[Analysis of current situation of outcome indicators in randomized controlled trials on traditional Chinese medicine in treatment of Alzheimer's disease].

This study aims to analyze the current situation of outcome indicators in randomized controlled trial(RCT) of traditional Chinese medicine(TCM) treatment for Alzheimer's disease(AD), so as to provide a reference for establishing a core indicator set in this field. The researchers systematically searched CNKI, Wanfang, VIP, Sino Med, EMbase, PubMed, Medline, and Cochrane Library. Independent screening of literature and extraction of information was conducted according to the inclusion and exclusion criteria. In addition, the Ro B 2. 0 tool was used for bias risk assessment. A total of 78 RCTs were included, involving 6 379 patients,with 122 kinds of outcome indicators. According to functional attributes, the outcome indicators could be categorized into seven groups:TCM diseases(3 kinds, 13 times), symptoms and signs(26 kinds, 196 times), physical and chemical tests(68 kinds, 149 times),qua-lity of life(1 kind, 2 times), long-term prognosis(2 kinds, 2 times), economic evaluation(0 kind), safety events(21 kinds,194 times), and other indicators(1 kind, 1 time). The results show that the literature evaluation of RCTs of TCM treatment for AD is generally risky, and there are some problems in the selection of outcome indicators, such as lack of TCM characteristics, insignificant distinction between primary and secondary outcome indicators, lack of long-term prognosis and economic evaluation indicators, and non-standard safety event reports. It is suggested that future researchers should establish a core indicator set for AD that highlights the characteristics of TCM and then work to improve the quality of clinical trials.

Metabolomics combined with network pharmacology reveals the potential development value of Campanumoea javanica Bl. and its metabolite differences with Codonopsis Radix.

Campanumoea javanica Bl. (CJ) traditionally used in Southwestern China, is now widely consumed as a health food across the nation. Due to its similar efficacy to Codonopsis Radix (CR) and their shared botanical family, CJ is often used as a substitute for CR. According to the Chinese Pharmacopoeia, Codonopsis pilosula var. modesta (Nannf.) L.T. Shen (CPM), Codonopsis pilosula (Franch.) Nannf. (CP), and Codonopsis tangshen Oliv. (CT) are the primary sources of CR. However, details on the differences in composition, effectiveness, and compositional between CJ and CR are still limited. Besides, there is little evidence to support the application of CJ as a drug. In this study, we employed widely targeted metabolomics, network pharmacology analysis, and molecular docking to explore the disparities in metabolite profiles between CJ and CR and to predict the pharmacological mechanisms of the dominant differential metabolites of CJ and their potential medicinal applications. The widely targeted metabolomics results indicated that 1,076, 1,102, 1,102, and 1,093 compounds, most phenolic acids, lipids, amino acids, and flavonoids, were characterized in CJ, CPM, CP, and CT, respectively. There were an average of 1061 shared compounds in CJ and CRs, with 95.07% similarity in metabolic profiles. Most of the metabolites in CJ were previously unreported. Twelve of the seventeen dominant metabolites found in CJ were directly associated with treating cancer and lactation, similar to the traditional medicinal efficacy. The molecular docking results showed that the dominant metabolites of CJ had good docking activity with the core targets PIK3R1, PIK3CA, ESR1, HSP90AA1, EGFR, and AKT1. This study provides a scientific basis for understanding the similarities and differences between CJ and CR at the metabolome level, offering a theoretical foundation for developing innovative medications from CJ. Additionally, it significantly enhances the metabolite databases for both CJ and CR.

Structural basis for odorant recognition of the insect odorant receptor OR-Orco heterocomplex.

Insects detect and discriminate a diverse array of chemicals using odorant receptors (ORs), which are ligand-gated ion channels comprising a divergent odorant-sensing OR and a conserved odorant receptor co-receptor (Orco). In this work, we report structures of the ApOR5-Orco heterocomplex from the pea aphid Acyrthosiphon pisum alone and bound to its known activating ligand, geranyl acetate. In these structures, three ApOrco subunits serve as scaffold components that cannot bind the ligand and remain relatively unchanged. Upon ligand binding, the pore-forming helix S7b of ApOR5 shifts outward from the central pore axis, causing an asymmetrical pore opening for ion influx. Our study provides insights into odorant recognition and channel gating of the OR-Orco heterocomplex and offers structural resources to support development of innovative insecticides and repellents for pest control.

Effects of different traditional Chinese exercise in the treatment of essential hypertension: a systematic review and network meta-analysis.

Background: As a therapy to prevent and treat essential hypertension (EH), traditional Chinese exercises (TCEs) were widely used in clinical practice. However, there is a lack of strictly comparison of the antihypertensive efficacy of different TCEs, which not conducive to the selection of the best and most optimal treatment. This study aimed to perform a network meta-analysis to objectively evaluate which TCE has the best effects in assisting with lowering blood pressure. Methods: PubMed, Embase, the Cochrane Library, Chinese National Knowledge Infrastructure (CNKI), VIP, SinoMed and Wanfang Data were searched for all randomized controlled trials (RCTs) on TCEs for the treatment of EH published up to July 10, 2023. RoB2.0 tool was utilized to evaluate the quality of the RCTs. The network meta-analysis was performed by R 4.1.2 and Stata 17.0. Weighted mean difference (WMD) was calculated for continuous outcomes. Results: A total of 29 studies, including 2,268 patients were included to analyze 6 different interventions. The network meta-analysis results presented that in comparison with control group, Tai Chi + antihypertensive medication [WMD = -10.18, 95% CI, (-14.94, -5.44)] is the most effective intervention for lowering systolic blood pressure (SBP), and Wuqinxi + antihypertensive medication [WMD = -10.36, 95% CI (-18.98, -1.66)] is the most effective intervention for lowering diastolic blood pressure (DBP). Conclusion: TCEs combined with antihypertensive medication may be able to achieve more prominent antihypertensive effects with Tai Chi and Wuqinxi potentially being the higher-priority options. However, well-designed randomized studies are warranted to further verify currently conclusion.

Frontiers in all electrical control of magnetization by spin orbit torque.

Achieving all electrical control of magnetism without assistance of an external magnetic field has been highly pursued for spintronic applications. In recent years, the manipulation of magnetic states through spin-orbit torque (SOT) has emerged as a promising avenue for realizing energy-efficient spintronic memory and logic devices. Here, we provide a review of the rapidly evolving research frontiers in all electrical control of magnetization by SOT. The first part introduces the SOT mechanisms and SOT devices with different configurations. In the second part, the developments in all electrical SOT control of magnetization enabled by spin current engineering are introduced, which include the approaches of lateral symmetry breaking, crystalline structure engineering of spin source material, antiferromagnetic order and interface-generated spin current. The third part introduces all electrical SOT switching enabled by magnetization engineering of the ferromagnet, such as the interface/interlayer exchange coupling and tuning of anisotropy or magnetization. At last, we provide a summary and future perspectives for all electrical control of magnetization by SOT.

A seven-sex species recognizes self and non-self mating-type via a novel protein complex.

Although most species have two sexes, multisexual (or multi-mating type) species are also widespread. However, it is unclear how mating-type recognition is achieved at the molecular level in multisexual species. The unicellular ciliate Tetrahymena thermophila has seven mating types, which are determined by the MTA and MTB proteins. In this study, we found that both proteins are essential for cells to send or receive complete mating-type information, and transmission of the mating-type signal requires both proteins to be expressed in the same cell. We found that MTA and MTB form a mating-type recognition complex that localizes to the plasma membrane, but not to the cilia. Stimulation experiments showed that the mating-type-specific regions of MTA and MTB mediate both self- and non-self-recognition, indicating that T. thermophila uses a dual approach to achieve mating-type recognition. Our results suggest that MTA and MTB form an elaborate multifunctional protein complex that can identify cells of both self and non-self mating types in order to inhibit or activate mating, respectively.

Analysis of Amplitude Modulation of EEG Based on Holo-Hilbert Spectrum Analysis During General Anesthesia.

OBJECTIVE: The study aims to investigate the relationship between amplitude modulation (AM) of EEG and anesthesia depth during general anesthesia. METHODS: In this study, Holo-Hilbert spectrum analysis (HHSA) was used to decompose the multichannel EEG signals of 15 patients to obtain the spatial distribution of AM in the brain. Subsequently, HHSA was applied to the prefrontal EEG (Fp1) obtained during general anesthesia surgery in 15 and 34 patients, and the α-θ and α-δ regions of feature (ROFs) were defined in Holo-Hilbert spectrum (HHS) and three features were derived to quantify AM in ROFs. RESULTS: During anesthetized phase, an anteriorization of the spatial distribution of AMs of α-carrier in brain was observed, as well as AMs of α-θ and α-δ in the EEG of Fp1. The total power ([Formula: see text]), mean carrier frequency ([Formula: see text]) and mean amplitude frequency ([Formula: see text]) of AMs changed during different anesthesia states. CONCLUSION: HHSA can effectively analyze the cross-frequency coupling of EEG during anesthesia and the AM features may be applied to anesthesia monitoring. SIGNIFICANCE: The study provides a new perspective for the characterization of brain states during general anesthesia, which is of great significance for exploring new features of anesthesia monitoring.

Integrated widely targeted metabolomics and network pharmacology revealed quality disparities between Guizhou and conventional producing areas of Codonopsis Radix.

Introduction: With the internationalization of traditional Chinese medicine, the demand for medicinal and edible Codonopsis Radix (CR) has increased, and its medicinal resources have attracted attention. CR is a well-known traditional Chinese medicine with a long pharmaceutical and edible history. The Guizhou province in China has abundant CR resources, but in the absence of systematic studies on species identification and chemical compositions, the capacity of the capacity of the province to CR resource has not been fully utilized. Methodology: We used plant morphology and DNA barcoding techniques to identify Luodang (LD) and Weidang (WD) species. To investigate the differences in metabolites between LD and WD, as well as three Chinese Pharmacopeia CRs, and to predict pharmacological mechanisms of action for the dominant differential metabolites, we utilized widely targeted metabolomics and network pharmacology. The results also revealed the material basis for the excellent food properties of both LD and WD. Results: The plant traits and DNA barcoding molecular identification results indicated that Luodang and Weidang from Guizhou were Codonopsis tangshen and Codonopsis pilosula, respectively. Widely targeted metabolomics analysis revealed that a total of 1,116 metabolites from 14 categories, including phenolic acids, lipids, flavonoids, were found in five CRs and shared 1,054 (94.4%) metabolites. LD and WD each contained 3 and 10 dominant differential metabolites, respectively, which were primarily flavonoids and amino acids. Amino acids, phenolic acids, and organic acids play important roles in their excellent food attributes. In CR, eight dominant differential metabolites were discovered for the first time, including isoorientin-7-O-(6″-feruloyl) glucoside, N-formyl-L-methionine, and cyclo (Phe-Glu), among others. Network pharmacology analyses showed that, in LD, dominant differential metabolites were closely related to anti-tumor, cardiovascular disease improvement, nervous system protection, and metabolic disease treatment, whereas in WD, they were closely related to nervous system protection and cardiovascular disease improvement. Conclusion: The species of LD and WD were included in the Chinese Pharmacopeia, and their metabolite profiles were remarkably similar to CR from traditional producing areas. Therefore, LD and WD can be used and promoted medicinally as CR, and they have potential value for new drug development. This study enriched the database of CR compounds and provided a reference for quality control, resource development, and new drug development of CR.

The LIKE SEX FOUR 1-malate dehydrogenase complex functions as a scaffold to recruit ß-amylase to promote starch degradation.

In plant leaves, starch is composed of glucan polymers that accumulate in chloroplasts as the products of photosynthesis during the day; starch is mobilized at night to continuously provide sugars to sustain plant growth and development. Efficient starch degradation requires the involvement of several enzymes, including ß-amylase and glucan phosphatase. However, how these enzymes cooperate remains largely unclear. Here, we show that the glucan phosphatase LIKE SEX FOUR 1 (LSF1) interacts with plastid NAD-dependent malate dehydrogenase (MDH) to recruit ß-amylase (BAM1), thus reconstituting the BAM1-LSF1-MDH complex. The starch hydrolysis activity of BAM1 drastically increased in the presence of LSF1-MDH in vitro. We determined the structure of the BAM1-LSF1-MDH complex by a combination of cryo-electron microscopy, crosslinking mass spectrometry, and molecular docking. The starch-binding domain of the dual-specificity phosphatase and carbohydrate-binding module of LSF1 was docked in proximity to BAM1, thus facilitating BAM1 access to and hydrolysis of the polyglucans of starch, thus revealing the molecular mechanism by which the LSF1-MDH complex improves the starch degradation activity of BAM1. Moreover, LSF1 is phosphatase inactive, and the enzymatic activity of MDH was dispensable for starch degradation, suggesting nonenzymatic scaffold functions for LSF1-MDH in starch degradation. These findings provide important insights into the precise regulation of starch degradation.

Structural Anisotropy-Driven Atomic Mechanisms of Phase Transformations in the Pt-Sn System.

Using in situ atomic-resolution scanning transmission electron microscopy, atomic movements and rearrangements associated with diffusive solid to solid phase transformations in the Pt-Sn system are captured to reveal details of the underlying atomistic mechanisms that drive these transformations. In the PtSn4 to PtSn2 phase transformation, a periodic superlattice substructure and a unique intermediate structure precede the nucleation and growth of the PtSn2 phase. At the atomic level, all stages of the transformation are templated by the anisotropic crystal structure of the parent PtSn4 phase. In the case of the PtSn2 to Pt2Sn3 transformation, the anisotropy in the structure of product Pt2Sn3 dictates the path of transformation. Analysis of atomic configurations at the transformation front elucidates the diffusion pathways and lattice distortions required for these phase transformations. Comparison of multiple Pt-Sn phase transformations reveals the structural parameters governing solid to solid phase transformations in this technologically interesting intermetallic system.

Robust negative longitudinal magnetoresistance and spin-orbit torque in sputtered Pt3Sn and Pt3SnxFe1-x topological semimetal.

Contrary to topological insulators, topological semimetals possess a nontrivial chiral anomaly that leads to negative magnetoresistance and are hosts to both conductive bulk states and topological surface states with intriguing transport properties for spintronics. Here, we fabricate highly-ordered metallic Pt3Sn and Pt3SnxFe1-x thin films via sputtering technology. Systematic angular dependence (both in-plane and out-of-plane) study of magnetoresistance presents surprisingly robust quadratic and linear negative longitudinal magnetoresistance features for Pt3Sn and Pt3SnxFe1-x, respectively. We attribute the anomalous negative longitudinal magnetoresistance to the type-II Dirac semimetal phase (pristine Pt3Sn) and/or the formation of tunable Weyl semimetal phases through symmetry breaking processes, such as magnetic-atom doping, as confirmed by first-principles calculations. Furthermore, Pt3Sn and Pt3SnxFe1-x show the promising performance for facilitating the development of advanced spin-orbit torque devices. These results extend our understanding of chiral anomaly of topological semimetals and can pave the way for exploring novel topological materials for spintronic devices.

The microRNA-7322-5p/p38/Hsp19 axis modulates Chilo suppressalis cell-defences against Cry1Ca: an effective target for a stacked transgenic rice approach.

Bacillus thuringiensis (Bt)-secreted crystal (Cry) toxins form oligomeric pores in host cell membranes and are a common element in generating insect-resistant transgenic crops. Although Cry toxin function has been well documented, cellular defences against pore-formation have not been as well developed. Elucidation of the processes underlying this defence, however, could contribute to the development of enhanced Bt crops. Here, we demonstrate that Cry1Ca-mediated downregulation of microRNA-7322-5p (miR-7322-5p), which binds to the 3' untranslated region of p38, negatively regulates the susceptibility of Chilo suppressalis to Cry1Ca. Moreover, Cry1Ca exposure enhanced phosphorylation of Hsp19, and hsp19 downregulation increased susceptibility to Cry1Ca. Further, Hsp19 phosphorylation occurs downstream of p38, and pull-down assays confirmed the interactions between Hsp19 and Cry1Ca, suggesting that activation of Hsp19 by the miR-7322-5p/p38/Hsp19 pathway promotes Cry1Ca sequestration. To assess the efficacy of targeting this pathway in planta, double-stranded RNA (dsRNA) targeting C. suppressalis p38 (dsp38) was introduced into a previously generated cry1Ca-expressing rice line (1CH1-2) to yield a single-copy cry1Ca/dsp38 rice line (p38-rice). Feeding on this rice line triggered a significant reduction in C. suppressalis p38 expression and the line was more resistant to C. suppressalis than 1CH1-2 in both short term (7-day) and continuous feeding bioassays as well as field trials. These findings provide new insights into invertebrate epithelium cellular defences and demonstrate a potential new pyramiding strategy for Bt crops.

Chemistry-mechanics-geometry coupling in positive electrode materials: a scale-bridging perspective for mitigating degradation in lithium-ion batteries through materials design.

Despite their rapid emergence as the dominant paradigm for electrochemical energy storage, the full promise of lithium-ion batteries is yet to be fully realized, partly because of challenges in adequately resolving common degradation mechanisms. Positive electrodes of Li-ion batteries store ions in interstitial sites based on redox reactions throughout their interior volume. However, variations in the local concentration of inserted Li-ions and inhomogeneous intercalation-induced structural transformations beget substantial stress. Such stress can accumulate and ultimately engender substantial delamination and transgranular/intergranular fracture in typically brittle oxide materials upon continuous electrochemical cycling. This perspective highlights the coupling between electrochemistry, mechanics, and geometry spanning key electrochemical processes: surface reaction, solid-state diffusion, and phase nucleation/transformation in intercalating positive electrodes. In particular, we highlight recent findings on tunable material design parameters that can be used to modulate the kinetics and thermodynamics of intercalation phenomena, spanning the range from atomistic and crystallographic materials design principles (based on alloying, polymorphism, and pre-intercalation) to emergent mesoscale structuring of electrode architectures (through control of crystallite dimensions and geometry, curvature, and external strain). This framework enables intercalation chemistry design principles to be mapped to degradation phenomena based on consideration of mechanics coupling across decades of length scales. Scale-bridging characterization and modeling, along with materials design, holds promise for deciphering mechanistic understanding, modulating multiphysics couplings, and devising actionable strategies to substantially modify intercalation phase diagrams in a manner that unlocks greater useable capacity and enables alleviation of chemo-mechanical degradation mechanisms.

The cytoplasmic synthesis and coupled membrane translocation of eukaryotic polyphosphate by signal-activated VTC complex.

Inorganic polyphosphate (polyP) is an ancient energy metabolite and phosphate store that occurs ubiquitously in all organisms. The vacuolar transporter chaperone (VTC) complex integrates cytosolic polyP synthesis from ATP and polyP membrane translocation into the vacuolar lumen. In yeast and in other eukaryotes, polyP synthesis is regulated by inositol pyrophosphate (PP-InsP) nutrient messengers, directly sensed by the VTC complex. Here, we report the cryo-electron microscopy structure of signal-activated VTC complex at 3.0 Å resolution. Baker's yeast VTC subunits Vtc1, Vtc3, and Vtc4 assemble into a 3:1:1 complex. Fifteen trans-membrane helices form a novel membrane channel enabling the transport of newly synthesized polyP into the vacuolar lumen. PP-InsP binding orients the catalytic polymerase domain at the entrance of the trans-membrane channel, both activating the enzyme and coupling polyP synthesis and membrane translocation. Together with biochemical and cellular studies, our work provides mechanistic insights into the biogenesis of an ancient energy metabolite.

Structural insights into DNA N6-adenine methylation by the MTA1 complex.

N6-methyldeoxyadenine (6mA) has recently been reported as a prevalent DNA modification in eukaryotes. The Tetrahymena thermophila MTA1 complex consisting of four subunits, namely MTA1, MTA9, p1, and p2, is the first identified eukaryotic 6mA methyltransferase (MTase) complex. Unlike the prokaryotic 6mA MTases which have been biochemically and structurally characterized, the operation mode of the MTA1 complex remains largely elusive. Here, we report the cryogenic electron microscopy structures of the quaternary MTA1 complex in S-adenosyl methionine (SAM)-bound (2.6 Å) and S-adenosyl homocysteine (SAH)-bound (2.8 Å) states. Using an AI-empowered integrative approach based on AlphaFold prediction and chemical cross-linking mass spectrometry, we further modeled a near-complete structure of the quaternary complex. Coupled with biochemical characterization, we revealed that MTA1 serves as the catalytic core, MTA1, MTA9, and p1 likely accommodate the substrate DNA, and p2 may facilitate the stabilization of MTA1. These results together offer insights into the molecular mechanism underpinning methylation by the MTA1 complex and the potential diversification of MTases for N6-adenine methylation.

An integrated information theory index using multichannel EEG for evaluating various states of consciousness under anesthesia.

BACKGROUND: The integrated information theory (IIT) of consciousness introduces a measure Φ to quantify consciousness in a physical system. Directly related to this, general anesthesia aims to induce reversible and safe loss of consciousness (LOC). We sought to propose an electroencephalogram (EEG)-based IIT index ΦEEG to evaluate various states of consciousness under general anesthesia. METHODS: Based on the definition of mutual information, we estimated the ΦEEG by maximizing the integrated information under various time lags. We used the binning method to cut the nonGaussian EEG data for estimating mutual information. We tested two EEG databases collected from propofol- (n=20) and sevoflurane-induced (n=15) anesthesia, and especially, we compared the ΦEEG of drowsy (n=7) and responsive participants (n=13) under propofol anesthesia. We compared the effectiveness of ΦEEG with the estimated bispectral index (eBIS). RESULTS: In all EEG frequency bands, we observed a negative correlation between ΦEEG and end-tidal sevoflurane concentration under sevoflurane-induced anesthesia (p<0.001,BF10>6000). Under propofol-induced anesthesia, drowsy participants in moderate sedation (6.96±0.26(mean±SD)) showed decreased alpha-band ΦEEG compared with baseline (7.40±0.53,p=0.016,BF10=3.58), no significant difference was observed for responsive participants. Oppositely, the responsive participants in moderate sedation (-5.32±0.38) showed decreased eBIS compared with baseline (-4.94±0.40,p=0.03,BF10=2.41). CONCLUSIONS: These findings may enable monitors of the anesthetic state that can distinguish consciousness and unconsciousness rather than the changes of anesthetic concentrations. The alpha-band ΦEEG is promising for deriving the gold standard for depth of anesthesia monitoring.