Supramolecular CRISPR-OFF switches with host-guest chemistry.

CRISPR (Clustered Regularly Interspaced Short Palindromic Repeat) technology is a powerful tool in biology and medicine. However, the safety and application of this technology is hampered by excessive activity of CRISPR machinery. It is particularly important to develop methods for switching off CRISPR activity in human cells. The current study demonstrates the concept of supramolecular CRISPR-OFF switches by employing host-guest chemistry. We demonstrate that the CRISPR systems show considerable tolerance to adamantoylation on guide RNAs (gRNAs), whereas supramolecular complexation tremendously affects the function of adamantoyl gRNAs. Host-guest chemistry is demonstrated to be novel and effective tools to reduce unwanted excessive activities of CRISPR complexes in human cells. This work indicates considerable potential of supramolecular strategy for controlling and enhancing CRISPR systems.

[Pseudo-targeted metabolomics for differential components of Rhei Radix et Rhizoma from three plant species].

Rhei Radix et Rhizoma is common traditional Chinese medicine with multiple original plants. The content and proportion of the active components in Rhei Radix et Rhizoma from different plant species were compared to accurately evaluate the medicine qua-lity and provide a theoretical basis for precise use of this medicine in clinical practice. In this study, fresh Rhei Radix et Rhizoma samples were collected from the four-year-old plants of Rheum palmatum, R. tanguticum, and R. officinale. The relative content of 220 anthraquinones, anthrones, and tannins in the samples were determined by pseudo-targeted metabolomics, and the differential components were screened by multivariate statistical methods. The principal component analysis classified the samples into three clusters according to the original plants. The orthogonal partial least squares-discriminant analysis(OPLS-DA) screened out 117 differential components, including 8 free anthraquinones, 18 anthraquinone glycosides, 80 anthrones, and 11 tannins. Twenty-eight components had the highest content in R. tanguticum, mainly including sennosides, anthraquinone glycosides, and procyanidins. Thirty-five components showed the highest content in R. officinale, mainly including free anthraquinones and catechines. Fifty-four components showed the highest content in R. palmatum, mainly including dianthrones, while the structures of most of them cannot be determined temporarily. The content distribution of differential components in the three original plants indicates that R. tanguticum has the strongest effect of purging, while R. officinale has the strongest effect of clearing heat and purging fire, and both have stronger effects of resolvong stasis and dredging meridians than R. palmatum.

Controlled oligomeric guest stacking by cucurbiturils in water.

Previously, we reported a guest molecule containing a viologen (V), a phenylene (P) and an imidazole (I) fragment (VPI) forming a host : guest 2 : 2 complex with cucurbit[8]uril (CB[8]) and an unprecedented 2 : 3 complex with cucurbit[10]uril (CB[10]). To better address the structural features required to form these complexes, two VPI analogues were designed and synthesized: the first with a tolyl (T) group grafted on the V part (T-VPI) and the second with a naphthalene (N) fused on the imidazole (I) part (VPI-N). While VPI-N afforded a discrete well-defined 2 : 2 complex with CB[8] and a 2 : 3 complex with CB[10], T-VPI organized also as a 2 : 2 complex with CB[8] but no well-defined complex was obtained with CB[10]. These complexes were studied by NMR spectroscopy, notably DOSY, which allowed us to estimate binding constants for 2 : 2 complex formation with CB[8], pointing to more stable 2 : 2 complexes with more hydrophobic guests. UV-vis and fluorescence spectroscopy confirmed complex formation, suggesting host-stabilized charge-transfer interactions. Therefore, the simple addition of CB[8] or CB[10] enabled us to control the level of guest stacking (dimer or trimer) using relevant pairs of synthetic hosts through spontaneous host : guest quaternary or quinary self-assembly.

[Precise application of Beichaihu and Nanchaihu in classical formulas].

To maintain the precision and stability of the efficacy of classical formulas, this study compared the origins and specifications of Bupleuri Radix and revealed the precise application regularity of Bupleurum chinense(Beichaihu) and Bupleurum scorzonerifolium(Nanchaihu) in classical formulas. The efficacy and indications of formulas with Bupleuri Radix as the sovereign drug in the Treatise on Cold Damage and Miscellaneous Diseases(Shang Han Za Bing Lun) were investigated. The difference in the efficacy of Bupleuri Radix as well as the differences in the chemical composition, and liver-protecting and lipid-lowering effects of the decoctions of Beichaihu and Nanchaihu were analyzed with LC-MS technology based on the CCl_4-induced liver injury model in mice and sodium oleate-induced HepG2 hyperlipidemia cell model. The results showed that seven classical formulas with Bupleuri Radix as the sovereign drug in the Treatise on Cold Damage and Miscellaneous Diseases were mainly used in the treatment of digestive, metabolic, immune, circulatory, and other diseases. Bupleuri Radix mainly played the functions of protecting the liver, benefiting the gallbladder, and lowering the lipid, and had different focuses in different formulas. There were 14 differential components in the decoctions of Beichaihu and Nanchaihu, and the chemical structures of 11 components were identified, including 10 saponins and one flavonoid. The results of the liver-protecting efficacy experiment showed that compared with the Nanchaihu decoction, Beichaihu decoction could reduce the serum aspartate aminotransferase(AST) activity in liver injury model mice(P<0.01). The results of the lipid-lowering efficacy experiment proved that Beichaihu and Nanchaihu decoctions both showed highly significant differences in lowering the total cholesterol(TC) and triglyceride(TG) content in HepG2 cells(P<0.01), and Nanchaihu decoction was superior to Beichaihu decoction in lowering the lipid. The results of this study preliminarily proved that there were differences in chemical composition, and liver-protecting and lipid-lowering effects of Beichaihu and Nanchaihu decoctions, indicating that it was necessary to determine the precise origin of Bupleuri Radix in the clinical formulation of traditional Chinese medicine. The study provides a scientific basis for both precise clinical medication and purpose-based accurate quality evaluation of traditional Chinese medicine in clinical application.

Sequential Formation of Heteroternary Cucurbit[10]uril (CB[10]) Complexes.

The globular and monocationic guest molecule trimethyl-azaphosphatrane (AZAP, a protonated Verkade superbase) was shown to form a host:guest 1 : 1 complex with the cucurbit[10]uril (CB[10]) macrocycle in water. Molecular dynamics calculations showed that CB[10] adopts an 8-shape with AZAP occupying the majority of the internal space, CB[10] contracting around AZAP and leaving a significant part of the cavity unoccupied. This residual space was used to co-include planar and monocationic co-guest (CG) molecules, affording heteroternary CB[10]⋅AZAP⋅CG complexes potentially opening new perspectives in supramolecular chemistry.

Conservation and Divergence of the Trihelix Genes in Brassica and Expression Profiles of BnaTH Genes in Brassica napus under Abiotic Stresses.

Trihelix (TH) proteins are a family of plant-specific transcription factors that play a role in light response and are extensively involved in plant growth and development, as well as in various stress responses. However, the function of TH genes in Brassica napus (B. napus) remains unclear, as does the evolution and differentiation pattern of TH genes in Brassica plants. Here, we identified a total of 455 TH genes in seven species, including six Brassica species and Arabidopsis, which were grouped into five clades, GT-1, GT-2, GTγ, SH4, and SIP1, each with 69, 142, 44, 55, and 145 members, respectively. The types and distributions of motifs of the TH proteins and the structures of the TH genes are conserved in the same subgroup, and some variations in certain amino acid residues occur in B. napus when inheriting motifs from Brassica rapa (B. rapa) and Brassica oleracea (B. oleracea). Collinearity analysis revealed that the massive expansion of TH genes in tetraploid species was attributed to the hetero-tetraploidization of diploid ancestors and gene duplication events within the tetraploid species. Comparative analysis of the membership numbers of five subgroups in different species revealed that the GT-2 and SIP1 genes underwent significant expansion during evolution, possibly to support the better adaptation of plants to their environments. The differential expression of the BnaTH genes under five stresses indicates that the BnaTH genes are involved in plant responses to stresses such as drought, cold, and heat. The presence of different stress-responsive cis-elements in the upstream promoter region of the genes indicated that BnaTH genes have the potential to cope with variable environments. Meanwhile, qRT-PCR analyses also confirmed that five TH genes respond to different abiotic stresses. Our results provide information and candidates for further studies on the role of TH genes in stress resistance of B. napus.

[Identification and quality evaluation of germplasm resources of commercial Scutellaria baicalensis based on DNA barcode and HPLC].

Scutellaria baicalensis is a commonly used Chinese medicinal herb. In this study, we identified the germplasm resources of commercial S. baicalensis samples based on trnH-psbA, petA-psbJ, and ycf4-cemA sequences according to the available chloroplast genome sequencing results, and measured the content of baicalin by HPLC. Through the above means we determined the best DNA barcode that can be used to detect the germplasm resources and evaluate the quality of commercial S. baicalensis samples. A total of 104 samples were collected from 24 provinces, from which DNA was extracted for PCR amplification. The amplification efficiencies of trnH-psbA, petA-psbJ, and ycf4-cemA sequences were 100%, 59.62%, and 25.96%, respectively. The results of sequence analysis showed that 5, 4, and 2 haplotypes were identified based on trnH-psbA, petA-psbJ, and ycf4-cemA sequences, respectively. However, the sequences of haplotypes in commercial samples were different from that of the wild type, and the joint analysis of three fragments of S. baicalensis only identified 6 haplotypes. Furthermore, the phylogenetic analysis and genetic distance analysis indicated that trnH-psbA could be used to identify S. baicalensis from adulterants. The above analysis showed that trnH-psbA was the best fragment for identifying the germplasm resources of commercial S. baicalensis samples. We then analyzed the haplotypes(THap1-THap5) of commercial S. baicalensis samples based on trnH-psbA and found that THap2 was the main circulating haplotype of the commercial samples, accounting for 86.55% of the total samples, which indicated the scarce germplasm resources of commercial S. baicalensis samples. The content of baicalin in all the collected commercial S. baicalensis samples exceeded the standard in Chinese Pharmacopoeia and had significant differences(maximum of 12.21%) among samples, suggesting that the quality of commercial S. baicalensis samples varied considerably. However, there was no significant difference in baicalin content between different provinces or between different haplotypes. This study facilitates the establishment of the standard identification system for S. baicalensis, and can guide the commercial circulation and reasonable medication of S. baicalensis.

Rotaxanating Metallo-supramolecular Nano-cylinder Helicates to Switch DNA Junction Binding.

A class of rotaxane is created, not by encapsulating a conventional linear thread, but rather by wrapping a large cucurbit[10]uril macrocycle about a three-dimensional, cylindrical, nanosized, self-assembled supramolecular helicate as the axle. The resulting pseudo-rotaxane is readily converted into a proper interlocked rotaxane by adding branch points to the helicate strands that form the surface of the cylinder (like branches and roots on a tree trunk). The supramolecular cylinder that forms the axle is itself a member of a unique and remarkable class of helicate metallo-drugs that bind Y-shaped DNA junction structures and induce cell death. While pseudo-rotaxanation does not modify the DNA-binding properties, proper, mechanically-interlocked rotaxanation transforms the DNA-binding and biological activity of the cylinder. The ability of the cylinder to de-thread from the rotaxane (and thus to bind DNA junction structures) is controlled by the extent of branching: fully-branched cylinders are locked inside the cucurbit[10]uril macrocycle, while cylinders with incomplete branch points can de-thread from the rotaxane in response to competitor guests. The number of branch points can thus afford kinetic control over the drug de-threading and release.

EPR Spectroscopy: A Powerful Tool to Analyze Supramolecular Host•Guest Complexes of Stable Radicals with Cucurbiturils.

Stable organic free radicals are increasingly studied compounds due to the multiple and unusual properties imparted by the single electron(s). However, being paramagnetic, classical methods such as NMR spectroscopy can hardly be used due to relaxation and line broadening effects. EPR spectroscopy is thus better suited to get information about the immediate surroundings of the single electrons. EPR has enabled obtaining useful data in the context of host•guest chemistry, and a classical example is reported here for the stable (2,2,6,6-tetramethyl-4-oxo-piperidin-1-yl)oxyl or 4-oxo-TEMPO nitroxide (TEMPONE) inside the macrocycle host cucurbit[7]uril (CB[7]). Generally and also observed here, a contraction of the spectrum is observed as a result of the reduced nitrogen coupling constant due to inclusion complexation in the hydrophobic cavity of the host. Simulations of EPR spectra allowed determining the corresponding binding constant pointing to a weaker affinity for CB[7], compared to TEMPO with CB[7]. We complement this work by the results of EPR spectroscopy of a biradical: bis-TEMPO-bis-ketal (bTbk) with cucurbit[8]uril (CB[8]). Initial investigations pointed to very weak effects on the spectrum of the guest and incorrectly led us to conclude an absence of binding. However, simulations of EPR spectra combined with NMR data of reduced bTbk allowed showing inclusion complexation. EPR titrations were performed, and the corresponding binding constant was determined. 1H NMR spectra with reduced bTbk suggested a shuttle mechanism, at nearly one equivalent of CB[8], for which the host moves rapidly between two stations.

Fabrication, characterization and adsorption properties of cucurbit[7]uril-functionalized polycaprolactone electrospun nanofibrous membranes.

The fabrication of electrospun nanofibers comprising cucurbit[7]uril (CB[7]) and poly(ε-caprolactone) (PCL) is reported. Various techniques such as SEM, FTIR, XRD, DSC and TG were utilized to characterize the morphology, composition and properties of the nanofibers. Uniform bead-free electrospun nanofibers were obtained from PCL/CB[7] mixed solutions and the average fiber diameter of the nanofibers increases with the increase of CB[7] content. The nanofibers are composed of a physical mixture of PCL and CB[7], and CB[7] itself is present in the PCL fiber matrix in an uncomplexed state. The static adsorption behavior of the PCL/CB[7] nanofibers towards methylene blue (MB) was also preliminary investigated. The results indicate that the adsorption of MB onto the nanofibrous membranes fits the second-order kinetic model and Langmuir isotherm model.

Effects of cucurbit[n]uril (n = 7, 8, 10) hosts on the formation and stabilization of a naphthalenediimide (NDI) radical anion.

Most 1,4,5,8-naphthalenediimide (NDI) derivatives, especially those with mild π-acidity cannot achieve photoinduced electron-transfer (PET). Here we report our investigations on the binding interactions of a NDI diammonium dichloride salt (NDI·Cl2) with cucurbit[n]uril (CB[n], n = 8, 10) and the formation process of a NDI radical anion upon photoexcitation of the NDI derivative in the presence of CB[n] (n = 8, 10). As a comparison, the influence of CB[7] on the PET process was also evaluated. The results show that the NDI core can be partially or fully encapsulated in CB[8] or CB[10] to form inclusion complexes at molar ratios of 1 : 1 (CB[8]·NDI2+) or 1 : 2 (CB[10]·2NDI2+). In the presence of the host, quick formation of the NDI radical anion was observed with respect to no radical anion formation without the host. According to the spectral results, interesting CB[8]-promoted charge-transfer interactions between the NDI radical anion and NDI2+ are assumed during UV irradiation. Moreover, from the UV/Vis and EPR spectra, the observation of intense signals of the NDI radical anion in the presence of CB[10], could presumably be related to a much better stabilized NDI radical anion encapsulated in CB[10].

Effect of genotype and environment on five bioactive components of cultivated licorice (Glycyrrhiza uralensis) populations in northern China.

Methods to improve the bioactive component content of cultivated licorice have become the bottleneck of industrial licorice extraction for pharmaceutical use. To evaluate the effects of genotype, environment and their interaction on major bioactive components, we analyzed the five bioactive components: liquiritin (LQ), liquiritigenin (LQG), glycyrrhizin (GL), isoliquiritin (ILQ) and isoliquiritigenin (ILQG) of four diverse licorice varieties grown in four distinct environments in northern China during 2010-11. Analysis of variance showed that environmental and genotypic effects were significant (p<0.01) for all five bioactive components. Additionally, their interaction was significant (p<0.05) for GL in the 2-year study period. LQ and ILQ were mainly affected by genetic factors and have great potential for genetic improvement, whereas LQG and ILQG were mainly affected by environmental factors. GL was similarly affected by environmental and genetic factors. Biplot of the principal component analysis showed that for quality breeding, G2 (WNT-1) and G3 (JX-1) are two relatively preferable genotypes, and E2 (Chifeng) location is suitable for accumulation of the bioactive components of these two genotypes. Stepwise regression analysis showed that sunshine and rainfall are the dominant environmental factors for licorice bioactive component accumulation; increased duration of sunshine is advantageous to GL accumulation whereas declining rainfall is conducive to LQG and ILQG accumulation. These results provide a theoretical basis for initiating licorice breeding programs with increased bioactive components and improved quality.

Effect of genotype and environment on five bioactive components of cultivated licorice (Glycyrrhiza uralensis FISCH.) populations in northern China.

Methods to improve the bioactive component content of cultivated licorice have become the bottleneck of industrial licorice extraction for pharmaceutical use. To evaluate the effects of genotype, environment and their interaction on major bioactive components, we analyzed the five bioactive components: liquiritin (LQ), liquiritigenin (LQG), glycyrrhizin (GL), isoliquiritin (ILQ) and isoliquiritigenin (ILQG) of four diverse licorice varieties grown in four distinct environments in northern China during 2010-11. Analysis of variance showed that environmental and genotypic effects were significant (P<0.01) for all five bioactive components. Additionally, their interaction was significant (P<0.05) for GL in the 2-year study period. LQ and ILQ were mainly affected by genetic factors and have great potential for genetic improvement, whereas LQG and ILQG were mainly affected by environmental factors. GL was similarly affected by environmental and genetic factors. Biplot of the principal component analysis showed that for quality breeding, G2 (WNT-1) and G3 (JX-1) are two relatively preferable genotypes, and E2 (Chifeng) location is suitable for accumulation of the bioactive components of these two genotypes. Stepwise regression analysis showed that sunshine and rainfall are the dominant environmental factors for licorice bioactive component accumulation; increased duration of sunshine is advantageous to GL accumulation whereas declining rainfall is conducive to LQG and ILQG accumulation. These results provide a theoretical basis for initiating licorice breeding programs with increased bioactive components and improved quality.

Changes in mental health levels among Chinese athletes from 1995 to 2023.

Objective: In recent years, with the increasing intensity of sports competition and social pressure, the issue of mental health among athletes have gradually attracted attention. Understanding the changing trends of athletes' mental health is of great significance for formulating effective intervention measures and safeguarding the mental health of athletes. Methods: A total of 306 articles were accumulated from September to November 2023 by selecting literature from databases that measured the mental health of Chinese athletes using the Symptom Checklist-90 (SCL-90). Based on the screening criteria, 28 articles (N = 4,227) were finally included. A cross-sectional historical meta-analysis of these 28 studies using the SCL-90 between 1995 and 2023 was conducted. Based on cross-sectional historical meta-analysis methods, specific statistical methods, such as correlation and regression analyses, were used to examine trends over time in the scores of the nine SCL-90 factors measured by the athletes in the studies, as well as athlete type and gender differences. Results: (1) Athletes' scores on the depression, hostility, phobic anxiety, and paranoid ideation factors gradually increased with the change of era, and the explanation rate of the variation of each factor by era ranged from 18.8 to 27.2%; (2) During the period from 1995 to 2023, the mental health of athletes in China gradually deteriorated on the factors of depression, hostility, and phobic anxiety, the rate of change was rapid, with a medium to large magnitude (0.28-0.42); (3) The scores of female athletes on the depression and psychoticism factors scores showed a significant upward trend, while male mental health scores for each factor did not improve significantly over the years; (4) College athletes' scores on the depression, anxiety, hostility, phobic anxiety, paranoid ideation, and psychoticism factors showed an upward trend as the years changed. Conclusion: Chinese athletes' mental health has been on a downward trend for the past 28 years, which needs to be a cause for concern.

Brief Mindfulness Training Mitigates College Students' Mobile Phone Addiction: The Mediating Effect of the Sense of Meaning in Life.

Objective: To explore the impact of brief mindfulness training on college students' mobile phone addiction and the mediating effect of the sense of meaning in life between them. Methods: This study has employed the mixed experimental design of 2 (experimental conditions) × 2 (time points), randomly assigned 44 college students into a mindfulness training group and a control group (22 college students in each group), and selected the Freiburg Mindfulness Inventory (FMI), Mobile Phone Addiction Tendency Scale (MPATS), and Chinese Meaning in Life Questionnaire (C-MLQ) to conduct separate tests before and after mindfulness training. Results: The results show that: (1) in the pretest, the differences between the mindfulness training group and the control group in the level of mindfulness, the level of mobile phone addiction, and the sense of meaning in life are not statistically significant; (2) in the posttest, compared with those of the control group, both the FMI score (p=0.013) and the C-MLQ score (p<0.001) of the mindfulness training group improve significantly, while the MPATS score (p=0.008) of the mindfulness training group declines significantly; and (3) the Bootstrap analysis of the mediating effect shows that after the change in C-MLQ (95% CI [0.537, 11.630]) enters the equation, the direct effect of mindfulness training is not significant (95% CI [-3.254, 5.861]). Conclusion: The results of this study reveal the impact and mechanism of brief mindfulness training on college students' mobile phone addiction, and provide an empirical basis for intervening on mobile phone addiction.

The influence of sport motivation on college students' subjective exercise experience: a mediation model with moderation.

Background: The degree to which an individual experiences a positive emotional state after exercise is a measurement of how much enjoyment sports bring to the individual. This can also be seen as the individual's essential motivation for engaging in sports, and an indirect means of improving the individual's physical health. Therefore, it is necessary to explore the factors that affect college students' subjective exercise experience and their effecting mechanism, thereby providing a basis for promoting college students' positive emotional experience after exercise. Methods: A questionnaire survey on 600 college students was conducted to examine the mediating effect of sport-confidence on the relationship between college students' sport motivation and their subjective exercise experience, and to investigate whether this process is moderated by the feelings of inadequacy. Results: The indirect effect of sport-confidence was significant (95% CI [0.133, 0.276]), and the index of moderated mediation Bootstrap 95% CI [0.003, 0.017] did not contain 0. Conclusion: The results indicated that: (1) sport-confidence had a partial mediating effect between college students' sport motivation and their subjective exercise experience; (2) the mediating effect of sport-confidence was moderated by the feelings of inadequacy, and the feelings of inadequacy moderated the latter half path of the mediating process of sport motivation - sport-confidence - subjective exercise experience. Therefore, the influence of college students' sport motivation on their subjective exercise experience is a moderated mediating model.

Cucurbit[7]uril-Based Supramolecular DNA Nanogel for Targeted Codelivery of Chemo/Photodynamic Drugs.

Nanodrug delivery systems for the delivery of combination therapeutics have shown their exceptionally potential clinical application by facilitating better synergistic anticancer effects. Herein, we developed a universal strategy to fabricate supramolecular DNA nanogels from DNA tetrahedron skeleton and cucurbit[7]uril-based host-guest interaction for codelivery the chemo and photodynamic therapy drugs. The constructed supramolecular DNA nanogels showed the size tunability, host-guest competition and DNA enzyme responsibility. The cell uptake and MTT experiments demonstrated that the nanogel has excellent biocompatibility and specificity, and achieved the enrichment and slow release of drug in cells. Finally, the combined chemo/photodynamic therapy was realized by coloading doxorubicin hydrochloride and methylene blue. It was proven to be a better stragety to promote apoptosis of cancer cells compared to single chemotherapy or photodynamic therapy. These results suggest that our proposed supramolecular nanogels have provided an effective nanoplatform for drug delivery in the combinational therapy for cancer.

Time course efficiency of MICE and HIIE on inhibitory control and HRV in adolescents with obesity and different cardiorespiratory fitness.

Background: Adolescent obesity is associated with impaired inhibitory control. Acute exercise can improve executive function. However, due to the influence of exercise intensity, cognitive test timing, and cardiorespiratory fitness (CF) level, the most effective exercise program remains controversial. Methods: The current study investigated the time-course effects of moderate-intensity continuous exercise (MICE) and high-intensity interval exercise (HIIE) on inhibitory control (Stroop) and task-related heart rate variability (HRV) in adolescents with different CF. A mixed experimental design of 2 CF levels (high CF, HCF; low CF, LCF) × 3 exercise methods (MICE, HIIE, CON) × 3 test timing (pre, post-0, post-20) was adopted. Heart rate variability (HRV) and Stroop task tests were conducted before exercise (pre), immediately after exercise (post-0), and 20 min after exercise (post-20). Results: Individuals with HCF exhibited a positive decrease in Stroop response time immediately and 20 min after MICE and HIIE, compared to pretest response times (RT). Conversely, individuals with LCF showed a slight increase in Stroop task (RT) only immediately after HIIE. All individuals had a slight increase in ACC after MICE and HIIE compared to before exercise. In addition, compared with the control group, the time-domain index (the square root of the mean squared differences of successive NN intervals, RMSSD) of HRV was significantly decreased, the frequency-domain index (the absolute power of the Low-Frequency band/the absolute power of the High-Frequency band ratio, LF/HF) was significantly increased after MICE and HIIE, and the effect of HIIE on RMSSD and LF/HF was significantly greater than that of MICE. Conclusion: The current study found that the acute effects of MICE and HIIE on inhibitory control in obese adolescents were influenced by the interaction of cognitive test timing and cardiorespiratory fitness. Individuals with high cardiorespiratory fitness performed better on the Stroop task than individuals with low cardiorespiratory fitness. The inhibitory control of HIIE in high-cardiorespiratory obese adolescents produced positive effects similar to those in MICE but more lasting, suggesting that HIIE is more beneficial for high-cardiorespiratory obese adolescents. MICE promoted inhibitory control in obese adolescents with low cardiorespiratory fitness, but HIIE impaired inhibitory control in obese adolescents with low cardiorespiratory fitness immediately after exercise, suggesting that low cardiopulmonary fitness obese adolescents may be suitable for MICE rather than HIIE exercise intervention. The shift from balanced HRV to sympathetic dominance after acute exercise reflects increased arousal levels and may be one of the underlying mechanisms by which acute exercise brings benefits to executive function.

Emerging extracellular vesicle-based carriers for glioblastoma diagnosis and therapy.

Glioblastoma (GBM) treatment is still a big clinical challenge because of its highly malignant, invasive, and lethal characteristics. After treatment with the conventional therapeutic paradigm of surgery combined with radio- and chemotherapy, patients bearing GBMs generally exhibit a poor prognosis, with high mortality and a high disability rate. The main reason is the existence of the formidable blood-brain barrier (BBB), aggressive growth, and the infiltration nature of GBMs. Especially, the BBB suppresses the delivery of imaging and therapeutic agents to lesion sites, and thus this leads to difficulties in achieving a timely diagnosis and treatment. Recent studies have demonstrated that extracellular vesicles (EVs) exhibit favorable merits including good biocompatibility, a strong drug loading capacity, long circulation time, good BBB crossing efficiency, specific targeting to lesion sites, and high efficiency in the delivery of a variety of cargos for GBM therapy. Importantly, EVs inherit physiological and pathological molecules from the source cells, which are ideal biomarkers for molecularly tracking the malignant progression of GBMs. Herein, we start by introducing the pathophysiology and physiology of GBMs, followed by presenting the biological functions of EVs in GBMs with a special focus on their role as biomarkers for GBM diagnosis and as messengers in the modulation of the GBM microenvironment. Furthermore, we provide an update on the recent progress of using EVs in biology, functionality, and isolation applications. More importantly, we systematically summarize the most recent advances of EV-based carriers for GBM therapy by delivering different drugs including gene/RNA-based drugs, chemotherapy drugs, imaging agents, and combinatory drugs. Lastly, we point out the challenges and prospects of future research on EVs for diagnosing and treating GBMs. We hope this review will stimulate interest from researchers with different backgrounds and expedite the progress of GBM treatment paradigms.

Epidemiological Analysis of Avian Reovirus in China and Research on the Immune Protection of Different Genotype Strains from 2019 to 2020.

Avian reovirus (ARV) is the primary pathogen responsible for viral arthritis. In this study, 2340 samples with suspected viral arthritis were collected from 2019 to 2020 in 16 provinces of China to investigate the prevalence of ARV in China and to characterize the molecular genetic evolution of epidemic strains. From 113 samples analyzed by RT-PCR, 46 strains of avian reovirus were successfully isolated and identified. The genetic evolution of the σC gene showed that 46 strains were distributed in 1-5 branches, with the largest number of strains in branches 1 and 2. The σC gene homology among the strains was low, with approximately 62% homology in branches 4 and 5 and about 55% in the remaining branches. The strains circulating during the ARV epidemic in different provinces were distributed in different branches. The SPF chickens were immunized with inactivated vaccines containing strains from branches 1 and 4 to analyze the cross-immune protection elicited by different branches of ARV strains. A challenge protection test was performed using strains in branches 1, 2, 4, and 5. Our results showed that inactivated vaccines containing strains from branches 1 and 4 could fully protect from strains in branches 1, 4, and 5. The results of this study revealed the genetic diversity among the endemic strains of ARV in China from 2019 to 2020. Each genotype strain elicited partial cross-protection, providing a scientific basis for the prevention and control of ARV.