Effectiveness of traditional chinese medicine (TCM) exercise therapy intervention on the cognitive function in the elderly: A systematic review and meta-analysis.

OBJECTIVES: There exists a deficiency in a distinct understanding of the intervention effects of Traditional Chinese Medicine (TCM) exercise therapies (Tai Chi, Yi Jin Jing, Ba Duan Jin, Liu Zi Jue, Qigong, Wu Qin Xi etc.) on cognitive function and its moderating variables in the elderly. This study aims to systematically evaluate the effects of TCM exercise therapies on the cognitive function of the elderly and further propose the best exercise intervention programme to delay the cognitive decline of the elderly. METHODS: PubMed, EBSCO host, Web of Science, EMbase, China National Knowledge Infrastructure and Wan Fang databases were searched for the effects of TCM exercise therapies on the cognitive function in older adults until July 2022. A meta-analysis of the included literature was performed using Stata 12.0 software, with a subgroup analysis of seven moderating variables: subject type, intervention content, intervention duration, intervention frequency, intervention period, study type and sample size. A random effects model was used to combine the overall effect sizes and to test for heterogeneity and publication bias across studies. RESULTS: A total of 20 publications with 1975 subjects were included. The TCM exercise therapies delayed cognitive decline in older adults (d = 0.83; 95 % CI [0.62-1.04]; P < 0.001). Subgroup analysis found that intervention content, intervention duration, intervention frequency, and intervention period were significant moderating variables influencing the effectiveness of the intervention. Among them, the Ba Duan Jin intervention (d = 0.85; 95 % CI [0.65-1.06]; P < 0.001), the duration of each exercise session of 60 min or more (d = 0.86; 95 % CI [0.71-1.00]; P < 0.001), the frequency of exercise of more than 5 times per week (d = 0.80; 95 % CI [0.64-0.96]; P < 0.001) and exercise cycles of 6-9 months (d = 0.96; 95 % CI [0.80-1.12]; P < 0.001) produced the largest effect sizes. CONCLUSION: TCM exercise therapies can effectively improve the cognitive function of the elderly. The best effect on the cognitive function of the elderly was achieved by choosing Ba Duan Jin and exercising at least five times a week for at least 60 min each time for a total of 6-9 months. The effect size of the TCM exercise therapy interventions on the cognitive function in older adults may be overestimated because of publication bias. In addition, large-sample, multicenter, high-quality randomised controlled trials should be conducted to validate this result.

A Photoactivatable Luminescent Motif through Ring-Flipping Isomerization for Multiple Photopatterning.

Photoactivatable luminescent materials have garnered enormous attention in the field of intelligent responsive materials, yet their design and applications remain challenging due to the limited variety of photoactivatable motifs. In the work described herein, we discovered a new photoactivatable luminescent motif that underwent ring-flipping isomerization under UV irradiation. The emission of this motif exhibited a rapid transformation from dark yellow to bright green, accompanied by a significant enhancement of quantum yield from 1.9% to 34.2%. Experimental and theoretical studies revealed that the effective intramolecular motion (EIM) was crucial to the distinct luminescence performance between two isomers. In addition, polymers containing this motif were achieved through a one-pot alkyne polymerization, exhibiting both photofluorochromic and photo-cross-linking properties. Furthermore, multiple types of photopatterning, including luminescent encryption, fluorescent grayscale imaging, and high-resolution photolithographic patterns, were realized. This work developed a new photoactivatable luminescent motif and demonstrated its potential applications in both small molecules and macromolecules, which will help in the future design of photoactivatable luminescent materials.

A Tetradentate Ligand Enables Iron-Catalyzed Asymmetric Hydrogenation of Ketones in a CO- or Isocyanide-Free Fashion.

We herein reported the design and synthesis of a ferrocene-based tetradentate ligand that is featured with modular synthesis and rigid skeleton. Its iron(II) complex facilitates asymmetric direct hydrogenation of ketones without the participation of extra strong-field ligand such as CO and isocyanide. Hydride donor lithium aluminum hydride (LAH) converted non-reactive Fe(II) species to reactive Fe(II) hydride species. With this catalyst, various chiral alcohols including the intermediate for montelukast could be prepared with satisfactory yields and enantioinduction.

Electricity-driven asymmetric bromocyclization enabled by chiral phosphate anion phase-transfer catalysis.

Electricity-driven asymmetric catalysis is an emerging powerful tool in organic synthesis. However, asymmetric induction so far has mainly relied on forming strong bonds with a chiral catalyst. Asymmetry induced by weak interactions with a chiral catalyst in an electrochemical medium remains challenging due to compatibility issues related to solvent polarity, electrolyte interference, etc. Enabled by a properly designed phase-transfer strategy, here we have achieved two efficient electricity-driven catalytic asymmetric bromocyclization processes induced by weak ion-pairing interaction. The combined use of a phase-transfer catalyst and a chiral phosphate catalyst, together with NaBr as the bromine source, constitutes the key advantages over the conventional chemical oxidation approach. Synergy over multiple events, including anodic oxidation, ion exchange, phase transfer, asymmetric bromination, and inhibition of Br2 decomposition by NaHCO3, proved critical to the success.

Re-evaluation of Mirror Visual Feedback Therapy for a Systematic Evaluation/Meta-analysis of Physical Function Re-education After Stroke.

OBJECTIVE: The aim of the study is to re-evaluate the methodological quality and quality of evidence for a systematic evaluation/meta-analysis of the effect of mirror visual feedback therapy on physical function re-education after stroke. METHODS: Systematic evaluations/meta-analyses of mirror visual feedback therapy on physical function re-education after stroke were searched in the China Knowledge Network database, Wanfang database, Vipers database, China Biomedical Literature database, PubMed, Web of Science, and Embase using a computer, and the search time frame was up to January 2022. Methodological quality and quality of evidence ratings of the included studies were determined using the AMSTAR2 scale and GRADE classification by two authors. RESULTS: Seventeen publications were included. The evaluation with the AMSTAR2 scale showed that one study had an intermediate quality rating, five had a low-quality rating, and the remaining 11 were all very low quality. The GRADE scale showed 93 outcome indicators, of which 6 were intermediate, 23 were low grades, and the rest were very low grades, with low overall quality. CONCLUSIONS: Mirror visual feedback therapy is efficacious for physical function re-education after stroke and promotes recovery from physical dysfunction, but the methodological quality and quality of evidence from the related systematic evaluations/meta-analyses are low.

Numerical Investigation of Special Heat Transfer Phenomenon in Wire-Wrapped Fuel Rod of SFR.

Sodium-cooled reactors (SFR) have always been recognized as one of the most promising candidates for the fourth-generation nuclear systems as announced by the Generation-IV International Forum. In the design of SFR, helical wire-wrapped rod is applied to stabilize the structure of the rod bundle and enhance coolant mixing. Although there has been considerable research on SFR in computational fluid dynamics (CFD), the phenomenon of heat transfer has rarely been paid attention to. This article discovered that there exists reversed heat flux from coolant to wrapped wire, which is contrary to our usual understanding. This phenomenon has not been reported in previous CFD calculations. Hence, a solid heat conduction model is proposed to prove this phenomenon and analyze the heat transfer process. The simulation results show that the wrapping wire embedding depth, the shape of the calculation domain and the physical properties of all components have great influence on the magnitude of the reversed heat flux. The present findings will have strong influence on the temperature field and maximum value of the fuel rod as well as profound reference value for future flow calculation, especially in grid generation and treatment of the junction between the winding wire and fuel rod.

Rhoda-Electrocatalyzed Bimetallic C-H Oxygenation by Weak O-Coordination.

Rhodium-electrocatalyzed arene C-H oxygenation by weakly O-coordinating amides and ketones have been established by bimetallic electrocatalysis. Likewise, diverse dihydrooxazinones were selectively accessed by the judicious choice of current, enabling twofold C-H functionalization. Detailed mechanistic studies by experiment, mass spectroscopy and cyclovoltammetric analysis provided support for an unprecedented electrooxidation-induced C-H activation by a bimetallic rhodium catalysis manifold.

Nickel-Catalyzed Asymmetric Hydrogenation of Cyclic Alkenyl Sulfones, Benzo[b]thiophene 1,1-Dioxides, with Mechanistic Studies.

A highly efficient catalytic system based on the cheap transition metal nickel for the asymmetric hydrogenation of challenging cyclic alkenyl sulfones, 3-substituted benzo[b]thiophene 1,1-dioxides, was first successfully developed. A series of hydrogenation products, chiral 2,3-dihydrobenzo[b]thiophene 1,1-dioxides, were obtained in high yields (95-99%) with excellent enantioselectivities (90-99% ee). According to the results of nonlinear effect studies, deuterium-labeling experiments, and DFT calculation investigations, a reasonable catalytic mechanism for this nickel-catalyzed asymmetric hydrogenation was provided, which displayed that the two added hydrogen atoms of the hydrogenation products could be from H2 through the insertion of Ni-H and subsequent hydrogenolysis.

Ruthenaelectro-Catalyzed Domino Three-Component Alkyne Annulation for Expedient Isoquinoline Assembly.

The electrochemical three-component assembly of isoquinolines has been accomplished by ruthenaelectro-catalyzed C-H/N-H functionalization. The robustness of the electrocatalysis was reflected by an ample substrate scope, an efficient electrooxidation, and an operationally friendly procedure. The isolation of key intermediates and detailed mechanistic studies, including unprecedented cyclovoltammetric analysis of a seven-membered ruthenacycle, provided support for an unusual ruthenium(II/III/I) regime.

Circular RNA microarray expression profile and potential function of circ0005875 in clear cell renal cell carcinoma.

Background: Circular RNAs (circRNAs), a novel class of endogenous noncoding RNAs, are involved in a variety of diseases, including several types of cancers. We hypothesized that circRNAs are involved in the tumorigenesis and development of clear cell renal cell carcinoma (ccRCC). Methods: To verify our hypothesis, we explored the circRNA expression profiles in 4 pairs of ccRCC tissues and their adjacent non-carcinoma tissues via microarray analysis. Selected circRNAs were further validated by qPCR. Moreover, hsa_circ_0005875 was selected for further study and the potential clinical values of hsa_circ_0005875 were investigated in 60 pairs of ccRCC tissues and adjacent normal controls. In addition, the role of hsa_circ_0005875 in ccRCC progression were performed using colony formation assay, Transwell assay and Martrigel-Transwell assay respectively. Finally, interactions between the circRNAs and miRNAs were predicted using Arraystar's miRNA target prediction software. Luciferase reporter assays were performed to evaluate the interaction between hsa_circ_0005875 and hsa_miR-145-5p. Results: The microarray data showed 1988 circRNAs were significantly dysregulated circRNAs, including 1033 upregulated and 955 downregulated ones in the ccRCC tissues. Hsa_circ_0005875 was confirmed to be significantly upregulated in the ccRCC tumor tissues and renal carcinoma cells. Further analysis revealed that hsa_circ_0005875 expression was associated with tumor size, pathological TNM stage, histological differentiation, and lymphatic metastasis. Functional experiments demonstrated that overexpression of hsa_circ_0005875 increased proliferation, migration and invasion abilities. Moreover, bioinformatics analysis and luciferase reporter assays suggest that hsa_circ_0005875 may serve as a ceRNA (competing endogenous RNA) of miR-145-5p to relieve the repressive effect of miR-145-5p on target ZEB2. Conclusions: These data indicate that hsa_circ_0005875 might play a role in promoting tumor growth and metastasis and be a potential biomarker of ccRCC.

Ni-Catalyzed asymmetric reduction of α-keto-ß-lactams via DKR enabled by proton shuttling.

Chiral α-hydroxy-ß-lactams are key fragments of many bioactive compounds and antibiotics, and the development of efficient synthetic methods for these compounds is of great value. The highly enantioselective dynamic kinetic resolution (DKR) of α-keto-ß-lactams was realized via a novel proton shuttling strategy. A wide range of α-keto-ß-lactams were reduced efficiently and enantioselectively by Ni-catalyzed asymmetric hydrogenation, providing the corresponding α-hydroxy-ß-lactam derivatives with high yields and enantioselectivities (up to 92% yield, up to 94% ee). Deuterium-labelling experiments indicate that phenylphosphinic acid plays a pivotal role in the DKR of α-keto-ß-lactams by promoting the enolization process. The synthetic potential of this protocol was demonstrated by its application in the synthesis of a key intermediate of Taxol and (+)-epi-Cytoxazone.

Iridium-Catalyzed Asymmetric Hydrogenation of α-Fluoro Ketones via a Dynamic Kinetic Resolution Strategy.

The discrimination of a fluorine atom from a hydrogen atom has been challenging in asymmetric catalysis. We herein report iridium-catalyzed hydrogenation of α-fluoro ketones using a strategy of dynamic kinetic resolution. Both enantiomeric and diastereomeric selectivities were satisfactory in the preparation of ß-fluoro alcohols. The DFT calculation revealed a C-F···Na charge-dipole interaction in the transition state of hydride transfer. This noncovalent interaction would be responsible for the diastereomeric control.

Direct Synthesis of Chiral NH Lactams via Ru-Catalyzed Asymmetric Reductive Amination/Cyclization Cascade of Keto Acids/Esters.

Lactams with a stereogenic center adjacent to the N atom have existed in many medicinal agents and bioactive alkaloids. Herein we report a broadly applicable synthesis of enantioenriched NH lactams through a one-pot asymmetric reductive amination/cyclization sequence of easily available keto acids/esters. Such cascade processes alleviate the demand for protecting group manipulations as well as intermediate purification. This strategy is capable of constructing enantioenriched lactams and benzo-lactams of a five-, six-, or seven-membered ring in generally high yield and with excellent enantioselectivities (up to 97% ee). Scalable and concise syntheses of key drug intermediates have further displayed the importance of this methodology.

Copper-Catalyzed Asymmetric Hydrosilylation of ß-Nitroethyl Aryl Ketones.

A copper-catalyzed asymmetric hydrosilylation of ß-nitroethyl aryl ketones has been disclosed, and the corresponding chiral alcohols could be obtained in high yields (up to 99% yield) and excellent enantioselectivities (up to 96% ee). Moreover, the reaction worked well on a gram scale with 0.3 mol % of ligand loading, indicating that our protocol has potential applications in the synthesis of important pharmaceuticals such as Tranylcypromine and Ticagrelor.

Elevation of casein kinase 1ε associated with TDP-43 and tau pathologies in Alzheimer's disease.

Alzheimer's disease (AD) is characterized by the presence of extracellular amyloid ß plaques and intraneuronal neurofibrillary tangles of hyperphosphorylated microtubule-associated protein tau in the brain. Aggregation of transactive response DNA-binding protein of 43 kDa (TDP-43) in the neuronal cytoplasm is another feature of AD. However, how TDP-43 is associated with AD pathogenesis is unknown. Here, we found that casein kinase 1ε (CK1ε) phosphorylated TDP-43 at Ser403/404 and Ser409/410. In AD brains, the level of CK1ε was dramatically increased and positively correlated with the phosphorylation of TDP-43 at Ser403/404 and Ser409/410. Overexpression of CK1ε promoted its cytoplasmic aggregation and suppressed TDP-43-promoted tau mRNA instability and tau exon 10 inclusion, leading to an increase of tau and 3R-tau expressions. Levels of CK1ε and TDP-43 phosphorylation were positively correlated with the levels of total tau and 3R-tau in human brains. Furthermore, we observed, in pilot immunohistochemical studies, that the severe tau pathology was accompanied by robust TDP-43 pathology and a high level of CK1ε. Taken together, our findings suggest that the elevation of CK1ε in AD brain may phosphorylate TDP-43, promote its cytoplasmic aggregation and suppress its function in tau mRNA processing, leading to acceleration/exacerbation of tau pathology. Thus, the elevation of CK1ε may link TDP-43 to tau pathogenesis in AD brain.

C-H Oxygenation Reactions Enabled by Dual Catalysis with Electrogenerated Hypervalent Iodine Species and Ruthenium Complexes.

The catalytic generation of hypervalent iodine(III) reagents by anodic electrooxidation was orchestrated towards an unprecedented electrocatalytic C-H oxygenation of weakly coordinating aromatic amides and ketones. Thus, catalytic quantities of iodoarenes in concert with catalytic amounts of ruthenium(II) complexes set the stage for versatile C-H activations with ample scope and high functional group tolerance. Detailed mechanistic studies by experiment and computation substantiate the role of the iodoarene as the electrochemically relevant species towards C-H oxygenations with electricity as a sustainable oxidant and molecular hydrogen as the sole by-product. para-Selective C-H oxygenations likewise proved viable in the absence of directing groups.

SQSTM1/p62 is involved in docosahexaenoic acid-induced cellular autophagy in glioblastoma cell lines.

Docosahexaenoic acid (DHA) is the most abundant n-3 polyunsaturated fatty acid in the human brain and works as an anticancer agent to induce cell cycle arrest and apoptosis in glioblastoma multiforme (GBM) cell lines. However, little is known about the connection between DHA and autophagy in GBM cells. We found that high-dose DHA caused cellular autophagy in cultured U251 and U118 GBM cell lines, but there was no effect with a low dose. Moreover, after treatment with a high dose of DHA at 12, 24, and 48 h, the protein expression of SQSTM1/p62 decreased in DHA-treated U251 cells at 12 and 24 h, but increased at 48 h, while in DHA-treated U118 cells, the protein expression increased at all time points. Interestingly, the level of SQSTM1/p62 mRNA was elevated in both DHA-treated U251 and U118 cells at all time points, indicating that DHA activated SQSTM1/p62 transcription in both cell lines. Furthermore, downregulation of SQSTM1/p62 by siRNA attenuated DHA-induced cellular autophagy in both cell lines. This report confirms that high-dose DHA induces cellular autophagy in GBM cells, and demonstrates that SQSTM1/p62 acts as a regulator and participates in DHA-induced autophagy.

Nickel-Catalyzed Asymmetric Hydrogenation of Cyclic Sulfamidate Imines: Efficient Synthesis of Chiral Cyclic Sulfamidates.

Chiral cyclic sulfamidates are useful building blocks to construct compounds, such as chiral amines, with important applications. Often these compounds can only be generated through expensive precious metal catalysts. Here, Ni(OAc)2/(S, S)-Ph-BPE-catalyzed highly efficient asymmetric hydrogenation of cyclic sulfamidate imines was successfully developed, affording various chiral cyclic sulfamidates with high yields and excellent enantioselectivities (up to 99% yield, >99% enantiomeric excess [ee]). This Ni-catalyzed asymmetric hydrogenation on a gram scale has been achieved with only 0.1 mol% catalyst loading in 99% yield with 93% ee. Other types of N-sulfonyl ketimines were also hydrogenated well to obtain the corresponding products with >99% conversion, 96%-97% yields, and 97%->99% ee. In addition, this asymmetric methodology could produce other enantioenriched organic molecules, such as chiral ß-fluoroamine, amino ether, and phenylglycinol. Moreover, a reasonable catalytic cycle was provided according to the deuterium-labeling studies, which could reveal a possible mechanism for this Ni-catalyzed asymmetric hydrogenation.

A cheap metal for a challenging task: nickel-catalyzed highly diastereo- and enantioselective hydrogenation of tetrasubstituted fluorinated enamides.

Nickel-catalyzed asymmetric hydrogenation of challenging tetrasubstituted fluorinated enamides has been achieved, affording chiral α-fluoro-ß-amino esters in high yields with excellent diastereo- and enantioselectivities (up to 98% yield, >99 : 1 dr, up to >99% ee). Deuterium-labeling experiments and control experiments were conducted to probe the mechanism, and the results indicated that the acidity of the solvent plays a critical role in the control of diastereoselectivity by trapping the adduct of nickel hydride to C[double bond, length as m-dash]C bonds via protonolysis, giving the hydrogenation product with stereospecific syn-selectivity. This protocol provides efficient access to chiral α-fluoro-ß-amino esters which have important potential applications in organic synthesis and medicinal chemistry.