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Ting Li,1,&ast; Ling Hu,1,&ast; Xiao-Ling Yin,1 Yi Zou,1 Hai-Yan Fu,1 Hong-Lin Li2 1Department of Endocrinology, The First Hospital of Nanchang (The Third Affiliated Hospital of Nanchang University), Nanchang, Jiangxi, People’s Republic of China; 2Department of Biochemistry, Medical College of Georgia, Augusta, GA, USA&ast;These authors contributed equally to this workCorrespondence: Ling Hu, Department of Endocrinology, The First Hospital of Nanchang (The Third Affiliated Hospital of Nanchang University), No.128 of Xiangshan North Road, Donghu District, Nanchang, Jiangxi, 330008, People’s Republic of China, Tel +86 0791-88862350, Fax +86 0791-6782945, Email ythulingh@163.comObjective: To retrospectively review the clinical data of type 2 diabetes mellitus (T2DM) patients hospitalized in Nanchang, China, summarized the prevalence of osteoporosis (OP) in T2DM patients in this area, and analyzed related influencing factors.Methods: The clinical data of hospitalized patients with T2DM were collected retrospectively. According to the results of bone mineral density test, the subjects were divided into the normal bone mass group, the osteopenia group, and the OP group. Age, gender, educational background, body mass index (BMI), waist-to-hip ratio (WHR), duration of T2DM, glycosylated hemoglobin, serum lipids, and complications of T2DM in the three groups were analyzed and compared.Results: The prevalence of OP in patients with T2DM was 35.77%. There were statistically significant differences in age, gender, BMI, WHR, duration of T2DM, educational background, the level of high-density lipoprotein cholesterol (HDL-C), the prevalence of diabetic retinopathy (DR), and diabetic peripheral neuropathy among the three groups (P < 0.05). Logistic regression analysis showed that increasing age, prolonged duration of T2DM, low BMI, high levels of HDL-C, and complicated DR were risk factors for osteopenia and OP.Conclusion: The prevalence of OP in T2DM was high. Risk factors for abnormal bone mass in T2DM might be females, advanced age, long duration of T2DM, low BMI, high levels of HDL-C, and diabetic microangiopathy.Keywords: type 2 diabetes mellitus, osteoporosis, risk-factors, prevalence

Ling Hu,* Ting Li,* Yi Zou, Xiao-Ling Yin, Hui Gan Department of Endocrinology, The Third Affiliated Hospital of Nanchang University, Nanchang 330000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ling HuDepartment of Endocrinology, The Third Affiliated Hospital of Nanchang University, No. 128 of Xiangshan North Road, Donghu District, Nanchang 330000, People’s Republic of ChinaTel +86 13970075119Email drhu_hl1172@163.comObjective: This study aimed to explore the clinical value of the fracture risk assessment tool (FRAX) in the fracture risk prediction of Chinese patients after replacing rheumatoid arthritis (RA) with type 2 diabetes mellitus (T2DM) in the FRAX algorithm.Methods: A total of 1,047 patients with T2DM from the Endocrinology Department of the Third Affiliated Hospital of Nanchang University were enrolled in this study. Dual-energy X-ray absorptiometry (DXA) was then used to detect their bone density. RA in the FRAX algorithm was replaced with T2DM, and the new RA-adjusted FRAX was used to assess the fracture risk of the patients.Results: The sensitivity, specificity, and Youden’s index of the RA-adjusted FRAX to the treatment opinions on T2DM-associated hip fractures were 0.4761, 0.9642, and 0.4403, respectively, while the sensitivity, specificity, and Youden’s index of RA-adjusted FRAX to the treatment opinions on T2DM-associated major bone osteoporotic fractures were 0.0080, 1.0000, 0.0080, respectively. The DXA and RA-adjusted FRAX both showed acceptable consistency in the treatment recommendations for hip fractures in patients with T2DM (κ = 0.49) but had poor consistency in treatment recommendations for major bone osteoporotic fractures (κ = 0.010). The body mass index (BMI) scores, femoral neck-bone mineral densities, and number of males in the same treatment opinion group were significantly higher than in the different treatment opinions group (P < 0.001).Conclusion: RA-adjusted FRAX is a useful clinical tool for evaluation of hip fracture risk for Chinese patients with T2DM, and the accuracy of fracture risk prediction for male patients with T2DM and patients with T2DM with high BMI scores or high femoral neck-bone mineral density is higher.Keywords: type 2 diabetes mellitus, FRAX, fracture risk, bone mineral density, osteoporosis

Leiqiang Han, Tianqi Wang, Jingliang Wu, Xiaolan Yin, Hao Fang, Na Zhang School of Pharmaceutical Science, Shandong University, Ji’nan, Shandong, People’s Republic of China Abstract: Small molecule-based nanodrugs with nanoparticles (NPs) that are mainly composed of small molecules, have been considered as a promising candidate for a next-generation nanodrug, owing to their unique properties. Vorinostat (SAHA) is a canonical US Food and Drug Administration-approved histone deacetylase (HDAC) inhibitor for the treatment of cutaneous T-cell lymphoma. However, the lack of efficacy against solid tumors hinders its progress in clinical use. Herein, a novel nanodrug of SAHA was developed based on disulfide-linked prodrug SAHA-S-S-VE. SAHA-S-S-VE could self-assemble into 148 nm NPs by disulfide-induced mechanisms, which were validated by molecular dynamics simulations. Under reduced conditions, the redox-responsive behavior of SAHA-S-S-VE was investigated, and the HDAC inhibition results verified the efficient release of free SAHA. With a biocompatible d-a-tocopheryl polyethylene glycol succinate (TPGS) functionalization, the SAHA-S-S-VE/TPGS NPs exhibited low critical aggregation concentration of 4.5 µM and outstanding stability in vitro with drug-loading capacity of 24%. In vitro biological assessment indicated that SAHA-S-S-VE/TPGS NPs had significant anticancer activity against HepG2. Further in vivo evaluation demonstrated that the resulting NPs could be accumulated in the tumor region and inhibit the tumor growth effectively. This approach, which turned SAHA into a self-assembled redox-responsive nanodrug, provided a new channel for the use of HDAC inhibitor in solid tumor therapy. Keywords: SAHA, HDAC, small molecule, nanoparticles, self-assemble, disulfide bond

The article presents findings of a meta-analysis that examines benefits of providing health education to patients with hypertension in China as of March 2014. Topics discussed include identification of important role played by health education in controlling blood pressure in hypertensive patients, description of risk factors linked with hypertension concerning cardiovascular and kidney diseases, and methodologies used in the study. It mentions that the study can be used to form such programs.

Objectives: Post-resuscitation myocardial dysfunction yields high rates of mortality, but its potential mechanism remains poorly understood. This study investigated whether endoplasmic reticulum (ER) stress-mediated apoptosis is activated in the heart after cardiac arrest (CA) and resuscitation.Methods: Wistar rats were subjected to 5 min electrically induced CA and then resuscitated by mechanical chest compression and epinephrine administration. Animals were decapitated at 3, 6, 12 and 24h (n=8, per group) after return of spontaneous circulation (ROSC). Myocardial specimens were analysed using electron microscopy, terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) assay, reverse transcription polymerase chain reaction, Western blotting and immunohistochemistry.Results: The ER, mitochondria and nuclei in cardiomyocytes from the experimental groups were seriously damaged. Typical apoptotic nuclei were observed in cardiomyocytes 24h after resuscitation. TUNEL showed an approximately two-fold increase in the percentage of apoptotic cardiomyocytes 24h post-ROSC. The mRNA levels of glucose-regulated protein78 (GRP78) and calreticulin (CRT) were significantly elevated 3-24h after reperfusion. The transcription of the ER stress-associated apoptotic gene chop increased. The protein expressions of GRP78 and CRT were up-regulated at first; the C/EBP (CCAAT enhancer binding protein) homologous protein (CHOP) then increased, along with elevations in the active form of caspase-3. In situ immunostaining of ER stress markers also demonstrated that ER stress occurred in the myocardium after CA and resuscitation.Conclusion: ER stress and the CHOP apoptotic pathway are activated in the myocardium after CA and resuscitation. ER stress-mediated apoptosis may be one of the main pathological mechanisms of post-resuscitation myocardial injury. [ABSTRACT FROM AUTHOR]

Hyperbilirubinemia (HB) is a key risk factor for hearing loss in neonates, particularly premature infants. Here, we report that bilirubin (BIL)-dependent cell death in the auditory brainstem of neonatal mice of both sexes is significantly attenuated by ZD7288, a blocker for hyperpolarization-activated cyclic nucleotide-gated (HCN) channel-mediated current ( I h ), or by genetic deletion of HCN1. GABAergic inhibitory interneurons predominantly express HCN1, on which BIL selectively acts to increase their intrinsic excitability and mortality by enhancing HCN1 activity and Ca 2+ -dependent membrane targeting. Chronic BIL elevation in neonatal mice in vivo increases the fraction of spontaneously active interneurons and their firing frequency, I h , and death, compromising audition at the young adult stage in HCN1 +/+ , but not in HCN1 -/- genotype. We conclude that HB preferentially targets HCN1 to injure inhibitory interneurons, fueling a feedforward loop in which lessening inhibition cascades hyperexcitability, Ca 2+ overload, neuronal death, and auditory impairments. These findings rationalize HCN1 as a potential target for managing HB encephalopathy., Competing Interests: The authors declare no competing financial interests., (Copyright © 2024 the authors.)

Objective: This study aims to explore the influence of combining autologous platelet-rich gel (APG) with continuous vacuum-sealed drainage (CVSD) and the exogenous recombinant human acidic fibroblast growth factor (rh-aFGF) on the healing processes of diabetic foot ulcers (DFU). The primary objective is to elucidate the complex molecular mechanisms associated with DFU, providing innovative perspectives for its treatment., Methods: Ninety patients diagnosed with DFU were randomly allocated into three distinct groups. Group A underwent CVSD following wound cleansing to facilitate healing. In Group B, in addition to conventional treatment, negative pressure wound therapy was applied, and rh-aFGF was introduced into normal saline for lavage, building upon the procedures of Group A. Group C received APG along with the interventions applied in Group B. The clinical efficacy of each group was systematically observed and analyzed. Additionally, changes in plasma oxidative stress, inflammatory markers, vascular endothelial growth factor (VEGF), and pigment epithelium-derived factor (PEDF) were assessed both before treatment and 14 days post-treatment., Results: Following treatment, all groups exhibited commendable clinical efficacy. Group C demonstrated a superior wound healing rate, reduced frequency of dressing changes, and shorter wound healing duration (P< 0.05). Compared to baseline measurements, the levels of superoxide dismutase and PEDF increased, while malondialdehyde, VEGF, interleukin-6, interleukin-8, and monocyte chemotactic factor MCP-1 decreased in the wound tissue across all groups. Notably, Group C showed the most significant improvement in clinical efficacy and fortification of molecular mechanisms against oxidative stress (all P< 0.05)., Conclusions: The integrative therapeutic approach combining APG with CVSD and rh-aFGF demonstrates notable efficacy in advancing wound healing. This effectiveness is evident through the reduced frequency of dressing changes and alleviation of wound-related pain. Additionally, the treatment regimen improves the cure rate for challenging, refractory wounds. These favorable outcomes can be attributed to the reduction of oxidative stress levels, attenuation of the local inflammatory response, and the enhancement of the balance between PEDF and VEGF., 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 Sheng, Hu, Li, Zou, Fu, Xiong, Zhu, Deng, Xiong and Yin.)

Objective To explore the effect and mechanism of uric acid (UA) in regulating the larval growth and development of Drosophila melanogaster . Methods A total of 1350 newly hatched first-instar larvae of wild-type Drosophila melanogaster (W1118) were collected,and the Drosophila melanogaster model of hyperuricemia was constructed with a high purine diet.The larvae were assigned into three groups ( n =150):control (standard corn meal medium),low-dose adenine (corn meal medium containing 0.05% adenine),and high-dose adenine (corn meal medium containing 0.10% adenine),and two parallel groups were set up.The growth and development of larvae in each group was observed,and the UA and hormone levels were measured.In addition,the expression levels of genes involved in growth and development were determined. Results Compared with the control group,the low- and high-dose adenine groups showed elevated UA levels (both P <0.001) and prolonged developmental period ( P =0.024, P <0.001).The high-dose adenine group showed decreased survival rate,pupation rate,and eclosion rate and elevated levels of juvenile hormone (JH) and 20-hydroxyecdysone (20E) (all P <0.001).The PCR results showed that compared with the control group,high-dose adenine upregulated the mRNA levels of reactive oxygen species (ROS),forkhead box O (FOXO),and mammalian target of rapamycin (mTOR) while downregulating the mRNA levels of Sestrin,mTOR complex 1(mTORC1),and AMP-activated protein kinase (all P <0.001). Conclusion High concentrations of UA may promote the expression of ROS/FOXO/mTORC1/mTOR signaling pathway by regulating the levels of JH and 20E,thereby inhibiting the larval growth and development of Drosophila melanogaster .

CO 2 -to-high value-added chemicals via a photocatalytic route is of interest but strangled by the low efficiency. Herein, a novel Fe-TiO 2-x /TiO 2 S-scheme homojunction was designed and constructed by using a facile surface modification approach whereby oxygen vacancy (OV) and Fe introducing on the TiO 2 nanorod surface. The as-synthesized Fe-TiO 2-x /TiO 2 S-scheme homojunction exhibits positive properties on promoting photocatalytic CO 2 reduction: i) the nanorod structure provides numerous active sites and a radical charge transfer path; ii) the doped Fe and OV not only synergistically enhance light utilization but also promote CO 2 adsorption; iii) the Fe-TiO 2-x /TiO 2 S-scheme homojunction benefits photoexcited charge separation and retains stronger redox capacity. Thanks to those good characters, the Fe-TiO 2-x /TiO 2 homojunction exhibits superior CO 2 reduction performances with optimized CO/CH 4 generation rates of 122/22 μmol g -1 h -1 which exceed those of pure TiO 2 by more than 9.4/7.3 folds and most currently reported catalytic systems. This manuscript develops a facile and universal approach to synthesize well-defined homojunction and may inspire the construction of other more high-efficiency photocatalysts toward CO 2 reduction and beyond., 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.)

The duration of storage significantly influences the quality and market value of Qingzhuan tea (QZT). Herein, a high-resolution multiple reaction monitoring (MRM HR ) quantitative method for markers of QZT storage year was developed. Quantitative data alongside multivariate analysis were employed to discriminate and predict the storage year of QZT. Furthermore, the content of the main biochemical ingredients, catechins and alkaloids, and free amino acids (FAA) were assessed for this purpose. The results show that targeted marker-based models exhibited superior discrimination and prediction performance among four datasets. The R 2 X cum , R 2 Y cum and Q 2 cum of orthogonal projection to latent structure-discriminant analysis discrimination model were close to 1. The correlation coefficient (R 2 ) and the root mean square error of prediction of the QZT storage year prediction model were 0.9906 and 0.63, respectively. This study provides valuable insights into tea storage quality and highlights the potential application of targeted markers in food quality evaluation., 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.)

Swin Transformer is an important work among all the attempts to reduce the computational complexity of Transformers while maintaining its excellent performance in computer vision. Window-based patch self-attention can use the local connectivity of the image features, and the shifted window-based patch self-attention enables the communication of information between different patches in the entire image scope. Through in-depth research on the effects of different sizes of shifted windows on the patch information communication efficiency, this article proposes a Dual-Scale Transformer with double-sized shifted window attention method. The proposed method surpasses CNN-based methods such as U-Net, AttenU-Net, ResU-Net, CE-Net by a considerable margin (Approximately 3% ∼ 6% increase), and outperforms the Transformer based models single-scale Swin Transformer(SwinT)(Approximately 1% increase), on the datasets of the Kvasir-SEG, ISIC2017, MICCAI EndoVisSub-Instrument and CadVesSet. The experimental results verify that the proposed dual scale shifted window attention benefits the communication of patch information and can enhance the segmentation results to state of the art. We also implement an ablation study on the effect of the shifted window size on the information flow efficiency and verify that the dual-scale shifted window attention is the optimized network design. Our study highlights the significant impact of network structure design on visual performance, providing valuable insights for the design of networks based on Transformer architectures., (© 2024. The Author(s).)

Among refractive errors, astigmatism is the most common optical aberration, where refraction changes in different meridians of the eye. It causes blurred vision at any distance and includes corneal, lenticular, and retinal astigmatism. Cataract surgery used to cause a progressive increase in the pre-exisiting corneal astigmatism because of creating a surgically induced astigmatism, for example, a large size surgery incision. The development of surgical techniques during last decades has made cataract surgery interchange to treat preoperative corneal astigmatism at time of surgery. Nowadays, three surgical approaches can be used. By placing a sutureless clear corneal incision on the steep meridian of the cornea, a preoperative corneal astigmatism less than 1.0 D can be corrected. Single or paired peripheral corneal relaxing incisions (PCRIs) provide 1.0-3.0 D corneal astigmatism correction. PCRIs are typically used for treating 1.0-1.5 D of regular corneal astigmatism, if more than 2.0 D, the risk of overcorrection and irregular astigmatism is increased. When toric intraocular lenses (IOLs) are unavailable in markets, PCRIs are still a reasonable option for patients with up to 3.0 D of pre-existing corneal astigmatism. Toric IOLs implantation can correct 1.0-4.5 D of corneal astigmatism. Several IOLs are approved to correct a high degree of corneal astigmatism with cylinder power up to 12.0 D. These approaches can be used alone or in combination., Competing Interests: Conflicts of Interest: Yin XL, None; Ji ZY, None; Li XX, None; Liang XM, None; Ji SX, None., (International Journal of Ophthalmology Press.)

Objective: To analyze the effects of changes in the spectrum of deaths from malignant tumors on the life expectancies of residents of different ages, sexes, and regions (urban or rural) in Tianjin from 1999 to 2019. Methods: The Abridged Life Table method and the Arriaga's decomposition method were used to calculate the effects of changes in spectrum of deaths from malignant tumors on the life expectancies of Tianjin residents of different ages, sexes, and regions. Results: During 1999-2019, the life expectancies increased by 4.96 years and 5.69 years for males and females, respectively, in Tianjin. The decreases in the mortalities from malignant neoplasms contributed 0.12 year (3.30%) and 0.03 year (0.77%) for males and females, respectively, to the increase during 1999-2007, and 0.05 year (3.13%) and 0.12 year (6.08%) for males and females, respectively, during 2007-2019. The decreases in the mortality rates of malignant tumors contributed the most to the increase among residents in the 60-69 years group, and the decreases in mortality rates of lung, gastric, esophageal, and liver cancers had relatively larger contribution. Lung cancer had a negative effect on the life expectancies of men and rural residents, but a positive effect on those of women and urban residents. The significant increases in the mortality rates of lung, colorectal, and pancreatic cancers in the ≥85 years group had a large negative effect on the overall life expectancy. Breast and ovarian cancers contributed negatively to the life expectancy of female residents. Conclusion: The overall increase in the life expectancy in Tianjin from 1999 to 2019 was mainly attributed to the elderly and the decreases in the mortality rates of gastric, esophageal, and liver cancers, among other malignancies, while the increases in the mortality rates of lung, colorectal, gallbladder, pancreatic, and breast cancers were the most significant factors hindering the increase of the life expectancy in Tianjin.

One new lanostane-type triterpenoid, 3 β -acetoxy-7,11-dioxolanosta-8,24-dien-21-oic acid ( 1 ), together with six known analogues ( 2 - 7 ), were isolated from the cultures of a marine fungus Ceriporia lacerata CD7-5, which was derived from the shellfish Ostrea denselamellosa . Their structures were determined by detailed analysis of spectroscopic data and comparison with the literature reported. The biological activities of these lanostane triterpenoids against marine-derived microalgae, zooplankton, and pathogenic bacteria were also evaluated in this study.

Fluorescence spectroscopy is a powerful tool to determine polycyclic aromatic hydrocarbons (PAHs) owing to the strong endogenous fluorescence of these compounds. However, the presence of unknown interferences and overlapped spectra hinders the accurate determination of PAHs in oilfield produced water. Moreover, surfactants frequently coexist in oilfield produced water and will seriously affect the fluorescence signals of PAHs. Herein, a new methodology applying third-order calibration to process four-way (4D) fluorescence data was proposed to solve these problems and achieve accurate determination of pyrene, fluorene, phenanthrene, and fluoranthene as an example in oilfield produced water. The methodology is based on excitation-emission matrix fluorescence modulated by different concentrations of sodium dodecyl benzene sulfonate (SDBS) in the analyzed samples. The 4D fluorescence data were processed by third-order calibration methods including four-way parallel factor analysis (4-PARAFAC) and alternating weighted residue constraint quadrilinear decomposition (AWRCQLD), and the results were compared with those of second-order calibration methods. It was proved that third-order calibration was capable of accurately identifying and quantifying PAHs together with SDBS in oilfield produced water, which has better quantitative results and figures of merit compared to second-order calibration. This study provided a new approach to generating 4D fluorescence data and opened up an avenue for the accurate determination of PAHs in complex oilfield produced water with surfactants., 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.)

The accurate identification of tea grade is crucial to the quality control of tea. However, existing methods lack sufficient generalization ability in identifying tea grades due to the effect of temporal and spatial factors. In this study, we analyzed the effect of cultivar and altitude on EnshiYulu (ESYL) tea grades and established a robust model to evaluate their quality. Principal component analysis (PCA) revealed that differences in variety and elevation can mask grade differences. Orthogonal projection to latent structure-discriminant analysis (OPLS-DA) was used for grade identification of samples from different altitudes. For ESYL tea samples above and below 800 m altitude, 75 and 35 grade differentiated metabolites were discovered, with 14 common differentiated metabolites. Based on reconstructed OPLS-DA models, the grades of multi-altitude sources ESYL were discriminated with a rate > 85%. These results demonstrate the potential of a grade discrimination model based on common differential metabolites, which exhibits generalization ability., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

In order to better support the construction of the capital water conservation functional area and ecological environment support area， research on the chemical characteristics of groundwater and its formation mechanism in the dry period in the Zhangjiakou area can provide a great reference for the rational development and utilization of groundwater resources. A total of 41 groups of groundwater samples were collected， and the hydrochemical types， composition characteristics， and control factors of groundwater in the study area were analyzed by using the combined method of descriptive statistical analysis， Piper triplot， correlation analysis， Gibbs plot， and ion ratio. The results showed that the groundwater in the study area was weakly alkaline， with the total hardness and ρ （TDS） ranging from 105.00 mg·L -1 to 1 433.00 mg·L -1 and 137.00 mg·L -1 to 2 286.00 mg·L -1 ， respectively. The total hardness and TDS mass concentrations of groundwater in the Bashang area were higher than those in the Baxia area. HCO 3 - and Na + were the main dominant anions and cations in the groundwater in the study area. The highest overstandard rate of the main components in groundwater was that of total hardness （36.59%）. The overstandard rate and maximum excess multiple of each component in groundwater in the Bashang area were greater than those in the Baxia area. HCO 3 -Ca·Mg·Na was the main type of groundwater hydrochemistry in the study area， and there was little difference between the Bashang area and the Baxia area. SO 4 2- ， Cl - ， HCO 3 - ， Na + ， and Mg 2+ contributed the most to TDS. The chemical characteristics of groundwater were affected by weathering and filtration of rock minerals such as salt rock， albite， and dolomite； cation exchange； and human activities. Evaporative crystallization and atmospheric precipitation contributed to a small part of the main ion source of groundwater in the area. The effect of human activities on groundwater in the Bashang area was greater than that in the Baxia area， and NO 3 - mainly originated from agricultural activities.

Wine is a very popular alcoholic drink owing to its health benefits of antioxidant effects. However, profits-driven frauds of wine especially false declarations of variety frequently occurred in markets. In this work, an UHPLC-QTOF-MS-based untargeted metabolomics method was developed for metabolite profiling of 119 bottles of Chinese red wines from four varieties (Cabernet Sauvignon, Merlot, Cabernet Gernischt, and Pinot Noir). The metabolites of red wines from different varieties were assessed using orthogonal partial least-squares discriminant analysis (OPLS-DA) and analyzed using KEGG metabolic pathway analysis. Results showed that the differential compounds among different varieties of red wines are mainly flavonoids, phenols, indoles and amino acids. The KEGG metabolic pathway analysis showed that indoles metabolism and flavonoids metabolism are closely related to wine varieties. Based on the differential compounds, OPLS-DA models could identify external validation wine samples with a total correct rate of 90.9 % in positive ionization mode and 100 % in negative ionization mode. This study indicated that the developed untargeted metabolomics method based on UHPLC-QTOF-MS is a potential tool to identify the varieties of Chinese red wines., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

The fibroblast growth factor receptor 2 (FGFR2) is a key component in cellular signaling networks, and its dysfunctional activation has been implicated in various diseases including cancer and developmental disorders. Mutations at the activation loop (A-loop) have been suggested to trigger an increased basal kinase activity. However, the molecular mechanism underlying this highly dynamic process has not been fully understood due to the limitation of static structural information. Here, we conducted multiple, large-scale Gaussian accelerated molecular dynamics simulations of five (K659E, K659N, K659M, K659Q, and K659T) FGFR2 mutants at the A-loop, and comprehensively analyzed the dynamic molecular basis of FGFR2 activation. The results quantified the population shift of each system, revealing that all mutants had a higher proportion of active-like states. Using Markov state models, we extracted the representative structure of different conformational states and identified key residues related to the increased kinase activity. Furthermore, community network analysis showed enhanced information connections in the mutants, highlighting the long-range allosteric communication between the A-loop and the hinge region. Our findings may provide insights into the dynamic mechanism for FGFR2 dysfunctional activation and allosteric drug discovery.Communicated by Ramaswamy H. Sarma.

Petroleum-containing substance (PCS) is a general term used for petroleum and its derivatives. A comprehensive characterization of PCSs is crucial for resource exploitation, economic development and environmental protection. Fluorescence spectroscopy, especially excitation-emission matrix fluorescence (EEMF) spectroscopy, has been proved to be a powerful tool to characterize PCSs since its remarkable sensitivity, selectivity, simplicity and high efficiency. However, there is a lack of systematic review focusing on this field in the literature. This paper reviews the fundamental principles and measurements of EEMF for characterizing PCSs, and makes a systematic introduction to various information mining methods including basic peak information extraction, spectral parameterization and some commonly used chemometric methods. In addition, recent advances in applying EEMF to characterize PCSs during the whole life-cycle process of petroleum are also revisited. Furthermore, the current limitations of EEMF in the measurement and characterization of PCSs are discussed and corresponding solutions are provided. For promoting the future development of this field, the urgent need to build a relatively complete EEMF fingerprint library to trace PCSs, not only pollutants but also crude oil and petroleum products, is proposed. Finally, the extensions of EEMF to high-dimensional chemometrics and deep learning are prospected, with the expectation of solving more complex systems and problems.

In this study, we conducted molecular dynamic simulations to investigate the thermal expansion behavior of Janus MoSSe nanotubes. We focused on understanding how the intrinsic strain in these nanotubes affects their thermal expansion coefficient (TEC). Interestingly, we found that Janus MoSSe nanotubes with sulfur (S) on the outer surface (MoSeS) exhibit a different intrinsic strain compared to those with selenium (Se) on the outer surface (MoSSe). In light of this observation, we explored the influence of this intrinsic strain on the TEC of the nanotubes. Our results revealed distinct trends for the TEC along the radial direction (TEC- r ) and the axial direction (TEC- l x ) of the MoSSe and MoSeS nanotubes. The TEC- r of MoSeS nanotubes was found to be significantly greater than that of MoSSe nanotubes. Moreover, the TEC- l x of MoSeS nanotubes was smaller than that of MoSSe nanotubes. Further analysis showed that the TEC- r of MoSeS nanotubes decreased by up to 37% as the radius increased, while that of MoSSe nanotubes exhibited a slight increase with increasing radius. On the other hand, the TEC- l x of MoSeS nanotubes increased by as much as 45% with increasing radius, whereas that of MoSSe nanotubes decreased gradually. These opposite tendencies of the TECs with respect to the radius were attributed to the presence of intrinsic strain within the nanotubes. The intrinsic strain was found to play a crucial role in inducing thermally induced bending and elliptization of the nanotubes' cross-section. These effects are considered key mechanisms through which intrinsic strain influences the TEC. Overall, our study provides valuable insights into the thermal stability of Janus nanotubes. By understanding the relationship between intrinsic strain and the thermal expansion behavior of nanotubes, we contribute to the broader understanding of these materials and their potential applications., (© 2023 IOP Publishing Ltd.)

A 16-year-old female patient experienced a rapid decline in bilateral visual acuity accompanied by central scotomas for 5 days following coronavirus disease 2019 infection. Ocular examination revealed findings consistent with acute macular neuroretinopathy. Structural en face imaging using optical coherence tomography demonstrated a wedge-shaped lesion with low reflectivity directed towards the fovea in both eyes. B-scan images revealed localized hyperreflective bands involving the outer nuclear layer and photoreceptor layer, with discontinuity of the ellipsoid zone. Based on clinical presentation and examination findings, a diagnosis of bilateral acute macular neuroretinopathy was established.

It's generally believed that the longer the storage, the better the quality of dark tea, but the chemical differences of Qingzhuan tea (QZT) with different storage years is still unclear. Herein, in this work, an untargeted metabolomic approach based on SWATH-MS was established to investigate the differential compounds of QZT with 0-9 years' storage time. These QZT samples were roughly divided into two categories by principal component analysis (PCA). After orthogonal projections to latent structures discriminant analysis (OPLS-DA), 18 differential compounds were putatively identified as chemical markers for the storage year variation of QZT. Heatmap visualization showed that the contents of catechins, fatty acids, and some phenolic acids significantly reduced, flavonoid glycosides, triterpenoids, and 8-C N-ethyl-2-pyrrolidinone-substituted flavan-3-ols (EPSFs) increased with the increase of storage time. Furthermore, these chemical markers were verified by the peak areas corresponding to MS2 ions from SWATH-MS. Based on the extraction chromatographic peak areas of MS and MS2 ions, a duration time prediction model was built for QZT with correlation coefficient R 2 of 0.9080 and 0.9701, and RMSEP value of 0.85 and 1.24, respectively. This study reveals the chemical differences of QZT with different storage years and provides a theoretical basis for the quality evaluation of stored dark tea., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Further investigation of secondary metabolites of a marine-alga-derived fungus Aspergillus sp. RR-YLW-12 led to isolate one new ophiobolin-type sesterterpenoid (1), four new drimane-type sesquiterpenoids (2-5) and one natural occurring compound (6), together with seven known compounds (7-13). Their structures and stereochemistry were elucidated by extensive spectroscopic analysis of NMR and HRMS experiments, and by comparison with the literature data. All isolates were evaluated for growth inhibition of five marine harmful microalgae. The new compounds exhibited significant to moderate inhibitory effects towards all tested microalgae species with IC 50 values ranging from 5.8 to 54.5 μg/mL., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2023. Published by Elsevier B.V.)

One new diterpene, harziaketal A (1), and one new highly degraded sterol, trichosterol A (2), along with three known compounds, including one diterpene, harzianone (3), and two steroids, (22E,24R)-5α,6α-epoxy-ergosta-8(14),22-dien-3β,7α-diol (4) and isoergokonin B (5), were isolated from the culture of the marine-alga-epiphytic fungus Trichoderma sp. Z43 by silica gel column chromatography (CC), Sephadex LH-20 CC, and preparative thin-layer chromatography (TLC). Their structures and relative configurations were assigned by nuclear magnetic resonance (NMR) and high resolution electrospray ionisation mass spectrometry (HR-ESI-MS) data, and the absolute configuration of 1 was established by X-ray diffraction. Compound 1 features a hemiketal unit situated at the four-membered ring of harziane-type diterpenes for the first time, while 2 represents the rare occurrence of sterols with rings A and B being degraded. Compounds 1 and 2 displayed weak inhibition against the tested phytoplankton (Amphidinium carterae, Heterocapsa circularisquama, Heterosigma akashiwo, and Prorocentrum donghaiense) with half maximal inhibitory concentration (IC 50 ) ranging from 14 to 53 μg/mL., (© 2023 Wiley-VHCA AG, Zurich, Switzerland.)

The quality and safety of agricultural products are strongly related to human livelihood. Thus, the government and consumers have recently paid increased attention to the quality and safety of agricultural products. The development of efficient, rapid, and sensitive analytical methods for detecting pesticides, veterinary drugs, heavy metals, mycotoxins, and environmental pollutants in agricultural products is of great significance. Owing to the complexity of many sample matrices and the low concentration of pollutants in a typical sample, appropriate sample pretreatment steps are necessary to enrich pollutants in agricultural products. Solid-phase extraction (SPE) is the most widely used sample pretreatment technology; in this technique, the adsorbent generally determines the selectivity and efficiency of the extraction process. An increasing number of novel materials have been used as SPE adsorbents. The extraction efficiency, extraction selectivity, and analytical throughput of SPE could be greatly improved by combining these novel materials with various extraction modes (e. g., solid-phase microextraction, dispersed SPE, and magnetic SPE (MSPE)) during sample preparation. Because of their large specific surface area and high affinity toward target analytes, nanomaterials are often used as SPE adsorbents, thereby greatly improving the selectivity and sensitivity of the analytical technology. More importantly, these materials have become a priority area of research on preconcentration technologies for trace compounds in agricultural products. This paper summarizes the adsorption characteristics of several new nanomaterials, including magnetic materials, carbon-based materials, metal nanomaterials (MNs), metal oxide nanomaterials (MONs), metal organic frameworks (MOFs), and covalent organic frameworks (COFs). These nanomaterials present numerous advantages, such as large specific surface areas, high adsorption capacities, and tailorable structural designs. MSPE employs magnetic materials as sorbents to afford fast dispersion and efficient recycling when applied to complex sample matrices under an external magnetic field. The use of MSPE can avoid several typical problems associated with SPE such as poor adsorbent packing and high pressure, thereby greatly simplifying the pretreatment process and providing a high flux for sample analysis. Carbon-based materials are powdered or bulk nonmetallic solid materials with carbon as the main component; carbon and nitrogen materials, mesoporous carbon, carbon nanotubes, and graphene are some examples of these materials. These materials provide large specific surface areas, abundant pore structures, good thermal stability, high mechanical strength and adsorption capacity, and controllable morphology. Pure and modified carbon nanomaterials have been successfully used to purify target analytes from agricultural products. Given their unique physical and chemical properties, MNs and MONs have attracted significant interest for use in sample preparation. MNs and MONs with excellent thermal and mechanical stabilities show good resistance to a wide pH range and diverse organic solvents, which is crucial in adsorbent-based extraction methods. The surface of these materials can be easily modified with various ligands to improve their selectivity. MOFs and COFs present many advantages such as large specific surface areas, high porosity, adjustable pore performance, and good thermal stability. Several methods that employ novel adsorbent materials to analyze pollutants in a variety of agricultural products, such as chromatography, spectroscopy, mass spectrometry, and other detection technologies, have been established. This paper also reviews the application of adsorbent materials in the analysis of agricultural product quality and safety, and discusses the future development trends of these sorbents in sample preparation for the safety analysis of agricultural products.

Six new lipids, trichoderols B-G ( 1 - 6 ), along with a known one, triharzianin B ( 7 ), were isolated from the culture of Trichoderma sp. Z43 obtained from the surface of the marine brown alga Dictyopteris divaricata . Their structures and relative configurations were identified by interpretation of 1D/2D NMR and MS data. Compounds 1 - 7 were assayed for inhibiting the growth of three phytopathogenic fungi ( Fusarium graminearum , Gaeumannomyces graminis , and Glomerella cingulata ), four marine phytoplankton species ( Amphidinium carterae , Heterocapsa circularisquama , Heterosigma akashiwo , and Prorocentrum donghaiense ), and one marine zooplankton ( Artemia salina ). Compounds 1 , 4 , and 7 exhibited weak antifungal activities against three phytopathogenic fungi tested with MIC ≥ 64 μg/mL. All compounds displayed moderate antimicroalgal activity with IC 50 ≥ 15 μg/mL and low toxicity to the brine shrimp Artemia salina .

Uric acid (UA) is the final product of purine metabolism in human body,and its metabolic disorder will induce hyperuricemia (HUA).The occurrence and development of HUA are associated with a variety of pathological mechanisms such as oxidative stress injury,activation of inflammatory cytokines,and activation of renin-angiotensin-aldosterone system.These mechanisms directly or indirectly affect the bioavailability of endogenous nitric oxide (NO).The decrease in NO bioavailability is common in the diseases with high concentration of UA as an independent risk factor.In this review,we summarize the mechanisms by which high concentrations of UA affect the endogenous NO bioavailability,with a focus on the mechanisms of high-concentration UA in decreasing the synthesis and/or increasing the consumption of NO.This review aims to provide references for alleviating the multisystem symptoms and improving the prognosis of HUA,and lay a theoretical foundation for in-depth study of the correlations between HUA and other metabolic diseases.

Taking the soil of a vegetable planting area in Wanquan District of Zhangjiakou City as the research object, 132 surface and 80 deep soil samples were collected to test and analyze the contents of eight heavy metals such as As, Cd, Cr, Hg, Cu, Ni, Pb, and Zn and the occurrence forms of Cr and Ni. By applying geostatistical analysis and the PMF receptor model and combining three heavy metal pollution evaluation methods, the spatial distribution characteristics of soil heavy metals in the study area, the degree of heavy metal pollution, and the distribution of Cr and Ni fugitive forms in the vertical layer were clarified, and the sources and contribution rates of soil heavy metal pollution were analyzed. The results showed that the average contents of Cd and Pb in surface soils were higher than the background values of soils in Hebei Province, and the spatial distribution characteristics of Cr, Ni, Cu, Cd, Pb, and Zn in surface soils were similar. The ground accumulation index method showed that the study area was mainly free of pollution, with a small number of lightly polluted sites, and most of them were polluted with Cd. The enrichment factor method showed that the study area was mainly free-weakly polluted, with medium pollution of all elements; the significantly polluted elements in the background area were As, Pb, and Hg, and the significantly polluted element in the key area was Cd. The potential ecological risk index method showed that the study area was mainly lightly polluted, with local distribution. The potential ecological risk index method showed that the study area was mainly lightly polluted, with a local distribution of "medium" and "strong" risk points, with "very strong" risk points for Hg in the background area and "very strong" risk points for Cd in the focus area. These three evaluation results indicated that the background area was dominated by Cd and Hg pollution, whereas the focus area was dominated by Cd pollution. The study on the fugitive morphology of vertical soil showed that Cr was dominated by the residue state (F4) and supplemented by the oxidizable state (F3), and the vertical direction was dominated by the surface aggregation type and supplemented by the weak migration type. Ni was dominated by the residue state (F4) and supplemented by the reducible state (F2), and the vertical direction was dominated by the strong migration type and supplemented by the weak migration type. The sources of heavy metals in the surface soil were divided into three categories; Cr, Cu, and Ni were mainly from natural geological background sources. The contributions of Cr, Cu, and Ni were 66.9%, 66.9%, and 76.1%, respectively. As, Cd, Pb, and Zn were mainly from anthropogenic sources, with contributions of 77.38%, 59.2%, 83.5%, and 59.5%, respectively. Hg was mainly from dry and wet atmospheric deposition, with a contribution of 87.8%.

Stroke prognosis is negatively associated with an elevation of serum bilirubin, but how bilirubin worsens outcomes remains mysterious. We report that post-, but not pre-, stroke bilirubin levels among inpatients scale with infarct volume. In mouse models, bilirubin increases neuronal excitability and ischemic infarct, whereas ischemic insults induce the release of endogenous bilirubin, all of which are attenuated by knockout of the TRPM2 channel or its antagonist A23. Independent of canonical TRPM2 intracellular agonists, bilirubin and its metabolic derivatives gate the channel opening, whereas A23 antagonizes it by binding to the same cavity. Knocking in a loss of binding point mutation for bilirubin, TRPM2-D1066A, effectively antagonizes ischemic neurotoxicity in mice. These findings suggest a vicious cycle of stroke injury in which initial ischemic insults trigger the release of endogenous bilirubin from injured cells, which potentially acts as a volume neurotransmitter to activate TRPM2 channels, aggravating Ca 2+ -dependent brain injury., Competing Interests: Declaration of interests We have filed a patent application for the bilirubin-binding cavity on the TRPM2 channel for developing therapeutics to treat brain injury in stroke and jaundice., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Eight myrochromanol analogues, including three pairs of epimers at C-2 with the myrochromanol scaffold and two examples of myrochromanol with sugar moiety linked at C-4, together with twelve trichothecene derivatives were isolated from the cultures of a shellfish-derived fungus Albifimbria verrucaria CD1-4. Among them, eight compounds named 2-epi-myrochromanol, ent-myrochromanol B, 4-epi-myrochromanol B, 2-epi-myrochromanol A, myrochromanosides A and B, 6',7'-erythro-(2'E,4'Z)-trichoverrol B, 3R,8S-dihyroxyroridin H were previously undescribed fungal metabolites. Their planar structures and relative configurations were established by 1D and 2D NMR, and HR-MS data analysis, and their absolute configurations were determined using the modified Mosher's method and electronic circular dichrosim calculations. Almost all isolates were evaluated for growth rate inhibition of three marine harmful microalgae Chattonella marina, Heterosigma akashiwo, and Prorocentrum donghaiense, and lethal activity to one marine zooplankton, Artemia salina. Myrochromanosides A and B exhibited obvious inhibitory against three tested microalgae with IC 50 values in the range of 9.2-108.9 μM. 8α-Hydroxyroridin H, roridin A and verrucarin A exhibited significant inhibition against P. donghaiense with IC 50 values of 6.1, 5.8, and 6.0 μM and toxicity against brine shrimp larvae with LC 50 values of 1.4, 2.8, and 0.26 μM, respectively., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

This meta-analysis aims to systemically evaluate the efficacy of vacuum sealing drainage (VSD) combined with autologous platelet-rich plasma (PRP) in the treatment of diabetic foot ulcers (DFU). The China HowNet, China Biomedical Literature, VIP periodical resource integration service platform, Wanfang, Embase, Cochrane Central, and PubMed databases were retrieved using the computer. The retrieval period was up to July 2021. Randomised controlled trials on VSD combined with PRP in the treatment of DFU were collected. Those trials that met the inclusion criteria were included for meta-analysis using RevMan 5.3 software. A total of 13 articles were included. In the trial group, 477 patients with DFU were treated with VSD combined with PRP, while in the control group, 482 patients with DFU were treated with conventional dressings and/or VSD. The meta-analysis showed that, compared with the control group, VSD combined with PRP has significant advantages in shortening healing time (standardised mean difference [SMD] = -0.87, 95% confidence interval [CI]: -1.07 to -0.67, P < .00001), improving ulcer healing rates (odds ratio = 4.01, 95% CI: 2.95 ~ 5.46, P < .00001), and reducing hospital stays (mean difference = -15.29, 95% CI: -16.05 to -14.54, P < .00001), but the differences in dressing change times (SMD = -1.27, 95% CI: -2.71 to 0.17, P = .08) and hospitalisation expenses (SMD = -0.16, 95% CI: -13.40 to 13.07, P = .98) were not statistically significant. VSD combined with autologous PRP has good curative efficacy in the treatment of DFU and is a better treatment option. However, this treatment is limited in patients with platelet dysfunction, thrombocytopenia, leukaemia, and poor general condition., (© 2022 The Authors. International Wound Journal published by Medicalhelplines.com Inc (3M) and John Wiley & Sons Ltd.)

The vegetable planting base in the Beixintun area of Zhangjiakou City was selected as the study area, divided into the focus area and regional range as well as the upstream area. A total of 132 surface soil samples, 16 vertical soil profiles, 3 groups of surface profiles, and 4 samples each of colored pepper fruit, purple kale fruit, and corn fruit were collected. From the soil, rock, and crop sample Sc, Cr, Mo, Cd, V, Zn, Sr, Pb, Co Ni, Cu, Ge, and REE on the basis of the referenced germanium (Ge) enrichment standards and enrichment factor levels, it was found that the regional Ge enrichment rate was not high (19.7%), whereas the key area had a high Ge enrichment rate (52%). The spatial distribution of Ge and rare earth elements in the soils of the regional scope and the focal area showed a more obvious consistency, and further comparison of the correlation characteristics of Ge and rare earth elements in soil and crops showed that the ranking of rare earth content was purple kale>colored pepper>maize, whereas the ranking of the Ge element uptake intensity was maize (weak uptake)>purple kale (very weak uptake)>colored pepper (very weak uptake), and there was no obvious synergy between the uptake of Ge and rare earth elements by crops. The PMF and RDA analysis of 28 elements and indicators of soil in the study area showed that the source of regional Ge was dominated by natural geological background factors (66.3%), supplemented by anthropogenic activity-influenced factors (27%) and river deposition factors (6.7%). The source of Ge in the focal area was dominated by natural geological background factors (33.8%) and anthropogenic activity-influenced factors (27.2%), with river sedimentation factors (18.5%) and atmospheric dry and wet deposition factors Ge (20.5%) being supplemented. Soil Ge was positively correlated with rare earth elements and trace elements such as Cd, Zn, Mn, Ni, V, Co, and Cr and negatively correlated with the main elements ČNa 2 [KG-*2/5]O, SiO 2 , and K 2 [KG-*2/5]O and pH. Finally, by combining the analysis of soil lateral profiles with vertical profiles, it was found that the Ge migrating from the source area to the area was primarily in the main river pathway, supplemented by the secondary river and flood flow pathways.

Objective: To investigate the safety and efficacy of reinforced radiculoplasty in the treatment of symptomatic sacral Tarlov cysts (TCs)., Methods: A retrospective analysis was performed on the clinical data and follow-up data of 71 patients with symptomatic sacral TCs who underwent reinforced radiculoplasty in the Neurosurgery Department of Peking University Third Hospital from June 2018 to March 2021. All the operations were performed under neuroelectrophysiological monitoring. Intraoperative cyst exploration, partial resection of the cyst wall, narrowing of the leak, nerve root sleeve radiculoplasty and artificial dural reinforcement were performed. The incidence of postoperative complications and new neurological dysfunction was analyzed. Visual analogue scale (VAS) was used to assess the changes of pain before and after surgery. The Japanese Orthopedics Association (JOA) low back pain score was used to evaluate the changes in nerve function before and after surgery., Results: In the study, 71 patients had 101 TCs, 19 (18.8%) TCs originated from the left S1 nerve, 26 (25.7%) originated from the left S2 nerve, 3 (3.0%) originated from the left S3 nerve, 14 (13.9%) originated from the right S1 nerve, 33 (32.7%) originated from the right S2 nerve, 6 (5.9%) originated from the right S3 nerve, all the TCs underwent reinforced radiculoplasty. Deep infection (1 case), subcutaneous effusion (1 case), fat li-quefaction (1 case) and urinary tract infection (4 cases) were recorded postoperatively. The patients were followed up for 12-43 months (median, 26 months). Two cases had new urinary retention after operation, and the catheter was removed at the end of the first and second months respectively. One case had new fecal weakness, which improved after 3 months. Compared with preoperation, VAS decreased significantly at the last follow-up [median, 6 (4-9) vs . 1 (0-5), Z =-7.272, P < 0.001], JOA score increased significantly [median, 20 (16-25) vs . 27 (18-29), Z =-7.265, P < 0.001]. There were 18 cured cases (25.4%), 41 excellent cases (57.7%), 8 effective cases (11.3%), and 4 invalid cases (5.6%). The total efficiency was 94.4% (67/71). Two (1.98%) cysts recurred., Conclusion: For patients with symptomatic sacral TCs, reinforced radiculoplasty can significantly improve the pain and nerve function, which is safe and reliable.

Objective: The purpose of this study was to investigate whether integrin levels are associated with axon regeneration after central nervous system (CNS) injury., Materials and Methods: By using immunohistochemistry, we performed a detailed investigation of the changes in and colocalization of integrins αv and α5, with Nogo-A in the retina after optic nerve injury., Results: We confirmed that integrins αv and α5 were expressed in the rat retina and colocalized with Nogo-A. After optic nerve transection, we found that integrin α5 levels increased over 7 days, but integrin αv levels remained unchanged, while Nogo-A levels increased., Conclusions: It seems that the inhibition of axonal regeneration by the Amino-Nogo-integrin signaling pathway may not occur via changes in integrin levels.

Growing evidence has indicated that circular RNAs (circRNAs) play crucial roles in the tumorigenesis and progression of diverse malignancies. However, the majority of circRNAs involved in esophageal squamous cell carcinoma (ESCC) remain undefined and the exact functions and underlying mechanisms of circRNAs in ESCC still need further exploration. In this study, we identified a novel onco-circRNA hsa&#95;circ&#95;0002938, derived from the exons of cysteine-rich transmembrane BMP regulator 1 (CRIM1) pre-mRNA, referred to as circCRIM1. We found that the expression of circCRIM1 was higher in ESCC tissues, compared to para-carcinoma tissues. Increased expression of circCRIM1 was positively correlated with clinical parameters of ESCC patients including tumor-node-metastasis (TNM) stage, tumor invasion range, and lymph node metastasis. Functionally, the results from the experiments in vitro showed that the knockdown of circCRIM1 suppressed proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) in ESCC cells. By conducting bioinformatics algorithms analyses and microRNA (miRNA) rescue experiments, we found that circCRIM1 could act as a competing endogenous RNA (ceRNA) to sponge miR-342-3p in ESCC cells, and thereby upregulated the expression of transcription factor 12 (TCF12), a key regulator promoting the EMT process. Taken together, circCRIM1 facilitates the progression of ESCC by sponging miR-342-3p to regulate TCF12 and promote EMT, and the circCRIM1/miR-342-3p/TCF12 axis may be regarded as a potential predictive biomarker and therapeutic target for treating ESCC.

Objective: Dose de-escalation of adjuvant therapy (DART) in patients with HPV(+)OPSCC was investigated in two prospective Phase II and III clinical trials (MC1273 and MC1675). We report the 30-day morbidity and mortality associated with primary TORS resection in patients enrolled in these trials., Materials and Methods: Patients with HPV(+)OPSCC, who underwent TORS resection between 2013 and 2020 were considered in this analysis. The severity of postoperative transoral bleeding was graded using both the Hinni Grade (HG) transoral surgery bleeding scale and the Common Terminology for Adverse Events (CTCAE) v5.0. Post-surgical complications within 30 days of surgery, as well as rates of tracheostomy, PEG and nasogastric tube placement., Results: 219 patients were included. A total of 7 (3.2 %) patients had a tracheostomy placed at the time of surgery, and all were decannulated within 26 days (median: 5, range: 2-26). There were 33 (15.1 %) returns to the emergency department (ED) with 10 (4.6 %) patients requiring readmission. Using the HG scale, 10 (4.6 %) patients experienced ≥ Grade 3 bleeding with no Grade 5 or 6 bleeds. In contrast, using the CTCAE scale, 15 patients (6.8 %) experienced ≥ Grade 3 bleeding with no Grade 5 bleeds. There was one post-operative death in a patient withdrawn from the trial, and no deaths related to hemorrhage., Conclusion and Relevance: TORS for HPV(+)OPSCC in carefully selected patients at a high volume center was associated with low morbidity and mortality., 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 © 2022 Elsevier Ltd. All rights reserved.)