Dynamic Changes of Capsular-Intraocular Lens Adhesion in Plate-Haptic Hydrophilic and Loop-Haptic Hydrophobic Eyes.

INTRODUCTION: The aim of this work is to investigate the dynamic changes of capsular-intraocular lens (IOL) adhesion in plate-haptic hydrophilic and loop-haptic hydrophobic eyes. METHODS: Cataract eyes that met the inclusion criteria were randomly assigned to receive implantation of a plate-haptic hydrophilic or loop-haptic IOL. The anterior capsular adhesion, posterior capsular adhesion, and the configurations of the capsular bend were evaluated using swept-source optical coherence tomography at 1 day, 1 week, 1 month, and 3 months postoperatively. RESULTS: In total, 66 eyes of 66 patients were eligible for the analysis: 33 in the plate-haptic group and 33 in the loop-haptic group. The contact between the anterior capsule and IOL in the plate-haptic group was earlier than that in the loop-haptic group upon comparing the measurements taken at 1 day and 1 week (p = 0.001, p = 0.003, respectively). The complete attachment of the posterior capsule and IOL in the plate-haptic group was significantly greater at 1 week, 1 month, and 3 months (p = 0.001, p = 0.000, p = 0.001, respectively). The capsular bend index of the plate-haptic group was significantly greater than that of the loop-haptic group at each time points except at 1 day (p = 0.007, p = 0.049, p = 0.005, respectively). Furthermore, a new type of capsular bend, "cocked adhesion," was observed in the plate-haptic eyes. CONCLUSIONS: The plate-haptic IOL demonstrated excellent capsular adhesion compared to the loop-haptic IOL, which was probably attributed to haptic compressibility. A special cocked configuration of the capsular bend in plate-haptic IOL was observed for the first time. Further studies are warranted to confirm the effect of the new type of capsular bend.

Combined Study of Gene Expression and Chromosome Three-Dimensional Structure in Escherichia coli During Growth Process.

The chromosome structure of different bacteria has its unique organization pattern, which plays an important role in maintaining the spatial location relationship between genes and regulating gene expression. Conversely, transcription also plays a global role in regulating the three-dimensional structure of bacterial chromosomes. Therefore, we combine RNA-Seq and Hi-C technology to explore the relationship between chromosome structure changes and transcriptional regulation in E. coli at different growth stages. Transcriptome analysis indicates that E. coli synthesizes many ribosomes and peptidoglycan in the exponential phase. In contrast, E. coli undergoes more transcriptional regulation and catabolism during the stationary phase, reflecting its adaptability to changes in environmental conditions during growth. Analyzing the Hi-C data shows that E. coli has a higher frequency of global chromosomal interaction in the exponential phase and more defined chromosomal interaction domains (CIDs). Still, the long-distance interactions at the replication termination region are lower than in the stationary phase. Combining transcriptome and Hi-C data analysis, we conclude that highly expressed genes are more likely to be distributed in CID boundary regions during the exponential phase. At the same time, most high-expression genes distributed in the CID boundary regions are ribosomal gene clusters, forming clearer CID boundaries during the exponential phase. The three-dimensional structure of chromosome and expression pattern is altered during the growth of E. coli from the exponential phase to the stationary phase, clarifying the synergy between the two regulatory aspects.

Characteristic cytokine profile of the aqueous humor in eyes with congenital cataract and pre-existing posterior capsule dysfunction.

Objectives: To investigate the characteristic cytokine profile of the aqueous humor in eyes with congenital cataract and pre-existing posterior capsule dysfunction (PCD). Methods: In this cross-sectional study, the enrolled eyes with congenital cataract and PCD were included in the PCD group, while those with an intact posterior capsule were included in the control group. Demographic data and biometric parameters were recorded. The levels of 17 inflammatory factors in the aqueous humor collected from the enrolled eyes were detected using Luminex xMAP technology, and intergroup differences in the collected data were analyzed. Results: The PCD group comprised 41 eyes from 31 patients with congenital cataract and PCD, whereas the control group comprised 42 eyes from 27 patients with congenital cataract and an intact posterior capsule. Lens thickness was significantly thinner in the PCD group than in the control group. However, the levels of monocyte chemoattractant protein-1 (MCP-1), transforming growth factor-ß2 (TGF-ß2), and vascular endothelial growth factor (VEGF) were significantly higher in the PCD group than in the control group. Multivariate logistic regression confirmed that lens thickness and TGF-ß2 level were independent risk factors for PCD. Conclusion: A thinner lens thickness in eyes with congenital cataract and PCD could serve as a biometric feature of these eyes. The higher levels of MCP-1, TGF-ß2, and VEGF in eyes with PCD indicated a change in their intraocular inflammatory microenvironment, which possibly led to cataract progression. Lens thickness and TGF-ß2 level are independent risk factors for PCD.

Exploration of the in vitro Antiviral Effects and the Active Components of Changyanning Tablets Against Enterovirus 71.

Purpose: This study aims to investigate the in vitro antiviral effects of the aqueous solution of Changyanning (CYN) tablets on Enterovirus 71 (EV71), and to analyze its active components. Methods: The in vitro anti-EV71 effects of CYN solution and its herbal ingredients were assessed by testing the relative viral RNA (vRNA) expression level and the cell viability rates. Material basis analysis was performed using HPLC-Q-TOF-MS/MS detection. Potential targets and active components were identified by network pharmacology and molecular docking. The screened components were verified by in vitro antiviral experiments. Results: CYN solution exerted anti-EV71 activities as the vRNA is markedly reduced after treatment, with a half maximal inhibitory concentration (IC50) of 996.85 µg/mL. Of its five herbal ingredients, aqueous extract of Mosla chinensis (AEMC) and leaves of Liquidambar formosana Hance (AELLF) significantly inhibited the intracellular replication of EV71, and the IC50 was tested as 202.57 µg/mL and 174.77 µg/mL, respectively. Based on HPLC-Q-TOF-MS/MS results, as well as the comparison with the material basis of CYN solution, a total of 44 components were identified from AEMC and AELLF. Through network pharmacology, AKT1, ALB, and SRC were identified as core targets. Molecular docking performed between core targets and the components indicated that 21 components may have anti-EV71 effects. Of these, nine were selected for in vitro pharmacodynamic verification, and only rosmarinic acid manifested in vitro anti-EV71 activity, with an IC50 of 11.90 µg/mL. Moreover, rosmarinic acid can stably bind with three core targets by forming hydrogen bonds. Conclusion: CYN solution has inhibitory effects on EV71 replication in vitro, and its active component was identified as rosmarinic acid. Our study provides a new approach for screening and confirmation of the effective components in Chinese herbal preparation.

Impact of anterior capsule polishing on capsule opacification and capsule bend after age-related cataract surgery.

PURPOSE: To investigate the effect of anterior capsule polishing on postoperative capsule opacification and capsular bend in patients with age-related cataract displaying normal axial length. SETTING: Eye Hospital of Wenzhou Medical University at Hangzhou. DESIGN: Prospective self-controlled trial. METHODS: Patients with age-related cataracts aged 56 to 84 years displaying normal axial length were enrolled. Before surgery, a coin-toss method was used to randomly select 1 eye for intraoperative 360 degrees anterior capsule polishing (polishing group); the contralateral eye received no treatment (control group). Capsular bend index (CBI), anterior capsule opacification (ACO), posterior capsule opacification (PCO), and anterior capsule opening area (ACOA) were recorded at 1 week, 1 month, 3 months, 6 months, and 12 months postoperatively using swept-source optical coherence tomography and slitlamp examination. RESULTS: 21 patients (42 eyes) were enrolled. Within-group comparisons showed that both groups had significant differences in CBI between 1 week and 1 month postoperatively, and between 6 months and 12 months postoperatively ( P < .05). Between-group comparisons revealed a significant difference in CBI at 1 week postoperatively ( P < .05); at 12 months postoperatively, there was a significant difference in ACOA ( P < .05). There were no significant between-group differences regarding ACO or PCO at any timepoint ( P > .05). CONCLUSIONS: For patients with age-related cataracts and normal axial length, 360 degrees anterior capsule polishing can delay early capsular bag deformation without increasing the risks of ACO and PCO. This approach can also limit contraction of the anterior capsule opening.

Correction: Zhang et al. Parkin, as a Regulator, Participates in Arsenic Trioxide-Triggered Mitophagy in HeLa Cells. Curr. Issues Mol. Biol. 2022, 44, 2759-2771.

In the published publication [...].

CADM1 impairs the effect of miR-1246 on promoting cell cycle progression in chemo-resistant leukemia cells.

The interruption of normal cell cycle execution acts as an important part to the development of leukemia. It was reported that microRNAs (miRNAs) were closely related to tumorigenesis and progression, and their aberrant expression had been demonstrated to play a crucial role in numerous types of cancer. Our previous study showed that miR-1246 was preferentially overexpressed in chemo-resistant leukemia cell lines, and participated in process of cell cycle progression and multidrug resistant regulation. However, the underlying mechanism remains unclear. In present study, bioinformatics prediction and dual luciferase reporter assay indicated that CADM1 was a direct target of miR-1246. Evidently decreased expression of CADM1 was observed in relapsed primary leukemia patients and chemo-resistant cell lines. Our results furtherly proved that inhibition of miR-1246 could significantly enhance drug sensitivity to Adriamycin (ADM), induce cell cycle arrest at G0/G1 phase, promote cell apoptosis, and relieve its suppression on CADM1 in K562/ADM and HL-60/RS cells. Interference with CADM1 could reduce the increased drug sensitivity induced by miR-1246 inhibition, and notably restore drug resistance by promoting cell cycle progression and cell survival via regulating CDKs/Cyclins complexes in chemo-resistant leukemia cells. Above all, our results demonstrated that CADM1 attenuated the role of miR-1246 in promoting cell cycle progression and cell survival, thus influencing multidrug resistance within chemo-resistant leukemia cells via CDKs/Cyclins. Higher expression of miR-1246 and lower expression of CADM1 might be risk factors for leukemia.

Cancer-associated fibroblast related gene signature in Helicobacter pylori-based subtypes of gastric carcinoma for prognosis and tumor microenvironment estimation in silico analysis.

Introduction: Gastric cancer (GC) remains the major constituent of cancer-related deaths and a global public health challenge with a high incidence rate. Helicobacter pylori (HP) plays an essential role in promoting the occurrence and progression of GC. Cancer-associated fibroblasts (CAFs) are regarded as a significant component in the tumor microenvironment (TME), which is related to the metastasis of GC. However, the regulation mechanisms of CAFs in HP-related GC are not elucidated thoroughly. Methods: HP-related genes (HRGs) were downloaded from the GSE84437 and TCGA-GC databases. The two databases were combined into one cohort for training. Furthermore, the consensus unsupervised clustering analysis was obtained to sort the training cohort into different groups for the identification of differential expression genes (DEGs). Weighted correlation network analysis (WGCNA) was performed to verify the correlation between the DEGs and cancer-associated fibroblasts which were key components in the tumor microenvironment. The least absolute shrinkage and selection operator (LASSO) was executed to find cancer-associated fibroblast-related differential expression genes (CDEGs) for the further establishment of a prognostic model. Results and discussion: In this study, 52 HP-related genes (HRGs) were screened out based on the GSE84437 and TCGA-GC databases. A total of 804 GC samples were analyzed, respectively, and clustered into two HP-related subtypes. The DEGs identified from the two subtypes were proved to have a relationship with TME. After WGCNA and LASSO, the CAFs-related module was identified, from which 21 gene signatures were confirmed. Then, a CDEGs-Score was constructed and its prediction efficiency in GC patients was conducted for validation. Overall, a highly precise nomogram was established for enhancing the adaptability of the CDEGs-Score. Furthermore, our findings revealed the applicability of CDEGs-Score in the sensitivity of chemotherapeutic drugs. In general, our research provided brand-new possibilities for comprehending HP-related GC, evaluating survival, and more efficient therapeutic strategies.

ProPan: a comprehensive database for profiling prokaryotic pan-genome dynamics.

Compared with conventional comparative genomics, the recent studies in pan-genomics have provided further insights into species genomic dynamics, taxonomy and identification, pathogenicity and environmental adaptation. To better understand genome characteristics of species of interest and to fully excavate key metabolic and resistant genes and their conservations and variations, here we present ProPan (https://ngdc.cncb.ac.cn/propan), a public database covering 23 archaeal species and 1,481 bacterial species (in a total of 51,882 strains) for comprehensively profiling prokaryotic pan-genome dynamics. By analyzing and integrating these massive datasets, ProPan offers three major aspects for the pan-genome dynamics of the species of interest: 1) the evaluations of various species' characteristics and composition in pan-genome dynamics; 2) the visualization of map association, the functional annotation and presence/absence variation for all contained species' gene clusters; 3) the typical characteristics of the environmental adaptation, including resistance genes prediction of 126 substances (biocide, antimicrobial drug and metal) and evaluation of 31 metabolic cycle processes. Besides, ProPan develops a very user-friendly interface, flexible retrieval and multi-level real-time statistical visualization. Taken together, ProPan will serve as a weighty resource for the studies of prokaryotic pan-genome dynamics, taxonomy and identification as well as environmental adaptation.

TWAS Atlas: a curated knowledgebase of transcriptome-wide association studies.

Transcriptome-wide association studies (TWASs), as a practical and prevalent approach for detecting the associations between genetically regulated genes and traits, are now leading to a better understanding of the complex mechanisms of genetic variants in regulating various diseases and traits. Despite the ever-increasing TWAS outputs, there is still a lack of databases curating massive public TWAS information and knowledge. To fill this gap, here we present TWAS Atlas (https://ngdc.cncb.ac.cn/twas/), an integrated knowledgebase of TWAS findings manually curated from extensive literature. In the current implementation, TWAS Atlas collects 401,266 high-quality human gene-trait associations from 200 publications, covering 22,247 genes and 257 traits across 135 tissue types. In particular, an interactive knowledge graph of the collected gene-trait associations is constructed together with single nucleotide polymorphism (SNP)-gene associations to build up comprehensive regulatory networks at multi-omics levels. In addition, TWAS Atlas, as a user-friendly web interface, efficiently enables users to browse, search and download all association information, relevant research metadata and annotation information of interest. Taken together, TWAS Atlas is of great value for promoting the utility and availability of TWAS results in explaining the complex genetic basis as well as providing new insights for human health and disease research.

The C-Terminal Repeat Units of SpaA Mediate Adhesion of Erysipelothrix rhusiopathiae to Host Cells and Regulate Its Virulence.

Erysipelothrix rhusiopathiae is a causative agent of erysipelas in animals and erysipeloid in humans. However, current information regarding E. rhusiopathiae pathogenesis remains limited. Previously, we identified two E. rhusiopathiae strains, SE38 and G4T10, which were virulent and avirulent in pigs, respectively. Here, to further study the pathogenic mechanism of E. rhusiopathiae, we sequenced and assembled the genomes of strains SE38 and G4T10, and performed a comparative genomic analysis to identify differences or mutations in virulence-associated genes. Next, we comparatively analyzed 25 E. rhusiopathiae virulence-associated genes in SE38 and G4T10. Compared with that of SE38, the spaA gene of the G4T10 strain lacked 120 bp, encoding repeat units at the C-terminal of SpaA. To examine whether these deletions or splits influence E. rhusiopathiae virulence, these 120 bp were successfully deleted from the spaA gene in strain SE38 by homologous recombination. The mutant strain ΔspaA displayed attenuated virulence in mice and decreased adhesion to porcine iliac artery endothelial cells, which was also observed using the corresponding mutant protein SpaA'. Our results demonstrate that SpaA-mediated adhesion between E. rhusiopathiae and host cells is dependent on its C-terminal repeat units.

C-C Bond Activation of Cyclopropanes Enabled by Phosphine-Catalyzed In Situ Formation of High-Strain Methylenecycopropane Intermediate.

An effective strategy for the ring-opening/elaboration of cyclopropanes by phosphine catalyst is documented, providing the 2,4-pentadiene sulfonamides and isoindolines in moderate to good yields. The key to the success of this reaction is phosphine-catalyzed introduction of a trigonal center into cyclopropanes, which results in the formation of higher ring strain cyclopropylidenemethyl phosphonium salt. Moreover, this methodology is employed as the key step for the synthesis of bioactive molecules.

Dihydroartemisinin Triggers Ferroptosis in Multidrug-Resistant Leukemia Cells.

The molecular mechanisms and role of ferroptosis in tumor drug resistance remain unclear. In this study, we found that multidrug-resistant (MDR) K562/adriamycin (ADM) leukemia cells possessed higher glutathione (GSH) levels and iron-regulatory protein 2 (IRP2), transferrin receptor, ferritin heavy chain 1 (FTH1), and peroxidase-4 (GPX4) expression than parental drug-sensitive K562 leukemia cells. These elevations might have increased the antioxidant ability of K562/ADM cells and granted them increased buffering capacity against iron disorder, protecting them from ferroptosis and favoring drug resistance. However, dihydroartemisinin (DHA) restrained MDR K562/ADM cell viability and enhanced the sensitivity to ADM by strengthening ferroptosis induced by downregulation of GSH levels and GPX4, IRP2, and FTH expression, upregulation of reactive oxygen species (ROS) levels, and the consequent suppression of total serine/threonine kinase (AKT), total mammalian target of rapamycin (t-mTOR), phosphorylated mTOR (p-mTOR), and p-mTOR/t-mTOR levels. Moreover, compared with K562 cells, MDR K562/ADM cells exhibited greater ROS increases, GSH decreases, and viability rescue after ferroptosis inhibitor treatment owing to further suppression of FTH1, GPX4, p-mTOR, and p-mTOR/t-mTOR. Collectively, the increase in oxidative damage and the blockade of antioxidant defence shaped DHA-induced ferroptosis, which was responsible for the sensitivity of MDR leukemia cells to DHA. Regulating iron homeostasis/ROS/AKT/mTOR might be a potential chemotherapeutic strategy for sensitizing drug-resistant leukemia.

Parkin, as a Regulator, Participates in Arsenic Trioxide-Triggered Mitophagy in HeLa Cells.

Parkin is a well-established synergistic mediator of mitophagy in dysfunctional mitochondria. Mitochondria are the main target of arsenic trioxide (ATO) cytotoxicity, and the effect of mitophagy on ATO action remains unclear. In this study, we used stable Parkin-expressing (YFP-Parkin) and Parkin loss-of-function mutant (Parkin C431S) HeLa cell models to ascertain whether Parkin-mediated mitophagy participates in ATO-induced apoptosis/cell death. Our data showed that the overexpression of Parkin significantly sensitized HeLa cells to ATO-initiated proliferation inhibition and apoptosis; however, the mutation of Parkin C431S significantly weakened this Parkin-mediated responsiveness. Our further investigation found that ATO significantly downregulated two fusion proteins (Mfn1/2) and upregulated fission-related protein (Drp1). Autophagy was also activated as evidenced by the formation of autophagic vacuoles and mitophagosomes, increased expression of PINK1, and recruitment of Parkin to impaired mitochondria followed by their degradation, accompanied by the increased transformation of LC3-I to LC3-II, increased expression of Beclin1 and decreased expression of P62 in YFP-Parkin HeLa cells. Enhanced mitochondrial fragmentation and autophagy indicated that mitophagy was activated. Furthermore, during the process of mitophagy, the overproduction of ROS implied that ROS might represent a key factor that initiates mitophagy following Parkin recruitment to mitochondria. In conclusion, our findings indicate that Parkin is critically involved in ATO-triggered mitophagy and functions as a potential antiproliferative target in cancer cells.

TMED2/9/10 Serve as Biomarkers for Poor Prognosis in Head and Neck Squamous Carcinoma.

Background: Head and neck squamous carcinoma (HNSC) is one of the most common malignant tumors with high incidence and poor prognosis. Transmembrane emp24 structural domain (TMED) proteins are involved in protein transport and vesicle budding processes, which have implicated various malignancies' progression. However, the roles of TMEDs in HNSC, especially in terms of development and prognosis, have not been fully elucidated. Methods: We applied TIMER 2.0, UALCAN, GEPIA 2, Kaplan-Meier plotter, GEO, The Human Protein Atlas (HPA), cBioPortal, Linkedomics, Metascape, GRNdb, STRING, and Cytoscape to investigate the roles of TMED family members in HNSC. Results: Compared with normal tissues, the mRNA expression levels of TMED1/2/4/5/7/8/9/10 were significantly increased in the TCGA HNSC dataset. And we combined GEPIA 2 and Kaplan-Meier Plotter to select TMED2/9/10 with prognostic value. Then we detected the levels of mRNA in the GEO HNSC database and the protein expression in HPA. It was found that the mRNA and protein expression levels of TMED2/9/10 were increased in HNSC. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that TMED2/9/10 and their co-expressed genes promoted the malignant behavior of tumors by participating in biological processes such as intracellular transferase complex, protein transport, focal adhesion, intracellular protein processing. Single-cell analysis and immune infiltration analysis suggested that immune responses of cancer-associated fibroblasts and endothelial cells might be associated with prognosis. Finally, the transcription factors-genes network and protein-protein functional interaction network pointed to genes such as X-box binding protein 1 (XBP1) and TMED7, which might cooperate with TMED2/9/10 to change the progression of HNSC. Conclusions: Our study implied that TMED2/9/10 and related genes mightjointly affect the prognosis of HNSC, providing specific clues for further experimental research, personalized diagnosis strategies, and targeted clinical therapy for HNSC.

The effects of incorporation of the counterparts and mimics of L-lysine on the antimicrobial activity, hemolytic activity, cytotoxicity and tryptic stability of antimicrobial peptide polybia-MPII.

Due to the limited effects of conventional antibiotics on the increasing emergence of drug-resistant bacteria and fungi, novel antimicrobial agents were urgently needed to alleviate this phenomenon. Nowadays, antimicrobial peptides are believed to be a promising candidate for a new generation of antimicrobial drugs. Antimicrobial peptide polybia-MPII (MPII) was first isolated from the venom of the social wasp Polybia paulista with a broad spectrum of antimicrobial activity. In the present study, the counterparts and mimics of cationic amino acids of Lys, such as Arg, His, Orn, Dab and Dap were employed to substitute Lys in the sequence of MPII. The effects of the incorporation of these amino acids on its antimicrobial activity, hemolytic activity, cytotoxicity, enzyme stability and therapeutic potential were explored. Our results showed that although the incorporation of Arg could improve its antimicrobial activity, there is no improvement in enzyme stability. The incorporation of His makes MPII exert its antimicrobial activity in a pH-dependent manner. Notably, incorporating Dap could effectively decrease its hemolytic activity and cytotoxicity and enhance its enzyme stability against trypsin. In conclusion, this study would provide an effective strategy to improve the bioavailability and metabolic stability of AMPs while decrease their hemolytic activity and cytotoxicity.

CancerSCEM: a database of single-cell expression map across various human cancers.

With the proliferating studies of human cancers by single-cell RNA sequencing technique (scRNA-seq), cellular heterogeneity, immune landscape and pathogenesis within diverse cancers have been uncovered successively. The exponential explosion of massive cancer scRNA-seq datasets in the past decade are calling for a burning demand to be integrated and processed for essential investigations in tumor microenvironment of various cancer types. To fill this gap, we developed a database of Cancer Single-cell Expression Map (CancerSCEM, https://ngdc.cncb.ac.cn/cancerscem), particularly focusing on a variety of human cancers. To date, CancerSCE version 1.0 consists of 208 cancer samples across 28 studies and 20 human cancer types. A series of uniformly and multiscale analyses for each sample were performed, including accurate cell type annotation, functional gene expressions, cell interaction network, survival analysis and etc. Plus, we visualized CancerSCEM as a user-friendly web interface for users to browse, search, online analyze and download all the metadata as well as analytical results. More importantly and unprecedentedly, the newly-constructed comprehensive online analyzing platform in CancerSCEM integrates seven analyze functions, where investigators can interactively perform cancer scRNA-seq analyses. In all, CancerSCEM paves an informative and practical way to facilitate human cancer studies, and also provides insights into clinical therapy assessments.

Metformin and arsenic trioxide synergize to trigger Parkin/pink1-dependent mitophagic cell death in human cervical cancer HeLa cells.

Mitochondria are involved in various biological processes including intracellular homeostasis, proliferation, senescence, and death, and mitochondrial mitophagy is closely related to the development and regression of malignant tumors. Recent studies confirmed that the hypoglycemic drug metformin (Met) exerted various antitumor effects, protected neural cells, and improved immunity, while arsenic trioxide (ATO) is an effective chemotherapeutic agent for the clinical treatment of leukemia and various solid tumors. However, the possible combined antitumor effects of Met and ATO and their cellular molecular mechanisms are unclear. We investigated the role of Parkin-mediated mitochondrial mitophagy in the anti-tumor mechanism of Met and ATO by studying the effects of Met and/or ATO on the proliferation and apoptosis of cervical cancer HeLa cells. Both Met and ATO effectively inhibited the proliferative activity of HeLa cells and induced apoptosis by activating Bax and inhibiting Bcl-2. Met and ATO treatment alone or in combination stimulated mitophagosome accumulation in HeLa cells, increased the conversion of microtubule-associated protein light chain 3 (LC3)-I to LC3-II, and decreased levels of the mitophagic lysosomal substrate protein P62. The mitochondrial membrane potential of HeLa cells also decreased, accompanied by activation of the mitochondrial translocase TOM system and the Pink1/Parkin signaling pathway. These results suggested that Met and/or ATO could induce mitophagy in HeLa cells via the Pink1/Parkin signaling pathway, leading to mitophagic apoptosis and inhibition of tumor cell proliferation. The combination of Met and ATO thus has enhanced antitumor effects, suggesting that this combination has potential clinical applications for the treatment of cervical cancer and other tumors.

A Time Division Multiplexing Inspired Lightweight Soft Exoskeleton for Hip and Ankle Joint Assistance.

Exoskeleton robots are frequently applied to augment or assist the user's natural motion. Generally, each assisted joint corresponds to at least one specific motor to ensure the independence of movement between joints. This means that as there are more joints to be assisted, more motors are required, resulting in increasing robot weight, decreasing motor utilization, and weakening exoskeleton robot assistance efficiency. To solve this problem, the design and control of a lightweight soft exoskeleton that assists hip-plantar flexion of both legs in different phases during a gait cycle with only one motor is presented in this paper. Inspired by time-division multiplexing and the symmetry of walking motion, an actuation scheme that uses different time-periods of the same motor to transfer different forces to different joints is formulated. An automatic winding device is designed to dynamically change the loading path of the assistive force at different phases of the gait cycle. The system is designed to assist hip flexion and plantar flexion of both legs with only one motor, since there is no overlap between the hip flexion movement and the toe-offs movement of the separate legs during walking. The weight of the whole system is only 2.24 kg. PD iterative control is accomplished by an algorithm that utilizes IMUs attached on the thigh recognizing the maximum hip extension angle to characterize toe-offs indirectly, and two load cells to monitor the cable tension. In the study of six subjects, muscle fatigue of the rectus femoris, vastus lateralis, gastrocnemius and soleus decreased by an average of 14.69%, 6.66%, 17.71%, and 8.15%, respectively, compared to scenarios without an exoskeleton.

Biomechanical and Physiological Evaluation of a Multi-Joint Exoskeleton with Active-Passive Assistance for Walking.

How to improve the walking efficiency while ensuring the wearability is an important issue of lower limb exoskeletons. Active devices can provide greater forces, while the passive devices have advantage in weight. We presented a multi-joint exoskeleton with active hip extension assistance and passive ankle plantarflexion assistance in this work. An admittance controller based on a feedforward model was proposed to track the desired active force of the hip extension. An underfoot clutch mechanism was adapted to realize the passive ankle plantarflexion assistance. To assess the efficacy of the multi-joint exoskeleton in assisting walking, we conducted comprehensive experiments to evaluate the force tracking performance, lower limb muscle activities and metabolic cost. The results demonstrated that: (i) The average tracking error of the peak hip extension assistance force from three subjects was less than 3%. (ii) The reductions of normalized root-mean-square EMG in the lateral soleus, medial soleus and gluteus maximus of eight subjects achieved 15.33%, 11.11%, and 3.74%, respectively. (iii) The average metabolic cost of six subjects was reduced by 10.41% under exoskeleton on (EO) condition comparing to the condition of walking with no exoskeleton (NE). This work proved that the concept of the multi-joint exoskeleton with active-passive assistance can improve the walking efficiency.