Photochemical radical decarboxylative disulfuration of α-keto acids and oxamic acids.

A visible-light-induced directed decarboxylative disulfuration of α-keto acids and oxamic acids was developed. As a result, a series of versatile mono acyl disulfide derivatives was synthesized under mild and sustainable reaction conditions. This protocol has a broad substrate scope, good functional-group tolerance, and excellent synthetic applications.

Digital therapeutics as an emerging new therapy for diabetes mellitus: potentials and concerns.

The global burden of controlling and managing diabetes mellitus (DM) is a significant challenge. Despite the advancements in conventional DM therapy, there remain hurdles to overcome, such as enhancing medication adherence and improving patient prognosis. Digital therapeutics (DTx), an innovative digital application, has been proposed to augment the traditional disease management workflow, particularly in managing chronic diseases like DM. Several studies have explored DTx, yielding promising results. However, certain concerns about this innovation persist. In this review, we aim to encapsulate the potential of DTx and its applications in DM management, thereby providing a comprehensive overview of this technique for public health policymakers.

The mechanism of Sangdantongluo granule in treating post-stroke spasticity based on multimodal fMRI combined with TMS: Study protocol.

Introduction: Post-stroke spasticity (PSS) is among the prevalent complications of stroke, greatly affecting motor function recovery and reducing patients' quality of life without timely treatment. Sangdantongluo granule, a modern traditional Chinese patent medicine, has significant clinical efficacy in treating PSS. However, the mechanism of Sangdantongluo granule in treating PSS is still unknown. We designed this study to explore the mechanism of Sangdantongluo granule in treating PSS through multimodal functional magnetic resonance imaging (fMRI) combined with transcranial magnetic stimulation (TMS). Methods and analysis: In a single-center, randomized, double-blind, parallel placebo-controlled study, 60 PSS patients will be recruited in China and randomly assigned to either the experimental or control groups at a ratio of 1:1. For eight weeks, Sangdantongluo granule or placebo will be utilized for intervention. The main outcome is the Modified Ashworth Scale (MAS), the secondary outcome includes the Fugl-Meyer Assessment Scale-upper Extremity (FMA-UE), National Institute of Health Stroke Scale (NIHSS), and Modified Rankin Scale (mRS), the mechanism measure is the changes in cortical excitability and multimodal fMRI at baseline and after eight weeks. Ethics and dissemination: This study was approved by the Ethics Committee of the Affiliated Hospital of Hunan Academy of Traditional Chinese Medicine (approval number: [202364]). Clinical trial registration: Chinese Clinical Trial Registry, identifier: ChiCTR2300074793. Registered on 16 August 2023.

ZBTB7A interferes with the RPL5-P53 feedback loop and reduces endoplasmic reticulum stress-induced apoptosis of pancreatic cancer cells.

Endoplasmic reticulum (ER) stress is a primary mechanism leading to cell apoptosis, making it of great research interests in cancer management. This study delves into the function of ribosomal protein L5 (RPL5) in ER stress within pancreatic cancer (PCa) cells and investigates its regulatory mechanisms. Bioinformatics predictions pinpointed RPL5 as an ER stress-related gene exhibiting diminished expression in PCa. Indeed, RPL5 was found to be poorly expressed in PCa tissues and cells, with this reduced expression correlating with an unfavorable prognosis. Moreover, RPL5 overexpression led to heightened levels of p-PERK, p-eIF2α, and CHOP, bolstering the proapoptotic effect of Tunicamycin, an ER stress activator, on PCa cells. Additionally, the RPL5 overexpression curbed cell proliferation, migration, and invasion. Tunicamycin enhanced the binding between RPL5 and murine double minute 2 (MDM2), thus suppressing MDM2-mediated ubiquitination and degradation of P53. Consequently, P53 augmentation intensified ER stress, which further enhanced the binding between RPL5 and MDM2 through PERK-dependent eIF2α phosphorylation, thereby establishing a positive feedback loop. Zinc finger and BTB domain containing 7A (ZBTB7A), conspicuously overexpressed in PCa samples, repressed RPL5 transcription, thereby reducing P53 expression. Silencing of ZBTB7A heightened ER stress and subdued the malignant attributes of PCa cells, effects counteracted upon RPL5 silencing. Analogous outcomes were recapitulated in vivo employing a xenograft tumor mouse model, where ZBTB7A silencing dampened the tumorigenic potential of PCa cells, an effect reversed by additional RPL5 silencing. In conclusion, this study suggests that ZBTB7A represses RPL5 transcription, thus impeding the RPL5-P53 feedback loop and mitigating ER-induced apoptosis in PCa cells.

The association between weight-adjusted-waist index and psoriasis: A cross-sectional study.

INTRODUCTION: This study explored the association between psoriasis and the weight-adjusted waist index (WWI), a newly developed measure of adiposity. The research was conducted among adults in the United States. METHODS: Utilizing survey data from the National Health and Nutrition Examination Survey (NHANES) spanning the years 2009 to 2014, the present study aimed to investigate the potential correlation between psoriasis and WWI within a sample of 15,920 adult participants. Employing multivariable logistic regression and nonlinear curve fitting techniques, we analyzed this plausible association. Additionally, a subgroup analysis was conducted to ascertain the consistency across diverse populations. RESULTS: A significant positive association was discovered between psoriasis and WWI in the investigated sample of 15,920 adults. After conducting a comprehensive adjustment of the model, it was observed that each incremental unit of WWI was significantly associated with an 14% elevated likelihood of developing psoriasis (OR = 1.16, 95% CI 1.01-1.36). Moreover, individuals belonging to the highest quartile of WWI exhibited a 47% higher risk of psoriasis compared to those in the lowest quartile (OR = 1.44, 95% CI 1.01-2.06). This positive correlation remained consistent across various subgroups. The study also compared WWI with BMI and waist circumference, finding that WWI is a more stable metric of obesity. CONCLUSIONS: Our study suggested that in US adults, there is a positive association between WWI and psoriasis. It also indicated that WWI showed potential as a valuable index of psoriasis among the general population.

Angiotensin Receptor Blockers for Hypertension and Risk of Epilepsy.

Importance: Animal and human studies have suggested that the use of angiotensin receptor blockers (ARBs) may be associated with a lower risk of incident epilepsy compared with other antihypertensive medications. However, observational data from the US are lacking. Objective: To evaluate the association between ARB use and epilepsy incidence in subgroups of US patients with hypertension. Design, Setting, and Participants: This retrospective cohort study used data from a national health administrative database from January 2010 to December 2017 with propensity score (PS) matching. The eligible cohort included privately insured individuals aged 18 years or older with diagnosis of primary hypertension and dispensed at least 1 ARB, angiotensin-converting enzyme inhibitor (ACEI), ß-blocker, or calcium channel blocker (CCB) from 2010 to 2017. Patients with a diagnosis of epilepsy at or before the index date or dispensed an antiseizure medication 12 months before or 90 days after initiating the study medications were excluded. The data analysis for this project was conducted from April 2022 to April 2024. Exposures: Propensity scores were generated based on baseline covariates and used to match patients who received ARBs with those who received either ACEIs, ß-blockers, CCBs, or a combination of these antihypertensive medications. Main Outcomes and Measures: Cox regression analyses were used to evaluate epilepsy incidence during follow-up comparing the ARB cohort with other antihypertensive classes. Subgroup and sensitivity analyses were conducted to examine the association between ARB use and epilepsy incidence in various subgroups. Results: Of 2 261 964 patients (mean [SD] age, 61.7 [13.9] years; 1 120 630 [49.5%] female) included, 309 978 received ARBs, 807 510 received ACEIs, 695 887 received ß-blockers, and 448 589 received CCBs. Demographic and clinical characteristics differed across the 4 comparison groups prior to PS matching. Compared with ARB users, patients receiving ACEIs were predominantly male and had diabetes, CCB users were generally older (eg, >65 years), and ß-blocker users had more comorbidities and concurrent medications. The 1:1 PS-matched subgroups included 619 858 patients for ARB vs ACEI, 619 828 patients for ARB vs ß-blocker, and 601 002 patients for ARB vs CCB. Baseline characteristics were equally distributed between comparison groups after matching with propensity scores. Use of ARBs was associated with a decreased incidence of epilepsy compared with ACEIs (adjusted hazard ratio [aHR], 0.75; 95% CI, 0.58-0.96), ß-blockers (aHR, 0.70; 95% CI, 0.54-0.90), and a combination of other antihypertensive classes (aHR, 0.72; 95% CI, 0.56-0.95). Subgroup analyses revealed a significant association between ARB use (primarily losartan) and epilepsy incidence in patients with no preexisting history of stroke or cardiovascular disease. Conclusions and Relevance: This cohort study found that ARBs, mainly losartan, were associated with a lower incidence of epilepsy compared with other antihypertensive agents in hypertensive patients with no preexisting stroke or cardiovascular disease. Further studies, such as randomized clinical trials, are warranted to confirm the comparative antiepileptogenic properties of antihypertensive medications.

High SARS-CoV-2 infection rate in children unvaccinated with COVID-19 vaccine in Changzhou, China, shortly after lifting zero-COVID-19 policy in December 2022.

BACKGROUND: China experienced an overwhelming COVID-19 pandemic from middle December 2022 to middle January 2023 after lifting the zero-COVID-19 policy on December 7, 2022. However, the infection rate was less studied. We aimed to investigate the SARS-CoV-2 infection rate in children shortly after discontinuation of the zero-COVID-19 policy. METHODS: From February 20 to April 10, 2023, we included 393 children aged 8 months to less than 3 years who did not receive COVID-19 vaccination and 114 children aged 3 to 6 years who received inactivated COVID-19 vaccines based on the convenience sampling in this cross-sectional study. IgG and IgM antibodies against nucleocapsid (N) and subunit 1 of spike (S1) of SARS-CoV-2 (anti-N/S1) were measured with commercial kits (Shenzhen YHLO Biotech, China). RESULTS: Of the 393 unvaccinated children (1.5 ± 0.6 years; 52.2% boys), 369 (93.9%) were anti-N/S1 IgG positive. Of the 114 vaccinated children (5.3 ± 0.9 years; 48.2% boys), 112 (98.2%) were anti-N/S1 IgG positive. None of the unvaccinated or vaccinated children was anti-N/S1 IgM positive. The median IgG antibody titers in vaccinated children (344.91 AU/mL) were significantly higher than that in unvaccinated children (42.80 AU/mL) (P < 0.0001). The positive rates and titers of anti-N/S1 IgG had no significant difference between boys and girls respectively. CONCLUSION: Vast majority of children were infected with SARS-CoV-2 shortly after ending zero-COVID-19 policy in China. Whether these unvaccinated infected children should receive COVID-19 vaccine merits further investigation.

Leveraging Senescent Cancer Cell Membrane to Potentiate Cancer Immunotherapy Through Biomimetic Nanovaccine.

Senescent cancer cells are endowed with high immunogenic potential that has been leveraged to elicit antitumor immunity and potentially complement anticancer therapies. However, the efficacy of live senescent cancer cell-based vaccination is limited by interference from immunosuppressive senescence-associated secretory phenotype and pro-tumorigenic capacity of senescent cells. Here, a senescent cancer cell-based nanovaccine with strong immunogenicity and favorable potential for immunotherapy is reported. The biomimetic nanovaccine integrating a senescent cancer cell membrane-coated nanoadjuvant outperforms living senescent cancer cells in enhancing dendritic cells (DCs) internalization, improving lymph node targeting, and enhancing immune responses. In contrast to nanovaccines generated from immunogenic cell death-induced tumor cells, senescent nanovaccines facilitate DC maturation, eliciting superior antitumor protection and improving therapeutic outcomes in melanoma-challenged mice with fewer side effects when combined with αPD-1. The study suggests a versatile biomanufacturing approach to maximize immunogenic potential and minimize adverse effects of senescent cancer cell-based vaccination and advances the design of biomimetic nanovaccines for cancer immunotherapy.

Plasma Ionomic Profile and Interaction Patterns in Coronary Artery Disease Patients.

Humans are exposed to various chemical elements that have been associated with the development and progression of diseases such as coronary artery disease (CAD). Unlike previous research, we employed a multi-element approach to investigate CAD patients and those with comorbid conditions such as diabetes (CAD-DM2), high blood pressure (CAD-HBP), or high blood lipids (CAD-HBL). Plasma concentrations of 21 elements, including lithium (Li), boron (B), aluminum (Al), calcium (Ca), titanium (Ti), vanadium (V), chromium (Cr), manganese (Mn), iron (Fe), cobalt (Co), nickel (Ni), copper (Cu), zinc (Zn), arsenic (As), selenium (Se), strontium (Sr), cadmium (Cd), tin (Sn), stibium (Sb), barium (Ba), and lead (Pb), were measured in CAD patients (n = 201) and healthy subjects (n = 110) using inductively coupled plasma-mass spectrometry (ICP-MS). Principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) models were utilized to analyze the ionomic profiles. Spearman correlation analysis was employed to identify the interaction patterns among individual elements. We found that levels of Ba, Li, Ni, Zn and Pb were elevated in the CAD group compared to the healthy group, while Sb, Ca, Cu, Ti, Fe, and Se were lower. Furthermore, the CAD-DM2 group exhibited higher levels of Ni and Cd, while the CAD-HBP group showed lower levels of Co and Mn. In the CAD-HBL group, Ti was increased, whereas Ba, Cr, Cu, Co, Mn, and Ni were reduced. In conclusion, ionomic profiles can be utilized to differentiate CAD patients from healthy individuals, potentially providing insights for future treatment or dietary interventions.

Immunogenicity, Safety, and Immune Persistence of One Dose of SARS-CoV-2 Recombinant Adenovirus Type-5 Vectored Vaccine in Children and Adolescents Aged 6-17 Years: An Immunobridging Trial.

BACKGROUND: Though children infected by SARS-CoV-2 generally experience milder symptoms compared to adults, severe cases can occur. Additionally, children can transmit the virus to others. Therefore, the availability of safe and effective COVID-19 vaccines for children and adolescents is crucial. METHOD: A single-center, randomized, double-blind clinical trial was conducted in Funing County, Yancheng City, Jiangsu Province, China. Healthy children and adolescents were divided into two subgroups (6-12 years old or 13-17 years old) and randomly assigned to one of three groups to receive one dose of Ad5-nCoV (3 × 1010 vp/dose). Another group, aged 18-59, received one dose of Ad5-nCoV (5 × 1010 vp/dose) as the control group. At 28, 90, 180, and 360 days post-vaccination, we measured the geometric mean titer (GMT)/concentration (GMC) of neutralizing and binding antibodies against the prototype SARS-CoV-2 strain, as well as serum antibody levels against the BA.4/5 variant. We also evaluated the incidence of adverse events within 28 days post-vaccination. RESULTS: A total of 2413 individuals were screened from 3 June 2021 to 25 July 2021, of whom 2021 eligible participants were enrolled, including 1009 aged 6~17 years in the children and adolescent group and 1012 aged 18-59 years in the adults group. The GMT of anti-wild SARS-CoV-2 neutralizing antibodies was 18.6 (95% CI, 16.6-20.9) in children and adolescents and 13.2 (95% CI, 11.6-15.0) in adults on day 28. The incidence of solicited adverse reactions between the adult group (49.4% [124/251]) and the children and adolescent group (46.3% [156/337]) was not statistically significant. The neutralizing antibody levels decreased by a factor of 3.29 from day 28 to day 360 post-vaccination. CONCLUSIONS: A single dose of Ad5-nCoV at 3 × 1010 virus particles/dose is safe in children and adolescents, and it elicited significant immune response, which was not only non-inferior but also superior to that in adults aged 18-59 years.

MiR-3680-3p is a novel biomarker for the diagnosis and prognosis of liver cancer and is involved in regulating the progression of liver cancer.

MicroRNAs (miRNAs) are small non-coding RNAs that can actively participate in post-transcriptional regulation of genes. A number of studies have shown that miRNAs can serve as important regulators of cancer cell growth, differentiation, and apoptosis. They can also act as markers for the diagnosis and prognosis of certain cancers. To explore the potential prognosis-related miRNAs in liver cancer patients, to provide theoretical basis for early diagnosis and prognosis of liver cancer, as well as to provide a new direction for the targeted therapy of liver cancer. The miRNA expression profiles of liver cancer patients in the the Cancer Genome Atlas database were comprehensively analyzed and various prognostic-related miRNAs of liver cancer were screened out. The data was further subjected to survival analysis, prognostic analysis, gene ontology and kyoto encyclopedia of genes and genomes enrichment analysis, microenvironment analysis, and drug sensitivity analysis by R Language version 4.2.0. Finally, the screened miRNAs were further validated by different experiments. Thus, miNRAs involved in liver cancer diagnosis and prognosis were identified. MiRNA-3680-3p was found to be significantly different in 10 different cancers, including liver cancer, and was significantly associated with the microenvironment, survival, and prognosis of liver cancer patients. In addition, drug sensitivity analysis revealed that miRNA-3680-3p can provide a useful reference for drug selection in targeted therapy for liver cancer. MiRNA-3680-3p can serve as a biomarker for the diagnosis and prognosis of liver cancer patients and down-regulation of miRNA-3680-3p could significantly inhibit both the proliferation and migration of liver cancer cells.

Screening for viral hepatitis carriage.

Viral hepatitis during pregnancy is common globally. In this review, we focus on the antenatal screen for hepatitis A, B, C and E, the prevention of mother-to-child transmission (MTCT) of hepatitis B and C, and the management of hepatitis A, B, C and E during pregnancy. Neonatal timely administration of hepatitis B immunoglobulin and hepatitis B vaccine is the cornerstone for preventing MTCT of hepatitis B virus (HBV), and perinatal antiviral prophylaxis with tenofovir disoproxil fumarate in mothers with positive HBeAg or HBV DNA >2 × 105 IU/ml also plays important roles in further reducing MTCT. Avoidance of risk practices in managing labor and delivery process of women with HCV infection may be useful to reduce MTCT of HCV. Early recognition of severe hepatic injury or liver failure associated with hepatitis viruses by regular liver function tests is critical to prevent maternal mortality associated with hepatitis.

The FABD domain is critical for the oncogenicity of BCR/ABL in chronic myeloid leukaemia.

BACKGROUND: Abnormally expressed BCR/ABL protein serves as the basis for the development of chronic myeloid leukaemia (CML). The F-actin binding domain (FABD), which is a crucial region of the BCR/ABL fusion protein, is also located at the carboxyl end of the c-ABL protein and regulates the kinase activity of c-ABL. However, the precise function of this domain in BCR/ABL remains uncertain. METHODS: The FABD-deficient adenovirus vectors Ad-BCR/ABL△FABD, wild-type Ad-BCR/ABL and the control vector Adtrack were constructed, and 32D cells were infected with these adenoviruses separately. The effects of FABD deletion on the proliferation and apoptosis of 32D cells were evaluated by a CCK-8 assay, colony formation assay, flow cytometry and DAPI staining. The levels of phosphorylated BCR/ABL, p73, and their downstream signalling molecules were detected by western blot. The intracellular localization and interaction of BCR/ABL with the cytoskeleton-related protein F-actin were identified by immunofluorescence and co-IP. The effect of FABD deletion on BCR/ABL carcinogenesis in vivo was explored in CML-like mouse models. The degree of leukaemic cell infiltration was observed by Wright‒Giemsa staining and haematoxylin and eosin (HE) staining. RESULTS: We report that the loss of FABD weakened the proliferation-promoting ability of BCR/ABL, accompanied by the downregulation of BCR/ABL downstream signals. Moreover, the deletion of FABD resulted in a change in the localization of BCR/ABL from the cytoplasm to the nucleus, accompanied by an increase in cell apoptosis due to the upregulation of p73 and its downstream proapoptotic factors. Furthermore, we discovered that the absence of FABD alleviated leukaemic cell infiltration induced by BCR/ABL in mice. CONCLUSIONS: These findings reveal that the deletion of FABD diminished the carcinogenic potential of BCR/ABL both in vitro and in vivo. This study provides further insight into the function of the FABD domain in BCR/ABL.

Prognostic factors of 87 ovarian yolk sac tumor (OYST) patients and molecular characteristics of persistent and recurrent OYST.

OBJECTIVE: We aimed to explore the characteristics of OYST, particularly for persistent and recurrent OYST, in order to explore potential treatment options and thereby improve patient outcomes. METHODS: We retrospectively reviewed the clinical records of all patients with OYST at Fudan university Shanghai Cancer Center from December 3, 2005 to November 27, 2020. Furthermore, and performed whole-exome sequencing on 17 paired OYST (including 8 paired persistent and recurrent OYST) tumor and blood samples to elucidate the aberrant molecular features. RESULTS: Totally, 87 OYST patients were included between 2007/03/13 and 2020/11/17. With a median follow-up of 73 [3-189] months, 22 patients relapsed or disease persisted. Overall, 17 patients died with a median overall survival of 21 [3-54] months. Univariate and multivariate analysis revealed tumor histology and residual lesions were independently associated with event free survival and overall survival, cycles to AFP normalization were another independent risk factor for overall survival. For the 8 persistent and recurrent OYST: cancer driver genes including ANKRD36, ANKRD62, DNAH8, MUC5B, NUP205, RYR2, STARD9, MUC16, TTN, ARID1A and PIK3CA were frequently mutated; cell cycle, ABC transporters, HR, NHEJ and AMPK signal pathway demonstrated as the most significantly enriched pathways; TMB, DNA MMR gene mutation and MSI were significantly higher. Mutation signature 11, 19 and 30 were the dominant contributors in persistent and recurrent OYST mutation. CONCLUSION: Persistent and recurrent OYST associated with poor prognosis, and probably susceptible to immune checkpoint blockade therapy. Molecular characteristics contributed to predict the persistence and recurrence of OYST.

Real experience of caregivers of patients with HIV/AIDS from the perspective of iceberg theory: a qualitative research.

OBJECTIVE: This study aimed to investigate the caregiving behaviours and supportive needs of caregivers of patients with HIV/AIDS and provide a basis for healthcare institutions to carry out caregiver interventions. DESIGN: A purposive sampling method was used to select 11 caregivers of patients with HIV/AIDS in the Infectious Disease Department of a tertiary hospital in Nanjing, China, to conduct semistructured interviews. Colaizzi analysis was used to collate and analyse the interview data. SETTING: All interviews were conducted at a tertiary hospital specialising in infectious diseases in Nanjing, Jiangsu Province. PARTICIPANTS: We purposively sampled 11 caregivers of people with HIV/AIDS, including nine women and two men. RESULTS: Analysing the results from the perspective of iceberg theory, three thematic layers were identified: behavioural, value and belief. The behavioural layer includes a lack of awareness of the disease, physical and mental coping disorders, and an increased sense of stigma; the values layer includes a heightened sense of responsibility, the constraints of traditional gender norms, the influence of strong family values and the oppression of public opinion and morality and the belief layer includes the faith of standing together through storms and stress. CONCLUSION: Healthcare professionals should value the experiences of caregivers of patients with HIV/AIDS and provide professional support to improve their quality of life.

Mefunidone ameliorates acute liver failure in mice by inhibiting MKK4-JNK pathway.

Acute liver failure (ALF) is a critical condition that can lead to substantial liver dysfunction. It is characterized by complex clinical manifestations and rapid progression, presenting significant challenges in diagnosis and treatment. We investigated the protective effect of mefunidone (MFD), a novel antifibrosis pyridone agent, on ALF in mice, and explored its potential mechanism of action. MFD pretreatment can alleviate lipopolysaccharide (LPS) and d-galactosamine (D-GalN)-induced ALF, reduce hepatocyte apoptosis, and reduce inflammation and oxidative stress. Additionally, MFD alleviated LPS/D-GalN-stimulated reactive oxygen species (ROS) production and cell death in AML12 cells. RNA sequencing enrichment analysis showed that MFD significantly affected the Mitogen-Activated Protein Kinase (MAPK) pathway. In vivo and in vitro experiments showed that MFD inhibited MKK4 and JNK phosphorylation. JNK activation caused by MKK4 and JNK activators could eliminate the therapeutic effect of MFD on AML12. In addition, MFD pretreatment alleviated ConA-induced ALF, reduced inflammation and oxidative stress in mice, and reduced mouse mortality. These results suggest that MFD can potentially protect against ALF, partially by inhibiting the MKK4-JNK pathway, and is a promising new therapeutic drug for ALF.

CuH-Catalyzed Reductive Coupling of Nitroarenes with Phosphine Oxides for the Direct Synthesis of Phosphamides.

A CuH-catalyzed reductive coupling of nitroarenes with phosphine oxides is developed, which produces a series of phosphamides in moderate to excellent yields with good functional group tolerance. Gram-scale synthesis and late-stage modification of nitro-aromatic functional molecule niclosamide are also successfully conducted. The mechanism study shows that the nitro group is transformed after being reduced to nitroso and a nucleophilic addition procedure is involved during the reaction.

DNA Origami Plasmonic Nanoantenna for Programmable Biosensing of Multiple Cytokines in Cancer Immunotherapy.

Herein, we report a DNA origami plasmonic nanoantenna for the programmable surface-enhanced Raman scattering (SERS) detection of cytokine release syndrome (CRS)-associated cytokines (e.g., tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ)) in cancer immunotherapy. Typically, the nanoantenna was made of self-assembled DNA origami nanotubes (diameter: ∼19 nm; length: ∼90 nm) attached to a silver nanoparticle-modified silicon wafer (AgNP/Si). Each DNA origami nanotube contains one miniature gold nanorod (AuNR) inside (e.g., length: ∼35 nm; width: ∼7 nm). Intriguingly, TNF-α and IFN-γ logically regulate the opening of the nanotubes and the dissociation of the AuNRs from the origami structure upon binding to their corresponding aptamers. On this basis, we constructed a complete set of Boolean logic gates that read cytokine molecules as inputs and return changes in Raman signals as outputs. Significantly, we demonstrated that the presented system enables the quantification of TNF-α and IFN-γ in the serum of tumor-bearing mice receiving different types of immunotherapies (e.g., PD1/PD-L1 complex inhibitors and STING agonists). The sensing results are consistent with those of the ELISA. This strategy fills a gap in the use of DNA origami for the detection of multiple cytokines in real systems.

Nicotinamide riboside attenuates myocardial ischemia-reperfusion injury via regulating SIRT3/SOD2 signaling pathway.

Ischemic heart disease invariably leads to devastating damage to human health. Nicotinamide ribose (NR), as one of the precursors of NAD+ synthesis, has been discovered to exert a protective role in various neurological and cardiovascular disorders. Our findings demonstrated that pretreatment with 200 mg/kg NR for 3 h significantly reduced myocardial infarct area, decreased levels of CK-MB and LDH in serum, and improved cardiac function in the rats during myocardial ischemia-reperfusion (I/R) injury. Meanwhile, 0.5 mM NR also effectively increased the viability and decreased the LDH release of H9c2 cells during OGD/R. We had provided evidence that NR pretreatment could decrease mitochondrial reactive oxygen species (mtROS) production and MDA content, and enhance SOD activity, thereby mitigating mitochondrial damage and inhibiting apoptosis during myocardial I/R injury. Further investigations revealed that NR increased NAD+ content and upregulated SIRT3 protein expression in myocardium. Through using of SIRT3 small interfering RNA and the SIRT3 deacetylase activity inhibitor 3-TYP, we had confirmed that the cardioprotective effect of NR on cardiomyocytes was largely dependent on the inhibition of mitochondrial oxidative stress via SIRT3-SOD2 axis. Overall, our study suggested that exogenous supplementation with NR mitigated mitochondrial damage and inhibited apoptosis during myocardial I/R injury by reducing mitochondrial oxidative stress via SIRT3-SOD2-mtROS pathway.

Genomic and phenotypic characterization of Thermosynechococcus-like strains reveals eight species within the genus Thermosynechococcus and a novel genus Parathermosynechococcus gen. nov.

Thermophilic unicellular cyanobacteria of the family Thermosynechococcaceae are essential primary producers and integral components of many microbial mats found in hot springs of Asia and North America. Historically, based on their simple morphology, these organisms, along with members of taxonomically unrelated thermophilic Thermostichaceae have been described with a generic term, "Synechococcus", used for elongated unicellular cyanobacteria. This has created significant misperception in the scientific literature regarding the taxonomic status of these essential thermophilic primary producers and their relationship with Synechococcus sensu stricto. In this manuscript, we attempted a genome-driven taxonomic reevaluation of the family Thermosynechococcaceae. Application of genomic analyses such as GTDB classification, ANI/AAI and phylogenomics support the delineation of eight species within genus Thermosynechococcus. Two subspecies were further identified within T. taiwanensis by dDDH and phylogenomics. Moreover, the results also suggest the presence of two putative new genera phylogenetically alongside genus Thermosynechococcus, a thermophilic genus Parathermosynechococcus represented by PCC 6715 and a non-thermophilic genus represented by PCC 6312. The proposed genospecies and new genera were further integrated with morphological and/or ecological information. Interestingly, the phylogeny of 16S-23S ITS achieved a better taxonomic relationship than that of 16S rRNA and supported the genome-based classification of Thermosynechococcus spp. Finally, the pan-genome analysis indicated a conserved pattern of genomic core among known members of Thermosynechococcus.