Controlling Redox Potential of a Manganese(III)-Bis(hydroxo) Complex through Protonation and the Hydrogen-Atom Transfer Reactivity.

A series of mononuclear manganese(III)-hydroxo and -aqua complexes, [MnIII(TBDAP)(OH)2]+ (1), [MnIII(TBDAP)(OH)(OH2)]2+ (2) and [MnIII(TBDAP)(OH2)2]3+ (3), were prepared from a manganese(II) precursor and confirmed using various methods including X-ray crystallography. Thermodynamic analysis showed that protonation from hydroxo to aqua species resulted in increased redox potentials (E1/2) in the order of 1 (-0.15 V) < 2 (0.56 V) < 3 (1.11 V), while pKa values exhibited a reverse trend in the order of 3 (3.87) < 2 (11.84). Employing the Bordwell Equation, the O-H bond dissociation free energies (BDFE) of [MnII(TBDAP)(OH)(OH2)]+ and [MnII(TBDAP)(OH2)2]2+, related to the driving force of 1 and 2 in hydrogen atom transfer (HAT), were determined as 75.3 and 77.3 kcal mol-1, respectively. It was found that the thermodynamic driving force of 2 in HAT becomes greater than that of 1 as the redox potential of 2 increases through protonation from 1 to 2. Kinetic studies on electrophilic reactions using a variety of substrates revealed that 1 is only weakly reactive with O-H bonds, whereas 2 can activate aliphatic C-H bonds in addition to O-H bonds. The reaction rates increased by 1.4 × 104-fold for the O-H bonds by 2 over 1, which was explained by the difference in BDFE and the tunneling effect. Furthermore, 3, possessing the highest redox potential value, was found to undergo an aromatic C-H bond activation reaction under mild conditions. These results provide valuable insights into enhancing electrophilic reactivity by modulating the redox potential of manganese(III)-hydroxo and -aqua complexes through protonation.

Effectiveness and safety of hominis placental pharmacopuncture for chronic temporomandibular disorder: A multi-center randomized controlled trial.

Background: Hominis placental (HPP) extract has been approved by the Ministry of Food and Drug Safety in Korea for treating chronic liver diseases and postmenopausal syndrome. However, its efficacy and safety for treating chronic temporomandibular disorder (TMD) remains unclear. We aimed to assess the effectiveness and safety of HPP for treating chronic TMD compared with physical therapy (PT). Methods: This study is a 2-arm parallel, multi-center, randomized controlled trial. We enrolled 82 chronic TMD patients from 2 Korean medicine hospitals between December 2019 and January 2021. We included patients with chronic TMD and randomly assigned them to undergo HPP or PT. The primary outcome was the difference in the scores for temporomandibular joint (TMJ) pain at baseline and week 6. The secondary outcomes were the scores for TMJ pain and bothersomeness, TMJ range of motion, the Korean version of Beck's depression index-Ⅱ, jaw functional limitation scale (JFLS) score, patient global impression of change (PGIC) scores, EuroQoL 5-dimension 5-level score, and short form-12 health survey (SF-12) scores. Results: Compared with PT, HPP showed significantly superior effects on TMJ pain and bothersomeness, protrusive movement pain, JFLS (verbal, emotional, and global), SF-12, and PGIC scores at week 6 (P < 0.05). Compared with the PT group, the HPP group showed a significantly higher recovery rate (≥50 % reduction in the scores for TMJ pain at the 24-week follow-up). Conclusion: HPP was more effective than PT managing pain and improving function and quality of life. Our findings demonstrate the effectiveness and safety of HPP for TMD treatment. Trial registration: This study has been registered at clinicalTrials.gov (NCT04087005), Clinical Research Information Service (CRIS) (KCT0004437), and Ministry of Food and Drug Safety (No. 31886).

Survey on the current usage of ultrasound-guided procedures in Korean Medicine Clinics and Hospitals.

Ultrasound-guidance is applied during the administration of Korean medicine (KM) interventions to improve the safety and effectiveness of the interventions. Although many case series and reports on the use of ultrasound-guided KM interventions have been reported, no study has investigated the current use of ultrasound-guidance in clinical practice by doctors of Korean medicine (KMDs). An online survey was conducted with questions examining the status of ultrasound-guidance usage among KMDs practicing in various KM clinical settings. Survey responses from 335 KMDs were collected. Ultrasound started to be widely used in the clinical practice of KM since 2022. The primary objective of using ultrasound-guidance was "To improve the accuracy and efficacy" by 54.6%. Ultrasound-guidance was most frequently applied for shoulder joint diseases, and pharmacopuncture was the most frequently used intervention (76.1% and 90.4%, respectively). The respondents reported that effectiveness could be enhanced the most in nerve entrapment syndromes and especially when used in shoulder joints. Over 90% of KMDs responded that the safety and efficacy of treatment, specialty, and patients' satisfaction were improved after adopting ultrasound-guidance. Moreover, 94.9% of KMDs agreed with the necessity for reimbursement of ultrasound-guidance in KM under national health insurance coverage. Most KMDs responded that they had positive perceptions regarding the clinical use of ultrasound-guidance in KM in terms of treatment effects, safety, and patient satisfaction, and the need for national health insurance coverage of the service. Our findings may provide practice-based evidence for conducting clinical studies.

Bibliometric analysis of auriculotherapy research trends over the past 20 years.

OBJECTIVES: Auriculotherapy has long been used to treat various diseases. We analyzed and visualized auriculotherapy's geographical distribution, key contributors, and thematic trends over the past 20 years to provide current trends in auriculotherapy field and to offer recommendations for future research directions. DESIGN/SETTING: We searched for relevant studies in the Web of Science between January 10, 2003, and December 31, 2022. A bibliometric analysis was performed using VOSviewer for annual publications, journals, countries, institutions, authors, and keywords. RESULTS: A total of 800 studies were included in the analysis, and the number of studies steadily increased over the 20 examined years. In 2018, there was a noteworthy rise in publications, nearly twice as many as the preceding year. Integrative & complementary medicine was the most researched area, with most articles published in Evidence-Based Complementary and Alternative Medicine. China was the country with the most published research, and the most active organization was Guangzhou University of Chinese Medicine in China, followed by Kyung Hee University in South Korea. The most prolific author was Yeh Mei-ling, who reported the effects of auriculotherapy on dysmenorrhea and smoking cessation. Keyword analysis revealed four clusters: pain, mental health, obesity, and smoking cessation. CONCLUSION: Auriculotherapy research primarily focused on clinical studies related to pain, obesity, smoking cessation, and depression. Future research should place greater emphasis on verifying the mechanisms of auriculotherapy for specific ailments and may require efforts to enhance the robustness of clinical trials. Through visual analysis, our study may serve as a foundational resource, offering valuable insights into the trajectory of auriculotherapy research.

Timosaponin A3 Induces Anti-Obesity and Anti-Diabetic Effects In Vitro and In Vivo.

Obesity is a serious global health challenge, closely associated with numerous chronic conditions including type 2 diabetes. Anemarrhena asphodeloides Bunge (AA) known as Jimo has been used to address conditions associated with pathogenic heat such as wasting-thirst in Korean Medicine. Timosaponin A3 (TA3), a natural compound extracted from AA, has demonstrated potential therapeutic effects in various disease models. However, its effects on diabetes and obesity remain largely unexplored. We investigated the anti-obesity and anti-diabetic properties of TA3 using in vitro and in vivo models. TA3 treatment in NCI-H716 cells stimulated the secretion of glucagon-like peptide 1 (GLP-1) through the activation of phosphorylation of protein kinase A catalytic subunit (PKAc) and 5'-AMP-activated protein kinase (AMPK). In 3T3-L1 adipocytes, TA3 effectively inhibited lipid accumulation by regulating adipogenesis and lipogenesis. In a high-fat diet (HFD)-induced mice model, TA3 administration significantly reduced body weight gain and food intake. Furthermore, TA3 improved glucose tolerance, lipid profiles, and mitigated hepatic steatosis in HFD-fed mice. Histological analysis revealed that TA3 reduced the size of white adipocytes and inhibited adipose tissue generation. Notably, TA3 downregulated the expression of lipogenic factor, including fatty-acid synthase (FAS) and sterol regulatory element-binding protein 1c (SREBP1c), emphasizing its potential as an anti-obesity agent. These findings revealed that TA3 may be efficiently used as a natural compound for tackling obesity, diabetes, and associated metabolic disorders, providing a novel approach for therapeutic intervention.

Synthesis, Characterization, and Reactivity of a Highly Oxidative Mononuclear Manganese(IV)-Bis(Fluoro) Complex.

Recently, transition-metal terminal nonoxo complexes have shown a remarkable ability to activate and functionalize C-H bonds via proton-coupled electron transfer (PCET). Here we report the first example of a mononuclear manganese(IV) bis(fluoro) complex bearing a tetradentate pyridinophane ligand, [MnIV(TBDAP)(F)2]2+ (3), with an X-ray single crystal structure and physicochemical characterization. The manganese(IV) bis(fluoro) complex has a very high reduction potential of 1.61 V vs SCE, thereby enabling the four-electron oxidation of mesitylene to 3,5-dimethylbenzaldehyde. Kinetic studies, including the kinetic isotope effect and employment of other toluene derivatives, reveal the electron transfer (ET)-driven PCET in the C-H bond activation of mesitylene by 3. This novel metal halide intermediate would be prominently valuable for expanding transition-metal halide chemistry.

Effects of electroacupuncture on obesity: A systematic review and meta-analysis.

BACKGROUND: This systematic review and meta-analysis evaluated the efficacy of electroacupuncture for the treatment of obesity. METHODS: We searched 8 electronic databases for articles published between 2005 and 2021, including only randomized controlled trials (RCTs) in the review. The intervention groups received either electroacupuncture alone or electroacupuncture with standard care, whereas the control groups received sham electroacupuncture, standard care, or no treatment. The primary outcome was the body mass index (BMI), and the secondary outcomes were the body weight (BW), waist circumference (WC), hip circumference, waist-to-hip ratio (WHR), body fat mass, body fat percentage, and adverse effects. Continuous outcome data are presented as mean differences (MDs) with 95% confidence intervals (CIs). RESULTS: This systematic review and meta-analysis included 13 RCTs involving 779 participants. Results revealed that the BMI (MD: -0.98; 95% CI: -1.35 to -0.61), BW (MD: -1.89; 95% CI: -2.97 to -0.80), WC (MD: -2.67; 95% CI: -4.52 to -0.82), and WHR (MD: -0.03; 95% CI: -0.06 to -0.01) were significantly improved in the intervention groups compared with those in the control groups. Adverse effects were reported in 5 studies. The most commonly used acupoint in the abdomen was ST25, whereas the most commonly used acupoints in other regions were ST36 and SP6 for the treatment of obesity. ST25 was the most commonly used acupoint connected by electroacupuncture. CONCLUSION: This systematic review and meta-analysis suggested that electroacupuncture is an effective and safe therapy for simple obesity. To increase the reliability of this study, further detailed, long-term studies should be conducted on the effects of electroacupuncture on obesity.

Synthetic Advances for Mechanistic Insights: Metal-Oxygen Intermediates with a Macrocyclic Pyridinophane System.

ConspectusMetalloenzymes, which are proteins containing earth-abundant transition-metal ions as cofactors in the active site, generate various metal-oxygen intermediates via activating a dioxygen molecule (O2) to mediate vital metabolic functions, such as the oxidative metabolism of xenobiotics and the biotransformation of naturally occurring molecules. By replicating the active sites of metalloenzymes, many bioinorganic chemists have studied the geometric and electronic properties and reactivities of model complexes to understand the nature of enzymatic intermediates and develop bioinspired metal catalysts. Among the reported model complexes, nonporphyrinic macrocyclic ligands are the predominant coordination system widely used in stabilizing and isolating diverse metal-oxygen intermediates, which allows us to extensively investigate the physicochemical characteristics of the analogs of reactive intermediates of metalloenzymes. In particular, it has been reported that the ring size of the macrocyclic ligands, defined by the number of atoms in the macrocyclic ring, drastically affects the identity of the metal-oxygen intermediate. Thus, systematic modification of the macrocyclic ligands has been a great subject being examined in various inorganic fields.In this Account, we describe synthetic advances of a macrocyclic ligand system by introducing pyridine donors into a 12-membered tetraazamacrocyclic ligand (12-TMC) that initially has 4 amine donors. Interestingly, the backbone of the pyridinophane ligand with 2 pyridine and 2 amine donors in a 12-membered ring is shown to be much more folded than in other macrocyclic ligands, thereby allowing the axial and equatorial donors to separately control the electronic structure of metal complexes. Then, we looked over independent electronic and steric effects on metal-oxygen species with thorough physicochemical analysis. The NiIII-peroxo complexes exhibit nucleophilic reactivity dependent on the steric hindrance of the second coordination sphere. Furthermore, the C-H bond strength of the second coordination sphere has also been an important factor in determining the stability of MnIV-bis(hydroxo) intermediates. Electronic tuning on CoIII-hydroperoxo intermediates results in a trend between the electron-donating abilities of para-substituents on pyridine in the pyridinophane ligand and electrophilic reactivities, from which mechanistic insights into the metal-hydroperoxo species have been gained. Importantly, the metal-oxygen intermediates supported by the pyridinophane ligand system have revealed quite challenging chemical reactions, including dioxygenase-like nitrile activation by CoIII-peroxo intermediates and the oxidation of aldehyde and aromatic compounds by manganese-oxygen intermediates. Based on the fine substitution of donors, we have addressed that those novel reactions originated from the unique framework of the pyridinophane system incorporating spin-crossover behavior and high redox potentials of the metal-oxygen intermediates. These results will be valuable for the structure-activity relationship of metal-oxygen intermediates, giving a better understanding on the enzymatic coordination system where amino acid ligands vary for specific chemical reactions.

Effect of Moxibustion Combined with Other Interventions on Body Weight Reduction in the Treatment of Obesity: A Systematic Review and Meta-Analysis.

Background: Moxibustion has been used in the treatment and prevention of obesity. However, there has been no systematic review or meta-analysis conducted on the use of moxibustion on obesity treatment. This study aimed to evaluate the role of moxibustion in the treatment of obesity. Methods: The Cochrane Central Register of Controlled Trials, EMBASE, and MEDLINE/PubMed databases were searched to identify all randomized controlled trials (RCTs) that evaluated the effect of moxibustion on obesity. The primary outcome was body weight. The secondary outcomes were the body mass index (BMI), waist circumference (WC), hip circumference (HC), and waist-to-hip ratio (WHR). The risk of bias assessment and meta-analysis were conducted using the Cochrane Collaboration tool. Results: Eleven RCTs involving 761 participants were included in this systematic review and meta-analysis. Other interventions that were included in the analyses were manual acupuncture, electroacupuncture, embedding therapy, herbal medicine, and diet control. Moxibustion combined with other interventions resulted in a significant improvement in body weight reduction (mean difference [MD] -3.32, 95% confidence interval [CI: -4.25 to -2.38]; I2 = 17%), BMI (MD -1.51, 95% CI [-1.88 to -1.14]; I2 = 76%), and WC (MD -2.82, 95% CI [-3.50 to -2.13]; I2 = 75%), but did not improve HC (MD -2.05, 95% CI [-4.21 to 0.11]; I2 = 0%) or WHR (MD -0.01, 95% CI [-0.03 to 0.01]; I2 = 57%). Conclusions: Moxibustion can be used with other interventions to improve body weight, BMI, and WC in people with obesity. However, the conclusions of this review should be cautiously applied to clinical practice because most of the included studies had a high or unclear risk of bias.

Mechanistic Insights into Nitrile Activation by Cobalt(III)-Hydroperoxo Intermediates: The Influence of Ligand Basicity.

The versatile applications of nitrile have led to the widespread use of nitrile activation in the synthesis of pharmacologically and industrially valuable compounds. We reported the activation of nitriles using mononuclear cobalt(III)-hydroperoxo complexes, [CoIII(Me3-TPADP)(O2H)(RCN)]2+ [R = Me (2) and Ph (2Ph)], to form cobalt(III)-peroxyimidato complexes, [CoIII(Me3-TPADP)(R-C(=NH)O2)]2+ [R = Me (3) and Ph (3Ph)]. The independence of the rate on the nitrile concentration and the positive Hammett value of 3.2(2) indicated that the reactions occur via an intramolecular nucleophilic attack of the hydroperoxide ligand to the coordinated nitrile carbon atom. In contrast, the previously reported cobalt(III)-hydroperoxo complex, [CoIII(TBDAP)(O2H)(CH3CN)]2+ (2TBDAP), exhibited the deficiency of reactivity toward nitrile. The comparison of pKa values and redox potentials of 2 and 2TBDAP showed that Me3-TPADP had a stronger ligand field strength than that of TBDAP. The density functional theory calculations for 2 and 2TBDAP support that the strengthened ligand field in 2 is mainly due to the replacement of two tert-butyl amine donors in TBDAP with methyl groups in Me3-TPADP, resulting in the compression of the Co-Nax bond lengths. These results provide mechanistic evidence of nitrile activation by the cobalt(III)-hydroperoxo complex and indicate that the basicity dependent on the ligand framework contributes to the ability of nitrile activation.

Visual bibliometric analysis of electroacupuncture research in stroke treatment: a 20-year overview.

Background: Electroacupuncture has been used as a treatment; however, a visual bibliometric analysis has not yet been performed in this field. In this study, we aimed to suggest future research topics and directions related to the field by examining the last 20 years of research trends and hotspots of electroacupuncture in stroke. Methods: We searched the Web of Science database on electroacupuncture as a treatment for stroke published from 2003 to 2022. We analyzed the papers by annual publication, research fields, nations, affiliations, authors, journals, and keywords. VOSviewer software was used to visualize the bibliometric analysis and results. A total of 440 papers were included in the analysis. Results: The number of publications has gradually increased every year, and neuroscience has become the most actively studied field. Neural Regeneration Research journal and China had the most publications. Fujian University of Traditional Chinese Medicine, as an affiliated institute, published the most articles. Chen Lidian and Tao Jing presented the largest number of papers, making them the leading contributors in this field. Four clusters were created by analyzing keywords, such as "neuroprotection," "clinical rehabilitation," "neuroplasticity," and "pretreatment-induced tolerance". Conclusion: This study is the first to analyze the research trends in electroacupuncture as a treatment for stroke using the VOSviewer. It shows the current state of research in the field by visualizing research trends and hotspots. This will help offer reference data for future studies.

Is acupuncture an effective treatment for temporomandibular disorder?: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Acupuncture is used for treating various disorders, but its effects on temporomandibular disorder (TMD) remain unclear. This study aimed to assess the effectiveness and safety of acupuncture for TMD via a systematic review of randomized clinical trials. METHODS: A total of 11 Korean and worldwide databases were searched to identify acupuncture studies in adults with TMD. A Cochrane risk of bias assessment was performed on all articles; a meta-analysis, which involved the categorization according to the type of control used (inactive control, active control, or add-on), was subsequently performed. The quality of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation methodology. RESULTS: The qualitative analysis of randomized clinical trials with acupuncture as the intervention included 32 articles, 22 of which were included in the quantitative analysis (471 participants). Acupuncture significantly improved outcomes (effect rate, relative risk [RR]: 7.00, 95% confidence interval [CI]: 1.91, 25, 62; visual analog scale, standardized mean difference: 0.49, 95% CI: 0.24, 0.73) versus active controls (effect rate, RR: 1.19; 95% CI: 1.12, 1.27). In the analysis of add-ons, acupuncture significantly improved the effect rate and pain intensity (effect rate, RR: 1.36; 95% CI: 1.04, 1.77; visual analog scale, mean difference: -1.23; 95% CI -1.79, -0.67). However, the quality of evidence was determined to range from low to very low. CONCLUSION: Acupuncture in TMD significantly improved outcomes versus active controls and when add-on treatments were applied. However, as the quality of evidence was determined to be low, well-designed clinical trials should be conducted in the future.

Korean Medicine Clinical Practice Guideline Update for Temporomandibular Disorders: An Evidence-Based Approach.

Many updated clinical research results have been published since the Korean Medicine Clinical Practice Guidelines (KMCPGs) for temporomandibular disorders (TMDs) were published in 2018. Therefore, it is necessary to update the existing clinical practice guidelines (CPGs). This study presents updated recommendations for TMD treatment based on current research data published up to February 2020. The draft version of the level of evidence and grade of recommendation was determined through an assessment of the risk of bias and a meta-analysis of selected literature based on the Grading of Recommendations Assessment, Development, and Evaluation (GRADE). The final guidelines were derived using the Delphi method. Eighteen recommendations were derived for eight items of Korean medicine treatment for TMDs. Compared with previous Korean medicine CPGs for TMDs, the grades of seven recommendations, including acupuncture, pharmacopuncture, and Chuna manual therapy, were increased. The grades of the two recommendations have been changed. Six new recommendations were added to fully reflect clinical reality. Acupuncture, pharmacopuncture, and Chuna manual therapy are recommended for TMD patients in clinical practice. Concurrent conventional conservative therapy with Korean medicine or a combination of Korean medicines should be considered in clinical practice in patients with temporomandibular disorders.

Systematic review and meta-analysis of the anti-obesity effect of cupping therapy.

BACKGROUND: Cupping therapy is a common practice in Korean medicine. Despite developments in this clinical and research area, the current knowledge is insufficient to identify the effects of cupping therapy on obesity. We aimed to assess the effects and safety of cupping therapy on obesity by performing a systematic review and meta-analysis of the effects of cupping therapy. METHODS: A systematic search of databases was conducted, including MEDLINE/PubMed, EMBASE, Cochrane Central Register of Controlled Trials, Chinese National Knowledge Infrastructure, Citation Information by the National Institute of Informatics, KoreaMed, Oriental Medicine Advanced Searching Integrated System, and ScienceON, for full-text randomized controlled trials (RCTs) published through January 14, 2023, with no language restrictions. The experimental groups received cupping therapy combined with traditional Chinese medicine (TCM) and conventional therapy. The control groups received no treatment, conventional therapy, or TCM treatments alone. The experimental and control groups were compared in terms of body weight (BW), body mass index (BMI), hip circumference (HC), waist circumference (WC), waist-hip ratio (WHR), and body fat percentage (BFP). We evaluated the risk of bias using the 7 domains stipulated by the Cochrane Collaboration Group and performed a meta-analysis using Cochrane Collaboration software (Review Manager Software Version 5.3). RESULTS: A total of 21 RCTs were included in this systematic review and meta-analysis. The analysis revealed improvements in BW (P < .001), BMI (P < .001), HC (P = .03), and WC (P < .001). However, there were no clinically significant changes in WHR (P = .65) or BFP (P = .90), both of which had very low certainty of evidence. No adverse events were reported. CONCLUSION: Overall, our results show that cupping therapy can be used to treat obesity in terms of BW, BMI, HC, and WC and is a safe intervention for the treatment of obesity. However, the conclusions of this review should be interpreted with caution in clinical practice because of the uncertain quality of the included studies.

Application of critical pathway of integrative medical service for lumbar herniated nucleus pulposus: A protocol for single-centered prospective observational study.

BACKGROUND: Lumbar herniated nucleus pulposus (L-HNP) is a condition in which fibroblasts escape due to degenerative changes or external forces in the intervertebral disc, causing neurological symptoms by compressing the dura mater or nerve root. OBJECTIVES: The purpose of this study is to analyze and compare the effectiveness, economic feasibility, and safety of using an integrated medical service critical pathway (CP) in L-HNP patients. METHODS: This single-center prospective observational study will be performed at Kyung Hee University Medicine Hospital and Kyung Hee University Korean Medicine Hospital. The inclusion criteria are a diagnosis of L-HNP on magnetic resonance imaging or computed tomography scans, age under 80 years, a visual analog scale score of 7 or higher for either lower back pain or lower extremity pain. The included 102 participants will be classified into 6 groups (n = 17 in each group): CP application with conservative treatment; CP application with open discectomy; CP application with intrabody fusion; conservative treatment without CP application; open discectomy without CP application; and interbody fusion without CP application. We will collect data on the visual analog scale, ODI, SF-36, and EQ-5D-3L scores; number of admission days; medical staff satisfaction; patients health service satisfaction; waiting time for consultations; use of pain relievers; and CP application and completion rates. CONCLUSION: In future, this study is expected to serve as a basis for follow-up studies on the development and application of CPs in integrated medical services for various diseases, including lumbar herniated nucleus pulposus.

Fenton-like Chemistry by a Copper(I) Complex and H2O2 Relevant to Enzyme Peroxygenase C-H Hydroxylation.

Lytic polysaccharide monooxygenases have received significant attention as catalytic convertors of biomass to biofuel. Recent studies suggest that its peroxygenase activity (i.e., using H2O2 as an oxidant) is more important than its monooxygenase functionality. Here, we describe new insights into peroxygenase activity, with a copper(I) complex reacting with H2O2 leading to site-specific ligand-substrate C-H hydroxylation. [CuI(TMG3tren)]+ (1) (TMG3tren = 1,1,1-Tris{2-[N2-(1,1,3,3-tetramethylguanidino)]ethyl}amine) and a dry source of hydrogen peroxide, (o-Tol3P═O·H2O2)2 react in the stoichiometry, [CuI(TMG3tren)]+ + H2O2 → [CuI(TMG3tren-OH)]+ + H2O, wherein a ligand N-methyl group undergoes hydroxylation giving TMG3tren-OH. Furthermore, Fenton-type chemistry (CuI + H2O2 → CuII-OH + ·OH) is displayed, in which (i) a Cu(II)-OH complex could be detected during the reaction and it could be separately isolated and characterized crystallographically and (ii) hydroxyl radical (·OH) scavengers either quenched the ligand hydroxylation reaction and/or (iii) captured the ·OH produced.

Systematic Electronic Tuning on the Property and Reactivity of Cobalt-(Hydro)peroxo Intermediates.

A series of cobalt(III)-peroxo complexes, [CoIII(R2-TBDAP)(O2)]+ (1R2; R2 = Cl, H, and OMe), and cobalt(III)-hydroperoxo complexes, [CoIII(R2-TBDAP)(O2H)(CH3CN)]2+ (2R2), bearing electronically tuned tetraazamacrocyclic ligands (R2-TBDAP = N,N'-di-tert-butyl-2,11-diaza[3.3](2,6)-p-R2-pyridinophane) were prepared from their cobalt(II) precursors and characterized by various physicochemical methods. The X-ray diffraction and spectroscopic analyses unambiguously showed that all 1R2 compounds have similar octahedral geometry with a side-on peroxocobalt(III) moiety, but the O-O bond lengths of 1Cl [1.398(3) Å] and 1OMe [1.401(4) Å] were shorter than that of 1H [1.456(3) Å] due to the different spin states. For 2R2, the O-O bond vibration energies of 2Cl and 2OMe were identical at 853 cm-1 (856 cm-1 for 2H), but their Co-O bond vibration frequencies were observed at 572 cm-1 for 2Cl and 550 cm-1 for 2OMe, respectively, by resonance Raman spectroscopy (560 cm-1 for 2H). Interestingly, the redox potentials (E1/2) of 2R2 increased in the order of 2OMe (0.19 V) < 2H (0.24 V) < 2Cl (0.34 V) according to the electron richness of the R2-TBDAP ligands, but the oxygen-atom-transfer reactivities of 2R2 showed a reverse trend (k2: 2Cl < 2H < 2OMe) with a 13-fold rate enhancement at 2OMe over 2Cl in a sulfoxidation reaction with thioanisole. Although the reactivity trend contradicts the general consideration that electron-rich metal-oxygen species with low E1/2 values have sluggish electrophilic reactivity, this could be explained by a weak Co-O bond vibration of 2OMe in the unusual reaction pathway. These results provide considerable insight into the electronic nature-reactivity relationship of metal-oxygen species.

Multiple traditional Chinese medicinal approaches in collaboration with conservative conventional medicine for lumbar herniated intervertebral discs: A systematic review and meta-analysis.

BACKGROUND: This review aimed to verify the clinical effects of traditional Chinese medicine in collaboration with conservative conventional medicine for lumbar herniated intervertebral discs (LHIVD). METHODS: The CENTRAL, EMBASE, MEDLINE/PubMed, JMAS, CNKI, and seven Korean databases were searched using pre-planned strategies. The risk of bias was assessed using the Cochrane Collaboration tool and a meta-analysis was conducted accordingly. RESULTS: Twenty-eight randomized controlled trials (RCTs) were included in this systematic review and meta-analysis. All RCTs included 2746 participants. The experimental group showed more significant improvements in VAS (Mean differences (MD) -1.61, 95% Confidence Intervals (CI) [-2.44, -0.79]; I2 = 98%), Oswestry Disability Index (ODI) (MD -8.52, 95% CI [-11.71, -5.34]; I2 = 96%), and Japanese Orthopaedic Association (JOA) scores (MD 4.83, 95% CI [3.49, 6.17]; I2 = 85%) than the control group. However, the difference in the incidence of adverse events between the experimental and control groups was not significant (Relative Risk (RR) 0.05, 95% CI [0.23, 1.10]; I2 = 46%). CONCLUSION: Traditional Chinese medicine in collaboration with conservative conventional medicine can be used to relieve pain and facilitate better function of the lumbar spine in lumbar herniated intervertebral disc cases. However, this conclusion should be applied with caution in clinical practice owing to the low quality of the included studies.

Oxidation of Aldehydes into Carboxylic Acids by a Mononuclear Manganese(III) Iodosylbenzene Complex through Electrophilic C-H Bond Activation.

The oxidation of aldehyde is one of the fundamental reactions in the biological system. Various synthetic procedures and catalysts have been developed to convert aldehydes into corresponding carboxylic acids efficiently under ambient conditions. In this work, we report the oxidation of aldehydes by a mononuclear manganese(III) iodosylbenzene complex, [MnIII(TBDAP)(OIPh)(OH)]2+ (1), with kinetic and mechanistic studies in detail. The reaction of 1 with aldehydes resulted in the formation of corresponding carboxylic acids via a pre-equilibrium state. Hammett plot and reaction rates of 1 with 1°-, 2°-, and 3°-aldehydes revealed the electrophilicity of 1 in the aldehyde oxidation. A kinetic isotope effect experiment and reactivity of 1 toward cyclohexanecarboxaldehyde (CCA) analogues indicate that the reaction of 1 with aldehyde occurs through the rate-determining C-H bond activation at the formyl group. The reaction rate of 1 with CCA is correlated to the bond dissociation energy of the formyl group plotting a linear correlation with other aliphatic C-H bonds. Density functional theory calculations found that 1 electrostatically interacts with CCA at the pre-equilibrium state in which the C-H bond activation of the formyl group is performed as the most feasible pathway. Surprisingly, the rate-determining step is characterized as hydride transfer from CCA to 1, affording an (oxo)methylium intermediate. At the fundamental level, it is revealed that the hydride transfer is composed of H atom abstraction followed by a fast electron transfer. Catalytic reactions of aldehydes by 1 are also presented with a broad substrate scope. This novel mechanistic study gives better insights into the metal oxygen chemistry and would be prominently valuable for development of transition metal catalysts.

Effectiveness of Chuna (or Tuina) Manual Therapy for Temporomandibular Disorder: A Systematic Review.

Background: Temporomandibular disorder (TMD) affects patients' quality of life (QoL) because of the resulting structural and functional impairment and pain. Objective: This study aimed to evaluate the evidence regarding the effectiveness, safety and improvement in QoL in patients who underwent Chuna manual therapy (CMT) for TMD. Methods: We searched 11 databases and included randomized controlled trials (RCT) on CMT for TMD published before March 2020. A meta-analysis was conducted, and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) method was used to evaluate the evidence level. We included 12 RCTs that compared CMT and conventional care. Results: CMT showed significantly better patient pain reduction, functional improvement and QoL. A superior result was seen in the use of CMT in conjunction with Traditional Chinese Medicine (TCM) or conventional care. CMT showed no minor or serious adverse events compared with medical treatments. The evidence level was low for all outcomes, except QoL. Conclusions: We found that CMT for TMD resulted in functional improvement, pain reduction and improvement in QoL, with fewer adverse events. However, since the evidence level varied from very low to moderate due to imprecision and the risk of bias with the included studies, we are limited in determining the efficacy of Chuna therapy using these studies. High-quality, well-designed and large-scale RCTs are needed to conclusively determine the clinical efficacy of CMT in TMD.