: - 0.41 (p = 0.049). Burst similarity measured with bursts of equal lengths was not associated with mean ADC value with cross-correlation or DTW, except for DTW at 60-72 h (- 0.96, p = 0.04)., Conclusions: Burst similarity on EEG after cardiac arrest may be associated with acute brain injury severity on MRI. This association was time dependent when measured using DTW., (© 2024. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

A novel electrochemical method is presented for ultrasensitive detection of the organophosphate pesticide (OPP) fenitrothion by using Ti 3 C 2 MXene/CoAl-LDH nanocomposite as the electrode modifier. The Ti 3 C 2 MXene/CoAl-LDH nanocomposite is synthesized by growing CoAl-LDH in situ on MXene nanosheets. The combination of two ultrathin 2D materials provides more active sites, larger specific surface area, superior adsorption properties, and better electrical conductivity, which leads to rapid electron-transfer and mass-transfer between the substrate electrode and analytes when it is acted as the electrochemical sensing material. In addition, through the chelation of phosphate groups with the Ti defect sites enriched in MXene, OPP is adsorbed on the electrode. Consequently, the corresponding modified electrode gives rise to a wide linear response range of 0.03 ~ 120 μmol/L for the differential pulse voltammetry detection of fenitrothion with a low detection limit of 5.8 nmol/L (3σ). The method offers good repeatability, stability, selectivity, and practicability for real samples. This strategy provides a reference platform for the electrochemical monitoring of trace OPPs residue by using MXene/LDH-based nanocomposites., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Combining the urea oxidation reaction (UOR) with the hydrogen evolution reaction (HER) is an effective technology for energy-saving hydrogen production. Herein, a bifunctional electrocatalyst with CoNiP nanosheet coating on P-doped MoO 2 nanorods (P-MoO 2 @CoNiP) is obtained via a two-step hydrothermal followed a phosphorization process. The catalyst demonstrates exceptional alkaline HER performance due to the formation of MoO 2 and the dissolution/absorption of Mo. Meanwhile, the inclusion of Co and P in the P-MoO 2 @CoNiP catalyst facilitated the formation of NiOOH, enhancing UOR performance. Density functional theory calculations reveal that the hydrogen adsorption Gibbs free energy (ΔG H* ) of P-MoO 2 @CoNiP is closer to 0 eV than CoNiP, favoring the HER. The catalyst only needs -0.08 and 1.38 V to reach 100 mA cm -2 for catalyzing the HER and UOR, respectively. The full urea electrolysis system driven by P-MoO 2 @CoNiP requires 1.51 V to achieve 100 mA cm -2 , 120 mV lower than the traditional water electrolysis., 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.)

Background: Breast cancer is the most common malignancy that occurs in women. Due to the pain caused by the disease itself and the adverse reactions in the treatment process, breast cancer patients are prone to anxiety, depression, fear of recurrence, and other negative emotions, which seriously affect the quality of life. As a systematic stress reduction therapy, mindfulness-based stress reduction is widely applied to the treatment of breast cancer patients and has been found by a growing number of studies to relieve stress, regulate mood, and improve the state. However, due to the absence of recent research and uniform outcome measures, previous studies have failed to fully explain the role of mindfulness-based stress reduction in improving the quality of life in breast cancer patients., Objective: We conducted a systematic review and meta-analysis to evaluate and compare the effects of mindfulness-based stress reduction therapy and standard care on the quality of life and psychological status of breast cancer patients., Methods: We searched PubMed, Web of Science, Embase, China's National Knowledge Infrastructure and the Cochrane Central Registry of Controlled Trials up to July 2023 to identify candidate randomized clinical trials addressing the values of mindfulness-based stress reduction in breast cancer patients., Results: A total of 1644 patients participated in 11 randomized controlled trials. The results of the meta-analysis showed that mindfulness-based stress reduction therapy can significantly reduce negative emotions such as perceived stress (MD = -1.46, 95%CI = -2.53 to -0.38, p = 0.03), depression (MD = -1.84, 95%CI = -3.99 to -0.30, p = 0.0004), anxiety (MD = -2.81, 95%CI = -5.31 to -0.32, p = 0.002), and fear of recurrence (MD = -1.27, 95%CI = -3.44 to 0.90, p = 0.0004). Mindfulness-based stress reduction therapy also has certain advantages in improving the coping ability (MD = 1.26, 95%CI = -3.23 to5.76, p = 0.03) and the emotional state (MD = -7.73, 95%CI = -27.34 to 11.88, p = 0.0007) of patients with breast cancer., Conclusion: Our analyses support that, compared with standard care, mindfulness-based stress reduction therapy can significantly improve patients' coping ability, reduce adverse emotions and improve patients' emotional states., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Wang 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.)

Developing Janus fabrics with excellent one-way sweat transport capacity is an attractive way for providing comfort sensation and protecting the health during exercise. In this work, a 3D wetting gradient Janus fabric (3DWGJF) is first proposed to address the issue of excessive sweat accumulation in women's breasts, followed by integration with a sponge pad to form a 3D wetting gradient Janus sports bra (3DWGJSB). The 3D wetting gradient enables the prepared fabric to control the horizontal migration of sweat in one-way mode (x/y directions) and then unidirectionally penetrate downward (z direction), finally keeping the water content on the inner side of 3DWGJF (skin side) at ≈0%. In addition, the prepared 3DWGJF has good water vapor transmittance rate (WVTR: 0.0409 g cm -2  h -1 ) and an excellent water evaporation rate (0.4704 g h -1 ). Due to the high adhesion of transfer prints to the fabrics and their excellent mechanical properties, the 3DWGJF is remarkably durable and capable of withstanding over 500 laundering cycles and 400 abrasion cycles. This work may inspire the design and fabrication of next-generation moisture management fabrics with an effective sweat-removal function for women's health., (© 2024 Wiley‐VCH GmbH.)

Developing highly active electrocatalysts is crucial for the application of electrocatalytic water splitting. In this study, we prepared vanadium oxide-graphene carbon nanocomposites (V x O y /C) with abundant defects using a carbon- and oxygen-rich hexavanadate derivative Na 2 [V 6 O 7 {(OCH 2 ) 3 CCH 3 } 4 ] as a precursor without the addition of an extra carbon source. Subsequently, the V x O y /C was used as a catalyst support to load a small amount of Ir, forming the Ir/V x O y /C nanoelectrocatalyst. This catalyst exhibited low hydrogen evolution overpotentials of only 18.90 and 13.46 mV at a working current density of 10 mA cm -2 in 1.0 M KOH and 0.5 M H 2 SO 4 electrolyte systems, outperforming the commercial Pt/C catalysts. Additionally, the catalyst showed excellent chemical stability and long-term durability. This work provides a new strategy for the design and synthesis of highly active electrocatalysts for water splitting.

Objective: Assess the safety of ambulatory surgery performed for obstructive sleep apnea., Study Design: Retrospective chart review., Setting: Tertiary care hospital., Methods: Demographic data including age, gender, race, body mass index, insurance status, socioeconomic status, and distance traveled for surgery was collected, as well as comorbidities, and apnea-hypopnea index (AHI). Outcome variables included continuous positive airway pressure reinitiation, planned/unplanned postoperative admission, emergency department (ED) presentation, or readmission within 7 and 14 days of surgery., Results: A total of 601 patients were included, who underwent sleep surgery between 2017 and 2022. The median age was 55 years [interquartile range: 19]. A total of 437 patients (73%) were male, 502 (84%) were Caucasian, and the median distance traveled was 20 miles [27]. The median AHI was 27.1 [26]. A total of 286 hypoglossal nerve stimulators, 12 tonsillectomies, 160 expansion sphincteroplasties (ESP), and 201 nasal procedures were performed. There were 9 (1%) planned and 23 (4%) total admissions postoperatively. Sixteen patients (2%) presented to ED within 7 days, and 22 (3%) within 14 days. Nine (1%) were readmitted within 7 days, and 12 (2%) within 14 days. There were significantly more planned admissions, unplanned admissions, ED presentations, and readmissions for ESP. There were no significant differences in demographic or clinical data between patients who underwent single versus multiple surgeries., Conclusion: Outpatient sleep surgery is generally safe. Close postoperative monitoring is necessary and overnight observation should be considered in those with very severe sleep apnea and/or significant comorbidities. The distance a patient travels should also be considered for overnight admission., (© 2024 The Authors. Otolaryngology–Head and Neck Surgery published by Wiley Periodicals LLC on behalf of American Academy of Otolaryngology–Head and Neck Surgery Foundation.)

Wood has gained popularity as a building and decorative material due to its environmentally friendly and sustainable characteristics. Yet, its long maturation time poses a limitation on meeting the growing demand for wood products. This challenge has led to the plantation of fast-growing wood as an alternative solution. Unfortunately, the poor mechanical properties of fast-growing wood hinder its application. In this study, we developed novel densification-modified wood by combining alkali chemical pretreatment, cyclic impregnation, and mechanical hot-pressing techniques. Additionally, the response surface method was employed to rapidly determine the optimal preparation parameters, reducing the cost of preparation under various conditions. The optimized parameters resulted in densification-modified wood with a flexural strength and modulus of elasticity of 337.04 MPa and 27.43 GPa, respectively. Furthermore, the densified wood achieved excellent dimensional stability by reducing the water-absorbing thickness swelling to 1.15 % for 72-h water soaking. The findings indicated that the densification-modified wood possessed high tensile strength and elastic modulus, along with excellent dimensional stability. The proposed densified wood modification technology in this study offers new perspectives and design guidance for the application of outdoor engineering structures, energy-efficient buildings, and decorative materials., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Seawater electrolysis to generate hydrogen offers a clean, green, and sustainable solution for new energy. However, the catalytic activity and durability of anodic catalysts are plagued by the corrosion and competitive oxidation reactions of chloride in high concentrations. In this study, we find that the additive CrO 4 2- anions in the electrolyte can not only promote the formation and stabilization of the metal oxyhydroxide active phase but also greatly mitigate the adverse effect of Cl - on the anode. Linear sweep voltammetry, accelerated corrosion experiments, corrosion polarization curves, and charge transfer resistance results indicate that the addition of CrO 4 2- distinctly improves oxygen evolution reaction (OER) kinetics and corrosion resistance in alkaline seawater electrolytes. Especially, the introduction of CrO 4 2- even in the highly concentrated NaCl (2.5 M) electrolyte prolongs the durability of NiFe-LDH to almost five times the case without CrO 4 2- . Density functional theory calculations also reveal that the adsorption of CrO 4 2- can tune the electronic configuration of active sites of metal oxyhydroxides, enhance conductivity, and optimize the intermediate adsorption energies. This anionic additive strategy can give a better enlightenment for the development of efficient and stable oxygen evolution reactions for seawater electrolysis., 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.)

Human chorionic gonadotropin (HCG), a vital protein for pregnancy determination and a marker for trophoblastic diseases, finds application in monitoring early pregnancy and ectopic pregnancy. This study presents an innovative approach employing electrochemical immunosensors for enhanced HCG detection, utilizing Anti-HCG antibodies and gold nanoparticles (AuNPs) in the sensor platform. Two sensor configurations were optimized: BSA/Anti-HCG/c-AuNPs/MEL/e-AuNPs/SPCE with [Fe(CN) 6 ] 3-/4- as a redox probe (1) and BSA/Anti-HCG/PPy/e-AuNPs/SPCE using polypyrrole (PPy) as a redox probe (2). The first sensor offers linear correlation in the 0.10-500.00 pg∙mL -1 HCG range, with a limit of detection (LOD) of 0.06 pg∙mL -1 , sensitivity of 32.25 μA∙pg -1 ∙mL∙cm -2 , RSD <2.47 %, and a recovery rate of 101.03-104.81 %. The second sensor widens the HCG detection range (40.00 fg∙mL -1 -5.00 pg∙mL -1 ) with a LOD of 16.53 fg∙mL -1 , ensuring precision (RSD <1.04 %) and a recovery range of 94.61-106.07 % in serum samples. These electrochemical immunosensors have transformative potential in biomarker detection, offering enhanced sensitivity, selectivity, and stability for advanced healthcare diagnostics., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Extracellular matrix sponge plays a positive role in the wound healing process, but requires proper structural strength and biological properties. In order to solve the problem of lyophilized dissolution of placenta-derived sponge, glutaraldehyde was selected for use in the lyophilized crosslinking process to improve the necessary mechanical properties of the placental decellularization matrix sponge. In this work, the effects of three cross-linking methods of glutaraldehyde (Fumigation/Slurry/Soak) on the physical and biological characteristics of lyophilised sponges derived from placental acellular matrix was investigated. The results revealed that the sponges prepared by all three cross-linking methods exhibited excellent blood coagulation ability and stability. The fumigation cross-linked sponges had good mechanical properties of soft and elastic, and safe cytotoxicity, which were more compatible with the requirements of wound dressing. The slurry cross-linking process was uneven due to the stacked matrix materials, resulting in obvious cracks and easy to break when stretching. The soak crosslinking can obtain a higher degree of crosslinking, which leads to the poor antibacterial performance and the harder sponge scaffold with larger elastic modulus and smaller tensile ratio. In general, fumigation cross-linking is more suitable for the preparation of acellular sponge derived from placenta materials which can maintain basic mechanical properties and biological validity., Competing Interests: Declaration of competing interest The authors declare no competing financial interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Rituximab (RTX) is considered the first-line treatment for pemphigus vulgaris (PV), which is a B-cell-mediated acquired autoimmune disease. However, no consensus on the optimum dosage has been achieved., Objectives: To investigate the efficacy and safety of low-dose RTX (a single infusion of 500 mg) for the treatment of PV, a cohort study was conducted for patients with PV, along with a 12-month follow-up following the administration of RTX., Methods: Patients with moderate or severe PV were divided into group A (low-dose RTX combined with corticosteroids) and group B (corticosteroids alone). Data on complete remission (CR) rates, doses of corticosteroids, cumulative doses of corticosteroids at the third, sixth, and twelfth months, pemphigus disease area index and adverse effects (AEs) were collected., Results: Forty-four patients with moderate or severe PV were enrolled in this study (19 in group A and 25 in group B). Patients treated with low-dose RTX had higher CR rates, lower doses of corticosteroids at the third, sixth, and twelfth months, lower cumulative doses of corticosteroids at the sixth and twelfth months, and fewer AEs than those who received corticosteroids alone., Conclusions: This study indicated that low-dose RTX may be a beneficial and secure therapy option for patients with moderate to severe PV.

Objective: MAGnetic resonance Imaging Compilation (MAGiC) is typical method of synthetic magnetic resonance imaging (MRI). The present aimed to investigate the role of MAGiC parameters of relaxation time (T1), transverse relaxation time (T2) and proton density (PD) to predict the treatment efficacy of breast cancer patients after neoadjuvant chemotherapy (NAC)., Methods: The present prospective cohort study enrolled 120 breast cancer patients who received NAC during 2021-2023. Demographic data and clinical characteristics including tumor node metastasis (TNM) stage, pathological type, molecular classification and lymph node metastasis were collected. The levels of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER-2) were measured. Patients were divided by treatment efficacy using the Miller-Payne grading as partial pathological response (pPR) group and pathological complete response (pCR). The values of MAGiC parameters of longitudinal T1, T2, and PD values were recorded., Results: In all 120 patients, 73 (60.83%) cases were with pPR and 47 (39.17%) cases were with pCR after treatment. T2 values were markedly lower in pPR patients compared with pCR patients. However, no significant difference was found for T1 and PD values. No significant correlation was observed between any of MAGiC parameters and HER-2, ER or PR. ROC curve showed T2 could be used for prediction of pPR with AUC 0.780. Lymph node metastasis and low levels of T2 were found as independent risk factors for pPR after treatment., Conclusion: The T2 value parameter from MAGiC is an independent risk factor for pPR following NAC in breast cancer patients, suggesting its potential as a biomarker for predicting treatment efficacy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Developing inexpensive, efficient, and stable catalysts is crucial for reducing the cost of electrolytic hydrogen production. Recently, polyoxometalates (POMs) have gained attention and widespread use due to their excellent electrocatalytic properties. This study designed and synthesized three composite materials, NF/PMo n W 12- n , by using phosphomolybdic-tungstic heteropolyacids as precursors to grow in situ on nickel foam via the hydrothermal process and subsequent calcination. Then, their catalytic performances are systematically investigated. This work demonstrates that the NF/PMo n W 12- n catalysts generate more low valent oxides under the synergistic effect of Mo and W, further enhancing activity for hydrogen evolution reaction (HER). Among these electrocatalysts, NF/PMo 6 W 6 exhibits the perfect HER performance, η 10 is only 74 mV. It also shows great stability during long-term electrolysis. The current study introduces a fresh approach for producing electrocatalysts that are both cost-effective and highly efficient.

Background: The analysis of cell membrane permeability plays a crucial role in improving the procedures of cell cryopreservation, which will affect the specific parameter settings in loading, removal and cooling processes. However, existing studies have mostly focused on deriving permeability parameters through osmotic theoretical models and cell volume response analysis, and there is still a lack of the direct experimental evidence and analysis at the single-cell level regarding the migration of cryoprotectants., Results: In this work, a side perfusion microfluidics chips combined with Raman spectroscopy system was built to monitor in situ the Raman spectroscopy of extracellular and intracellular solution during loading and elution process with different cryoprotectant solution systems (single and dual component). And it was found that loading a high concentration cryoprotectant solution system through a single elution cycle may result in significant residual protective agent, which can be mitigated by employing a multi-component formula but multiple elution operations are still necessary. Furthermore, the collected spectral signals were marked and analyzed to was perform preliminary relative quantitative analysis. The results showed that the intracellular concentration changes can be accurately quantified by the Raman spectrum and are closely related to the extracellular solution concentration changes., Significance and Novelty: By using the method of small flow perfusion (≤20 μL/min) in the side microfluidic chip after the gravity sedimentation of cells, the continuous loading and elution process of different cryoprotectants on chip and the spectral acquisition can be realized. The intracellular and extracellular concentrations can be quantified in situ based on the ratio of spectral peak intensities. These results indicate that spectroscopic analysis can be used to effectively monitor intracellular cryoprotectant residues., Competing Interests: Declaration of competing interest The authors declare no competing financial interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objectives: Certain low-level immune-related adverse events (irAEs) have been associated with survival benefits in patients with various solid tumors on immune checkpoint inhibitors (ICIs). We aimed to investigate the association between irAEs and response to neoadjuvant ICIs in patients with head and neck squamous cell carcinoma (HNSCC) and to identify differences in circulating cytokine levels based on irAE status., Methods: This was a retrospective cohort study including three neoadjuvant clinical trials from July 2017 to January 2022: NCT03238365 (nivolumab ± tadalafil), NCT03854032 (nivolumab ± BMS986205), NCT03618654 (durvalumab ± metformin). The presence and type of irAEs, pathologic treatment response, and survival were compared. Canonical linear discriminant analysis (LDA) was performed to identify combinations of circulating cytokines predictive of irAEs using plasma sample multiplex assay., Results: Of 113 participants meeting inclusion criteria, 32 (28.3%) developed irAEs during treatment or follow-up. Positive p16 status was associated with irAEs (odds ratio [OR] 2.489; 95% CI 1.069-6.119; p = 0.043). irAEs were associated with pathologic treatment response (OR 3.73; 95% CI 1.34-10.35; p = 0.011) and with higher OS in the combined cohort (HR 0.319; 95% CI 0.113-0.906; p = 0.032). Patients with irAEs within the nivolumab cohort had significant elevations of select cytokines pre-treatment. Canonical LDA identified key drivers of irAEs among all trials, which were highly predictive of future irAE status., Conclusions: irAEs are associated with response to neoadjuvant ICI therapy in HNSCC and can serve as clinical indicators for improved clinical outcomes. irAEs can be predicted by concentrations of several circulating cytokines prior to treatment., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

Beauveria bassiana and Metarhizium rileyi are extensively utilized to investigate fungal pathogenic mechanisms and to develop biological control agents. Notwithstanding, notable distinctions exist in their pathogenicity against the same host insect. This study aimed to elucidate the pathogenic differences between M. rileyi and B. bassiana by examining the impact of various ratios of B. bassiana strain AJS91881 and M. rileyi strain SXBN200920 on fifth instar larvae of Spodoptera litura , focusing on early infection stages and intestinal microbial community structure. The lethal time 50 (LT 50 ) for B. bassiana was significantly lower than that for M. rileyi , indicating greater efficacy. Survival analyses in mixed groups (ratios of 1:9, 1:1, and 9:1 M. rileyi to B. bassiana ) consistently demonstrated higher virulence of B. bassiana . Intestinal microbial diversity analysis revealed a significant increase in Achromobacter and Pseudomonas in larvae infected with M. rileyi , whereas Weissella was notably higher in those infected with B. bassiana. Additionally, significant shifts in microbial genera abundances were observed across all mixed infection groups. KEGG pathway enrichment analysis indicated that M. rileyi and B. bassiana employ distinct pathogenic strategies during early infection stages. In vitro tests confirmed the superior growth and stress resistance of B. bassiana compared to M. rileyi, but the antifungal ability of M. rileyi was better than that of B. bassiana. In conclusion, our findings provide preliminary insights into the differential pathogenic behaviors of M. rileyi and B. bassiana during the early infection stages in S. litura larvae, enhancing our understanding of their mechanisms and informing biological pest control strategies in agriculture and forestry.

To predict outcome to combination bevacizumab (BVZ) therapy, we employed cell-free DNA (cfDNA) to determine chromosomal instability (CIN), nucleosome footprints (NF) and methylation profiles in metastatic colorectal cancer (mCRC) patients. Low-coverage whole-genome sequencing (LC-WGS) was performed on matched tumor and plasma samples, collected from 74 mCRC patients from the AC-ANGIOPREDICT Phase II trial (NCT01822444), and analysed for CIN and NFs. A validation cohort of plasma samples from the University Medical Center Mannheim (UMM) was similarly profiled. 61 AC-ANGIOPREDICT plasma samples collected before and following BVZ treatment were selected for targeted methylation sequencing. Using cfDNA CIN profiles, AC-ANGIOPREDICT samples were subtyped with 92.3% accuracy into low and high CIN clusters, with good concordance observed between matched plasma and tumor. Improved survival was observed in CIN-high patients. Plasma-based CIN clustering was validated in the UMM cohort. Methylation profiling identified differences in CIN-low vs. CIN high (AUC = 0.87). Moreover, significant methylation score decreases following BVZ was associated with improved outcome (p = 0.013). Analysis of CIN, NFs and methylation profiles from cfDNA in plasma samples facilitates stratification into CIN clusters which inform patient response to treatment., (© 2024. The Author(s).)

Follicle-stimulating hormone (FSH) binds to its membrane receptor (FSHR) in granulosa cells to activate various signal transduction pathways and drive the gonadotropin-dependent phase of folliculogenesis. Both FSH insufficiency (due to genetic or nongenetic factors) and FSH excess (as encountered with ovarian stimulation in assisted reproductive technology [ART]) can cause poor female reproductive outcomes, but the underlying molecular mechanisms remain elusive. Herein, we conducted single-follicle and single-oocyte RNA sequencing analysis along with other approaches in an ex vivo mouse folliculogenesis and oogenesis system to investigate the effects of different concentrations of FSH on key follicular events. Our study revealed that a minimum FSH threshold is required for follicle maturation into the high estradiol-secreting preovulatory stage, and such threshold is moderately variable among individual follicles between 5 and 10 mIU/mL. FSH at 5, 10, 20, and 30 mIU/mL induced distinct expression patterns of follicle maturation-related genes, follicular transcriptomics, and follicular cAMP levels. RNA sequencing analysis identified FSH-stimulated activation of G proteins and downstream canonical and novel signaling pathways that may critically regulate follicle maturation, including the cAMP/PKA/CREB, PI3K/AKT/FOXO1, and glycolysis pathways. High FSH at 20 and 30 mIU/mL resulted in noncanonical FSH responses, including premature luteinization, high production of androgen and proinflammatory factors, and reduced expression of energy metabolism-related genes in oocytes. Together, this study improves our understanding of gonadotropin-dependent folliculogenesis and provides crucial insights into how high doses of FSH used in ART may impact follicular health, oocyte quality, pregnancy outcome, and systemic health., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. 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. See the journal About page for additional terms.)

Background: Dihydroxyacetone (DHA) stands as a crucial chemical material extensively utilized in the cosmetics industry. DHA production through the dephosphorylation of dihydroxyacetone phosphate, an intermediate product of the glycolysis pathway in Escherichia coli, presents a prospective alternative for industrial production. However, insights into the pivotal enzyme, dihydroxyacetone phosphate dephosphorylase (HdpA), remain limited for informed engineering. Consequently, the development of an efficient tool for high-throughput screening of HdpA hypermutants becomes imperative., Results: This study introduces a methylglyoxal biosensor, based on the formaldehyde-responding regulator FrmR, for the selection of HdpA. Initial modifications involved the insertion of the FrmR binding site upstream of the -35 region and into the spacer region between the -10 and -35 regions of the constitutive promoter J23110. Although the hybrid promoter retained constitutive expression, expression of FrmR led to complete repression. The addition of 350 μM methylglyoxal promptly alleviated FrmR inhibition, enhancing promoter activity by more than 40-fold. The methylglyoxal biosensor system exhibited a gradual increase in fluorescence intensity with methylglyoxal concentrations ranging from 10 to 500 μM. Notably, the biosensor system responded to methylglyoxal spontaneously converted from added DHA, facilitating the separation of DHA producing and non-producing strains through flow cytometry sorting. Subsequently, the methylglyoxal biosensor was successfully applied to screen a library of HdpA mutants, identifying two strains harboring specific mutants 267G > T and D110G/G151C that showed improved DHA production by 68% and 114%, respectively. Expressing of these two HdpA mutants directly in a DHA-producing strain also increased DHA production from 1.45 to 1.92 and 2.29 g/L, respectively, demonstrating the enhanced enzyme properties of the HdpA mutants., Conclusions: The methylglyoxal biosensor offers a novel strategy for constructing genetically encoded biosensors and serves as a robust platform for indirectly determining DHA levels by responding to methylglyoxal. This property enables efficiently screening of HdpA hypermutants to enhance DHA production., (© 2024. The Author(s).)

When designing confirmatory Phase 3 studies, one usually evaluates one or more efficacious and safe treatment option(s) based on data from previous studies. However, several retrospective research articles reported the phenomenon of "diminished treatment effect in Phase 3" based on many case studies. Even under basic assumptions, it was shown that the commonly used estimator could substantially overestimate the efficacy of selected group(s). As alternatives, we propose a class of computational methods to reduce estimation bias and mean squared error with a broader scope of multiple treatment groups and flexibility to accommodate summary results by group as input. Based on simulation studies and a real data example, we provide practical implementation guidance for this class of methods under different scenarios. For more complicated problems, our framework can serve as a starting point with additional layers built in. Proposed methods can also be widely applied to other selection problems., (© 2024 John Wiley & Sons Ltd.)

The development of compact CRISPR systems has facilitated delivery but has concurrently reduced gene editing efficiency, thereby limiting the further utilization of CRISPR systems. Enhancing the efficiency of CRISPR systems poses a challenging task and holds significant implications for the advancement of biotechnology. In our work, we report a synthetic dual-antibody system that can stably exist in the intracellular environment, specifically inhibiting the functions of NF-κB and β-catenin. This not only elevates the transgenic expression of the CRISPR system by suppressing the innate immune response within cells to enhance the gene editing efficiency but also demonstrates a notable tumor inhibitory effect. Based on the specific output expression regulation of CRISPR-CasΦ, we constructed a CRISPR-based gene expression platform, which includes sensor modules for detecting intracellular β-catenin and NF-κB, as well as an SDA module to enhance overall efficiency. In vitro experiments revealed that the CRISPR-based gene expression platform exhibited superior CDK5 expression inhibition efficiency and specific cytotoxicity towards tumor cells. In vitro experiments, we found that CRISPR-based gene expression platforms can selectively kill bladder cancer cells through T cell-mediated cytotoxicity. Our design holds significant assistant potential of transgene therapy and may offer the capability to treat other diseases requiring transgene therapy., (© 2024. The Author(s).)

The haemagglutinin-neuraminidase (HN) protein, a vital membrane glycoprotein, plays a pivotal role in the pathogenesis of Newcastle disease virus (NDV). Previously, we demonstrated that a mutation in the HN protein is essential for the enhanced virulence of JS/7/05/Ch, a velogenic variant NDV strain originating from the mesogenic vaccine strain Mukteswar. Here, we explored the effects of the HN protein during viral infection in vitro using three viruses: JS/7/05/Ch, Mukteswar, and an HN-replacement chimeric NDV, JS/MukHN. Through microscopic observation, CCK-8, and LDH release assays, we demonstrated that compared with Mukteswar and JS/MukHN, JS/7/05/Ch intensified the cellular damage and mortality attributed to the mutant HN protein. Furthermore, JS/7/05/Ch induced greater levels of apoptosis, as evidenced by the activation of caspase-3/8/9. Moreover, JS/7/05/Ch promoted autophagy, leading to increased autophagosome formation and autophagic flux. Subsequent pharmacological experiments revealed that inhibition of apoptosis and autophagy significantly impacted virus replication and cell viability in the JS/7/05/Ch-infected group, whereas less significant effects were observed in the other two infected groups. Notably, the mutant HN protein enhanced JS/7/05/Ch-induced apoptosis and autophagy by suppressing NF-κB activation, while it mitigated the effects of NF-κB on NDV infection. Overall, our study offers novel insights into the mechanisms underlying the increased virulence of NDV and serves as a reference for the development of vaccines., (© 2024. The Author(s).)

Background: Psoriasis is an inflammatory skin disease that impacts a heterogeneous group of patients and can have multiple clinical manifestations. Risankizumab is approved for the treatment of moderate-to-severe plaque psoriasis., Objectives: To evaluate the long-term efficacy of risankizumab according to baseline patient characteristics, and for the treatment of high-impact disease manifestations (nail, scalp and palmoplantar psoriasis), through 256 weeks of continuous treatment in the phase 3 LIMMitless study., Methods: This subgroup analysis evaluated pooled data from patients with moderate-to-severe plaque psoriasis who were randomized to risankizumab 150 mg during two double-blind, phase 3, 52-week base studies (UltIMMa-1/2; NCT02684370/NCT02684357) and were enrolled in the phase 3 LIMMitless open-label extension study (NCT03047395). Subgroup assessments included the proportion of patients who achieved ≥90%/100% improvement in Psoriasis Area and Severity Index (PASI 90/100). Among patients with nail, scalp and/or palmoplantar psoriasis in addition to skin psoriasis, assessments included changes from baseline in and resolution of these three psoriatic manifestations., Results: Overall, a numerically similar proportion of patients (N = 525) achieved PASI 90/100 through Week 256, regardless of their baseline age, sex, body mass index, weight, PASI or psoriatic arthritis status. Patients with nail, scalp and/or palmoplantar psoriasis experienced substantial improvements in manifestation-specific indices (mean improvement from baseline to Week 256 of >81%, >94% and >97%, respectively); in patients with all three manifestations (N = 121), 44.6% achieved complete clearance of these manifestations at Week 256., Conclusions: Risankizumab demonstrated generally consistent efficacy through 256 weeks across patient subgroups and showed durable long-term efficacy for psoriatic disease manifestations., (© 2024 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)

Importance: Total neoadjuvant therapy (TNT) is the standard treatment for locally advanced rectal cancer, especially for patients with high-risk factors. However, the efficacy of TNT combined with immunotherapy for patients with proficient mismatch repair (pMMR) rectal cancer is unknown., Objectives: To evaluate the safety and efficacy of TNT with induction chemoimmunotherapy followed by long-course chemoradiation in patients with high-risk, pMMR rectal cancer and to identify potential molecular biomarkers associated with treatment efficacy., Design, Setting, and Participants: This cohort study was a single-arm phase 2 trial conducted at Gastrointestinal Cancer Center, Peking University Cancer Hospital & Institute, from June 2020 to October 2021. Biopsies and plasma were collected before treatment for whole-exome sequencing and cell-free DNA sequencing, respectively. Data were analyzed from May 2022 to September 2022., Interventions: Participants received 3 cycles of induction oxaliplatin and capecitabine combined with camrelizumab and radiotherapy (50.6 Gy in 22 fractions) with concurrent capecitabine. Patients without disease progression received 2 cycles of consolidation oxaliplatin/capecitabine., Main Outcomes and Measures: The primary end point was pathologic complete response rate., Results: Of 25 patients enrolled (19 men [76%]; 6 women [24%]; median [IQR] age, 58 [48-64] years), 22 patients (88%) completed the TNT schedule. The pathologic complete response rate was 33.3% (7/21). Twelve patients (48%) achieved clinical complete response, and 4 patients (16%) chose to watch and wait. R0 resection was achieved in 21 of 21 patients, and the major pathologic response rate was 38.1% (8/21). The most common adverse event was nausea (80%, 20/25); grade 3 toxic effects occurred in 9 of 25 patients (36%). Patients with tumor shrinkage of 50% or greater after induction oxaliplatin/capecitabine and camrelizumab or clinical complete response had higher percentages of LRP1B mutation. Mutation of LRP1B was associated with high tumor mutation burden and tumor neoantigen burden. Patients with high tumor mutation burden all benefited from therapy., Conclusions and Relevance: This study found that TNT with induction chemoimmunotherapy followed by long-course chemoradiation was safe and effective for patients with high-risk rectal cancer with pMMR status. Longer follow-up and larger clinical studies are needed to validate this innovative regimen. There is also an urgent need to further validate the predictive value of LRP1B and discover other novel biomarkers with potential predictive value for rectal cancer.

Background: An enriching learning environment is integral to resident wellness and education. Integrated vascular (VS) and general surgery (GS) residents share 18 months of core GS rotations during the postgraduate years 1-3 (PGY1-3); differences in their experiences may help identify practical levers for change., Methods: We used a convergent mixed-methods design. Cross-sectional surveys were administered after the 2020 American Board of Surgery In-Training Examination and Vascular Surgery In-Training Examination, assessing eight domains of the learning environment and resident wellness. Multivariable logistic regression models identified factors associated with thoughts of attrition between categorical PGY1-3 residents at 57 institutions with both GS and VS programs. Resident focus groups were conducted during the 2022 Vascular Annual Meeting to elicit more granular details about the experience of the learning environment. Transcripts were analyzed using inductive and deductive logics until thematic saturation was achieved., Results: Surveys were completed by 205 VS and 1198 GS PGY1-3 residents (response rates 76.8% for VS and 82.5% for GS). After adjusting for resident demographics, PGY level, and program type, GS residents were more likely than their VS peers to consider leaving their programs (odds ratio [OR]: 2.61, 95% confidence interval [CI]: 1.37-4.99). This finding did not persist after adjusting for differences in perceptions of the learning environment, specifically: GS residents had higher odds of mistreatment (OR: 1.99, 95% CI: 1.36-2.90), poorer work-life integration (OR: 2.88, 95% CI: 1.41-5.87), less resident camaraderie (OR: 3.51, 95% CI: 2.26-5.45), and decreased meaning in work (OR: 2.94, 95% CI: 1.80-4.83). Qualitative data provided insight into how the shared learning environment was perceived differently: (1) vascular trainees expressed that early specialization and a smaller, more invested faculty allow for an apprenticeship model with early operative exposure, hands-on guidance, frequent feedback, and thus early skill acquisition (meaning in work); (2) a smaller program is conducive to closer relationships with co-residents and faculty, increasing familiarity (camaraderie and work-life integration); and (3) due to increased familiarity with program leadership, vascular trainees feel more comfortable reporting mistreatment, allowing for prompt responses (mistreatment)., Conclusions: Despite sharing a learning environment, VS and GS residents experience training differently, contributing to differential thoughts of attrition. These differences may be attributable to intrinsic features of the integrated training paradigm that are not easily replicated by GS programs, such as smaller program size and higher faculty investment due to early specialization. Alternative strategies to compensate for these inherent differences should be considered (eg, structured operative entrustment programs and faculty incentivization)., Competing Interests: Disclosures None., (Copyright © 2023 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Sterols are ubiquitous membrane constituents that persist to a large extent in the environment due to their water insolubility and chemical inertness. Recently, an oxygenase-independent sterol degradation pathway was discovered in a cholesterol-grown denitrifying bacterium Sterolibacterium (S.) denitrificans. It achieves hydroxylation of the unactivated primary C26 of the isoprenoid side chain to an allylic alcohol via a phosphorylated intermediate in a four-step ATP-dependent enzyme cascade. However, this pathway is incompatible with the degradation of widely distributed steroids containing a double bond at C22 in the isoprenoid side chain such as the plant sterol stigmasterol. Here, we have enriched a prototypical delta-24 desaturase from S. denitrificans, which catalyzes the electron acceptor-dependent oxidation of the intermediate stigmast-1,4-diene-3-one to a conjugated (22,24)-diene. We suggest an α 4 β 4 architecture of the 440 kDa enzyme, with each subunit covalently binding an flavin mononucleotide cofactor to a histidyl residue. As isolated, both flavins are present as red semiquinone radicals, which can be reduced by stigmast-1,4-diene-3-one but cannot be oxidized even with strong oxidizing agents. We propose a mechanism involving an allylic radical intermediate in which two flavin semiquinones each abstract one hydrogen atom from the substrate. The conjugated delta-22,24 moiety formed allows for the subsequent hydroxylation of the terminal C26 with water by a heterologously produced molybdenum-dependent steroid C26 dehydrogenase 2. In conclusion, the pathway elucidated for delta-22 steroids achieves oxygen-independent hydroxylation of the isoprenoid side chain by bypassing the ATP-dependent formation of a phosphorylated intermediate., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Rationale: Idiopathic pulmonary fibrosis (IPF) is an irreversible, fatal interstitial lung disease lacking specific therapeutics. Nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme of the nicotinamide adenine dinucleotide (NAD) salvage biosynthesis pathway and a cytokine, has been previously reported as a biomarker for lung diseases; however, the role of NAMPT in pulmonary fibrosis has not been elucidated. Methods: We identified the NAMPT level changes in pulmonary fibrosis by analyzing public RNA-Seq databases, verified in collected clinical samples and mice pulmonary fibrosis model by Western blotting, qRT-PCR, ELISA and Immunohistochemical staining. We investigated the role and mechanism of NAMPT in lung fibrosis by using pharmacological inhibition on NAMPT and Nampt transgenic mice. In vivo macrophage depletion by clodronate liposomes and reinfusion of IL-4-induced M2 bone marrow-derived macrophages (BMDMs) from wild-type mice, combined with in vitro cell experiments, were performed to further validate the mechanism underlying NAMPT involving lung fibrosis. Results: We found that NAMPT increased in the lungs of patients with IPF and mice with bleomycin (BLM)-induced pulmonary fibrosis. NAMPT inhibitor FK866 alleviated BLM-induced pulmonary fibrosis in mice and significantly reduced NAMPT levels in bronchoalveolar lavage fluid (BALF). The lung single-cell RNA sequencing showed that NAMPT expression in monocytes/macrophages of IPF patients was much higher than in other lung cells. Knocking out NAMPT in mouse monocytes/macrophages ( Nampt fl/fl ;Cx3cr1 CreER ) significantly alleviated BLM-induced pulmonary fibrosis in mice, decreased NAMPT levels in BALF, reduced the infiltration of M2 macrophages in the lungs and improved mice survival. Depleting monocytes/macrophages in Nampt fl/fl ;Cx3cr1 CreER mice by clodronate liposomes and subsequent pulmonary reinfusion of IL-4-induced M2 BMDMs from wild-type mice, reversed the protective effect of monocyte/macrophage NAMPT-deletion on lung fibrosis. In vitro experiments confirmed that the mechanism of NAMPT engaged in pulmonary fibrosis is related to the released NAMPT by macrophages promoting M2 polarization in a non-enzyme-dependent manner by activating the STAT6 signal pathway. Conclusions: NAMPT prompts bleomycin-induced pulmonary fibrosis by driving macrophage M2 polarization in mice. Targeting the NAMPT of monocytes/macrophages is a promising strategy for treating pulmonary fibrosis., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

As process nodes of advanced integrated circuits continue to decrease below 10 nm, the requirement for overlay accuracy is becoming stricter. The alignment sensor measures the position of the alignment mark relative to the wafer; thus, sub-nanometer alignment position accuracy is vital. The Phase Grating Alignment (PGA) method is widely used due to its high precision and stability. However, the alignment error caused by the mark asymmetry is the key obstacle preventing PGA technology from achieving sub-nanometer alignment accuracy. This error can be corrected using many methods, such as process verification and multi-channel weighted methods based on multi-diffraction, multi-wavelength and multi-polarization state alignment sensors. However, the mark asymmetry is unpredictable, complex and difficult to obtain in advance. In this case, the fixed-weight method cannot effectively reduce the alignment error. Therefore, an adaptive weighted method based on the error distribution characteristic of a multi-channel is proposed. Firstly, the simulation result proves that the error distribution characteristic of the multi-alignment result has a strong correlation with the mark asymmetry. Secondly, a concrete method of constructing weight values based on error distribution is described. We assume that the relationship between the weight value of each channel and the deviations of all channels' results is second-order linear. Finally, without other prior process correction in the simulation experiment, the residual error's Root Mean Square (RMS) of fixed weighted method is 14.0 nm, while the RMS of the adaptive weighted method is 0.01 nm, when dealing with five typical types of mark asymmetry. The adaptive weighted method exhibits a more stable error correction effect under unpredictable and complicated mark asymmetry.

Background: Panel gene sequencing is an established diagnostic tool for precision oncology of solid tumors, but its utility for the treatment of cancers of the digestive system in clinical routine is less well documented., Methods: We retrospectively identified patients with advanced or metastatic gastrointestinal, pancreaticobiliary or hepatic cancers who received panel gene sequencing at a tertiary university hospital from 2015 to 2022. For these cases, we determined the spectrum of genetic alterations, clinicopathological parameters and treatment courses. Assessment of actionability of genetic alterations was based on the OncoKB database, cancer-specific ESMO treatment guidelines, and recommendations of the local molecular tumor board., Results: In total, 155 patients received panel gene sequencing using either the Oncomine Focus (62 cases), Comprehensive (91 cases) or Childhood Cancer Research Assay (2 cases). The mean age of patients was 61 years (range 24-90) and 37% were female. Most patients suffered from either colorectal cancer (53%) or cholangiocellular carcinoma (19%). 327 genetic alterations were discovered in 123 tumor samples, with an average number of 2.1 alterations per tumor. The most frequently altered genes were TP53, KRAS and PIK3CA. Actionable gene alterations were detected in 13.5-56.8% of tumors, according to ESMO guidelines or the OncoKB database, respectively. Thirteen patients were treated with targeted therapies based on identified molecular alterations, with a median progression-free survival of 8.8 months., Conclusions: Actionable genetic alterations are frequently detected by panel gene sequencing in patients with advanced cancers of the digestive tract, providing clinical benefit in selected cases. However, for the majority of identified actionable alterations, sufficient clinical evidence for targeted treatments is still lacking., (© 2024. The Author(s).)

Understanding interfacial interactions of graphene oxide (GO) is important to evaluate its colloidal behavior and environmental fate. Single-layer GO is the fundamental unit of GO colloids, and its interfacial aqueous layers critically dictate these interfacial interactions. However, conventional techniques like X-ray diffraction are limited to multilayer systems and are inapplicable to single-layer GO. Therefore, our study employed atomic force microscopy to precisely observe the in situ dynamic behaviors of interfacial aqueous layers on single-layer GO. The interfacial aqueous layer height was detected at the subnanometer level. In real-time monitoring, the single-layer height increased from 1.17 to 1.70 nm within 3 h immersion. This sluggish process is different from the rapid equilibration of multilayer GO in previous studies, underscoring a gradual transition in hydration kinetics. Ion strength exhibited negligible influence on the single-layer height, suggesting a resilient response of the interfacial aqueous layer to ion-related perturbations due to intricate ion interactions and electrical double-layer compression. Humic acid led to a substantial increase in the interfacial aqueous layers, improving the colloidal stability of GO and augmenting its potential for migration. These findings hold considerable significance regarding the environmental behaviors of the GO interfacial aqueous layer in ion- and organic-rich water and soil.

Wilson's disease is caused by abnormal copper metabolism resulting in deposition in various organs, including the brain, liver, and cornea, thus disrupting organ function. It is characterized by encephalopathy, extrapyramidal symptoms, progressive liver failure, and copper ring deposition in the cornea. Management of this disease should include quality of life maintenance; however, relevant studies on this topic are lacking. This study aimed to assess the factors affecting the quality of life (QoL) of patients with Wilson's disease. A cross-sectional survey using convenience sampling was conducted between July 2020 and March 2021 at the hospital. Data on patient characteristics, 36-item Short-Form General Health Survey, Uniform Wilson Disease Rating Scale, and Hamilton Depression Rating Scale scores were collected. Associations among quality of life depression, anxiety, and Wilson's disease progression were examined using Pearson correlation analysis. Factors affecting the quality of life of patients, including depression, anxiety, liver function, clinical symptoms, diet, liver function, brain magnetic resonance imaging (MRI) findings, disease duration, Barthel Index, and Morse scores were examined using multivariate linear regression analysis. This study included 134 patients with Wilson's disease whose mean age was 29.12 ± 8.59 years. The mean QoL score in the patient group was 71.38 ± 9.55 points and was negatively correlated with anxiety (r = - 0.883, P = 0.000), depression (r = - 0.852 P = 0.000), and clinical symptoms (r = - 0.542, P = 0.000) scores. Anxiety, depression, and clinical symptoms severity are vital factors for the QoL of patients with Wilson's disease. The study provides foundational evidence to design novel interventions, including symptom management, diet, and self-care ability, which can help in improving the quality of life in patients with Wilson's disease and decreasing the burden associated with this disease., (© 2024. The Author(s).)

Polyoxometalates (POMs) are promising inorganic drug candidates for cancer chemotherapy. They are becoming attractive because of their easy accessibility and low cost. Herein, we report the synthesis and antitumor activity studies of four Lindqvist-type POMs with mixed-addenda atoms Na 2 [V 4 W 2 O 16 {(OCH 2 ) 3 CR}] (R=-CH 2 OH, -CH 3 , -CH 2 CH 3 ) and (Bu 4 N) 2 [V 3 W 3 {(OCH 2 ) 3 CH 2 OOCCH 2 CH 3 }]. Compared with the current clinical applied antitumor drug 5-fluorouracil (5-FU) or Gemcitabine, analysis of MTT/CCK-8 assay, colony formation and wound healing assay revealed that the {V 4 W 2 } POMs had acceptable cytotoxicity in normal cells (293T) and significant inhibitory effects on cell proliferation and migration in three human tumor cell lines: human lung carcinoma cells (A549), human cervical carcinoma cells (HeLa), and human breast cancer cells (MCF-7). Interestingly, among the POMs analyzed, the therapeutic index (TI) of the {V 4 W 2 } POM with R= -CH 2 OH was relatively the most satisfactory. Thus, it was subsequently used for further studies. Flow cytometry analysis showed it prompted cellular apoptosis rate. qRT-PCR and Western blotting analysis indicated that multiple cell death pathways were activated including apoptosis, autophagy, necroptosis and pyroptosis during the POM-mediated antitumor process. In conclusion, our study shows that the polyoxotungstovanadate has great potential to be developed into a broad-spectrum antitumor chemotherapeutic drug., (© 2024 Wiley‐VHCA AG, Zurich, Switzerland.)

The process of atmospheric organic carbon (OC) entering the ocean through wet deposition plays a crucial role in the global carbon cycle. To gain insights into the biogeochemical dynamics of OC at the land-sea margin, we conducted an extensive four-year investigation on precipitation OC in Jiaozhou Bay (JZB). The results showed that the volume-weighted mean concentration of particulate OC (POC) and dissolved OC (DOC) in precipitation were 0.38 and 2.06 mg C L -1 with an average wet deposition flux of OC for 2666.5 mg C m -2  yr -1 . The source of POC in precipitation is predominantly by the C3 plant emission and burning and fossil fuel combustion. Wet deposition contributed 986.6 t yr -1 of OC of which 506.3 t yr -1 of bioavailable DOC, which could have significant implications for carbon cycle in the JZB. This study could enhance the understanding of the marine atmospheric OC in coastal areas., 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.)

Emerging literatures have concentrated on the association between cardiovascular diseases risk of typical endocrine disruptor bisphenols, which also put forward the further studies need respect to the potential mechanism. Herein, we investigated the endothelial dysfunction effects of bisphenols and brominated bisphenols involved in aortic pathological structure, endothelial nitric oxide synthase (eNOS) protein phosphorylation, synthase activity and nitric oxide (NO) production in human umbilical vein endothelial cells (HUVECs) and C57BL/6 mice. Bisphenol A (BPA) and bisphenol S (BPS) increased NO production by 85.7% and 68.8% at 10 -6  M level in vitro and 74.3%, 41.5% in vivo, respectively, while tetrabromobisphenol S (TBBPS) significantly inhibited NO by 55.7% at 10 -6  M in vitro and 28.9% in vivo at dose of 20 mg/kg BW/d. Aortic transcriptome profiling revealed that the process of 'regulation of NO mediated signal transduction' was commonly induced. The mRNA and protein expression of phosphorylated eNOS at Ser 1177 were promoted by BPA and BPS but decreased by TBBPA and TBBPS in HUVECs. Phosphorylation and enzymatic activity of eNOS were significantly increased by 43.4% and 13.8% with the treatment of BPA and BPS at 10 -7  M, but decreased by 16.9% after exposure to TBBPS at 10 -6  M in vitro. Moreover, only TBBPS was observed to increase aorta thickness significantly in mice and induce endothelial dysfunction. Our work suggests that bisphenols and brominated bisphenols may exert adverse outcome on vascular health differently in vitro and in vivo, and emphasizes areas of public health concern similar endocrine disruptors vulnerable on the vascular endothelial function., 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.)

Na superionic conductor (NASICON) materials hold promise as solid-state electrolytes due to their wide electrochemical stability and chemical durability. However, their limited ionic conductivity hinders their integration into sodium-ion batteries. The conventional approach to electrolyte design struggles with comprehending the intricate interactions of factors impacting conductivity, encompassing synthesis parameters, structural characteristics, and electronic descriptors. Herein, we explored the potential of machine learning in predicting ionic conductivity in NASICON. We compile a database of 211 datasets, covering 160 NASICON materials, and employ facile descriptors, including synthesis parameters, test conditions, molecular and structural attributes, and electronic properties. Random forest (RF) and neural network (NN) models were developed and optimized, with NN performing notably better, particularly with limited data (R 2 =0.820). Our analysis spotlighted the pivotal role of Na stoichiometric count in ionic conductivity. Furthermore, the NN algorithm highlighted the comparable significance of synthesis parameters to structural factors in determining conductivity. In contrast, the impact of electronegativity on doped elements appears less significant, underscoring the importance of dopant size and quantity. This work underscores the potential of machine learning in advancing NASICON electrolyte design for sodium-ion batteries, offering insights into conductivity drivers and a more efficient path to optimizing materials., (© 2023 Wiley‐VCH GmbH.)

Thyroid dysfunction is associated with the risk of cardiovascular disease; however, whether plasma thyroid-stimulating hormone (TSH) levels in subjects with euthyroidism affect the risk of cardiovascular disease remains unclear. This study aimed to investigate the causal association between plasma TSH levels and cardiovascular diseases, particularly ischemic heart disease and heart failure (HF). Summary statistics from the Integrative Epidemiology Unit Open genome-wide association studies Project and FinnGen consortium were used to investigate the causal relationship between plasma TSH levels and the risk of cardiovascular diseases. Two-sample Mendelian randomization analysis using inverse-variance weighting as the primary method was performed. The MR Pleiotropy RESidual Sum and Outlier and leave-one-out methods were used to ensure the robustness of our findings. Genetically determined plasma TSH levels were associated with major coronary heart disease events (OR 1.0557, 95% CI 1.0141-1.0991), all-cause HF (OR 0.9587, 95% CI 0.9231-0.9956), and HF + non-ischemic cardiomyopathy (OR 0.9318, 95% CI 0.8786-0.9882). After the Bonferroni correction, the causation described above disappeared. In the secondary analysis, genetically determined higher TSH levels were associated with a higher risk for unstable angina pectoris (OR 1.0913, 95% CI 1.0350-1.1507), but were associated with a lower risk for HF + overweight (OR 0.9265, 95% CI 0.8821-0.9731). These results were further validated using sensitivity analysis. Our findings show that increased plasma TSH levels in patients with euthyroidism may increase the risk of unstable angina pectoris but reduce the risk of HF in overweight patients. This evidence indicates that plasma TSH levels may need to be carefully controlled in specific patients., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objectives: The COVID-19 pandemic was disruptive for trainees and may have affected career decisions for some learners. This study examined the impact of the pandemic on emergency medicine (EM) resident perceptions of their mental health, perceptions of personal safety, and career choice regret., Methods: This was a cross-sectional survey study administered following the 2021 American Board of Emergency Medicine In-Training Examination (ITE). Survey measures included suicidal ideation (SI), COVID concerns in terms of infection prevention and control (IPC) training, COVID risk to self and/or COVID risk to family, and COVID-related career regret. COVID concerns were compared by gender and race/ethnicity using Pearson's chi-square tests. Multivariable logistic regression models were used to test the association between SI and COVID concerns, resident characteristics, and program characteristics., Results: A total of 6980 out of 8491 EM residents (82.2%) from 244 programs completed the survey. Only 1.1% of participants reported insufficient training in COVID IPC practices. Participants were concerned about COVID risk to themselves (40.3%) and to their families (63.3%) due to their job roles. These concerns were more common among women or nonbinary (vs. men); all other races/ethnicities (vs. non-Hispanic Whites); senior residents (vs. PGY-1, PGY-2 residents); and residents who were married or in relationships (vs. single or divorced). A total of 6.1% of participants reported that COVID made them reconsider choosing EM as their career. Career regret in this cohort was higher than that in the proportion (3.2%) expressing career regret in the 2020 ITE ( p  < 0.001). Career regret was more common among women or nonbinary (vs. men); all other races/ethnicities (vs. non-Hispanic Whites); and senior residents (vs. PGY-1, PGY-2 residents). The overall SI rate was 2.6%, which did not differ from that of the 2020 sample of EM residents (2.5%, p  = 0.88)., Conclusions: Many EM residents reported concerns about COVID risks to themselves and their families. Although the rate of SI remained unchanged, more EM residents reported career regret during the COVID pandemic., Competing Interests: Drs. Barton and Reisdorff are employees of the American Board of Emergency Medicine. The other authors declare no conflicts of interest., (© 2024 Society for Academic Emergency Medicine.)

Pulmonary fibrosis is a challenging lung disease characterized by a bleak prognosis. A pivotal element in the progression of this disease is the dysregulated recruitment of macrophages. Nicotinamide phosphoribose transferase (NAMPT), secreted by alveolar epithelial cells and inflammatory cells, has been previously identified to influence macrophage inflammation in acute lung injury through the nicotinamide adenine dinucleotide (NAD) rescue synthesis pathway. Nonetheless, the exact role of NAMPT in the regulation of lung fibrosis is yet to be elucidated. In our research, we employed bleomycin (BLM) to induce pulmonary fibrosis in Nampt flox/flox ;Cx3cr1 CreER mice, using Nampt flox/flox mice as controls. Our findings revealed an augmented expression of NAMPT concurrent with a marked increase in the secretion of NAD and inflammatory cytokines such as IL-6, TNF-α, and TGF-β1 post-BLM treatment. Furthermore, an upsurge in NAMPT-positive macrophages was observed in the lungs of BLM-treated Nampt flox/flox mice. Notably, a conditional knockout of NAMPT (NAMPT cKO) in lung macrophages curtailed the BLM-induced inflammatory responses and significantly mitigated pulmonary fibrosis. This was associated with diminished phospho-Sirt1 (p-Sirt1) expression levels and a concomitant rise in mothers against decapentaplegic homolog 7 (Smad7) expression in BLM-treated mouse lungs and murine RAW 264.7 macrophage cells. Collectively, our data suggests that NAMPT exacerbates macrophage-driven inflammation and pulmonary fibrosis via the Sirt1-Smad7 pathway, positioning NAMPT as a promising therapeutic target for pulmonary fibrosis intervention., Competing Interests: Declaration of competing interest The authors report no declarations of interest in this work., (Copyright © 2024. Published by Elsevier B.V.)

Since the approval for the treatment of melanoma in 2014, immune checkpoint inhibitors (ICIs) have revolutionized the therapy pattern across various malignancies. Coinciding with their frequent usage, their adverse effects, including fever, cannot be neglected. In the context of cancer diseases and cancer treatments, fever of unknown origin (FUO), which has long posed a challenge for clinicians in terms of diagnosis and management, brings forth new connotation and significance. In this paper review, we present the concept of ICIs-associated FUO, consider activated immune system and elevated cytokines as common mechanisms by which ICIs induce fever and various immune-related adverse events (irAEs), summarize and compare the primary etiologies of ICI-associated FUO, and compare it with conventional types of FUO., 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 Tong, Zhan, Dong and Xu.)

Context.—: Mutant KRAS is the main oncogenic driver in pancreatic ductal adenocarcinomas (PDACs). However, the clinical and phenotypic implications of harboring different mutant KRAS alleles remain poorly understood., Objective.—: To characterize the potential morphologic and clinical outcome differences in PDACs harboring distinct mutant KRAS alleles., Design.—: Cohort 1 consisted of 127 primary conventional PDACs with no neoadjuvant therapy, excluding colloid/mucinous, adenosquamous, undifferentiated, and intraductal papillary mucinous neoplasm-associated carcinomas, for which an in-house 42-gene mutational panel had been performed. A morphologic classification system was devised wherein each tumor was assigned as conventional, papillary/large duct (P+LD, defined as neoplastic glands with papillary structure and/or with length ≥0.5 mm), or poorly differentiated (when the aforementioned component was 60% or more of the tumor). Cohort 2 was a cohort of 88 PDACs in The Cancer Genome Atlas, which were similarly analyzed., Results.—: In both cohorts, there was significant enrichment of P+LD morphology in PDACs with KRAS G12V and G12R compared with G12D. In the entire combined cohort, Kaplan-Meier analyses showed longer overall survival (OS) with KRAS G12R as compared with G12D (median OS of 1255 versus 682 days, P = .03) and in patients whose PDACs displayed P+LD morphology as compared with conventional morphology (median OS of 1175 versus 684 days, P = .04). In the adjuvant-only subset, KRAS G12R had the longest OS compared with G12D, G12V, and other alleles (median OS unreached/undefined versus 1009, 1129, and 1222 days, respectively)., Conclusions.—: PDACs with different mutant KRAS alleles are associated with distinct morphologies and clinical outcomes, with KRAS G12R allele associated with P+LD morphology and longer OS when compared with G12D using Kaplan-Meier studies., Competing Interests: The authors have no relevant financial interest in the products or companies described in this article., (© 2024 College of American Pathologists.)

Background: Hashimoto thyroiditis (HT) is a common autoimmune thyroid disease for which there is no specific treatment. Oral levothyroxine sodium tablets significantly improved thyroid function but did not promote a reduction in thyroid-related antibody concentrations. Acupuncture can improve clinical symptoms and thyroid function in HT patients, reduce serum TPOAb and TGAb levels in HT patients, and improve patients' quality of life., Methods: We conducted a systematic review and meta-analysis to evaluate the effect of acupuncture versus levothyroxine sodium tablets on Hashimoto thyroiditis. We searched Web of Science, Embase, China National Knowledge Infrastructure, WanFang, VIP, SinoMed and the Cochrane Central Registry of Controlled Trials to identify candidate randomized controlled trials (RCTs)., Results: A total of 1020 patients participated in 14 randomized controlled trials. The results of meta-analysis showed that acupuncture regulated TPOAb content (mean difference [MD] = -63.18, 95%CI = -91.73 to -34.62, P < .00001), TGAb content (MD = -68.56, 95%CI = -101.55 to -35.57, P < .00001), serum free triiodothyronine (FT3) content (MD = 0.74, 95%CI = 0.20 to 1.27, P < .00001), serum free thyroxine (FT4) content (MD = 1.10, 95%CI = 0.29 to 1.92, P < .00001), TSH content (MD = -2.16, 95%CI = -3.14 to -1.19, P < .00001) had a significant effect., Conclusion: Compared with levothyroxine sodium tablets alone, acupuncture can significantly regulate the contents of TPOAb, TGAb, FT3, FT4 and TSH., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Transgender women may have concerns of drug interactions between feminizing hormone therapy (FHT) and antiretrovirals, leading to nonadherence. This randomized, three-period crossover, open-label, phase I trial assessed the effects of doravirine (DOR) and tenofovir disoproxil fumarate (TDF) on the pharmacokinetics (PKs) of estradiol, spironolactone, and total testosterone and vice versa in healthy transgender women. Volunteers were randomized 1:1 into two sequences containing three treatment groups (DOR, lamivudine [3TC], and TDF alone; estradiol, spironolactone, and placebo; and DOR/3TC/TDF, estradiol, and spironolactone). Eight subjects enrolled in the study and six had completed all study periods. The geometric mean ratios for DOR area under the concentration-time curve from zero to last measured concentration (AUC 0-last ), maximum concentration (C max ), and concentration at 24 h (C 24 ) were similar. However, tenofovir (TFV) AUC 0-last , C max , and C 24 moderately increased by 14%-38%. Last, estradiol AUC 0-last , C max , and C 24 were increased by 10%-13%. Whereas most 90% confidence intervals did not meet the bioequivalence bounds of 80%-125%, the point estimates fell within the intervals. Log-transformed DOR, TFV, and estradiol PK parameters computed with and without co-administration were not statistically different (p > 0.05). There were no serious adverse events. There is not a clinically significant impact of FHT on DOR/TFV PKs. Similarly, there is no observed impact on estradiol PKs and total testosterone following use of DOR/3TC/TDF., (© 2024 The Authors. Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Under the high current density, the excessive strong adsorption of H* intermediates and H 2 accumulation the catalysts are the major obstacle to the industrial application of hydrogen evolation reaction (HER) catalysts. Herein, through experimental exploration, it is found that the superaerophobic Nitrogen (N)-doped carbon material can promote the rapid release of H 2 and provide H* desorption site for the hydrogen spillover process, which makes it have great potential as the catalysts support for hydrogen spillover. Based on this discovery, this work develops the hydrogen spillover catalyst with electron-rich Pt sites loaded on N-doped carbon nanocage (N-CNC) with adjustable work function. Through a series of comprehensive electrochemical tests, the existence of hydrogen spillover effort has been proved. Moreover, the in situ tests showed that pyrrolic-N can activate adjacent carbon sites as the desorption sites for hydrogen spillover. The Pt@N-1-CNC with the minimum work function difference (ΔΦ) between Pt NPs and support shows superior hydrogen evolution performance, only needs overpotential of 12.2 mV to reach current density of 10 mA cm -2 , outstanding turnover frequency (TOF) (44.7 s -1 @100 mV) and superior durability under the 360 h durability tests at current density of 50 mA cm -2 ., (© 2023 Wiley-VCH GmbH.)

The asymmetric catalytic inverse-electron-demand hetero-Diels-Alder reaction of dioxopyrrolidines with a variety of simple olefins has been accomplished, significantly expanding the applicability of this cyclization to both cyclic hetero-dienes and dienophiles. A new type of strong Lewis acid catalyst of ferric salt enables the LUMO activation of dioxopyrrolidines via formation of cationic species, this method yields a range of bicyclic dihydropyran derivatives with exceptional outcomes, including high yields (up to 99%), diastereoselectivity (up to 99 : 1) and enantioselectivity (up to 99% ee) under mild conditions. This facile protocol was available for the late-stage modification of several bioactive molecules and transformation into macrocycle molecules as well. The origins of enantioselectivity were elucidated based on control experiments., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)