Biosynthesis and functions of triterpenoids in cereals.

BACKGROUND: Triterpenoids are versatile secondary metabolites with a diverse array of physiological activities, possessing valuable pharmacological effects and influencing the growth and development of plants. As more triterpenoids in cereals are unearthed and characterized, their biological roles in plant growth and development are gaining recognition. AIM OF THE REVIEW: This review provides an overview of the structures, biosynthetic pathways, and diverse biological functions of triterpenoids identified in cereals. Our goal is to establish a basis for further exploration of triterpenoids with novel structures and functional activities in cereals, and to facilitate the potential application of triterpenoids in grain breeding, thus accelerating the development of superior grain varieties. KEY SCIENTIFIC CONCEPTS OF THE REVIEW: This review consolidates information on various triterpenoid skeletons and derivatives found in cereals, and summarizes the pivotal enzyme genes involved, including oxidosqualene cyclase (OSC) and other triterpenoid modifying enzymes like cytochrome P450, glycosyltransferase, and acyltransferase. Triterpenoid-modifying enzymes exhibit specificity towards catalytic sites within triterpenoid skeletons, generating a diverse array of functional triterpenoid derivatives. Furthermore, triterpenoids have been shown to significantly impact the nutritional value, yield, disease resistance, and stress response of cereals.

The Effects of Antofine on the Morphological and Physiological Characteristics of Phytophthora capsici.

Phytophthora capsici is an important plant pathogenic oomycete that causes great losses to vegetable production around the world. Antofine is an important alkaloid isolated from Cynanchum komarovii Al. Iljinski and exhibits significant antifungal activity. In this study, the effect of antofine on the mycelial growth, morphology, and physiological characteristics of P. capsici was investigated using colorimetry. Meanwhile, the activity of mitochondrial respiratory chain complexes of P. capsici was evaluated following treatment with a 30% effective concentration (EC30), as well as EC50 and EC70, of antofine for 0, 12, 24, and 48 h. The results showed that antofine had a significant inhibitory effect against P. capsici, with an EC50 of 5.0795 µg/mL. After treatment with antofine at EC50 and EC70, the mycelia were rough, less full, and had obvious depression; they had an irregular protrusion structure; and they had serious wrinkles. In P. capsici, oxalic acid and exopolysaccharide contents decreased significantly, while cell membrane permeability and glycerol content increased when treated with antofine. Reactive oxygen species (ROS) entered a burst state in P. capsici after incubation with antofine for 3 h, and fluorescence intensity was 2.43 times higher than that of the control. The activities of the mitochondrial respiratory chain complex II, III, I + III, II + III, V, and citrate synthase in P. capsici were significantly inhibited following treatment with antofine (EC50 and EC70) for 48 h compared to the control. This study revealed that antofine is likely to affect the pathways related to the energy metabolism of P. capsici and thus affect the activity of respiratory chain complexes. These results increase our understanding of the action mechanism of antofine against P. capsici.

Repetitive temporal interference stimulation improves jump performance but not the postural stability in young healthy males: a randomized controlled trial.

BACKGROUND: Temporal interference (TI) stimulation, an innovative non-invasive brain stimulation technique, has the potential to activate neurons in deep brain regions. The objective of this study was to evaluate the effects of repetitive TI stimulation targeting the lower limb motor control area (i.e., the M1 leg area) on lower limb motor function in healthy individuals, which could provide evidence for further translational application of non-invasive deep brain stimulation. METHODS: In this randomized, double-blinded, parallel-controlled trial, 46 healthy male adults were randomly divided into the TI or sham group. The TI group received 2 mA (peak-to-peak) TI stimulation targeting the M1 leg area with a 20 Hz frequency difference (2 kHz and 2.02 kHz). Stimulation parameters of the sham group were consistent with those of the TI group but the current input lasted only 1 min (30 s ramp-up and ramp-down). Both groups received stimulation twice daily for five consecutive days. The vertical jump test (countermovement jump [CMJ], squat jump [SJ], and continuous jump [CJ]) and Y-balance test were performed before and after the total intervention session. Two-way repeated measures ANOVA (group × time) was performed to evaluate the effects of TI stimulation on lower limb motor function. RESULTS: Forty participants completed all scheduled study visits. Two-way repeated measures ANOVA showed significant group × time interaction effects for CMJ height (F = 8.858, p = 0.005) and SJ height (F = 6.523, p = 0.015). The interaction effect of the average CJ height of the first 15 s was marginally significant (F = 3.550, p = 0.067). However, there was no significant interaction effect on the Y balance (p > 0.05). Further within-group comparisons showed a significant post-intervention increase in the height of the CMJ (p = 0.004), SJ (p = 0.010) and the average CJ height of the first 15 s (p = 0.004) in the TI group. CONCLUSION: Repetitive TI stimulation targeting the lower limb motor control area effectively increased vertical jump height in healthy adult males but had no significant effect on dynamic postural stability.

Genome-wide identification, expression and function analysis of the MTP gene family in tulip (Tulipa gesneriana).

Currently, soil heavy metal contamination is a severe issue, particularly with Cd pollution. The metal tolerance protein (MTP) proteins, as plant divalent cation transporters, play a crucial role in the transport and tolerance of heavy metals in plants. This study conducted comprehensive identification and characterization of the MTP gene family in the tulip. A total of 11 TgMTP genes were identified and phylogenetically classified into three subfamilies. Conserved motif and gene structure analyses unveiled commonalities and variations among subfamily members. Expression profiling demonstrated several TgMTPs were markedly upregulated under Cd exposure, including the TgMTP7.1. Heterologous expression in yeast validated that TgMTP7.1 could ameliorate Cd sensitivity and enhance its tolerance. These results provide primary insights into the MTP gene family in tulip. Phylogenetic relationships and functional analyses establish a framework for elucidating the transporters and molecular mechanisms governing Cd accumulation and distribution in tulip. Key TgMTPs identified, exemplified by TgMTP7.1, may illuminate molecular breeding efforts aimed at developing Cd-tolerant cultivars for the remediation of soil Cd contamination.

Enzymatic Galvanic Redox Potentiometry for In Vivo Biosensing.

Redox potentiometry has emerged as a new platform for in vivo sensing, with improved neuronal compatibility and strong tolerance against sensitivity variation caused by protein fouling. Although enzymes show great possibilities in the fabrication of selective redox potentiometry, the fabrication of an enzyme electrode to output open-circuit voltage (EOC) with fast response remains challenging. Herein, we report a concept of novel enzymatic galvanic redox potentiometry (GRP) with improved time response coupling the merits of the high selectivity of enzyme electrodes with the excellent biocompatibility and reliability of GRP sensors. With a glucose biosensor as an illustration, we use flavin adenine dinucleotide-dependent glucose dehydrogenase as the recognition element and carbon black as the potential relay station to improve the response time. We find that the enzymatic GRP biosensor rapidly responds to glucose with a good linear relationship between EOC and the logarithm of glucose concentration within a range from 100 µM to 2.65 mM. The GRP biosensor shows high selectivity over O2 and coexisting neurochemicals, good reversibility, and sensitivity and can in vivo monitor glucose dynamics in rat brain. We believe that this study will pave a new platform for the in vivo potentiometric biosensing of chemical events with high reliability.

Fronto-parietal theta high-definition transcranial alternating current stimulation may modulate working memory under postural control conditions in young healthy adults.

Objects: This study aimed to investigate the immediate effects of fronto-parietal θ HD-tACS on a dual task of working memory-postural control. Methods: In this within-subject cross-over pilot study, we assessed the effects of 20 min of 6 Hz-tACS targeting both the left dorsolateral prefrontal cortex (lDLPFC) and posterior parietal cortex (PPC) in 20 healthy adults (age: 21.6 ± 1.3 years). During each session, single- and dual-task behavioral tests (working memory single-task, static tandem standing, and a dual-task of working memory-postural control) and closed-eye resting-state EEG were assessed before and immediately after stimulation. Results: Within the tACS group, we found a 5.3% significant decrease in working memory response time under the dual-task following tACS (t = -3.157, p = 0.005, Cohen's d = 0.742); phase synchronization analysis revealed a significant increase in the phase locking value (PLV) of θ band between F3 and P3 after tACS (p = 0.010, Cohen's d = 0.637). Correlation analyses revealed a significant correlation between increased rs-EEG θ power in the F3 and P3 channels and faster reaction time (r = -0.515, p = 0.02; r = -0.483, p = 0.031, respectively) in the dual-task working memory task after tACS. However, no differences were observed on either upright postural control performance or rs-EEG results (p-values <0.05). Conclusion: Fronto-parietal θ HD-tACS has the potential of being a neuromodulatory tool for improving working memory performance in dual-task situations, but its effect on the modulation of concurrently performed postural control tasks requires further investigation.

Chronotype characteristics of professional athletes in China: a comprehensive descriptive study.

BACKGROUND: Chronotype has gained recognition as a significant factor in enhancing athletic performance. This study aimed to deepen our understanding of athletes' sleep chronotypes and provide a foundation for developing evidence-based training and competition programs. By comprehensively describing and analyzing the chronotype characteristics of Chinese professional athletes, considering individual and sports factors, sleep quality and habits, and mental energy, this research aimed to contribute valuable insights to the field. METHODS: A sample of 1069 professional athletes from sports teams in Shanghai completed the Athlete Sleep Screening Questionnaire and the Athlete Mental Energy Scale to assess chronotype, sleep quality, sleep-influencing habits, and mental energy. RESULTS: Among athletes, sleep typology fell within the intermediate range, slightly leaning toward morningness. Male athletes and those who engaged in static sports displayed a greater propensity for morningness. Age correlated with a preference for eveningness. High-level athletes exhibited a stronger inclination toward eveningness. Sleep quality issues were associated with an inclination toward eveningness. Daily caffeine intake and the habit of using electronic devices before bedtime are also linked to eveningness. Chronotype demonstrated the ability to predict various dimensions of athletes' mental energy. It was the strongest predictor of vigor, but the loadings were smaller than those of sleep quality. CONCLUSION: Chinese athletes' chronotypes primarily exhibit distinct characteristics related to individual factors such as gender, sports discipline, and ranking, as well as habits like caffeine consumption and electronic device use. Moreover, these sleep patterns demonstrate predictive capabilities across all dimensions of athletes' mental energy. This study sheds light on Chinese athletes' unique sleep chronotype attributes, enriching our understanding of sleep patterns among professional athletes under various systems. These insights offer an initial basis for enhancing the effectiveness of athlete scheduling and training management.

Reliability and validity of the Chinese version of the Athens insomnia scale for non-clinical application in Chinese athletes.

Purpose: This study aimed to revise and examine the reliability and validity of the Chinese version of the Athens Insomnia Scale for Non-clinical Application (AIS-NCA) among Chinese athletes. Additionally, the study tested the scale in non-athlete individuals with similar sleep management practices to further analyze its cultural specificity among Chinese athletes and make preliminary inferences about its applicability in other Chinese populations. Methods: Four hundred twenty-six Chinese professional athletes and 779 high school students participated in this research. Both athletes and students were divided into two parallel groups for exploratory and confirmatory factor analyses. Additionally, three athlete samples and one student sample were established for reliability and validity assessments. Among athletes, the Pittsburgh Sleep Quality Index, the Epworth Sleepiness Scale, the Athlete Sleep Screening Questionnaire, and the Warwick-Edinburgh Mental Well-Being Scale were employed to evaluate convergent and discriminant validity. Re-test reliability was evaluated at intervals of 1 and 2 weeks. In the case of students, convergent and discriminant validity were tested using the Pittsburgh Sleep Quality Index and the General Self-Efficacy Scale, with re-test reliability assessed at two-week intervals. Results: The Chinese version of the AIS-NCA consists of six items, categorized into two dimensions: sleep problems and daytime functioning. This structure explained 65.08% (athletes) and 66.22% (students) of the variance. Confirmatory factor analysis revealed good model fit, with values of χ2/df = 2.217, CFI = 0.975, AGFI = 0.929, TLI = 0.953, and RMSEA = 0.076 among athletes, and χ2/df = 3.037, CFI = 0.979, AGFI = 0.947, TLI = 0.961, and RMSEA = 0.072 among students. The scale demonstrated a reasonable degree of measurement invariance. The overall scale and two subscales exhibited strong reliability and validity among athletes. Similar results in terms of reliability and validity were also observed within the student sample. Conclusion: The Chinese version of the AIS-NCA shows promise as an assessment tool for evaluating the sleep quality of Chinese athletes. It effectively captures both sleep-related concerns and daytime functionality within the athlete population. The scale demonstrates solid reliability and validity in professional athletes and holds potential for application across various other demographic groups in China.

Genome-Wide Identification and Expression Analysis of the MADS Gene Family in Tulips (Tulipa gesneriana).

To investigate the cold response mechanism and low temperature regulation of flowering in tulips, this study identified 32 MADS-box transcription factor family members in tulips based on full-length transcriptome sequencing, named TgMADS1-TgMADS32. Phylogenetic analysis revealed that these genes can be divided into two classes: type I and type II. Structural analysis showed that TgMADS genes from different subfamilies have a similar distribution of conserved motifs. Quantitative real-time PCR results demonstrated that some TgMADS genes (e.g., TgMADS3, TgMADS15, TgMADS16, and TgMADS19) were significantly upregulated in buds and stems under cold conditions, implying their potential involvement in the cold response of tulips. In summary, this study systematically identified MADS family members in tulips and elucidated their evolutionary relationships, gene structures, and cold-responsive expression patterns, laying the foundation for further elucidating the roles of these transcription factors in flowering and the cold adaptability of tulips.

Advanced maternal age: copy number variations and pregnancy outcomes.

Objective: Adverse pregnancy outcomes are closely related to advanced maternal age (AMA; age at pregnancy ≥35 years). Little research has been reported on aneuploid abnormalities and pathogenic copy number variations (CNVs) affecting pregnancy outcomes in women with AMA. The purpose of this study was to assess CNVs associated with AMA in prenatal diagnosis to determine the characteristics of pathogenic CNVs and assist with genetic counseling of women with AMA. Methods: Among 277 fetuses of women with AMA, 218 (78.7%) were isolated AMA fetuses and 59 (21.3%) were non-isolated AMA fetuses and showed ultrasound anomalies from January 2021 to October 2022. Isolated AMA was defined as AMA cases without sonographic abnormalities. Non-isolated AMA was defined as AMA cases with sonographic abnormalities such as sonographic soft markers, widening of the lateral ventricles, or extracardiac structural anomalies. The amniotic fluid cells underwent routine karyotyping followed by single nucleotide polymorphism array (SNP-array) analysis. Results: Of the 277 AMA cases, karyotype analysis identified 20 chromosomal abnormalities. As well as 12 cases of chromosomal abnormalities corresponded to routine karyotyping, the SNP array identified an additional 14 cases of CNVs with normal karyotyping results. There were five pathogenetic CNVs, seven variations of uncertain clinical significance (VOUS), and two benign CNVs. The detection rate of abnormal CNVs in non-isolated AMA cases was increasing (13/59; 22%) than in isolated AMA cases (13/218; 5.96%) (p < 0.001). We also determined that pathogenic CNVs affected the rate of pregnancy termination in women with AMA. Conclusion: Aneuploid abnormalities and pathogenic CNVs affect pregnancy outcomes in women with AMA. SNP array had a higher detection rate of genetic variation than did karyotyping and is an important supplement to karyotype analysis, which enables better informed clinical consultation and clinical decision-making.

Preparation of a Red-Emitting, Chitosan-Stabilized Copper Nanocluster Composite and Its Application as a Hydrogen Peroxide Detection Probe in the Analysis of Water Samples.

Hydrogen peroxide (H2O2) is an important reactive oxygen species that mediates a variety of physiological functions in biological processes, and it is an essential mediator in food, pharmaceutical, and environmental analysis. However, H2O2 can be dangerous and toxic at certain concentrations. It is crucial to detect the concentration of H2O2 in the environment for human health and environmental protection. Herein, we prepared the red-emitting copper nanoclusters (Cu NCs) by a one-step method, with lipoic acid (LA) and sodium borohydride as protective ligands and reducing agents, respectively, moreover, adding chitosan (CS) to wrap LA-Cu NCs. The as-prepared LA-Cu NCs@CS have stronger fluorescence than LA-Cu NCs. We found that the presence of H2O2 causes the fluorescence of LA-Cu NCs@CS to be strongly quenched. Based on this, a fluorescent probe based on LA-Cu NCs@CS was constructed for the detection of H2O2 with a limit of detection of 47 nM. The results from this research not only illustrate that the as--developed fluorescent probe exhibits good selectivity and high sensitivity to H2O2 in environmental water samples but also propose a novel strategy to prepare red-emitting copper nanoclusters (Cu NCs) by a one-step method.

Associations between major dietary patterns and blood pressure among Southwest Chinese: A cross-sectional analysis based on the China Multi-Ethnic Cohort (CMEC) study.

BACKGROUND AND AIMS: In the less developed multi-ethnic regions (LEMRs) of Southwest China, the associations between dietary patterns and blood pressure (BP) values remain unclear. We aimed to investigate such associations and related effect modifiers. METHODS AND RESULTS: This study included 81,433 participants from the China Multi-Ethnic Cohort Study. Dietary intakes during the year before the interview were measured with the Quantitative Food Frequency Questionnaire. Three major dietary patterns that were highly in line with geographical and ethnic distributions of the study population, i.e., "Sichuan Basin," "Yunnan-Guizhou Plateau," and "Qinghai-Tibet Plateau," were derived using principal component factor analysis. The multilinear regression model combined with inverse probability of exposure weighting was used to estimate the associations between dietary patterns and BP values. Comparing the highest with the lowest quintiles, the Sichuan Basin dietary pattern (characterized by urban lifestyles) was associated with 2.67 mmHg lower systolic blood pressure (SBP) (95% CI: -3.07 to -2.27) and 0.89 mmHg lower diastolic blood pressure (95% CI: -1.12 to -0.65). In contrast, both the Yunnan-Guizhou Plateau (characterized by agricultural lifestyles) and the Qinghai-Tibet Plateau dietary patterns (characterized by nomadic lifestyles) showed positive associations with BP. In the stratified analysis, the associations between dietary patterns and SBP were significantly stronger in women than in men for all three kinds of dietary patterns. CONCLUSION: Both major dietary patterns and their associations with BP showed a substantial disparity in LEMRs of Southwest China. Dietary patterns in regions of higher socioeconomic status are more conducive to reducing the rising of BP, especially for women and urban residents, which might provide insights into the BP control in LEMRs of Southwest China.

Intravaginal delivery for CRISPR-Cas9 technology: For example, the treatment of HPV infection.

The increasing incidence of sexually transmitted diseases in women, including human papillomavirus (HPV) infection, has led to the need to develop user-friendly potential prevention methods. At present, although there are several therapeutic parts, none of them has a preventive effect, but they are only limited to providing patients with symptom relief. Researchers have now recognized the need to find effective local preventive agents. One of the potential undiscovered local fungicides is the vaginal delivery of CRISPR/Cas9. CRISPR/Cas9 delivery involves silencing gene expression in a sequence-specific manner in the pathogenic agent, thus showing microbicidal activity. However, vaginal mucosal barrier and physiological changes (such as pH value and variable epithelial thickness in the menstrual cycle) are the main obstacles to effective delivery and cell uptake of CRISPR/Cas9. To enhance the vaginal delivery of CRISPR/Cas9, so far, nano-carrier systems such as lipid delivery systems, macromolecular systems, polymer nanoparticles, aptamers, and cell-penetrating peptides have been extensively studied. In this paper, various nano-carriers and their prospects in the preclinical stage are described, as well as the future significance of CRISPR/Cas9 vaginal delivery based on nano-carriers.

Deciphering the network of cholesterol biosynthesis in Paris polyphylla laid a base for efficient diosgenin production in plant chassis.

Cholesterol serves as a key precursor for many high-value chemicals such as plant-derived steroidal saponins and steroidal alkaloids, but a plant chassis for effective biosynthesis of high levels of cholesterol has not been established. Plant chassis have significant advantages over microbial chassis in terms of membrane protein expression, precursor supply, product tolerance, and regionalization synthesis. Here, using Agrobacterium tumefaciens-mediated transient expression technology, Nicotiana benthamiana, and a step-by-step screening approach, we identified nine enzymes (SSR1-3, SMO1-3, CPI-5, CYP51G, SMO2-2, C14-R-2, 8,7SI-4, C5-SD1, and 7-DR1-1) from the medicinal plant Paris polyphylla and established detailed biosynthetic routes from cycloartenol to cholesterol. Specfically, we optimized HMGR, a key gene of the mevalonate pathway, and co-expressed it with the PpOSC1 gene to achieve a high level of cycloartenol (28.79 mg/g dry weight, which is a sufficient amount of precursor for cholesterol biosynthesis) synthesis in the leaves of N. benthamiana. Subsequently, using a one-by-one elimination method we found that six of these enzymes (SSR1-3, SMO1-3, CPI-5, CYP51G, SMO2-2, and C5-SD1) were crucial for cholesterol production in N. benthamiana, and we establihed a high-efficiency cholesterol synthesis system with a yield of 5.63 mg/g dry weight. Using this strategy, we also discovered the biosynthetic metabolic network responsible for the synthesis of a common aglycon of steroidal saponin, diosgenin, using cholesterol as a substrate, obtaining a yield of 2.12 mg/g dry weight in N. benthamiana. Our study provides an effective strategy to characterize the metabolic pathways of medicinal plants that lack a system for in vivo functional verification, and also lays a foundation for the synthesis of active steroid saponins in plant chassis.

The complete chloroplast genome of Tulipa sinkiangensis Z. M. Mao (Liliaceae) with multi-flower.

Tulipa sinkiangensis Z. M. Mao 1980 is endemic to Xinjiang Province, China. In this study, we reported the complete chloroplast genome of T. sinkiangensis. The complete chloroplast genome of T. sinkiangensis comprises 151,929 bp and was divided into four typical regions: a large single-copy region of 82,062 bp, a pair of inverse repeats of 26,361 bp each, and a small single-copy region of 17,145 bp. A total of 136 genes were identified in this chloroplast, of which 87 were protein-coding, 38 were tRNA, eight were rRNA, and three were pseudogene. The results of this study will provide valuable information for understanding evolution and identification of different species belonging to genus Tulipa.

Association of major dietary patterns and different obesity phenotypes in Southwest China: the China Multi-Ethnic Cohort (CMEC) Study.

PURPOSE: Dietary behavior is an important part of lifestyle interventions for obesity and its cardiovascular comorbidities. However, little is known about associations between dietary patterns and obesity phenotypes in Southwest China, a region with unique dietary patterns and significant heterogeneity in obesity. METHODS: Data from the baseline survey of the China Multi-Ethnic Cohort in Southwest China were analyzed (n = 64,448). Dietary intakes during the past year were measured with the semi-quantitative Food Frequency Questionnaire (s-FFQ). Principal component factor analysis (PCFA) was used to identify dietary patterns. Multinomial logistic regressions were used to examine the associations between dietary patterns and obesity phenotypes and stratified analyses were performed to assess whether the associations differed across demographic variables. RESULTS: Three dietary patterns were identified and then named according to their apparent regional gathering characteristics: the Sichuan Basin dietary pattern (characterized by high intakes of various foods), the Yunnan-Guizhou Plateau dietary pattern (characterized by agricultural lifestyles), and the Qinghai-Tibet Plateau dietary pattern (characterized by animal husbandry lifestyles), respectively. Higher adherence to the Sichuan Basin dietary pattern was positively associated with metabolically healthy overweight/obesity (MHO, OR 1.13, 95% CI 1.05-1.21) but negatively associated with metabolically unhealthy normal weight (MUNW, OR 0.78, 95% CI 0.65-0.95). Higher adherence to the other two dietary patterns was positively associated with MHO and metabolically unhealthy overweight/obesity (MUO). Besides, differences in socioeconomic status also affected the relationship between dietary patterns and obesity phenotypes. CONCLUSIONS: Adherence to the more diverse Sichuan basin dietary pattern performed a mixed picture, while the other two may increase the risk of obesity phenotypes, which indicates nutritional interventions are urgently needed.

CRISPR/Cas9-HPV-liposome enhances antitumor immunity and treatment of HPV infection-associated cervical cancer.

Increasing evidence shows that human papillomavirus (HPV) E6/E7 deletion in cervical cancer cells may be related to the immunosuppressive tumor microenvironment and adverse reactions or resistance to immune checkpoint blockade. Here, we demonstrate that liposome delivery of CRISPR/cas9 can effectively knock out HPV, which, in turn, induces autophagy and triggers cell death-related immune activation by releasing damage-related molecular patterns. The results of in vivo experiments showed that HPV-targeting guide RNA-liposomes could promote CD8+ T cell infiltration in tumor tissues; enhance the expression of proinflammatory cytokines, such as interleukin-12, tumor necrosis factor-α, and interferon-γ, and reduce regulatory T cells and myeloid suppressor cells. The combination of HPV-targeting guide RNA-liposomes with immune checkpoint inhibitors and antiprogrammed death-1 antibodies produced highly effective antitumor effects. In addition, combination therapy induced immune memory in the cervical cancer model.

Temporal interference stimulation targeting right frontoparietal areas enhances working memory in healthy individuals.

Background: Temporal interference (TI) stimulation is a novel technique that enables the non-invasive modulation of deep brain regions. However, the implementation of this technology in humans has not been well-characterized or examined, including its safety and feasibility. Objective: We aimed to examine the feasibility, safety, and blinding of using TI on human participants in this pilot study. Materials and methods: In a randomized, single-blinded, and sham-controlled pilot study, healthy young participants were randomly divided into four groups [TI and transcranial alternating current stimulation (tACS) targeting the right frontoparietal region, TI-sham, and tACS-sham]. Each participant was asked to complete N-back (N = 1 to 3) tasks before, during, and after one session of stimulation to assess their working memory (WM). The side effects and blinding efficacy were carefully assessed. The accuracy, reaction time (RT), and inverse efficiency score (IES, reaction time/accuracy) of the N-back tasks were measured. Results: No severe side effects were reported. Only mild-to-moderate side effects were observed in those who received TI, which was similar to those observed in participants receiving tACS. The blinding efficacy was excellent, and there was no correlation between the severity of the reported side effects and the predicted type of stimulation that the participants received. WM appeared to be only marginally improved by TI compared to tACS-sham, and this improvement was only observed under high-load cognitive tasks. WM seemed to have improved a little in the TI-sham group. However, it was not observed significant differences between TI and TI-sham or TI and tACS in all N-back tests. Conclusion: Our pilot study suggests that TI is a promising technique that can be safely implemented in human participants. Studies are warranted to confirm the findings of this study and to further examine the effects of TI-sham stimulation as well as the effects of TI on deeper brain regions.

Three Dimensional-Arterial Spin Labeling Evaluation of Improved Cerebral Perfusion After Limb Remote Ischemic Preconditioning in a Rat Model of Focal Ischemic Stroke.

Purpose: To investigate the application value of 3D arterial spin labeling (3D-ASL) for evaluating distal limb ischemic preconditioning to improve acute ischemic stroke (AIS) perfusion. Materials and Methods: A total of 40 patients with AISs treated in our hospital from January 2020 to December 2020 were recruited, and 15 healthy individuals who were examined in our hospital during the same period were included as the control group; all of these participants were scored on the National Institutes of Health Stroke Scale (NIHSS) and examined by MRI. Sequences included conventional sequences, diffusion-weighted imaging (DWI), magnetic resonance angiography (MRA), and 3D-ASL, and cerebral infarct volume and cerebral blood flow (CBF) in the area of the infarct lesion were measured. After 3 months of treatment, patients with AIS were scored on the modified Rankin Scale (mRS) and divided into good prognosis and poor prognosis groups. In total, 55 adult male Sprague-Dawley rats were divided randomly into three groups: 20 in the middle cerebral artery occlusion (MCAO) group, 20 in the MCAO + limb remote ischemic preconditioning (LRP) group, and 15 in the sham group. In total, 48 h after the procedures, conventional MRI, DWI, and 3D-ASL sequence data were collected, and 2,3,5-trphenyltetrazolium chloride monohydrate (TTC) staining and behavioral scoring were performed. CBF was recorded in the infarct lesion area and the corresponding contralateral area, and the affected/contralateral relative values (rCBF) were calculated to compare the differences in rCBF between different groups. The pathological changes in brain tissues were observed by HE staining, and the expression of vascular endothelial growth factor (VEGF) and platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31) in brain tissues was detected by immunofluorescence and real-time quantitative polymerase chain reaction (RT-qPCR). The protein expression of VEGF was detected by western blotting. Results: Hypertension and internal carotid atherosclerosis are high-risk factors for ischemic stroke, and CBF values in the infarct area are significantly lower than those in the corresponding areas on the contralateral side. NIHSS and mRS scores and CBF values have higher specificity and sensitivity for the prognosis of patients with AIS. LRP significantly reduces the infarct area, improves behavioral deficits in rats with cerebral ischemia, reduces neurological injury and histological damage, protects vascular structures, and promotes neovascularization. In addition, 3D-ASL showed a significant increase in brain tissue perfusion in the ischemic area after LRP, and the expression of VEGF and CD31 showed a significant positive correlation with CBF values. Conclusion: Three dimensional (3D) ASL can be used to evaluate LRP to improve stroke perfusion, and its protective effect may be closely related to LRP-induced vascular regeneration.

The complete chloroplast genome sequence of Hemerocallis minor (Asphodelaceae).

Hemerocallis minor is a kind of wild plant with high ornamental value. In this study, we sequenced the complete chloroplast genome of H. minor by using Illumina sequencing techniques. The whole chloroplast genome was 156,063 bp in size, consisting of a large single-copy (LSC) region of 84,820 bp, a small single-copy (SSC) region of 18,505 bp, and a pair of inverted repeats (IRa and IRb) regions of 26,369 bp. The chloroplast genome contained 134 genes in total, including 88 protein-coding genes, 38 tRNA genes, and eight rRNA genes. The overall GC content was 37.34%. Phylogenetic analysis showed that H. minor was closely related to Hemerocallis citrina of the same genus.