A bionic mimosa soft robot based on a multi-responsive PNIPAM-PEGDA hydrogel composition.

Deformation plays a vital role in the survival of natural organisms. One example is that plants deform themselves to face the sun for sufficient sunlight exposure, which allows them to produce nutrients through photosynthesis. Drawing inspiration from nature, researchers have been exploring the development of 3D deformable materials. However, the traditional approach to manufacturing deformable hydrogels relies on complex technology, which limits their potential applications. In this study, we simulate the stress variations observed in the plant tissue to create a 3D structure from a 2D material. Using UV curing technology, we create a single-layer poly(N-isopropylacrylamide) hydrogel sheet with microchannels that exhibit distinct swelling rates when subjected to stimulation. After a two-step curing process, we produce a poly(N-isopropylacrylamide)-polyethylene glycol diacrylatedouble-layer structure that can be manipulated to change its shape by controlling the light and solvent content. Based on the double-layer structure, we fabricate a dual-response driven bionic mimosa robot that can perform a variety of functions. This soft robot can not only reversibly change its shape but also maintain a specific shape without continuous stimulation. Its capacity for reversible deformation, resulting from internal stress, presents promising application prospects in the biomedical and soft robotics domain. This study delivers an insightful framework for the development of programmable soft materials.

Longitudinal manipulation of local nonseparability in vector beams.

The inherent nonseparability of vector beams presents a unique opportunity to explore novel optical functionalities, expanding new degrees of freedom for optical information processing. In this Letter, we introduce a novel, to the best of our knowledge, method for tailoring the local nonseparability along the propagation axis of vector beams. Employing higher-order Bessel vector beams, the longitudinal control over the local nonseparability is achieved through targeted amplitude modulation of constituent orthogonal polarization components within the main ring region. Experimental demonstrations of diverse longitudinal nonseparability profiles corroborate the efficacy and versatility of our approach, opening avenues for further exploration of the nonseparability manipulation in vector beams.

Spatial transcriptomics reveals gene interactions and signaling pathway dynamics in rat embryos with anorectal malformation.

Anorectal malformation (ARM) is a prevalent early pregnancy digestive tract anomaly. The intricate anatomy of the embryonic cloaca region makes it challenging for traditional high-throughput sequencing methods to capture location-specific information. Spatial transcriptomics was used to sequence libraries of frozen sections from embryonic rats at gestational days (GD) 14 to 16, covering both normal and ARM cases. Bioinformatics analyses and predictions were performed using methods such as WGCNA, GSEA, and PROGENy. Immunofluorescence staining was used to verify gene expression levels. Gene expression data was obtained with anatomical annotations of clusters, focusing on the cloaca region's location-specific traits. WGCNA revealed gene modules linked to normal and ARM cloacal anatomy development, with cooperation between modules on GD14 and GD15. Differential gene expression profiles and functional enrichment were presented. Notably, protein levels of Pcsk9, Hmgb2, and Sod1 were found to be downregulated in the GD15 ARM hindgut. The PROGENy algorithm predicted the activity and interplay of common signaling pathways in embryonic sections, highlighting their synergistic and complementary effects. A competing endogenous RNA (ceRNA) regulatory network was constructed from whole transcriptome data. Spatial transcriptomics provided location-specific cloaca region gene expression. Diverse bioinformatics analyses deepened our understanding of ARM's molecular interactions, guiding future research and providing insights into gene regulation in ARM development.

Examining the Mechanism of Treatment for Primary Dysmenorrhea with Wenjing Huoxue Decoction Based on Transcriptomics, Metabolomics, and Network Pharmacology.

BACKGROUND: Wenjing Huoxue Decoction (WJHXD) is a traditional treatment for primary dysmenorrhea (PD) that can quickly relieve various symptoms caused by PD. Previous clinical studies have shown that WJHXD has better long-term efficacy than ibuprofen in the treatment of PD and can reverse the disorder of T cell subsets. OBJECTIVE: To investigate the effect of WJHXD on serum-related factors in the treatment of PD, including the identification of key targets, pathways, and active ingredients. METHODS: In order to study the effects of the WJHXD intervention in Parkinson's Disease (PD) rats, we used transcriptomics and metabolomics methods to examine the differentially expressed genes (DEGs) and differentially expressed metabolites (DEMs). We also utilized network pharmacology to predict the target and effective route of WJHXD in treating PD. Finally, we employed molecular docking (MD) technology to confirm the placement of important targets and metabolites. RESULTS: WJHXD has been found to be effective in prolonging the onset time and decreasing the number of writhing episodes in PD rats after oxytocin injection. It has also been observed to reduce the levels of PGF2, COX-2, AVP, and PGE2 in the serum of PD rats to different degrees. Transcriptomics analysis has revealed that the core targets of WJHXD include KRT1, KRT16, CCL5, F2, NOS2, RAC2, and others, while the core pathways are Calcium signaling and cAMP signaling. The Estrogen signaling pathway was found to be downregulated in PD rats compared to normal uterine tissue, but WJHXD was able to up-regulate the pathway. A combined transcriptomics and metabolomics analysis suggested that WJHXD may be involved in eight metabolism-related pathways, with the most reliable ones being mucin-type O-glycan biosynthesis and glycolysis or gluconeogenesis. MD has shown that Hydroxyisocaproic acid may bind to important targets such as SLC6A4, PTGER3, IGFBP3, and IGF2. CONCLUSION: In WJHXD, the most targeted herbs were Corydalis rhizoma, licorice, and Myrrha. The most targeted active ingredients include quercetin, 3'-Hydroxy-4'-O-methylglabridin, shinpterocarpin, and isorhamnetin. Potential targets include PTGS2, NOS2, AR, SCN5A, and GAS6. Analysis revealed 72 highly reliable relationships between group A and B DEGs and DEMs, with 23 positive correlations and 49 negative correlations among them. A combined analysis of transcriptomics, metabolomics, and network pharmacology was used to identify possible targets, pathways, and active ingredients of WJHXD in PD treatment, and the correlation between DEGs and DEMs was investigated. However, further research is required to confirm the relationship between active ingredients, targets, and metabolites.

Key residues in the VDAC2-BAK complex can be targeted to modulate apoptosis.

BAK and BAX execute intrinsic apoptosis by permeabilising the mitochondrial outer membrane. Their activity is regulated through interactions with pro-survival BCL-2 family proteins and with non-BCL-2 proteins including the mitochondrial channel protein VDAC2. VDAC2 is important for bringing both BAK and BAX to mitochondria where they execute their apoptotic function. Despite this important function in apoptosis, while interactions with pro-survival family members are well characterised and have culminated in the development of drugs that target these interfaces to induce cancer cell apoptosis, the interaction between BAK and VDAC2 remains largely undefined. Deep scanning mutagenesis coupled with cysteine linkage identified key residues in the interaction between BAK and VDAC2. Obstructive labelling of specific residues in the BH3 domain or hydrophobic groove of BAK disrupted this interaction. Conversely, mutating specific residues in a cytosol-exposed region of VDAC2 stabilised the interaction with BAK and inhibited BAK apoptotic activity. Thus, this VDAC2-BAK interaction site can potentially be targeted to either inhibit BAK-mediated apoptosis in scenarios where excessive apoptosis contributes to disease or to promote BAK-mediated apoptosis for cancer therapy.

YANK2 activated by Fyn promotes glioma tumorigenesis via the mTOR-independent p70S6K activation pathway.

Glioma, particularly glioblastomas (GBM), is incurable brain tumor. The most targeted receptor tyrosine kinase (RTKs) drugs did not bring benefit to GBM patients. The mechanism of glioma growth continues to be explored to find more effective treatment. Here, we reported that Ser/Thr protein kinase YANK2 (yet another kinase 2) is upregulated in glioma tissues and promotes the growth and proliferation of glioma in vitro and in vivo. Further, we confirmed that oncogene Fyn directly activated YANK2 through phosphorylation its Y110, and Fyn-mediated YANK2 phosphorylation at Y110 site promotes glioma growth by increasing its stability. Finally, YANK2 was proved to be a novel upstream kinase of p70S6K and promotes glioma growth by directly phosphorylating p70S6K at T389. Taken together, we found a new mTOR-independent p70S6K activation pathway, Fyn-YANK2-p70S6K, which promotes glioma growth, and YANK2 is a potential oncogene and serves as a novel therapeutic target for glioma.

[Effects of plumbagin on proliferation and apoptosis of human hepatocellular carcinoma cells based on CKB/p53 signaling pathway].

To investigate the effects of plumbagin on the proliferation and apoptosis of human hepatoma Huh-7 cells and its mechanism based on the creatine kinase B(CKB)/p53 signaling pathway. Huh-7 cells were treated with plumbagin from 1 to 12 µmol·L~(-1) for cell counting kit-8(CCK-8) assay, and 1, 3, and 6 µmol·L~(-1) were determined as low, medium, and high concentrations of plumbagin for subsequent experiments. CKB gene was knocked out in Huh-7 cells by clustered regularly interspaced short palindromic repeats(CRISPR)/CRISPR-associated proteins(Cas)-9 gene editing technology. CKB overexpression lentivirus was transfected into Huh-7 cells to up-regulate the expression of CKB. Cell proliferation and apoptosis were detected by plate cloning assay and flow cytometry. The mRNA expression of CKB was detected by quantitative real-time PCR(qRT-PCR). CKB, p53, mouse double minute 2 homolog(MDM2), B-cell lymphoma 2(Bcl-2), Bcl-2 associated X protein(Bax), and caspase-3 protein were detected by Western blot(WB). The results showed that plumbagin significantly inhibited the proliferation of Huh-7 cells and induced cell apoptosis. Compared with the control group, the apoptosis level was significantly increased in the plumbagin group, while the apoptosis level was significantly decreased in the plumbagin combined with the apoptosis inhibitor group. Plumbagin significantly down-regulated the protein expression levels of CKB, Bcl-2, and MDM2 and up-regulated the protein expression levels of p53, Bax, and caspase-3. Knockdown of the CKB gene decreased the proliferative ability of Huh-7 cells, increased the apoptotic rate, decreased the expression levels of Bcl-2 and MDM2 proteins, and increased the expression levels of p53, Bax, and caspase-3 proteins. After up-regulation of CKB expression, the proliferation ability of Huh-7 cells was enhanced, and the protein expression levels of Bcl-2 and MDM2 were elevated. The protein expression levels of p53, Bax, and caspase-3 were decreased. In addition, plumbagin reversed the effect of overexpression of CKB on the proliferation and apoptosis of Huh-7 cells. In conclusion, plumbagin significantly inhibited the proliferative ability of Huh-7 cells, and the mechanism may be related to the inhibition of CKB expression, activation of the p53 signaling pathway, and regulation of the expression of mitochondrial-associated apoptotic proteins, ultimately inducing cell apoptosis.

[Determination of nine components of fried Ziziphi Spinosae Semen extract in beagle dog plasma by UPLC-MS/MS and its application in pharmacokinetic research].

This study established a convenient, rapid, and sensitive ultra-performance liquid chromatography tandem mass spectrometry(UPLC-MS/MS) method for simultaneous determination of magnoflorine,(R)-coclaurine, vicenin Ⅱ, isospinosin, spinosin, swertisin, N-nornuciferine, 6-feruloylspinosin, and jujuboside B in beagle dog plasma after oral administration of fried Ziziphi Spinosae Semen(FZSS) extract. The Waters HSS-T3 C_(18) column(2.1 mm×100 mm, 1.8 µm) was used. The methanol-aqueous solution(containing 0.01% formic acid) was adopted as the mobile phase for gradient elution. The nine components and two internal standards were completely separated within 8 min. The mass spectrometry detection was performed in multiple reaction monitoring(MRM) mode by positive and negative ion switching of electrospray ionization. The analytical method was validated in terms of specificity, selectivity, linear range, accuracy, precision, recovery, matrix effect, and stability. It could meet the requirement of pharmacokinetic research after oral administration of FZSS extract to beagle dogs. The results showed that the time to reach the peak concentration(T_(max)) of magnoflorine,(R)-coclaurine, vicenin Ⅱ, isospinosin, spinosin, 6-feruloylspinosin, and jujuboside B was 2.40-3.20 h, and the elimination halflife(t_(1/2)) was 2.08-6.79 h after a single-dose oral administration of FZSS to beagle dogs. The exposure of magnoflorine and spinosin was high, with a peak concentration(C_(max)) of 76.7 and 31.5 ng·mL~(-1) and an area under the curve(AUC_(0-∞)) of 581 and 315 ng·h·mL~(-1), respectively. The exposure of the remaining five compounds was lower, with a C_(max) of 0.81-13.0 ng·mL~(-1) and an AUC_(0-∞) of 6.00-106 ng·h·mL~(-1). This study provides a reference for the follow-up research of FZSS.

Global, regional, and national cancer burdens of respiratory and digestive tracts in 1990-2044: A cross-sectional and age-period-cohort forecast study.

BACKGROUND: Understanding the current status and future trends of cancer burdens by systems provides important information for specialists, policymakers, and specific risk populations. METHODS: The aim of this study was to compare the current and future cancer burdens of the gastrointestinal (GI) and respiratory tracts in terms of their magnitude and distribution. Data from a total of eight cancers of the digestive and respiratory tracts in the Global Burden of Disease (GBD) database were collected. The age-standardized incidence/death rates (ASIR/ASDRs), disability-adjusted life years (DALYs), and estimated annual percentage changes (EAPCs) were analyzed. Future trends were predicted with Bayesian age-period-cohort (BAPC) and NORDPRED models. RESULTS: In 2019, there was a significant increase in DALY for both digestive and respiratory tract cancers compared to 1990. Meanwhile, ASIR increased slightly and ASDR decreased notably. In 2019, the global cancer burdens of respiratory and digestive tracts were 38568363.53 and 66912328.72 in DALY, 34.28 and 55.32 in ASIR, and 656.82 and 808.22 in ASDR per 100,000 population with changes of +54.63% and +43.93%, +2.92% and +5.65%, and -17.39% and -26.83% compared to those in 1990, respectively. Significant cross-regional differences in the cancer burdens were observed among the regions. Compared to four representative chronic diseases, the burden of cancers showed less remission and greater global inequalities. The burdens of both digestive and respiratory tract cancers were higher in males than in females in terms of the ASIR, ASDR, and DALY. The incidence and mortality rates of respiratory tract cancers were up to 3-4 times higher in males than in females, whereas the difference between male and female rates of digestive tract cancers was relatively smaller. The main risk factor associated with all kinds of digestive and respiratory tract cancers is tobacco, leading to 18.5 in ASDR and 3.38×107 in DALY for respiratory tract cancers; 8.29 in ASDR and 1.60×107 in DALY for digestive tract cancers, in 2019. Additionally, alcohol use contributes to most digestive and respiratory tract cancers (1.23/1.03 in ASDR and 1.60×106/2.57×106 in DALY for respiratory tract cancers; 4.19/3.82 in ASDR and 4.49×106/8.06×106 in DALY for digestive tract cancers), except for stomach cancer and tracheal, bronchus, and lung cancer. The cancer burdens of respiratory and digestive tracts are likely to decrease substantially between 2020 and 2044. For most metrics, except for the ASIR and male-to-female ratios of ASDR and ASDALY in digestive tract cancers, the worldwide variances of burden metrics have been decreasing in the past decades and will possibly maintain stable trends in the future. CONCLUSIONS: The epidemiology of respiratory and GI tract cancers has common features and individual characteristics that are reflected in geography, age characteristics, and risk factors. Current epidemiological status, future trends, and the globalization of these disease burdens are important factors for making scientific planning of resources to minimize the cancer burden metrics and their cross-regional inequalities.

OsMADS6-OsMADS32 and REP1 control palea cellular heterogeneity and morphogenesis in rice.

Precise regulation of cell proliferation and differentiation is vital for organ morphology. Rice palea, serving as sepal, comprises two distinct regions: the marginal region (MRP) and body of palea (BOP), housing heterogeneous cell populations, which makes it an ideal system for studying organ morphogenesis. We report that the transcription factor (TF) REP1 promotes epidermal cell proliferation and differentiation in the BOP, resulting in hard silicified protrusion cells, by regulating the cyclin-dependent kinase gene, OsCDKB1;1. Conversely, TFs OsMADS6 and OsMADS32 are expressed exclusively in the MRP, where they limit cell division rates by inhibiting OsCDKB2;1 expression and promote endoreduplication, yielding elongated epidermal cells. Furthermore, reciprocal inhibition between the OsMADS6-OsMADS32 complex and REP1 fine-tunes the balance between cell division and differentiation during palea morphogenesis. We further show the functional conservation of these organ identity genes in heterogeneous cell growth in Arabidopsis, emphasizing a critical framework for controlling cellular heterogeneity in organ morphogenesis.

The characteristic and prognostic role of blood inflammatory markers in patients with Huntington's disease from China.

Objectives: This study aims to elucidate the role of peripheral inflammation in Huntington's disease (HD) by examining the correlation of peripheral inflammatory markers with clinical manifestations and disease prognosis. Methods: This investigation involved 92 HD patients and 92 matched healthy controls (HCs). We quantified various peripheral inflammatory markers and calculated their derived metrics including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), and systemic immune-inflammation index (SII). Clinical assessments spanning cognitive, motor, and disease severity were administered. Comparative analysis of inflammatory markers and clinical correlations between HD and controls was performed. Kaplan-Meier survival analysis and Cox regression model were used to assess the effect of inflammatory markers on survival. Results: The study revealed that HD patients had significantly reduced lymphocyte counts, and LMR. Conversely, NLR, PLR, and SII were elevated compared to HCs. Lymphocyte levels inversely correlated with the age of onset and monocyte levels inversely correlated with the UHDRS-total functional capacity (TFC) scores. After adjusting for age, sex, and CAG repeat length, lymphocyte count, NLR, PLR, and SII were significantly correlated with the progression rate of TFC scores. Elevated levels of white blood cells and monocytes were associated with an increased risk of disability and mortality in the HD cohort. Conclusion: Our findings indicate that HD patients display a distinct peripheral inflammatory profile with increased NLR, PLR, and SII levels compared to HCs. The peripheral inflammation appears to be linked with accelerated disease progression and decreased survival in HD.

A Delphi Method Comfort Status Scale for Patients With Lung Cancer After Thoracoscopic Surgery.

PURPOSE: To construct the comfort status scale for patients with lung cancer after thoracoscopic surgery. DESIGN: Delphi method inquiry to 15 clinical and nursing experts. METHODS: On the basis of the comfort status scale and the subjective experience and objective symptoms of patients with lung cancer after thoracoscopic surgery, the relevant literature was consulted, semistructured interviews and group discussions were conducted, the pool of items of the postoperative comfort status scale for patients with lung cancer was initially formed, and the postoperative comfort status scale for patients with lung cancer was finally established. FINDINGS: The positive coefficient of experts was 100%, the coefficient of authority was 0.92 and 0.93, and the Kendal's W was 0.257 and 0.298, the degree of coordination of expert opinions was statistically significant (P < .05). Finally, a total of 28 items in four dimensions were formed to assess the postoperative comfort status of patients with lung cancer after thoracoscopic surgery. CONCLUSIONS: The Delphi method-based comfort status scale for patients with lung cancer after thoracoscopic surgery is scientific and reliable, and can provide a quantitative basis for the evaluation of the comfort status of patients after lung cancer thoracoscopic surgery, to further provide individual comfort care measures.

Cross-talk between BCKDK-mediated phosphorylation and STUB1-dependent ubiquitination degradation of BCAT1 promotes GBM progression.

Branched-chain amino acid transferase 1 (BCAT1) is highly expressed in multiple cancers and is associated with poor prognosis, particularly in glioblastoma (GBM). However, the post-translational modification (PTM) mechanism of BCAT1 is unknown. Here, we investigated the cross-talk mechanisms between phosphorylation and ubiquitination modifications in regulating BCAT1 activity and stability. We found that BCAT1 is phosphorylated by branched chain ketoacid dehydrogenase kinase (BCKDK) at S5, S9, and T312, which increases its catalytic and antioxidant activity and stability. STUB1 (STIP1 homology U-box-containing protein 1), the first we found and reported E3 ubiquitin ligase of BCAT1, can also be phosphorylated by BCKDK at the S19 site, which disrupts the interaction with BCAT1 and inhibits its degradation. In addition, we demonstrate through in vivo and in vitro experiments that BCAT1 phosphorylation inhibiting its ubiquitination at multiple sites is associated with GBM proliferation and that inhibition of the BCKDK-BCAT1 axis enhances the sensitivity to temozolomide (TMZ). Overall, we identified novel mechanisms for the regulation of BCAT1 modification and elucidated the importance of the BCKDK-STUB1-BCAT1 axis in GBM progression.

Acute ischemic stroke in tuberculous meningitis.

Background: The underlying mechanism for stroke in patients with tuberculous meningitis (TBM) remains unclear. This study aimed to investigate the predictors of acute ischemic stroke (AIS) in TBM and whether AIS mediates the relationship between inflammation markers and functional disability. Methods: TBM patients admitted to five hospitals between January 2011 and December 2021 were consecutively observed. Generalized linear mixed model and subgroup analyses were performed to investigate predictors of AIS in patients with and without vascular risk factors (VAFs). Mediation analyses were performed to explore the potential causal chain in which AIS may mediate the relationship between neuroimaging markers of inflammation and 90-day functional outcomes. Results: A total of 1,353 patients with TBM were included. The percentage rate of AIS within 30 days after admission was 20.4 (95% CI, 18.2-22.6). A multivariate analysis suggested that age ≥35 years (OR = 1.49; 95% CI, 1.06-2.09; P = 0.019), hypertension (OR = 3.56; 95% CI, 2.42-5.24; P < 0.001), diabetes (OR = 1.78; 95% CI, 1.11-2.86; P = 0.016), smoking (OR = 2.88; 95% CI, 1.68-4.95; P < 0.001), definite TBM (OR = 0.19; 95% CI, 0.06-0.42; P < 0.001), disease severity (OR = 2.11; 95% CI, 1.50-2.90; P = 0.056), meningeal enhancement (OR = 1.66; 95% CI, 1.19-2.31; P = 0.002), and hydrocephalus (OR = 2.98; 95% CI, 1.98-4.49; P < 0.001) were associated with AIS. Subgroup analyses indicated that disease severity (P for interaction = 0.003), tuberculoma (P for interaction = 0.008), and meningeal enhancement (P for interaction < 0.001) were significantly different in patients with and without VAFs. Mediation analyses revealed that the proportion of the association between neuroimaging markers of inflammation and functional disability mediated by AIS was 16.98% (95% CI, 7.82-35.12) for meningeal enhancement and 3.39% (95% CI, 1.22-6.91) for hydrocephalus. Conclusion: Neuroimaging markers of inflammation were predictors of AIS in TBM patients. AIS mediates < 20% of the association between inflammation and the functional outcome at 90 days. More attention should be paid to clinical therapies targeting inflammation and hydrocephalus to directly improve functional outcomes.

Detection and treatment of mono and polycyclic aromatic hydrocarbon pollutants in aqueous environments based on electrochemical technology: recent advances.

Mono and polycyclic aromatic hydrocarbons are widely distributed and severely pollute the aqueous environment due to natural and human activities, particularly human activity. It is crucial to identify and address them in order to reduce the dangers and threats they pose to biological processes and ecosystems. In the fields of sensor detection and water treatment, electrochemistry plays a crucial role as a trustworthy and environmentally friendly technology. In order to accomplish trace detection while enhancing detection accuracy and precision, researchers have created and studied sensors using a range of materials based on electrochemical processes, and their results have demonstrated good performance. One cannot overlook the challenges associated with treating aromatic pollutants, including mono and polycyclic. Much work has been done and good progress has been achieved in order to address these challenges. This study discusses the mono and polycyclic aromatic hydrocarbon sensor detection and electrochemical treatment technologies for contaminants in the aqueous environment. Additionally mentioned are the sources, distribution, risks, hazards, and problems in the removal of pollutants. The obstacles to be overcome and the future development plans of the field are then suggested by summarizing and assessing the research findings of the researchers.

Rack1-mediated ferroptosis affects hindgut development in rats with anorectal malformations: Spatial transcriptome insights.

Anorectal malformation (ARM), a common congenital anomaly of the digestive tract, is a result of insufficient elongation of the urorectal septum. The cytoplasmic protein Receptor of Activated C-Kinase 1 (Rack1) is involved in embryonic neural development; however, its role in embryonic digestive tract development and ARM formation is unexplored. Our study explored the hindgut development and cell death mechanisms in ARM-affected rats using spatial transcriptome analysis. We induced ARM in rats by administering ethylenethiourea via gavage on gestational day (GD) 10. On GDs 14-16, embryos from both normal and ARM groups underwent spatial transcriptome sequencing, which identified key genes and signalling pathways. Rack1 exhibited significant interactions among differentially expressed genes on GDs 15 and 16. Reduced Rack1 expression in the ARM-affected hindgut, verified by Rack1 silencing in intestinal epithelial cells, led to increased P38 phosphorylation and activation of the MAPK signalling pathway. The suppression of this pathway downregulated Nqo1 and Gpx4 expression, resulting in elevated intracellular levels of ferrous ions, reactive oxygen species (ROS) and lipid peroxides. Downregulation of Gpx4 expression in the ARM hindgut, coupled with Rack1 co-localisation and consistent mitochondrial morphology, indicated ferroptosis. In summary, Rack1, acting as a hub gene, modulates ferrous ions, lipid peroxides, and ROS via the P38-MAPK/Nqo1/Gpx4 axis. This modulation induces ferroptosis in intestinal epithelial cells, potentially influencing hindgut development during ARM onset.

Safety and immunogenicity of heterologous boosting with a bivalent SARS-CoV-2 mRNA vaccine (XBB.1.5/BQ.1) in Chinese participants aged 18 years or more: A randomised, double-blinded, active-controlled phase 1 trial.

Continuous emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants urges the development of new vaccines. We assessed the safety and immunogenicity of SYS6006.32, a bivalent vaccine (XBB.1.5/BQ.1), in healthy adults who had received SARS-CoV-2 primary vaccination. In a randomised, double-blinded, active-controlled trial, 200 participants were randomised to receive one dose of SYS6006.32 (N = 100) or a prototype-based, monovalent control vaccine SYS6006 (N = 100). Adverse events (AEs) were collected through the study. Immunogenicity was assessed by live-virus neutralising antibody (Nab) and pseudovirus Nab. 61 (61.0 %) and 60 (60.0 %) participants reported AE in the SYS6006.32 and SYS6006 groups, respectively. Most AEs were grade 1 or 2. Pain and fever were the most common injection-site and systemic AEs, respectively. No serious AEs were observed. SYS6006.32 heterologous boosting induced robust Nab responses against BA.5, XBB.1.5 and EG.5 with live-virus Nab geometric mean titres (GMTs) increased by 17.1-, 34.0-, and 48.0-fold, and pseudovirus Nab GMTs increased by 12.2-, 32.0-, and 35.1-fold, respectively, 14 days after vaccination. SYS6006.32 demonstrated a superior immunogenicity to SYS6006. SYS6006.32 also induced robust pseudovirus Nab responses against XBB.1.16, XBB.2.3, and BA.2.86, with GMTs 3- to 6-fold higher than those induced by SYS6006. In conclusion, SYS6006.32 showed good safety profile and superior immunogenicity to the monovalent vaccine SYS6006.

Sulfur in Waste-Free Sustainable Synthesis: Advancing Carbon-Carbon Coupling Techniques.

This review explores the pivotal role of sulfur in advancing sustainable carbon-carbon (C-C) coupling reactions. The unique electronic properties of sulfur, as a soft Lewis base with significant mesomeric effect make it an excellent candidate for initiating radical transformations, directing C-H-activation, and facilitating cycloaddition and C-S bond dissociation reactions. These attributes are crucial for developing waste-free methodologies in green chemistry. Our mini-review is focused on existing sulfur-directed C-C coupling techniques, emphasizing their sustainability and comparing state-of-the-art methods with traditional approaches. The review highlights the importance of this research in addressing current challenges in organic synthesis and catalysis. The innovative use of sulfur in photocatalytic, electrochemical and metal-catalyzed processes not only exemplifies significant advancements in the field but also opens new avenues for environmentally friendly chemical processes. By focusing on atom economy and waste minimization, the analysis provides broad appeal and potential for future developments in sustainable organic chemistry.

Genome-Wide Search Links Senescence-Associated Secretory Proteins With Susceptibility for Coronary Artery Disease in Mouse and Human.

Advanced age is an independent risk factor for coronary artery disease (CAD), the leading global cause of mortality. Senescent vascular cells in the atherosclerotic plaques exhibit senescence-associated secretory phenotype (SASP). How SASP contributes to atherosclerosis and CAD, however, remains unclear. Here, we integrated RNA-array datasets of senescent human coronary arterial endothelial cells (HCAECs) and aortic smooth muscle cells (HASMCs) as well as genome-wide association data for CAD. We identified 26 genes from HCAECs and 6 genes from HASMCs related to SASP and CAD in both in-house and published datasets. Of which, Cystatin C (CST3), a CAD susceptibility gene, was found to be expressed in both HCAECs and HASMCs, thus, it was prioritized for further investigation. We demonstrated it was significantly elevated in senescent vascular cells, aged arteries, and early atherosclerosis. In vitro experiments showed that CST3 enhances the monocyte-endothelial cell adhesion. Additionally, ligand-receptor pairing analyses revealed two important pathways, COL4A1-ITGA1 and LPL-LRP1 pathways, linked to the critical processes in the development of atherosclerosis, including cell adhesion, inflammation response, extracellular matrix organization, and lipid metabolism. We further demonstrated a reduced monocyte-endothelial cell adhesion following the knockdown of COL4A1 or ITGA1 and a significantly increased expression of COL4A1, ITGA1, and LPL in arterial intima of aged mice and ApoE-/- mice. Our findings demonstrate that vascular cell-derived SASP proteins increase the CAD susceptibility and identify CST3 functionally contributing to atherosclerosis.

Corrigendum to "Cilengitide inhibits osteoclast adhesion through blocking the αvß3-mediated FAK/Src signaling pathway" [Heliyon 9(7) (July 2023) e17841].

[This corrects the article DOI: 10.1016/j.heliyon.2023.e17841.].