Wideband PRM: Highly Accurate and Sensitive Method for High-Throughput Targeted Proteomics.

Targeted mass spectrometry (MS) approaches, which are powerful methods for uniquely and confidently quantifying a specific panel of proteins in complex biological samples, play a crucial role in validating and clinically translating protein biomarkers discovered through global proteomic profiling. Common targeted MS methods, such as multiple reaction monitoring (MRM) and parallel-reaction monitoring (PRM), employ specific mass spectrometric technologies to quantify protein levels by comparing the transitions of surrogate endogenous (ENDO) peptides with those of stable isotope-labeled (SIL) peptide counterparts. These methods utilizing amino acid analyzed (AAA) SIL peptides warrant sensitive and precise measurements required for targeted MS assays. Compared with MRM, PRM provides higher experimental throughput by simultaneously acquiring all transitions of the target peptides and thereby compensates for different ion suppressions among transitions of a target peptide. However, PRM still suffers different ion suppressions between ENDO and SIL peptides due to spray instability, as the ENDO and SIL peptides were monitored at different liquid chromatography (LC) retention times. Here we introduce a new targeted MS method, termed wideband PRM (WBPRM), that is designed for high-throughput targeted MS analysis. WBPRM employs a wide isolation window for simultaneous fragmentation of both ENDO and SIL peptides along with multiplexed single ion monitoring (SIM) scans for enhanced MS sensitivity of the target peptides. Compared with PRM, WBPRM was demonstrated to provide increased sensitivity, precision, and reproducibility of quantitative measurements of target peptides with increased throughput, allowing more target peptide measurements in a shortened experiment time. WBPRM is a straightforward adaptation to a manufacturer-provided MS method, making it an easily implementable technique, particularly in complex biological samples where the demand for higher precision, sensitivity, and efficiency is paramount.

Assessing the Utility of Acoustic Radiation Force Impulse in the Evaluation of Non-Alcoholic Fatty Liver Disease with Severe Obesity or Steatosis.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) encompasses a heterogeneous spectrum ranging from simple steatosis to fibrosis and cirrhosis. Fibrosis, associated with long-term overall mortality and liver-related events, requires evaluation. Traditionally, liver biopsy has been the gold standard for diagnosing fibrosis. However, its invasive nature, potential complications, and sampling variability limit widespread use. Consequently, various non-invasive tests have been developed as alternatives for diagnosing fibrosis in NAFLD patients. AIM: This study aimed to compare the accuracy of non-invasive tests (NITs) and evaluate the diagnostic accuracy of acoustic radiation force impulse (ARFI), one of the point shear wave techniques, compared to conventional methods, assessing its effective role in diagnosis. METHODS: This is a retrospective study; a total of 136 patients diagnosed with fatty liver disease through ultrasonography were enrolled. The anthropometric data of the patients were collected on the day of admission and blood tests, measurements of ARFI, and a point shear test were conducted using abdominal ultrasound; a biopsy was performed the following day. In addition, we calculated the aspartate aminotransferase-to-platelet ratio index (APRI) index based on four factors (FIB-4) and the NAFLD fibrosis score (NFS). Subsequently, we assessed the diagnostic accuracy of NITs within various subgroups based on the extent of obesity, steatosis, or NAFLD activity score. RESULTS: ARFI has been shown to have the highest diagnostic value among various NITs, with AUROC values of 0.832, 0.794, 0.767, and 0.696 for ARFI, APRI, FIB-4, and NFS, respectively. In the morbidly obese subgroup, the AUROC values of ARFI, APRI, FIB-4, and NFS were 0.805, 0.769, 0.736, and 0.674. In the group with severe steatosis or non-alcoholic steatohepatitis (NASH), the AUROC values were 0.679, 0.596, 0.661, and 0.612, respectively, for severe steatosis and 0.789, 0.696, 0.751, and 0.691, respectively, for NASH. CONCLUSIONS: In conclusion, ARFI is not affected by various factors and maintains diagnostic accuracy compared to serum NITs. Therefore, we can recommend ARFI as a valuable diagnostic test to screen for advanced fibrosis in patients with NAFLD.

Primary Ewing sarcoma of the kidney mimicking cystic papillary renal cell carcinoma in an older patient: A case report.

BACKGROUND: Ewing's sarcoma (ES) is a neuroectodermal tumor that typically occurs in the bones and soft tissues of children and young adults. Primary renal ES is rare; only a few cases and a small case series have been documented, and only four cases involved primary renal ES in older people (> 65 years old). CASE SUMMARY: Herein, we describe the radiological and pathological features of primary renal ES in an older person. A 76-year-old man complained of poor oral intake and was found to have a large cystic renal mass with indistinct margins on computed tomography. Ultrasound-guided biopsy revealed that the tumor contained small round blue cells. The patient underwent a right radical nephrectomy. The tumor cells showed diffuse membranous CD99, and nuclear friend leukemia integration 1 transcription factor and NK2 Homeobox 2. Fluorescence in situ hybridization revealed EWSR1 translocation. Postoperatively, 18F-fluorodeoxyglucose positron emission tomography revealed no evidence of metastasis. The patient was diagnosed with primary renal ES. Six months following the surgery, local recurrence and distant metastasis were observed. Primary renal ES is rare and often lethal in older individuals. The specific imaging findings are unknown, and treatment protocols have not been standardized. CONCLUSION: This case report describes the radiological and pathological features of primary renal ES in an older person.

Smartphone application-based rehabilitation in patients with chronic respiratory and cardiovascular diseases.

Rehabilitation improves symptoms, quality of life, and survival in patients with chronic respiratory or cardiovascular disease. We evaluated smartphone application-based rehabilitation programs for patients with chronic respiratory or cardiovascular diseases. This was a single-center prospective single arm study. Participants underwent smartphone application-based pulmonary or cardiac rehabilitation for 12 weeks. A total of 93 participants were recruited, and 75 visited after rehabilitation. Their median age was 67.0 (interquartile range, 60.0-70.8) years, and 60 (80.0%) were men. For patients with chronic respiratory disease (n = 41), VO2peak (median 13.7 to 15.4 ml/kg/min, P = 0.049), chronic obstructive pulmonary disease assessment test (median 14 to 6, P < 0.001), Euro-QoL 5-Dimension 5-Level (EQ-5D-5L) index (median 0.795 to 0.862, P = 0.001), and Health-related Quality of Life Instrument with 8 Items (HINT-8) index (median 0.784 to 0.855, P < 0.001) were significantly improved. For patients with chronic cardiovascular disease (n = 34), VO2peak (median 21.8 to 23.3, P = 0.007), EQ-5D-5L index (median 0.871 to 1.000, P = 0.037), and HINT-8 index (median 0.890 to 0.903, P < 0.001) were significantly improved. The smartphone application-based rehabilitation program improved exercise capacity and quality of life in patients with chronic respiratory or cardiovascular disease.Trial registration: https://clinicaltrials.gov/ct2/show/NCT05383950 (20/05/2022).

Ashwagandha Ethanol Extract Attenuates Sarcopenia-Related Muscle Atrophy in Aged Mice.

The investigation focused on the impact of Withania somnifera (ashwagandha) extract (WSE) on age-related mechanisms affecting skeletal muscle sarcopenia-related muscle atrophy in aged mice. Beyond evaluating muscular aspects, the study explored chronic low-grade inflammation, muscle regeneration, and mitochondrial biogenesis. WSE administration, in comparison to the control group, demonstrated no significant differences in body weight, diet, or water intake, affirming its safety profile. Notably, WSE exhibited a propensity to reduce epidermal and abdominal fat while significantly increasing muscle mass at a dosage of 200 mg/kg. The muscle-to-fat ratio, adjusted for body weight, increased across all treatment groups. WSE administration led to a reduction in the pro-inflammatory cytokines TNF-α and IL-1ß, mitigating inflammation-associated muscle atrophy. In a 12-month-old mouse model equivalent to a 50-year-old human, WSE effectively preserved muscle strength, stabilized grip strength, and increased muscle tissue weight. Positive effects were observed in running performance and endurance. Mechanistically, WSE balanced muscle protein synthesis/degradation, promoted fiber differentiation, and enhanced mitochondrial biogenesis through the IGF-1/Akt/mTOR pathway. This study provides compelling evidence for the anti-sarcopenic effects of WSE, positioning it as a promising candidate for preventing sarcopenia pending further clinical validation.

Necking Reduction at Low Temperature in Aspect Ratio Etching of SiO2 at CF4/H2/Ar Plasma.

This study investigated the effect of temperature on the aspect-ratio etching of SiO2 in CF4/H2/Ar plasma using patterned samples of a 200 nm trench in a low-temperature reactive-ion etching system. Lower temperatures resulted in higher etch rates and aspect ratios for SiO2. However, the plasma property was constant with the chuck temperature, indicated by the line intensity ratio from optical emission spectroscopy monitoring of the plasma. The variables obtained from the characterization of the etched profile for the 200 nm trench after etching were analyzed as a function of temperature. A reduction in the necking ratio affected the etch rate and aspect ratio of SiO2. The etching mechanism of the aspect ratio etching of SiO2 was discussed based on the results of the surface composition at necking via energy-dispersive X-ray spectroscopy with temperature. The results suggested that the neutral species reaching the etch front of SiO2 had a low sticking coefficient. The bowing ratio decreased with lowering temperature, indicating the presence of directional ions during etching. Therefore, a lower temperature for the aspect ratio etching of SiO2 could achieve a faster etch rate and a higher aspect ratio of SiO2 via the reduction of necking than higher temperatures.

Variability of Transrectal Shear Wave Elastography in a Phantom Model.

Purpose: This study aimed to assess the variability of transrectal shear wave elastography (SWE) using a designed phantom. Materials and Methods: In a phantom, the SWE values were examined by two radiologists using agarose and emulsion silicone of different sizes (1, 2, and 3 cm) and shapes (round, cubic) at three depths (1, 2, and 3 cm), two region of interest (ROI) and locations (central, peripheral) using two ultrasound machines (A, B from different vendors). Variability was evaluated using the coefficient of variation (CV). Results: The CVs decreased with increasing phantom size. Significant changes in SWE values included; agarose phantom at 3 cm depth (p < 0.001; machine A), 1 cm depth (p = 0.01; machine B), emulsion silicone at 2 cm depth (p = 0.047, p = 0.020; both machines). The CVs increased with increasing depth. Significant changes in SWE values included; 1 cm agarose (p = 0.037, p = 0.021; both machines) and 2 cm agarose phantom (p = 0.047; machine A). Significant differences in SWE values were observed between the shapes for emulsion silicone phantom (p = 0.032; machines A) and between ROI locations on machine B (p ≤ 0.001). The SWE values differed significantly between the two machines (p < 0.05). The intra-/inter-operator agreements were excellent (intraclass correlation coefficient > 0.9). Conclusion: The phantom size, depth, and different machines affected the variability of transrectal SWE.

Novel Cu(II) complexes as DNA-destabilizing agents and their DNA nuclease activity.

Here, we report a series of four novel Cu complexes, namely 2-(piperidin-1-ylmethyl)quinoline copper(II) nitrate, [LACu(NO3)2] (Cu1), 4-(quinolin-2-ylmethyl)morpholine copper(II) nitrate, [LBCu(NO3)2] (Cu2), 4-(quinolin-2-ylmethyl)morpholine copper(II) chloride, [LBCuCl2] (Cu3), and 2-(piperidin-1-ylmethyl)pyridine copper(II) chloride, [LCCu(µ-Cl)Cl]2 (Cu4). X-ray diffraction studies revealed that the geometry around the Cu(II) center could be best described as distorted octahedral in Cu1 and Cu2, whereas Cu3 and Cu4 showed distorted tetrahedral and square pyramidal geometries, respectively. DNA binding studies showed that Cu complexes Cu1-3 containing quinoline interacted via minor groove binding, whereas the Cu4 complex containing pyridine interacted via intercalation. All Cu complexes containing quinoline and pyridine caused destabilization of DNA at specific homogeneous G-C regions. The Cu1-3 complexes as groove binders destabilized the DNA structure much more than the Cu4 complex as an intercalator. Regarding groove binders, the Cu2 complex containing quinoline and morpholine caused the highest distortion and destabilization of the DNA structure, leading to high DNA cleavage efficiency.

Synthesis of S-Carbamidomethyl Cysteine and Its Use for Quantification of Cysteinyl Peptides by Targeted Proteomics.

Proteomics has played a central role in the identification of reliable disease biomarkers, which are the basis of precision medicine, a promising approach for tackling recalcitrant diseases such as cancer, that elude conventional treatments. Among proteomic methodologies, targeted proteomics employing stable isotope-labeled (SIL) internal standards is particularly suited for the clinical translation of biomarker information owing to its high throughput and accuracy in the quantitative analysis of patient-derived proteomes. Using SIL internal standards ensures the utmost level of confidence in detection and precision in targeted MS experiments. For successfully establishing assays based on targeted proteomics, it is crucial to secure broad coverage when selecting the SIL standard peptide panel. However, cysteinyl peptides have often been excluded because of cysteine's high chemical reactivity. To address this limitation, a new cysteine building block was developed by incorporating a sulfhydryl group configured with an S-carbamidomethyl group, which is commonly used in proteome sampling. This compound was found to be chemically stable and applicable to a variety of solid-phase peptide synthesis (SPPS) campaigns. Furthermore, a direct comparison of the synthesized SIL peptides and tryptic endogenous peptides demonstrated the potential utility of an SPPS flow based on the new cysteine building block for improving the success of targeted proteomic applications.

Smartphone application-based rehabilitation in patients with chronic respiratory and cardiovascular diseases: a randomised controlled trial study protocol.

INTRODUCTION: Rehabilitation is well known to improve clinical symptoms and decrease the risk of mortality in patients with chronic respiratory or cardiovascular diseases. We will evaluate the efficacy of smartphone application-based rehabilitation programmes in patients with chronic respiratory or cardiovascular diseases. METHODS AND ANALYSIS: This single-centre single-blind randomised controlled trial will recruit a total of 162 participants from Asan Medical Center (81 patients each for pulmonary and cardiac rehabilitation, respectively). Participants will be assigned to the pulmonary or cardiac rehabilitation groups based on their underlying disease. Participants will be allocated randomly into the intervention or control groups at the ratio of 2:1 (54 and 27 patients). The intervention group will be provided with a smartphone application and undergo smartphone application-based rehabilitation for 12 weeks. The control group will receive the usual outpatient medical treatment without rehabilitation. Participants will be evaluated at baseline and at the end of the rehabilitation. The primary outcomes will be exercise capacity, such as maximal oxygen consumption on cardiopulmonary exercise test for both groups, chronic obstructive pulmonary disease assessment test for the pulmonary rehabilitation group, and Health-related Quality of Life Instrument with 8 Items questionnaires for the cardiac rehabilitation group. The secondary outcomes will include quality of life questionnaires, symptom scores, pulmonary function test and limb muscle test. ETHICS AND DISSEMINATION: The study protocol was approved by the Institutional Review Board of Asan Medical Center. Written informed consent will be obtained from all participants prior to inclusion. The findings from this study will be disseminated through peer-reviewed scientific journals and conferences. TRIAL REGISTRATION NUMBER: NCT05610358.

SMARCA4-deficient undifferentiated thoracic tumor: A case report.

BACKGROUND: SMARCA4-deficient undifferentiated tumors (SMARCA4-DUTs) present with diverse clinical manifestations and progress to metastasis and even cause death within a few months. This novel subset of undifferentiated tumors occurs in the middle-aged population and is strongly associated with a smoking history. Distinguishing it from other malignancies is challenging. CASE SUMMARY: A 62-year-old man presented with chest pain for 7 d. The patient had no respiratory symptoms and normal pulmonary function test results. The patient had been a smoker for 8 years and quit smoking 2 years ago. Chest computed tomography revealed a huge mass involving the left upper and lower lung lobes with pericardial invasion and multiple metastases. Tumor samples were obtained using open frozen biopsy, after several unsuccessful attempts. The tumor was composed of sheets of undifferentiated disclosive cells with vesicular nuclei and prominent nucleoli. The differential diagnosis included high-grade lymphoma, germ cell tumor, NUT carcinoma, undifferentiated carcinoma, and sarcoma. The tumor cells were large, arranged in sheets, and did not exhibit glandular or squamous differentiation. Frequent foci of necrosis were noted. There was no evidence of epithelial differentiation on immunohistochemical staining. The SMARCA4 stain showed complete loss of expression of SMARCA4, which is diagnostic. CONCLUSION: In the present case, thoracic SMARCA4-DUT was diagnosed based on clinical features, absence of epithelial differentiation, and negative SMARCA4 expression.

Adult-Onset Leukoencephalopathy with Axonal Spheroid and Pigmented Glia: Different Histological Spectrums Presented in Autopsy Cases of Siblings and a Surgical Case of Stereotactic Biopsy.

Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia encompasses hereditary diffuse leukoencephalopathy with axonal spheroids and pigmented orthochromatic leukodystrophy. We describe the clinicopathological and genetic findings of three patients with this disorder. All patients presented with dysarthria, with or without cognitive decline. The first and second patients were siblings who died of the disease at ages 42 and 54, respectively, while the third patient has been bedridden. Brain magnetic resonance imaging revealed T2 hyperintensities in the subcortical and periventricular white matter. Pathological diagnosis was established by brain autopsy in cases 1 and 2, and a stereotactic brain biopsy in case 3, followed by genetic analysis of colony stimulating factor-1 receptor gene. A heterozygous c.2345G > A (p.R782H) variant was identified in the autopsy-proven cases, and a c.1765G > A (p.G589R) variant in the biopsy-proven case. Postmortem examination revealed severe white matter degeneration involving the bilateral frontoparietal lobes, but sparing the subcortical U-fibers. All cases revealed widespread loss of myelinated axons in the white matter lesions; however, axonal spheroids and pigmented macrophages were abundant in cases 1 and 3 and much less in case 2. Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia should be considered in patients with presenile dementia and diffuse white matter lesions.

A Case of Cerebellar Intraparenchymal Subependymoma with Next-Generation Sequencing Analysis.

Subependymomas are rare, intraventricular glial tumors histologically characterized by clusters of small uniform cells distributed in an abundant fibrillary matrix. These tumors can arise in the parenchyma of the cerebrum, cerebellum, or spinal cord. Herein, we report an extremely rare case of cerebellar intraparenchymal subependymoma in a 62-year-old woman. The patient presented with dizziness for several years, and brain magnetic resonance imaging revealed a well-defined solid mass in the right cerebellum, upon which a stereotactic biopsy was performed. Histologically, the tumor showed a distinctive multinodular pattern with unevenly distributed glial cells and an abundant fibrillary matrix. Next-generation sequencing analysis showed balanced genomes without genetic alterations, including single-nucleotide variants, small insertions, deletions, or copy number alterations. Follow-up magnetic resonance imaging revealed that the size of the mass has not changed; the patient has not received any surgical treatments since the pathologic diagnosis and is living healthily.

Lipid Profiles Obtained from MALDI Mass Spectrometric Imaging in Liver Cancer Metastasis Model.

Liver cancer metastasis is known to be a poor prognosis and a leading cause of mortality. To overcome low therapeutic efficacy, understanding the physiological properties of liver cancer metastasis is required. However, the metastatic lesion is heterogeneous and complex. We investigate the distribution of lipids using matrix-assisted laser desorption/ionization-mass spectrometry imaging (MALDI-MSI) in an experimental metastasis model. We obtained the differentially expressed mass peaks in comparison between normal sites and metastatic lesions. The relationship of mass to charge ratio (m/z) and intensity were measured, m/z-indicated species were analyzed by MALDI-MS/MS analysis, and identification of these mass species was confirmed using the METASPACEannotation platform and Lipid Maps®. MALDI-MSI at m/z 725.6, 734.6, 735.6, 741.6, 742.6, 744.6, 756.6, and 772.6 showed significantly higher intensity, consistent with the metastatic lesions in hematoxylin-stained tissues. Sphingomyelin SM [d18:0/16:1], phosphatidylcholine (PC) [32:0], PC [31:0], PC [31:1], and PE [36:2] were highly expressed in metastatic lesions. Our results could provide information for understanding metastatic lesions. It suggests that the found lipids could be a biomarker for the diagnosis of metastatic lesions.

Measurement of re-entry plasma density using microwave reflectometer in laboratory.

A laboratory-scale experiment was conducted to reproduce plasma with properties similar to re-entry plasma and measure the plasma density using a microwave reflectometer system. To reproduce a similar re-entry plasma, a high-temperature refractory anode vacuum arc plasma method was used among arc plasma discharge methods, and arc plasma having high temperature, high speed, and high-density plasma characteristics was discharged inside a vacuum chamber. A hot refractory anode made of tungsten was used to show high-temperature plasma characteristics, and high-density plasma characteristics were demonstrated using re-evaporation around the anode. In addition, high-speed plasma characteristics were exhibited using a brass cathode. This kind of arc plasma discharge has a high temperature and is characterized by high fluctuation. It was determined that a microwave reflectometer system with good spatial resolution and non-invasiveness would be suitable to measure plasma with these characteristics. The reflection coefficient was measured using a reflector system by comparing the voltage between the traveling wave applied to the plasma and the reflected wave reflected by the plasma, and the technique of analyzing the plasma density using the difference between these reflection coefficients was used. In this study, the plasma density according to the pressure change was typically measured as 1012-1013 cm-3, which showed a similar tendency to the result of measuring the actual re-entry plasma density.

Chrysin-Induced G Protein-Coupled Estrogen Receptor Activation Suppresses Pancreatic Cancer.

Pancreatic cancer (PC) has a high mortality rate due to its poor prognosis and the possibility of surgical resection in patients with the disease. Importantly, adjuvant chemotherapy is necessary to improve PC prognosis. Chrysin, a natural product with anti-inflammatory, antioxidant, and anticancer properties, has been studied for several years. Our previous study demonstrated that chrysin induced G protein-coupled estrogen receptor (GPER) expression and regulated its activity in breast cancer. Herein, we investigated whether chrysin-induced GPER activation suppresses PC progression in MIA PaCa-2 cells and a xenograft model. To determine its mechanism of action, cytotoxicity and clonogenic assays, a FACS analysis, and Western blotting were performed. Furthermore, the delay in tumor growth was evaluated in the MIA PaCa-2-derived xenograft model. Tumor tissues were investigated by Western blotting, immunohistochemistry, and a proteomic analysis. Chrysin caused cell cycle arrest and significantly decreased cell viability. Following co-treatment with chrysin and 17ß-estradiol, the inhibitory effect of chrysin on cell proliferation was enhanced. In the xenograft model, chrysin and G1 (a GPER agonist) significantly delayed tumor growth and reduced both Ki-67 (a proliferation marker) and c-Myc expressions in tumor tissues. The proteomic analysis of tumor tissues identified that rho-associated coiled-coil containing protein kinase 1 (ROCK1), transgelin 2 (TAGLN2), and FCH and Mu domain containing endocytic adaptor 2 (FCHO2) levels were significantly reduced in chrysin-treated tumor tissues. High ROCK1, TAGLN2, and FCHO2 expressions were indicative of low overall PC survival as found using the Kaplan-Meier plotter. In conclusion, our results suggest that chrysin suppresses PC progression through the activation of GPER and reductions in ROCK1, TAGLN2, and FCHO2 expressions.

Immunomodulatory Effect of Polysaccharide from Fermented Morinda citrifolia L. (Noni) on RAW 264.7 Macrophage and Balb/c Mice.

This study aims to determine the immunomodulatory effects of a polysaccharide fraction from fermented M. citrifolia L. (FMP) in RAW 264.7 macrophages and Balb/c mice. M. citrifolia was fermented for 72 h using Lactobacillus brevis; polysaccharides were extracted using ethanol precipitation. The RAW 264.7 cells exposed to FMP (50, 100, and 200 µg/mL) for 24 h showed increased NO production, proinflammatory cytokine (IL-1ß, IL-6, and TNF-α) release, and COX-2 and iNOS protein expression. FMP (100, 200 mg/kg) and deacetylasperulosidic acid (DAA) (20 mg/kg) administered orally to Balb/c mice for 14 days upregulated NO production and NK cytotoxicity in abdominal cavity and spleen, respectively. Th1 and Th2 cytokines production and immune cell numbers increased in spleen, mesenteric lymph nodes (MLN), peritoneal exudate cells (PEC), Peyer's patches (PP), and peripheral blood mononuclear cells (PBMC). Therefore, FMP containing DAA can be used as materials for health functional foods to enhance immune responses.

High performance transition metal-based electrocatalysts for green hydrogen production.

Hydrogen energy is a promising energy source that is environmentally friendly due to its long-term, large-capacity storage and low greenhouse gas emissions. However, the mass production of hydrogen is still technically difficult due to limitations in efficiency, stability, and cost, even though it can satisfy all of the current energy demands. Water splitting using an electrocatalyst is an efficient method for environmentally friendly hydrogen production, and various catalyst-related studies are being conducted for this purpose. For the last decade, transition metal-based compositions have been at the center of water splitting catalyst research. Despite numerous studies and developments, studies on transition metal-based catalysts so far still have various problems to be solved. Although excellent review papers on transition metal-based catalysts have been reported, the overall scope of transition metal-based catalysts has rarely been covered in the reports. In this review, we present the research about overall transition metal-based electrocatalysts for hydrogen production from four different categories, namely, alloys, transition-metal dichalcogenides (TMDs), layered double hydroxides (LDHs), and single-atom catalysts (SACs). The fundamental roles of metal alloying and unique electrical properties of TMDs, LDHs, and SACs are mainly discussed. Furthermore, we present the recent advances in photovoltaic-electrochemical (PV-EC) systems for sustainable hydrogen production. Finally, perspectives on the issues to be addressed in the research on transition metal-based electrocatalysts are provided.

Clinical Significance of Ventricular Premature Contraction Provoked by the Treadmill Test.

Background and Objectives: The treadmill test (TMT) is a predictive tool for myocardial ischemia. Recently, exercise-provoked ventricular premature contracture (VPC) during TMT was shown to have a relation with coronary artery disease and cardiovascular mortality. Therefore, we evaluate clinical correlates of exercise-provoked VPC and compare the predictive power for myocardial ischemia and cardiovascular events. Method: Data of 408 patients (≥18 years of age) who underwent TMT for work up of angina, palpitation, dyspnea, syncope, or arrhythmia between February 2015, and January 2016, were collected with consent at Samsung Medical Center, Seoul, Republic of Korea. Among total of 408 patients, 208 were excluded according to the previous history of PCI or CABG, previous MI, decreased left ventricular ejection fraction lower than 50%, arrhythmia that could affect ST-segment change on ECG. Results: Among 200 patients, 32 (16.0%) developed exercise-provoked VPC (21 patients in the exercise phase, 20 patients in the recovery phase). Of them, 20 patients (10.0%) showed positive TMT, and 4 patients (2.0%) underwent revascularization after TMT. Among 21 patients showing exercise phase VPC, 5 (23.8%) showed positive TMT results. In patients younger than 65 years, exercise phase VPC was associated with positive TMT (odds ratio 6.879, 1.458-32.453) considering demographics and previous medical history in multivariable analysis. Among the 20 patients showing recovery phase VPC, 2 (10.0%) underwent revascularization after TMT. In multivariable analysis, recovery phase VPC was associated with revascularization (odds ratio 9.381, 1.144-76.948) considering age, sex, BMI, and TMT result. Conclusion: VPC during the treadmill test was a useful predictor of myocardial ischemia in this study.

Reformulation of Trivers-Willard hypothesis for parental investment.

The Trivers-Willard hypothesis (TWH) plays a central role in understanding the optimal investment strategies to male and female offspring. Empirical studies of TWH, however, yielded conflicting results. Here, we present models to predict optimal comprehensive multi-element parental strategies composed of primary sex ratio, brood size, resource allocation among offspring, and the resultant secondary sex ratio. Our results reveal that the optimal strategy depends on sex differences in the shape of offspring fitness function rather than in fitness variance. Also, the slope of the tangent line (through the origin) to the offspring fitness function can be used to predict the preferred offspring sex. We also briefly discuss links between the model and the empirical research. This comprehensive reformulation of TWH will offer a thorough understanding of multi-element parental investment strategies beyond the classical TWH.