BACKGROUND: Deep brain stimulation (DBS) is a promising therapy for refractory Gilles de la Tourette syndrome (GTS). However, its long-term efficacy, safety, and recommended surgical age remain controversial, requiring evidence to compare different age categories. METHODS: This retrospective cohort study recruited 102 GTS patients who underwent DBS between October 2006 and April 2022 at two national centers. Patients were divided into two age categories: children (aged < 18 years; n = 34) and adults (aged ≥ 18 years; n = 68). The longitudinal outcomes as tic symptoms were assessed by the YGTSS, and the YBOCS, BDI, and GTS-QOL were evaluated for symptoms of obsessive-compulsive disorder (OCD), depression, and quality of life, respectively. RESULTS: Overall, these included patients who finished a median 60-month follow-up, with no significant difference between children and adults (p = 0.44). Overall, the YGTSS total score showed significant postoperative improvements and further improved with time (improved 45.2%, 51.6%, 55.5%, 55.6%, 57.8%, 61.4% after 6, 12, 24, 36, 48, and ≥ 60 months of follow-up compared to baseline, respectively) in all included patients (all p < 0.05). A significantly higher improvement was revealed in children than adults at ≥ 60 months of follow-up in the YGTSS scores (70.1% vs 55.9%, p = 0.043), and the time to achieve 60% improvement was significantly shorter in the children group (median 6 months vs 12 months, p = 0.013). At the last follow-up, the mean improvements were 45.4%, 48.9%, and 55.9% and 40.3%, 45.4%, and 47.9% in YBOCS, BDI, and GTS-QOL scores for children and adults, respectively, which all significantly improved compared to baseline (all p < 0.05) but without significant differences between these two groups (all p > 0.05), and the children group received significantly higher improvement in GTS-QOL scores than adults (55.9% vs. 47.9%, p = 0.049). CONCLUSIONS: DBS showed acceptable long-term efficacy and safety for both children and adults with GTS. Surgeries performed for patients younger than 18 years seemed to show acceptable long-term efficacy and safety and were not associated with increased risks of loss of benefit compared to patients older than 18 at the time of surgery. However, surgeries for children should also be performed cautiously to ensure their refractoriness and safety.
Deep Brain Stimulation , Tourette Syndrome , Humans , Tourette Syndrome/therapy , Deep Brain Stimulation/methods , Male , Female , Child , Adult , Adolescent , Retrospective Studies , Follow-Up Studies , Young Adult , Treatment Outcome , Quality of Life , Middle Aged , Age Factors
The overuse and misuse of tetracycline (TCs) antibiotics, including tetracycline (TTC), oxytetracycline (OTC), doxycycline (DC), and chlortetracycline (CTC), pose a serious threat to human health. However, current rapid sensing platforms for tetracyclines can only quantify the total amount of TCs mixture, lacking real-time identification of individual components. To address this challenge, we integrated a deep learning strategy with fluorescence and colorimetry-based multi-mode logic gates in our self-designed smartphone-integrated toolbox for the real-time identification of natural TCs. Our ratiometric fluorescent probe (CD-Au NCs@ZIF-8) encapsulated carbon dots and Au NCs in ZIF-8 to prevent false negative or positive results. Additionally, our independently developed WeChat app enabled linear quantification of the four natural TCs using the fluorescence channels. The colorimetric channels were also utilized as outputs of logic gates to achieve real-time identification of the four individual natural tetracyclines. We anticipate this strategy could provide a new perspective for effective control of antibiotics.
Pinus armandii is an ecologically and economically important evergreen tree species native to western China. Dendroctonus armandi and pathogenic ophiostomatoid fungi pose substantial threats to P. armandii. With the interplay between species, the defense mechanisms of P. armandii have evolved to withstand external biotic stressors. However, the interactions between P. armandii and pathogenic ophiostomatoid fungal species/strains remain poorly understood. We aimed to analyze the pathophysiological and molecular changes in P. armandii following artificial inoculation with four ophiostomatoid species (Graphilbum parakesiyea, Leptographium qinlingense, Ophiostoma shennongense, and Ophiostoma sp. 1). The study revealed that L. qinlingense produced the longest necrotic lesions, and G. parakesiyea produced the shortest. All strains induced monoterpenoid release, and monoterpene levels of P. armandii were positively correlated with fungal virulence (R2 = 0.93, P < 0.01). Co-inoculation of two dominant highly (L. qinlingense) and weakly virulent (O. shennongense) pathogens reduced the pathogenicity of the highly virulent fungi. Transcriptomic analysis of P. armandii (LQ: L. qinlingense treatments, QS: co-inoculation treatments, and OS: O. shennongense treatments) showed that the expression pattern of differentially expressed genes (DEGs) between QS and OS was similar, but different from that of LQ. The DEGs (LQ vs. QS) involved in flavonoid biosynthesis and phenylpropanoid biosynthesis were downregulated. Notably, compared with LQ, QS significantly decreased the expression of host defense-related genes. This study provides a valuable theoretical basis for managing infestations of D. armandi and associated ophiostomatoid fungi.
OBJECTIVE: This study aims to investigate the prevalence of familial cerebral cavernous malformations (FCCMs) in first-degree relatives (FDRs) using familial screening, to describe the distribution of initial symptoms, lesion count on cranial MRI and pathogenic gene in patients. METHODS: Patients with multiple CCMs who enrolled from the Treatments and Outcomes of Untreated Cerebral Cavernous Malformations in China database were considered as probands and FDRs were recruited. Cranial MRI was performed to screen the CCMs lesions, and whole-exome sequencing was performed to identify CCM mutations. MRI and genetic screening were combined to diagnose FCCM in FDRs, and the results were presented as prevalence and 95% CIs. The Kaplan-Meier (KM) method was used to calculate the cumulative incidence of FCCM. RESULTS: 33 (76.74%) of the 43 families (110 FDRs) were identified as FCCM (85 FDRs). Receiver operating characteristic analysis revealed three lesions on T2-weighted imaging (T2WI) were the strong indicator for distinguishing probands with FCCM (sensitivity, 87.10%; specificity, 87.50%). Of the 85 FDRs, 31 were diagnosed with FCCM, resulting in a prevalence of 36.5% (26.2%-46.7%). In families with FCCMs, the mutation rates for CCM1, CCM2 and CCM3 were 45.45%, 21.21% and 9.09%, respectively. Furthermore, 53.13% of patients were asymptomatic, 17.19% were intracranial haemorrhage and 9.38% were epilepsy. The mean age of symptom onset analysed by KM was 46.67 (40.56-52.78) years. CONCLUSION: Based on MRI and genetic analysis, the prevalence of CCMs in the FDRs of families with FCCMs in China was 36.5%. Genetic counselling and MRI screening are recommended for FDRs in patients with more than three CCM lesions on T2WI.
Introduction: TT-01025-CL is an oral, irreversible small molecule that potently inhibits vascular adhesion protein-1 (VAP-1) for the treatment of inflammation associated with non-alcoholic steatohepatitis (NASH). The objectives of this study were to evaluate the safety/tolerability, pharmacokinetics, and pharmacodynamics of TT-01025-CL, a VAP-1 inhibitor, in healthy Chinese volunteers. Methods: Double-blind, placebo-controlled, dose-escalation studies were conducted in subjects randomized to receive oral once-daily TT-01025-CL (ranges: 10-300 mg [single dose]; 20-100 mg for 7 days [multiple doses]) or placebo under fasting conditions. Safety and tolerability were monitored throughout the study. Pharmacokinetic (PK) parameters were determined using non-compartment analysis. The activity of semicarbazide-sensitive amine oxidase (SSAO)-specific amine oxidase and the accumulation of methylamine in plasma were evaluated as pharmacodynamic (PD) biomarkers. Results: A total of 36 (single-dose group) and 24 (multiple-dose group) subjects were enrolled in the study. No serious adverse events (AEs) were reported, and no subject discontinued due to an AE. All treatment-emergent adverse events (TEAEs) were mild and moderate in intensity. No dose-dependent increase in the intensity or frequency of events was observed. TT-01025-CL was rapidly absorbed after administration. In the single-ascending dose (SAD) study, median Tmax ranged from 0.5 to 2 h and mean t1/2z ranged from 2.09 to 4.39 h. PK was linear in the range of 100-300 mg. The mean Emax of methylamine ranged from 19.167 to 124.970 ng/mL, with mean TEmax ranging from 13.5 to 28.0 h. The complete inhibition (>90%) of SSAO activity was observed at 0.25-0.5 h post-dose and was maintained 48-168 h post-dose. In the multiple-ascending dose (MAD) study, a steady state was reached by day 5 in the 40 mg and 100 mg dose groups. Negligible accumulation was observed after repeated dosing. PK was linear in the range of 20-100 mg. Plasma methylamine appeared to plateau at doses of 20 mg and above, with mean Emax ranging from 124.142 to 156.070 ng/mL and mean TEmax ranging from 14.2 to 22.0 h on day 7. SSAO activity in plasma was persistently inhibited throughout the treatment period. No evident change in methylamine and SSAO activity was observed in the placebo groups. Conclusion: TT-01025-CL was safe and well-tolerated at a single dose of up to 300 mg and multiple doses of up to 100 mg once daily for 7 consecutive days. Absorption and elimination occurred rapidly in healthy volunteers. Linearity in plasma exposure was observed. TT-01025-CL inhibited SSAO activity rapidly and persistently in humans. The profile of TT-01025-CL demonstrates its suitability for further clinical development.
This study aims to identify candidate genes related to ovarian development after ovarian tissue transplantation through transcriptome sequencing (RNA-seq) and expression network analyses, as well as to provide a reference for determining the molecular mechanism of improving ovarian development following ovarian tissue transplantation. We collected ovarian tissues from 15 thirty-day-old ducks and split each ovary into 4 equal portions of comparable sizes before orthotopically transplanting them into 2-day-old ducks. Samples were collected on days 0 (untransplanted), 3, 6, and 9. The samples were paraffin sectioned and then subjected to Hematoxylin-Eosin (HE) staining and follicular counting. We extracted RNA from ovarian samples via the Trizol method to construct a transcriptome library, which was then sequenced by the Illumina Novaseq 6000 sequencing platform. The sequencing results were examined for differentially expressed genes (DEG) through gene ontology (GO) function and the Kyoto encyclopedia of genes and genomes (KEGG) pathway analyses, gene set enrichment analysis (GSEA), weighted correlation network analysis (WGCNA), and protein-protein interaction (PPI) networks. Some of the candidate genes were selected for verification using real-time fluorescence quantitative PCR (qRT-PCR). Histological analysis revealed a significant reduction in the number of morphologically normal follicles at 3, 6, and 9 d after ovarian transplantation, along with significantly higher abnormality rates (P < 0.05). The transcriptome analysis results revealed 2,114, 2,224, and 2,257 upregulated DEGs and 2,647, 2,883, and 2,665 downregulated DEGs at 3, 6, and 9 d after ovarian transplantation, respectively. Enrichment analysis revealed the involvement multiple pathways in inflammatory signaling, signal transduction, and cellular processes. Furthermore, WGCNA yielded 13 modules, with 10, 4, and 6 candidate genes mined at 3, 6 and 9 d after ovarian transplantation, respectively. Transcription factor (TF) prediction showed that STAT1 was the most important TF. Finally, the qRT-PCR verification results revealed that 12 candidate genes exhibited an expression trend consistent with sequencing data. In summary, significant differences were observed in the number of follicles in duck ovaries following ovarian transplantation. Candidate genes involved in ovarian vascular remodeling and proliferation were screened using RNA-Seq and WGCNA.
Aberrant tumor mechanical microenvironment (TMME), featured with overactivated cancer-associated fibroblasts (CAFs) and excessive extracellular matrix (ECM), severely restricts penetration and accumulation of cancer nanomedicines, while mild-hyperthermia photothermal therapy (mild-PTT) has been developed to modulate TMME. However, photothermal agents also encounter the barriers established by TMME, manifesting in limited penetration and heterogeneous distribution across tumor tissues and ending with attenuated efficiency in TMME regulation. Herein, it is leveraged indocyanine green (ICG)-loaded soft nanogels with outstanding deformability, for efficient tumor penetration and uniform distribution, in combination with mild-PTT to achieve potent TMME regulation by inhibiting CAFs and degrading ECM. As a result, doxorubicin (DOX)-loaded stiff nanogels gain greater benefits in tumor penetration and antitumor efficacy than soft counterparts from softness-mediated mild-PTT. This study reveals the crucial role of nanomedicine mechanical properties in tumor distribution and provides a novel strategy for overcoming the barriers of solid tumors with soft deformable nanogels.
OBJECTIVE: This study aimed to investigate the correlation and influencing factors between neurophysiological examinations, serum uric acid (SUA), and glucose metabolism in patients with Diabetic Peripheral Neuropathy (DPN). METHODS: A total of 114 patients with DPN who received treatment at the Endocrinology Department of our hospital from January 2022 to December 2023 were included. According to the median blood uric acid level, the patients were divided into high SUA group and low SUA group, and the demographic data, blood glucose indexes and motor nerve electrophysiological examination results of the two groups were compared. RESULTS: The level of FPG and HbA1c was higher in the high SUA group. The motor nerve latency of the high SUA group was higher, the motor nerve amplitude and motor nerve conduction velocity of the high SUA group were lower than those of the low SUA group. SUA was positively correlated with motor nerve latency and negatively correlated with motor nerve amplitude and conduction velocity. CONCLUSION: In DPN, high SUA levels are associated with poor glycemic control. With the increase in SUA levels, the motor nerve latency in patients with T2DM is prolonged, and amplitude and conduction velocity decrease, and high SUA is a risk factor and potential predictor of DPN.
Inflammatory bowel disease (IBD) is distinguished by persistent immune-mediated inflammation of the gastrointestinal tract. Previous experimental investigations have shown encouraging outcomes for the use of mesenchymal stem cell (MSC)-based therapy in the treatment of IBD. However, as a primary medication for IBD patients, there is limited information regarding the potential interaction between 5-aminosalicylates (5-ASA) and MSCs. In this present study, we employed the dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) mouse model to examine the influence of a combination of MSCs and 5-ASA on the development of UC. The mice were subjected to weight measurement, DAI scoring, assessment of calprotectin expression, and collection of colons for histological examination. The findings revealed that both 5-ASA and MSCs have demonstrated efficacy in the treatment of UC. However, it is noteworthy that 5-ASA exhibits a quicker onset of action, while MSCs demonstrate more advantageous and enduring therapeutic effects. Additionally, the combination of 5-ASA and MSC treatment shows a less favorable efficacy compared to the MSCs alone group. Moreover, our study conducted in vitro revealed that 5-ASA could promote MSC migration, but it could also inhibit MSC proliferation, induce apoptosis, overexpress inflammatory factors (IL-2, IL-12P70, and TNF-α), and reduce the expression of PD-L1 and PD-L2. Furthermore, a significant decrease in the viability of MSCs within the colon was observed as a result of 5-ASA induction. These findings collectively indicate that the use of 5-ASA has the potential to interfere with the therapeutic efficacy of MSC transplantation for the treatment of IBD.
Colitis, Ulcerative , Dextran Sulfate , Disease Models, Animal , Mesalamine , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells , Animals , Colitis, Ulcerative/therapy , Colitis, Ulcerative/drug therapy , Colitis, Ulcerative/immunology , Colitis, Ulcerative/pathology , Colitis, Ulcerative/chemically induced , Mesalamine/pharmacology , Mesalamine/therapeutic use , Mesenchymal Stem Cells/drug effects , Mesenchymal Stem Cells/metabolism , Mice , Humans , Mice, Inbred C57BL , Colon/pathology , Colon/drug effects , Colon/immunology , Cells, Cultured , Male , Cell Proliferation/drug effects , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use
BACKGROUND: Cancer stem cells (CSCs) are a specific subpopulation of cancer cells with the ability of self-renewal, infinite proliferation, multidifferentiation and tumorigenicity, and play critical roles in cancer progression and treatment resistance. CSCs are tightly regulated by the tumor microenvironment, such as hypoxia; however, how hypoxia regulates CSCs in non-small cell lung cancer (NSCLC) remains unclear. METHODS: The proportion of ALDHhi cells was examined using the Aldefluor assay. Tankyrase inhibitor XAV939 and siRNA were used to inhibit ß-catenin while pcDNA3-ß-catenin (S33Y) plasmid enhanced the expression of ß-catenin. Western blot was administered for protein detection. The mRNA expression was measured by quantitative real-time PCR. RESULTS: We found that hypoxia led to an increase in the proportion of ALDHhi cells in lung squamous carcinoma (LUSC) H520 cells, while causing a decrease in the ALDHhi cell proportion in lung adenocarcinoma (LUAD) A549 cells. Similarly, ß-catenin expression was upregulated in H520 cells but downregulated in A549 cells upon exposure to hypoxia. Mechanically, the proportion of ALDHhi cells in both cell lines was decreased by ß-catenin inhibitor or siRNA knockdown, whereas increased after ß-catenin overexpression. Furthermore, hypoxia treatment suppressed E-cadherin expression in H520 cells and enhanced N-cadherin and ß-catenin expression, while this effect was completely opposite in A549 cells. CONCLUSION: The hypoxia-EMT-ß-catenin axis functions as an important regulator for the proportion of CSCs in NSCLC and could potentially be explored as therapeutic targets in the future.
Treatment for triple negative breast cancer (TNBC) remains a huge challenge due to the lack of targeted therapeutics and tumor heterogenicity. Cisplatin (Cis) have demonstrated favorable therapeutic response in TNBC and thus is used together with various kinase inhibitors to fight the heterogenicity of TNBC. The combination of Cis with SRC inhibitor dasatinib (DAS) has shown encouraging anti-TNBC efficacy although the additive toxicity was commonly observed. To overcome the severe side effects of this Cis involved therapy, here we co-encapsulated Cis and DAS into a self-assembled hyaluronan (HA) nanogel (designated as HA/Cis/DAS (HCD) nanogel) to afford the TNBC targeted delivery by using the 4T1 mouse model. The acquired HCD nanogel was around 181 nm in aqueous solution, demonstrating the pharmacological activities of both Cis and DAS. Taking advantages of HA's targeting capability towards CD44 that is overexpressed on many TNBC cells, the HCD could well maintain the anticancer efficacy of the Cis and DAS combination, significantly increase the maximum tolerated dose and relieve the renal toxicity in vivo. The current HCD nanogel provides a potent strategy to improve the therapeutic outcome of Cis and DAS combination and thus representing a new targeted treatment option for TNBC.
Cisplatin , Dasatinib , Hyaluronic Acid , Nanogels , Triple Negative Breast Neoplasms , Triple Negative Breast Neoplasms/drug therapy , Triple Negative Breast Neoplasms/pathology , Hyaluronic Acid/chemistry , Animals , Dasatinib/pharmacology , Dasatinib/chemistry , Mice , Cisplatin/pharmacology , Cisplatin/chemistry , Female , Nanogels/chemistry , Cell Line, Tumor , Humans , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Polyethyleneimine/chemistry , Mice, Inbred BALB C , Hyaluronan Receptors/metabolism
Objectives To find out the prevalence rate of pre-myopia among primary school students in the Mianyang Science City Area, analyze its related risk factors, and thus provide a reference for local authorities to formulate policies on the prevention and control of myopia for primary school students. Methods From September to October 2021, Cluster sampling was adopted by our research group to obtain the vision levels of primary school students employing a diopter test in the Science City Area. In addition, questionnaires were distributed to help us find the risk factors associated with pre-myopia. Through the statistical analysis, we identify the main risk factors for pre-myopia and propose appropriate interventions. Results The prevalence rate of pre-myopia among primary school students in the Science City Area was 45.27% (1020/2253), of which 43.82% were boys and 46.92% were girls, with no statistically significant difference in the prevalence rate of myopia between boys and girls (2 =2.171, P=0.141). The results of the linear trend test showed that the prevalence rate of pre-myopia tends to decrease with increasing age (Z=296.521, P=0.000). Logistic regression analysis demonstrated that the main risk factors for pre-myopia were having at least one parent with myopia, spending less than 2 hours a day outdoors, using the eyes continuously for more than 1 hour, looking at electronic screens for more than 2 hours, and having an improper reading and writing posture. Conclusion The Science City Area has a high prevalence rate of pre-myopia among primary school students. It is proposed that students, schools, families, and local authorities work together to increase the time spent outdoors, reduce digital screens and develop scientific use of eye habits.
The disposal of electroplating sludge (ES) is a major challenge for the sustainable development of the electroplating industry. ESs have a significant environmental impact, occupying valuable land resources and incurring high treatment costs, which increases operational expenses for companies. Additionally, the high concentration of hazardous substances in ES poses a serious threat to both the environment and human health. Despite extensive scholarly research on the harmless treatment and resource utilization of ES, current technology and processes are still unable to fully harness its potential. This results in inefficient resource utilization and potential environmental hazards. This article analyzes the physicochemical properties of ES, discusses its ecological hazards, summarizes research progress in its treatment, and elaborates on methods such as solidification/stabilization, heat treatment, wet metallurgy, pyrometallurgy, biotechnology, and material utilization. It provides a comparative summary of different treatment processes while also discussing the challenges and future development directions for technologies aimed at effectively utilizing ES resources. The objective of this text is to provide useful information on how to address the issue of ES treatment and promote sustainable development in the electroplating industry.
Background: Neck pain has become very common in China and has greatly affected individuals, families, and society in general. In this study, we aimed to report on the rates and trends of the prevalence, incidence, and years lived with disability (YLDs) caused by neck pain in the general population of China from 1990 to 2019. Methods: We used data from the Global Burden of Diseases, Injuries, and Risk Factors Study 2019 (GBD 2019) study to estimate the number and age standardised rates per 100 000 population of neck pain point prevalence, annual incidence, and YLDs in 33 provinces/municipalities/autonomous regions of China, stratified by age, sex, and sociodemographic index (SDI) from 1990 to 2019. We then compared these estimates with other G20 countries. Results: There were 6.80 × 107 patients with neck pain in 2019, presenting an increase from 3.79 × 107 in 1990. Likewise, the national age-standardised point prevalence increased slightly from 3.53% in 1990 to 3.57% in 2019. The YLDs increased by 78.08%, from 3814 × 103 in 1990 to 6792 × 103 in 2019. The age-standardised YLDs rate increased 1.50% from 352.84 in 1990 to 358.10 in 2019. The point prevalence of neck pain in 2019 was higher in females compared with males. These estimates were all above the global average level and increased more rapidly among G20 countries from 1990 to 2019. We generally observed a positive association between age-standardised YLD rates for neck pain and SDI, suggesting the burden is higher at higher sociodemographic indices. Conclusions: Neck pain is a serious public health problem in the general population in China, especially in its central and western regions, with an overall increasing trend in the last three decades. This is possibly related to changes of people's lifestyles and work patterns due to improvements in societal well-being and technology. Raising awareness of risk factors for neck pain in the general population and establishing effective preventive and treatment strategies could help reduce the future burden of neck disorders.
Disabled Persons , Global Burden of Disease , Male , Female , Humans , Neck Pain/epidemiology , Prevalence , Incidence , China/epidemiology , Global Health
Polysaccharides have a significant impact on the physicochemical properties of starch, and the objective of this study was to examine the effect of incorporating soluble soybean polysaccharide (SSPS) on the gelatinization and retrogradation of corn starches (CS) with varying amylose content. In contrast to high-amylose corn starch (HACS), the degree of gelatinization of waxy corn starch (WCS) and normal corn starch (NCS) decreased with the addition of SSPS. The inclusion of SSPS resulted in reduced swelling power in all CS, and led to a decrease in gel hardness of the starches. The intermolecular forces between SSPS and CS were primarily hydrogen bonding, and a gel network structure was formed, thereby retarding the short-term and long-term retrogradation of CS. Scanning electron microscopy results revealed that the addition of SSPS in starches led to a loose network structure with larger poles and a reduced ordered structure after retrogradation, as observed from the cross-section of formed gels. These findings suggested that SSPS has great potential for applications in starchy foods, as it can effectively retard both gelatinization and retrogradation of starches.
Amylose , Glycine max , Zea mays , Starch , Polysaccharides , Amylopectin
Carotenoids are photosynthetic pigments and antioxidants that contribute to different plant colors. However, the involvement of TOPLESS (TPL/TPR)-mediated histone deacetylation in the modulation of carotenoid biosynthesis through ethylene-responsive element-binding factor-associated amphiphilic repression (EAR)-containing transcription factors (TFs) in apple (Malus domestica Borkh.) is poorly understood. MdMYB44 is a transcriptional repressor that contains an EAR repression motif. In the present study, we used functional analyses and molecular assays to elucidate the molecular mechanisms through which MdMYB44-MdTPR1-mediated histone deacetylation influences carotenoid biosynthesis in apples. We identified two carotenoid biosynthetic genes, MdCCD4 and MdCYP97A3, that were confirmed to be involved in MdMYB44-mediated carotenoid biosynthesis. MdMYB44 enhanced ß-branch carotenoid biosynthesis by repressing MdCCD4 expression, whereas MdMYB44 suppressed lutein level by repressing MdCYP97A3 expression. Moreover, MdMYB44 partially influences carotenoid biosynthesis by interacting with the co-repressor TPR1 through the EAR motif to inhibit MdCCD4 and MdCYP97A3 expression via histone deacetylation. Our findings indicate that the MdTPR1-MdMYB44 repressive cascade regulates carotenoid biosynthesis, providing profound insights into the molecular basis of histone deacetylation-mediated carotenoid biosynthesis in plants. These results also provide evidence that the EAR-harboring TF/TPL repressive complex plays a universal role in histone deacetylation-mediated inhibition of gene expression in various plants.
BACKGROUND: The pea leafminer, Liriomyza huidobrensis, is one of the most important insect pests on vegetables and ornamentals. The survival and egg-laying behavior of leafminers are markedly affected by the environment temperature. However, the mechanisms underlying the relationship between egg-laying and temperature are still largely unknown. RESULTS: Here, we find that leafminers have evolved an adaptive strategy to overcome the stress from high or low temperature by regulating oviposition-punching plasticity. We further show that this oviposition-punching plasticity is mediated by the expression of pyx in the ovipositor when subjected to disadvantageous temperature. Specifically, down-regulation of pyx expression in leafminers under low temperature stress led to a significant decrease in the swing numbers of ovipositor and puncture area of the egg spot, and consequently the lower amount of egg-laying compared to leafminers at ambient temperature. Conversely, activation of pyx expression under high temperature stress increased the swing numbers and puncture area, still resulting in a reduction of egg-laying amount. CONCLUSION: Thereby, leafminers are able to coordinate pyx channel expression level and accordingly depress the oviposition. Our study uncovers a molecular mechanism underlying the adaptive strategy in insects that can avoid disadvantageous temperature for reproducing offspring. © 2024 Society of Chemical Industry.
Microalgae is an effective bioremediation technique employed for treating piggery effluent. However, there is insufficient study on how the presence of microplastics (MPs) in wastewater affects the ability of microalgae to remove heavy metals from piggery effluent. This study aims to investigate the influence of two prevalent heavy metals found in piggery wastewater, Cu2+ (2 mg/L) and Zn2+ (2 mg/L), on their removal by microalgae (Desmodesmus sp. CHX1) in the presence of four types of MPs: polyethylene (PE), polyvinyl chloride (PVC), polypropylene (PP), and polyethylene terephthalate (PET). The results revealed that smaller particle size MPs promoted chlorophyll accumulation, while larger particles inhibits it. Additionally, higher concentrations of MPs promoted chlorophyll accumulation, while lower concentrations inhibited it. As for heavy metals, the presence of microplastics reduced the removal efficiency of Cu2+ and Zn2+ by Desmodesmus sp. CHX1. The highest inhibition of Cu2+ was 30%, 10%, 19%, and 16% of the control (CK), and the inhibition of Zn2+ was 7%, 4%, 4%, and 13%, respectively, under the treatments of PE, PVC, PP and PET MPs. Furthermore, Desmodesmus sp. CHX1 can secrete more extracellular polymeric substances (EPS) and form heterogeneous aggregates with MPs to counteract their pressure. These findings elucidate the impact of MPs on microalgae in bioremediation settings and offer useful insights into the complex relationships between microalgae, MPs, and heavy metals in the environment.
Biodegradation, Environmental , Metals, Heavy , Microalgae , Microplastics , Waste Disposal, Fluid , Wastewater , Water Pollutants, Chemical , Microalgae/metabolism , Metals, Heavy/metabolism , Wastewater/chemistry , Water Pollutants, Chemical/metabolism , Animals , Waste Disposal, Fluid/methods , Swine
Hyperbolic metamaterial (HMM) biosensors based on metals have superior performance in comparison with conventional plasmonic biosensors in the detection of low concentrations of molecules. In this study, a nanorod HMM (NHMM) biosensor based on refractive index changes for carcinoembryonic antigen (CEA) detection is developed using secondary antibody modified gold nanoparticle (AuNP-Ab2) nanocomposites as signal amplification element for the first time. Numerical analysis based on finite element method is conducted to simulate the perturbation of the electric field of bulk plasmon polariton (BPP) supported by a NHMM in the presence of a AuNP. The simulation reveals an enhancement of the localized electric field, which arises from the resonant coupling of BPP to the localized surface plasmon resonance supported by AuNPs and is beneficial for the detection of changes of the refractive index. Furthermore, the AuNP-Ab2 nanocomposites-based NHMM (AuNP/Ab2-NHMM) biosensor enables CEA detection in the visible and near-infrared regions simultaneously. The highly sensitive detection of CEA with a wide linear range of 1-500 ng/mL is achieved in the near-infrared region. The detectable concentration of the AuNP/Ab2-NHMM biosensor has a 50-fold decrease in comparison with a NHMM biosensor. A low detection limit of 0.25 ng/mL (1.25 pM) is estimated when considering a noise level of 0.05 nm as the minimum detectable wavelength shift. The proposed method achieves high sensitivity and good reproducibility for CEA detection, which makes it a novel and viable approach for biomedical research and early clinical diagnostics.
Biosensing Techniques , Carcinoembryonic Antigen , Gold , Limit of Detection , Metal Nanoparticles , Nanotubes , Surface Plasmon Resonance , Gold/chemistry , Carcinoembryonic Antigen/blood , Carcinoembryonic Antigen/analysis , Metal Nanoparticles/chemistry , Nanotubes/chemistry , Humans , Surface Plasmon Resonance/methods , Biosensing Techniques/methods , Antibodies, Immobilized/chemistry
Self-charging power systems are considered as promising alternatives for off-grid energy devices to provide sustained electricity supply. However, the conventional self-charging systems are severely restricted by the energy availability and time-consuming charging process as well as insufficient capacity. Herein, we developed an ultrafast H2O2 self-charging aqueous Zn/NaFeFe(CN)6 battery, which simultaneously integrates the H2O2 power generation and energy storage into a battery configuration. In such battery, the chemical energy conversion of H2O2 can generate electrical energy to self-charge the battery to 1.7â V through the redox reaction between H2O2 and NaFeFe(CN)6 cathode. The thermodynamically and kinetically favorable redox reaction contributes to the ultrafast H2O2 self-charging rate and the extremely short self-charging time within 60â seconds. Moreover, the rapid H2O2 power generation can promptly compensate the energy consumption of battery to provide continuous electricity supply. Impressively, this self-charging battery shows excellent scalability of device architecture and can be designed to a H2O2 single-flow battery of 7.06â Ah to extend the long-term energy supply. This work not only provides a route to design self-charging batteries with fast charging rate and high capacity, but also pushes forward the development of self-charging power systems for advanced large-scale energy storage applications.
