Association between triglyceride-glucose index and arterial stiffness progression: A retrospective cohort study. / ç”˜æ²¹ä¸‰é ¯-è‘¡è„ç³–ä¹˜ç§¯æŒ‡æ•°ä¸ŽåŠ¨è„‰ç¡¬åŒ–è¿›å±•çš„å›žé¡¾æ€§é˜Ÿåˆ—ç ”ç©¶.

OBJECTIVES: Insulin resistance (IR) is closely associated with atherosclerosis and adverse cardiovascular events. The triglyceride-glucose (TyG) index is an effective indicator for assessing IR. This study aims to explore the relationship between the TyG index and the risk of arterial stiffness progression. METHODS: This retrospective cohort study included adults who had undergone at least 2 health examinations with arteriosclerosis testing at the Health Management Medical Center of the Third Xiangya Hospital, Central South University, between January 2012 and December 2022. Clinical data were collected. The TyG index was calculated using the formula of ln (triglycerides×fasting blood glucose/2). The baseline TyG index was assessed as both a continuous variable and as a quartile-based categorical variable. The progression of arteriosclerosis was evaluated by the annual change rate of brachial-ankle pulse wave velocity (baPWV) and the new onset of increased arterial stiffness. Linear regression model and Cox proportional hazard model were used to explore whether the TyG index is an independent risk factor for arterial stiffness progression. Subgroup analyses were performed based on age, gender, body mass index (BMI), and the presence of type 2 diabetes, hypertension, or hyperlipidemia to determine the characteristics of the association between the TyG index and arterial stiffness progression. RESULTS: A total of 4 971 participants were included, with a follow-up period of (3.01±1.98) years. During follow-up, the annual baPWV change rate was (24.94±81.15) cm/s, and 278 cases of new onset of increased aterial stiffness were recorded. After fully adjusting for confounding factors, the baseline TyG index was independently positively correlated with both the annual baPWV change rate (ß=17.5, 95% CI 9.00 to 25.94, P<0.001) and the risk of new onset of increased aterial stiffness [hazard ratio (HR)=1.43, 95% CI 1.18 to 1.74, P<0.001] when the TyG index was treated as a continuous variable. When treated as a categorical variable, higher TyG index quartiles were associated with progressively higher baPWV change rates and new onset of increased arterial stiffness (all P<0.05). In subgroups of participants aged ≥45 years, males, BMI<28 kg/m2, those with or without hypertension, and those without type 2 diabetes or hyperlipidemia, the baseline TyG index (both continuous and categorical) was significantly associated with new onset of increased arterial stiffness (all P<0.05), with no significant interactions observed across subgroups (all P>0.05). CONCLUSIONS: The TyG index is independently associated with an increased risk of arterial stiffness progression and may serve as a useful indicator for assessing arterial stiffness progression risk in health check-up populations.

Associations of triglyceride-glucose index cumulative exposure and variability with the transitions from normoglycaemia to prediabetes and prediabetes to diabetes: Insights from a cohort study.

AIM: This study aimed to investigate the separate and joint associations of triglyceride-glucose (TyG) index accumulation and variability with prediabetes and diabetes risk. METHODS: Health check-up participants who underwent 3 sequential health examinations during 2012-2016 and were followed up from 2017 to 2021 were enrolled and categorized into two subcohorts: (a) progression from normoglycaemia to prediabetes subcohort (n = 9373) and (b) progression from prediabetes to diabetes subcohort (n = 4563). Cumulative TyG (cumTyG) and TyG variability from Exams 1-3 were the exposures of interest in our study. The outcomes were newly incident prediabetes or diabetes. RESULTS: In the prediabetes development subcohort, 2,074 participants developed prediabetes over a 2.42-year follow-up. Higher cumTyG (HR, 2.02; 95 % CI, 1.70-2.41), but not greater TyG variability alone, was significantly associated with increased prediabetes risk. In the diabetes development subcohort, 379 participants developed diabetes over a 3.0-year follow-up. Higher cumTyG (HR, 3.54; 95 % CI, 2.29-5.46), but not greater TyG variability alone, was significantly associated with increased diabetes risk. The "cumTyG+variability" combination had the highest predictive value for prediabetes and diabetes beyond a single baseline TyG measurement. CONCLUSION: Higher cumTyG exposure independently predicts prediabetes and diabetes incidence. Coexisting cumTyG and variability could further yield incrementally greater risks.

Mitochondrial targeted modification and anticancer mechanism of natural product ergosterol peroxide.

Ergosterol peroxide (EP) isolated from the edible medicinal fungus Pleurotus ferulae has a wide range of anti-tumor activity, but poor water solubility and low bioavailability limit further application. In this study, EP was structurally modified using triphenylphosphine (TPP+), which combines mitochondrial targeting, amphiphilicity, and cytotoxicity. A series of TPP+-conjugated ergosterol peroxide derivatives (TEn) with different length linker arms were synthesized. The structure-activity relationship showed that the anticancer activity of TEn gradually decreased with the elongation of the linker arm. The compound TE3 has the optimal and broadest spectrum of antitumor effects. It mainly through targeting mitochondria, inducing ROS production, disrupting mitochondrial function, and activating mitochondria apoptosis pathway to exert anti-cervical cancer activity. Among them, TPP+ only acted as a mitochondrial targeting group, while EP containing peroxide bridge structure served as an active group to induce ROS. In vivo experiments have shown that TE3 has better anti-cervical cancer activity and safety than the first-line anticancer drug cisplatin, and can activate the immune response in mice. Although TE3 exhibits some acute toxicity, it is not significant at therapeutic doses. Therefore, TE3 has the potential for further development as an anti-cervical cancer drug.

Use of Silk Fibroin Material Composites for Green, Flexible Supercapacitors.

Within the context of seeking eco-friendly and readily available materials for energy storage, there is a pressing demand for energy storage solutions that employ environmentally sustainable, high-performance, and adaptable constituents. Specifically, such materials are essential for use in wearable technology, smart sensors, and implantable medical devices, whereas, more broadly, their use plays a pivotal role in shaping their efficiency and ecological footprint. Here, we demonstrate an entirely biopolymer-based supercapacitor with a remarkable performance, achieving a capacitance greater than 0.2 F cm-2 at a charge-discharge current of 10 mA cm-2 with 94% capacitance retention after 20,000 cycles. The supercapacitor is composed of three distinct silk fibroin (SF) composite materials, namely, photo-cross-linkable SF (Sil-MA) hydrogel, SF-polydopamine (SF-PDA), and SF bioplastic, to create a gel electrolyte, electrode binder, and encapsulation, respectively. Together, these elements form a mechanically and electrochemically robust skeleton for biofriendly energy storage devices. Moreover, these biomaterial-based supercapacitor devices show stretchability, flexibility, and compressibility while maintaining their electrochemical performance. The biomaterials and fabrication techniques presented can serve as a foundation for investigating various aqueous electrochemical energy storage systems, especially for emerging applications in wearable electronics and environmentally friendly material systems.

Phytopathogenic Fungicidal Activity and Mechanism Approach of Three Kinds of Triphenylphosphonium Salts.

The triphenylphosphonium (TPP) cation has been widely used as a carrier for mitochondria-targeting molecules. We synthesized two commonly employed targeting systems, namely, ω-triphenylphosphonium fatty acids (group 2) and ω-triphenylphosphonium fatty alcohols (group 3), to assess the impact of the TPP module on the biological efficacy of mitochondria-targeting molecules. We evaluated their fungicidal activities against nine plant pathogenic fungi in comparison to alkyl-1-triphenylphosphonium compounds (group 1). All three compound groups exhibited fungicidal activity and displayed a distinct "cut-off effect", which depended on the length of the carbon chain. Specifically, group 1 compounds showed a cut-off point at C10 (compound 1-7), while group 2 and 3 compounds exhibited cut-off points at C15 (compound 2-12) and C14 (compound 3-11), respectively. Notably, group 1 compounds displayed significantly higher fungicidal activity compared to groups 2 and 3. However, group 2 and 3 compounds showed similar activity to each other, although susceptibility may depend on the pathogen tested. Initial investigations into the mechanism of action of the most active compounds suggested that their fungicidal performance may be primarily attributed to their ability to damage the membrane, as well as uncoupling activity and inhibition of fungal respiration. Our findings suggest that the TPP module used in delivery systems as aliphatic acyl or alkoxyl derivatives with carbon chains length < 10 will contribute negligible fungicidal activity to the TPP-conjugate compared to the effect of high level of accumulation in mitochondria due to its mitochondria-targeting ability. These results provide a foundation for utilizing TPP as a promising carrier in the design and development of more effective mitochondria-targeting drugs or pesticides.

CRISPR-Based Modular Assembly for High-Throughput Construction of a UAS-cDNA/ORF Plasmid Library.

Functional genomics screening offers a powerful approach to probe gene function and relies on the construction of genome-wide plasmid libraries. Conventional approaches for plasmid library construction are time-consuming and laborious. Therefore, we recently developed a simple and efficient method, CRISPR-based modular assembly (CRISPRmass), for high-throughput construction of a genome-wide upstream activating sequence-complementary DNA/open reading frame (UAS-cDNA/ORF) plasmid library. Here, we present a protocol for CRISPRmass, taking as an example the construction of a GAL4/UAS-based UAS-cDNA/ORF plasmid library. The protocol includes massively parallel two-step test tube reactions followed by bacterial transformation. The first step is to linearize the existing complementary DNA (cDNA) or open reading frame (ORF) cDNA or ORF library plasmids by cutting the shared upstream vector sequences adjacent to the 5' end of cDNAs or ORFs using CRISPR/Cas9 together with single guide RNA (sgRNA), and the second step is to insert a UAS module into the linearized cDNA or ORF plasmids using a single step reaction. CRISPRmass allows the simple, fast, efficient, and cost-effective construction of various plasmid libraries. The UAS-cDNA/ORF plasmid library can be utilized for gain-of-function screening in cultured cells and for constructing a genome-wide transgenic UAS-cDNA/ORF library in Drosophila.

Natural killer cell-related anti-tumour adoptive cell immunotherapy.

Chimeric antigen receptor- (CAR-)modified T cells have been successfully used to treat blood cancer. With the improved research on anti-tumour adoptive cell therapy, researchers have focused on immune cells other than T lymphocytes. Natural killer (NK) cells have received widespread attention as barriers to natural immunity. Compared to T lymphocyte-related adoptive cell therapy, the use of NK cells to treat tumours does not cause graft-versus-host disease, significantly improving immunity. Moreover, NK cells have more sources than T cells, and the related modified cells are less expensive. NK cells function through several pathways in anti-tumour mechanisms. Currently, many anti-tumour clinical trials have used NK cell-related adoptive cell therapies. In this review, we have summarized the recent progress in NK cell-related adoptive cellular immunotherapy for tumour treatment and propose the current challenges faced by CAR-NK cell therapy.

Novel Hsp90-Targeting PROTACs: Enhanced synergy with cisplatin in combination therapy of cervical cancer.

The development of effective drugs for cervical cancer is urgently required because of its high mortality rate and the limited treatment options. Herein, we report the design, synthesis, and evaluation of a series of novel and effective Hsp90-targeting PROTACs. These compounds exhibited potent anti-proliferative activity against cervical cancer cells with low IC50 values. Compound lw13 effectively degraded Hsp90 at a concentration of only 0.05 µM. In addition, it can inhibit the metastasis of cancer cells and induce significant cell cycle arrest and apoptosis. Furthermore, lw13 demonstrated remarkable antitumor activity both in vitro and in vivo, and has a synergistic effect in combination with cisplatin. Moreover, lw13 can prevent the activation of the HER2/AKT/mTOR signaling pathway by indirectly reducing the levels of HER2 and AKT. This study paves the way for cancer treatment and provides valuable insights into the combination therapy of cervical cancer.

Embryo Microinjection for Transgenesis in Drosophila.

Transgenesis in Drosophila is an essential approach to studying gene function at the organism level. Embryo microinjection is a crucial step for the construction of transgenic flies. Microinjection requires some types of equipment, including a microinjector, a micromanipulator, an inverted microscope, and a stereo microscope. Plasmids isolated with a plasmid miniprep kit are qualified for microinjection. Embryos at the pre-blastoderm or syncytial blastoderm stage, where nuclei share a common cytoplasm, are subjected to microinjection. A cell strainer eases the process of dechorionating embryos. The optimal time for dechorionation and desiccation of embryos needs to be determined experimentally. To increase the efficiency of embryo microinjection, needles prepared by a puller need to be beveled by a needle grinder. In the process of grinding needles, we utilize a foot air pump with a pressure gauge to avoid the capillary effect of the needle tip. We routinely inject 120-140 embryos for each plasmid and obtain at least one transgenic line for around 85% of plasmids. This article takes the phiC31 integrase-mediated transgenesis in Drosophila as an example and presents a detailed protocol for embryo microinjection for transgenesis in Drosophila.

Long non-coding RNA NEAT1 promotes aerobic glycolysis and progression of cervical cancer through WNT/ß-catenin/PDK1 axis.

BACKGROUND: Cervical cancer is one of the most common gynecological cancers. Accumulated evidence shows that long non-coding RNAs (lncRNAs) play essential roles in cervical cancer occurrence and progression, but their specific functions and mechanisms remain to be further explored. METHODS: The RT-qPCR assay was used to detect the expression of NEAT1 in cervical cancer tissues and cell lines. CCK-8, colony formation, flow cytometry, western blotting, and Transwell assays were used to evaluate the impact of NEAT1 on the malignant behavior of cervical cancer cells. Glucose consumption, lactate production, ATP levels, ROS levels, MMP levels, and the mRNA expressions of glycolysis-related genes and tricarboxylic acid cycle-related genes were detected to analyze the effect of NEAT1 on metabolism reprograming in cervical cancer cells. The expressions of PDK1, ß-catenin and downstream molecules of the WNT/ß-catenin signaling pathway in cervical cancer cells and tissues were detected by western blotting, RT-qPCR, immunofluorescence and immunohistochemistry assays. RESULTS: This study investigated the role and possible molecular mechanism of lncRNA nuclear paraspeckle assembly transcript 1 (NEAT1) in cervical cancer. Our results showed that NEAT1 was highly expressed in cervical cancer tissues and cell lines. Downregulation of NEAT1 inhibited the proliferation, migration, invasion and glycolysis of cervical cancer cells, while overexpression of NEAT1 led to the opposite effects. Mechanistically, NEAT1 upregulated pyruvate dehydrogenase kinase (PDK1) through the WNT/ß-catenin signaling pathway, which enhanced glycolysis and then facilitated cervical cancer metastasis. Furthermore, NEAT1 maintained the protein stability of ß-catenin but did not affect its mRNA level. We also excluded the direct binding of NEAT1 to the ß-catenin protein via RNA pull-down assay. The suppressive impact of NEAT1 knockdown on cell proliferation, invasion, and migration was rescued by ß-catenin overexpression. The WNT inhibitor iCRT3 attenuated the carcinogenic effect induced by NEAT1 overexpression. CONCLUSION: In summary, these findings indicated that NEAT1 may contribute to the progression of cervical cancer by activating the WNT/ß-catenin/PDK1 signaling axis.

A cost-effective, machine learning-driven approach for screening arterial functional aging in a large-scale Chinese population.

Introduction: An easily accessible and cost-free machine learning model based on prior probabilities of vascular aging enables an application to pinpoint high-risk populations before physical checks and optimize healthcare investment. Methods: A dataset containing questionnaire responses and physical measurement parameters from 77,134 adults was extracted from the electronic records of the Health Management Center at the Third Xiangya Hospital. The least absolute shrinkage and selection operator and recursive feature elimination-Lightweight Gradient Elevator were employed to select features from a pool of potential covariates. The participants were randomly divided into training (70%) and test cohorts (30%). Four machine learning algorithms were applied to build the screening models for elevated arterial stiffness (EAS), and the performance of models was evaluated by calculating the area under the receiver operating characteristic curve (AUC), sensitivity, specificity, and accuracy. Results: Fourteen easily accessible features were selected to construct the model, including "systolic blood pressure" (SBP), "age," "waist circumference," "history of hypertension," "sex," "exercise," "awareness of normal blood pressure," "eat fruit," "work intensity," "drink milk," "eat bean products," "smoking," "alcohol consumption," and "Irritableness." The extreme gradient boosting (XGBoost) model outperformed the other three models, achieving AUC values of 0.8722 and 0.8710 in the training and test sets, respectively. The most important five features are SBP, age, waist, history of hypertension, and sex. Conclusion: The XGBoost model ideally assesses the prior probability of the current EAS in the general population. The integration of the model into primary care facilities has the potential to lower medical expenses and enhance the management of arterial aging.

Fluorescence modulation of quantum dots in subsurface defects of optical elements by a linearly polarized light.

The limited excitation efficiency of quantum dots in the detection of subsurface defects in optical elements by quantum dot fluorescence gives rise to insufficient accuracy. To enhance the excitation efficiency of quantum dots, we studied the modulation of the polarization direction of linearly polarized incident light on quantum dot fluorescence. We first apply density matrix evolution theory to study the quantum dots interacting with linearly polarized incident light and emitting fluorescence. The fluorescence intensity exhibits cosine oscillations versus modulated laser polarization. It reaches a maximum value at the polarization angle zero, and then decreases as the angle becomes larger until π/2. The experimental results for the quantum dot in both solutions and subsurface defect of optical elements confirmed these results. For optical elements tagged with CdSe/ZnS quantum dots, the fluorescence intensity increases by 61.7%, and the area for the detected subsurface defects increases by 142.9%. Similarly, for C and InP/ZnS quantum dots, there are also increases in both the fluorescence intensity and the area of subsurface defects. Our study suggests that the subsurface defect detection in optical elements by the linearly polarized incident light could enhance the detection accuracy of subsurface defects in optical elements, and potentially achieve super-resolution imaging of subsurface defects.

Production of iron-enriched yeast and it's application in the treatment of iron-deficiency anemia.

Iron deficiency anemia (IDA) is one of the most serious forms of malnutrition. Wild type strains of Saccharomyces cerevisiae have higher tolerance to inorganic iron and higher iron conversion and accumulation capacity. The aim of this study was to investigate the effect of S. cerevisiae enriched iron as a potential organic iron supplement on mice with iron deficiency anemia. 60 male Kunming mice (KM mice, with strong adaptability and high reproduction rate, it can be widely used in pharmacology, toxicology, microbiology and other research) were randomly divided into normal control group and iron deficiency diet model group to establish IDA model. After the model was established, IDA mice were randomly divided into 5 groups: normal control group, IDA group, organic iron group (ferrous glycinate), inorganic iron group (ferrous sulfate) and S. cerevisiae enriched iron group. Mice in the experimental group were given different kinds of iron by intragastric administration once a day for 4w. The results showed that S. cerevisiae enriched iron had an effective recovery function, and the body weight and hematological parameters of IDA mice returned to normal levels. The activities of superoxide dismutase, glutathione peroxidase and total antioxidant capacity in serum were increased. In addition, the strain no. F8, able to grow in an iron-rich environment, was more effective in alleviating IDA and improving organ indices with fewer side effects compared to ferrous glycinate and ferrous sulfate groups. This study suggests that the iron-rich strain no. F8 may play an important role in improving IDA mice and may be developed as a new iron supplement.

ADNP modulates SINE B2-derived CTCF-binding sites during blastocyst formation in mice.

CTCF is crucial for chromatin structure and transcription regulation in early embryonic development. However, the kinetics of CTCF chromatin occupation in preimplantation embryos have remained unclear. In this study, we used CUT&RUN technology to investigate CTCF occupancy in mouse preimplantation development. Our findings revealed that CTCF begins binding to the genome prior to zygotic genome activation (ZGA), with a preference for CTCF-anchored chromatin loops. Although the majority of CTCF occupancy is consistently maintained, we identified a specific set of binding sites enriched in the mouse-specific short interspersed element (SINE) family B2 that are restricted to the cleavage stages. Notably, we discovered that the neuroprotective protein ADNP counteracts the stable association of CTCF at SINE B2-derived CTCF-binding sites. Knockout of Adnp in the zygote led to impaired CTCF binding signal recovery, failed deposition of H3K9me3, and transcriptional derepression of SINE B2 during the morula-to-blastocyst transition, which further led to unfaithful cell differentiation in embryos around implantation. Our analysis highlights an ADNP-dependent restriction of CTCF binding during cell differentiation in preimplantation embryos. Furthermore, our findings shed light on the functional importance of transposable elements (TEs) in promoting genetic innovation and actively shaping the early embryo developmental process specific to mammals.

Tunable Emission of Low-Dimensional Organic Metal Halides by Stoichiometric Ratio and Metal Center.

Low-dimensional (LD) organic metal halides (OMHs) have a bright future due to their excellent photoelectric characteristics and unique structure. However, the synthesis and emission control of LD-OMHs are still unclear. Herein, the different dimensional (zero-dimensional (0D), one-dimensional (1D), and three-dimensional (3D)) of OMHs were obtained by the reaction of 1,4-diazabicyclo (2.2.2) octane with PbBr2 in different stoichiometric ratios. This discovery shows that the structure and properties of OMHs can be regulated while maintaining the functional organic cations of OMHs, which broadens the path for the development of functional LD-OMHs. Among them, 0D-OMH 1 and 1D-OMH 3 have narrow-band (full width at half-maximum (fwhm) = 74 nm) and broad-band (fwhm = 201 nm) emission, respectively. We found that when organic cations have no contribution to the formation of conduction band minimum and valence band maximum, and the distances between polyhedrons are larger than the van der Waals diameter of the halogen atom, the effect of phonons on exciton transitions can be reduced to achieve a narrow-band emission. Further, Cu(I)- and Mn (II)-based 0D-OMHs were synthesized, which have high photoluminescence quantum yield (PLQY) (33.97 and 47.33%, respectively). When the emitting of 0D-OMHs produced by the interaction of the metal-center and halogens, the asymmetric planar metal-halogen structure will result in a higher PLQY.

Signatures of tumor-associated macrophages correlate with treatment response in ovarian cancer patients.

Ovarian cancer (OC) ranks as the second leading cause of death among gynecological cancers. Numerous studies have indicated a correlation between the tumor microenvironment (TME) and the clinical response to treatment in OC patients. Tumor-associated macrophages (TAMs), a crucial component of the TME, exert influence on invasion, metastasis, and recurrence in OC patients. To delve deeper into the role of TAMs in OC, this study conducted an extensive analysis of single-cell data from OC patients. The aim is to develop a new risk score (RS) to characterize the response to treatment in OC patients to inform clinical treatment. We first identified TAM-associated genes (TAMGs) in OC patients and examined the protein and mRNA expression levels of TAMGs by Western blot and PCR experiments. Additionally, a scoring system for TAMGs was constructed, successfully categorizing patients into high and low RS subgroups. Remarkably, significant disparities were observed in immune cell infiltration and immunotherapy response between the high and low RS subgroups. The findings revealed that patients in the high RS group had a poorer prognosis but displayed greater sensitivity to immunotherapy. Another important finding was that patients in the high RS subgroup had a higher IC50 for chemotherapeutic agents. Furthermore, further experimental investigations led to the discovery that THEMIS2 could serve as a potential target in OC patients and is associated with EMT (epithelial-mesenchymal transition). Overall, the TAMGs-based scoring system holds promise for screening patients who would benefit from therapy and provides valuable information for the clinical treatment of OC.

Metabolic health phenotype better predicts subclinical atherosclerosis than body mass index-based obesity phenotype in the non-alcoholic fatty liver disease population.

Background: Non-alcoholic fatty liver disease (NAFLD), especially lean NAFLD is associated with an increased risk of atherosclerotic cardiovascular disease (CVD). It is not currently known which clinical phenotypes of NAFLD contribute most to individual subclinical atherosclerosis risk. We examined the relationship between body mass index (BMI), the metabolically healthy status, and subclinical atherosclerosis in the NAFLD population. Methods: Data from asymptomatic NAFLD subjects who participated in a routine health check-up examination were collected. Participants were stratified by BMI (cutoff values: 24.0-27.9 kg/m2 for overweight and ≥28.0 kg/m2 for obesity) and metabolic status, which was defined by Adult Treatment Panel III criteria. Subclinical atherosclerosis was evaluated by brachial-ankle pulse wave velocity (baPWV) in 27,738 participants and by carotid plaque in 14,323 participants. Results: Within each BMI strata, metabolically unhealthy subjects had a significantly higher prevalence of subclinical atherosclerosis than metabolically healthy subjects, whereas fewer differences were observed across subjects within the same metabolic category. When BMI and metabolic status were assessed together, a metabolically unhealthy status was the main contributor to the association of clinical phenotypes with the subclinical atherosclerosis burden (all p < 0.001). When BMI and metabolic abnormalities were assessed separately, the incidence of subclinical disease did not increase across BMI categories; however, it increased with an increase in the number of metabolic abnormalities (0, 1, 2 and ≥3). Conclusion: A metabolically healthy status in NAFLD patients was closely correlated with subclinical atherosclerosis, beyond that of the BMI-based obesity phenotype. The application of metabolic phenotyping strategies could enable more precise classification in evaluating cardiovascular risk in NAFLD.

Design and control of a fast steering mirror based on flexible supports and piezoelectric ceramic actuators.

The use of the fast steering mirror in an optical path requires strict volume control, and traditional structures have low space-utilization efficiency, resulting in traditional actuators having limited output in narrow spaces. The design in this paper adopts a combination of flexible universal supports and piezoelectric ceramic actuators, greatly reducing the layout space of the rotating-shaft system. We accurately model the design structure and develop closed-loop control methods to further improve the closed-loop control accuracy of the system. The experimental results indicate that the developed control method effectively improves the response speed and bandwidth and thus has good potential for use in engineering applications.

The complete chloroplast genome sequence of Aconitum tschangbaischanense (Ranunculaceae).

The perennial herbal medicine species Aconitum tschangbaischanense, is endemic to Changhai Mountain, Jilin province. In this study, we attempted to uncover the complete chloroplast (cp) genome of A. tschangbaischanense based on sequencing data using the Illumina sequencing technology. As per the results: (1) the length of its complete cp genome is 155,881 bp with a typical tetrad structure; (2) the structure of its cp genome contains large single-copy and small single-copy (LSC and SSC) regions of 86,351 and 16,9444 bp, respectively, isolated by two inverted repeat regions (IRs) of 26,293 bp; (3) we annotated a total 131 genes, consisting of 86 protein-coding genes, eight rRNA genes, and 37 tRNA genes. According to the maximum-likelihood phylogenetic tree based on complete cp genomes, A. tschangbaischanense, showed close association with A. carmichaelii, which belongs to clade I. Finally, this study provides the characteristics of the cp genome of A. tschangbaischanense, and its phylogenetic position.

Stapled peptide PROTAC induced significantly greater anti-PD-L1 effects than inhibitor in human cervical cancer cells.

Introduction: Immune checkpoint inhibitors (ICIs) are monoclonal antibodies that target immune checkpoints that suppress immune cell activity. Low efficiency and high resistance are currently the main barriers to their clinical application. As a representative technology of targeted protein degradation, proteolysis-targeting chimeras (PROTACs) are considered to have potential for addressing these limitations. Methods: We synthesized a stapled peptide-based PROTAC (SP-PROTAC) that specifically targeted palmitoyltransferase ZDHHC3 and resulted in the decrease of PD-L1 in human cervical cancer cell lines. Flow cytometry, confocal microscopy, protein immunoblotting, Cellular Thermal Shift Assay (CETSA), and MTT assay analyses were conducted to evaluate the effects of the designed peptide and verify its safety in human cells. Results: In cervical cancer celllines C33A and HeLa, the stapled peptide strongly downregulated PD-L1 to < 50% of baseline level at 0.1 µM. DHHC3 expression decreased in both dosedependentand time-dependent manners. MG132, the proteasome inhibitor, can alleviate the SP-PROTAC mediated degradation of PD-L1 in human cancer cells. In a co-culture model of C33A and T cells, treatment with the peptide induced IFN-γ and TNF-α release in a dose-dependent manner by degrading PD-L1. These effects were more significant than that of the PD-L1 inhibitor, BMS-8. Conclusions: Cells treated with 0.1 µM of SP-PROTAC or BMS-8 for 4 h revealed that the stapled peptide decreased PD-L1 more effectively than BMS-8. DHHC3-targeting SP-PROTAC decreased PD-L1 in human cervical cancer more effectively than the inhibitor BMS-8.