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Ze-Jiao He,1,2,&ast; Tao Hu,3,&ast; Zi-Shu Zhang,3 Tian-Cheng Wang,3 Wei Huang3 1Guizhou Medical University, Guiyang, Guizhou, People’s Republic of China; 2Department of Radiology, The First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang, People’s Republic of China; 3Department of Radiology, The Second Xiangya Hospital of Central South University, Changsha, 410011, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wei Huang, Department of Radiology, The Second Xiangya Hospital of Central South University, 139 Renmin Middle Road, Changsha, 410011, People’s Republic of China, Email 2204150303@csu.edu.cnBackground: Bone mineral density (BMD) and monocyte-to-lymphocyte ratio (MLR) were recently identified as novel risk factors for patients with several malignancies. The objective of this study was to validate the role of preoperative BMD/MLR as a potential prognostic biomarker in patients with hepatocellular carcinoma (HCC) undergoing liver resection.Methods: This investigation enrolled 442 adult patients diagnosed with HCC who underwent liver resection. The patients were classified into high- and low-BMD/MLR groups based on the median, and forward stepwise logistic regression was employed to identify independent predictors for early HCC recurrence. To mitigate the impact of confounding factors, a propensity score matching (PSM) analysis was conducted between patients in the high- and low-BMD/MLR groups. The Kaplan-Meier method was employed to assess and compare the disease-free survival (DFS) and overall survival (OS) between the two cohorts.Results: The study categorized patients into high-BMD/MLR and low-BMD/MLR groups. Forward stepwise logistic regression analysis revealed that low BMD/MLR (P < 0.001), tumor size > 50 mm (P < 0.001), and AFP > 200 ug/L (P = 0.001) were significantly associated with the early recurrence of HCC. Moreover, the results suggested that DFS and OS were significantly shorter in the low-BMD/MLR group compared to the high-BMD/MLR group, both before and after PSM (P < 0.05).Conclusion: Preoperative BMD/MLR held promise as a prognostic biomarker for early recurrence and prognosis in patients with HCC who underwent liver resection. Furthermore, the integration of tumor size, AFP level, and BMD/MLR demonstrated a robust predictive capacity for early recurrence within this patient population.Keywords: hepatocellular carcinoma, resection, bone mineral density, recurrence, prognosis

Zi-jun He,1,2,&ast; Jin-tao Wei,1,&ast; Hai-mei Jiang,1 Jin-yong Wang,1 Jiong-yao Lai,1 Shu-qing Li,1 Zhi Chen,1 Qing-lu Luo1– 3 1Department of Rehabilitation Medicine, The Tenth Affiliated Hospital of Southern Medical University (Dongguan People’s Hospital), Dongguan, People’s Republic of China; 2Dongguan Experimental Centre for Sports Rehabilitation Research, Dongguan, People’s Republic of China; 3Dongguan Key Specialty of Traditional Chinese Medicine (Rehabilitation Department), Dongguan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qing-lu Luo; Zhi Chen, Department of Rehabilitation Medicine, The Tenth Affiliated Hospital of Southern Medical University (Dongguan People’s hospital), Wanjiang District, Dongguan, Guangdong, 510280, People’s Republic of China, Email luo_qinglu@126.com; 13686616688@139.comObjective: To identify distinct developmental trajectories of weight-bearing pain (WBP) and non-weight-bearing pain (NWBP) and examine the trajectory predictors in individuals with or at risk of knee osteoarthritis.Methods: We included 971 participants from the Osteoarthritis Initiative whose baseline magnetic resonance imaging data and 9-year follow-up data on pain were available. We applied group-based trajectory modeling to identify WBP and NWBP trajectories over 9 years. Univariate and multivariate multinomial logistic regression analyses were performed to examine the predictors of identified trajectories.Results: Three distinct WBP trajectories were identified: “no pain” (32.4%), “mild pain” (44.6%), and “moderate pain” (23%). Three distinct NWBP trajectories were identified: “no pain” (50.9%), “mild pain” (33.4%), and “moderate pain” (15.7%). In multivariate analyses, high body mass index, depression, multisite pain, radiographic knee OA, and comorbidities were associated with worse development trajectories for WBP and NWBP. Weak quadriceps strength and bone marrow lesion were only associated with worse WBP trajectories, whereas low education level was only associated with worse NWBP trajectories.Conclusion: The developmental course of pain is heterogeneous in WBP or NWBP. Quadriceps strength and bone marrow leisure may be WBP-specific predictors, whereas education level may be a NWBP-specific predictor. The assessment of knee pain should be more accurate, which may help select appropriate therapeutic targets.Keywords: knee osteoarthritis, pain, weight-bearing, trajectories, predictors

Wen Wu,1,2,&ast; Yu-Pei Zhang,1,2,&ast; Yu-Meng Pan,2 Zhen-Jie He,1,2 Yan-Ping Tan,1 Ding-Deng Wang,1,2 Xing-Guang Qu,1,2 Zhao-Hui Zhang1,2 1Department of Critical Care Medicine, Yichang Central People’s Hospital, Yichang, Hubei, 443003, People’s Republic of China; 2The First College of Clinical Medical Science, China Three Gorges University, Yichang, Hubei, 443003, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhao-Hui Zhang, Department of Critical Care Medicine, Yichang Central People’s Hospital, Yichang, 443003, Hubei, People’s Republic of China, Tel/Fax +86-0717-6481546, Email zhaohuizhang0630@163.comPurpose: This study aims to evaluate the predictive efficacy of the C-reactive protein/albumin ratio (CAR), a cost-effective, easily accessible, and reproducible biomarker obtained from standard blood tests, in forecasting acute kidney injury (AKI) among patients undergoing acute pancreatitis (AP). Considering that changes in the CAR are associated with AKI incidence in AP cases, this work aims to explore whether CAR can be used as the innovative, inflammation-based diagnostic marker for AKI in AP patients.Methods: The current retrospective cohort study consecutively enrolled AP patients admitted to First College of Clinical Medical Science of China Three Gorges University during the period from January 2019 to October 2023. Data were extracted systematically in electronic medical records from these hospitalized individuals, including baseline demographic and clinical characteristics. To ascertain the association of the CAR level with the development of AKI, we carried out multivariate logistic regression, adjusting for potential confounders. These confounders were initially identified through univariate regression. Furthermore, the potential effect modifiers in the relationship between CAR and AKI occurrence were explored by stratified logistic regression.Results: Totally, 1514 AP were recruited, including 257 (16.9%) with AKI. CAR was positively correlated with AKI. When adjusting for potential confounders, the AKI risk in patients in the upper CAR tertile (2.628– 22.994) increased by 83% relative to those in lower tertile (0.05– 0.289) (OR 1.83, 95% CI 1.13– 2.96, P = 0.013). The AKI risk tended to increase according to the increasing CAR tertile (P for trend = 0.013). No significant interactions were observed among subgroups based on age, sex, BMI, admission to ICU, hypertension, DM, chronic obstructive pulmonary disease, severity of AP, etiology of AP, demand for CRRT, mechanical ventilation, and blood transfusion (all P > 0.05).Conclusion: A higher CAR is significantly related to the higher AKI incidence in AP patients in the Chinese population.Keywords: acute pancreatitis, acute kidney injury, CRP/albumin ratio, cohort study

Fei Pei,1,2,* Guan-Rong Zhang,3,* Li-Xin Zhou,4 Ji-Yun Liu,5 Gang Ma,6 Qiu-Ye Kou,7 Zhi-Jie He,8 Min-Ying Chen,1 Yao Nie,1 Jian-Feng Wu,1,2 Xiang-Dong Guan1 On behalf of the China Critical Care Immunotherapy Research Group1Department of Critical Care Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, People’s Republic of China; 2Clinical Trial Unit, The First Affiliated Hospital, Sun Yat-sen University & The University of Birmingham, Guangzhou 510080, People’s Republic of China; 3Information and Statistics Center, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, People’s Republic of China; 4Department of Critical Care Medicine, Foshan First Municipal People’s Hospital, Foshan 528000, People’s Republic of China; 5Department of Critical Care Medicine, Guangzhou First Municipal People’s Hospital, Guangzhou 510180, People’s Republic of China; 6Department of Critical Care Medicine, Sun Yat-sen University Cancer Center, Sun Yat-sen University, Guangzhou 510060, People’s Republic of China; 7Department of Critical Care Medicine, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, People’s Republic of China; 8Department of Critical Care Medicine, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jian-Feng Wu Email wujianf@mail.sysu.edu.cnXiang-Dong Guan Email guanxiangdong1962@163.comPurpose: Although immune dysfunction has been investigated in adult septic patients, early immune status remains unclear. In this study, our primary aim was to assess early immune status in adult patients with sepsis stratified by age and its relevance to hospital mortality.Patients and Methods: A post hoc analysis of a multicenter, randomized controlled trial was conducted; 273 patients whose immune status was evaluated within 48 hours after onset of sepsis were enrolled. Early immune status was evaluated by the percentage of monocyte human leukocyte antigen-DR (mHLA-DR) in total monocytes within 48 hours after onset of sepsis and it was classified as immunoparalysis (mHLA-DR ≤ 30%) or non-immunoparalysis (> 30%). Three logistic regression models were conducted to explore the associations between early immunoparalysis and hospital mortality. We also developed two sensitivity analyses to find out whether the definition of early immune status (24 hours vs 48 hours after onset of sepsis) and immunotherapy affect the primary outcome.Results: Of the 181 elderly (≥ 60yrs) and 92 non-elderly (< 60yrs) septic patients, 71 (39.2%) and 25 (27.2%) died in hospital, respectively. The percentage of early immunoparalysis in the elderly was twice of that in the non-elderly patients (32% vs 16%, p=0.006). For the elderly, hospital mortality was higher in the immunoparalysis ones than the non-immunoparalysis ones (53.4% vs 32.5%, p=0.009). But there was no significant difference in hospital mortality between immunoparalysis non-elderly patients and non-immunoparalysis non-elderly ones (33.5% vs 26.0%, p=0.541). By means of logistic regression models, we found that early immunoparalysis was independently associated with increased hospital mortality in elderly, but not in non-elderly patients. Sensitivity analysis further confirmed the definition of early immune status and immunotherapy did not affect the outcomes.Conclusion: The elderly were more susceptible to early immunoparalysis after onset of sepsis. Early immunoparalysis was independently associated with poor prognosis in elderly, but not in non-elderly patients.Keywords: early immune status, elderly, mHLA-DR, immunosuppression, immunoparalysis, sepsis

Teng Leng Ooi, 1 Zijiang J He 2 1College of Optometry, The Ohio State University, Columbus, OH, USA; 2Department of Psychological and Brain Sciences, University of Louisville, Louisville, KY, USACorrespondence: Teng Leng OoiCollege of Optometry, The Ohio State University, 338 West 10th Ave, Columbus, OH 43210, USATel +1 614 292 1384Fax +1 614 292 7493Email ooi.22@osu.eduAbstract: Eye dominance refers to the preference to use one eye more than the fellow eye to accomplish a task. However, the dominant eye revealed can be task dependent especially when the tasks are as diverse as instructing the observer to sight a target through a ring, or to report which half-image is perceived more of during binocular rivalry stimulation. Conventionally, the former task is said to reveal motor eye dominance while the latter task reveals sensory eye dominance. While the consensus is that the motor and sensory-dominant eye could be different in some observers, the reason for it is still unclear and has not been much researched. This review mainly focuses on advances made in recent studies of sensory eye dominance. It reviews studies conducted to quantify and relate sensory eye dominance to other visual functions, in particular to stereopsis, as well as studies conducted to explore its plasticity. It is recognized that sensory eye dominance in observers with clinically normal vision shares some similarity with amblyopia at least at the behavioral level, in that both exhibit an imbalance of interocular inhibition. Furthermore, sensory eye dominance is probably manifested at multiple sites along the visual pathway, perhaps including the level of ocular dominance columns. But future studies with high-resolution brain imaging approaches are required to confirm this speculation in the human visual system.Keywords: amblyopia, binocular combination, binocular rivalry, excitatory-inhibitory balance, plasticity, stereopsis

Xiao-Ai Chen1,5*, Li-Jun Zhang2*, Zhi-Jie He3, Wei-Wei Wang4, Bo Xu1, Qian Zhong1, Xin-Tao Shuai4, Li-Qun Yang4, Yu-Bin Deng11Department of Pathophysiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China; 2Futian Affiliated Hospital, Guangdong Medical College, Shenzhen, China; 3Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China; 4Institute of Polymer Science, School of Chemistry and Chemical Engineering, BME Center, State Key Laboratory of Optoelectronic Materials and Technologies, Sun Yat-sen University, Guangzhou, China; 5Yunnan Cancer Hospital, The Third Affiliated Hospital, Kunming Medical College, Kunming, China*Both authors contributed equally to this workBackground: Mesenchymal stem cell transplantation is a promising method in regenerative medicine. Gene-modified mesenchymal stem cells possess superior characteristics of specific tissue differentiation, resistance to apoptosis, and directional migration. Viral vectors have the disadvantages of potential immunogenicity, carcinogenicity, and complicated synthetic procedures. Polyethylene glycol-grafted polyethylenimine (PEG-PEI) holds promise in gene delivery because of easy preparation and potentially targeting modification.Methods: A PEG8k-PEI25k graft copolymer was synthesized. Agarose gel retardation assay and dynamic light scattering were used to determine the properties of the nanoparticles. MTT reduction, wound and healing, and differentiation assays were used to test the cytobiological characteristics of rat mesenchymal stem cells, fluorescence microscopy and flow cytometry were used to determine transfection efficiency, and atomic force microscopy was used to evaluate the interaction between PEG-PEI/plasmid nanoparticles and mesenchymal stem cells.Results: After incubation with the copolymer, the bionomics of mesenchymal stem cells showed no significant change. The mesenchymal stem cells still maintained high viability, resettled the wound area, and differentiated into adipocytes and osteoblasts. The PEG-PEI completely packed plasmid and condensed plasmid into stable nanoparticles of 100–150 nm diameter. After optimizing the N/P ratio, the PEG-PEI/plasmid microcapsules delivered plasmid into mesenchymal stem cells and obtained an optimum transfection efficiency of 15%–21%, which was higher than for cationic liposomes.Conclusion: These data indicate that PEG-PEI is a valid gene delivery agent and has better transfection efficiency than cationic liposomes in mesenchymal stem cells.Keywords: stem cells, gene delivery, nanoparticles, atomic force microscopy

A one-pot Nazarov cyclization/oxidative 1,2-carbon rearrangement/Ritter reaction has been explored for the first time, facilitating the synthesis of the unprecedented 2,3-disubstituted-5-quaternary-4-amidocyclopent-2-enone and 2-quaternary-3-amidoindanones. This transformation features convenient operation, good yields (up to 70%), and good to excellent diastereoselectivity (up to 20 : 1). The proposed reaction mechanism is supported by some experimental results.

Background: Oral squamous cell carcinoma (OSCC) is one of the most common malignancies. However, there is no effective treatment for OSCC., Purpose: This study aimed to identify a natural compound with significant efficacy against OSCC and elucidate its primary mechanism of action., Methods: An FDA-approved drug library and an MCE autophagy-related molecular compound library were screened through high-throughput screening to identify an effective natural compound against OSCC. The IC50 value of sanguinarine (Sang) in OSCC cells was determined using a CCK8 assay. Immunoblotting and immunofluorescence staining were used to assess the effect of Sang on autophagic flux in OSCC cells. Changes in the acidic lysosomal environment were evaluated using RFP-GFP-LC3B and LysoSensor Green DND-189. Furthermore, limited proteolysis-coupled mass spectrometry (LiP-MS) and virtual screening techniques were utilized to identify direct binding targets of Sang, which were subsequently validated by surface plasmon resonance (SPR) and microscale thermophoresis (MST). Molecular docking combined with molecular dynamics analysis identified the binding site between the target protein and Sang. In vitro and in vivo investigations with mutant plasmids confirmed this finding., Results: Screening led to the identification of the naturally occurring autophagy modulator Sang as a potent inhibitor of OSCC progression. Moreover, Sang impaired lysosomal function through reducing lysosomal-associated membrane proteins, inhibiting lysosomal proteolysis, and altering the lysosomal pH. These effects contributed to defects in autophagic clearance and subsequently suppressed OSCC progression. Notably, Sang bound the phenylalanine 26 (F26) residue in pyruvate kinase M2 (PKM2) and inhibited PKM2 enzymatic activity, subsequently suppressing transcription factor EB (TFEB) expression to inhibit lysosomal function and blocking autophagic flux in OSCC cells., Conclusion: Our results demonstrate for the first time that Sang can suppress the PKM2/TFEB axis, and influence lysosomal function, thereby blocking autophagy and inhibiting the progression of OSCC, making it a promising therapeutic option for the treatment of OSCC., 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 GmbH. All rights reserved.)

A new aglycone derivative ( 1 ) and five known compounds ( 2-6 ) have been isolated from a saprophytic fungus Tubeufia rubra for the first time. Their structures and absolute configurations were determined by nuclear magnetic resonance, high resolution mass spectrometry data and electronic circular dichroism. The bioactivities of all compounds were evaluated by cell analysis. Compound 5 showed significant toxicity to human cancer A549 cells, and the IC 50 value was 32. 89 μg/mL. Compound 6 could reverse the multidrug resistance of A549/DDP cells, and the reversal value was 2.92. With the extension of the action time, the IC50 value of compound 6 decreased from 424.72 μg/mL at 24 h to 9.45 μg/mL at 72 h.

Lignin is a promising feedstock for producing vanillin, one of the most extensively used flavor enhancers. However, the biotransformation performance of lignin derivatives into vanillin is still unsatisfactory. In this study, an efficient conversion strategy of lignin into vanillin was established by employing engineered Saccharomyces cerevisiae as a whole-cell biocatalyst. Optimization of cell culture media and whole-cell bioconversion improved the production efficiency of vanillin. The vanillin titer reached 15.3 mM with a molar yield of 71 % in fed-batch fermentation mode, while incorporating in-situ product separation, demonstrated a remarkable 2.6-fold increase. The whole-cell bioconversion, coupled with in-situ separation, successfully converted real lignin hydrolysate into a record vanillin titer of 21.1 mM, equivalent to 1.8 mg of vanillin per gram of wheat bran biomass. The whole-cell bioconversion process integrated in-situ product separation, represents a sustainable approach for vanillin production and offers a promising pathway for lignin valorization., 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.)

Purpose: Binocular depth discrimination in the near distance range (< 2 m) improves with stimulus duration. However, whether the same response-pattern holds in the intermediate distance range (approximately 2-25 m) remains unknown because the spatial coding mechanisms are thought to be different., Methods: We used the two-interval forced choice procedure to measure absolute depth discrimination of paired asynchronous targets (3, 6, or 16 arc min). The paired targets (0.2 degrees) were located over a distance and height range, respectively, of 4.5 to 7.0 m and 0.15 to 0.7 m. Experiment 1 estimated duration thresholds for binocular depth discrimination at varying target durations (40-1610 ms), in the presence of a 2 × 6 array of parallel texture-elements spanning 1.5 × 5.83 m on the floor. The texture-elements provided a visible background in the light-tight room (9 × 3 m). Experiment 2 used a similar setup to control for viewing conditions: binocular versus monocular and with versus without texture background. Experiment 3 compared binocular depth discrimination between brief (40, 80, and 125 ms) and continuous texture background presentation., Results: Stimulus duration threshold for depth discrimination decreased with increasing disparity in experiment 1. Experiment 2 revealed depth discrimination performance with texture background was near chance level with monocular viewing. Performance with binocular viewing degraded without texture background. Experiment 3 showed continuous texture background presentation enhances binocular depth discrimination., Conclusions: Absolute depth discrimination improves with target duration, binocular viewing, and texture background. Performance further improved with longer background duration underscoring the role of ground surface representation in spatial coding.

Purpose: The aim of this study was to explore the potential correlation between the nuclear receptor subfamily 3 group C member 2 (NR3C2) and outcomes of colon cancer, along with the mechanisms underlying this association., Method: mRNA (messenger RNA) data and clinical records pertaining to colon cancer were retrieved from The Cancer Genome Atlas (TCGA) database. The analysis of NR3C2 expression discrepancies between normal colon and tumor tissues was conducted using R software. In addition, we also studied the relationship between NR3C2 expression and prognosis, pathological parameters. The relative role of NR3C2 were further predicted through bioinformatics methods and receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value of NR3C2 in colon cancer. Single-cell data from colon cancer samples in the GEO (Gene Expression Omnibus) database further investigated the mechanism of the lower survival associated with NR3C2 dysregulation. NR3C2 expression in three fresh colon cancer samples and their respective paracancer samples was determined. Furthermore, colon cancer cell models overexpressing NR3C2 and with knockdown NR3C2 were constructed by lentiviral vector transfection. Cell Counting Kit-8 assay, transplantation of tumors in nude mice and transwell assays were used to examine the proliferation, migration and invasion of colon cancer cells. The effect on the Wnt/β-catenin pathway, activities of cellular autophagy and cell apoptosis were examined by assessing the expression levels of several key proteins, including Bcl-2, Bax, and LC3., Results: We found that NR3C2 was found a significantly lower level in colon cancer tissues than in adjacent tissues, which was associated with distant and lymphatic metastases, clinical stage, and poor clinical outcome, and it was an independent prognostic factor and potential marker of colon cancer. Single-cell transcriptome data identified the subset of circulating T and B cells with high expression of NR3C2, which is involved in TNF signaling pathway. Functional experiments show that downregulation of NR3C2 resultsed in the activation of the Wnt/β-catenin signaling pathway, and promotesd the proliferation and invasion of colon cancer cells while suppressing cell autophagy and apoptosis., Conclusion: NR3C2 may regulate Wnt/β-catenin to affect the proliferation, invasion apoptosis and autophagy of colon cancer, and this axis is a potential target for the treatment of colon cancer., (© 2024. The Author(s).)

We reliably judge locations of static objects when we walk despite the retinal images of these objects moving with every step we take. Here, we showed our brains solve this optical illusion by adopting an allocentric spatial reference frame. We measured perceived target location after the observer walked a short distance from the home base. Supporting the allocentric coding scheme, we found the intrinsic bias , which acts as a spatial reference frame for perceiving location of a dimly lit target in the dark, remained grounded at the home base rather than traveled along with the observer. The path-integration mechanism responsible for this can utilize both active and passive (vestibular) translational motion signals, but only along the horizontal direction. This asymmetric path-integration finding in human visual space perception is reminiscent of the asymmetric spatial memory finding in desert ants, pointing to nature's wondrous and logically simple design for terrestrial creatures., Competing Interests: LZ, WW, TO, ZH No competing interests declared, (© 2023, Zhou et al.)

Pulmonary drug delivery is critical for the treatment of respiratory diseases. However, the human airway surface presents multiple barriers to efficient drug delivery. Here, we report a bottlebrush poly(ethylene glycol) (PEG-BB) nanocarrier that can translocate across all barriers within the human airway surface. Guided by a molecular theory, we design a PEG-BB molecule consisting of a linear backbone densely grafted by many (∼1000) low molecular weight (∼1000 g/mol) polyethylene glycol (PEG) chains; this results in a highly anisotropic, wormlike nanocarrier featuring a contour length of ∼250 nm, a cross-section of ∼20 nm, and a hydrodynamic diameter of ∼40 nm. Using the classic air-liquid-interface culture system to recapitulate essential biological features of the human airway surface, we show that PEG-BB rapidly penetrates through endogenous airway mucus and periciliary brush layer (mesh size of 20-40 nm) to be internalized by cells across the whole epithelium. By quantifying the cellular uptake of polymeric carriers of various molecular architectures and manipulating cell proliferation and endocytosis pathways, we show that the translocation of PEG-BB across the epithelium is driven by bottlebrush architecture-enhanced endocytosis. Our results demonstrate that large, wormlike bottlebrush PEG polymers, if properly designed, can be used as a carrier for pulmonary and mucosal drug delivery.

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors, and the expression and function of an uncharacterized protein RNF214 in HCC are still unknown. Phase separation has recently been observed to participate in the progression of HCC. In this study, we investigated the expression, function, and phase separation of RNF214 in HCC. We found that RNF214 was highly expressed in HCC and associated with poor prognosis. RNF214 functioned as an oncogene to promote the proliferation, migration, and metastasis of HCC. Mechanically, RNF214 underwent phase separation, and the coiled-coil (CC) domain of RNF214 mediated its phase separation. Furthermore, the CC domain was necessary for the oncogenic function of RNF214 in HCC. Taken together, our data favored that phase separation of RNF214 promoted the progression of HCC. RNF214 may be a potential biomarker and therapeutic target for HCC., (© 2024. The Author(s).)

A new alkaloid, neohelicomyine A ( 1 ), along with two known alkaloids ( 2 - 3 ), were isolated from the fermentation of Neohelicomyces hyalosporus PF11-1. The structures of these compounds were elucidated by extensive analyses of spectroscopic methods including 1 D and 2 D NMR, HRESIMS and ECD. The bioactivities of all compounds were evaluated using cellular assays, and compounds 2 and 3 displayed moderate cytotoxicities against human cancer (A549, TCA, RD) cells with IC 50 values of 26-87 μg/mL.

Four new drimane-type sesquiterpenoids and two new nucleoside derivatives (1-6), were isolated from the fungus Helicoma septoconstrictum. Their structures were determined based on the combination of the analysis of their HR-ESI-MS, NMR, ECD calculations data and acid hydrolysis. All the isolated compounds were detected for their bio-activities against MDA-MB-231, A549/DDP, A2780 and HepG2 cell lines. Helicoside C (4) exhibited superior cytotoxicity against the A2780 cell line with IC 50 7.5 ± 1.5 µM. The analysis of reactive oxygen species (ROS) revealed that Helicoside C induced an increase in intracellular ROS. Furthermore, the flow cytometry and mitochondrial membrane potential (MMP) analyses unveiled that Helicoside C mediated mitochondrial-dependent apoptosis in A2780 cells. The western blotting test showed that Helicoside C could suppress the STAT3's phosphorylation. These findings offered crucial support for development of H. septoconstrictum and highlighted the potential application of drimane-type sesquiterpenoids in pharmaceuticals., 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.)

Since its invention in the late 1980s, the air-liquid-interface (ALI) culture system has been the standard in vitro model for studying human airway biology and pulmonary diseases. However, in a conventional ALI system, cells are cultured on a porous plastic membrane that is much stiffer than human airway tissues. Here, we develop a gel-ALI culture system by simply coating the plastic membrane with a thin layer of hydrogel with tunable stiffness matching that of healthy and fibrotic airway tissues. We determine the optimum gel thickness that does not impair the transport of nutrients and biomolecules essential to cell growth. We show that the gel-ALI system allows human bronchial epithelial cells (HBECs) to proliferate and differentiate into pseudostratified epithelium. Furthermore, we discover that HBECs migrate significantly faster on hydrogel substrates with stiffness matching that of fibrotic lung tissues, highlighting the importance of mechanical cues in human airway remodeling. The developed gel-ALI system provides a facile approach to studying the effects of mechanical cues in human airway biology and in modeling pulmonary diseases. NEW & NOTEWORTHY In a conventional ALI system, cells are cultured on a plastic membrane that is much stiffer than human airway tissues. We develop a gel-ALI system by coating the plastic membrane with a thin layer of hydrogel with tunable stiffness matching that of healthy and fibrotic airway tissues. We discover that human bronchial epithelial cells migrate significantly faster on hydrogel substrates with pathological stiffness, highlighting the importance of mechanical cues in human airway remodeling.

The present study aims to investigate the effect of cathepsin K (CatK) on ischemic angiogenesis in high-fat diet fed mice. The mice were subjected to unilateral hindlimb ischemic surgery, and the ischemic blood flow was measured with a laser Doppler blood flow imager. Immunohistochemical staining was used to observe the quantity of new capillaries in the ischemic lower extremity, and Western blot was used to detect the expression of insulin receptor substrate-1 (IRS-1), p-Akt, Akt and vascular endothelial growth factor (VEGF). Firstly, the effect of high-fat diet on ischemic angiogenesis was observed in wild-type mice, which were randomly divided into control group and high-fat diet group and were fed with normal diet or 60% high-fat diet respectively for 16 weeks. The results showed the body weight and the plasma CatK concentration of the high-fat diet group was significantly increased compared with the control group (P < 0.05), and the blood flow recovery of the high-fat diet group was significantly lower than control group (P < 0.05). Then, wild-type and CatK knock out (CatK -/- ) mice were both fed with high-fat diet to further observe the effect and mechanism of CatK on ischemic angiogenesis under high-fat diet. The results showed that the blood flow recovery in the CatK -/- group was significantly greater than the wild-type group, and the number of CD31 positive cells was significantly increased (P < 0.05). At the same time, the protein expression levels of IRS-1, p-Akt and VEGF in the ischemic skeletal muscle were significantly increased in the CatK -/- group compared with the wild-type group (P < 0.05). These results suggest that the deficiency of CatK improves ischemic angiogenesis in high-fat diet fed mice through IRS-1-Akt-VEGF signaling pathway.

Lung cancer has a high incidence rate and requires more effective treatment strategies and drug options for clinical patients. EGFR is a common genetic alteration event in lung cancer that affects patient survival and drug strategy. Our study discovered aberrant aldolase A (ALDOA) expression and dysfunction in lung cancer patients with EGFR mutations. In addition to investigating relevant metabolic processes like glucose uptake, lactate production, and ATPase activity, we examined multi-omics profiles (transcriptomics, proteomics, and pull-down assays). It was observed that phosphodiesterase 3A (PDE3A) enzyme and ALDOA exhibit correlation, and furthermore, they impact M2 macrophage polarization through β-catenin and downstream ID3. In addition to demonstrating the aforementioned mechanism of action, our experiments discovered that the PDE3 inhibitor trequinsin has a substantial impact on lung cancer cell lines with EGFR mutants. The trequinsin medication was found to decrease the M2 macrophage polarization status and several cancer phenotypes, in addition to transduction. These findings have potential prognostic and therapeutic applications for clinical patients with EGFR mutation and lung cancer., 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.)

It is unclear whether the atherogenic index of plasma (AIP) is associated with major adverse cardiovascular events (MACEs) in the general population. A total of 361,644 participants (aged 56.19 ± 8.09 years; 44.79% male) free of a history of MACEs at baseline from the UK Biobank data were included in the analysis. The AIP was calculated using log (triglyceride/high-density lipoprotein-cholesterol). Over a mean follow-up of 12.19 ± 1.60 years, 16,683 participants developed MACEs. After adjustment for traditional risk factors, each 1 unit increase in AIP was associated with a 45.3% higher risk of incident MACEs (hazard ratio (HR), 1.453 [95% confidence interval (CI) 1.371-1.540], P < 0.001). Results were similar when individuals were categorized by the AIP quartiles (HR, 1.283 [95% CI 1.217-1.351]; comparing extreme quartiles). The subgroup analyses showed that the association between AIP and risk of incident MACEs was more obvious in female participants who are < 60 years old and free of hypertension or diabetes. Sensitivity analysis included participants without any lipid-lowering medication or excluded incident MACEs in the first 2 years of follow-up confirming the robustness of the findings. Elevated AIP is a risk factor of incident MACEs in the general population, independent of traditional risk factors.Dynamic monitoring of the AIP may help select the population at high risk of cardiovascular events and guide primary prevention.

Endophytic fungi are an important source of novel antitumor substances. Previously, we isolated an endophytic fungus, Alternaria alstroemeria, from the medicinal plant Artemisia artemisia, whose crude extracts strongly inhibited A549 tumor cells. We obtained a transformant, namely AaLaeA OE26 , which completely loses its antitumor activity due to overexpression of the global regulator AaLaeA. Re-sequencing analysis of the genome revealed that the insertion site was in the noncoding region and did not destroy any other genes. Metabolomics analysis revealed that the level of secondary antitumor metabolic substances was significantly lower in AaLaeA OE26 compared with the wild strain, in particular flavonoids were more downregulated according to the metabolomics analysis. A further comparative transcriptome analysis revealed that a gene encoding FAD-binding domain protein (Fla1) was significantly downregulated. On the other hand, overexpression of AaFla1 led to significant enhancement of antitumor activity against A549 with a sevenfold higher inhibition ratio than the wild strain. At the same time, we also found a significant increase in the accumulation of antitumor metabolites including quercetin, gitogenin, rhodioloside, liensinine, ginsenoside Rg2 and cinobufagin. Our data suggest that the global regulator AaLaeA negatively affects the production of antitumor compounds via controlling the transcription of AaFla1 in endophytic A. alstroemeria., (© 2023 Wiley-VCH GmbH.)

The first organocatalytic diastereoselective (4 + 1) cycloaddition of o -hydroxyphenyl-substituted secondary phosphine oxides (SPOs) has been established, which makes use of o -hydroxyphenyl substituted SPOs as suitable four-atom phosphorus-containing 1,4-dinucleophiles and 3-indolylformaldehydes as competent 1,1-dielectrophiles under Bro̷nsted acid catalysis. The reaction mechanism was suggested to involve the formation of 3-indolylmethanol intermediates and vinyliminium intermediates, which played an important role in controlling the reactivity and diastereoselectivity of the (4 + 1) cycloaddition under Bro̷nsted acid catalysis. By this approach, a series of benzo oxaphospholes bearing P - and C -stereocenters were synthesized in moderate to good yields (50%-95% yields) with excellent diastereoselectivities (all >95:5 dr). This reaction not only represents the first organocatalytic diastereoselective (4 + 1) cycloaddition of o -hydroxyphenyl-substituted SPOs but also provides an efficient and diastereoselective method for the construction of phosphorus-containing benzo five-membered heterocyclic skeletons bearing both P -stereocenter and C -stereocenter.

A 41-month-old boy was presented to our hospital because of an intracranial mass suspected of cerebrovascular malformation. He was admitted and received cerebral angiography. The angiography result confirmed the intracranial mass was the dilated vein of Galen resulting from a pial arteriovenous fistula, which quite resembling the vein of Galen aneurysmal malformation. Considering one-time embolization of the fistula may greatly change the distribution of intracranial blood flow, we decided to perform staged embolization. In the first stage, we partially embolized the fistula, resulting in a sharp decrease in blood flow to the lesion. The second intervention was performed one month later, and completely embolized the fistula. The boy recoverd well and returned to normal childhood without any neurological deficits. Follow-up MR images obtained at 10 months after the last procedure showing total obliteration of the pAVF, gradually shrinking of the varix, and remodeling of the vein of Galen.

Lignocellulosic biomass (LCB) is the promising feedstock for value-added products, which would contribute to the bioeconomy and sustainable development. The efficient pretreatment is still required in the biorefinery of LCB. To make a simultaneous utilization of carbohydrates and lignin, a novel easy-recycled ethylenediamine (EDA) pretreatment was designed and evaluated in the present study. The results highlighted that this pretreatment yielded 96% glucose and 70% xylose in enzymatic hydrolysis. It simultaneously promoted the depolymerization of lignin into small molecules and functionalized the yielded lignin with Schiff base and amide structures. These animated-lignins showed a pH-responsive behavior and the excellent flocculation capacity by reducing more than 90% turbidity of kaolin suspensions. Therefore, easy-recycled EDA pretreatment hold the promise to simultaneously enhance the enzymatic hydrolysis of carbohydrates and endowed the new functionality of lignin toward downstream valorization, which improved the process feasibility and potentially enable the sustainability of LCB utilization., 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.)

Malignant colorectal tumors and precancerous lesions are closely associated with chronic inflammation. Specific dietary patterns can increase chronic inflammation in the body, thereby promoting the occurrence of tumors and precancerous lesions. We have conducted a case-control study in Kashgar Prefecture, Xinjiang, China, to explore the association between the energy-adjusted dietary inflammatory index (E-DII) and the risk of colorectal adenomatous polyps (CAP). A total of 52 newly diagnosed patients with CAP and 192 controls at the First People's Hospital of Kashgar Prefecture were enrolled in this study. Dietary information was collected using a food frequency questionnaire. The E-DII was calculated based on dietary data, reflecting an individual's dietary inflammatory potential. Logistic regression models were used to evaluate the relationship between the E-DII and the risk of CAP, with adjustments for potential confounding factors. The results showed that the maximum anti- and pro-inflammatory values of E-DII were -4.33 and +3.48, respectively. Higher E-DII scores were associated with an increased risk of CAP, and this association remained statistically significant after adjusting for age, sex, body mass index, smoking status, and other relevant variables. Notably, a more pro-inflammatory dietary pattern may be related to an increased risk of developing CAP in Kashgar Prefecture.

Background: Esophageal carcinoma accompanied by a right aortic arch (RAA) is very rare. When combined with Kommerell diverticulum (KD), a right aortic arch forms a vascular ring encircling both the esophagus and trachea. Due to abnormal anatomy of the upper mediastinum, it is very difficult to dissociate the esophagus and its surrounding tissues, especially the left recurrent laryngeal nerve. Herein, we report a case of successful thoracoscopic esophagectomy in an esophageal cancer patient concurrent with a RAA and KD., Case Presentation: A 62-year-old male patient was diagnosed with esophageal squamous carcinoma in the middle esophagus at clinical stage I (cT1N0M0) according to UICC-TNM classification 8th edition. Further examinations revealed RAA and KD. Based on the three-dimensional CT (3D-CT) reconstruction, a Mckeown esophagectomy via a left thoracoscopic approach in semi-prone position was performed. During the operation, the left recurrent laryngeal nerve was accurately exposed and well protected. Postoperatively, severe complications, including anastomotic leakage and recurrent laryngeal nerve palsy, were not observed. The patient was discharged 12 days after the surgery., Conclusion: Preoperative 3D-CT reconstruction is useful to clarify the vascular malformation in esophageal cancer patients with RAA, and helpful to formulate a reasonable surgical approach., 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 Yu, Guo, Huang, Zhao, He, Pan and Chen.)

Objective: To investigate whether risk factors related to pain vary at different stages of knee osteoarthritis (OA)., Methods: Individuals from the Osteoarthritis Initiative with available Kellgren/Lawrence (K/L) grade and numerical rating scale (NRS) data at baseline were included in this study. Pain severity was classified into 3 categories based on NRS scores: no pain, mild pain, and moderate/severe pain. Knee OA severity was stratified into 4 categories according to the K/L system. Pain risk factors were evaluated using generalized ordinal logistic regression analysis, and a heatmap was created to compare differences in standardized regression coefficients between subgroups of patients with different knee OA severities., Results: A total of 4,446 subjects were included in this study: 1,574 individuals without pain (35.4%), 1,138 individuals with mild pain (25.6%), and 1,734 individuals with moderate/severe pain (39.0%). For the entire population and subjects in the premorbid-stage subgroup, knee injury history, diabetes mellitus, depression, use of nonsteroidal anti-inflammatory drugs (NSAIDs), and valgus malaligned knees were associated with more severe pain. Older age and stronger quadriceps muscles were associated with milder pain. As the disease progressed, the number of significant risk factors decreased. Only age and quadriceps muscle force remained significant in end-stage disease., Conclusion: Multiple factors are associated with pain in patients with knee OA. As the disease progresses, the number of significant risk factors gradually reduces. These findings suggest that strategies for managing pain related to knee OA should vary depending on radiographic grades., (© 2022 American College of Rheumatology.)

A new spirostane, namely neohelicomyine B (1), together with six known steroids (2-7) were isolated from the fermentation of fungus Neohelicomyces hyalosporus. The structures of these compounds were elucidated by extensive analyses of spectroscopic methods including 1D and 2D NMR and HR-ESI-MS. The absolute configuration of 1 was confirmed by single-crystal X-ray diffraction. The bioactivities of compounds 1-7 were evaluated using cellular assays. Compound 1 displayed moderate cytotoxicity against HepG2 cells (hepatoma cells) with IC 50 value of 8.4±2.1 μM. Compound 7 also exhibited cytotoxic activity against HepG2 cells with the IC 50 value of 3.0±0.2 μM., (© 2023 Wiley-VHCA AG, Zurich, Switzerland.)

Objective: To investigate the location and anatomical structure of "Shaochong"(HT9), "Shaofu"(HT8), "Shenmen"(HT7), "Lingdao"(HT4) and "Shaohai"(HT3) in the rabbit's forelimb., Methods: Sixteen rabbits (half male and half female) were used in the present study. By referring to the national standards on the location of acupoints in the human body and the literature about the location of acupoints in the rabbit, and by using the method of comparative anatomy, the location and needling operation of the Five-shu acupoints of Shaoyin Heart Meridian on the rabbit's forelimb were defined, and these acupoints were needled and CT three-dimensional reconstruction were conducted. Then, the rabbits were killed, and intravascular perfusion was performed, followed by inserting acupuncture needles into these five acupoints for observing the anatomical relationship between the inserted acupuncture needle and the structure of surrounding tissues., Results: HT9 is located at the medial side of the little finger of forelimb, about 1 mm beside the nail root, and is adjacent to the superficial flexor tendon of the finger, the dorsal branches of the proper palmar digital artery and vein, and the endings of dorsal branch of palmar digital proper nerve of the ulnar nerve on the fifth finger side. HT8 is located at the palm side of the forelimb, horizontally parallel to the proximal end of the 5th metacarpophalangeal joint and between the 4th and 5th metacarpal bones, and is adjacent to the lumbricalis, the 4th and 5th interossei, and common palmar digital artery and vein and the palmar digital proper nerve of the ulnar nerve. HT7 is located at the medial margin of the extensor carpal tendon on the ulnar side, between the distal end of the ulna and the ulnar carpal bone, and is adjacent to the tendons of flexor carpi ulnaris and extensor carpi ulnaris, ulnar artery, ulnar vein and ulnar nerve. HT4 is located at the medial border of the ulnar flexor tendon, about 1.5 cun superior to HT7, and is adjacent to extensor carpi ulnaris, flexor carpi ulnaris, flexor digitorum superficialis, flexor digitorum profundus, ulnar artery, vein and ulnar nerve. HT3 is located at the depression, medial to the condyle of humerus when the elbow is bent at 90°, its neighbor structure is composed of pronator teres, biceps brachii, brachial artery and vein, radial collateral artery, radial collateral vein, medial antebrachial cutaneous nerve and median nerve., Conclusion: In the rabbit, there is a close relationship between HT9, HT8, HT7, HT4 and HT3 regions and brachial vascular and its branches, cephalic vein and its branches, medial antebrachial cutaneous nerve, median nerve and ulnar nerve, which is the morphological basis of the Five-shu acupoints of Shaoyin Heart Meridian for treating some related clinical disorders.

'On Water'-promoted the three-component tandem Michael addition/D-A cycloaddition reaction in 80 °C at 3 h has been developed without employing any catalyst and organic solvent. The process allows facile access to polycyclic N-heterocycles derivatives contain indole and maleimide from easily accessible starting materials in moderate to high yields (up to 91 %). Compared with conventional reaction conditions, this reaction not only improves the reaction efficiency and rate but also minimizes the side reaction., (© 2023 Wiley-VHCA AG, Zurich, Switzerland.)

Diabetic ulcer(DU) is a chronic and refractory ulcer which often occurs in the foot or lower limbs. It is a diabetic complication with high morbidity and mortality. The pathogenesis of DU is complex, and the therapies(such as debridement, flap transplantation, and application of antibiotics) are also complex and have long cycles. DU patients suffer from great economic and psychological pressure while enduring pain. Therefore, it is particularly important to promote rapid wound healing, reduce disability and mortality, protect limb function, and improve the quality of life of DU patients. By reviewing the relevant literatures, we have found that autophagy can remove DU wound pathogens, reduce wound inflammation, and accelerate ulcer wound healing and tissue repair. The main autophagy-related factors microtubule-binding light chain protein 3(LC3), autophagy-specific gene Beclin-1, and ubiquitin-binding protein p62 mediate autophagy. The traditional Chinese medicine(TCM) treatment of DU mitigates clinical symptoms, accelerates ulcer wound healing, reduces ulcer recurrence, and delays further deterioration of DU. Furthermore, under the guidance of syndrome differentiation and treatment and the overall concept, TCM treatment harmonizes yin and yang, ameliorates TCM syndrome, and treats underlying diseases, thereby curing DU from the root. Therefore, this article reviews the role of autophagy and major related factors LC3, Beclin-1, and p62 in the healing of DU wounds and the intervention of TCM, aiming to provide reference for the clinical treatment of DU wounds and subsequent in-depth studies.

Diabetic ulcer(DU) is one of the common complications of diabetes often occurring in the peripheral blood vessels of lower limbs or feet with a certain degree of damage. It has high morbidity and mortality, a long treatment cycle, and high cost. DU is often clinically manifested as skin ulcers or infections in the lower limbs or feet. In severe cases, it can ulcerate to the surface of tendons, bones or joint capsules, and even bone marrow. Without timely and correct treatment, most of the patients will have ulceration and blackening of the extremities. These patients will not be able to preserve the affected limbs through conservative treatment, and amputation must be performed. The etiology and pathogenesis of DU patients with the above condition are complex, which involves blood circulation interruption of DU wound, poor nutrition supply, and failure in discharge of metabolic waste. Relevant studies have also confirmed that promoting DU wound angiogenesis and restoring blood supply can effectively delay the occurrence and development of wound ulcers and provide nutritional support for wound healing, which is of great significance in the treatment of DU. There are many factors related to angiogenesis, including pro-angiogenic factors and anti-angiogenic factors. The dynamic balance between them plays a key role in angiogenesis. Meanwhile, previous studies have also confirmed that traditional Chinese medicine can enhance pro-angiogenic factors and down-regulate anti-angiogenic factors to promote angiogenesis. In addition, many experts and scholars have proposed that traditional Chinese medicine regulation of DU wound angiogenesis in the treatment of DU has broad prospects. Therefore, by consulting a large number of studies available, this paper expounded on the role of angiogenesis in DU wound and summarized the research advance in traditional Chinese medicine intervention in promoting the expression of angiogenic factors [vascular endothelial growth factor(VEGF), fibroblast growth factor(FGF), and angiopoietin(Ang)] which played a major role in promoting wound angiogenesis in the treatment of DU to provide ideas for further research and new methods for clinical treatment of DU.

Seven undescribed guaiane-type sesquiterpenoids named biscogniauxiaols A-G ( 1 - 7 ) were isolated from the endophytic fungus Biscogniauxia petrensis on Dendrobium orchids. Their structures were determined by extensive spectroscopic analyses, electronic circular dichroism (EC) and specific rotation (SR) calculations. Compound 1 represented a new family of guaiane-type sesquiterpenoids featuring an unprecedented [5/6/6/7] tetracyclic system. A plausible biosynthetic pathway for compounds 1 - 7 was proposed. The anti-fungal, anti-inflammatory and multidrug resistance reversal activities of the isolates were evaluated. Compounds 1 , 2 and 7 exhibited potent inhibitory activities against Candida albicans with MIC values ranging from 1.60 to 6.30 μM, and suppressed nitric oxide (NO) production with IC 50 ranging from 4.60 to 20.00 μM. Additionally, all compounds (100 μg/mL) enhanced the cytotoxicity of cisplatin in cisplatin-resistant non-small cell lung cancer cells (A549/DDP). This study opened up a new source for obtaining bioactive guaiane-type sesquiterpenoids and compounds 1 , 2 , and 7 were promising for further optimization as multifunctional inhibitors for anti-fungal ( C . albicans ) and anti-inflammatory purposes.

Diazinon (DZN) is a refractory organophosphorus pesticide (OP) in the surrounding environment due to its overuse in agriculture. The antioxidant activity of Epigallocatechin gallate (EGCG) from green tea is at least 100 times greater than that of vitamin C. This study aimed to study the effects of DZN on the meiotic maturation of porcine oocytes, as well as the protective roles of EGCG. Firstly, the effects of DZN and EGCG on meiotic nuclear maturation of porcine oocytes were detected, and then embryonic development was investigated by chemical parthenogenetic activation. Next, the spindle assembly, mitochondrial membrane potential (MMP), reactive oxygen species (ROS), DNA damage, and finally the early apoptosis of oocytes were examined by immunofluorescence staining. The results revealed that DZN exposure significantly reduced the quality of porcine oocytes, such as failure of nuclear and cytoplasmic maturation, evidenced by abnormal spindle assembly, disordered chromosome alignment, low MMP, observably increased ROS, severe DNA damage, and early apoptosis. Appropriate EGCG could significantly reduce all these defects caused by DZN. In conclusion, EGCG can help prevent the harm that DZN exposure can do. These findings offer convincing support for enhancing the oocyte quality from EGCG through daily ordinary beverages., (Copyright © 2022. Published by Elsevier Inc.)

Rechargeable batteries are key in the field of electrochemical energy storage, and the development of advanced electrode materials is essential to meet the increasing demand of electrochemical energy storage devices with higher density of energy and power. Anode materials are the key components of batteries. However, the anode materials still suffer from several challenges such as low rate capability and poor cycling stability, limiting the development of high-energy and high-power batteries. In recent years, heterojunctions have received increasing attention from researchers as an emerging material, because the constructed heterostructures can significantly improve the rate capability and cycling stability of the materials. Although many research progress has been made in this field, it still lacks review articles that summarize this field in detail. Herein, this review presents the recent research progress of heterojunction-type anode materials, focusing on the application of various types of heterojunctions in lithium/sodium-ion batteries. Finally, the heterojunctions introduced in this review are summarized, and their future development is anticipated., (© 2022 Wiley-VCH GmbH.)

Lignin-based activated carbon (LAC) is a promising high-quality functional material due to high surface area, abundant porous structure, and various functional groups. Modification is the most important step to functionalize LAC by altering its porous and chemical properties. This Review summarizes the state-of-the-art modification technologies of LAC toward advanced applications. Promising modification approaches are reviewed to display their effects on the preparation of LAC. The multiscale changes in the porosity and the surface chemistry of LAC are fully discussed. Advanced applications are then introduced to show the potential of LAC for supercapacitor electrode, catalyst support, hydrogen storage, and carbon dioxide capture. Finally, the mechanistic structure-function relationships of LAC are elaborated. These results highlight that modification technologies play a special role in altering the properties and defining the functionalities of LAC, which could be a promising porous carbon material toward industrial applications., (© 2022 Wiley-VCH GmbH.)

Objective: To analyse the efficacy of recombinant human growth hormone (rhGH) treatment in children born small for gestational age (SGA) with syndormic and non-syndormic short stature. Methods: The clinical data of 59 children born SGA who were diagnosed as short stature and admitted to the Center of Endocrinology, Genetics and Metabolism, Beijing Children's Hospital from July 2012 to June 2021 were collected and analyzed. According to the 2019 consensus on short stature, they were divided into syndromic group and non-syndromic group. Before treatment and 6, 12, 18 and 24 months after treatment, height standard deviation score (Ht-SDS), difference of height standard deviation (∆Ht-SDS) and homeostasis model assessment-insulin resistance index (HOMA-IR) were compared between groups, while Ht-SDS and HOMA-IR were compared before and after treatment. Independent t test or Kruskal-Wallis test were used for comparison between the 2 groups, and paired t test or Mann-Whitney U test were used for the intra-group comparison. Results: Among the 59 cases, 37 were males and 22 females, aged (5.5±2.3) years. There was no significant difference in Ht-SDS after 12 months of treatment between 2 groups (0.9±0.4 vs. 1.2±0.4, t= 1.68, P= 0.104) or in height SDS after 24 months of treatment (1.4±0.7 vs. 1.9±0.5, t= 1.52, P= 0.151). After 12 months of treatment, the insulin resistance index of the non-syndromic group was significantly higher than that of the syndromic group (2.29 (1.43, 2.99) vs. 0.90 (0.55, 1.40), Z= -2.95, P= 0.003). There were significant differences in Ht-SDS between 6 months and before treatment, 12 months and 6 months in syndromic type ( Z =7.65, 2.83 P <0.001, P =0.020), but all were significant differences in non-syndromic type between 6 months and before treatment, 12 months and 6 months, 18 months and 12 months, 24 months and 18 months ( Z =11.95, 7.54, 4.26, 3.83, all P <0.001). Conclusion: The efficacy of rhGH treatment in children born SGA is comparable between syndromic and non-syndromic short stature cases, but non-syndromic children treated with rhGH need more frequent follow-up due to the risk of insulin resistance.

With the excessive consumption of fossil energy, technologies that transform bio-based resources into materials have received more and more attention from researchers in recent decades. In this paper, a series of poly(ethylene 2,5-tetrahydrofuran dimethyl terephthalate; PEFTs) with different components were synthesized from 2,5-tetrahydrofuran dimethanol (THFDM), terephthalic acid (TPA), and ethylene glycol (EG). Their chemical structures and compositions were determined by FTIR, 1 H NMR, and 13 C NMR. With the increase in THFDM content, the crystallization, T m , and tensile strength of PEFTs gradually decrease because the introduced THFDM breaks the order of molecular chains, while the thermal stability and T g remain stable. PEFTs seem to present a significant shear thinning phenomenon, which was indicated by the rheological test. Electrospinning technology was used to explore the spinnability of PEFT; it was found that PEFTs have better spinning performance than PET. In addition, due to the good hydrophobicity and porosity of PEFT nanofiber films, they have potential application value in the manufacture of hydrophobic nanofiber and filter films., Competing Interests: There are no conflicts of interest to declare., (This journal is © The Royal Society of Chemistry.)

A novel thio-Ritter-type reaction of alkyl bromides, nitriles, and hydrogen sulfide has been explored, providing a straightforward approach toward functionally important thioamides. This transformation features a broad substrate scope, operational simplicity, use of available feedstock chemicals, and late-stage functionalizations of bioactive molecules. The reaction mechanism is also proposed.

A high-precision human metabolic measurement system is designed. The system uses STM32F103 as the main control chip to acquire oxygen, carbon dioxide and flow signals to calculate four quantitative indicators: oxygen consumption( V O 2 ), carbon dioxide production( V CO 2 ), respiratory entropy( RQ ) and resting energy metabolism( REE ), and finally uses an upper computer to display the calculation results.In this paper, the signal acquisition circuit design was carried out for the oxygen sensor, carbon dioxide sensor and flow sensor, and the validity of the device was verified with the American machine MGCDiagnositcs using Bland-Altman analysis method, and the results showed that the four parameters of V O 2 , V CO 2 , RQ and REE of both devices fell in the agreement interval of more than 95%. The device thus provides accurate metabolic measurements and offers an effective tool for the field of general health and clinical nutrition support in China.

Malignant tumors seriously threaten people's health and life worldwide. Natural products, with definite pharmacological effects and known chemical structures, present dual advantages of Chinese herbs and chemotherapeutic drug. Some of them exhibit favorable anti-cancer activity. Natural products were categorized into eight classes according to their chemical structures, including alkaloids, terpenoids and volatile oils, inorganic salts, phenylpropanoids, flavonoids and isoflavones, quinone, saponins and polysaccharides. The review focused on the latest advances in anti-cancer activity of representative natural products for every class. Additionally, anti-cancer molecular mechanism and derivatization of natural products were summarized in detail, which would provide new core structures and new insights for anti-cancer new drug development., Competing Interests: Author A-HL is employed by Shaanxi Pharmaceutical Holding Group Co., LTD, China. Author H-LC previously acted as an advisor for Shaanxi Pharmaceutical Holding Group Co., LTD, China. The remaining 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 © 2022 Guo, Jin, Zhao, Rong, Cao, Li, Sun, Jia, Wang, Huang, Li, He, Li, Ma, Lv, Shao and Cao.)

Background: The aim of this study was to investigate the role of ILF3-AS1 in regulating the survival of melanoma and its molecular mechanism., Methods: The relative expression level of ILF3-AS1 in melanoma was assessed by qPCR. The effect of ILF3-AS1 and PDK1 on the cell viability was tested by MTT assay. Glucose uptake colorimetric assay, lactate assay, the measurements of extracellular acidification rate (ECAR) and Oxygen consumption rate (OCR) were performed to test the effect of ILF3-AS1 and PDK1 on the cellular glycolysis. Luciferase assay was conducted to detect the interactions of ILF3-AS1, miR-493-5p and PDK1. RNA immunoprecipitation chip (RIP) assay was used to detect the enrichments of ILF3-AS1 and miR-493-5p in the complex. Protein level of PDK1 was detected by western blot analysis., Results: qPCR revealed that ILF3-AS1 was upregulated in human melanoma cell lines. MTT assay showed that ILF3-AS1 knockdown blunted cell proliferation, which was rescued by the overexpression of PDK1. Glucose uptake colorimetric assay, lactate assay, the measurements of ECAR and OCR indicated that ILF3-AS1 promoted glycolysis through PDK1. Western blotting results showed that ILF3-AS1 overexpression promoted PDK1 expression, which was prevented by miR-493-5p overexpression in SK-MEL-1 cells., Conclusions: ILF3-AS1 promotes the aerobic glycolysis and survival of melanoma cells involving miR-493-5p/PDK1 pathway.

Matrine is an alkaloid extracted from traditional Chinese herbs including Sophora flavescentis , Sophora alopecuroides , Sophora root, etc. It has the dual advantages of traditional Chinese herbs and chemotherapy drugs. It exhibits distinct benefits in preventing and improving chronic diseases such as cardiovascular disease and tumors. The review introduced recent research progresses on extraction, synthesis and derivatization of Matrine. The summary focused on the latest research advances of Matrine on anti-atherosclerosis, anti-hypertension, anti-ischemia reperfusion injury, anti-arrhythmia, anti-diabetic cardiovascular complications, anti-tumor, anti-inflammatory, anti-bacterium, anti-virus, which would provide new core structures and new insights for new drug development in related fields., Competing Interests: Authors A-HL and H-LC are employed by Shaanxi Pharmaceutical Holding Group Co., LTD, China. The remaining 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 © 2022 Sun, Jia, Rong, Zhou, Cao, Li, Guo, Jin, Wang, Huang, Li, He, Li, Ma, Lv, Shao, Zhang and Cao.)

To assess the amino acid and fatty acid metabolite patterns between infants with and without bronchopulmonary dysplasia in different nutritional stages after birth and identify metabolic indicators of bronchopulmonary dysplasia. This was an observational cohort of preterm infants born at a gestational age ≤32 + 6 weeks and with a body weight ≤2000 g. Amino acid and carnitine profiles were measured in dried blood spots (DBSs) during the early nutrition transitional phase using tandem mass spectrometry. Bronchopulmonary dysplasia was defined as oxygen dependence at 36 weeks of postmenstrual age or 28 days after birth. Metabolomic analysis was employed to define metabolites with significant differences, map significant metabolites into pathways, and identify metabolic indicators of bronchopulmonary dysplasia. We evaluated 45 neonates with and 40 without bronchopulmonary dysplasia. Four amino acids and three carnitines showed differences between the groups. Three carnitines (C0, C2, and C6:1) were high in the bronchopulmonary dysplasia group mostly; conversely, all four amino acids (threonine, arginine, methionine, and glutamine (Gln)) were low in the bronchopulmonary dysplasia group. Pathway analysis of these metabolites revealed two pathways with significant changes (p < 0.05). ROC analysis showed Gln/C6:1 at total parenteral nutrition phase had both 80% sensitivity and specificity for predicting the development of bronchopulmonary dysplasia, with an area under the curve of 0.81 (95% confidence interval 0.71-0.89). Amino acid and fatty acid metabolite profiles changed in infants with bronchopulmonary dysplasia after birth during the nutrition transitional period, suggesting that metabolic dysregulation may participate in the development of bronchopulmonary dysplasia. Our findings demonstrate that metabolic indicators are promising for forecasting the occurrence of bronchopulmonary dysplasia among preterm neonates.