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Yue Chen,1,&ast; Yan-Chang Yang,2,&ast; Li-Ying Tang,3,&ast; Qian-Min Ge,4 Wen-Qing Shi,1,4 Ting Su,3,5 Hui-Ye Shu,1,4 Yi-Cong Pan,1,4 Rong-Bin Liang,4 Qiu-Yu Li,4 Yi Shao4 1Department of Dermatology, The Eighth Affiliated Hospital of Sun Yat-sen University, Shenzhen, Guangzhou, 518033, People’s Republic of China; 2Department of Anesthesiology, Nanchang University, Nanchang, Jiangxi, 330006, People’s Republic of China; 3Department of Ophthalmology, Zhongshan Hospital of Xiamen University, Xiamen, Fujian Province, 361102, People’s Republic of China; 4Department of Geriatric Medicine and Ophthalmology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006, People’s Republic of China; 5Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Boston, MA, 02114, USA&ast;These authors contributed equally to this workCorrespondence: Yi ShaoDepartment of Geriatric Medicine and Ophthalmology, The First Affiliated Hospital of Nanchang University, No. 17, YongWaiZheng Street, DongHu District, Nanchang, Jiangxi, 330006, People’s Republic of ChinaTel/Fax +86 791-88692520Email freebee99@163.comObjective: Gastric adenocarcinoma originates from the glands in the superficial layer or mucosa of the stomach. It is prone to metastases, of which ocular metastasis (OM) is rare, but once it occurs the disease is considered more serious. The aim of this study was to investigate the risk factors for OM in gastric adenocarcinoma.Methods: Patients with gastric adenocarcinoma were recruited to this study between June 2003 and July 2019. Demographic data and serological indicators (SI) were compared between patients with and without OM, and binary logistic regression was used to explore whether the relevant SI may be risk factors for OM of gastric adenocarcinoma. Receiver operating characteristic (ROC) curves were used to analyze different SIs for OM in gastric cancer patients.Results: Chi-square tests showed significant between-groups difference in gender composition (P < 0.05), but not in age or histological grade (P > 0.05). t-test results showed that low-density lipoprotein (LDL) and carbohydrate antigen-724 (CA724) were significantly higher in patients with than without OM (P < 0.05). Binary logistic regression analysis showed that LDL was an independent risk factor for OM (P < 0.001). ROC curve analysis showed that the areas under the curves (AUC) for LDL and CA724 were 0.903 and 0.913 respectively, with higher AUC for combined LDL and CA724 (0.934; P < 0.001).Conclusion: LDL and CA724 have value as predictors for OM in patients with gastric adenocarcinoma, with higher predictive value when these factors are combined.Keywords: gastric adenocarcinoma, serological indicators, ocular metastases, risk factors, ROC curve

Ya-Jie Yu,1,* Rong-Bin Liang,1,* Qi-Chen Yang,2,* Qian-Min Ge,1 Qiu-Yu Li,1 Biao Li,1 Wen-Qing Shi,1 Yi Shao1 1Department of Ophthalmology, The First Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi, People’s Republic of China; 2Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong 999077, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yi Shao Tel/ Fax +86 791-88692520Email freebee99@163.comObjective: Previous studies demonstrated that myopia could result in alterations of brain activity in specific areas. However, whether the visual function could improve by Lasik surgery, with the brain activity alterations also change, is still unknown. Here, we intended to use the amplitude of low-frequency fluctuation (ALFF) technique to investigate the intrinsic brain activity changes in pre-Lasik (PRL) and post-Lasik (POL) patients.Methods: A total of 15 patients with myopia (nine male and six female) were recruited in our study, who were matched according to age, weight, and height. These patients comprised both the PRL and POL groups, which is self-controlled. The patients all underwent resting-state functional magnetic resonance imaging (MRI), and the spontaneous brain activity changes were recorded by the ALFF technique. The data were recorded and arranged in the receiver operating characteristic (ROC) curve, which presented how intrinsic activities altered in different brain regions. Moreover, by Graphpad prism 8, we can analyze the linear correlation between HADS (Hospital Anxiety and Depression Scale) and ALFF values as well.Results: Differences in ALFF values existed in brain regions between the same patient before and after the Lasik operation. The regions with increased ALFF values after Lasik surgery were the left parahippocampal gyrus, cerebellar vermis, and left posterior cingulate cortex. The regions with decreased ALFF values after Lasik surgery were the left supramarginal gyrus and right trigonometric inferior frontal gyrus.Conclusion: We demonstrated significant fluctuations of ALFF values in specific brain areas between the same patients before and after the Lasik surgery. The altered ALFF values reflected the hyperactivity or hypoactivity of the specific brain areas, which may help predict the recovery level of patients’ vision after Lasik surgery. Furthermore, based on the experimental results that presented significant activity alterations in specific brian regions, patients could be speculated equipped with a better visual function.Keywords: myopia, Lasik, resting-state functional MRI, amplitude of low-frequency fluctuation

Zhou Zhou,1– 3 Pei-Wen Zhu,3 Wen-Qing Shi,3 You-Lan Min,3 Qi Lin,3 Qian-Min Ge,3 Biao Li,3 Qing Yuan,3 Yi Shao3 1Institute of Pathogenic Biology, Medical College, University of South China, Hengyang 421001, Hunan, People’s Republic of China; 2Hunan Provincial Key Laboratory for Special Pathogens Prevention and Control, Hengyang 421001, Hunan, People’s Republic of China; 3Department of Ophthalmology, The First Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi Province, People’s Republic of ChinaCorrespondence: Yi ShaoDepartment of Ophthalmology, The First Affiliated Hospital of Nanchang University, No. 17, Yongwaizheng Street, Donghu District, Nanchang 330006, Jiangxi Tel/ Fax +86 791-88692520Email freebee99@163.comPurpose: Brain function in patients with acute eye pain (EP) has not been extensively studied. An understanding of the alterations in short-range functional connectivity density (shortFCD) and long-range functional connectivity density (longFCD) in patients with EP remains elusive. The aim of the present study was to compare the functional connectivity density (FCD) between patients with EP and healthy controls (HCs) using resting-state functional connectivity.Methods: A total of 40 patients with EP (26 males and 14 females) and 40 HCs (26 males and 14 females) of similar age underwent functional magnetic resonance (MR) examination at the resting state. The shortFCD and longFCD values were compared using the one-sample t-test. The differences between patients with EP and the HCs were evaluated using receiver operating characteristic (ROC) curves.Results: In the patients with EP, significantly reduced shortFCD values were observed in the left posterior lobe of the cerebellum, right inferior parietal lobule, and left anterior lobe of the cerebellum, and significantly reduced longFCD values were observed in both the left and right posterior lobe of the cerebellum. Significantly increased shortFCD values were also observed in both superior frontal gyri (Brodmann area 6), and increased longFCD values were observed in the left inferior temporal gyrus and left superior frontal gyri (Brodmann area 11). Compared with the HCs, less reduction was noted among the shortFCD values of patients with EP in the right posterior lobe of the cerebellum, right supramarginal gyrus, left middle temporal gyrus, bilateral superior frontal gyri, and bilateral caudate nuclei.Conclusion: EP patients shown variation of binarized shortFCD and long FCD in brain areas including premotor cortex, ventral cortical visual system, newest part of the cerebellum, cerebellum control unconscious proprioception, inhibition of involuntary movement, somatosensory association cortex, nucleus involving reward system and ventral cortical visual system which might provide an explanation of brain functional compensation for chronic eye pain and visual impairment in the EP patients.Keywords: eye pain, magnetic resonance imaging, functional connectivity density

Shou-Long Hu,1,2,* Li-Ying Tang,3,* Jian-Wen Fang,2,* Ting Su,3 Qian-Min Ge,2 Qi Lin,2 Biao Li,2 Wen-Qing Shi,2 Qiu-Yu Li,2 Rong-Bin Liang,2 Yi Shao2 1National Center for Children’s Health, MOE Key Laboratory of Major Diseases in Children, Department of Ophthalmology, Beijing Children’s Hospital, Capital Medical University, Beijing 100045, People’s Republic of China; 2Department of Ophthalmology, The First Affiliated Hospital of Nanchang University, Jiangxi Province Clinical Ophthalmology Institute, Nanchang 330006, Jiangxi, People’s Republic of China; 3Department of Ophthalmology, Xiang’an Hospital of Xiamen University; Fujian Provincial Key Laboratory of Ophthalmology and Visual Science; Eye Institute of Xiamen University; Xiamen University School of Medicine, Xiamen 361102, Fujian Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yi Shao Email freebee99@163.comPurpose: To investigate differences in the functional connectivity (FC) of the primary visual cortex between patients with corneal ulcer (CU) and healthy controls (HCs) using resting-state functional magnetic resonance imaging.Patients and Methods: A total of 30 patients with CU and 30 HCs were closely matched in terms of sex, age, and level of education. Two-sample t-test, receiver operating characteristic curve, and Pearson’s correlation coefficient analyses were used to determine the differences in FC between the two groups, the mean FC value of patients with CU and HCs, and the correlation between FC signal values and clinical manifestations in different brain regions of patients.Results: The CU group showed significantly elevated FC in the left and right middle frontal gyri and lower FC with the right cuneus compared with the HC group. In addition, the FC of the right cingulate and left superior frontal gyri also increased in the CU group. The receiver operating characteristic curve revealed high diagnostic value in those brain regions.Conclusion: CU involves aberrant FC of the primary visual cortex in different brain areas, including visual-related and cognitive-related regions. This finding may unveil the underlying neural mechanisms of impaired visual function in CU.Keywords: corneal ulcer, functional magnetic resonance imaging, resting state, spontaneous brain activity, primary visual cortex

Qian-Min Ge,* Yu-Ting Zou,* Wen-Qing Shi, Yu-Qing Zhang, Biao Li, You-Lan Min, Qing Yuan, Yi Shao Department of Ophthalmology, The First Affiliated Hospital of Nanchang University, Jiangxi Province Ocular Disease Clinical Research Center, Nanchang, Jiangxi 330006, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yi ShaoDepartment of Ophthalmology, The First Affiliated Hospital of Nanchang University, No. 17, YongWaiZheng Street, DongHu District, Nanchang, Jiangxi 330006, People’s Republic of ChinaTel/Fax +86 791-88692520Email freebee99@163.comObjective: At present, little is known regarding the specific risk factors of ocular metastasis (OM) in elderly patients with lung cancer. This study aimed to find out the risk factors of ocular metastasis.Methods: A total of 1615 elderly patients with lung cancer were recruited into this retrospective study between April 2001 and July 2016. These patients were divided into two groups, namely OM and non-ocular metastasis (NOM). Student’s t-tests, nonparametric rank sum tests, and Chi-square tests were applied to describe whether there were significant differences between the OM group and NOM group. We compared a range of serum biomarkers between the two groups of patients, including alkaline phosphatase, calcium, hemoglobin, alpha-fetoprotein, carcinoembryonic antigen, CA-125, CA-199, CA-153, CA-724, cytokeratin-19 fragment (CYFRA21-1), TPSA and neuron specific enolase (NSE). We used binary logistic regression analysis to determine the risk factors and receiver operating curve (ROC) analyses to assess the diagnostic value for OM in CRC patients.Results: The incidence of OM in elderly patients with lung cancer was 2.0%. Binary logistic regression indicated that CA-125, CA-153, and total prostate specific antigen (TPSA) were identified as independent risk factors of OM in patients with lung cancer (P< 0.001, P< 0.001, and P=0.003, respectively). The sensitivity and specificity of OM diagnosis were as follows: CA-125, 81.25% and 81.57%; CA-153, 68.75% and 83.78%; and TPSA, 81.25% and 90.03%, respectively.Conclusion: The serum concentrations of CA-125, CA-153, and TPSA have predictive value in the diagnosis of OM in elderly patients with lung cancer.Keywords: elderly people, lung cancer, ocular metastases, risk factors

Yuan-Yuan Wu,* Shui-Feng Wang,* Pei-Wen Zhu, Qing Yuan, Wen-Qing Shi, Qi Lin, Biao Li, You-Lan Min, Qiong Zhou, Yi Shao Department of Ophthalmology, The First Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qiong Zhou; Yi ShaoDepartment of Ophthalmology, The First Affiliated Hospital of Nanchang University, 17 Yongwaizheng Street, Donghu, Nanchang, Jiangxi 330006, People’s Republic of ChinaEmail 1357483244@qq.com; freebee99@163.comPurpose: The purpose was to investigate the differences in spontaneous functional connectivity (FC) of the primary visual cortex (V1) between patients with neovascular glaucoma (NVG) and healthy controls (HCs) using resting-state functional magnetic resonance imaging data.Methods: A total of 18 patients with NVG (nine males and nine females) and 18 HCs with similar age and sex background were enrolled in the study and inspected using resting-state functional magnetic resonance imaging. The differences in FC of the V1 between the two groups were compared using the independent samples t-test. We used the receiver operating characteristic (ROC) curve to compare the average FC values of NVG subjects with those of HCs.Results: FC in the left V1 and right fusiform gyrus, bilateral cuneus, and left precuneus was significantly decreased in the NVG group compared with that reported in the HC group. Meanwhile, patients with NVG presented increased FC between the right V1 and bilateral middle frontal gyrus. However, they also exhibited declining FC between the right V1 and left precuneus, and bilateral cuneus. The ROC curve analysis of each brain region indicated that the accuracy of the area under the ROC curves regarding NVG was excellent.Conclusion: NVG involves aberrant FC in the V1 in different brain areas, including the visual-related and cognitive-related regions. These findings may assist in unveiling the underlying neural mechanisms of impaired visual function in NVG.Keywords: neovascular glaucoma, functional connectivity, spontaneous brain activity, primary visual cortex

Pei-Wen Zhu,* Ying-Xin Gong,* You-Lan Min, Qi Lin, Biao Li, Wen-Qing Shi, Qing Yuan, Lei Ye, Yi ShaoDepartment of Ophthalmology, The First Affiliated Hospital of Nanchang University, Jiangxi Province Ocular Disease Clinical Research Center, Nanchang 330006, Jiangxi, People’s Republic of China*These authors have contributed equally to this workPurpose: Colorectal cancer (CRC) is a common tumor of the digestive tract that tends to metastasize and leads to high mortality. Ocular metastases (OM) from colorectal cancer are being increasingly diagnosed, and they can lead to a poor prognosis. Serum lipids are a known risk factor for cardiovascular disease, and are also relevant to the occurrence of CRC. In this study, we examined the levels of serum lipids and tried to determine whether there were correlations with the occurrence of OM in patients with colorectal cancer, in order to determine whether serum lipid levels may be a risk factor for OM in this patient population.Patients and methods: Records from a total of 703 patients treated for colorectal cancer from August 2005 to August 2017 were involved in this study. Student’s t-tests, nonparametric rank sum tests, and Chi-square tests were applied to describe whether there were significant differences between the OM group and non-ocular metastases (NOM) group. We used binary logistic regression analysis to determine the risk factors and receiver operating curve (ROC) analyses to assess the diagnostic value for OM in CRC patients.Results: There were no significant differences in gender, age, histopathology type, or tumor classifications between the OM and NOM groups. The levels of serum TC, HDL, and LDL were significantly different between patients with and without lymph node metastases as well as male and female patients. The OM group had higher serum HDL levels compared to the NOM group. Binary logistic regression indicated that HDL was a risk factor for OM in colorectal cancer patients. The ROC curves showed that the AUC of HDL was 0.660. The cutoff value of HDL was 1.27 mmol/L, with a sensitivity of 0.619 and a specificity of 0.650. Conclusion: HDL levels are correlated with ocular metastases in colorectal cancer patients. Keywords: high-density lipoprotein, ocular metastases, colorectal cancer, independent risk factor

Jia-Xiang Liu, Qing Yuan, You-Lan Min, Ying He, Qian-Hui Xu, Biao Li, Wen-Qing Shi, Qi Lin, Qing-Hai Li, Pei-Wen Zhu, Yi ShaoDepartment of Ophthalmology, The First Affiliated Hospital of Nanchang University, Jiangxi Province Clinical Ophthalmology Institute, Nanchang, Jiangxi 330006, People’s Republic of ChinaObjective: Breast cancer is the most common primary lesion resulting in intraocular metastasis (IOM). In this study, we investigated the differences between breast cancer patients with and without IOM, and clarified the risk factors for IOM in patients with breast cancer.Methods: A total of 2,381 patients with breast cancer were included in this study from January 2005 to December 2017. The chi-square test and Student’s t-test were applied to evaluate differences between the IOM and non-IOM (NIOM) groups. Risk factors were calculated using binary logistic regression analysis. Receiver operating curve (ROC) analysis was used to assess the diagnostic value of IOM in patients with breast cancer.Results: The IOM incidence in patients with breast cancer was 1.35%. No significant differences were detected in age, gender, menopausal status, or histopathology between the IOM and NIOM groups. The IOM group had more axillary lymph node metastases, lower ApoA1 and higher ApoB, compared with the NIOM group. Binary logistic regression indicated that ApoA1 and ApoB were risk factors for IOM in breast cancer patients (P-values and P-values=0.005, respectively). ROC curve analysis revealed area under the curve values for ApoA1 and ApoB of 0.871 and 0.633, using cutoff values of 1.165 and 0.835 g/L, respectively. The sensitivity and specificity values for ApoA1 were 0.813 and 0.849, respectively, while those for ApoB were 0.813 and 0.481.Conclusion: Our data indicate that ApoA1 and ApoB are risk factors for IOM in patients with breast cancer and that ApoA1 is more reliable than ApoB at distinguishing IOM from NIOM in patients with breast cancer.Keywords: breast cancer, intraocular metastases, apolipoprotein A1, apolipoprotein B

Jun Yang,1 Bin Li,2 Qiu-Yue Yu,2 Lei Ye,3 Pei-Wen Zhu,3 Wen-Qing Shi,3 Qing Yuan,3 You-Lan Min,3 Yu-Lin He,2 Yi Shao3 1Department of Prosthodontics, The Affiliated Stomatological Hospital of Nanchang University, Nanchang, China; 2Department of Radiology, The First Affiliated Hospital of Nanchang University, Nanchang, China; 3Department of Ophthalmology, The First Affiliated Hospital of Nanchang University, Nanchang, China Background: The results of previous studies have indicated that pain-associated diseases can result in marked functional and anatomical alterations in the brain. However, differences in spontaneous brain activity occurring in toothache (TA) patients remain unclear.Objective: This study investigated intrinsic brain activity changes in TA subjects using the amplitude of low-frequency fluctuation (ALFF) technique.Methods: A total of 18 patients with TA (eight males, and 10 females) and 18 healthy controls (HCs) who were matched for gender, age, and educational status were enrolled. Resting-state functional MRI was used to examine the participants. Spontaneous cerebral activity variations were investigated using the ALFF technique. The mean ALFF values of the TA patients and the HCs were classified using receiver operating characteristic (ROC) curves. The correlations between ALFF signals of distinct regions of the cerebrum and the clinical manifestations of the TA patients were evaluated using Pearson’s correlation analysis.Results: Compared with HCs, TA patients showed notably higher ALFF in the left postcentral gyrus, right paracentral lobule, right lingual gyrus, right inferior occipital gyrus, left fusiform gyrus, and right superior occipital gyrus. ROC curve analysis of each brain region showed that the accuracy area under the curve was excellent. In the TA group, the visual analog scale of the left side was positively correlated with the ALFF signal values of the right paracentral lobule (r=0.639, P=0.025).Conclusion: Multiple brain regions, including pain- and vision-related areas, exhibited aberrant intrinsic brain activity patterns, which may help to explain the underlying neural mechanisms in TA. Keywords: toothache, functional MRI, ALFF, intrinsic brain activity, pain, resting-state

You-Lan Min,1,* Ting Su,2,* Yong-Qiang Shu,3 Wen-Feng Liu,1 Ling-Long Chen,3 Wen-Qing Shi,1 Nan Jiang,2 Pei-Wen Zhu,1 Qing Yuan,1 Xiao-Wei Xu,1 Lei Ye,1 Yi Shao1 1Department of Ophthalmology, The First Affiliated Hospital of Nanchang University, Jiangxi Province Clinical Ophthalmology Institute, Nanchang 330006 Jiangxi, China; 2Eye Institute of Xiamen University, Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, Xiamen 361102, Fujian, China; 3Department of Radiology, The First Affiliated Hospital of Nanchang University, Nanchang 330006 Jiangxi, China *These authors contributed equally to this work Objective: Previous studies have demonstrated that strabismus or amblyopia can result in markedly brain function and anatomical alterations. However, the differences in spontaneous brain activities of strabismus with amblyopia (SA) patients still remain unclear. This current study intended to use the amplitude of low-frequency fluctuation (ALFF) technique to investigate the intrinsic brain activity changes in SA subjects. Patients and methods: A total of 16 patients with SA (6 males and 10 females) and 16 healthy controls (HCs; 6 males and 10 females) similarly matched in age, gender, and education status were recruited and examined with the resting-state functional MRI. The spontaneous brain activity changes were investigated using the ALFF technique. The receiver operating characteristic curve was performed to classify the mean ALFF signal values of the SA patients from HCs. The correlations between the ALFF values of distinct brain regions and the clinical manifestations in SA patients were evaluated in terms of the Pearson’s correlation analysis. Results: Compared with HCs, SA patients had significantly decreased ALFF in the left cerebellum posterior lobe, left middle frontal gyrus, and bilateral thalamus. In contrast, SA patients showed increased ALFF values in the right superior frontal gyrus, right precuneus, left cuneus, and bilateral precentral gyrus. Nonetheless, there was no linear correlation between the mean ALFF values in brain regions and clinical features. Conclusion: Diverse brain regions including vision-related and motion-related areas exhibited aberrant intrinsic brain activity patterns, which imply the neuropathologic mechanisms of oculomotor disorder and vision deficit in the SA patients. Keywords: strabismus, amblyopia, functional MRI, ALFF, spontaneous brain activity

Tailoring the surface ligands of metal nanoclusters is important for engineering unique configurations of metal nanoclusters. Thiacalix[4]arene has found extensive applications in the construction of metal nanoclusters. In this investigation, we present the synthesis and characterization of the first all-calixarene-protected silver nanoclusters, [Ag(CH 3 CN) 4 ] 2 [Ag 44 (BTCA) 6 ] ( Ag 44 , H 4 BTCA = p-tert -butylthiacalix[4]arene). Single-crystal X-ray structural analysis reveals that all silver atoms are in a face-centered cubic ( fcc ) arrangement. The formation of such an fcc structure is attributed to the selectively passivation on {100} facets by BTCA 4- . Thiacalixarene substantially facilitates the stability of Ag 44 due to its multiple coordination sites and bulkiness. Mass spectrometry and theoretical calculations reveal that Ag 44 is a superatomic silver nanocluster with 22 free electrons in the following configuration: 1S 2 1P 6 1D 6 1F 2 2S 2 1D 4 . This work not only elucidates the impact of macrocyclic ligands on the stabilization of silver clusters but also furnishes an approach for assembling atomically precise fcc nanoclusters.

Background: Currently, there are no optimal biomarkers available for distinguishing patients who will respond to immune checkpoint inhibitors (ICIs) therapies. Consequently, the exploration of novel biomarkers that can predict responsiveness to ICIs is crucial in the field of immunotherapy., Methods: We estimated the proportions of 22 immune cell components in 10 cancer types (6,128 tumors) using the CIBERSORT algorithm, and further classified patients based on their tumor immune cell proportions in a pan-cancer setting using k-means clustering. Differentially expressed immune genes between the patient subgroups were identified, and potential predictive biomarkers for ICIs were explored. Finally, the predictive value of the identified biomarkers was verified in patients with urothelial carcinoma (UC) and esophageal squamous cell carcinoma (ESCC) who received ICIs., Results: Our study identified two subgroups of patients with distinct immune infiltrating phenotypes and differing clinical outcomes. The patient subgroup with improved outcomes displayed tumors enriched with genes related to immune response regulation and pathway activation. Furthermore, CCL5 and CSF2 were identified as immune-related hub-genes and were found to be prognostic in a pan-cancer setting. Importantly, UC and ESCC patients with high expression of CCL5 and low expression of CSF2 responded better to ICIs., Conclusion: We demonstrated CCL5 and CSF2 as potential novel biomarkers for predicting the response to ICIs in patients with UC and ESCC. The predictive value of these biomarkers in other cancer types warrants further evaluation in future studies., (© 2024. The Author(s).)

Ipomoeassin F (Ipom-F) is a natural compound with embedded carbohydrates that exhibits a potent cytotoxic effect on triple-negative breast cancer (TNBC) cells. The mechanism behind this selective potency remains unclear. To elucidate this mechanism, we analyzed the proteome profiles of the TNBC MDA-MB-231 cells after exposure to Ipom-F at different time points and increasing doses using a quantitative proteomic method. Our proteomic data demonstrate that the major effect of Ipom-F on MDA-MB-231 cells is the inhibition of membrane and secreted protein expression. Our proteomic data are consistent with the recently uncovered molecular mechanism of action of Ipom-F, which binds to Sec61-α and inhibits the co-translational import of proteins into the endoplasmic reticulum. We have defined a subset of membrane and secreted proteins particularly sensitive to Ipom-F. Analysis of the expression of these Ipom-F-sensitive proteins in cancer cell lines and breast cancer tissues demonstrates that some of these proteins are upregulated in TNBC cells. Thus, it is likely that TNBC cells may have adapted to the elevated levels of some proteins identified as sensitive to Ipom-F in this study; inhibition of the expression of these proteins leads to a crisis in proliferation and/or survival for the cells.

It is challenging to attain strong near-infrared (NIR) emissive gold nanoclusters. Here we show a rod-shaped cluster with the composition of [Au 28 (p-MBT) 14 (Hdppa) 3 ](SO 3 CF 3 ) 2 (1 for short, Hdppa is N,N-bis(diphenylphosphino)amine, p-MBT is 4-methylbenzenethiolate) has been synthesized. Single crystal X-ray structural analysis reveals that it has a rod-like face-centered cubic (fcc) Au 22 kernel built from two interpenetrating bicapped cuboctahedral Au 15 units. 1 features NIR luminescence with an emission maximum at 920 nm, and the photoluminescence quantum yield (PLQY) is 12%, which is 30-fold of [Au 21 (m-MBT) 12 (Hdppa) 2 ]SO 3 CF 3 (2, m-MBT is 3-methylbenzenethiolate) with a similar composition and 60-fold of Au 30 S(S‑t‑Bu) 18 with a similar structure. time-dependent DFT(TDDFT)calculations reveal that the luminescence of 1 is associated with the Au 22 kernel. The small Stokes shift of 1 indicates that it has a very small excited state structural distortion, leading to high radiative decay rate (k r ) probability. The emission of cluster 1 is a mixture of phosphorescence and thermally activated delayed fluorescence(TADF), and the enhancement of the NIR emission is mainly due to the promotion of k r rather than the inhibition of k nr . This work demonstrates that the metal kernel and the surface structure are both very important for cluster-based NIR luminescence materials., (© 2024. The Author(s).)

Toxoplasma gondii is a widespread protozoan parasite approximately infecting one-third of the world population and can cause serious public health problems. In this study, we investigated the protective effect of the attenuated vaccine Pru:Δcdpk2 against acute toxoplasmosis and explored the underlying immune mechanisms of the protection in pigs. The systemic T-cell and natural killer (NK) cell responses were analyzed, including kinetics, phenotype, and multifunctionality (interferon [IFN]-γ, tumor necrosis factor [TNF]-α), and the IFN-γ levels were analyzed in PBMCs. Our results showed that T. gondii -specific antibodies were induced by Pru:Δcdpk2. After challenging with RH, the antibodies were able to respond quickly in the immunized group, and the expression level was significantly higher than that in the unimmunized group. The expression level of IFN-γ significantly increased after vaccination, and the CD3+ γδ-, NK, and CD3+ γδ+ cell subsets also significantly increased. At the same time, functional analysis indicated that these cells were polarized toward a Th1 phenotype, showing the ability to secrete IFN-γ and TNF-α. The CD4+CD8α-T cell population exhibited a higher frequency of IFN-γ+ producing cells compared with the CD4-CD8α+ and CD4+CD8α+ cell populations during the early days of vaccination. Our results indicated that the attenuated vaccine could induce the expression of NK, γδ, and CD3αβ cells in pigs, and IFN-γ and TNF-α secreted by these cells are important for resistance to T. gondii infection.

Excellent "CHON" compatible ligands based on a heterocyclic skeleton for the separation of trivalent actinides [An(III)] from lanthanides [Ln(III)] have been widely explored, the aim being spent nuclear fuel reprocessing. The combination mode of a soft/hard (N/O) donor upon the coordination chemistry of An(III) and Ln(III) should play a vital role with respect to the performance of ligands. As such, in this work, two typical experimentally available phenanthroline-derived tetradentate ligands, CyMe 4 -BTPhen ( L 1 ) and Et-Tol-DAPhen ( L 4 ), and two theoretically designed asymmetric tetradentate heterocyclic ligands, L 2 and L 3 , with various N/O donors were investigated using scalar relativistic density functional theory. We have evaluated the electronic structures of L 1 - L 4 and their coordination modes, bonding properties, and extraction reactions with Am(III) and Eu(III). We found that the Am/Eu-N interactions play a more important role in the orbital interactions between the ligand and Am(III)/Eu(III) ions. Compared with those of L 1 , the coordinated O atoms of L 2 and L 4 weaken the metal-N bonds. The Am(III)/Eu(III) selectivity follows the order L 1 > L 2 > L 4 based on the change in Gibbs free energy, reflecting the fact that the Am(III)/Eu(III) selectivity of the ligand is affected by the number of coordinated N atoms. In addition, L 3 displays the strongest binding ability for Am(III)/Eu(III) ions and the smallest Am(III)/Eu(III) selectivity among the four ligands, due to its structural preorganization. This work clarifies the influence of the number of coordinated N and O atoms of ligands on Am(III)/Eu(III) selectivity, which provides valuable fundamental information for the design of efficient ligands with N and O donors for An(III)/Ln(III) separation.

Fascin actin-bundling protein 1 (Fascin) is highly expressed in a variety of cancers, including esophageal squamous cell carcinoma (ESCC), working as an important oncogenic protein and promoting the migration and invasion of cancer cells by bundling F-actin to facilitate the formation of filopodia and invadopodia. However, it is not clear how exactly the function of Fascin is regulated by acetylation in cancer cells. Here, in ESCC cells, the histone acetyltransferase KAT8 catalyzed Fascin lysine 41 (K41) acetylation, to inhibit Fascin-mediated F-actin bundling and the formation of filopodia and invadopodia. Furthermore, NAD-dependent protein deacetylase sirtuin (SIRT) 7-mediated deacetylation of Fascin-K41 enhances the formation of filopodia and invadopodia, which promotes the migration and invasion of ESCC cells. Clinically, the analysis of cancer and adjacent tissue samples from patients with ESCC showed that Fascin-K41 acetylation was lower in the cancer tissue of patients with lymph node metastasis than in that of patients without lymph node metastasis, and low levels of Fascin-K41 acetylation were associated with a poorer prognosis in patients with ESCC. Importantly, K41 acetylation significantly blocked NP-G2-044, one of the Fascin inhibitors currently being clinically evaluated, suggesting that NP-G2-044 may be more suitable for patients with low levels of Fascin-K41 acetylation, but not suitable for patients with high levels of Fascin-K41 acetylation. © 2024 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd., (© 2024 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.)

Objective: To evaluate the efficacy of Guanxin Danshen Dripping Pill (GXDSDP) in treating anxiety and depression in patients with coronary heart disease (CHD)., Methods: A total of 1,428 patients diagnosed with CHD screened for anxiety, depression, and quality of life (QOL) at baseline received 0.4 g of GXDSDP treatment 3 times per day and returned for monthly reassessment. Patients were recruited after stable treatment for CHD and received assessment of General Anxiety Disorder-7 (GAD-7), Patient Health Questionnaire-9 (PHQ-9), and Seattle Angina Questionnaire (SAQ) for evaluating anxiety, depression, and QOL. Patients were followed up 3 times, once every 4 weeks, during outpatient visits for 12 weeks., Results: At the third follow-up (F3), the anxiety symptom of 63.79% (673/1,055) of the patients improved to sub-clinical level, and the GAD-7 score improved significantly (8.11 vs. 3.87, P<0.01); 57.52% (585/1,017) patients' depressive symptoms improved to sub-clinical level, with a significant improvement in PHQ-9 score (8.69 vs. 4.41, P<0.01) at F3. All aspects of QOL significantly improved at the end of treatment compared to those at baseline (all P<0.01) as assessed by SAQ: physical limitation (31.17 vs. 34.14), anginal stability (2.74 vs. 4.14), anginal frequency (8.16 vs. 9.10), treatment satisfaction (13.43 vs. 16.29), and disease perception (8.69 vs. 11.02)., Conclusions: A fixed dosage of GXDSDP may be a potential treatment option for CHD patients comorbid with anxiety or depression. (Registration No. ChiCTR2100051523)., (© 2023. The Chinese Journal of Integrated Traditional and Western Medicine Press and Springer-Verlag GmbH Germany, part of Springer Nature.)

Separation of lanthanide (Ln) and minor actinide (MA) elements and mutual separation between minor actinide elements ( e.g. Am(III) and Cm(III)) represent a crucial undertaking. However, separating these elements poses a significant challenge owing to their highly similar physicochemical properties. Asymmetric N-heterocyclic ligands such as N -ethyl-6-(1 H -pyrazol-3-yl)- N -( p -tolyl)picolinamide (Et- p -Tol-A-PzPy) and N -ethyl- N -( p -tolyl)-1,10-phenanthroline-2-carboxamide (ETPhenAm) have recently received considerable attention in the separation of MAs over Ln from acid solutions. By changing the central skeleton structures of these ligands and introducing substituents with different properties on the side chains, their complexation behavior with Am(III), Cm(III), and Eu(III) may be affected. In this work, we explore four different asymmetric N-containing heterocyclic ligands, namely Et- p -Tol-A-PzPy (L 1 ), N -ethyl-6'-(1 H -pyrazol-3-yl)- N -( p -tolyl)-[2,2'-bipyridine]-6-carboxamide (L 2 ), N -ethyl-9-(1 H -pyrazol-3-yl)- N -( p -tolyl)-1,10-phenanthroline-2-carboxamide (L 3 ), and ETPhenAm (L 4 ) using density functional theory (DFT). The calculated results demonstrate the potential of ligands L 1 -L 4 for the extraction and separation of Am(III), Cm(III), and Eu(III). Ligand analysis shows that ligand L 3 binds more easily to the central metal atom, in line with the stronger extraction capacity of L 3 . In spite of the higher covalence between the side chain and the central metal atom for complexes with L 1 -L 3 , the main chain seems to control the stability of the extraction complexes. The preorganized 1,10-phenanthroline backbone also further enhances the extraction performance of L 3 and L 4 . The difference in coordination ability between the side chain donors of these ligands and metal ions may affect their separation efficiency. This work presents theoretical insights into synthesizing novel ligands for separating trivalent actinides by adjusting N-heterocyclic ligands.

The attributes of good solubility and the redox-neutral nature of molten salt fluxes enable them to be useful for the synthesis of novel crystalline actinide compounds. In this work, a flux growth method under an inert atmosphere is proposed to explore the valence diversity of uranium, and a series of five uranium silicate structures, [K 3 Cl][(U VI O 2 )(Si 4 O 10 )] ( 1 ), Cs 3 [(U V O 2 )(Si 4 O 10 )] ( 2 ), K 2 [U IV (Si 2 O 7 )] ( 3 ), K 8 [(U VI O 2 )(U V O 2 ) 2 (Si 8 O 22 )] ( 4 ), and Cs 6 [U IV (U V O) 2 (Si 12 O 32 )] ( 5 ), were synthesized using different metal halide salt and feeding U/Si ratios. Crystal structure analysis reveals that the utilization of argon atmosphere that helps to avoid possible oxidation of low-valence uranium generates a variety of oxidation states of uranium including U(VI), U(V), U(IV), mixed-valence U(V) and U(VI), and mixed-valence U(IV) and U(V). Characterization of physicochemical properties of representative compounds shows that all these uranium silicate compounds have bandgaps among the range of 2.0-3.4 eV, and mixed-valence uranium silicate compounds have relatively narrower bandgaps. Density functional theory calculations on formation enthalpies, lattice energies, and bandgaps of all five compounds were also performed to provide more structural information about these uranium silicates. This work enriches the library of variable-valence uranium silicate compounds and provides a feasible way to produce novel actinide compounds with intriguing properties through the flux growth method that might show potential application in relevant fields such as storage media for nuclear waste.

Dilanthanide complexes with one-electron delocalization are important targets for understanding the specific 4f/5d-bonding feature in lanthanide chemistry. Here, we report an isolable azide-bridged dicerium complex 3 [{(Trapen TMS )Ce} 2 (μ-N 3 )] • [Trapen = tris (2-aminobenzyl)amine; TMS = SiMe 3 ], which is synthesized by the reaction of tripodal ligand-supported (Trapen TMS )Ce IV Cl complex 2 with NaN 3 . The structure and bonding nature of 3 are fully characterized by X-ray crystal diffraction analysis, electron paramagnetic resonance (EPR), magnetic measurement, cyclic voltammetry, X-ray absorption spectroscopy, and quantum-theoretical studies. Complex 3 presents a trans-bent central Ce-N 3 -Ce unit with a single electron of two mixed-valent Ce atoms. The unique low-temperature (2 K) anisotropic EPR signals [ g = 1.135, 2.003, and 3.034] of 3 indicate that its spin density is distributed on the central Ce-N 3 -Ce unit with marked electron delocalization. Quantum chemical analyses show strong 4f/5d orbital mixing in the singly occupied molecular orbital of 3 , which allows for the unpaired electron to extend throughout the cerium-azide-cerium unit via a multicentered one-electron (Ce-N 3 -Ce) interaction. This work extends the family of mixed-valent dilanthanide complexes and provides a paradigm for understanding the bonding motif of ligand-bridged dilanthanide complexes.

The role of extracellular matrix (ECM) remodeling in the axial elongation associated with myopia has not been fully elucidated, although it is considered a significant factor. EFEMP1, a regulator of ECM, has been associated with various pathological conditions. This study aimed to examine the involvement of EFEMP1 in scleral remodeling during form deprivation myopia. The results indicate a progressive increase in EFEMP1 expression following prolonged form deprivation treatment, followed by a subsequent decrease upon recovery. To gain a deeper understanding of the mechanism of EFEMP1, we conducted transcriptome sequencing on primary scleral fibroblasts that were subjected to lentivirus-mediated overexpression of EFEMP1. Validation was performed using lentivirus-induced overexpression and shRNA targeting EFEMP1 in combination with LY294002, a PI3K inhibitor. Our findings suggest that EFEMP1 may be involved in the development of FDM by regulating the expression of the PI3K/AKT/MMP2 axis. The AAV-mediated injection of shEFEMP1 under Tenon's capsule in guinea pigs was observed to effectively delay the progression of myopia and posterior scleral remodeling. In contrast, the AAV-mediated overexpression of EFEMP1 exacerbated the development of myopia and resulted in further thinning of collagen fibers in the posterior sclera. In summary, adjusting EFEMP1 concentrations could potentially serve as a viable approach to prevent and treat myopia by influencing the remodeling process of the posterior sclera., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

During the PUREX process, the separation between U(VI) and Pu(IV) is achieved by reducing Pu(IV) to Pu(III), which is complicated and energy-consuming. To address this issue, we report here the first case of separation of U(VI) from Pu(IV) by o -phenanthroline diamide ligands under high acidity. Two new o -phenanthroline diamide ligands (1,10-phenanthroline-2,9-diyl)bis(indolin-1-ylmethanone) (L1) and (1,10-phenanthroline-2,9-diyl)bis((2-methylindolin-1-yl)methanone) (L2) were synthesized, which can effectively separate U(VI) from Pu(IV) even at 4 mol/L HNO 3 . The highest separation factor of U(VI) and Pu(IV) can reach over 1000, setting a new record for the separation of U(VI) from Pu(IV) under high acidity. Furthermore, extracted U(VI) can be easily recovered with water or dilute nitric acid, and the extraction performance remains stable even after 150 kGy gamma irradiation, which provides solid experimental support for potential engineering applications. The results of UV-vis titration and single-crystal X-ray diffraction measurements show that the 1:1 complex formed by L1 with U(VI) is more stable than all of the previously reported phenanthroline ligands, which reasonably reveals that the ligand L1 designed in this work has excellent affinity for U(VI). The findings of this work promise to contribute to the facilitation of the PUREX process by avoiding the use of reducing agents. It also provides new clues for designing ligands to achieve efficient separation between U(VI) and Pu(IV) at high acidity.

Increasing storage root number is a pivotal approach to enhance both storage root (SR) yield and appearance quality of sweet potato. Here, 2-year field experiments were conducted to investigate the effect of 0 (K0), 120 (K1), 240 (K2), and 360 (K3) kg ha -1 potassium fertilizer (K 2 O) on lignin metabolism, root growth, storage root yield, and uniformity. The results demonstrated that potassium (K) application led to a decrease in the activities of key enzymes involved in lignin biosynthesis, including phenylalanine deaminase (PAL), 4-coumarate coenzyme A ligase (4-CL), cinnamic acid dehydrogenase (CAD), polyphenol oxidase (PPO), and peroxidase (POD). This resulted in a significant reduction in lignin and G-type lignin contents in potential SRs compared to K0 treatment within 10-30 days after planting (DAP). BJ553 exhibited a significant decrease in PAL activity, as well as lignin and G-type contents at 10 DAP, whereas YS25 showed delayed effects until 20 DAP. However, the number and distribution of secondary xylem conduits as well as the mid-column diameter area in roots were increased in K2 treatment. Interestingly, K2 treatment exhibited significantly larger potential SR diameter than other treatments at 15, 20, and 25 DAP. At harvest, K2 treatment increased the SR number, the single SR weight, and overall yield greatly compared with K0 treatment, with an average increase of 19.12%, 16.54%, and 16.92% respectively. The increase of SR number in BJ553 was higher than that of YS25. Furthermore, K2 treatment exhibited the lowest coefficient of variation for both SR length and diameter, indicating a higher yield of middle-sized SRs. In general, appropriate potassium application could effectively suppress lignin biosynthesis, leading to a reduction in the degree of pericycle lignification in potential SRs. This promotes an increase in the number of storage roots and ultimately enhances both yield and appearance quality of sweet potato. The effect of potassium fertilizer on lignin metabolism in BJ553 roots was earlier and resulted in a greater increase in the SR number compared to YS25., 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 Liu, Xv, Si, Shi, Ding, Tang, Xv, Shi and Liu.)

Metal nanoclusters have emerged as promising near-infrared (NIR)-emissive materials, but their room-temperature photoluminescence quantum yield (PLQY), especially in solution, is often low (<10%). We studied the photophysics of Au 22 ( t BuPhC≡C) 18 (Au 22 ) and its alloy counterpart Au 16 Cu 6 ( t BuPhC≡C) 18 (Au 16 Cu 6 ) (where t Bu is tert -butyl and Ph is phenyl) and found that copper (Cu) doping suppressed the nonradiative decay (~60-fold less) and promoted intersystem crossing rate (~300-fold higher). The Au 16 Cu 6 nanocluster exhibited >99% PLQY in deaerated solution at room temperature with an emission maximum at 720 nanometers tailing to 950 nanometers and 61% PLQY in the oxygen-saturated solution. The approach to achieve near-unity PLQY could enable the development of highly emissive metal cluster materials.

Adding hydrophilic ligands into aqueous solutions for the selective binding of actinides(III) is acknowledged as an advanced strategy in Ln(III)/An(III) separation. In view of the recycling and radioactive waste disposal of the minor actinide, there remains an urgent need to design and develop the appropriate ligand for selective separation of An(III) from Ln(III). Herein, four novel hydrophilic ligands with hard-soft hybrid donors, derived from the pyridine and phenanthroline skeletons, were designed and synthesized as masking agents for selective complexation of An(III) in the aqueous phase. The known N , N , N ', N '-tetraoctyl diglycolamide (TODGA) was used as lipophilic extractant in the organic phase for extraction of Ln(III), and a new strategy for the competitive extraction of An(III) and Ln(III) was developed based on TODGA and the above hydrophilic ligands. The optimal hydrophilic ligand of N , N '-bis(2-hydroxyethyl)-2,9-dicarboxamide-1,10-phenanthroline (2OH-DAPhen) displayed exceptional selectivity toward Am(III) over Ln(III), with the concentrations of HNO 3 ranging from 0.05 to 3.0 M. The maximum separation factors were up to 1365 for Eu/Am, 417.66 for Eu/Cm, and 42.38 for La/Am. The coordination mode and bonding property of 2OH-DAPhen with Ln(III) were investigated by 1 H NMR titration, UV-vis spectrophotometric titration, luminescence titration, FT-IR, ESI-HRMS analysis, and DFT calculations. The results revealed that the predominant species formed in the aqueous phase was a 1:1 ligand/metal complex. DFT calculations also confirmed that the affinity of 2OH-DAPhen for Am(III) was better than that for Eu(III). The present work using a competitive extraction strategy developed a feasible alternative method for the selective separation of trivalent actinides from lanthanides.

Electrospray Ionization Mass Spectrometry (ESI-MS) technique and density functional theory (DFT) calculations were combined to study the formation of the complexes of lanthanides (Ln = La, Ce, Nd, Sm, Eu, Yb) and actinides (UO 2 2+ , Th 4+ ) with CyMe 4 -BTBP (6,6'-bis(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-benzo-[1,2,4-]triazin-3-yl)-[2,2']bipyridine) to understand the mechanisms during the extraction process. Mass spectrometry titrations showed the formation of the complexation in acetonitrile. For lanthanides, only 1:2 complexes ([Ln(L) 2 ] 3+ , [Ln(L) 2 (CH 3 CN)] 3+ ), [Ln(L) 2 (NO 3 )] 2+ ) were found at low [Ln]/[L] concentration ratios, whereas the 1:1 complexes ([Ln(L)(NO 3 ) 2 ] + ) were observed when the [Ln]/[L] concentration ratio reached 1.0. For uranyl complexes, 1:1 complex ([UO 2 L(NO 3 )] + ) was the only species within the measuring range. Th 4+ complexes had two compositions: 1:1 and 1:2, in which 1:2 species was the dominant complex. Collision-induced dissociation (CID) was employed to characterize the fragmentation process. The fragmentation process was unfolded sequentially on both sides of CyMe 4 -BTBP ligand with the loss of alkyl groups and cleavage of triazinyl rings. The CID results of CyMe 4 -BTBP complexes revealed a slight difference depending on the metal center. The DFT calculations showed that the stable complexes formed in acetonitrile solution were consistent with the ESI-MS results., (© 2023 John Wiley & Sons Ltd.)

Objective: To evaluate the effect of hydroxychloroquine on conjunctival and retinal microvascular density in rheumatoid arthritis (RA) patients., Methods: Ten healthy controls, 10 RA patients who had not been treated with hydroxychloroquine, and 10 RA patients who had been treated with chloroquine for more than 5 years were recruited. Optical coherence tomography (OCTA) was used to examine the conjunctival and superficial and deep retinal microvascular density and compared the differences in microvascular density between the three groups., Results: The vascular density in RA group in superficial microvascular was significantly lower than that in control group (p < 0.001). Compared with RA group, the chloroquine group showed statistically significantly lower microvascular (p < 0.001) and deep microvascular (p = 0.018). Superficial microvascular was positively correlated with conjunctival vessel density in RA patients (r = 0.868, p = 0.0048)., Conclusions: The use of chloroquine could further reduce the vascular density in the absence of statistical difference in the course of the disease., (© 2023 The Authors. Journal of Biophotonics published by Wiley-VCH GmbH.)

Moisture harvesters with favourable attributes such as easy synthetic availability and good processability as alternatives for atmospheric moisture harvesting (AWH) are desirable. This study reports a novel nonporous anionic coordination polymer (CP) of uranyl squarate with methyl viologen (MV 2+ ) as charge balancing ions (named U-Squ-CP) which displays intriguing sequential water sorption/desorption behavior as the relative humidity (RH) changes gradually. The evaluation of AWH performance of U-Squ-CP shows that it can absorb water vapor under air atmosphere at a low RH of 20 % typical of the levels found in most dry regions of the world, and have good cycling durability, thus demonstrating the capability as a potential moisture harvester for AWH. To the authors' knowledge, this is the first report on non-porous organic ligand bridged CP materials for AWH. Moreover, a stepwise water-filling mechanism for the water sorption/desorption process is deciphered by comprehensive characterizations combining single-crystal diffraction, which provides a reasonable explanation for the special moisture harvesting behaviour of this non-porous crystalline material., (© 2023 Wiley-VCH GmbH.)

Its high coordination number and tendency to cluster make Th 4+ suitable for constructing metal-organic frameworks (MOFs) with novel topologies. In this work, two novel thorium-based heterometallic MOF isomers (IHEP-17 and IHEP-18) were assembled from a Th 6 cluster, a multifunctional organic ligand [4-(1 H -pyrazol-4-yl)benzoic acid (HPyba)], and Cu 2+ /Ni 2+ cations via the one-pot solvothermal synthesis strategy. The framework features a 6,12-connected new topology net and contains two kinds of supramolecular cage structures, Th 36 M 4 and Th 24 M 2 , suitable for guest exchange. Both MOF materials can efficiently adsorb I 2 . X-ray photoelectron spectroscopy, Raman spectroscopy, and single-crystal X-ray diffraction indicate that the adsorbed iodine is uniformly distributed within the Th 36 M 4 cage but not the Th 24 M 2 cage in the form of I 3 - .

The separation of plutonium (Pu) from spent nuclear fuel was achieved by effectively adjusting the oxidation state of Pu from +IV to +III in the plutonium uranium reduction extraction (PUREX) process. Acetaldoxime (CH 3 CHNOH) as a free salt reductant can rapidly reduce Pu(IV), but the reduction mechanism remains indistinct. Herein, we explore the reduction mechanism of two Pu(IV) ions by one CH 3 CHNOH molecule, where the second Pu(IV) reduction is the rate-determining step with the energy barrier of 19.24 kcal mol -1 , which is in line with the experimental activation energy (20.95 ± 2.34 kcal mol -1 ). Additionally, the results of structure and spin density analyses demonstrate that the first and second Pu(IV) reduction is attributed to hydrogen atom transfer and hydroxyl ligand transfer, respectively. Analysis of localized molecular orbitals unveils that the reduction process is accompanied by the breaking of the Pu-O OH bond and the formation of the O OH -H and C-O OH bonds. The reaction energies confirm that the reduction of Pu(IV) by acetaldoxime is both thermodynamically and kinetically accessible. In this work, we elucidate the reduction mechanism of Pu(IV) with CH 3 CHNOH, which provides a theoretical understanding of the rapid reduction of Pu(IV).

The Sec61 complex forms a protein-conducting channel in the endoplasmic reticulum membrane that is required for secretion of soluble proteins and production of many membrane proteins. Several natural and synthetic small molecules specifically inhibit Sec61, generating cellular effects that are useful for therapeutic purposes, but their inhibitory mechanisms remain unclear. Here we present near-atomic-resolution structures of human Sec61 inhibited by a comprehensive panel of structurally distinct small molecules-cotransin, decatransin, apratoxin, ipomoeassin, mycolactone, cyclotriazadisulfonamide and eeyarestatin. All inhibitors bind to a common lipid-exposed pocket formed by the partially open lateral gate and plug domain of Sec61. Mutations conferring resistance to the inhibitors are clustered at this binding pocket. The structures indicate that Sec61 inhibitors stabilize the plug domain in a closed state, thereby preventing the protein-translocation pore from opening. Our study provides the atomic details of Sec61-inhibitor interactions and the structural framework for further pharmacological studies and drug design., (© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Theileria , a tick-borne intracellular protozoan, can cause infections of various livestock and wildlife around the world, posing a threat to veterinary health. Although more and more Theileria species have been identified, genomes have been available only from four Theileria species to date. Here, we assembled a whole genome of Theileria luwenshuni , an emerging Theileria , through next-generation sequencing of purified erythrocytes from the blood of a naturally infected goat. We designated it T. luwenshuni str. Cheeloo because its genome was assembled by the researchers at Cheeloo College of Medicine, Shandong University, China. The genome of T. lunwenshuni str. Cheeloo was the smallest in comparison with the other four Theileria species. T. luwenshuni str. Cheeloo possessed the fewest gene gains and gene family expansion. The protein count of each category was always comparable between T. luwenshuni str. Cheeloo and T. orientalis str. Shintoku in the Eukaryote Orthologs annotation, though there were remarkable differences in genome size. T. luwenshuni str. Cheeloo had lower counts than the other four Theileria species in most categories at level 3 of Gene Ontology annotation. Kyoto Encyclopedia of Genes and Genomes annotation revealed a loss of the c-Myb in T. luwenshuni str. Cheeloo. The infection rate of T. luwenshuni str. Cheeloo was up to 81.5% in a total of 54 goats from three flocks. The phylogenetic analyses based on both 18S rRNA and cox1 genes indicated that T. luwenshuni had relatively low diversity. The first characterization of the T. luwenshuni genome will promote better understanding of the emerging Theileria . IMPORTANCE Theileria has led to substantial economic losses in animal husbandry. Whole-genome sequencing data of the genus Theileria are currently limited, which has prohibited us from further understanding their molecular features. This work depicted whole-genome sequences of T. luwenshuni str. Cheeloo, an emerging Theileria species, and reported a high prevalence of T. luwenshuni str. Cheeloo infection in goats. The first assembly and characterization of T. luwenshuni genome will benefit exploring the infective and pathogenic mechanisms of the emerging Theileria to provide scientific basis for future control strategies of theileriosis., Competing Interests: The authors declare no conflict of interest.

Efficient transfer of charge carriers through a fast transport pathway is crucial to excellent photocatalytic reduction performance in solar-driven CO 2 reduction, but it is still challenging to effectively modulate the electronic transport pathway between photoactive motifs by feasible chemical means. In this work, we propose a thermally induced strategy to precisely modulate the fast electron transport pathway formed between the photoactive motifs of a porphyrin metal-organic framework using thorium ion with large ionic radius and high coordination number as the coordination-labile metal node. As a result, the stacking pattern of porphyrin molecules in the framework before and after the crystal transformations has changed dramatically, which leads to significant differences in the separation efficiency of photogenerated carriers in MOFs. The rate of photocatalytic reduction of CO 2 to CO by IHEP-22(Co) reaches 350.9 μmol·h -1 ·g -1 , which is 3.60 times that of IHEP-21(Co) and 1.46 times that of IHEP-23(Co) . Photoelectrochemical characterizations and theoretical calculations suggest that the electron transport channels formed between porphyrin molecules inhibit the recombination of photogenerated carriers, resulting in high performance for photocatalytic CO 2 reduction. The interaction mechanism of CO 2 with IHEP-22(Co) was clarified by using in-situ electron paramagnetic resonance, in-situ diffuse reflectance infrared Fourier transform spectroscopy, in-situ extended X-ray absorption fine structure spectroscopy, and theoretical calculations. These results provide a new method to regulate the efficient separation and migration of charge carriers in CO 2 reduction photocatalysts and will be helpful to guide the design and synthesis of photocatalysts with superior performance for the production of solar fuels.

Background: Myopia has become a worldwide problem that endangers public health and adds a serious socioeconomic burden. Current research has focused on the pathogenesis and manifestations of pathological myopia (PM). However, few studies have been conducted on the spontaneous activity of the patient's brain., Purpose: To study the potential brain network activity in patients with PM by the degree centrality (DC) method., Materials and Methods: This experiment included 15 PM patients and 15 healthy controls (HCs). Every participant experienced a resting-state functional magnetic resonance imaging (rs-fMRI) scan. Receiver operating characteristic (ROC) curve analysis was used to distinguish between PM patients and HCs. Correlation analysis was used to explore the relationships between mean DC values and clinical performance in different brain regions., Results: It showed that patients with PM had lower DC values in the right fusiform gyrus (FR) and right cingulate (CAR). The ROC curve was used to indicate the accuracy of the correlation. It showed that in PM group, left best corrected visual acuity (BCVA-L) and right best corrected visual acuity (BCVA-R) were negatively correlated with the DC value of FR., Conclusion: The occurrence of PM is mainly related to the abnormal activity of the fusiform and cingulum. DC value might be used as a biological marker of abnormal brain activity in PM patients., (© 2023 The Authors. CNS Neuroscience & Therapeutics Published by John Wiley & Sons Ltd.)

Triple-negative breast cancer (TNBC) is an aggressive type of breast cancer where no effective therapy has been developed. Here, we report that the natural product ER translocon inhibitor ipomoeassin F is a selective inhibitor of TNBC cell growth. A proteomic analysis of TNBC cells revealed that ipomoeassin F significantly reduced the levels of ER molecular chaperones, including PDIA6 and PDIA4, and induced ER stress, unfolded protein response (UPR) and autophagy in TNBC cells. Mechanistically, ipomoeassin F, as an inhibitor of Sec61α-containing ER translocon, blocks ER translocation of PDIA6, inducing its proteasomal degradation. Silencing of PDIA6 or PDIA4 by RNA interferences or treatment with a small molecule inhibitor of the protein disulfide isomerases in TNBC cells successfully recapitulated the ipomoeassin F phenotypes, including the induction of ER stress, UPR and autophagy, suggesting that the reduction of PDIAs is the key mediator of the pharmacological effects of ipomoeassin F. Moreover, ipomoeassin F significantly suppressed TNBC growth in a mouse tumor xenograft model, with a marked reduction in PDIA6 and PDIA4 levels in the tumor samples. Our study demonstrates that Sec61α-containing ER translocon and PDIAs are potential drug targets for TNBC and suggests that ipomoeassin F could serve as a lead for developing ER translocon-targeted therapy for TNBC., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

The present paper is dedicated to the quantitative determination of oxygen-containing impurities in the LiF-NaF-KF eutectic using electrochemical (cyclic and square-wave voltammetry) and reduction melting methods. The LiF-NaF-KF melt was analyzed before and after purifying electrolysis. The amount of oxygen-containing impurities removed from the salt during purification was determined. It was found that after electrolysis, the concentration of oxygen-containing impurities decreased by 7 times. The results obtained via electrochemical techniques and reduction melting were well-correlated, which made it possible to evaluate the quality of the LiF-NaF-KF F melt. To verify the analysis conditions, mechanical mixtures of LiF-NaF-KF containing Li 2 O were analyzed using the reduction melting method. The oxygen concentration in the mixtures varied from 0.672 to 2.554 wt. %. Based on the analysis results, the dependence approximated by the straight line was obtained. These data may be used to draw calibration curves and to further develop the procedure of oxygen analysis of fluoride melts.

Separation of minor actinides from lanthanides is one of the biggest challenges in spent fuel reprocessing due to the similar physicochemical properties of trivalent lanthanides (Ln(III)) and actinides (An(III)). Therefore, developing ligands with excellent extraction and separation performance is essential at present. As an excellent pre-organization platform, calixarene has received more attention on Ln(III)/An(III) separation. In this work, we systematically explored the complexation behaviors of the diglycolamide (DGA)/dimethylacetamide (DMA)-functionalized calix[4]arene extractants for Eu(III) and Am(III) using relativistic density functional theory (DFT). These calix[4]arene-derived ligands were obtained by functionalization with two or four binding units at the narrow edge of the calix[4]arene platform. All bonding nature analyses suggested that the Eu-L complexes possess stronger interaction compared to Am-L analogues, resulting in the higher extraction capacity of the these calix[4]arene ligands toward Eu(III). Thermodynamic analysis demonstrates that these pre-organized ligands on the calix[4]arene platform with four binding units yield better extraction abilities than the single ligands. Although DMA-functionalized ligands show stronger complexation stability for metal ions, in acidic solutions, the calix[4]arene ligands with DGA binding units have better extraction performance for Eu(III) and Am(III) due to the basicity of the DMA ligand. This work enabled us to gain a deeper understanding of the bonding properties between supramolecular ligands and lanthanides/actinides and afford useful insights into designing efficient supramolecular ligands for separating Ln(III)/An(III).

An efficient approach to Np separation in the Plutonium Uranium Reduction EXtraction (PUREX) process is to adjust Np(VI) to Np(V) by free-salt reductants, such as hydrazine and its derivatives. Recently, carbohydrazide (CO(N 2 H 3 ) 2 ), a derivative of hydrazine and urea, has received much attention, which can reduce Np(VI) to Np(V) in the extraction reprocessing of spent nuclear fuel. Herein, according to the experimental observations, we examine the reduction mechanism of four Np(VI) by one carbohydrazide molecule using multiple theoretical calculations. The fourth Np(VI) reduction with a 22.26 kcal mol -1 energy barrier is the rate-determining step, which is in accordance with the experimental observations (20.54 ± 1.20 kcal mol -1 ). The results of spin density reflect that the reduction of the first and third Np(VI) ion is an outer-sphere electron transfer, while that of the second and fourth Np(VI) ion is the hydrogen transfer. Localized molecular orbitals (LMOs) uncover that the breaking of the N-H bond and formation of the O yl -H bond are accompanied by the reaction from initial complexes (ICs) to intermediates (INTs). This work offers basic perspectives for the reduction mechanism of Np(VI) to Np(V) by CO(N 2 H 3 ) 2 , which is also expected to design excellent free-salt Np(VI) reductants for the separation of Np in the advanced PUREX process.

It is an ongoing goal to achieve the effective regulation of the thermal expansion properties of materials. In this work, we propose a method for incorporating host-guest complexation into a framework structure and construct a flexible cucurbit[8]uril uranyl-organic polythreading framework, U 3 (bcbpy) 3 (CB8). U 3 (bcbpy) 3 (CB8) can undergo huge negative thermal expansion (NTE) and has a large volumetric coefficient of -962.9 × 10 -6 K -1 within the temperature range of 260 K to 300 K. Crystallographic snapshots of the polythreading framework at various temperatures reveal that, different from the intrinsic transverse vibrations of the subunits of metal-organic frameworks (MOFs) that experience NTE via a well-known hinging model, the remarkable NTE effect observed here is the result of a newly-proposed thermally induced relaxation process. During this process, an extreme spring-like contraction of the flexible CB8-based pseudorotaxane units, with an onset temperature of ∼260 K, follows a period of cumulative expansion. More interestingly, compared with MOFs that commonly have relatively strong coordination bonds, due to the difference in the structural flexibility and adaptivity of the weakly bonded U 3 (bcbpy) 3 (CB8) polythreading framework, U 3 (bcbpy) 3 (CB8) shows unique time-dependent structural dynamics related to the relaxation process, the first time this has been reported in NTE materials. This work provides a feasible pathway for exploring new NTE mechanisms by using tailored supramolecular host-guest complexes with high structural flexibility and has promise for the design of new kinds of functional metal-organic materials with controllable thermal responsive behaviour., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Use of abiotic chemical systems for understanding higher order superstructures is challenging. Here we report a ring-in-ring(s) system comprising a hydrogen-bonded macrocycle and cyclobis(paraquat-o-phenylene) tetracation (o-Box) or cyclobis(paraquat-p-phenylene) tetracation (CBPQT 4+ , p-Box) that assembles to construct discrete higher order structures with adaptive conformation. As indicated by mass spectrometry, computational modeling, NMR spectroscopy, and single-crystal X-ray diffraction analysis, this ring-in-ring(s) system features the box-directed aggregation of multiple macrocycles, leading to generation of several stable species such as H4G (1 a/o-Box) and H5G (1 a/o-Box). Remarkably, a dimeric shish-kebab-like ring-in-rings superstructure H7G2 (1 a/o-Box) or H8G2 (1 a/p-Box) is formed from the coaxial stacking of two ring-in-rings units. The formation of such unique dimeric superstructures is attributed to the large π-surface of this 2D planar macrocycle and the conformational variation of both host and guest., (© 2023 Wiley-VCH GmbH.)

The separation of lanthanides and actinides has attracted great attention in spent nuclear fuel reprocessing up to date. In addition, liquid-liquid extraction is a feasible and useful way to separate An(III) from Ln(III) based on their relative solubilities in two different immiscible liquids. The hydrophilic bipyridine- and phenanthroline-based nitrogen-chelating ligands show excellent performance in separation of Am(III) and Eu(III) as reported previously. To profoundly explore the separation mechanism, herein, we first of all designed four hydrophilic sulfonated and phosphorylated ligands L 1 , L 2 , L 3 , and L 4 based on the bipyridine and phenanthroline backbones. In addition, we studied the structures of these ligands and their neutral complexes [ML(NO 3 ) 3 ] (M = Am, Eu) as well as the thermodynamic properties of complexing reactions through the scalar relativistic density functional theory. According to the changes of the Gibbs free energy for the back-extraction reactions, the phenanthroline-based ligands L 2 and L 4 have stronger complexing capacity for both Am(III) and Eu(III) ions while the phosphorylated ligand L 3 with the bipyridine framework has the highest Am(III)/Eu(III) selectivity. In addition, the charge decomposition analysis revealed a higher degree of charge transfer from the ligand to Am(III), suggesting stronger donor-acceptor interactions in the Am(III) complexes. This study can provide theoretical insights into the separation of actinide(III)/lanthanide(III) using hydrophilic sulfonated and phosphorylated N-donor ligands.

As an aprotic O-donor ligand, 4,4'-bipyridine N , N '-dioxide (DPO) shows good potential for the preparation of uranyl coordination compounds. In this work, by regulating reactant compositions and synthesis conditions, diverse coordination assembly between uranyl and DPO under different reaction conditions was achieved in the presence of other coexisting O-donors. A total of ten uranyl-DPO compounds, U-DPO-1 to U-DPO-10, have been synthesized by evaporation or hydro/solvothermal treatment, and the possible competition and cooperation of DPO with other O-donors for the formation of these uranyl-DPO compounds are discussed. Starting with an aqueous solution of uranyl nitrate, it is found that an anionic nitrate or hydroxyl group is involved in the coordination sphere of uranyl in U-DPO-1 ((UO 2 )(NO 3 ) 2 (H 2 O) 2 ·(DPO)), U-DPO-2 ((UO 2 )(NO 3 ) 2 (DPO)), and U-DPO-3 ((UO 2 )(DPO)(μ 2 -OH) 2 ), where DPO takes three different kinds of coordination modes, i.e. uncoordinated, monodentate, and biconnected. The utilization of UO 2 (CF 3 SO 3 ) 2 in acetonitrile, instead of an aqueous solution of uranyl nitrate, precludes the participation of nitrate and hydroxyl, and ensures the engagement of DPO ligands (4-5 DPO ligands for each uranyl) in a uranyl coordination sphere of U-DPO-4 ([(UO 2 )(CF 3 SO 3 )(DPO) 2 ](CF 3 SO 3 )), U-DPO-5 ([UO 2 (H 2 O)(DPO) 2 ](CF 3 SO 3 ) 2 ) and U-DPO-6 ([(UO 2 )(DPO) 2.5 ](CF 3 SO 3 ) 2 ). Moreover, when combined with anionic carboxylate ligands, terephthalic acid (H 2 TPA), isophthalic acid (H 2 IPA), and succinic acid (H 2 SA), DPO works well with them to produce four mixed-ligand uranyl compounds with similar structures of two-dimensional (2D) networks or three-dimensional (3D) frameworks, U-DPO-7 ((UO 2 )(TPA)(DPO)), U-DPO-8 ((UO 2 ) 2 (DPO)(IPA) 2 ·0.5H 2 O), U-DPO-9 ((UO 2 )(SA)(DPO)·H 2 O), and U-DPO-10 ((UO 2 ) 2 (μ 2 -OH)(SA) 1.5 (DPO)). Density functional theory (DFT) calculations conducted to probe the bonding features between uranyl ions and different O-donor ligands show that the bonding ability of DPO is better than that of anionic CF 3 SO 3 - , nitrate, and a neutral H 2 O molecule and comparable to that of an anionic carboxylate group. Characterization of physicochemical properties of U-DPO-7 and U-DPO-10 with high phase purity including infrared (IR) spectroscopy, thermogravimetric analysis (TGA), and luminescence properties is also provided., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Purpose: To explore the possible molecular mechanism by which epidermal growth factor-containing fibulin-like extracellular matrix protein 1 (EFEMP1) regulates choroid thickness (CT) in the development of myopia., Methods: In total, 131 subjects were divided into the emmetropia (EM) group, non-high myopia (non-HM) group and high myopia (HM) group. Their age, refraction, intraocular pressure, and other ocular biometric parameters were collected. A 6 × 6 mm area centered on the optic disc was scanned by coherent optical tomography angiography (OCTA) to measure CT, and the tear concentrations of EFEMP1 were quantified using enzyme-linked immunosorbent assay (ELISA) analysis. Twenty-two guinea pigs were divided into the control group and the form-deprivation myopia (FDM) group. The right eye of the guinea pig in the FDM group was covered for 4 weeks, and the diopter and axial length of the right eye of the guinea pig were measured before and after the treatment. After the measurement, the guinea pig was euthanized, and the eyeball was removed. Quantitative reverse transcription polymerase chain reaction, western blotting assays and immunohistochemistry were used to assess the expression of EFEMP1 in the choroid., Results: There were significant differences in CT among the three groups ( p < 0.001). CT was positively correlated with age in HM ( r = -0.3613, p = 0.0021), but no significant correlation with SE ( p > 0.05) was observed. Furthermore, there were increased levels of EFEMP1 in the tears of myopic patients. After 4 weeks of covering the right eye of the FDM guinea pigs, there was a significant increase in axial length and a decrease in diopter ( p < 0.05). The mRNA and protein expression of EFEMP1 was significantly increased in the choroid., Conclusion: Choroidal thickness was significantly thinner in myopic patients, and the expression level of EFEMP1 in the choroid increased during the development of FDM. Therefore, EFEMP1 may be involved in the regulation of choroidal thickness in myopia patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Shi, Wan, Li, Li and Zhou.)

Separation of trivalent actinides (An(III)) and lanthanides (Ln(III)) poses a huge challenge in the reprocessing of spent nuclear fuel due to their similar chemical properties. N , N '-Diethyl- N , N '-ditolyl-2,9-diamide-1,10-phenanthroline (Et-Tol-DAPhen) is a potential ligand for the extraction of An(III) from Ln(III), while there are still few reports on the effect of its substituent including electron-withdrawing and electron-donating groups on An(III)/Ln(III) separation. Herein, the interaction of Et-Tol-DAPhen ligands modified by the electron-withdrawing groups (CF 3 , Br) and electron-donating groups (OH) with Am(III)/Eu(III) ions was investigated using scalar relativistic density functional theory (DFT). The analyses of bond order, quantum theory of atoms in molecules (QTAIM), and molecular orbital (MO) indicate that the substitution groups have a slight effect on the electronic structures of the [M( L-X )(NO 3 ) 3 ] (X = CF 3 , Br, OH) complexes. However, the thermodynamic results suggest that a ligand with the electron-donating group ( L-OH ) improves the extraction ability of metal ions, and the ligand modified by the electron-withdrawing group ( L-Br ) has the best Am(III)/Eu(III) selectivity. This work could render new insights into understanding the effect of electron-withdrawing and electron-donating groups in tuning the selectivity of Et-Tol-DAPhen derivatives and pave the way for designing new ligands modified by substituted groups with better extraction ability and An(III)/Ln(III) selectivity.