Using genetic association data to guide drug discovery and development: Review of methods and applications.

Evidence on the validity of drug targets from randomized trials is reliable but typically expensive and slow to obtain. In contrast, evidence from conventional observational epidemiological studies is less reliable because of the potential for bias from confounding and reverse causation. Mendelian randomization is a quasi-experimental approach analogous to a randomized trial that exploits naturally occurring randomization in the transmission of genetic variants. In Mendelian randomization, genetic variants that can be regarded as proxies for an intervention on the proposed drug target are leveraged as instrumental variables to investigate potential effects on biomarkers and disease outcomes in large-scale observational datasets. This approach can be implemented rapidly for a range of drug targets to provide evidence on their effects and thus inform on their priority for further investigation. In this review, we present statistical methods and their applications to showcase the diverse opportunities for applying Mendelian randomization in guiding clinical development efforts, thus enabling interventions to target the right mechanism in the right population group at the right time. These methods can inform investigators on the mechanisms underlying drug effects, their related biomarkers, implications for the timing of interventions, and the population subgroups that stand to gain the most benefit. Most methods can be implemented with publicly available data on summarized genetic associations with traits and diseases, meaning that the only major limitations to their usage are the availability of appropriately powered studies for the exposure and outcome and the existence of a suitable genetic proxy for the proposed intervention.

Relaxing parametric assumptions for non-linear Mendelian randomization using a doubly-ranked stratification method.

Non-linear Mendelian randomization is an extension to standard Mendelian randomization to explore the shape of the causal relationship between an exposure and outcome using an instrumental variable. A stratification approach to non-linear Mendelian randomization divides the population into strata and calculates separate instrumental variable estimates in each stratum. However, the standard implementation of stratification, referred to as the residual method, relies on strong parametric assumptions of linearity and homogeneity between the instrument and the exposure to form the strata. If these stratification assumptions are violated, the instrumental variable assumptions may be violated in the strata even if they are satisfied in the population, resulting in misleading estimates. We propose a new stratification method, referred to as the doubly-ranked method, that does not require strict parametric assumptions to create strata with different average levels of the exposure such that the instrumental variable assumptions are satisfied within the strata. Our simulation study indicates that the doubly-ranked method can obtain unbiased stratum-specific estimates and appropriate coverage rates even when the effect of the instrument on the exposure is non-linear or heterogeneous. Moreover, it can also provide unbiased estimates when the exposure is coarsened (that is, rounded, binned into categories, or truncated), a scenario that is common in applied practice and leads to substantial bias in the residual method. We applied the proposed doubly-ranked method to investigate the effect of alcohol intake on systolic blood pressure, and found evidence of a positive effect of alcohol intake, particularly at higher levels of alcohol consumption.

Estimating Time-Varying Exposure Effects Through Continuous-Time Modelling in Mendelian Randomization.

Mendelian randomization is an instrumental variable method that utilizes genetic information to investigate the causal effect of a modifiable exposure on an outcome. In most cases, the exposure changes over time. Understanding the time-varying causal effect of the exposure can yield detailed insights into mechanistic effects and the potential impact of public health interventions. Recently, a growing number of Mendelian randomization studies have attempted to explore time-varying causal effects. However, the proposed approaches oversimplify temporal information and rely on overly restrictive structural assumptions, limiting their reliability in addressing time-varying causal problems. This article considers a novel approach to estimate time-varying effects through continuous-time modelling by combining functional principal component analysis and weak-instrument-robust techniques. Our method effectively utilizes available data without making strong structural assumptions and can be applied in general settings where the exposure measurements occur at different timepoints for different individuals. We demonstrate through simulations that our proposed method performs well in estimating time-varying effects and provides reliable inference when the time-varying effect form is correctly specified. The method could theoretically be used to estimate arbitrarily complex time-varying effects. However, there is a trade-off between model complexity and instrument strength. Estimating complex time-varying effects requires instruments that are unrealistically strong. We illustrate the application of this method in a case study examining the time-varying effects of systolic blood pressure on urea levels.

A data-adaptive method for investigating effect heterogeneity with high-dimensional covariates in Mendelian randomization.

BACKGROUND: Mendelian randomization is a popular method for causal inference with observational data that uses genetic variants as instrumental variables. Similarly to a randomized trial, a standard Mendelian randomization analysis estimates the population-averaged effect of an exposure on an outcome. Dividing the population into subgroups can reveal effect heterogeneity to inform who would most benefit from intervention on the exposure. However, as covariates are measured post-"randomization", naive stratification typically induces collider bias in stratum-specific estimates. METHOD: We extend a previously proposed stratification method (the "doubly-ranked method") to form strata based on a single covariate, and introduce a data-adaptive random forest method to calculate stratum-specific estimates that are robust to collider bias based on a high-dimensional covariate set. We also propose measures based on the Q statistic to assess heterogeneity between stratum-specific estimates (to understand whether estimates are more variable than expected due to chance alone) and variable importance (to identify the key drivers of effect heterogeneity). RESULT: We show that the effect of body mass index (BMI) on lung function is heterogeneous, depending most strongly on hip circumference and weight. While for most individuals, the predicted effect of increasing BMI on lung function is negative, it is positive for some individuals and strongly negative for others. CONCLUSION: Our data-adaptive approach allows for the exploration of effect heterogeneity in the relationship between an exposure and an outcome within a Mendelian randomization framework. This can yield valuable insights into disease aetiology and help identify specific groups of individuals who would derive the greatest benefit from targeted interventions on the exposure.

The link between childhood physical activity enjoyment and adult kinesiophobia in individuals with chronic low back pain.

BACKGROUND: This study aimed to investigate the relationship between childhood physical activity enjoyment and current kinesiophobia among individuals with chronic low back pain (CLBP), considering the mediating influence of adult physical activity. METHODS: We recruited 648 adults (474 males, 174 females) with CLBP through an online platform. Of these, 99.1% (n = 642) were aged 18-60 years, and 0.9% (n = 6) were older than 60 years. Childhood physical activity enjoyment was retrospectively assessed using a single-item question to gauge participants' enjoyment during primary school. Kinesiophobia was measured with the 11-item Tampa Scale for Kinesiophobia (TSK-11), and physical activity was assessed focusing on walking, moderate, and vigorous physical activities. Age, sex, education, and income served as control variables in the analysis. RESULTS: A significant negative association was found between childhood physical activity enjoyment and adult kinesiophobia. Additionally, childhood physical activity enjoyment was positively associated with adult physical activity across the three types of physical activities. In the adjusted mediation model, walking was identified as the only statistically significant partial mediator. CONCLUSION: The findings highlight the long-term protective role of childhood physical activity enjoyment against the development of kinesiophobia in adulthood. Walking, in particular, holds unique therapeutic potential, emphasizing the importance of fostering physical activity enjoyment early in life for sustained physical activity and reduced risk of kinesiophobia among CLBP patients.

Genome-wide identification and expression analysis reveals spinach brassinosteroid-signaling kinase (BSK) gene family functions in temperature stress response.

BACKGROUND: Brassinosteroid (BR)- signaling kinase (BSK) is a critical family of receptor-like cytoplasmic kinase for BR signal transduction, which plays important roles in plant development, immunity, and abiotic stress responses. Spinach (Spinacia oleracea) is cold- tolerant but heat- sensitive green leafy vegetable. A study on BSK family members and BSKs- mediated metabolic processes in spinach has not been performed. RESULTS: We identified and cloned seven SoBSKs in spinach. Phylogenetic and collinearity analyses suggested that SoBSKs had close relationship with dicotyledonous sugar beet (Beta vulgaris) rather than monocotyledons. The analyses of gene structure and conserved protein domain/ motif indicated that most SoBSKs were relative conserved, while SoBSK6 could be a truncated member. The prediction of post-translation modification (PTM) sites in SoBSKs implied their possible roles in signal transduction, redox regulation, and protein turnover of SoBSKs, especially the N-terminal myristoylation site was critical for BSK localization to cell periphery. Cis-acting elements for their responses to light, drought, temperature (heat and cold), and hormone distributed widely in the promoters of SoBSKs, implying the pivotal roles of SoBSKs in response to diverse abiotic stresses and phytohormone stimuli. Most SoBSKs were highly expressed in leaves, except for SoBSK7 in roots. Many SoBSKs were differentially regulated in spinach heat- sensitive variety Sp73 and heat- tolerant variety Sp75 under the treatments of heat, cold, as well as exogenous brassinolide (BL) and abscisic acid (ABA). The bsk134678 mutant Arabidopsis seedlings exhibited more heat tolerance than wild- type and SoBSK1- overexpressed seedlings. CONCLUSIONS: A comprehensive genome- wide analysis of the BSK gene family in spinach presented a global identification and functional prediction of SoBSKs. Seven SoBSKs had relatively- conserved gene structure and protein function domains. Except for SoBSK6, all the other SoBSKs had similar motifs and conserved PTM sites. Most SoBSKs participated in the responses to heat, cold, BR, and ABA. These findings paved the way for further functional analysis on BSK- mediated regulatory mechanisms in spinach development and stress response.

Testing the mediatory role of kinesiophobia in the association between perceived greenspace and physical activity among individuals with chronic low back pain.

To test the mediatory role of kinesiophobia between greenspace and physical activity, we conducted a cross-sectional survey and recruited 801 participants with chronic low back pain. The level of greenspace was assessed using both perceived greenspace and the Normalized Difference Vegetation Index (NDVI). The frequency of walking and moderate and vigorous physical activities was measured using a brief assessment, while kinesiophobia was evaluated using the 11-item Tampa Scale for Kinesiophobia (TSK-11). The results revealed that perceived greenspace was positively associated with all measured physical activities, and was negatively associated with kinesiophobia. Meanwhile, NDVI was only positively associated with moderate and vigorous physical activity. Kinesiophobia played a marginal but significant mediating role in the association of perceived greenspace with walking, moderate physical activity, and vigorous physical activity. In conclusion, our findings offer early evidence of associations and pathways between greenspace and physical activity among individuals with chronic low back pain.

The relationship between health-promoting behaviors and negative emotions in college freshmen: a cross-lagged analysis.

Background: The prevalence of mental health issues has been gradually increasing among college students in recent years. Improvements in mental health can be achieved through changes in daily behavior and the use of psychological counseling. This study aims to investigate the relationship between health-promoting behaviors and negative emotions among college freshmen as they enter the university. It also examines the impact of various sub-dimensions of health-promoting behaviors and other factors on the negative emotions (stress, anxiety, and depression) experienced by college freshmen. Methods: Using the Negative Emotion and Health-Promoting Behavior scales, a 7-month longitudinal study was conducted on 4,252 college freshmen, with collection of data at two time points (T1: November 12, 2021; T2: June 17, 2022). Out of this longitudinal study, 3,632 valid samples were obtained. This research aimed to explore the association and impact between negative emotions and the level of health-promoting behaviors among college students during their time at the university. Results: ① There were significant differences in the levels of health-promoting behaviors and negative emotions over the course of 7 months (P < 0.05). Health-promoting behaviors were found to have a significant negative correlation with negative emotions (P < 0.05). ② Negative emotions at T1 significantly negatively predicted health-promoting behaviors at T2 (ß = -0.11, P < 0.01), while health-promoting behaviors at T1 significantly negatively predicted negative emotions at T2 (ß = -0.12, P < 0.001). ③ Stress management (ß = -0.104, P < 0.05; ß = -0.087, P < 0.05), self-actualization (ß = -0.282, P < 0.01; ß = -0.260, P < 0.05), health responsibility (ß = -0.057, P < 0.05; ß = -0.088, P < 0.05), and interpersonal relations (ß = 0.068, P < 0.01; ß = 0.138, P < 0.05) were important components in improving stress and anxiety. Self-actualization (ß = -0.437, P < 0.001), exercise (ß = 0.048, P < 0.001), nutrition (ß = 0.044, P < 0.001), and interpersonal relations (ß = 0.065, P < 0.001) were important components in improving depression. ④ Gender, place of household registration, and whether the individual is the only child were significant factors affecting negative emotions in college freshmen. Conclusion: The level of health-promoting behaviors is an important indicator for assessing the negative emotional states of college freshmen. Enhancing health-promoting behaviors across various dimensions can help alleviate different types of negative emotions. Gender, place of household registration, and being the only child are significant factors that influence negative emotions.

The impact of smartphone dependence on college students' sleep quality: the chain-mediated role of negative emotions and health-promoting behaviors.

Objective: Sleep disturbances among college students have become a significant issue affecting their daily lives. This study aims to explore the relationship between smartphone dependence and sleep quality and examine the mediating roles of negative emotions and health-promoting behaviors. Methods: A total of 23,652 college students were included in the study, and 21,314 valid questionnaires were collected. The survey assessed demographic factors, smartphone dependence, sleep quality, negative emotions, and health-promoting behaviors. A chain mediation analysis was conducted to examine the relationships among these factors. Results: Smartphone dependence was significantly positively correlated with sleep quality (r = 0.272, p < 0.001) and negative emotions (r = 0.414, p < 0.001), and significantly negatively correlated with health-promoting behaviors (r = -0.178, p < 0.001). Sleep quality was positively correlated with negative emotions (r = 0.472, p < 0.001) and negatively correlated with health-promoting behaviors (r = -0.218, p < 0.001).Smartphone dependence was a significant positive predictor of sleep quality. Moreover, negative emotions and health-promoting behaviors influenced the relationship between smartphone dependence and sleep quality. The total effect, direct effect, and indirect effect values were 0.304, 0.122, and 0.170, respectively. Conclusion: Different demographic factors (such as gender and place of residence) can lead to variations in different variables. Smartphone dependence and negative emotions have a positive impact on sleep quality among college students, while health-promoting behaviors have a negative impact. Smartphone dependence directly and positively affects sleep quality and can also influence it indirectly through the mediating effects of negative emotions and health-promoting behaviors, both individually and in a chain-like manner.

The chain mediating role of family health and physical activity in the relationship between life satisfaction and health-promoting lifestyles among young adults in China.

Background: Unhealthy lifestyles during adolescence are significant factors leading to chronic diseases in the future. Enhancing health-promoting lifestyles among young adults in China is crucial for preventing and reducing the risk factors of chronic diseases. Objective: This study aims to explore the relationships between life satisfaction, family health, physical activity, and health-promoting lifestyles among young adults in China. It also seeks to confirm the chain mediation role of family health and physical activity in the influence of life satisfaction on health-promoting lifestyles in this population. Methods: This study, conducted from August 2023 to November 2023, employed a random sampling method to recruit young adult participants aged 18-40 in the southwestern region of China. Variables were measured using the Satisfaction with Life Scale (SWLS), the Family Health Scale-Short Form (FHS-SF), the Physical Activity Rating Scale-3 (PARS-3), and the Health-Promoting Lifestyle Profile II Revised (HPLP-IIR). Data analysis was performed using SPSS 27.0 and the PROCESS macro version 4.1. Results: The results indicated that life satisfaction was positively correlated with family health (r = 0.225), physical activity (r = 0.245), and health-promoting lifestyles (r = 0.506). Family health was positively correlated with physical activity (r = 0.320) and health-promoting lifestyles (r = 0.312). Physical activity was positively correlated with health-promoting lifestyles (r = 0.429). Additionally, life satisfaction could influence health-promoting lifestyles directly (effect = 0.369) and through three mediation pathways: (a) family health (effect = 0.033); (b) physical activity (effect = 0.050); (c) family health and physical activity (effect = 0.020). Conclusion: This study supports the mediating role of family health and physical activity in the influence of life satisfaction on health behaviors among young adults in China. Therefore, we recommend that future public health initiatives place greater emphasis on family health and create conditions that facilitate physical activity for this group. This could be an important direction for further enhancing health-promoting lifestyles among young adults in China.

Exploring the impact of computer game playing on cognitive function, Alzheimer's disease risk, and brain-derived neurotrophic factor levels: Basic evidence from Mendelian randomization.

Introduction: The potential positive impact of computer game playing on cognitive function and its potential role in reducing the risk of Alzheimer's disease (AD) has been suggested. However, current observational studies have certain limitations. We utilized Mendelian randomization (MR) alongside extensive genome-wide association study (GWAS) data to examine the relationship between computer game playing, cognitive function, risk of AD, and levels of brain-derived neurotrophic factor (BDNF). Methods: We collected datasets on computer game playing, cognition function, risk of AD, and BDNF level from the IEU Open GWAS project. Causal effects were assessed using various MR methods, including inverse variance weighted (IVW), weighted median, MR-Egger, simple mode, and weighted mode. To ensure the accuracy of the results, sensitivity analyses were conducted. Results: Our analysis revealed a significant association between computer game playing and cognitive function (ß = 0.801, 95% CI: 0.351, 1.328, P = 0.001). There was no statistically significant association between computer game playing and either BDNF level or risk of AD (ß = -0.112, 95%CI: -1.315, 1.091, P = 0.855; OR = 1.000, 95% CI: 1.004, 0.997, P = 0.891, respectively). We further confirmed the reliability of our evidence through the MR-Egger intercept test, MR-PRESSO global test, Cochran's Q test, and funnel plots. Conclusion: The results of our study indicate that engaging in computer game playing may confer a safeguarding influence on cognitive function. This underscores the potential advantages associated with computer gaming. Nevertheless, given the constraints inherent in our research, further investigation is warranted to substantiate our findings and delve into the underlying mechanisms.

Estimation of time-varying causal effects with multivariable Mendelian randomization: some cautionary notes.

INTRODUCTION: For many exposures present across the life course, the effect of the exposure may vary over time. Multivariable Mendelian randomization (MVMR) is an approach that can assess the effects of related risk factors using genetic variants as instrumental variables. Recently, MVMR has been used to estimate the effects of an exposure during distinct time periods. METHODS: We investigated the behaviour of estimates from MVMR in a simulation study for different time-varying causal scenarios. We also performed an applied analysis to consider how MVMR estimates of body mass index on systolic blood pressure vary depending on the time periods considered. RESULTS: Estimates from MVMR in the simulation study were close to the true values when the outcome model was correctly specified: i.e. when the outcome was a discrete function of the exposure at the precise time points at which the exposure was measured. However, in more realistic cases, MVMR estimates were misleading. For example, in one scenario, MVMR estimates for early life were clearly negative despite the true causal effect being constant and positive. In the applied example, estimates were highly variable depending on the time period in which genetic associations with the exposure were estimated. CONCLUSIONS: The poor performance of MVMR to study time-varying causal effects can be attributed to model misspecification and violation of the exclusion restriction assumption. We would urge caution about quantitative conclusions from such analyses and even qualitative interpretations about the direction, or presence or absence, of a causal effect during a given time period.

[Calcaneal V-shaped osteotomy combined with subtalar arthrodesis for Stephens â ¡ and â ¢ calcaneal fractures malunion].

Objective: To investigate the effectiveness of calcaneal V-shaped osteotomy combined with subtalar arthrodesis in the treatment of Stephens Ⅱand Ⅲ calcaneal fracture malunion. Methods: The clinical data of 24 patients with severe calcaneal fracture malunion treated by calcaneal V-shaped osteotomy combined with subtalar arthrodesis between January 2017 and December 2021 were retrospectively analyzed. There were 20 males and 4 females with an average age of 42.8 years (range, 33-60 years). Conservative treatment of calcaneal fracture failed in 19 cases and operation failed in 5 cases. Stephens classification of calcaneal fracture malunion was type Ⅱ in 14 cases, and type Ⅲ in 10 cases. Preoperative Böhler angle of calcaneus was 4.0°-13.5° (mean, 8.6°), Gissane angle was 100°-152° (mean, 119.3°). The time from injury to operation was 6-14 months (mean, 9.7 months). American Orthopedic Foot and Ankle Society (AOFAS) ankle and hindfoot score and visual analogue scale (VAS) score were used to evaluate the effectiveness before operation and at last follow-up. Bone healing was observed and the healing time was recorded. The talocalcaneal height, talus inclination angle, Pitch angle, calcaneal width, and hindfoot alignment angle were measured. Results: Necrosis of the cuticle edge of the incision occurred in 3 cases, which were cured by dressing change and oral administration of antibiotic therapy. The other incisions healed by first intention. All the 24 patients were followed up 12-23 months, with an average of 17.1 months. The foot shape of the patients recovered well, the shoes were restored to the size before injury, and there was no anterior ankle impingement. Bone union was achieved in all patients, and the healing time ranged from 12 to 18 weeks, with an average of 14.1 weeks. At last follow-up, no adjacent joint degeneration occurred in all patients; 5 patients had mild foot pain during walking, which had no significant impact on daily life and work; no patient needed revision surgery. The AOFAS ankle and hindfoot score was significantly higher than that before operation ( P<0.001), the results were excellent in 16 cases, good in 4 cases, and poor in 4 cases, and the excellent and good rate was 83.3%. The VAS score, talocalcaneal height, talus inclination angle, Pitch angle, calcaneal width, and hindfoot alignment angle were significantly improved after operation ( P<0.001). Conclusion: Calcaneal V-shaped osteotomy combined with subtalar arthrodesis can effectively relieve hindfoot pain, correct talocalcaneal height, restore talus inclination angle, and reduce the risk of nonunion after subtalar arthrodesis.

Cysteine-rich receptor-like protein kinases: emerging regulators of plant stress responses.

Cysteine-rich receptor-like kinases (CRKs) belong to a large DUF26-containing receptor-like kinase (RLK) family. They play key roles in immunity, abiotic stress response, and growth and development. How CRKs regulate diverse processes is a long-standing question. Recent studies have advanced our understanding of the molecular mechanisms underlying CRK functions in Ca2+ influx, reactive oxygen species (ROS) production, mitogen-activated protein kinase (MAPK) cascade activation, callose deposition, stomatal immunity, and programmed cell death (PCD). We review the CRK structure-function relationship with a focus on the roles of CRKs in immunity, the abiotic stress response, and the growth-stress tolerance tradeoff. We provide a critical analysis and synthesis of how CRKs control sophisticated regulatory networks that determine diverse plant phenotypic outputs.

Socioecological influencers of health-promoting lifestyles in Chinese: a preliminary survey using convenient samples.

Background: Healthy lifestyles are considered important means to reduce the burden of diseases. This cross-sectional study was conducted based on the Ecological Model of Health Behavior (EMHB) to analyze the factors associated with the health-promoting lifestyles of Chinese residents. Methods: We carried out a cross-sectional investigation in July 2023. Our investigated factors included social-demographic characteristics (including sex, age, education level, employment status, marital status, personal monthly income, and daily behavioral habits [which were measured by a questionnaire)], health literacy [which was measured by the Chinese version of the Health Literacy Scale Short-Form scale (HLS-SF12)], and family health [which was measured by the Chinese version of the Short-Form of the Family Health Scale (FHS-SF)]. Our outcome was health promoting lifestyle, which was measured by a revised version of Health Promoting Lifestyle Profile-II (HPLP-IIR). Data were analyzed using stepwise regression. Results: A total of 1,402 participants were enrolled. Higher scores of HLS-SF12 (ß = 0.467), having regular exercise (ß = 0.212), and regular physical examination (ß = 0.088) were associated with better health-prompting lifestyles. However, older age (≥60 years) (ß = -0.046), drinking (ß = -0.066), and sleeping time (5-6 h/day) (ß = -0.048) were associated lower levels of health-prompting lifestyles. Living with family (ß = 0.077), FHS-SF (ß = 0.104), and married (ß = -0.077) were significant influencers. Unemployed (ß = -0.048), receiving retirement pay (ß = -0.053), and economic support provided by parents (ß = 0.094) were associated with better health-prompting lifestyles. There were multiple influencing factors of the six dimensions of the HPLP-IIR. Our findings indicate that community residents with higher health literacy, better family health, and health-related behaviors tend to have better health-promoting lifestyles. Conclusion: Our findings have confirmed the complex impacts of social-ecological factors on health-promoting lifestyles, which may help policy makers with health-promotion strategies making and also help researchers to control for confounding in study design.

Can Blood Flow Restriction Training Benefit Post-Activation Potentiation? A Systematic Review of Controlled Trials.

(1) Background: post-activation potentiation (PAP) plays an essential role in enhancing athletic performance. Various conditioning activities (CAs) have been developed to generate PAP before training or competitions. However, whether extra equipment can enhance the effectiveness of CAs is understudied. Hence, this systematic review aims to introduce and examine the effectiveness of blood flow restriction-based conditioning activities (BFR-CAs). (2) Methods: a literature search was conducted via Web of Science, PubMed, SPORTDiscus, and CNKI (a Chinese academic database). The systematic review included the literature concerning BFR-CAs and non-BFR-CAs. The methodological quality of included studies was considered to be "moderate quality" and "good quality" based on the Physiotherapy Evidence Database Scale. (3) Results: five studies were included in this study. Four studies were on lower limb strength training, and three of them suggested a greater PAP in BFR-CAs than in non-BFR counterparts. One study on upper limb strength training also supported the advantage of BFR-CAs. (4) Conclusions: BFR-CAs may be an emerging and promising strategy to generate PAP. Compared with non-BFR-CAs, BFR-CAs might be more efficient and practical for inexperienced sports people or athletes in non-power sports.

Selective Electrochemical Synthesis of 9-Aryl-10-sulfonyl Substituted Phenanthrene from Alkynes and Sulfonyl Hydrazides.

An efficient electrochemical synthesis of sulfonated phenanthrenes via the reaction of internal alkynes with sulfonyl hydrazides has been established. The protocol does not require a metal catalyst or external oxidants, providing a green and mild route to functionalized phenanthrenes. Moreover, the compatibility of various functional groups and decagram-scale experimental conditions demonstrate the practicality of the electrochemical strategy.