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Abstract 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.

Abstract 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.

As a significant technological innovation in the fields of medicine and geriatric care, smart care wheelchairs offer a novel approach to providing high-quality care services and improving the quality of care. The aim of this review article is to examine the development, applications and prospects of smart nursing wheelchairs, with particular emphasis on their assistive nursing functions, multiple-sensor fusion technology, and human–machine interaction interfaces. First, we describe the assistive functions of nursing wheelchairs, including position changing, transferring, bathing, and toileting, which significantly reduce the workload of nursing staff and improve the quality of care. Second, we summarized the existing multiple-sensor fusion technology for smart nursing wheelchairs, including LiDAR, RGB-D, ultrasonic sensors, etc. These technologies give wheelchairs autonomy and safety, better meeting patients’ needs. We also discussed the human–machine interaction interfaces of intelligent care wheelchairs, such as voice recognition, touch screens, and remote controls. These interfaces allow users to operate and control the wheelchair more easily, improving usability and maneuverability. Finally, we emphasized the importance of multifunctional-integrated care wheelchairs that integrate assistive care, navigation, and human–machine interaction functions into a comprehensive care solution for users. We are looking forward to the future and assume that smart nursing wheelchairs will play an increasingly important role in medicine and geriatric care. By integrating advanced technologies such as enhanced artificial intelligence, intelligent sensors, and remote monitoring, we expect to further improve patients’ quality of care and quality of life.

ObjectivesTo investigate the characteristic cytokine profile of the aqueous humor in eyes with congenital cataract and pre-existing posterior capsule dysfunction (PCD).MethodsIn 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.ResultsThe 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-β2 (TGF-β2), 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-β2 level were independent risk factors for PCD.ConclusionA 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-β2, and VEGF in eyes with PCD indicated a change in their intraocular inflammatory microenvironment, which possibly led to cataract progression. Lens thickness and TGF-β2 level are independent risk factors for PCD.

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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.

IntroductionGastric 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.MethodsHP-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 discussionIn 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.

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.

To unravel the genetic mechanisms of disease and physiological traits, it requires comprehensive sequencing analysis of large sample size in Chinese populations. Here, we report the primary results of the Chinese Academy of Sciences Precision Medicine Initiative (CASPMI) project launched by the Chinese Academy of Sciences, including the de novo assembly of a northern Han reference genome (NH1.0) and whole genome analyses of 597 healthy people coming from most areas in China. Given the two existing reference genomes for Han Chinese (YH and HX1) were both from the south, we constructed NH1.0, a new reference genome from a northern individual, by combining the sequencing strategies of PacBio, 10× Genomics, and Bionano mapping. Using this integrated approach, we obtained an N50 scaffold size of 46.63 Mb for the NH1.0 genome and performed a comparative genome analysis of NH1.0 with YH and HX1. In order to generate a genomic variation map of Chinese populations, we performed the whole-genome sequencing of 597 participants and identified 24.85 million (M) single nucleotide variants (SNVs), 3.85 M small indels, and 106,382 structural variations. In the association analysis with collected phenotypes, we found that the T allele of rs1549293 in KAT8 significantly correlated with the waist circumference in northern Han males. Moreover, significant genetic diversity in MTHFR, TCN2, FADS1, and FADS2, which associate with circulating folate, vitamin B12, or lipid metabolism, was observed between northerners and southerners. Especially, for the homocysteine-increasing allele of rs1801133 (MTHFR 677T), we hypothesize that there exists a “comfort” zone for a high frequency of 677T between latitudes of 35–45 degree North. Taken together, our results provide a high-quality northern Han reference genome and novel population-specific data sets of genetic variants for use in the personalized and precision medicine. Keywords: De novo assembly, Reference genome, Variation map, Phenotype association, Large population

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.

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.

The key technology of the prosthetic knee is to simulate the torque and angle of the biological knee. In this work, we proposed a novel prosthetic knee operated in semi-active mode. The structure with ball-screw driven by the motor and the passive hydraulic damping cylinder was presented. A four-bar linkage was adapted to track the instantaneous center motion of human knee. The mathematical models of hydraulic cylinder damping and active torque were established to simulate the knee torque and angle. The results show that the knee torque symmetry index is smaller than 10% in the whole gait. The knee angle symmetry index value is 34.7% in stance phase and 11.5% in swing phase. The angle in swing phase is closer to the intact knee. The semi-active prosthetic knee could provide similar torque and angle of the biological knee in the simulation. It has shown good potential in improving the gait symmetry of the transfemoral amputee.

An astronomical increase in microbial genome data in recent years has led to strong demand for bioinformatic tools for pan-genome analysis within and across species. Here, we present PGAweb, a user-friendly, web-based tool for bacterial pan-genome analysis, which is composed of two main pan-genome analysis modules, PGAP and PGAP-X. PGAweb provides key interactive and customizable functions that include orthologous clustering, pan-genome profiling, sequence variation and evolution analysis, and functional classification. PGAweb presents features of genomic structural dynamics and sequence diversity with different visualization methods that are helpful for intuitively understanding the dynamics and evolution of bacterial genomes. PGAweb has an intuitive interface with one-click setting of parameters and is freely available at http://PGAweb.vlcc.cn/.

Since the proposal for pangenomic study, there have been a dozen software tools actively in use for pangenomic analysis. By the end of 2014, Panseq and the pan-genomes analysis pipeline (PGAP) ranked as the top two most popular packages according to cumulative citations of peer-reviewed scientific publications. The functions of the software packages and tools, albeit variable among them, include categorizing orthologous genes, calculating pangenomic profiles, integrating gene annotations, and constructing phylogenies. As epigenomic elements are being gradually revealed in prokaryotes, it is expected that pangenomic databases and toolkits have to be extended to handle information of detailed functional annotations for genes and non-protein-coding sequences including non-coding RNAs, insertion elements, and conserved structural elements. To develop better bioinformatic tools, user feedback and integration of novel features are both of essence.

Cupriavidus sp. are generally heavy metal tolerant bacteria with the ability to degrade a variety of aromatic hydrocarbon compounds, although the degradation pathways and substrate versatilities remain largely unknown. Here we studied the bacterium Cupriavidus gilardii strain CR3, which was isolated from a natural asphalt deposit, and which was shown to utilize naphthenic acids as a sole carbon source. Genome sequencing of C. gilardii CR3 was carried out to elucidate possible mechanisms for the naphthenic acid biodegradation. The genome of C. gilardii CR3 was composed of two circular chromosomes chr1 and chr2 of respectively 3,539,530 bp and 2,039,213 bp in size. The genome for strain CR3 encoded 4,502 putative protein-coding genes, 59 tRNA genes, and many other non-coding genes. Many genes were associated with xenobiotic biodegradation and metal resistance functions. Pathway prediction for degradation of cyclohexanecarboxylic acid, a representative naphthenic acid, suggested that naphthenic acid undergoes initial ring-cleavage, after which the ring fission products can be degraded via several plausible degradation pathways including a mechanism similar to that used for fatty acid oxidation. The final metabolic products of these pathways are unstable or volatile compounds that were not toxic to CR3. Strain CR3 was also shown to have tolerance to at least 10 heavy metals, which was mainly achieved by self-detoxification through ion efflux, metal-complexation and metal-reduction, and a powerful DNA self-repair mechanism. Our genomic analysis suggests that CR3 is well adapted to survive the harsh environment in natural asphalts containing naphthenic acids and high concentrations of heavy metals.