Human leukocyte antigen (HLA) molecules are essential for presenting Epstein−Barr virus (EBV) antigens and are closely related to nasopharyngeal carcinoma (NPC). This study aims to systematically ...investigate the association between HLA‐bound EBV peptides and NPC risk through in silico HLA‐peptide binding prediction. A total of 455 NPC patients and 463 healthy individuals in NPC endemic areas were recruited, and HLA‐target sequencing was performed. HLA‐peptide binding prediction for EBV, followed by peptidome‐wide logistic regression and motif analysis, was applied. Binding affinity changes for EBV peptides carrying high‐risk mutations were analyzed. We found that NPC‐associated EBV peptides were significantly enriched in immunogenic proteins and core linkage disequilibrium (LD) proteins related to evolution, especially those binding HLA‐A alleles (p = 3.10 × 10−4 for immunogenic proteins and p = 8.10 × 10−5 for core LD proteins related to evolution). These peptides were clustered and showed binding motifs of HLA supertypes, among which supertype A02 presented an NPC‐risk effect (padj = 3.77 × 10−4) and supertype A03 presented an NPC‐protective effect (padj = 4.89 × 10−4). Moreover, a decreased binding affinity toward risk HLA supertype A02 was observed for the peptide carrying the NPC‐risk mutation BNRF1 V1222I (p = 0.0078), and an increased binding affinity toward protective HLA supertype A03 was observed for the peptide carrying the NPC‐risk mutation BALF2 I613V (p = 0.022). This study revealed the distinct preference of EBV peptides for binding HLA supertypes, which may contribute to shaping EBV population structure and be involved in NPC development.
Plasma low-density lipoprotein (LDL) is primarily cleared by LDL receptor (LDLR). LDLR can be proteolytically cleaved to release its soluble ectodomain (sLDLR) into extracellular milieu. However, the ...proteinase responsible for LDLR cleavage is unknown. Here we report that membrane type 1-matrix metalloproteinase (MT1-MMP) co-immunoprecipitates and co-localizes with LDLR and promotes LDLR cleavage. Plasma sLDLR and cholesterol levels are reduced while hepatic LDLR is increased in mice lacking hepatic MT1-MMP. Opposite effects are observed when MT1-MMP is overexpressed. MT1-MMP overexpression significantly increases atherosclerotic lesions, while MT1-MMP knockdown significantly reduces cholesteryl ester accumulation in the aortas of apolipoprotein E (apoE) knockout mice. Furthermore, sLDLR is associated with apoB and apoE-containing lipoproteins in mouse and human plasma. Plasma levels of sLDLR are significantly increased in subjects with high plasma LDL cholesterol levels. Thus, we demonstrate that MT1-MMP promotes ectodomain shedding of hepatic LDLR, thereby regulating plasma cholesterol levels and the development of atherosclerosis.
Abstract
One of the best ways to control COVID-19 is vaccination. Among the various SARS-CoV-2 vaccines, inactivated virus vaccines have been widely applied in China and many other countries. To ...understand the underlying protective mechanism of these vaccines, it is necessary to systematically analyze the humoral responses that are triggered. By utilizing a SARS-CoV-2 microarray with 21 proteins and 197 peptides that fully cover the spike protein, antibody response profiles of 59 serum samples collected from 32 volunteers immunized with the inactivated virus vaccine BBIBP-CorV were generated. For this set of samples, the microarray results correlated with the neutralization titers of the authentic virus, and two peptides (S1-5 and S2-22) were identified as potential biomarkers for assessing the effectiveness of vaccination. Moreover, by comparing immunized volunteers to convalescent and hospitalized COVID-19 patients, the N protein, NSP7, and S2-78 were identified as potential biomarkers for differentiating COVID-19 patients from individuals vaccinated with the inactivated SARS-CoV-2 vaccine. The comprehensive profile of humoral responses against the inactivated SARS-CoV-2 vaccine will facilitate a deeper understanding of the vaccine and provide potential biomarkers for inactivated virus vaccine-related applications.
Combining the LSPR effect with the Z-scheme heterojunction into the Zn2In2S5/W18O49 reaction system, the separation and transfer of the photo-generated charge carriers is enhanced via a dual-channel ...charge transfer pathway to improve the photocatalytic inactivation activity toward E. coil.
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•A novel Zn2In2S5/W18O49 heterojunction was fabricated successfully.•The Zn2In2S5/W18O49 composites show remarkable vis-NIR light absorption property.•The LSPR effect and Z-scheme mechanism generate dual-channel charge transfer path.•Hot electrons injection process occurred in the Zn2In2S5/W18O49 composites.•Zn2In2S5/W18O49possessed excellent molecular oxygen activation activity.
The semiconductor-based photocatalysts with local surface plasmon resonance (LSPR) effect can extend light response to near-infrared region (NIR), as well as promote charge-carriers transfer, which provide a novel insight into designing light-driven photocatalyst with excellent photocatalytic performance. Here, we designed cost-effective wide-spectrum Zn2In2S5/W18O49 composite with enhanced photocatalytic performance based on a dual-channel charge transfer pathway. Benefiting from the synergistic effect of Z-scheme heterostructure and unique LSPR effect, the interfacial charge-carriers transfer rate and light-absorbing ability of Zn2In2S5/W18O49 were enhanced significantly under visible and NIR (vis-NIR) light irradiation. More reactive oxygen species (ROS) were formed by efficient molecular oxygen activation, which were the critical factors for both Escherichia coli (E. coli) photoinactivation and tetracycline (TC) photodegradation. The enhancement of molecular oxygen activation (MOA) ability was verified via quantitative analyses, which evaluated the amount of ROS through degrading nitrotetrazolium blue chloride (NBT) and p-phthalic acid (TA). By combining theoretical calculations with diverse experimental results, we proposed a credible photocatalytic reaction mechanism for antibiotic degradation and bacteria inactivation. This study develops a new insight into constructing promising photocatalysts with efficient photocatalytic activity in practical wastewater treatment.
The piRNA machinery is known for its role in mediating epigenetic silencing of transposons. Recent studies suggest that this function also involves piRNA-guided cleavage of transposon-derived ...transcripts. As many piRNAs also appear to have the capacity to target diverse mRNAs, this raises the intriguing possibility that piRNAs may act extensively as siRNAs to degrade specific mRNAs. To directly test this hypothesis, we compared mouse PIWI （MI- WI）-associated piRNAs with experimentally identified cleaved mRNA fragments from mouse testes, and observed cleavage sites that predominantly occur at position 10 from the 5＇ end of putative targeting piRNAs. We also noted strong biases for U and A residues at nucleotide positions 1 and 10, respectively, in both piRNAs and mRNA frag- ments, features that resemble the pattern of piRNA amplification by the ＇ping-pong＇ cycle. Through mapping of MIWI-RNA interactions by CLIP-seq and gene expression profiling, we found that many potential piRNA-targeted mRNAs directly interact with MIWI and show elevated expression levels in the testes of Miwi catalytic mutant mice. Reporter-based assays further revealed the importance of base pairing between piRNAs and mRNA targets and the requirement for both the slicer activity and piRNA-loading ability of MIWI in piRNA-mediated target repression. Importantly, we demonstrated that proper turnover of certain key piRNA targets is essential for sperm formation. Together, these findings reveal the siRNA-like function of the piRNA machinery in mouse testes and its central requirement for male germ cell development and maturation.
Acute myeloid leukemia (AML) is still incurable due to its heterogeneity and complexity of tumor microenvironment. It is imperative therefore to understand the molecular pathogenesis of AML and ...identify leukemia-associated biomarkers to formulate effective treatment strategies. Here, we systematically analyzed the clinical characters and natural killer (NK) cells portion in seventy newly-diagnosis (ND) AML patients. We found that the proportion of NK cells in the bone marrow of ND-AML patients could predict the prognosis of patients by analyzing the types and expression abundance of NK related ligands in tumor cells. Furthermore, MCL1 inhibitor but not BCL2 inhibitor combined with NK cell-based immunotherapy could effectively improve the therapeutic efficiency via inhibiting proliferation and inducing apoptosis of AML primary cells as well as cell lines in vitro. There results provide valuable insights that could help for exploring new therapeutic strategies for leukemia treatment.
Three different microstructures with line pattern, grid pattern, and spot pattern were fabricated on titanium surfaces by nanosecond laser. Scanning electron microscopy (SEM), contact angle ...measurement, surface roughness gage, and X-ray photoelectron spectroscopy (XPS) analyses were used to characterize and measure the surface morphology, contact angle, surface roughness, and chemical composition of titanium after laser processing. The results indicate that the contact angle of titanium surface is 77.8° immediately after laser processing, which shows hydrophilicity, and the contact angle presents a rising tendency with time in general. At steady state, the maximum contact angles for line pattern, grid pattern, and spot pattern increased to 157.2°, 153°, and 132.5°, respectively. It can be found that the surface wettability has changed from hydrophilicity to hydrophobicity and even to superhydrophobicity. The influence of surface morphology on the surface wettability effects immediately after laser treatment and does not change with time, while the effect of surface chemical composition on the surface wettability will continue from the beginning of laser processing to the stabilization of surface chemical composition. Finally, it can be deduced that the accumulation of carbon on the surface is probably the critical factor to improve the surface hydrophobicity. Therefore, it is concluded that laser-induced modification of surface wettability correlates with surface morphology and surface chemical composition.
Objectives
Temporomandibular joint osteoarthritis (TMJOA) is approximately twice as prevalent in women than in men. Synoviocytes are believed to play a critical role in joint inflammation. However, ...it is unknown whether synoviocytes from different genders possess sexual dimorphisms that contribute to female‐predominant TMJOA.
Materials and Methods
Freund's complete adjuvant combined with monosodium iodoacetate was used to induce TMJOA in female and male rats. Histologic and radiographic features were used to evaluate TMJOA. The expression of CD68, MCP‐1, iNOS, and IL‐1β was detected by immunohistochemistry and real‐time PCR. Primary fibroblast‐like synoviocytes (FLSs) isolated from the synovial membrane of female and male rats were used for in vitro experiments.
Results
Female rats showed aggravated TMJOA features as compared to male rats. Increased expression of iNOS and IL‐1β was detected in synovial membrane from female TMJOA rats as compared to male rats. Furthermore, greater amounts of CD68‐positive macrophage infiltration and increased MCP‐1 expression around the synovial membrane were detected in female TMJOA rats compared to males. Primary cultured FLSs from female rats showed higher sensitivity to TNF‐α treatment and recruited increased macrophage migration than male FLSs. More important, ovariectomy (OVX) by ablation in female rats repressed the sensitivity of female FLSs to TNF‐α treatment due to the loss of estrogen production. Blockage of the estrogen receptor repressed estrogen‐potentiated TNF‐α‐induced pro‐inflammatory cytokine expression in OVX‐FLSs. Moreover, the injection of estrogen receptor antagonists relieved the cartilage destruction and bone deterioration of TMJOA in female rats.
Conclusion
Estrogen‐sensitized synoviocytes in female rats may contribute to gender differences in the incidence and progression of TMJOA.
A novel facile method of fabricating disposable and highly reproducible surface-enhanced Raman spectroscopy (SERS) arrays using screen printing was explored. The screen printing ink containing silver ...nanoparticles was prepared and printed on supporting materials by a screen printing process to fabricate SERS arrays (6 × 10 printed spots) in large batches. The fabrication conditions, SERS performance and application of these arrays were systematically investigated, and a detection limit of 1.6 × 10(-13) M for rhodamine 6G could be achieved. Moreover, the screen printed SERS arrays exhibited high reproducibility and stability, the spot-to-spot SERS signals showed that the intensity variation was less than 10% and SERS performance could be maintained over 12 weeks. Portable high-throughput analysis of biological samples was accomplished using these disposable screen printed SERS arrays.
Radiation-induced oral mucositis (OM) is one of the most common acute complications for head and neck cancer. Severe OM is associated with radiation treatment breaks, which harms successful tumor ...management. Radiogenomics studies have indicated that genetic variants are associated with adverse effects of radiotherapy.
A large-scale genome-wide scan was performed in 1467 nasopharyngeal carcinoma patients, including 753 treated with 2D-CRT from Genetic Architecture of the Radiotherapy Toxicity and Prognosis (GARTP) cohort and 714 treated with IMRT (192 from the GARTP and 522 newly recruited). Subgroup analysis by radiotherapy technique was further performed in the top associations. We also performed physical and regulatory mapping of the risk loci and gene set enrichment analysis of the candidate target genes.
We identified 50 associated genomic loci and 64 genes via positional mapping, expression quantitative trait locus (eQTL) mapping, chromatin interaction mapping and gene-based analysis, and 36 of these loci were replicated in subgroup analysis. Interestingly, one of the top loci located in TNKS, a gene relevant to radiation toxicity, was associated with increased OM risk with OR = 3.72 of the lead SNP rs117157809 (95% CI 2.10-6.57; P = 6.33 × 10
). Gene set analyses showed that the 64 candidate target genes were enriched in the biological processes of regulating telomere capping and maintenance and telomerase activity (Top P = 7.73 × 10
).
These results enhance the biological understanding of radiotherapy toxicity. The association signals enriched in telomere function regulation implicate the potential underlying mechanism and warrant further functional investigation and potential individual radiotherapy applications.
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