Cytoplasmic DNA sensing by KU complex in aged CD4+ T cell potentiates T cell activation and aging-related autoimmune inflammation.

Aging is associated with DNA accumulation and increased homeostatic proliferation of circulating T cells. Although these attributes are associated with aging-related autoimmunity, their direct contributions remain unclear. Conventionally, KU complex, the regulatory subunit of DNA-dependent protein kinase (DNA-PK), together with the catalytic subunit of DNA-PK (DNA-PKcs), mediates DNA damage repair in the nucleus. Here, we found KU complex abundantly expressed in the cytoplasm, where it recognized accumulated cytoplasmic DNA in aged human and mouse CD4+ T cells. This process enhanced T cell activation and pathology of experimental autoimmune encephalomyelitis (EAE) in aged mice. Mechanistically, KU-mediated DNA sensing facilitated DNA-PKcs recruitment and phosphorylation of the kinase ZAK. This activated AKT and mTOR pathways, promoting CD4+ T cell proliferation and activation. We developed a specific ZAK inhibitor, which dampened EAE pathology in aged mice. Overall, these findings demonstrate a KU-mediated cytoplasmic DNA-sensing pathway in CD4+ T cells that potentiates aging-related autoimmunity.

Association of positive childhood experiences with flourishing among children with ADHD: A population-based study in the United States.

BACKGROUND: Child flourishing includes healthy social and emotional development and an open, engaged approach to learning. However, there remains a significant knowledge gap concerning a minority of children with ADHD who may demonstrate flourishing in one or more areas of functioning. This study investigated the association between positive childhood experiences (PCEs) and flourishing among children with ADHD. METHOD: Data were derived from the 2021 National Survey of Children's Health in the United States. The analysis included a final sample of 3727 children with ADHD. Logistic regression, restricted cubic splines, and random forest were used to examine the associations between seven PCEs and flourishing. RESULTS: The adjusted odds of flourishing were 72% lower (odds ratio [OR] = 0.28,95% confidence interval [CI] = 0.21, 0.38) among children with PCE scores of 0-2 compared to those with scores of 3-5. In addition, the adjusted odds of flourishing were 2.45 times (95%CI = 2.00, 2.99) greater for children with PCE scores of 6-7 compared to those with scores of 3-5. These associations were consistent regardless of the level of adverse childhood experiences. Having a "connected caregiver" was the PCE most closely related to flourishing (unweighted OR = 3.24, 95%CI = 2.72, 3.89). CONCLUSIONS: Our findings revealed a positive association between higher levels of PCEs and greater flourishing among children with ADHD, regardless of the level of childhood adversity they experienced. These results highlight the importance of positive experiences in the lives of children with ADHD, with a specific focus on nurturing supportive relationships within families.

Transcriptomic and metabolomic profiling provide insight into the role of sugars and hormones in leaf senescence of Pinellia ternata.

KEY MESSAGE: The interaction network and pathway map uncover the potential crosstalk between sugar and hormone metabolisms as a possible reason for leaf senescence in P. ternata. Pinellia ternata, an environmentally sensitive medicinal plant, undergoes leaf senescence twice a year, affecting its development and yield. Understanding the potential mechanism that delays leaf senescence could theoretically decrease yield losses. In this study, a typical senescent population model was constructed, and an integrated analysis of transcriptomic and metabolomic profiles of P. ternata was conducted using two early leaf senescence populations and two stay-green populations. The result showed that two key gene modules were associated with leaf senescence which were mainly enriched in sugar and hormone signaling pathways, respectively. A network constructed by unigenes and metabolisms related to the obtained two pathways revealed that several compounds such as D-arabitol and 2MeScZR have a higher significance ranking. In addition, a total of 130 hub genes in this network were categorized into 3 classes based on connectivity. Among them, 34 hub genes were further analyzed through a pathway map, the potential crosstalk between sugar and hormone metabolisms might be an underlying reason of leaf senescence in P. ternata. These findings address the knowledge gap regarding leaf senescence in P. ternata, providing candidate germplasms for molecular breeding and laying theoretical basis for the realization of finely regulated cultivation in future.

Peli1 impairs microglial Aß phagocytosis through promoting C/EBPß degradation.

Amyloid-ß (Aß) accumulation in the brain is a hallmark of Alzheimer's disease (AD) pathology. However, the molecular mechanism controlling microglial Aß phagocytosis is poorly understood. Here we found that the E3 ubiquitin ligase Pellino 1 (Peli1) is induced in the microglia of AD-like five familial AD (5×FAD) mice, whose phagocytic efficiency for Aß was then impaired, and therefore Peli1 depletion suppressed the Aß deposition in the brains of 5×FAD mice. Mechanistic characterizations indicated that Peli1 directly targeted CCAAT/enhancer-binding protein (C/EBP)ß, a major transcription factor responsible for the transcription of scavenger receptor CD36. Peli1 functioned as a direct E3 ubiquitin ligase of C/EBPß and mediated its ubiquitination-induced degradation. Consequently, loss of Peli1 increased the protein levels of C/EBPß and the expression of CD36 and thus, promoted the phagocytic ability in microglial cells. Together, our findings established Peli1 as a critical regulator of microglial phagocytosis and highlighted the therapeutic potential by targeting Peli1 for the treatment of microglia-mediated neurological diseases.

Association between brachial-ankle pulse wave velocity and microvascular complications in type 2 diabetes mellitus.

PURPOSE/AIM: To investigate the relationship between brachial-ankle pulse wave velocity (baPWV) and microvascular complications in type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS: From 2019 to 2021, our hospital enrolled 322 patients with T2DM. Clinical information and biochemical indicators of patients were collected from the inpatient electronic medical record system and analyzed retrospectively. Fundus photography, nerve conduction testing, and sensory threshold measurement were all conducted on the subjects. We measured the pulse wave velocity on both sides of the arm and ankle, then averaged the results. The enrolled cases were divided into two groups based on the baPWV: Group 1 (

Network structure of mobile phone addiction and anxiety symptoms among rural Chinese adolescents.

BACKGROUND: The incidence of mobile phone addiction among adolescents in rural areas of China is increasing year by year, and has already exceeded that of some cities. And phone addiction increases the risk of anxiety and poor sleep. Therefore, this study used network analysis to investigate the relationship between mobile phone addiction and anxiety symptoms, and the predictability to sleep quality. METHODS: From September 2021 to March 2022, a total of 1920 rural adolescents in Xuzhou, China were included. The survey included information on phone addiction, anxiety symptoms, and sleep quality. Network analysis was used to estimate the network structure of adolescents' mobile phone addiction and anxiety symptoms. LOWESS curve and linear regression were used to test the predictive ability of node-centrality on sleep quality. RESULTS: In the network of mobile phone addiction-anxiety symptoms, the most influential symptoms were Failure to cut down the time, Anxiety if not used for some time, and Alleviate loneliness. Irritability was the most prominent bridging symptom. Gender difference had no effect on network structure. Nodes in the network are not predictive of sleep quality. CONCLUSION: Failure to cut down the time is the most important symptom, suggesting that measures should be taken to reduce the amount of time spent on mobile phones. For example, increase outdoor exercise, increase the real company of friends and family, in order to reduce the occurrence of mobile phone addiction and anxiety.

Prevalence and the age of onset patterns of stroke in Jiangsu Province, China.

OBJECTIVES: Little was known regarding the current age of onset patterns of stroke. This study aimed to examine the prevalence of stroke and explore the age of onset patterns of stroke in Jiangsu Province, China. MATERIALS AND METHODS: Participants were recruited from April 2012 to April 2013 in Jiangsu Province, China. Survival analysis models were used to evaluate the hazards of stroke by a single year of age. Kaplan-Meier analysis and the log-rank test were used to explore the disparities of the age of onset patterns of stroke. RESULTS: This population-based study was conducted among 39,887 participants aged ≥ 18 years in Jiangsu Province, China. Of the 740 (1.9%) events of stroke, 13.2% suffered from hemorrhagic stroke (HS) and 86.8% suffered from ischemic stroke (IS). The prevalence of HS and IS were 0.3% and 1.7%, respectively. The estimated mean age of onset of stroke was 71.98 (95% CI: 71.97-71.99) years by the survival model. Up to age of 45 years, the estimated hazards of stroke onset were at a relatively low level. From the age of 45 years, the increases in hazards accelerated and peaked at age 75 years. Urban, smoking, and drinking males had a higher risk of stroke than their counterparts (P < 0.05). However, no such difference was found among females. CONCLUSIONS: The findings emphasize the importance of implementing stroke prevention interventions in Jiangsu Province, China, especially for urban, smoking, and drinking males. It is of great significance to strengthen comprehensive management of health-related behaviors, including smoking cessation and moderate consumption of alcohol to have sustained beneficial effects on stroke risk. Chenlu He and Qian Chen contributed equally to this work.

Low-intensity red-light therapy in slowing myopic progression and the rebound effect after its cessation in Chinese children: a randomized controlled trial.

PURPOSE: To investigate the effect of low-intensity red-light (LRL) therapy on myopic control and the response after its cessation. METHODS: A prospective clinical trial. One hundred two children aged 6 to 13 with myopia were included in the LRL group (n = 51) and the single-focus spectacles (SFS) group (n = 51). In LRL group, subjects wore SFS and received LRL therapy provided by a laser device that emitted red-light of 635 nm and power of 0.35 ± 0.02 mW. One year after the control trial, LRL therapy was stopped for 3 months. The outcomes mainly included axial length (AL), spherical equivalent refraction (SER), subfoveal choroidal thickness (SFCT), and accommodative function. RESULTS: After 12 months of therapy, 46 children in the LRL group and 40 children in the SFS group completed the trial. AL elongation and myopic progression were 0.01 mm (95%CI: - 0.05 to 0.07 mm) and 0.05 D (95%CI: - 0 .08 to 0.19 D) in the LRL group, which were less than 0.39 mm (95%CI: 0.33 to 0.45 mm) and - 0.64 D (95%CI: - 0.78 to - 0.51 D) in the SFS group (p < 0.05). The change of SFCT in the LRL group was greater than that in the SFS group (p < 0.05). Accommodative response and positive relative accommodation in the LRL group were more negative than those in the SFS group (p < 0.05). Forty-two subjects completed the observation of LRL cessation, AL and SER increased by 0.16 mm (95%CI: 0.11 to 0.22 mm) and - 0.20 D (95%CI: - 0.26 to - 0.14 D) during the cessation (p < 0.05), and SFCT returned to baseline (p > 0.05). CONCLUSIONS: LRL is an effective measure for preventing and controlling myopia, and it may also have the ability to improve the accommodative function. There may be a slight myopic rebound after its cessation. The effect of long-term LRL therapy needs to be further explored. TRIAL REGISTRATION: Chinese Clinical Trial Registry: Chinese Clinical Trails registry: ChiCTR2100045250. Registered 9 April 2021; retrospectively registered. http://www.chictr.org.cn/showproj.aspx?proj=124250.

Melamine Foam-Derived Carbon Scaffold for Dendrite-Free and Stable Zinc Metal Anode.

Aqueous Zn-ion batteries (AZIBs) are one of the most promising large-scale energy storage devices due to the excellent characteristics of zinc metal anode, including high theoretical capacity, high safety and low cost. Nevertheless, the large-scale applications of AZIBs are mainly limited by uncontrollable Zn deposition and notorious Zn dendritic growth, resulting in low plating/stripping coulombic efficiency and unsatisfactory cyclic stability. To address these issues, herein, a carbon foam (CF) was fabricated via melamine-foam carbonization as a scaffold for a dendrite-free and stable Zn anode. Results showed that the abundant zincophilicity functional groups and conductive three-dimensional network of this carbon foam could effectively regulate Zn deposition and alleviate the Zn anode's volume expansion during cycling. Consequently, the symmetric cell with CF@Zn electrode exhibited lower voltage hysteresis (32.4 mV) and longer cycling performance (750 h) than the pure Zn symmetric cell at 1 mA cm-2 and 1 mAh cm-2. Furthermore, the full battery coupling CF@Zn anode with MnO2 cathode can exhibit a higher initial capacity and better cyclic performance than the one with the bare Zn anode. This work brings a new idea for the design of three-dimensional (3D) current collectors for stable zinc metal anode toward high-performance AZIBs.

Pathway from interpersonal sensitivity to depression among Chinese college students during the COVID-19 campus lockdown.

BACKGROUND: Due to the continuous spread of the epidemic, some colleges and universities have implemented a campus lockdown management policy in China. In the context of the campus lockdown, this study aimed to explore whether anxiety mediated the association between interpersonal sensitivity and depression, and investigate whether psychological capital moderated the indirect or direct effect of mediation model. METHODS: A total of 12945 undergrad students were recruited in China from April 10 to 19, 2022. These participants were asked to complete the online questionnaires measuring interpersonal sensitivity, anxiety, psychological capital, and depression. A moderated mediation model was examined by using PROCESS macro for SPSS 25.0, in which anxiety was a mediating variable, and psychological capital was a moderating variable. RESULTS: Interpersonal sensitivity was positively associated with depression among Chinese college students (r = 0.47, P < 0.001). Anxiety partially mediated the association between interpersonal sensitivity and depression (indirect effect = 2.31, 95%CI [2.18, 2.44], accounting for 70% of the total effect). Moreover, the interaction effect of interpersonal sensitivity and psychological capital on anxiety (ß = -0.04, t = -17.36, P < 0.001) and the interaction effect of anxiety and psychological capital on depression (ß = 0.002, t = 1.99, P < 0.05) were statistically significant. CONCLUSIONS: The current study explained the mediation role of anxiety and the moderation role of psychological capital in the relation between interpersonal sensitivity and depression. The findings suggested that strict monitoring anxiety and promoting psychological capital may decrease the risk of depression among Chinese college students during the campus lockdown.

How adverse and benevolent childhood experiences influence depression and suicidal ideation in Chinese undergraduates: a latent class analysis.

BACKGROUND: There has been minimal research on the role of benevolent childhood experiences (BCEs) and how such events may offer protection from the insidious effects of adverse childhood experiences (ACEs) or later in life. OBJECTIVES: This research aims to learn how BCEs and ACEs interact to affect adolescents' psychological distress. METHODS: Cross-sectional survey was conducted in three cities (Xuzhou, Nanjing, and Wuhan) in China from March 2021 to May 2021. Latent class analysis (LCA) was used to classify the patterns of ACEs and BCEs. We adopted hierarchical multivariable regression to examine the influences of ACEs and BCEs on depression and suicidal ideation. RESULTS: To explore the relationship between childhood experience and suicidal ideation and depression, LCA revealed three patterns of ACEs: (1) emotional abuse (10.57%); (2) high ACEs (0.55%); and (3) low ACEs classes (88.88%). Adolescents with emotional abuse (depression: OR = 3.82, 95%CI = 2.80-5.22, P < 0.001; suicidal ideation: OR = 5.766, 95%CI = 3.97-8.38, P < 0.001) and high ACEs class (suicidal ideation: OR = 5.93, 95%CI = 1.19-29.66, P < 0.05) had an increased risk of psychological distress (reference: low ACEs). LCA revealed four patterns of BCEs: (1) relationship support (14.54%); (2) low BCEs (4.85%); (3) high BCEs (55.34%); and (4) high quality of life classes (25.28%). Adolescents with a high quality of life (depression: OR = 0.09, 95%CI = 0.05-0.16, P < 0.001; suicidal ideation: OR = 0.22, 95%CI = 0.12-0.40, P < 0.001) and high BCEs (depression: OR = 0.05, 95%CI = 0.03-0.09, P < 0.001; suicidal ideation: OR = 0.15, 95%CI = 0.09-0.26, P < 0.001) protected the mental health of adolescents (reference: low BCEs). CONCLUSIONS: High ACEs and emotional abuse classes were significantly associated with poorer mental health symptoms, including suicidal ideation and depression. In contrast, high BCEs and high quality of life classes were associated with better mental health. These findings point out that it is more necessary to identify and support victims of ACEs, and it is urgent to increase BCEs in early childhood.

Impact of high blood pressure variability on the occurrence of acute type B aortic dissection.

BACKGROUND: Acute type B aortic dissection is a life-threatening medical emergency, and hypertension is believed to be an important predictor of aortic dissection; the impact of blood pressure variability on the onset and development of aortic dissection has attracted increasing attention. METHODS: A total of 120 acute type B aortic dissection patients and 57 hypertensive patients without aortic dissection were consecutively enrolled and retrospectively reviewed between January 2013 and November 2015. There were 60 acute type B aortic dissection patients in both high and low blood pressure variability groups. RESULTS: Blood pressure variability showed higher diagnostic value than hypertension in aortic dissection, and the best threshold of blood pressure variability is 5.71 mmHg. By performing multivariable logistic regression, we found that the history of hypertension was likely to be a risk factor of blood pressure variability (95% CI: 1.155-6.422, P = 0.022). Nine patients from high blood pressure variability group and two from low blood pressure variability group (χ2 = 4.90, P = 0.027) received emergency surgery within 24 hours after admission. The presence of multiple tears (>2, 55.0% vs. 45.0%, P = 0.001), configuration of the false lumen (spiral false lumen) (50.0% vs. 21.7%, P = 0.001), the diameter of the false lumen (49.6 ± 15.0 mm vs. 37.6 ± 10.8 mm, P < 0.001), the false/true lumen ratio (1.53 ± 1.02 vs. 0.929 ± 0.733, P < 0.001), and the number of visceral arteries involved (1.75 ± 0.942 vs. 0.800 ± 0.927, P < 0.001) showed significant differences between high and low blood pressure variability groups. Nine (30%) patients from the high blood pressure variability group showed a maximum diameter of false lumen over 60 mm, while none was found in the low blood pressure variability group. CONCLUSIONS: High blood pressure variability, the presence of multiple tears (>2), the configuration of false lumen, the diameter of the false lumen, false/true lumen ratio, and the number of visceral arteries involved were independent risk factors for acute type B aortic dissection.

A New Memristor with 2D Ti3 C2 Tx MXene Flakes as an Artificial Bio-Synapse.

Two-dimensional (2D) materials have attracted extensive research interest in academia due to their excellent electrochemical properties and broad application prospects. Among them, 2D transition metal carbides (Ti3 C2 Tx ) show semiconductor characteristics and are studied widely. However, there are few academic reports on the use of 2D MXene materials as memristors. In this work, reported is a memristor based on MXene Ti3 C2 Tx flakes. After electroforming, Al/Ti3 C2 Tx /Pt devices exhibit repeatable resistive switching (RS) behavior. More interestingly, the resistance of this device can be continuously modulated under the pulse sequence with 10 ns pulse width, and the pulse width of 10 ns is much lower than that in other reported work. Moreover, on the nanosecond scale, the transition from short-term plasticity to long-term plasticity is achieved. These two properties indicate that this device is favorable for ultrafast biological synapse applications and high-efficiency training of neural networks. Through the exploration of the microstructure, Ti vacancies and partial oxidation are proposed as the origins of the physical mechanism of RS behavior. This work reveals that 2D MXene Ti3 C2 Tx flakes have excellent potential for use in memristor devices, which may open the door for more functions and applications.

Vacancy-Induced Synaptic Behavior in 2D WS2 Nanosheet-Based Memristor for Low-Power Neuromorphic Computing.

Memristors with nonvolatile memory characteristics have been expected to open a new era for neuromorphic computing and digital logic. However, existing memristor devices based on oxygen vacancy or metal-ion conductive filament mechanisms generally have large operating currents, which are difficult to meet low-power consumption requirements. Therefore, it is very necessary to develop new materials to realize memristor devices that are different from the mechanisms of oxygen vacancy or metal-ion conductive filaments to realize low-power operation. Herein, high-performance and low-power consumption memristors based on 2D WS2 with 2H phase are demonstrated, which show fast ON (OFF) switching times of 13 ns (14 ns), low program current of 1 µA in the ON state, and SET (RESET) energy reaching the level of femtojoules. Moreover, the memristor can mimic basic biological synaptic functions. Importantly, it is proposed that the generation of sulfur and tungsten vacancies and electron hopping between vacancies are dominantly responsible for the resistance switching performance. Density functional theory calculations show that the defect states formed by sulfur and tungsten vacancies are at deep levels, which prevent charge leakage and facilitate the realization of low-power consumption for neuromorphic computing application.

Data Fusion of Fourier Transform Mid-Infrared (MIR) and Near-Infrared (NIR) Spectroscopies to Identify Geographical Origin of Wild Paris polyphylla var. yunnanensis.

Origin traceability is important for controlling the effect of Chinese medicinal materials and Chinese patent medicines. Paris polyphylla var. yunnanensis is widely distributed and well-known all over the world. In our study, two spectroscopic techniques (Fourier transform mid-infrared (FT-MIR) and near-infrared (NIR)) were applied for the geographical origin traceability of 196 wild P. yunnanensis samples combined with low-, mid-, and high-level data fusion strategies. Partial least squares discriminant analysis (PLS-DA) and random forest (RF) were used to establish classification models. Feature variables extraction (principal component analysis-PCA) and important variables selection models (recursive feature elimination and Boruta) were applied for geographical origin traceability, while the classification ability of models with the former model is better than with the latter. FT-MIR spectra are considered to contribute more than NIR spectra. Besides, the result of high-level data fusion based on principal components (PCs) feature variables extraction is satisfactory with an accuracy of 100%. Hence, data fusion of FT-MIR and NIR signals can effectively identify the geographical origin of wild P. yunnanensis.

Comparison of open surgery and endovascular procedures as a therapeutic choice for visceral artery aneurysms.

Objectives Visceral arterial aneurysms may be treated using open surgery or endovascular repair, but the best approach remains controversial. This was a retrospective study aiming to compare open surgery and endovascular treatment strategies for visceral arterial aneurysms. Methods The study included all 93 patients who were admitted with visceral artery aneurysms between January 2001 and January 2011 at the Department of Vascular Surgery, Changhai Hospital, Shanghai, China. All cases underwent either open or endovascular procedures. Overall survival and adverse events were compared between the groups. Success rate, blood loss, length of surgery, and length of hospital stay were also compared. The patients were followed up at three, six, and 12 months then every year until April 2014. Results Open surgery was performed on 34 patients and endovascular procedures on 59. There were no differences in characteristics of the patients between the open surgery and endovascular groups. The perioperative complication rate was 52.9 and 13.6% in the open surgery and endovascular groups, respectively. Mean follow-up was 36.8 months (range: 11 months to 10 years). The one- and five-year survival rates were 100 and 60.6%, respectively, in the open surgery group, compared to 100 and 84.5% in the endovascular group. Multivariate analysis for factors related to overall survival showed that there was a significant relationship with the treatment approach (HR = 0.479, 95%CI: 0.278-0.825; P = 0.008) and the presence of false aneurysm (HR = 2.929, 95%CI: 1.388-6.180, P = 0.005). Conclusions Endovascular repair could be considered as an effective method for visceral artery aneurysm. Endovascular repair showed lower perioperative complication rates and better long-term survival.

Comparison and Identification for Rhizomes and Leaves of Paris yunnanensis Based on Fourier Transform Mid-Infrared Spectroscopy Combined with Chemometrics.

Paris polyphylla, as a traditional herb with long history, has been widely used to treat diseases in multiple nationalities of China. Nevertheless, the quality of P. yunnanensis fluctuates among from different geographical origins, so that a fast and accurate classification method was necessary for establishment. In our study, the geographical origin identification of 462 P. yunnanensis rhizome and leaf samples from Kunming, Yuxi, Chuxiong, Dali, Lijiang, and Honghe were analyzed by Fourier transform mid infrared (FT-MIR) spectra, combined with partial least squares discriminant analysis (PLS-DA), random forest (RF), and hierarchical cluster analysis (HCA) methods. The obvious cluster tendency of rhizomes and leaves FT-MIR spectra was displayed by principal component analysis (PCA). The distribution of the variable importance for the projection (VIP) was more uniform than the important variables obtained by RF, while PLS-DA models obtained higher classification abilities. Hence, a PLS-DA model was more suitably used to classify the different geographical origins of P. yunnanensis than the RF model. Additionally, the clustering results of different geographical origins obtained by HCA dendrograms also proved the chemical information difference between rhizomes and leaves. The identification performances of PLS-DA and the RF models of leaves FT-MIR matrixes were better than those of rhizomes datasets. In addition, the model classification abilities of combination datasets were higher than the individual matrixes of rhizomes and leaves spectra. Our study provides a reference to the rational utilization of resources, as well as a fast and accurate identification research for P. yunnanensis samples.

Whole-genome sequencing in medicinal plants: current progress and prospect.

Advancements in genomics have dramatically accelerated the research on medicinal plants, and the development of herbgenomics has promoted the "Project of 1K Medicinal Plant Genome" to decipher their genetic code. However, it is difficult to obtain their high-quality whole genomes because of the prevalence of polyploidy and/or high genomic heterozygosity. Whole genomes of 123 medicinal plants were published until September 2022. These published genome sequences were investigated in this review, covering their classification, research teams, ploidy, medicinal functions, and sequencing strategies. More than 1,000 institutes or universities around the world and 50 countries are conducting research on medicinal plant genomes. Diploid species account for a majority of sequenced medicinal plants. The whole genomes of plants in the Poaceae family are the most studied. Almost 40% of the published papers studied species with tonifying, replenishing, and heat-cleaning medicinal effects. Medicinal plants are still in the process of domestication as compared with crops, thereby resulting in unclear genetic backgrounds and the lack of pure lines, thus making their genomes more difficult to complete. In addition, there is still no clear routine framework for a medicinal plant to obtain a high-quality whole genome. Herein, a clear and complete strategy has been originally proposed for creating a high-quality whole genome of medicinal plants. Moreover, whole genome-based biological studies of medicinal plants, including breeding and biosynthesis, were reviewed. We also advocate that a research platform of model medicinal plants should be established to promote the genomics research of medicinal plants.

Noninvasive Transdermal Administration of mRNA Vaccines Encoding Multivalent Neoantigens Effectively Inhibits Melanoma Growth.

It is difficult to obtain specific tumor antigens, which is one of the main obstacles in the development of tumor vaccines. The vaccines containing multivalent antigens are thought to be more effective in antitumor therapy. In this study, a mRNA encoding three neoantigens of melanoma were prepared and encapsulated into the mannosylated chitosan-modified ethosomes (EthsMC) to obtain a multivalent mRNA vaccine (MmRV) for transcutaneous immunization (TCI). MmRV can effectively induce maturation of dendritic cells, with a better performance than mRNA of a single neoantigen. TCI patches (TCIPs) loading MmRV or siRNA against PDL1 (siPDL1) were prepared and applied to the skin of melanoma-bearing mice. The results showed that TCIPs significantly increase the levels of TNF-α, IFN-γ, and IL-12 in both plasma and tumor tissues, inhibit tumor growth, as well as promote infiltration of CD4+ and CD8+ T cells in the tumor tissues. Furthermore, the combination of MmRV and siPDL1 showed much better antitumor effects than either monotherapy, suggesting a synergistic effect between the vaccine and PDL1 blocker. In addition, the treatment with the TCIPs did not cause damage to the skin, blood, and vital organs of the mice, showing good biosafety. To the best of our knowledge, this work is the first to construct a noninvasive TCI system containing MmRV and siPDL1, providing a convenient and promising approach for tumor treatment.

An immune sandwich electrochemical biosensor based on triple-modified zirconium derivatives for detection of CD146 in serum.

CD146, also known as melanoma cell adhesion molecule (MCAM), is overexpressed in various cancer patients, making it a valuable predictor for early diagnosis. In this work, an immune sandwich electrochemical biosensor is proposed for sensitive and non-invasive quantitative detection of CD146 in serum. Zirconium-based MOF (UIO-66) was modified by simultaneous copper atom doping, in situ growth carbon-based support and physical embedding of platinum nanoparticles (PtNPs). Triple-modified Cu-UIO-66@SWCNT/PtNPs nanocomposites with high stability and excellent electrochemical properties, serve as surface modification materials for glassy carbon electrodes. Anti-CD146 antibody (Ab1) was grafted onto the electrode surface via Pt-S bond. Meanwhile, the secondary antibody (Ab2) was conjugated with silver nanoparticles (AgNPs) to cooperate for CD146 capture and achieve secondary electrical signal amplification. Under optimal conditions, square wave voltammetry was employed to determine CD146 in the concentration range of 10-9-10-4 mg/mL and a limit of detection of 12 fg/mL was obtained. Finally, it was successfully applied to the analysis of CD146 in lung and liver cancer patients' serum samples.