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Developing efficient strategies for the deoxygenative functionalization of carbonyl compounds is crucial for enhancing the effective utilization of biomass and the upgrading of chemical feedstocks. In this study, we present an elegant cathodic reduction strategy that enables a tandem alkylation/dearomatization reaction between quinoline derivatives and aryl aldehydes/ketones in a one-pot process. Our approach can be executed via two distinct paths: the aluminum (Al)-facilitated spin-center shift (SCS) path and the Al-facilitated direct deoxygenation path. Both paths are theoretically substantiated by DFT calculations. The crux of this protocol is the in-situ activation of the alcohol intermediates by Al salts, which substantially lowers the activation energy necessary for the formation of key transition states, thereby effectively facilitating the deoxygenation process. Control experiments have not only successfully identified the intermediates but also established that the hydrogen source for the reaction is derived from water and tetrabutylammonium salt. Notably, this method is transition metal-free and compatible with water and oxygen. Developing efficient strategies for the deoxygenative functionalization of carbonyl compounds is crucial for enhancing the effective utilization of biomass and the upgrading of chemical feedstocks. In this study, the authors present an elegant cathodic reduction strategy that enables a tandem alkylation/dearomatization reaction between quinoline derivatives and aryl aldehydes/ketones in a one-pot process.

This paper investigates the outage performance of simultaneous wireless information and power transfer (SWIPT)-assisted device-to-device (D2D)-based hybrid satellite–terrestrial networks (HSTNs). In the considered system, an energy-constrained terrestrial user terminal (UT) harvests energy from the radio frequency (RF) signal of a terrestrial amplify-and-forward (AF) relay and utilizes the harvested energy to cooperate with the shadowed terrestrial Internet of Things (IoT) devices in a D2D communication. Both power splitting (PS)-based and time switching (TS)-based SWIPT-D2D schemes are adopted by the energy-constrained UT to obtain sustainable energy for transmitting information to the shadowed IoT device. Considering shadowed Rician fading for satellite–terrestrial links and Nakagami-m fading for terrestrial links, we analyze the system performance by deriving the closed-form expressions for the outage probability (OP) of both the UT and the IoT device. Our theoretical analyses are validated via Monte Carlo simulations.

The association between the dietary inflammatory index (DII) and visual impairment remains unclear. This study aimed to investigate the relationship between the DII and non-refractive visual impairment among US populations. A cross-sectional analysis was conducted using data from the National Health and Nutrition Examination Survey (NHANES) 2005–2008, including dietary information and visual impairment assessment. Participants with presenting visual impairment, defined as presenting visual acuity in the better-seeing eye worse than 20/40, were included. Participants whose visual acuity in the better-seeing eye could be corrected to 20/40 or better through automated refraction, were classified as having uncorrected refractive error, while others were considered to have non-refractive visual impairment. Logistic regression models, restricted cubic spline (RCS) analysis, subgroup analyses, and propensity score matching (PSM) were performed to assess the association between DII and the prevalence of non-refractive visual impairment. After adjusting for potential confounding factors, a positive association was observed between DII scores and the prevalence of non-refractive visual impairment (odds ratio [OR] = 1.277, 95% confidence interval [CI] = 1.017–1.603, P  < 0.05). RCS analysis demonstrated that there was no nonlinear relationship between them ( P for nonlinear > 0.05). Furthermore, sensitivity analysis by PSM indicated the robustness of this positive association. This study revealed a positive correlation between the DII and the prevalence of non-refractive visual impairment among those with presenting visual impairment in the United States. Further prospective studies are warranted to confirm a causal relationship and elucidate the underlying mechanisms involved.

To find potential α-glucosidase inhibitors, indolo[1,2-b]isoquinoline derivatives (1–20) were screened for their α-glucosidase inhibitory effects. All derivatives presented potential α-glucosidase inhibitory effects with IC50 values of 3.44 ± 0.36~41.24 ± 0.26 μM compared to the positive control acarbose (IC50 value: 640.57 ± 5.13 μM). In particular, compound 11 displayed the strongest anti-α-glucosidase activity, being ~186 times stronger than acarbose. Kinetic studies found that compounds 9, 11, 13, 18, and 19 were all reversible mix-type inhibitors. The 3D fluorescence spectra and CD spectra results revealed that the interaction between compounds 9, 11, 13, 18, and 19 and α-glucosidase changed the conformational changes of α-glucosidase. Molecular docking and molecular dynamics simulation results indicated the interaction between compounds and α-glucosidase. In addition, cell cytotoxicity and drug-like properties of compound 11 were also investigated.

The effect of MDANP effects on ER stress signalling not well known or elucidated. Endoplasmic reticulum (ER) stress plays a critical role in necrotizing enterocolitis (NEC) pathogenesis through the PERK-eIF2ɑ-QRICH1 axis. The present study aimed to explore the protective effects of MDANP in NEC development. Firstly, a function screening was designed to identify the candidate peptides in human milk, and then the identified peptides were validated in NEC patients. In vivo, NEC was induced in mice pups and divided into four groups: (1) control group, (2) NEC group, (3) MDANP + NEC group, and (4) NS + NEC group. In vitro, lentivirus-mediated QRICH1 silencing, was used to transfect NCM460 cell lines, then stimulated with LPS. After LPS stimulation, cells were treated with chemically synthesized MDANP, and the essential proteins in the QRICH1 signalling pathway in cells were tested and compared. After the small-scale screening, a peptide (SKSKKFRRPDIQYPDATDED) named MDANP was determined as the principal peptide. Its protective effect against NEC through inhibiting the expression of ERS key proteins and impeding the intestinal cells’ apoptosis was observed in the animal models. Furthermore, the inhibitive effect of MDANP on apoptosis of intestinal epithelial cells through modulating the PERK-eIF2ɑ-QRICH1 ERS pathway was also confirmed in vitro. Taken together, our data suggest that MDANP effectively ameliorates apoptosis in NEC through attenuating PERK-eIF2ɑ-QRICH1.

A mobile genetic element— sasX —has a key role in the pathogenesis of methicillin-resistant Staphylococcus aureus (MRSA) infection. This rapidly spreading determinant of MRSA pathogenic success markedly enhances nasal colonization, lung disease and immune evasion. The molecular processes underlying epidemic waves of methicillin-resistant Staphylococcus aureus (MRSA) infection are poorly understood 1 . Although a major role has been attributed to the acquisition of virulence determinants by horizontal gene transfer 2 , there are insufficient epidemiological and functional data supporting that concept. We here report the spread of clones containing a previously extremely rare 3 , 4 mobile genetic element–encoded gene, sasX. We demonstrate that sasX has a key role in MRSA colonization and pathogenesis, substantially enhancing nasal colonization, lung disease and abscess formation and promoting mechanisms of immune evasion. Moreover, we observed the recent spread of sasX from sequence type 239 (ST239) to invasive clones belonging to other sequence types. Our study identifies sasX as a quickly spreading crucial determinant of MRSA pathogenic success and a promising target for therapeutic interference. Our results provide proof of principle that horizontal gene transfer of key virulence determinants drives MRSA epidemic waves.

As the predominant modification in RNA, N 6 -methyladenosine (m 6 A) has attracted increasing attention in the past few years since it plays vital roles in many biological processes. This chemical modification is dynamic, reversible and regulated by several methyltransferases, demethylases and proteins that recognize m 6 A modification. M 6 A modification exists in messenger RNA and affects their splicing, nuclear export, stability, decay, and translation, thereby modulating gene expression. Besides, the existence of m 6 A in noncoding RNAs (ncRNAs) could also directly or indirectly regulated gene expression. Colorectal cancer (CRC) is a common cancer around the world and of high mortality. Increasing evidence have shown that the changes of m 6 A level and the dysregulation of m 6 A regulatory proteins have been implicated in CRC carcinogenesis and progression. However, the underlying regulation laws of m 6 A modification to CRC remain elusive and better understanding of these mechanisms will benefit the diagnosis and therapy. In the present review, the latest studies about the dysregulation of m 6 A and its regulators in CRC have been summarized. We will focus on the crucial roles of m 6 A modification in the carcinogenesis and development of CRC. Moreover, we will also discuss the potential applications of m 6 A modification in CRC diagnosis and therapeutics.

T cell senescence and exhaustion are major barriers to successful cancer immunotherapy. Here we show that miR-155 increases CD8 + T cell antitumor function by restraining T cell senescence and functional exhaustion through epigenetic silencing of drivers of terminal differentiation. miR-155 enhances Polycomb repressor complex 2 (PRC2) activity indirectly by promoting the expression of the PRC2-associated factor Phf19 through downregulation of the Akt inhibitor, Ship1. Phf19 orchestrates a transcriptional program extensively shared with miR-155 to restrain T cell senescence and sustain CD8 + T cell antitumor responses. These effects rely on Phf19 histone-binding capacity, which is critical for the recruitment of PRC2 to the target chromatin. These findings establish the miR-155–Phf19–PRC2 as a pivotal axis regulating CD8 + T cell differentiation, thereby paving new ways for potentiating cancer immunotherapy through epigenetic reprogramming of CD8 + T cell fate. The inability of T cells to properly mount anti-tumour immunity underlies failed cancer immune surveillance or therapy. Here the authors show that a microRNA, miR-155, suppresses Ship1 phosphatase expression to modulate epigenetic reprogramming of CD8 T cell differentiation via the Phf19/PRC2 axis, thereby implicating a novel aspect of cancer immunity regulation.

Congenital heart block (CHB) is the most high-risk and prognosis-poor phenotype of neonatal lupus erythematosus (NLE). This study aimed to investigate the clinical characteristics of NLE patients complicated by CHB. This was a multi-center retrospective study. Data were retrospectively collected from NLE patients diagnosed between January 1, 2011, and December 31, 2023, at the Affiliated Children’s Hospital of Soochow University, the Affiliated Suzhou Hospital of Nanjing Medical University, Yangzhou Maternity and Child Health Care Hospital, and Huai’an Maternity and Child Health Care Hospital. The patients were divided into CHB and non-CHB groups based on the presence or absence of CHB. Clinical data were compared between the two groups, and logistic regression analysis was performed to identify risk factors associated with CHB. The outcomes of patients in the CHB group were determined through follow-ups. Ninety-one NLE patients were included, with 15 cases complicated by CHB. Among the CHB patients, five had third-degree CHB (5.49%), four had second-degree CHB (4.40%), and six had first-degree CHB (6.59%). The CHB group had significantly higher levels of maternal allergic diseases and double-positive anti-SSA and anti-SSB antibodies compared with the non-CHB group, as well as higher serum levels of creatine kinase (CK), lactate dehydrogenase, and hydroxybutyrate dehydrogenase. Multivariate logistic regression analysis indicated that high serum CK levels predicted CHB in NLE patients. The most common organ involvement in the CHB group was hematologic, followed by the skin, structural heart abnormalities, digestive, and central nervous systems. However, no significant differences were observed between the two groups. In the CHB group, other symptoms resolved spontaneously within the first 2 years of life, and pacemaker implantation was performed in four patients with third-degree CHB at around 1 year of age. Elevated serum CK levels may indicate CHB in NLE patients. Hematologic involvement was most common in NLE patients with CHB. Pacemaker implantation was shown to effectively treat patients with third-degree CHB.

Triple-negative breast cancer (TNBC) is regarded as the deadliest subtype of breast cancer because of its high heterogeneity, aggressiveness, and limited treatment options. Toxoflavin has been reported to possess antitumor activity. In this study, a series of toxoflavin analogs were synthesized, among which D43 displayed a significant dose-dependent inhibitory effect on the proliferation of TNBC cells (MDA-MB-231 and HCC1806). Additionally, D43 inhibited DNA synthesis in TNBC cells, leading to cell cycle arrest at the G2/M phase. Furthermore, D43 consistently promoted intracellular ROS generation, induced DNA damage, and resulted in apoptosis in TNBC cells. These effects could be reversed by N-acetylcysteine. Moreover, D43 significantly inhibited the growth of breast cancer patient-derived organoids and xenografts with a favorable biosafety profile. In conclusion, D43 is a potent anticancer agent that elicits significant antiproliferation, oxidative stress, apoptosis, and DNA damage effects in TNBC cells, and D43 holds promise as a potential candidate for the treatment of TNBC.