microRNA-1 Regulates Metabolic Flexibility in Skeletal Muscle via Pyruvate Metabolism.

MicroRNA-1 (miR-1) is the most abundant miRNA in adult skeletal muscle. To determine the function of miR-1 in adult skeletal muscle, we generated an inducible, skeletal muscle-specific miR-1 knockout (KO) mouse. Integration of RNA-sequencing (RNA-seq) data from miR-1 KO muscle with Argonaute 2 enhanced crosslinking and immunoprecipitation sequencing (AGO2 eCLIP-seq) from human skeletal muscle identified miR-1 target genes involved with glycolysis and pyruvate metabolism. The loss of miR-1 in skeletal muscle induced cancer-like metabolic reprogramming, as shown by higher pyruvate kinase muscle isozyme M2 (PKM2) protein levels, which promoted glycolysis. Comprehensive bioenergetic and metabolic phenotyping combined with skeletal muscle proteomics and metabolomics further demonstrated that miR-1 KO induced metabolic inflexibility as a result of pyruvate oxidation resistance. While the genetic loss of miR-1 reduced endurance exercise performance in mice and in C. elegans, the physiological down-regulation of miR-1 expression in response to a hypertrophic stimulus in both humans and mice causes a similar metabolic reprogramming that supports muscle cell growth. Taken together, these data identify a novel post-translational mechanism of adult skeletal muscle metabolism regulation mediated by miR-1.

Satellite cell dynamics during skeletal muscle hypertrophy.

Skeletal muscle stem cells (MuSCs) display distinct behavior crucial for tissue maintenance and repair. Upon activation, MuSCs exhibit distinct modes of division: symmetric division, facilitating either self-renewal or differentiation, and asymmetric division, which dictates divergent cellular fates. This review explores the nuanced dynamics of MuSC division and the molecular mechanisms governing this behavior. Furthermore, it introduces a novel phenomenon observed in a subset of MuSCs under hypertrophic stimuli termed division-independent differentiation. Insights into the underlying mechanisms driving this process are discussed, alongside its broader implications for muscle physiology.

Natural product anticipation via chemical synthesis: Discovery of two new securinega alkaloids.

The isolation of a natural product conventionally precedes its chemical synthesis. Often, the isolation and structure determination of a natural product present in minute quantities in its natural source pose formidable challenges, akin to finding "a needle in a haystack." On the other hand, leveraging plausible biosynthetic insights and biomimetic synthetic expertise would allow for the prior synthesis of presumed natural products, followed by their verification in natural sources. In this study, we unveil two novel securinega alkaloids, securingines H and I, employing the natural product anticipation through synthesis approach. Structural analysis of securingines H and I suggests that they are biosynthetic derivatives of secu'amamine E and securinol A, respectively. We posit that this "synthesis first" strategy represents a valuable approach to the discovery of new natural products.

Methylome-proteome integration after late-life voluntary exercise training reveals regulation and target information for improved skeletal muscle health.

Exercise is a potent stimulus for combatting skeletal muscle ageing. To study the effects of exercise on muscle in a preclinical setting, we developed a combined endurance-resistance training stimulus for mice called progressive weighted wheel running (PoWeR). PoWeR improves molecular, biochemical, cellular and functional characteristics of skeletal muscle and promotes aspects of partial epigenetic reprogramming when performed late in life (22-24 months of age). In this investigation, we leveraged pan-mammalian DNA methylome arrays and tandem mass-spectrometry proteomics in skeletal muscle to provide detailed information on late-life PoWeR adaptations in female mice relative to age-matched sedentary controls (n = 7-10 per group). Differential CpG methylation at conserved promoter sites was related to transcriptional regulation genes as well as Nr4a3, Hes1 and Hox genes after PoWeR. Using a holistic method of -omics integration called binding and expression target analysis (BETA), methylome changes were associated with upregulated proteins related to global and mitochondrial translation after PoWeR (P = 0.03). Specifically, BETA implicated methylation control of ribosomal, mitoribosomal, and mitochondrial complex I protein abundance after training. DNA methylation may also influence LACTB, MIB1 and UBR4 protein induction with exercise - all are mechanistically linked to muscle health. Computational cistrome analysis predicted several transcription factors including MYC as regulators of the exercise trained methylome-proteome landscape, corroborating prior late-life PoWeR transcriptome data. Correlating the proteome to muscle mass and fatigue resistance revealed positive relationships with VPS13A and NPL levels, respectively. Our findings expose differential epigenetic and proteomic adaptations associated with translational regulation after PoWeR that could influence skeletal muscle mass and function in aged mice. KEY POINTS: Late-life combined endurance-resistance exercise training from 22-24 months of age in mice is shown to improve molecular, biochemical, cellular and in vivo functional characteristics of skeletal muscle and promote aspects of partial epigenetic reprogramming and epigenetic age mitigation. Integration of DNA CpG 36k methylation arrays using conserved sites (which also contain methylation ageing clock sites) with exploratory proteomics in skeletal muscle extends our prior work and reveals coordinated and widespread regulation of ribosomal, translation initiation, mitochondrial ribosomal (mitoribosomal) and complex I proteins after combined voluntary exercise training in a sizeable cohort of female mice (n = 7-10 per group and analysis). Multi-omics integration predicted epigenetic regulation of serine ß-lactamase-like protein (LACTB - linked to tumour resistance in muscle), mind bomb 1 (MIB1 - linked to satellite cell and type 2 fibre maintenance) and ubiquitin protein ligase E3 component N-recognin 4 (UBR4 - linked to muscle protein quality control) after training. Computational cistrome analysis identified MYC as a regulator of the late-life training proteome, in agreement with prior transcriptional analyses. Vacuolar protein sorting 13 homolog A (VPS13A) was positively correlated to muscle mass, and the glycoprotein/glycolipid associated sialylation enzyme N-acetylneuraminate pyruvate lyase (NPL) was associated to in vivo muscle fatigue resistance.

Microbial-Derived Exerkines Prevent Skeletal Muscle Atrophy.

Regular exercise yields a multitude of systemic benefits, many of which may be mediated through the gut microbiome. Here, we report that cecal microbial transplants (CMTs) from exercise-trained vs. sedentary mice have modest benefits in reducing skeletal muscle atrophy using a mouse model of unilaterally hindlimb-immobilization. Direct administration of top microbial-derived exerkines from an exercise-trained gut microbiome preserved muscle function and prevented skeletal muscle atrophy.

Development of an Easy-To-Handle Redox Active Group for Alcohols: Catalytic Transformation of Tertiary Alcohols to Nitriles.

The generation of radical intermediates via SET-mediated deoxygenation of activated alcohol derivatives is desirable, as alcohols can be utilized in various radical-mediated reactions. Herein, we introduce α-N-phthalimido-oxy isobutyrate (NPIB) as a novel activating group for alcohols. Essentially, it is a more chemically robust alternative to Overman's N-phthalimidoyl oxalate group. The utility of the NPIB group is showcased in the conversion of tertiary alcohols to nitriles under Ir/Cu dual catalysts and in the presence of TMSCN upon blue LED irradiation. With our newly developed NPIB handle, the reactivities of N-hydroxyphthalimide esters derived from carboxylic acids would be achievable with naturally and commercially more abundant alcohol substrates.

The effects of dietary self-monitoring intervention on anthropometric and metabolic changes via a mobile application or paper-based diary: a randomized trial.

BACKGROUND/OBJECTIVES: Weight loss via a mobile application (App) or a paper-based diary (Paper) may confer favorable metabolic and anthropometric changes. SUBJECTS/METHODS: A randomized parallel trial was conducted among 57 adults whose body mass indices (BMIs) were 25 kg/m2 or greater. Participants randomly assigned to either the App group (n = 30) or the Paper group (n = 27) were advised to record their foods and supplements through App or Paper during the 12-week intervention period. Relative changes of anthropometries and biomarker levels were compared between the 2 intervention groups. Untargeted metabolic profiling was identified to discriminate metabolic profiles. RESULTS: Out of the 57 participants, 54 participants completed the trial. Changes in body weight and BMI were not significantly different between the 2 groups (P = 0.11). However, body fat and low-density lipoprotein (LDL)-cholesterol levels increased in the App group but decreased in the Paper group, and the difference was statistically significant (P = 0.03 for body fat and 0.02 for LDL-cholesterol). In the metabolomics analysis, decreases in methylglyoxal and (S)-malate in pyruvate metabolism and phosphatidylcholine (lecithin) in linoleic acid metabolism from pre- to post-intervention were observed in the Paper group. CONCLUSIONS: In the 12-week randomized parallel trial of weight loss through a App or a Paper, we found no significant difference in change in BMI or weight between the App and Paper groups, but improvement in body fatness and LDL-cholesterol levels only in the Paper group under the circumstances with minimal contact by dietitians or health care providers. Trial Registration: Clinical Research Information Service Identifier: KCT0004226.

Synthesis of Suffranidine B.

Efficiently generating intricate molecular complexity is a coveted goal in organic synthesis. This can be realized through the implementation of inventive and audacious strategies coupled with the exploration and advancement of novel molecular reactivity pathways. Herein, we present a concise two-step synthesis of a high-oxidation state heterotrimeric securinega alkaloid, suffranidine B, from 2,3-dehydroallosecurinine and the vinylogous ketoaldehyde compound derived from kojic acid. Key to the success was the astute selection of appropriate acids during both the heterotrimerization and the desymmetrizing cyclization steps. This study underscores the value of biomimicry in the synthesis of complex natural products.

Controlling π-π Interactions of Highly Soluble Naphthalene Diimide Derivatives for Neutral pH Aqueous Redox Flow Batteries.

Organic redox-active molecules are a promising platform for designing sustainable, cheap, and safe charge carriers for redox flow batteries. However, radical formation during the electron-transfer process causes severe side reactions and reduces cyclability. This problem is mitigated by using naphthalene diimide (NDI) molecules and regulating their π-π interactions. The long-range π-stacking of NDI molecules, which leads to precipitation, is disrupted by tethering four ammonium functionalities, and the solubility approaches 1.5 m in water. The gentle π-π interactions induce clustering and disassembling of the NDI molecules during the two-electron transfer processes. When the radical anion forms, the antiferromagnetic coupling develops tetramer and dimer and nullifies the radical character. In addition, short-range-order NDI clusters at 1 m concentration are not precipitated but inhibit crossover. They are disassembled in the subsequent electron-transfer process, and the negatively charged NDI core strongly interacts with ammonium groups. These behaviors afford excellent RFB performance, demonstrating 98% capacity retention for 500 cycles at 25 mA cm-2 and 99.5% Coulombic efficiency with 2 m electron storage capacity.

Synthesis of High-Order and High-Oxidation State Securinega Alkaloids.

Securinega alkaloids, composed of more than 100 members characterized by the compact tetracyclic scaffold, have fascinated the synthetic community with their structural diversity and notable bioactivities. On the basis of the structural phenotype, oligomerizations and oxidations are major biosynthetic diversification modes of the basic Securinega framework. Despite the rich history of synthesis of basic monomeric Securinega alkaloids, the synthesis of oligomeric Securinega alkaloids, as well as oxidized derivatives, has remained relatively unexplored because of their extra structural complexity. In the first half of this Account, our synthetic studies toward high-order Securinega alkaloids are described. We aimed to establish a reliable synthetic method to form C14-C15' and C12-C15' bonds, which are prevalent connection modes between monomers. During our total synthesis of flueggenine C (9), we have invented an accelerated Rauhut-Currier reaction capable of forming the C14-C15' bond stereoselectively. Installation of the nucleophilic functionality to the Michael acceptor, which ushers the C-C bond forming conjugate addition to follow the intramolecular pathway, was the key to success. The C12-C15' linkage, which was inaccessible via an accelerated Rauhut-Currier reaction, was established by devising a complementary cross-coupling/conjugate reduction-based dimerization strategy that enabled the total synthesis of flueggenines D (11) and I (14). In this approach, the C12-C15' linkage was established via a Stille cross-coupling, and the stereochemistry of the C15' position was controlled during the following conjugate reduction step. In the later half of this Account, our achievements in the field of high-oxidation state Securinega alkaloids synthesis are depicted. We have developed oxidative transformations at the N1 and C2-C4 positions, where the biosynthetic oxidation event occurs most frequently. The discovery of a VO(acac)2-mediated regioselective Polonovski reaction allowed us to access the key 2,3-dehydroallosecurinine (112). Divergent synthesis of secu'amamine A (62) and fluvirosaones A (60) and B (61) was accomplished by exploiting the versatile reactivities of the C2/C3 enamine moiety in 112. We have also employed a fragment-coupling strategy between menisdaurilide and piperidine units, which allowed the installation of various oxygen-containing functionality on the piperidine ring. Combined with the late-stage, light-mediated epimerization and well-orchestrated oxidative modifications, collective total synthesis of seven C4-oxygenated securinine-type natural products was achieved. Lastly, the synthesis of flueggeacosine B (70) via two synthetic routes from allosecurinine (103) was illustrated. The first-generation synthesis (seven overall steps) employing Pd-catalyzed cross-coupling between stannane and thioester to form the key C3-C15' bond enabled the structural revision of the natural product. In the second-generation synthesis, we have invented visible-light-mediated, Cu-catalyzed cross-dehydrogenative coupling (CDC) between an aldehyde and electron-deficient olefin, which streamlined the synthetic pathway into four overall steps. Organisms frequently utilize dimerization (oligomerization) and oxidations during the biosynthesis as a means to expand the chemical space of their secondary metabolites. Therefore, methods and strategies for dimerizations and oxidations that we have developed using the Securinega alkaloids as a platform would be broadly applicable to other alkaloids. It is our sincere hope that lessons we have learned during our synthetic journey would benefit other chemists working on organic synthesis.

Collective total synthesis of C4-oxygenated securinine-type alkaloids via stereocontrolled diversifications on the piperidine core.

Securinega alkaloids have fascinated the synthetic chemical community for over six decades. Historically, major research foci in securinega alkaloid synthesis have been on the efficient construction of the fused tetracyclic framework that bears a butenolide moiety and tertiary amine-based heterocycles. These "basic" securinega alkaloids have evolved to undergo biosynthetic oxidative diversifications, especially on the piperidine core. However, a general synthetic solution to access these high-oxidation state securinega alkaloids is lacking. In this study, we have completed the total synthesis of various C4-oxygenated securinine-type alkaloids including securingines A, C, D, securitinine, secu'amamine D, phyllanthine, and 4-epi-phyllanthine. Our synthetic strategy features stereocontrolled oxidation, rearrangement, and epimerization at N1 and C2-C4 positions of the piperidine core within (neo)securinane scaffolds. Our discoveries provide a fundamental synthetic solution to all known securinine-type natural products with various oxidative and stereochemical variations around the central piperidine ring.

Synthesis of Dimeric Securinega Alkaloid Flueggeacosine B: From Pd-Catalyzed Cross-Coupling to Cu-Catalyzed Cross-Dehydrogenative Coupling.

We completed the synthesis of dimeric high-oxidation-state securinega alkaloid flueggeacosine B via two synthetic routes from allosecurinine. The first-generation synthesis (seven overall steps) involved a Liebeskind-Srogl cross-coupling reaction for the union of two functionalized fragments, the organostannane and the thioester. As a means to further streamline the synthetic route, we have developed a visible-light-mediated Cu-catalyzed cross-dehydrogenative coupling (CDC) reaction between an aldehyde and an electron-deficient olefin. This enabled the second-generation synthesis of flueggeacosine B from allosecurinine in four overall steps. The newly developed CDC reaction paves a direct way to a conjugated dicarbonyl moiety, a ubiquitous structural moiety present in various natural products.

On the Erosion of Enantiopurity of Rhodonoids via Their Asymmetric Total Synthesis.

Rhodonoid natural products are found in nature as a scalemic mixture. This interesting phytochemical feature is presumed to originate from a reversible electrocyclic ring opening of the chromene core present in the biogenetic precursors of rhodonoids. Herein, we systematically investigated factors that are responsible for this racemization event. This eventually led us to complete the asymmetric total synthesis of rhodonoids A, C, D, and G.

Test-retest reliability and validity of the Sitting Balance Measure-Korean in individuals with incomplete spinal cord injury.

STUDY DESIGN: Cross-cultural reliability and validity. OBJECTIVES: To develop and validate the Korean version of the Sitting Balance Measure (SBM-K) in Korean persons with incomplete spinal cord injury (ISCI). SETTING: Tertiary care center. METHODS: Twenty-nine persons with ISCI were evaluated using SBM-K, which was validated using the kappa coefficient and intraclass coefficient (ICC). The correlation between SBM-K individual items and total score was analyzed using Spearman's correlation, and the internal consistency of test items was measured using Cronbach's alpha. Additionally, the standard error measurement (SEM) and minimal detectable change (MDC) were measured. For the clinical validity of SBM-K, the correlation of SBM-K with the modified Sitting Balance Scale (mSBS) and the Korean-Spinal Cord Independence Measure-III (KSCIM-III) was determined via Spearman's correlation. Linear regression was performed to determine whether SBM-K could predict KSCIM-III. RESULTS: The weighted kappa score of the SBM-K individual items and ICC of SBM-K total score were 0.76-0.83 (good-very good) and 0.98 (0.95-0.99), respectively. The correlation between the SBM-K total score and individual items was notable (r = 0.78-0.98). Cronbach's alpha, SEM, and MDC of SBM-K were 0.98, 0.59, and 1.64, respectively. The clinical validity of SBM-K correlated with mSBS (r = 0.88) and KSCIM-III (r = 0.65-0.89). SBM-K accounted for 17-72% of the variance in predicting KSCIM-III. CONCLUSIONS: SBM-K showed sufficient test-retest reliability, validity, and marginal measurement errors. SBM-K can serve as an optimal clinical assessment tool for Korean ISCI patients and may provide clinicians with reliable sitting balance assessment in Korean clinical settings.

Interventional benefit of Pilates using Oov and mat on middle-aged women with lower urinary tract symptoms: emphasis on abdominal muscle thickness and muscular function.

Lower urinary tract symptoms (LUTS) have been considered as clinically prevalent symptom in women, and can be ameliorated by the change of abdominal muscles and pelvic floor muscle (PFM). This study investigated the efficacy of Pilates program using Oov and mat on the change of abdominal muscle thickness, PFM function, and LUTS clinical score. 53 women experiencing LUTS were randomly assigned to Oov Pilates exercise group (OPEG) (n=20), mat Pilates exercise group (MPEG) (n= 16), and symptomatic control group (SCG) (n=17), respectively, and two groups using Oov and mat participated in 8-week Pilates program. Thickness of abdominal muscle, functional movement of PFM, and LUTS clinical score were measured from all groups. Thickness of rectus abdominis, internal oblique abdominis, transversus abdominis was significantly improved in OPEG (P<0.05), however, MPEG showed a significant change only in transversus abdominis (P<0.05). In all abdominal muscles, OPEG had a significantly improved abdominal muscle thickness compared to SCG (P<0.05). Functional movement of PFM in OPEG was significantly decreased (P<0.005), but not in MPEG and SCG. In LUTS clinical score, OPEG and MPEG showed a significantly abated symptoms in degree of voiding-related symptoms and discomfort (P<0.005), but not in SCG. Our study highlighted that Pilates using Oov can be an effective intervention to ameliorate the quantitative quality of abdominal muscle thickness and PFM, which ultimately provides the satisfied self-clinical index in degree of voiding-related symptoms and discomfort.

The Efficacy of Pilates on Urinary Incontinence in Korean Women: A Metabolomics Approach.

Pilates has been known as exercise intervention that improves the function of pelvic floor muscle (PFM) associated with impacting urinary incontinence (UI). This study investigated the effect of Pilates on UI in Korean women by determining the change in functional movement of PFM (FMP) and metabolic profiles. UI group with Pilates (UIP, n = 13) participated in 8-weeks Oov Pilates program, and 8 subjects were assigned to Control and UI group with no Pilates (UINP), respectively. Before and after 8 weeks, plasma samples were collected from all participants, and ultrasonography was used to measure the functional change of PFM for calculating FMP ratio. Plasma samples were analyzed by mass spectrometry to identify the change of metabolic features. After 8-weeks intervention, FMP ratio was remarkably decreased in UIP (48.1% ↓, p < 0.001), but not in Control and UINP (p > 0.05). In metabolic features, L-Glutamine (m/z: 147.07 [M + H]+), L-Cystathionine (m/z: 240.09 [M + NH4]+), L-Arginine (m/z: 197.1 [M + Na]+), and L-1-Pyrroline-3-hydroxy-5-carboxylate (m/z: 147.07 [M + NH4]+) were significantly elevated solely in UIP (p < 0.001). Our study elucidated that Pilates can ameliorate the FMP and enhance the specific metabolic characteristics, which was potentially associated with invigorated PFM contractility to effectively control the bladder base and continence.

Biosynthetically Inspired Syntheses of Secu'amamine A and Fluvirosaones A and B.

Presented here is a concise synthesis of secu'amamine A, and fluvirosaones A and B from readily available allosecurinine and viroallosecurinine. The key C2-enamine derivative of (viro)allosecurinine, the presumed biosynthetic precursors of these natural products, was accessed, for the first time, by a VO(acac)2 -mediated regioselective Polonovski reaction. Formal hydration and 1,2-amine shift of this pluripotent enamine compound afforded secu'amamine A. Formal oxidative [3+2] cycloaddition reaction between this enamine and TMS-substituted methallyl iodide reagent paved the way to the precursors of fluvirosaones A and B. The relative stereochemistry at the C2 position of these advanced intermediates governs the fate of 1,2-amine shift leading to fluvirosaones A and B. The syntheses of potential biosynthetic precursors and investigations of their chemical reactivities have provided insights regarding the biogenesis of these natural products.

The effect of cardiac rehabilitation at 4 weeks postoperatively on quality of life in patients treated with totally thoracoscopic ablation.

There is a lack of evidence on the effect of exercise-based cardiac rehabilitation (EBCR) in patients treated with total thoracoscopic ablation (TTA) for atrial fibrillation (AF). Our study investigated the efficacy and safety of postoperative exercise intervention in patients recovering from TTA. Twenty-four patients participated in the study, and were divided into the two groups, exercise group (EG) (n=12) and control group (n= 12). Patients in EG performed the exercise intervention including the aerobic and resistance exercise program twice a week for 8 weeks, which was used as a hospital-based cardiac rehabilitation for the out-patient. A cardiopulmonary exercise test was administered to evaluate aerobic exercise capacity, and qualitative aspect of patient's life was assessed using the Short Form 36 questionnaires to compare pre and postoperative wellness of patient's life. Although there was an increase of VO2peak (peak oxygen uptake) after exercise intervention, no significant improvement was found (P=0.055). Two of 4 physical health scores (role-physical, P=0.013 and general health, P=0.05) and three of four mental health scores (vitality, P=0.027, social function, P=0.016, and mental health, P=0.003) were significantly improved after 8 weeks of EBCR. Each summarized scale in the physical (P=0.022) and mental (P= 0.004) survey section was also significantly improved in postoperative assessment compared to the preoperative one. In this context, we concluded that EBCR initiated at the time point of 4th week after TTA operation can guarantee the secure postoperative physical activity, and the 8 weeks of EBCR can effectively improve the quality of life in AF Patients.

Visible light induced alkene aminopyridylation using N-aminopyridinium salts as bifunctional reagents.

The development of intermolecular alkene aminopyridylation has great potential for quickly increasing molecular complexity with two valuable groups. Here we report a strategy for the photocatalytic aminopyridylation of alkenes using a variety of N-aminopyridinium salts as both aminating and pyridylating reagents. Using Eosin Y as a photocatalyst, amino and pyridyl groups are simultaneously incorporated into alkenes, affording synthetically useful aminoethyl pyridine derivatives under mild reaction conditions. Remarkably, the C4-regioselectivity in radical trapping with N-aminopyridinium salt can be controlled by electrostatic interaction between the pyridinium nitrogen and sulfonyl group of ß-amino radical. This transformation is characterized by a broad substrate scope, good functional group compatibility, and the utility of this transformation was further demonstrated by late-stage functionalization of complex biorelevant molecules. Combining experiments and DFT calculations on the mechanism of the reaction is investigated to propose a complete mechanism and regioselectivity.

Effect of 8-week Nordic walking training on nondominant hand grip and shoulder strength in middle-aged women.

Nordic walking (NW) is a full body training that can be performed with special pole, and has been recognized as an effective out-door activity which can improve the strength of upper extremity. Most previous studies mainly analyzed the effect of NW on the strength of dominant (DN) hand-grip strength, however, a clear scientific examination is needed whether nondominant (NDN) extremity can also be ameliorated by the NW. Therefore, the aim of our study is to investigate the effectiveness of 8 weeks NW training on the NDN handgrip and shoulder strength in healthy middle-aged women. 29 subjects were randomly divided into three groups: Nordic walking group (NWG, n=10), brisk walking group (BWG, n=11), and control group (CG, n=8). Handgrip and shoulder strength were measured by the hand dynamometer and isokinetic machine. NW training was performed 3 times a week, and had 10-min warm-up, 40-min main program consisted of ALFA (Attention, Long arms, Flat poles, Adaptes) technique and Turbo walking, and 10-min cool-down. In handgrip strength of DN hand and the shoulder flexor strength in the both sides, NWG and BWG showed significantly higher value compared to CG. In the NDN hand, NWG also showed significantly higher strength compared to CG, however, there was no significant difference in the handgrip strength/weight among groups. In NDN shoulder extension, significantly higher improvement was found in NWG and BWG compared to that of CG. In conclusion, our study showed that NW can improve the strength of upper extremity in subjects, and can be better approach to improve the NDN handgrip strength than brisk walking method could.