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Meng-Jie Gu,1,* Kun-Feng Li,1,* Lan-Xin Zhang,1 Huan Wang,1 Li-Si Liu,2 Zhuo-Zhao Zheng,2 Nan-Yin Han,1 Zhen-Jun Yang,1 Tian-Yuan Fan1 1State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 2Department of Radiology, Peking University Third Hospital, Beijing, People’s Republic of China *These authors contributed equally to this work Abstract: Novel gadolinium-loaded liposomes guided by GBI-10 aptamer were developed and evaluated in vitro to enhance magnetic resonance imaging (MRI) diagnosis of tumor. Nontargeted gadolinium-loaded liposomes were achieved by incorporating amphipathic material, Gd (III) [N,N-bis-stearylamidomethyl-N'-amidomethyl] diethylenetriamine tetraacetic acid, into the liposome membrane using lipid film hydration method. GBI-10, as the targeting ligand, was then conjugated onto the liposome surface to get GBI-10-targeted gadolinium-loaded liposomes (GTLs). Both nontargeted gadolinium-loaded liposomes and GTLs displayed good dispersion stability, optimal size, and zeta potential for tumor targeting, as well as favorable imaging properties with enhanced relaxivity compared with a commercial MRI contrast agent (CA), gadopentetate dimeglumine. The use of GBI-10 aptamer in this liposomal system was intended to result in increased accumulation of gadolinium at the periphery of C6 glioma cells, where the targeting extracellular matrix protein tenascin-C is overexpressed. Increased cellular binding of GTLs to C6 cells was confirmed by confocal microscopy, flow cytometry, and MRI, demonstrating the promise of this novel delivery system as a carrier of MRI contrast agent for the diagnosis of tumor. These studies provide a new strategy furthering the development of nanomedicine for both diagnosis and therapy of tumor. Keywords: magnetic resonance imaging, gadolinium, liposomes, tenascin-C, GBI-10 aptamer, tumor targeting

Xing-Hui Shao,1 Yan-Min Yang,1 Jun Zhu,1 Han Zhang,1 Yao Liu,1 Xin Gao,1 Li-Tian Yu,1 Li-Sheng Liu,1 Li Zhao,2 Peng-Fei Yu,3 Hua Zhang,4 Qing He,5 Xiao-Dan Gu6 1Emergency and Intensive Care Center, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 2Department of Emergency, Fu Xing Hospital, Capital Medical University, Beijing, 3Department of Cardiology, Pingdu People’s Hospital, Pingdu, 4Department of Emergency, Qingdao Municipal Hospital, Qingdao, 5Department of Emergency, West China Hospital, Sichuan University, Chengdu, 6Department of Emergency, Sixth People’s Hospital of Chengdu, Chengdu, People’s Republic of China Background: Atrial fibrillation (AF) disproportionately affects older adults. However, direct comparison of clinical features, medical therapy, and outcomes in AF patients aged 65–74 and ≥75 years is rare. The objective of the present study was to evaluate the differences in clinical characteristics and prognosis in these two age-groups of geriatric patients with AF.Materials and methods: A total of 1,336 individuals aged ≥65 years from a Chinese AF registry were assessed in the present study: 570 were in the 65- to 74-year group, and 766 were in the ≥75-year group. Multivariable Cox hazards regression was performed to analyze the major adverse cardiac events (MACEs) between groups.Results: In our population, the older group were more likely to have coronary artery disease, hypertension, previous stroke, cognitive disorder, or chronic obstructive pulmonary disease, and the 65- to 74-year group were more likely to have valvular heart disease, left ventricular systolic dysfunction, or sleep apnea. The older patients had 1.2-fold higher mean CHADS2 (congestive heart failure, hypertension, age ≥75 years, diabetes, stroke) scores, but less ­probability of being prescribed drugs. Compared with those aged 65–74 years, the older group had a higher risk of death (hazard ratio 2.881, 95% confidence interval 1.981–4.189; P

A reliable and efficient regeneration protocol from the cotyledons and hypocotyls is successfully established using three cauliflower genotypes. Thidiazuron (TDZ) is found to be an effective inducer of shoot formation. Both the hypocotyl and cotyledon segments are highly responsive (100%) to shoot formation and produce a maximum of 15.8 shoots per hypocotyl explant on MS salts with B5 vitamins medium containing TDZ at 0.2 mg L-1 and α-naphthaleneacetic acid at 0.01 mg L-1. Using this efficient regeneration protocol, the reporter β-glucuronidase (GUS) under the constitutive cauliflower mosaic virus (CaMV) 35S promoter is introduced into cauliflower cells of hypocotyls and cotyledons with Agrobacterium tumefaciens strain EHA105. By optimizing the parameters on the procedure of Agrobacterium-mediated transformation, a high transformation efficiency is demonstrated. The transformation efficiencies are 21.6% and 18.3% for cotyledons and hypocotyls, respectively. Integration of the transgenes in the plant genome is demonstrated by PCR and Southern hybridization analysis. Expression of the transgenes is confirmed by RT-PCR analysis and GUS staining. Compared with previous works, the present study provides higher regeneration and transformation efficiencies and establishes a highly efficient transformation system in cauliflower. [ABSTRACT FROM AUTHOR]

Exposure to particulate matter (PM) air pollution has been shown to exacerbate children's asthma, but the exposure sources and temporal characteristics are still under study. Children's exposure to PM is likely to involve both combustion-related ambient PM and PM related to a child's activity in various indoor and outdoor microenvironments. Among 19 children with asthma, 9-17 years of age, we examined the relationship of temporal changes in percent predicted forced expiratory volume in 1 sec (FEV[1]) to personal continuous PM exposure and to 24-hr average gravimetric PM mass measured at home and central sites. Subjects were followed for 2 weeks during either the fall of 1999 or the spring of 2000, in a southern California region affected by transported air pollution. FEV[1] was measured by subjects in the morning, afternoon, and evening. Exposure measurements included continuous PM using a passive nephelometer carried by subjects; indoor, outdoor home, and central-site 24-hr gravimetric PM[2.5] (PM of aerodynamic diameter < 2.5 microm) and PM[10]; and central-site hourly PM[10], nitrogen dioxide, and ozone. Data were analyzed with linear mixed models controlling for within-subject autocorrelation, FEV[1] maneuver time, and exposure period. We found inverse associations of FEV[1] with increasing PM exposure during the 24 hr before the FEV[1] maneuver and with increasing multiday PM averages. Deficits in percent predicted FEV[1] (95% confidence interval) for given PM interquartile ranges measured during the preceding 24-hr were as follows: 128 microg/m[3] 1-hr maximum personal PM, -6.0% (-10.5 to -1.4); 30 microg/m[3] 24-hr average personal PM, -5.9% (-10.8 to -1.0); 6.7 microg/m[3] indoor home PM[2.5], -1.6% (-2.8 to -0.4); 16 microg/m[3] indoor home PM[10], -2.1% (-3.7 to -0.4); 7.1 microg/m[3] outdoor home PM[2.5], -1.1% (-2.4 to 0.1); and 7.5 microg/m[3] central-site PM[2.5], -0.7% (-1.9 to 0.4). Stronger associations were found for multiday moving averages of PM for both personal and stationary-site PM. Stronger associations with personal PM were found in boys allergic to indoor allergens. FEV[1] was weakly associated with NO[2] but not with O[3]. Results suggest mixed respiratory effects of PM in asthmatic children from both ambient background exposures and personal exposures in various microenvironments. [ABSTRACT FROM AUTHOR]

In this article we present results from a 2-year comprehensive exposure assessment study that examined the particulate matter (PM) exposures and health effects in 108 individuals with and without chronic obstructive pulmonary disease (COPD), coronary heart disease (CHD), and asthma. The average personal exposures to PM with aerodynamic diameters < 2.5 microm (PM[2.5]) were similar to the average outdoor PM[2.5] concentrations but significantly higher than the average indoor concentrations. Personal PM[2.5] exposures in our study groups were lower than those reported in other panel studies of susceptible populations. Indoor and outdoor PM[2.5], PM[10] (PM with aerodynamic diameters < 10 microm), and the ratio of PM[2.5] to PM10 were significantly higher during the heating season. The increase in outdoor PM[10] in winter was primarily due to an increase in the PM[2.5] fraction. A similar seasonal variation was found for personal PM[2.5]. The high-risk subjects in our study engaged in an equal amount of dust-generating activities compared with the healthy elderly subjects. The children in the study experienced the highest indoor PM[2.5] and PM[10] concentrations. Personal PM[2.5] exposures varied by study group, with elderly healthy and CHD subjects having the lowest exposures and asthmatic children having the highest exposures. Within study groups, the PM[2.5] exposure varied depending on residence because of different particle infiltration efficiencies. Although we found a wide range of longitudinal correlations between central-site and personal PM[2.5] measurements, the longitudinal r is closely related to the particle infiltration efficiency. PM[2.5] exposures among the COPD and CHD subjects can be predicted with relatively good power with a microenvironmental model composed of three microenvironments. The prediction power is the lowest for the asthmatic children. [ABSTRACT FROM AUTHOR]

Background: Blood pressure is an important determinant of the risks of macrovascular and microvascular complications of type 2 diabetes, and guidelines recommend intensive lowering of blood pressure for diabetic patients with hypertension. We assessed the effects of the routine administration of an angiotensin converting enzyme (ACE) inhibitor-diuretic combination on serious vascular events in patients with diabetes, irrespective of initial blood pressure levels or the use of other blood pressure lowering drugs.Methods: The trial was done by 215 collaborating centres in 20 countries. After a 6-week active run-in period, 11 140 patients with type 2 diabetes were randomised to treatment with a fixed combination of perindopril and indapamide or matching placebo, in addition to current therapy. The primary endpoints were composites of major macrovascular and microvascular events, defined as death from cardiovascular disease, non-fatal stroke or non-fatal myocardial infarction, and new or worsening renal or diabetic eye disease, and analysis was by intention-to-treat. The macrovascular and microvascular composites were analysed jointly and separately. This trial is registered with ClinicalTrials.gov, number NCT00145925.Findings: After a mean of 4.3 years of follow-up, 73% of those assigned active treatment and 74% of those assigned control remained on randomised treatment. Compared with patients assigned placebo, those assigned active therapy had a mean reduction in systolic blood pressure of 5.6 mm Hg and diastolic blood pressure of 2.2 mm Hg. The relative risk of a major macrovascular or microvascular event was reduced by 9% (861 [15.5%] active vs 938 [16.8%] placebo; hazard ratio 0.91, 95% CI 0.83-1.00, p=0.04). The separate reductions in macrovascular and microvascular events were similar but were not independently significant (macrovascular 0.92; 0.81-1.04, p=0.16; microvascular 0.91; 0.80-1.04, p=0.16). The relative risk of death from cardiovascular disease was reduced by 18% (211 [3.8%] active vs 257 [4.6%] placebo; 0.82, 0.68-0.98, p=0.03) and death from any cause was reduced by 14% (408 [7.3%] active vs 471 [8.5%] placebo; 0.86, 0.75-0.98, p=0.03). There was no evidence that the effects of the study treatment differed by initial blood pressure level or concomitant use of other treatments at baseline.Interpretation: Routine administration of a fixed combination of perindopril and indapamide to patients with type 2 diabetes was well tolerated and reduced the risks of major vascular events, including death. Although the confidence limits were wide, the results suggest that over 5 years, one death due to any cause would be averted among every 79 patients assigned active therapy. [ABSTRACT FROM AUTHOR]

Background: Under normal circumstances, high-density lipoprotein (HDL) is considered to have cardiovascular protective effects, but the impact of oxidized HDL (ox-HDL) on vascular endothelial function remains poorly understood. Mitochondrial function is closely related to endothelial function, and hydrogen sulfide (H₂S) is a gas with endothelial protective properties. The novel hydrogen sulfide donor AP39 can target mitochondria to release H₂S, but the combined effects of ox-HDL and AP39 on vascular endothelium are not well studied., Methods: We established a cell model of ox-HDL-induced endothelial cell damage and mitochondrial dysfunction using human umbilical vein endothelial cells (HUVECs) and conducted AP39 pretreatment. The experiments confirmed the functional damage and mitochondrial dysfunction in HUVECs caused by ox-HDL. Additionally, to further explore the role of SIRT1 in AS, we analyzed SIRT1 expression in AS carotid artery tissue. This included the analysis of differentially expressed genes from AS-related datasets, presented through volcano plots and heatmaps, with enrichment analysis of downregulated genes in KEGG pathways and GO functions. Furthermore, we evaluated the differences in SIRT1 expression in coronary arteries with varying degrees of stenosis and in early and late-stage AS carotid artery tissues, and analyzed data from SIRT1 knockout mouse models., Results: The experimental results indicate that AP39 effectively alleviated ox-HDL-induced endothelial cell damage and mitochondrial dysfunction by upregulating SIRT1 expression. MTT and CCK-8 assays showed that ox-HDL treatment led to decreased cell viability and proliferation in HUVECs, reduced eNOS expression, and significantly increased levels of ICAM-1, IL-6, and TNF-α, along with enhanced monocyte adhesion. These findings reveal the damaging effects of ox-HDL on HUVECs. Transcriptomic data indicated that while SIRT1 expression did not significantly differ in coronary arteries with varying degrees of stenosis, it was notably downregulated in AS carotid artery tissues, especially in late-stage AS tissues. KEGG pathway enrichment analysis revealed that SIRT1 downregulated genes were associated with processes such as vascular smooth muscle contraction, while GO analysis showed that these downregulated genes were involved in muscle system processes and muscle contraction functions, further confirming SIRT1's critical role in AS pathology. In transcriptomic data from the SIRT1 knockout mouse model, elevated levels of inflammation-related proteins IL-6 and TNF-α were observed after SIRT1 knockout, along with decreased expression of the chaperone protein PGC-1α. The expression of mitochondrial-related functional proteins Nrf2 and PGC-1α was positively correlated with SIRT1 expression, while inflammation-related proteins ICAM-1, IL-6, IL-20, and TNF-α were negatively correlated with SIRT1 expression. We further discovered that ox-HDL triggered mitochondrial dysfunction, as evidenced by reduced expression of Mfn2, Nrf2, PGC1-α, UCP-1, and SIRT1, corroborating the results from the previous database analysis. Additionally, mitochondrial dysfunction was characterized by decreased mitochondrial membrane potential (MMP), increased mitochondrial ROS levels, and reduced ATP content, further impacting cellular energy metabolism and respiratory function. Subsequent experimental results showed that the addition of AP39 mitigated these adverse effects, as evidenced by decreased levels of ICAM-1, IL-6, and TNF-α, increased eNOS expression, reduced monocyte adhesion, increased mitochondrial H₂S content, and upregulated expression of SIRT1 protein associated with mitochondrial function, reduced ROS levels, and increased ATP content. Furthermore, validation experiments using the SIRT1 inhibitor EX527 confirmed that AP39 alleviated ox-HDL-induced endothelial cell damage and mitochondrial dysfunction by upregulating SIRT1 expression., Conclusion: Ox-HDL can induce damage and mitochondrial dysfunction in HUVECs, while AP39 inhibits ox-HDL-induced endothelial cell damage and mitochondrial dysfunction by upregulating SIRT1., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Apricot pectin polysaccharides' fine structure was performed using HPSEC, HPAEC-PAD, GC-MS, NMR and FTIR spectroscopies. Purified pectin fraction (F1AP) was composed of D-galacturonic acid, L-rhamnose, D-arabinose and D-galactose, Mw ∼ 1588 kDa. F1AP was eluted by water and with 0.2 M NaCl from DEAE Sepharose fraction resulting in two distinct fractions, F1AP1 and F1AP6, with different structures, molecular weights, and conformations, providing insights into their structural diversity. F1AP1 neutral properties were related to its association with protein. F1AP1 had a backbone of (1 → 4)-linked-D-galacturonic acid and (1 → 2)-linked-L-rhamnopyranosyl residues branched with arabinogalactan including multiple glycosidic linkages of T-α-Araf, 3-α-Araf, 5-α-Araf, T-α-Arap, 2-α-Arap, t-Galp, 2-Galp, 3-Galp, 4-Galp, 6-Galp, 2,4-Galp, 3,4-Galp, 3,6-Galp and 4,6-Galp side chains, having methyl and acetylated groups, and a high molecular weight (1945 kDa). The Mark-Houwink exponent was 0.276, indicating a compact spherical conformation. While the other F1AP6 fraction consists predominately of less methylated HG regions of pectin polysaccharides. The molar mass of this fraction was 117.5 kDa, which adopted a stiffer and random coil conformation. This knowledge allows us to evaluate how the balance of chemical structure and physical properties of the two pectin domains may manifest itself in the isolated structure of apricot pectin and its applications., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024. Published by Elsevier B.V.)

Triple-negative breast cancer (TNBC) remains a significant challenge in terms of treatment, with limited efficacy of chemotherapy due to side effects and acquired drug resistance. In this study, a threose nucleic acid (TNA)-mediated antisense approach is employed to target therapeutic Akt genes for TNBC therapy. Specifically, two new TNA strands (anti-Akt2 and anti-Akt3) are designed and synthesized that specifically target Akt2 and Akt3 mRNAs. These TNAs exhibit exceptional enzymatic resistance, high specificity, enhance binding affinity with their target RNA molecules, and improve cellular uptake efficiency compared to natural nucleic acids. In both 2D and 3D TNBC cell models, the TNAs effectively inhibit the expression of their target mRNA and protein, surpassing the effects of scrambled TNAs. Moreover, when administered to TNBC-bearing animals in combination with lipid nanoparticles, the targeted anti-Akt TNAs lead to reduced tumor sizes and decreased target protein expression compared to control groups. Silencing the corresponding Akt genes also promotes apoptotic responses in TNBC and suppresses tumor cell proliferation in vivo. This study introduces a novel approach to TNBC therapy utilizing TNA polymers as antisense materials. Compared to conventional miRNA- and siRNA-based treatments, the TNA system holds promise as a cost-effective and scalable platform for TNBC treatment, owing to its remarkable enzymatic resistance, inexpensive synthetic reagents, and simple production procedures. It is anticipated that this TNA-based polymeric system, which targets anti-apoptotic proteins involved in breast tumor development and progression, can represent a significant advancement in the clinical development of effective antisense materials for TNBC, a cancer type that lacks effective targeted therapy., (© 2024 The Author(s). Small Methods published by Wiley‐VCH GmbH.)

Malignant melanoma (MM) is a common and highly invasive malignant tumor in clinical practice that is prone to occur in the skin and mucosa and prone to early metastasis. The common sites of metastasis are the liver, lungs, brain, etc. Metastatic gastrointestinal mucosa is relatively rare. Once metastasis occurs, the prognosis of patients is significantly worse. This article reports a case diagnosed as MM with liver, stomach, and duodenal metastasis by ultrasound-guided endoscopic puncture at Fengdu People's Hospital in Chongqing, with gastrointestinal discomfort as the initial symptom and a history of melanoma. Therefore, when a patient has a history of melanoma surgery and presents with digestive symptoms, it is necessary to consider the disease. Regular endoscopic screening should be performed, and early surgical treatment and postoperative chemotherapy combined with targeted therapy may improve patient prognosis and prolong patient survival.

This feature article delves into the realm of α-L-threose nucleic acid (TNA), an artificial nucleic acid analog characterized by a backbone comprising an unconventional four-carbon sugar, α-L-threose, with phosphodiester linkages connecting at the 2' and 3' vicinal positions of the sugar ring. Within this article, we encapsulate the potential, progress, current state of the art, and persisting challenges within TNA research. Kicking off with a historical overview of xeno nucleic acids (XNAs), the discussion transitions to the compelling attributes and structure-property relationships of TNAs as advanced tools when contrasted with natural nucleic acids. Noteworthy aspects such as their advantageous spatial arrangements of functional groups around the sugar ring, stable Watson-Crick base pairing, high binding affinity, biostability, biocompatibility, and in vivo bio-safety are highlighted. Moreover, the narrative unfolds the latest advancements in chemical and biological methodologies for TNA synthesis, spanning from monomer and oligomer synthesis to polymerization, alongside cutting-edge developments in enzyme engineering aimed at bolstering large-scale TNA synthesis for in vitro selection initiatives. The article sheds light on the evolution of TNA aptamers over time, expounding on the tools and selection techniques engineered to unearth superior binding aptamers and TNA catalysts. Furthermore, the article accentuates the recent applications of TNAs across diverse domains such as molecular detection, immunotherapy, gene therapy, synthetic biology, and molecular computing. In conclusion, we summarize the key aspects of recent TNA research, address persisting gaps and challenges, and provide crucial insights and future perspectives in the dynamic domain of TNA research.

Engineering Kondo lattice with tailored functionality is desirable for elucidating the heavy fermion physics. We realize the construction of an artificial Kondo lattice/superconductor heterojunction by growing monolayer VSe 2 on bulk 2H-NbSe 2 with molecular beam epitaxy. Spectroscopic imaging scanning tunneling microscopy measurements show the emergence of a new charge density wave (CDW) phase with 3 × 3 periodicity on the monolayer VSe 2 . Unexpectedly, a pronounced Kondo resonance appears around the Fermi level, and distributes uniformly over the entire film, evidencing the formation of Kondo lattice. Density functional theory calculations suggest the existence of magnetic interstitial V atoms in VSe 2 /NbSe 2 , which play a key role in forming the CDW phase along with the Kondo lattice observed in VSe 2 . The Kondo origin is verified from both the magnetic field and temperature dependences of the resonance peak, yielding a Kondo temperature of ~ 44 K. Moreover, a superconducting proximity gap opens on monolayer VSe 2 , whose shape deviates from the function of one-band BCS superconductor, but is reproduced by model calculations with heavy electrons participating the pairing condensate. Our work lays the experimental foundation for studying interactions between the heavy fermion liquids and the superconducting condensate., (© 2024. The Author(s).)

The C677T polymorphism in the MTHFR gene and its role in folate metabolism, impacting serum folate metabolites like THF and 5-MTHF, is a critical but underexplored area in cancer research. This nested case-control study utilized data from CHHRS, involving 87,492 hypertensive adults without prior cancer. During a median of 2.02 years, we identified 1332 cancer cases and matched controls based on age, sex, and residency. Serum levels of folate, THF, and 5-MTHF were measured, and the MTHFR C677T gene polymorphism was considered. Statistical analyses included restricted cubic spline regression and conditional logistic regression models. Serum THF levels were inversely associated with overall cancer risk (OR per SD  = 0.90, 95% CI = 0.82-0.99), while 5-MTHF levels showed a negative association in the general cohort (OR Q3 vs. Q1  = 0.76, 95% CI = 0.60-0.96; OR Q4 vs. Q1  = 0.75, 95% CI = 0.58-0.98) and in individuals with MTHFR C677T (CC + CT) polymorphism (OR per SD  = 0.87, 95% CI = 0.77-0.99; OR Q4 VS. Q1  = 0.79, 95% CI = 0.61-0.98), but a positive association in the MTHFR C677T (TT) subgroup (OR per SD  = 1.89, 95% CI = 1.02-3.72; OR Q4 VS. Q1  = 2.17, 95% CI = 1.06-8.21). The impact of folate, THF, and 5-MTHF on cancer risk varied significantly across different cancer types and MTHFR C677T genotypes. This study provides novel insights into the variable effects of folate and its metabolites on cancer risk, influenced by genetic factors like the MTHFR C677T polymorphism and cancer type., (© 2024 The Author(s). International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Peritrophic membrane (PM) is a pellicle structure present in the midgut of some invertebrates, such as insects and crustaceans. It could isolate harmful components and pathogens in food from intestinal epithelial cells; and it also plays a role in improving digestion and absorption efficiency. So PM is important for survival of its owner. In current study, 44 PM proteins were identified in Litopenaeus vannamei by PM proteome analysis. Among these PM proteins, the Peritrophin-44 homologous protein (LvPT44) was further studied. Chitin-binding assay indicated that LvPT44 could bind to colloidal chitin, and immunoeletron microscopy analysis shown that it was located to PM of L. vannamei. Furthermore, LvPT44 promoter was found to be activated by L. vannamei STAT and c-Jun. Besides, LvPT44 was induced by ER-stress as well as white spot syndrome virus infection. Knocked-down expression of LvPT44 by RNA inference increased the cumulative mortality of shrimp that caused by ER-stress or white spot syndrome virus. These results suggested that LvPT44 has an important role in disease resistance., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Stimulator of interferon genes (STING) has been demonstrated as a critical mediator in the innate immune response to cytosolic DNA and RNA derived from different pathogens. While the role of Micropterus salmoides STING (MsSTING) in largemouth bass virus is still unknown. In this study, RT-qPCR assay and Western-blot assay showed that the expression levels of MsSTING and its downstream genes were up-regulated after LMBV infection. Pull down experiment proved that a small peptide called Fusion peptide (FP) that previously reported to target to marine and human STING as a selective inhibitor also interacted with MsSTING in vitro. Comparing with the RNA-seq of Largemouth bass infected with LMBV singly, 326 genes were significantly up-regulated and 379 genes were significantly down-regulated in the FP plus LMBV group in which Largemouth bass was treatment with FP before LMBV-challenged. KEGG analysis indicated that the differentially expressed genes (DEGs) were mainly related to signaling transduction, infectious disease viral, immune system and endocrine system. Besides, the survival rate of LMBV-infected largemouth bass was highly decreased following FP treatment. Taken together, our study showed that MsSTING played an important role in immune response against LMBV infection., (Copyright © 2024. Published by Elsevier Ltd.)

Nanodiamonds (NDs) are considered promising delivery platforms, but inaccurate and uncontrolled release of drugs at target sites is the biggest challenge of NDs in precision medicine. This study presents the development of phototriggerable ND-based drug delivery systems, utilizing ortho -nitrobenzyl ( o -NB) molecules as photocleavable linkers between drugs and nanocarriers. UV irradiation specifically cleaved o -NB molecules and then was followed by releasing antisense oligonucleotides from ND-based carriers in both buffer and cellular environments. This ND system carried cell nonpermeable therapeutic agents for bypassing lysosomal trapping and degradation. The presence of fluorescent nitrogen-vacancy centers also allowed NDs to serve as biological probes for tracing in cells. We successfully demonstrated phototriggered release of antisense oligonucleotides from ND-based nanocarriers, reactivating their antisense functions. This highlights the potential of NDs, photocleavable linkers, and light stimuli to create advanced drug delivery systems for controlled drug release in disease therapy, opening possibilities for targeted and personalized treatments.

The human genome's nucleotide sequence variation, such as single nucleotide mutations, can cause numerous genetic diseases. However, detecting nucleic acids accurately and rapidly in complex biological samples remains a major challenge. While natural deoxyribonucleic acid (DNA) has been used as biorecognition probes, it has limitations like poor specificity, reproducibility, nuclease-induced enzymatic degradation, and reduced bioactivity on solid surfaces. To address these issues, we introduce a stable and reliable biosensor called graphene oxide (GO)- threose nucleic acid (TNA). It comprises chemically modified TNA capture probes on GO for detecting and imaging target nucleic acids in vitro and in vivo, distinguishing single nucleobase mismatches, and monitoring dynamic changes in target microRNA (miRNA). By loading TNA capture probes onto the GO substrate, the GO-TNA sensing platform for nucleic acid detection demonstrates a significant 88-fold improvement in the detection limit compared to TNA probes alone. This platform offers a straightforward preparation method without the need for costly and labor-intensive isolation procedures or complex chemical reactions, enabling real-time analysis. The stable TNA-based GO sensing nanoplatform holds promise for disease diagnosis, enabling rapid and accurate detection and imaging of various disease-related nucleic acid molecules at the in vivo level. STATEMENT OF SIGNIFICANCE: The study's significance lies in the development of the GO-TNA biosensor, which addresses limitations in nucleic acid detection. By utilizing chemically modified nucleic acid analogues, the biosensor offers improved reliability and specificity, distinguishing single nucleobase mismatches and avoiding false signals. Additionally, its ability to detect and image target nucleic acids in vivo facilitates studying disease mechanisms. The simplified preparation process enhances practicality and accessibility, enabling real-time analysis. The biosensor's potential applications extend beyond healthcare, contributing to environmental analysis and food safety. Overall, this study's findings have substantial implications for disease diagnosis, biomedical research, and diverse applications, advancing nucleic acid detection and its impact on various fields., Competing Interests: Declaration of competing interest Pik Kwan Lo, Pan Li, Ling Sum Liu and Fei Wang are listed as inventors on a U. S. patent application by City University of Hong Kong describing the construction of GO-TNA biosensors and their application in biomolecule detection. The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Background: Endothelial-mesenchymal transition (EndMT) induced by low shear stress plays an important role in the development of atherosclerosis. However, little is known about the correlation between hydrogen sulfide (H 2 S), a protective gaseous mediator in atherosclerosis and the process of EndMT., Methods: We constructed a stable low-shear-stress-induced(2 dyn/cm 2 ) EndMT model, acombined with the pretreatment method of hydrogen sulfide slow release agent(GYY4137). The level of MEST was detected in the common carotid artery of ApoE -/- mice with local carotid artery ligation. The effect of MEST on atherosclerosis development in vivo was verified using ApoE -/- mice were given tail-vein injection of endothelial-specific overexpressed and knock-down MEST adeno-associated virus (AAV)., Results: These findings confirmed that MEST is up-regulated in low-shear-stress-induced EndMT and atherosclerosis. In vivo experiments showed that MEST gene overexpression significantly promoted EndMT and aggravated the development of atherosclerotic plaques and MEST gene knockdown significantly inhibited EndMT and delayed the process of atherosclerosis. In vitro, H 2 S inhibits the expression of MEST and EndMT induced by low shear stress and inhibits EndMT induced by MEST overexpression. Knockdown of NFIL3 inhibit the up regulation of MEST and EndMT induced by low shear stress in HUVECs. CHIP-qPCR assay and Luciferase Reporter assay confirmed that NFIL3 binds to MEST DNA, increases its transcription and H 2 S inhibits the binding of NFIL3 and MEST DNA, weakening NFIL3's transcriptional promotion of MEST. Mechanistically, H 2 S increased the sulfhydrylation level of NFIL3, an important upstream transcription factors of MEST. In part, transcription factor NFIL3 restrain its binding to MEST DNA by sulfhydration., Conclusions: H 2 S negatively regulate the expression of MEST by sulfhydrylation of NFIL3, thereby inhibiting low-shear-stress-induced EndMT and atherosclerosis., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: Powerful adjuvant strategies are required to improve the survival of patients with completely resected stage ΙΙΙA non-small cell lung cancer (NSCLC). We aimed to compare the efficacy of traditional Chinese medicine (TCM) treatment versus observation after adjuvant chemotherapy in these patients., Methods: Eligible patients were randomized 1:1 to receive either oral decoctions based on Qi-Yin syndrome differentiation (TCM group) or observation (observation group). The intervention lasted for 12 months. The primary endpoint was 1-year disease-free survival (DFS). Secondary endpoints were DFS, quality of life, regulatory T cells (Tregs), and cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) on the surface of Tregs in peripheral blood. We used EORTC QLQ-LC43 to evaluate quality of life., Results: Between Apr 29, 2019, and Nov 11, 2021, 75 patients were randomly assigned to oral decoctions based on Qi-Yin syndrome differentiation (n = 38) or observation (n = 37). The full analysis set included 35 patients in the TCM group and 35 in the observation group. After a median follow-up of 24.2 months, oral decoctions based on Qi-Yin syndrome differentiation improved DFS compared with observation (HR 0.378, 95% CI: 0.157-0.912; P  = .03). One-year DFS was 82.1% in the TCM group and 61.9% in the observation group ( P  = .06). Three months after randomization, scores of total health, role function, emotional function, and social function in the TCM group were higher than those in the observation group ( P  < .01 for all), scores of fatigue, pain, insomnia, appetite loss, constipation, cough, and chest pain were lower than those in the observation group ( P  < .05 for all); there was no significant difference in the proportion of Tregs between the TCM group and the observation group ( P  = .58); the proportion of CTLA-4 + Tregs in the TCM group was lower than that in the observation group ( P  = .046). There were no adverse events that occurred in both groups., Conclusions: Oral decoctions based on Qi-Yin syndrome differentiation after adjuvant chemotherapy prolonged DFS, reduced the risk of disease recurrence and metastasis, improved quality of life, and down-regulated the proportion of CTLA-4 + Tregs in completely resected stage ΙΙΙA NSCLC patients., Trial Registration: Chinese Clinical Trial Register, No. ChiCTR1800019396. Date of registration: 9 November 2018., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.