Addressing Challenges in Ion-Selectivity Characterization in Nanopores.

Ion selectivity is the basis for designing smart nanopore/channel-based devices, e.g., ion separators and biosensors. Quantitative characterization of ion selectivities in nanopores often employs the Nernst or Goldman-Hodgkin-Katz (GHK) equation to interpret transmembrane potentials. However, the direction of the measured transmembrane potential drop is not specified in these equations, and selectivity values calculated using absolute values of transmembrane potentials do not directly reveal the ion for which the membrane is selective. Moreover, researchers arbitrarily choose whether to use the Nernst or GHK equation and overlook the significant differences between them, leading to ineffective quantitative comparisons between studies. This work addresses these challenges through (a) specifying the transmembrane potential (sign) and salt concentrations in terms of working and reference electrodes and the solutions in which they reside when using the Nernst and GHK equations, (b) reporting of both Nernst-selectivity and GHK-selectivity along with solution compositions and transmembrane potentials when comparing different nanopores/channels, and (c) performing simulations to define an ideal selectivity for nanochannels. Experimental and modeling studies provide significant insight into these fundamental equations and guidelines for the development of nanopore/channel-based devices.

Pore-Size-Dependent Role of Functional Elements at the Outer Surface and Inner Wall in Single-Nanochannel Biosensors.

Biological nanopores feature functional elements on the outer surfaces (FEOS) and inner walls (FEIW), enabling precise control over ions and molecules with exceptional sensitivity and specificity. This provides valuable inspiration to scientists for the development of intelligent artificial nanochannel-based platforms, with a wide range of potential applications, including biosensors. Much effort has been dedicated to investigating the distinct contribution of FEOS and FEIW of multichannel membrane biosensors. However, the intricate interactions among neighboring pores in multichannel biosensors have presented challenges. This underscores the untapped potential of single nanochannels as ideal candidates in this field. Here, we employed single nanochannel membranes with different pore sizes to investigate the distinct contributions of FEIW and FEOS to single-nanochannel biosensors, combined with numerical simulations. Our findings revealed that alterations in the negative charges of FEIW and FEOS, induced by target binding, have differential effects on ion transport, contingent upon the degree of nanoconfinement. In the case of smaller pores, such as 20 nm, the ion concentration polarization driven by FEIW can independently control ion transport through the surface's electric double layer. However, as the pore size increases to 40-60 nm, both FEIW and FEOS become essential for effective ion concentration polarization. When the pore size reaches 100 nm, both FEIW and FEOS are ineffective and thus unsuitable for biosensors. Simulations demonstrate that the observed phenomena can be attributed to the interactions between the charges of FEIW and FEOS within the overlapping electric double layer under confinement. These results underscore the critical role of pore size as a key parameter in governing the functionality of probes within or on nanopore-based biosensors as well as in the design of nanopore-based devices.

Synthetic K+ Channels Constructed by Rebuilding the Core Modules of Natural K+ Channels in an Artificial System.

Different types of natural K+ channels share similar core modules and cation permeability characteristics. In this study, we have developed novel artificial K+ channels by rebuilding the core modules of natural K+ channels in artificial systems. All the channels displayed high selectivity for K+ over Na+ and exhibited a selectivity sequence of K+ ≈Rb+ during the transport process, which is highly consistent with the cation permeability characteristics of natural K+ channels. More importantly, these artificial channels could be efficiently inserted into cell membranes and mediate the transmembrane transport of K+ , disrupting the cellular K+ homeostasis and eventually triggering the apoptosis of cells. These findings demonstrate that, by rebuilding the core modules of natural K+ channels in artificial systems, the structures, transport behaviors, and physiological functions of natural K+ channels can be mimicked in synthetic channels.

Highly Rectifying Fluidic Diodes Based on Asymmetric Layer-by-Layer Nanofilms on Nanochannel Membranes.

Nanochannel-based fluidic diodes display ion selectivity and ion current rectification (ICR), which may prove to be important in energy-harvesting devices and biosensors. This paper reports asymmetric functionalization of the outer surface of a flexible nanochannel polymer membrane to create fluidic diodes that give ICR. Layer-by-layer (LbL) adsorption with cross-linking of only the underlying part of the polyelectrolyte nanofilm leads to a porosity step across the film. The combination of a high effective surface charge density and the porosity step in the film leads to a remarkable maximum ICR factor of ∼200 with a pH gradient across the film. Incorporation of pH-sensitive polyelectrolyte components enables the ICR factor to increase an order of magnitude on going from pH 8 to pH 3. Moreover, the coated membrane shows excellent anion selectivity. Thus, LbL adsorption with partial cross-linking provides a simple method for creating coated nanochannel membranes that serve as pH-responsive ionic diodes for potential chemical/biosensors.

Clinical characteristics of COVID-19 in children compared with adults in Shandong Province, China.

AIMS AND BACKGROUND: The COVID-19 outbreak spread in China and is a threat to the world. We reported on the epidemiological, clinical, laboratory, and radiological characteristics of children cases to help health workers better understand and provide timely diagnosis and treatment. METHODS: Retrospectively, two research centers' case series of 67 consecutive hospitalized cases including 53 adult and 14 children cases with COVID-19 between 23 Jan 2020 and 15 Feb 2020 from Jinan and Rizhao were enrolled in this study. Epidemiological, clinical, laboratory, and radiological characteristics of children and adults were analyzed and compared. RESULTS: Most cases in children were mild (21.4%) and conventional cases (78.6%), with mild clinical signs and symptoms, and all cases were of family clusters. Fever (35.7%) and dry cough (21.4%) were described as clinical manifestations in children cases. Dry cough and phlegm were not the most common symptoms in children compared with adults (p = 0.03). In the early stages of the disease, lymphocyte counts did not significantly decline but neutrophils count did in children compared with adults (p = 0.02). There was a lower level of CRP (p = 0.00) in children compared with adults. There were 8 (57.1%) asymptomatic cases and 6 (42.9%) symptomatic cases among the 14 children cases. The age of asymptomatic patients was younger than that of symptomatic patients (p = 0.03). Even among asymptomatic patients, 5 (62.5%) cases had lung injuries including 3 (60%) cases with bilateral involvement, which was not different compared with that of symptomatic cases (p = 0.58, p = 0.74). CONCLUSIONS: The clinical symptoms of children are mild, there is substantial lung injury even among children, but that there is less clinical disease, perhaps because of a less pronounced inflammatory response, and that the occurrence of this pattern appears to inversely correlate with age.

Natural variations of FT family genes in soybean varieties covering a wide range of maturity groups.

BACKGROUND: Flowering time and maturity are among the most important adaptive traits in soybean (Glycine max (L.) Merill). Flowering Locus T (FT) family genes function as key flowering integrators, with flowering-promoting members GmFT2a/GmFT5a and flowering-inhibiting members GmFT4/GmFT1a antagonistically regulating vegetative and reproductive growth. However, to date, the relations between natural variations of FT family genes and the diversity of flowering time and maturity in soybean are not clear. Therefore, we conducted this study to discover natural variations in FT family genes in association with flowering time and maturity. RESULTS: Ten FT family genes, GmFT1a, GmFT1b, GmFT2a, GmFT2b, GmFT3a, GmFT3b, GmFT4, GmFT5a, GmFT5b and GmFT6, were cloned and sequenced in the 127 varieties evenly covering all 14 known maturity groups (MG0000-MGX). They were diversified at the genome sequence polymorphism level. GmFT3b and GmFT5b might have experienced breeding selection in the process of soybean domestication and breeding. Haplotype analysis showed that a total of 17 haplotypes had correlative relationships with flowering time and maturity among the 10 FT genes, namely, 1a-H3, 1b-H1, 1b-H6, 1b-H7, 2a-H1, 2a-H3, 2a-H4, 2a-H9, 2b-H3, 2b-H4, 2b-H6, 2b-H7, 3b-H4, 5a-H1, 5a-H2, 5a-H4 and 5b-H1. Based on the association analysis, 38 polymorphic sites had a significant association with flowering time at the level of p < 0.01. CONCLUSIONS: Some natural variations exist within the 10 FT family genes, which might be involved in soybean adaptation to different environments and have an influence on diverse flowering time and maturity. This study will facilitate the understanding of the roles of FTs in flowering and maturity.

Strongly Coupled g-C3 N4 Nanosheets-Co3 O4 Quantum Dots as 2D/0D Heterostructure Composite for Peroxymonosulfate Activation.

The development of effective approaches for the preparation of 0D quantum dots (QDs)/2D nanosheets (NSs) heterostructures, which have been proven to be favorable for heterogeneous catalysis, is highly desirable but remains a great challenge. Herein, 0D metal oxide nanocrystals-2D ultrathin g-C3 N4 nanosheets (Co3 O4 /CNNS) heterostructures are synthesized via a facile chemical reaction, followed by annealing in air. Ultrafine Co3 O4 QDs (≈2.2-3.2 nm) are uniformly and tightly attached on the surface of g-C3 N4 nanosheets. Detailed characterization reveals that the specially designed unique 0D/2D structure is critical to the high photocatalytic performance for the degradation of tetracycline (TC) via peroxymonosulfate (PMS) activation. The optimal catalyst, namely, Co3 O4 /CNNS-1100, exhibits excellent performance and ≈98.7% TC can be degraded under visible light irradiation. Moreover, TC degradation is almost completely insusceptible to several real water samples. Meanwhile, other dye pollutants can also be efficiently degraded by the Co3 O4 /CNNS-1100/PMS/vis system. The quenching tests display that that the h+ , ∙OH, O2∙- , and SO4∙- are responsible for TC removal. The improved photocatalytic performance can be attributed to the synergistic effect of the photocatalytic- and chemical-processes in the PMS activation. This work gives an insight into the development of multifunctional 0D/2D nanocomposites for further potential applications which are not limited to environmental purification.

Functional diversification of Flowering Locus T homologs in soybean: GmFT1a and GmFT2a/5a have opposite roles in controlling flowering and maturation.

Soybean flowering and maturation are strictly regulated by photoperiod. Photoperiod-sensitive soybean varieties can undergo flowering reversion when switched from short-day (SD) to long-day (LD) conditions, suggesting the presence of a 'floral-inhibitor' under LD conditions. We combined gene expression profiling with a study of transgenic plants and confirmed that GmFT1a, soybean Flowering Locus T (FT) homolog, is a floral inhibitor. GmFT1a is expressed specifically in leaves, similar to the flowering-promoting FT homologs GmFT2a/5a. However, in Zigongdongdou (ZGDD), a model variety for studying flowering reversion, GmFT1a expression was induced by LD but inhibited by SD conditions. This was unexpected, as it is the complete opposite of the expression of flowering promoters GmFT2a/5a. Moreover, the key soybean maturity gene E1 may up-regulate GmFT1a expression. It is also notable that GmFT1a expression was conspicuously high in late-flowering varieties. Transgenic overexpression of GmFT1a delayed flowering and maturation in soybean, confirming that GmFT1a functions as a flowering inhibitor. This discovery highlights the complex impacts of the functional diversification of the FT gene family in soybean, and implies that antagonism between flowering-inhibiting and flowering-promoting FT homologs in this highly photoperiod-sensitive plant may specify vegetative vs reproductive development.

Universal Method to Transfer Membrane-Templated Nano-Objects to Aqueous Solutions.

A wide range of nano-objects are synthesized by combining template synthesis, using polycarbonate membrane as template, with different material deposition methods. The resulting nanostructures varied from robust inorganic gold nanowires grown by electrodeposition to rigid polypyrrole nanotubes synthesized by chemical polymerization and softer nanotubes made of different combinations of synthetic and natural polyelectrolytes fabricated by layer-by-layer (LbL) assembly. The morphology of these various nano-objects is characterized prior to and after their immersion in water, revealing that the rigidity degree of LbL nanotubes strongly decreases after being in contact with water, leading to highly swollen and flexible nanotubes in aqueous solution that tend to stick to any surface and are very difficult to collect and disperse quantitatively in aqueous solution. Different processes to collect these nano-objects and disperse them in aqueous medium for further analysis and application were then studied. Among them, a method based on simple filtration of nanotubes in the presence of a powdered dextran adjuvant leads to the quantitative collection and dispersion in water of all types of tested cylindrical nano-objects. This universal method to efficiently collect membrane templated nano-objects paves the way to further characterization of a large variety of nanotubes in aqueous solution and to their potential use as cargo nanocarriers or as nanoreactors.

Quantitative Collection and Enzymatic Activity of Glucose Oxidase Nanotubes Fabricated by Templated Layer-by-Layer Assembly.

We report on the fabrication of enzyme nanotubes in nanoporous polycarbonate membranes via the layer-by-layer (LbL) alternate assembly of polyethylenimine (PEI) and glucose oxidase (GOX), followed by dissolution of the sacrificial template in CH2Cl2, collection, and final dispersion in water. An adjuvant-assisted filtration methodology is exploited to extract quantitatively the nanotubes without loss of activity and morphology. Different water-soluble CH2Cl2-insoluble adjuvants are tested for maximal enzyme activity and nanotube stability; whereas NaCl disrupts the tubes by screening electrostatic interactions, the high osmotic pressure created by fructose also contributes to loosening the nanotubular structures. These issues are solved when using neutral, high molar mass dextran. The enzymatic activity of intact free nanotubes in water is then quantitatively compared to membrane-embedded nanotubes, showing that the liberated nanotubes have a higher catalytic activity in proportion to their larger exposed surface. Our study thus discloses a robust and general methodology for the fabrication and quantitative collection of enzymatic nanotubes and shows that LbL assembly provides access to efficient enzyme carriers for use as catalytic swarming agents.

Bandgap engineering and mechanism study of nonmetal and metal ion codoped carbon nitride: C+Fe as an example.

Bandgap narrowing and a more positive valence band (VB) potential are generally considered to be effective methods for improving visible-light-driven photocatalysts because of the significant enhancement of visible-light absorption and oxidation ability. Herein, an approach is reported for the synthesis of a novel visible-light-driven high performance polymer photocatalyst based on band structure control and nonmetal and metal ion codoping, that is, C and Fe-codoped as a model, by a simple thermal conversion method. The results indicate that compared to pristine graphitic carbon nitride (g-C3 N4 ), C+Fe-codoped g-C3 N4 shows a narrower bandgap and remarkable positively shifted VB; as a result the light-absorption range was expanded and the oxidation capability was increased. Experimental results show that the catalytic efficiency of C+Fe-codoped g-C3 N4 for photodegradation of rhodamine B (RhB) increased 14 times, compared with pristine g-C3 N4 under visible-light absorption at λ>420 nm. The synergistic enhancement in C+Fe-codoped g-C3 N4 photocatalyst could be attributed to the following features: 1) C+Fe-codoping of g-C3 N4 tuned the bandgap and improved visible-light absorption; 2) the porous lamellar structure and decreased particle size could provide a high surface area and greatly improve photogenerated charge separation and electron transfer; and 3) both increased electrical conductivity and a more positive VB ensured the superior electron-transport property and high oxidation capability. The results imply that a high-performance photocatalyst can be obtained by combining bandgap control and doping modification; this may provide a basic concept for the rational design of high performance polymer photocatalysts with reasonable electronic structures for unique photochemical reaction.

Stimuli-Responsive Ion Transport Regulation in Nanochannels by Adhesion-Induced Functionalization of Macroscopic Outer Surface.

Responsive regulation of ion transport through nanochannels is crucial in the design of smart nanofluidic devices for sequencing, sensing, and water-energy nexus. Functionalization of the inner wall of the nanochannel enhances interaction with ions and fluid but restricts versatile chemical approaches and accurate characterizations of fluidic interfaces. Herein, we reveal a responsive regulating mechanism of ion transport through nanochannels by polydopamine (PDA)-induced functionalization on the macroscopic outer surface of nanochannels. Responsive molecules were codeposited with PDA on the outer surface of nanochannels and formed a valve of nanometer thickness to manually manipulate ion transport by changing its gap spacing, surface charge, and wettability under external stimulus. The response ratio can be up to 100-fold by maximizing the proportion of responsive molecules on the outer surface. Laminating the codepositions of different responsive molecules with PDA on the channel's outer surface produces multiple responses. A nearly universal adhesion of PDA with responsive molecules on the open outer surface induces nanochannels responsive to different external stimuli with variable response ratios and arbitrary combinations. The results challenge the primary role of functionalization on the nanoconfined interface of nanofluidics and open opportunities for developing new-style nanofluidic devices through the functionalization of macroscopic interface.

Environmental-friendly, flexible silk fibroin-based film as dual-responsive shape memory material.

Bio-based shape memory materials have attracted wide attention due to their biocompatibility, degradability and safety. However, designing and manufacturing wearable bio-based shape memory films with excellent flexibility and toughness is still a challenge. In this work, silk fibroin substrate with a ß-sheet structure was combined with a tri-block shape memory copolymer to prepare a transparent composited shape memory film. The silk fibroin-based film showed a dual-responsive shape memory function, which can respond to both temperature and water stimuli. This film has a sensitive water-responsive shape memory, which starts deforming after exposure to water for 3 s and fully recovers in 30 s. In addition, the composite film shows highly stretchable (>300 %) and could maintain its high tensile properties after 5 cycles of regeneration. The films also exhibited rapid degradation ability. This study provides new insights for the design of dual-responsive shape memory materials by combining biocompatible matrix and multi-block SMP to simultaneously enhance the mechanical properties, which can be used for intelligent packaging, medical supplies, soft actuators and wearable devices.

Effect of web-implemented exercise interventions on depression and anxiety in patients with neurological disorders: a systematic review and meta-analysis.

Introduction: Web-implemented exercise intervention is the latest and innovative method to improve people's mental health. Currently, many studies have proven that web-implemented interventions are effective to improve depression and anxiety in adults. However, the influence of different web-implemented exercise interventions on depression and anxiety in patients with neurological disorders is still unclear. Objective: The study aims to systematically summarize the type and content of web-implemented exercise interventions and quantify the effect of different web-implemented exercise interventions on depression and anxiety in patients with neurological disorders. Methods: Four literature databases (PubMed, Web of Science, China National Knowledge Infrastructure, and WanFang data) were searched. The literature search considered studies published in English or Chinese before October 13, 2022. Randomized controlled trials (RCTs) that participants accepted web-implemented interventions were included. Two authors independently extracted data and assessed the risk of bias for included studies. Standardized mean differences (SMD) with 95% CI were used to integrate the effect size. Results: 16 RCTs (a total of 963 participants) were included. The results showed that web-implemented exercise intervention had a significant effect on depression (SMD = -0.80; 95% CI, -1.09 to -0.52; I2 = 75%; P < 0.00001) and anxiety (SMD = -0.80; 95% CI, -1.23 to -0.36; I2 = 75%; P = 0.0003) in patients with a neurological disorder. The subgroup analysis showed that the effectiveness of the web-implemented exercise intervention was influenced by several factors, such as web-implemented exercise intervention type, component, and intervention duration. Conclusion: Web-implemented exercise intervention has a relieving effect on depression and anxiety symptoms in patients with neurological disorders. Additionally, the intervention type, intervention duration, and component can influence the effect size. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/#recordDetails, identifier: CRD42023409538.

How to Test the On-Ice Aerobic Capacity of Speed Skaters? An On-Ice Incremental Skating Test for Young Skaters.

Aerobic capacity is important for speed skaters to achieve good results in middle-long distance events. The technical characteristics of speed skating cause intermittent blood flow blockage in the lower limbs. Therefore, an athlete's aerobic capacity on ice may differ from that measured by cycling or running. Now, the on-ice aerobic capacity lacks methods for conducting aerobic capacity tests on ice. Objective: The objective of this study was to develop a method for measuring on-ice aerobic capacity for young athletes and to compare it with the VO2max test on cycling. Methods: This study established a test method for the on-ice aerobic capacity of young, high-level speed skaters with incremental load (on-ice incremental skating test, OIST) through expert interviews and literature review. In the first part, OIST was used to test the aerobic abilities of 65 youth professional speed skaters (51 males and 14 females) on ice and to explore the correlation with their specific performance. The second part compares the relationship between aerobic capacity on ice and aerobic capacity on bicycle of 18 young high-level male athletes. The third part establishes the regression formula of ice ventilation threshold heart rate. The OIST established in this study can evaluate the on-ice aerobic capacity of athletes from National Level and Level 1&2 in China. The athletes' on-ice aerobic capacity indicators were significantly lower than those of the cycling test. However, the values of absolute VO2max and absolute ventilatory threshold had a high correlation (R = 0.532, p < 0.05; R = 0.584, p < 0.05). The regression formula of ventilatory threshold heart rate on ice = 0.921 × HRmax (Cycling test) -9.243. The OIST established in this study meets the characteristics and requirements of the VO2max measurement method. The OIST seems to be able to better evaluate the aerobic capacity of athletes skating on ice. The indicators of maximum oxygen uptake and ventilation threshold in OIST were significantly lower than those in the aerobic cycling test, but there was a good correlation. The aerobic cycling test can be used as an important selection index of the ice aerobic capacity of speed skaters. The regression formula will provide an important basis for coaches to accurately monitor the intensity of ice training.

A Flexible TENG Based on Micro-Structure Film for Speed Skating Techniques Monitoring and Biomechanical Energy Harvesting.

Wearable motion-monitoring systems have been widely used in recent years. However, the battery energy storage problem of traditional wearable devices limits the development of human sports training applications. In this paper, a self-powered and portable micro-structure triboelectric nanogenerator (MS-TENG) has been made. It consists of micro-structure polydimethylsiloxane (PDMS) film, fluorinated ethylene propylene (FEP) film, and lithium chloride polyacrylamide (LiCl-PAAM) hydrogel. Through the micro-structure, the voltage of the MS-TENG can be improved by 7 times. The MS-TENG provides outstanding sensing properties: maximum output voltage of 74 V, angular sensitivity of 1.016 V/degree, high signal-to-noise ratio, and excellent long-term service stability. We used it to monitor the running skills of speed skaters. It can also store the biomechanical energy which is generated in the process of speed skating through capacitors. It demonstrates capability of sensor to power electronic calculator and electronic watch. In addition, as a flexible electrode hydrogel, it can readily stretch over 1300%, which can help improve the service life and work stability of MS-TENG. Therefore, MS-TENG has great application potential in human sports training monitoring and big data analysis.

Hierarchical multi-active component yolk-shell nanoreactors as highly active peroxymonosulfate activator for ciprofloxacin degradation.

The reasonable design of the structure and composition of catalysts was essential to improve the catalytic performance of advanced oxidation processes (AOPs). Herein, we reported a simple strategy to synthesize hierarchical Co3O4-C@CoSiOx yolk-shell nanoreactors with multiple active components by using metal-organic frameworks (MOFs). The novel nanoreactors are further used to activate peroxymonosulfate (PMS) for ciprofloxacin (CIP) degradation. The effects of reaction parameters (pH value, co-existing ions, reaction temperature, etc.) on CIP degradation were systematically investigated. Especially, ∼98.2% of CIP was degraded within 17 min under the optimal conditions, together with the low cobalt leaching and excellent reusability. The appreciable catalytic performance improvement might be due to the synergistic effect of the structure and component design: (1) the hierarchical yolk-shell structure endowed the catalyst with high surface area (∼232.47 m2/g) and fully exposed active sites; (2) abundant highly active ≡Co-OH+ were formed on the surface of CoSiOx; (3) the presence of oxygen vacancies and nitrogen-doped carbon promoted the decomposition of PMS through a non-radical process. The results revealed both the radical (SO4∙-, ∙OH and O2∙-) and non-radical (1O2 and direct charge transfer) should be responsible for the CIP degradation. Moreover, the possible degradation pathways of CIP were proposed through the identification of intermediates using LC-MS/MS techniques and density functional theory (DFT) calculation. Our work highlights that multi-component catalysts derived from MOFs with novel structure have broad application prospects in AOPs.

Correction: Polyaniline nanorods dotted on graphene oxide nanosheets as a novel super adsorbent for Cr(VI).

Correction for 'Polyaniline nanorods dotted on graphene oxide nanosheets as a novel super adsorbent for Cr(VI)' by Shouwei Zhang et al., Dalton Trans., 2013, 42, 7854-7858, https://doi.org/10.1039/C3DT50149C.

Influence of handrail height and knee joint support on sit-to-stand movement.

Handrail height and knee joint support both significantly influence sit-to-stand (STS) movement. However, research on the associations between handrail height, knee joint support, and their cumulative effect on STS kinematics and changes in plantar pressure distribution during STS under different handrail heights and knee joint support is still unclear. The main objective of this study was to examine the influence of handrail height and knee joint support on the kinematics and the distribution of plantar pressure in healthy adults during STS. Twenty-six healthy adult subjects aged 23 to 58 years participated in this experiment. The subjects carried out STS movement experiments under 7 conditions: 6 experimental conditions of 3 different heights of handrail, with and without knee joint support, and 1 control condition of standing up naturally. The motions of the markers were recorded using cameras operating at 60 Hz, and total movement time, the percentage of movement time of each phase, trunk tilt angle, joint angle, plantar pressure, and the time from hindfoot to forefoot peak pressure were analyzed and compared. Handrail height significantly influences the percentage of movement time at phase I (P = .015) and the maximum trunk tilt angle (P < .05), knee joint support significantly influences the maximum trunk tilt angle and ankle angle (P = .033), and handrail height and knee joint support have an interaction on the time from hindfoot to forefoot peak pressure (P < .001). Subjects' STS performance was improved with the use of assistant devices but showed particular improvement under the condition of with knee joint support when the handrail height was middle handrail.

Mutational landscape of circulating tumor DNA identifies distinct molecular features associated with therapeutic response in patients with metastatic colorectal cancer.

BACKGROUND: We investigated the mutational landscape of circulating tumor DNA (ctDNA) in predicting tumor response to first-line treatment in patients with metastatic colorectal cancer (mCRC). METHODS: We included 41 patients with initially unresectable mCRC, treated with 5-fluorouracil/leucovorin/oxaliplatin (FOLFOX)/5-fluorouracil/leucovorin/irinotecan (FOLFIRI) with/without bevacizumab (Bev)/cetuximab (Cet). Blood samples were prospectively collected at two timepoints: at baseline and after four cycles of first-line treatment. Mutational status of 1086 genes were studied in ctDNA by targeted next-generation sequencing (NGS). Molecular mutational burden (MMB) was defined as mean mutation frequency among obtained mutations for each gene. To evaluate the association between molecular characteristics of cfDNA and therapeutic response better, we divided these patients into MMB-high and MMB-low group according to the median value of MMB (0.3). RESULTS: Among the 41 enrolled patients, alterations of six genes (TRIM24, SPEN, RNF43, PRKAR1A, KRAS, and KDM5 C) were found at baseline. Baseline MMB of six genes was significantly lower in partial response (PR)/stable disease (SD) patients than progression disease (PD) patients (p = 0.0012). Further analysis demonstrated that genomic profiling of ctDNA from pretreatment blood samples was significantly different between PR/SD (non-PD) group and PD group. By comparing the baseline levels of KRAS MMB in the two subgroups, we found that PD cases were all MMB-high, whereas non-PD cases were mainly in MMB-low subgroup. Furthermore, patients with low-KRAS MMB had superior response rate, significantly longer progression-free survival (PFS) and longer overall survival (OS) than high-KRAS MMB group. CONCLUSIONS: This prospective and serial genomic profiling study revealed the utility of ctDNA in predicting clinical outcomes in mCRC patients under first-line treatment. Levels of KRAS MMB might aid in monitoring therapeutic efficacy in mCRC patients at pretreatment/after four cycles of first-line treatment.