Search

Abstract Background Despite significant strides in lung cancer immunotherapy, the response rates for Kirsten rat sarcoma viral oncogene homolog (KRAS)‐driven lung adenocarcinoma (LUAD) patients remain limited. Fibrinogen‐like protein 1 (FGL1) is a newly identified immune checkpoint target, and the study of related resistance mechanisms is crucial for improving the treatment outcomes of LUAD patients. This study aimed to elucidate the potential mechanism by which FGL1 regulates the tumor microenvironment in KRAS‐mutated cancer. Methods The expression levels of FGL1 and SET1 histone methyltransferase (SET1A) in lung cancer were assessed using public databases and clinical samples. Lentiviruses were constructed for transduction to overexpress or silence FGL1 in lung cancer cells and mouse models. The effects of FGL1 and Yes‐associated protein (Yap) on the immunoreactivity of cytotoxic T cells in tumor tissues were evaluated using immunofluorescence staining and flow cytometry. Chromatin immunoprecipitation and dual luciferase reporter assays were used to study the SET1A‐directed transcriptional program. Results Upregulation of FGL1 expression in KRAS‐mutated cancer was inversely correlated with the infiltration of CD8+ T cells. Mechanistically, KRAS activated extracellular signal‐regulated kinase 1/2 (ERK1/2), which subsequently phosphorylated SET1A and increased its stability and nuclear localization. SET1A‐mediated methylation of Yap led to Yap sequestration in the nucleus, thereby promoting Yap‐induced transcription of FGL1 and immune evasion in KRAS‐driven LUAD. Notably, dual blockade of programmed cell death‐1 (PD‐1) and FGL1 further increased the therapeutic efficacy of anti‐PD‐1 immunotherapy in LUAD patients. Conclusion FGL1 could be used as a diagnostic biomarker of KRAS‐mutated lung cancer, and targeting the Yap‐FGL1 axis could increase the efficacy of anti‐PD‐1 immunotherapy.

Seasonal influenza remains a significant public health concern globally, with annual vaccinations as the most effectively preventive measure. This study examines influenza vaccination coverage rates across different age groups in Pudong New Area, Shanghai, China, from 2013 to 2023. This study extracted influenza vaccination data from the Shanghai Immunization Planning Information System (SIPIS) of the Center for Disease Control and Prevention Shanghai’s Pudong New Area from 2013 to 2023. The analysis utilized weighted linear regression to compare vaccination rates over the study period. From 2013 to 2023, a cumulative total of 1,421,295 influenza vaccinations were administered in Pudong New Area, with the quadrivalent inactivated influenza vaccines (IIV4) and trivalent inactivated influenza vaccines (IIV3) comprising 56.8% and 42.9%, respectively. The overall average influenza vaccine coverage rate was 2.27% (95% CI: 2.26, 2.28). The 0–4 years group exhibited the highest average annual coverage rate of 22.52% (95% CI: 22.47, 22.57) among different age groups, in stark contrast to that of the 20–24 years age group, which had the lowest at 0.32% (95% CI: 0.31, 0.33). In terms of repeat vaccinations, a significant majority (86.87%) of recipients received only 1–2 doses, while just 13.13% received 3 or more doses. Although influenza vaccination coverage among preschool children in Pudong New Area is relatively high, it falls significantly short of WHO recommendations. Enhance the level of awareness of influenza vaccine among adults and provide a free influenza vaccination strategy for specific groups such as doctors, which is helpful to increase influenza vaccination rates among populations.

The aim of this study was to investigate the level of inactivated A71 (EV-A71) vaccination in Pudong New Area of Shanghai and its effects on the epidemiology and pathogen spectrum of hand–foot–mouth disease (HFMD) in this area, as well as to provide a basis for improving the prevention and control strategy of HFMD in this area. Data were collected from the “Comprehensive Management Cloud Platform for Immunization Program” system from December 2016 to December 2022. The data on HFMD cases from January 2012 to December 2022 were extracted from the “China Information System for Disease Control and Prevention”. A total of 484,056 doses were administered. The vaccination rate of the first dose was 14.03%, and the full vaccination rate was 13.33%. There were significant differences between the first dose and the full vaccination rate in different years (χ2 = 46,538.831, p < 0.001, χ2 = 50,013.946, p < 0.001). A total of 91625 cases of HFMD were reported, including 58 severe cases, and no deaths. Before and after the administration of the inactivated EV-A71 vaccine, there were statistical differences in the distribution of HFMD cases in terms of gender, household registration, occupation, and age (p < 0.001). The etiological surveillance results showed that the rate of enterovirus positivity was 84.15%, with 9.85% being EV-A71, 23.74% CV-A16, and 50.56% non-EV-A71 and non-CV-A16. The coverage rate of the inactivated EV-A71 vaccine in Pudong New Area was not high, and the incidence of HFMD showed a downward trend after the postmarketing of the vaccine. The majority of HFMD infections were non-EV-A71 and non-CV-A16, with CV-A6 accounting for the highest proportion. It is recommended to accelerate the development of combined vaccines to provide more antibody protection.

Alzheimer’s disease (AD) is a chronic, progressive brain degenerative disease that is common in the elderly. So far, there is no effective treatment. The multi-target-directed ligands (MTDLs) strategy has been recognised as the most promising approach due to the complexity of the pathogenesis of AD. Herein, novel salicylic acid–donepezil–rivastigmine hybrids were designed and synthesised. The bioactivity results exhibited that 5a was a reversible and selective eqBChE inhibitor (IC50 = 0.53 μM), and the docking provided the possible mechanism. Compound 5a also displayed potential anti-inflammatory effects and significant neuroprotective effect. Moreover, 5a exhibited favourable stabilities in artificial gastrointestinal solution and plasma. Finally, 5a demonstrated potential cognitive improvement in scopolamine-induced cognitive dysfunction. Hence, 5a was a potential multifunctional lead compound against AD.

In this study, a series of naringenin-O-alkylamine derivatives were designed and obtained by introducing an alkylamine fragment into the naringenin skeleton. The in vitro biological activity results revealed that compounds 5f and 7k showed good antioxidant activity with ORAC values of 2.3eq and 1.2eq, respectively. Compounds 5f and 7k were reversible and excellent huAChE inhibitors with IC50 values of 0.91 μM and 0.57 μM, respectively. Moreover, compounds 5f and 7k could inhibit self-induced Aβ1–42 aggregation with 62.1% and 43.8% inhibition rate, respectively, and significantly inhibited huAChE-Aβ1–40 aggregation with 51.7% and 43.4% inhibition rate, respectively. In addition, compounds 5f and 7k were selective metal chelators and remarkably inhibited Cu2+-induced Aβ1–42 aggregation with 73.5% and 68.7% inhibition rates, respectively. Furthermore, compounds 5f and 7k could cross the blood-brain barrier in vitro and displayed good neuroprotective effects and anti-inflammatory properties. Further investigation showed that compound 5f did not show obvious hepatotoxicity and displayed a good hepatoprotective effect by its antioxidant activity. The in vivo study displayed that compound 5f significantly improved scopolamine-induced mice memory impairment. Therefore, compound 5f was a potential multifunctional candidate for the treatment of AD.

Objective: To investigate the expression level of TRAF3IP2 in psoriasis lesion, and to explore the functional roles of TRAF3IP2 on proliferation, apoptosis, cytokine expression and secretion of both keratinocytes and vascular endothelial cells in vitro. Methods: The expression of TRAF3IP2 in skin samples of patients with psoriasis was analyzed by immunohistochemistry and qRT-PCR. To identify the effect of TRAF3IP2 knockdown on HaCaT and HUVEC cells, a plasmid vector expressing siRNA targeting TRAF3IP2 mRNA was designed and transfected into cells with Lipofectamine 2000. The levels of cytokines were identified using the ELISA Kits and qRT-PCR. Furthermore, cell proliferation, cell cycle and apoptosis were examined by using MTT, PI and Annexin V-FITC/7AAD assays, respectively. Furthermore, the expression of apoptosis-related proteins (Cleaved-Caspase 3, Caspase 3 and Bax) were detected by western blotting. Results: TRAF3IP2 was significantly upregulated in psoriasis lesion. TRAF3IP2 knockdown reduced the expression of vascular endothelial growth factor A (VEGFA) and the release of IL-6, and IL-8, but had no effect on IL-23 in both HaCaT and HUVEC cells. In addition, knockdown of TRAF3IP2 significantly inhibited cell proliferation through blocking the cell cycle in the G2/M phase. Moreover, knockdown of TRAF3IP2 increased the expression of Caspase 3, Cleaved-Caspase 3 and Bax, which was supported by the increased apoptosis of both HaCaT and HUVEC cells. Conclusion: Taken together, these results indicated that TRAF3IP2 might play a contributive role in the pathogenesis of psoriasis and may serve as a new target for the treatment of psoriasis. VEGF related pathways may be involved in the mechanism beneath.

Alternanthera philoxeroides recently expanded its range northwards in China. It is unknown if the range expansion has a genetic and/or epigenetic basis, or merely an environmental basis due to a warming climate. To test these possibilities, we used an RNAseq approach with a common greenhouse design to examine gene expression in individuals from the northern edge and central portion of alligator weed range from China to determine if there were differences in their responses to cold temperatures. We hypothesized that if the recent range expansion was primarily environmental, we would observe few differences or only differences unrelated to low-temperature adaptations. We assembled over 75,000 genes of which over 65,000 had long open reading frames with similarity to sequences from arabidopsis. Differences in expression between northern and southern populations that were both exposed to low temperatures showed similar expression among genes in the C-REPEAT/DRE BINDING FACTOR (CBF) regulon. However, gene set and sub-network enrichment analysis indicated differences in the response of photosynthetic processes and oxidative stress responses were different between the two populations and we relate these differences to cold adaptation. The transcriptome differences in response to cold between the individuals from the two populations is consistent with adaptations potentiating or resulting from selection after expansion into colder environments and may indicate that genetic changes have accompanied the recent northward expansion of A. philoxeroides in China. However, we cannot rule out the possibility of epigenetic changes may have a role in this expansion.

We constructed lentiviral vectors containing the human wild-type GJB6 gene and the mutant variants A88V and G11R. The three proteins were stably expressed by the Tet-on system in the HaCaT cell line and used to study the functional effect of the variants. The CCK-8 assay and flow cytometric analyses were used to determine the levels of cell proliferation and apoptosis. Western blot analyses were performed to analyze the relevant clinical indicators of hidrotic ectodermal dysplasia and markers of apoptosis in transfected HaCaT cells. The CCK8 assay and the flow cytometry results showed a significant increase (P

Phytochemical study of the EtOAc fraction (active extract) of the fruits of Ulmus pumila L. resulted in the isolation of thirteen flavane derivatives, and they were identified by their precise spectral data and literature. All the compounds (1-13) were obtained from the fruits of U. pumila L. for the first time. Meanwhile, the compounds (1-13) were assayed for their hepatoprotective and neuroprotective activities, respectively. Compounds 1, 2, 5, 7 and 8 (10µM) exhibited remarkable hepatoprotective activities, and compounds 9, 10, and 13 showed significant neuroprotective activities with IC50 values of 4.08, 5.34, and 2.02µM, respectively. [ABSTRACT FROM AUTHOR]

A silver-catalyzed sequential formation of two C-C bonds for the construction of a series of polysubstituted quinolines from anilines, aldehydes, and alcohols under mild conditions has been developed. The transformation is effective for a broad range of substrates, including aliphatic alcohols, arylalkanols, cycloalkanols, and ethylene glycol, thereby permitting the expansion of the constituent architectures of the heterocyclic framework. [ABSTRACT FROM AUTHOR]

DNA pooling can provide an economic and efficient way to detect susceptibility loci to complex diseases. We carried out a genome screen with 400 microsatellite markers spaced at approximately 10 cm in two DNA pools consisting of 119 schizophrenia (SZ) patients and 119 controls recruited from a homogenous population in the Chang Le area of the Shandong peninsula of China. Association of D6S289, a dinucleotide repeat polymorphism in the JARID2 gene with SZ, was found and confirmed by individual genotyping (X2 = 17.89; P = .047). In order to refine the signal, we genotyped 14 single nucleotide polymorphisms (SNPs) covering JARID2 and the neighboring gene, DNTBP1, in an extended sample of 309 cases and 309 controls from Shandong peninsula (including the samples from the pools). However, rs2235258 and rs9654600 in JARID2 showed association in allelic, genotypic and haplotypic tests with SZ patients from Chang Le area. This was not replicates in the extended sample, we conclude that JARID2 could be a susceptibility gene for SZ. [ABSTRACT FROM AUTHOR]