The Gene vepN Regulated by Global Regulatory Factor veA That Affects Aflatoxin Production, Morphological Development and Pathogenicity in Aspergillus flavus.

Velvet (VeA), a light-regulated protein that shuttles between the cytoplasm and the nucleus, serves as a key global regulator of secondary metabolism in various Aspergillus species and plays a pivotal role in controlling multiple developmental processes. The gene vepN was chosen for further investigation through CHIP-seq analysis due to significant alterations in its interaction with VeA under varying conditions. This gene (AFLA_006970) contains a Septin-type guanine nucleotide-binding (G) domain, which has not been previously reported in Aspergillus flavus (A. flavus). The functional role of vepN in A. flavus was elucidated through the creation of a gene knockout mutant and a gene overexpression strain using a well-established dual-crossover recombinational technique. A comparison between the wild type (WT) and the ΔvepN mutant revealed distinct differences in morphology, reproductive capacity, colonization efficiency, and aflatoxin production. The mutant displayed reduced growth rate; dispersion of conidial heads; impaired cell wall integrity; and decreased sclerotia formation, colonization capacity, and aflatoxin levels. Notably, ΔvepN exhibited complete growth inhibition under specific stress conditions, highlighting the essential role of vepN in A. flavus. This study provides evidence that vepN positively influences aflatoxin production, morphological development, and pathogenicity in A. flavus.

Biomimetic Design of 3D Fe3O4/V-EVOH Fiber-Based Self-Floating Composite Aerogel to Enhance Solar Steam Generation Performance.

An interfacial solar steam generation evaporator for seawater desalination has attracted extensive interest in recent years. Nevertheless, challenges still remain in relatively low evaporation rate, unsatisfactory energy conversion efficiency, and salt accumulation. Herein, we have demonstrated a biomimetic bilayer composite aerogel consisting of bottom hydrophilic and vertically aligned EVOH channels and an upper hydrophobic conical Fe3O4 array. Thanks to the design merits, the 3D Fe3O4/V-EVOH evaporator exhibits a high evaporation rate of ∼2.446 kg m-2 h-1 and an impressive solar energy conversion efficiency of ∼165.5% under 1 sun illumination, which is superior to those of state-of-the-art evaporators reported so far. Moreover, the asymmetrical wettability not only allows the evaporator to self-float on the water but also facilitates the salt ion diffusion in the channels; thus, the evaporator shows no salt crystals on its surface and only a 6% decrease in evaporation performance even after the salt concentration increases from 0 to 10.0 wt %.

Biomimetic Mineralized 3D-Printed Polycaprolactone Scaffold Induced by Self-Adaptive Nanotopology to Accelerate Bone Regeneration.

Three-dimensional (3D)-printed biodegradable polymer scaffolds are at the forefront of personalized constructs for bone tissue engineering. However, it remains challenging to create a biological microenvironment for bone growth. Herein, we developed a novel yet feasible approach to facilitate biomimetic mineralization via self-adaptive nanotopography, which overcomes difficulties in the surface biofunctionalization of 3D-printed polycaprolactone (PCL) scaffolds. The building blocks of self-adaptive nanotopography were PCL lamellae that formed on the 3D-printed PCL scaffold via surface-directed epitaxial crystallization and acted as a linker to nucleate and generate hydroxyapatite crystals. Accordingly, a uniform and robust mineralized layer was immobilized throughout the scaffolds, which strongly bound to the strands and had no effect on the mechanical properties of the scaffolds. In vitro cell culture experiments revealed that the resulting scaffold was biocompatible and enhanced the proliferation and osteogenic differentiation of mouse embryolous osteoblast cells. Furthermore, we demonstrated that the resulting scaffold showed a strong capability to accelerate in vivo bone regeneration using a rabbit bone defect model. This study provides valuable opportunities to enhance the application of 3D-printed scaffolds in bone repair, paving the way for translation to other orthopedic implants.

BmNPV p35 regulates apoptosis in Bombyx mori via a novel target of interaction with the BmVDAC2-BmRACK1 complex.

Voltage-dependent anion channel 2 (VDAC2) is an important channel protein that plays a crucial role in the host response to viral infection. The receptor for activated C kinase 1 (RACK1) is also a key host factor involved in viral replication. Our previous research revealed that Bombyx mori VDAC2 (BmVDAC2) and B. mori RACK1 (BmRACK1) may interact with Bombyx mori nucleopolyhedrovirus (BmNPV), though the specific molecular mechanism remains unclear. In this study, the interaction between BmVDAC2 and BmRACK1 in the mitochondria was determined by various methods. We found that BmNPV p35 interacts directly with BmVDAC2 rather than BmRACK1. BmNPV infection significantly reduced the expression of BmVDAC2, and activated the mitochondrial apoptosis pathway. Overexpression of BmVDAC2 in BmN cells inhibited BmNPV-induced cytochrome c (cyto c) release, decrease in mitochondrial membrane potential as well as apoptosis. Additionally, the inhibition of cyto c release by BmVDAC2 requires the involvement of BmRACK1 and protein kinase C. Interestingly, overexpression of p35 inhibited cyto c release during mitochondrial apoptosis in a RACK1 and VDAC2-dependent manner. Even the mutant p35, which loses Caspase inhibitory activity, could still bind to VDAC2 and inhibit cyto c release. In summary, our results indicated that BmNPV p35 interacts with the VDAC2-RACK1 complex to regulate apoptosis by inhibiting cyto c release. These findings confirm the interaction between BmVDAC2 and BmRACK1, the interaction between p35 and the VDAC2-RACK1 complex, and a novel target that BmNPV p35 regulates apoptosis in Bombyx mori via interaction with the BmVDAC2-BmRACK1 complex. The result provide an initial exploration of the function of this interaction in the BmNPV-induced mitochondrial apoptosis pathway.

A Tellurium-Boosted High-Areal-Capacity Zinc-Sulfur Battery.

Aqueous rechargeable zinc-sulfur (Zn-S) batteries are a promising, cost-effective, and high-capacity energy storage technology. Still, they are challenged by the poor reversibility of S cathodes, sluggish redox kinetics, low S utilization, and unsatisfactory areal capacity. This work develops a facile strategy to achieve an appealing high-areal-capacity (above 5 mAh cm-2) Zn-S battery by molecular-level regulation between S and high-electrical-conductivity tellurium (Te). The incorporation of Te as a dopant allows for manipulation of the Zn-S electrochemistry, resulting in accelerated redox conversion, and enhanced S utilization. Meanwhile, accompanied by the S-ZnS conversion, Te is converted to zinc telluride during the discharge process, as revealed by ex-situ characterizations. This additional redox reaction contributes to the S cathode's total excellent discharge capacity. With this unique cathode structure design, the carbon-confined TeS cathode (denoted as Te1S7/C) delivers a high reversible capacity of 1335.0 mAh g-1 at 0.1 A g-1 with a mass loading of 4.22 mg cm-2, corresponding to a remarkable areal capacity of 5.64 mAh cm-2. Notably, a hybrid electrolyte design uplifts discharge plateau, reduces overpotential, suppresses Zn dendrites growth, and extends the calendar life of Zn-Te1S7 batteries. This study provides a rational S cathode structure to realize high-capacity Zn-S batteries for practical applications.

Circular polarizers and their effect on partial coherence.

We examine the action of a circular polarizer on an incident beam that is spatially partially coherent and partially polarized. It is found that the beam's coherence area can be significantly increased or decreased by the polarizer. Furthermore, an expression for the transmission efficiency is derived.

Clinical features and prognosis of ANCA-associated vasculitis patients who were double-seropositive for myeloperoxidase-ANCA and proteinase 3-ANCA.

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) patients with dual positivity for proteinase 3-ANCA (PR3-ANCA) and myeloperoxidase-ANCA (MPO-ANCA) are uncommon. We aimed to investigate these idiopathic double-positive AAV patients' clinical features, histological characteristics, and prognosis. We reviewed all the electronic medical records of patients diagnosed with AAV to obtain clinical data and renal histological information from January 2010 to December 2020 in a large center in China. Patients were assigned to the MPO-AAV group or PR3-AAV group or idiopathic double-positive AAV group by ANCA specificity. We explored features of idiopathic double-positive AAV. Of the 340 patients who fulfilled the study inclusion criteria, 159 (46.76%) were female, with a mean age of 58.41 years at the time of AAV diagnosis. Similar to MPO-AAV, idiopathic double-positive AAV patients were older and had more severe anemia, lower Birmingham Vasculitis Activity Score (BVAS) and C-reactive protein (CRP) levels, less ear, nose, and throat (ENT) involvement, higher initial serum creatinine and a lower estimated glomerular filtration rate (eGFR) when compared with PR3-AAV (P < 0.05). The proportion of normal glomeruli of idiopathic double-positive AAV was the lowest among the three groups (P < 0.05). The idiopathic double-positive AAV patients had the worst remission rate (58.8%) among the three groups (P < 0.05). The relapse rate of double-positive AAV (40.0%) was comparable with PR3-AAV (44.8%) (P > 0.05). Although there was a trend toward a higher relapse rate of idiopathic double-positive AAV (40.0%) compared with MPO-AAV (23.5%), this did not reach statistical significance (P > 0.05). The proportion of patients who progressed to ESRD was 47.1% and 44.4% in the idiopathic double-positive AAV group and MPO-AAV group respectively, without statistical significance. Long-term patient survival also varied among the three groups (P < 0.05). Idiopathic double-positive AAV is a rare clinical entity with hybrid features of MPO-AAV and PR3-AAV. MPO-AAV is the "dominant" phenotype in idiopathic double-positive AAV.

Anti-Solvent-Free Fabrication of Stable FA0.9Cs0.1PbI3 Perovskite Solar Cells with Efficiency Exceeding 24.0% through a Naphthalene-Based Passivator.

The anti-solvent-free fabrication of high-efficiency perovskite solar cells (PSCs) holds immense significance for the transition from laboratory-scale to large-scale commercial applications. However, the device performance is severely hindered by the increased occurrence of surface defects resulting from the lack of control over nucleation and crystallization of perovskite using anti-solvent methods. In this study, 2-(naphthalen-2-yl)ethylamine hydriodide (NEAI) is employed as the surface passivator for perovskite films without using any anti-solvent. Naphthalene demonstrates strong π-π conjugation, which aids in the efficient extraction of charge carriers. Additionally, the naphthalene-ring moieties form a tight attachment to the perovskite surface. After NEAI treatment, FA and I vacancies are selectively occupied by NEA+ and I- in NEAI respectively, thus effectively passivating the surface defects and isolating the surface from moisture. Ultimately, the optimized NEAI-treated device achieves a promising power conversion efficiency (PCE) of 24.19% (with a certified efficiency of 23.94%), featuring a high fill factor of 83.53%. It stands out as one of the reported high PCEs achieved for PSCs using the spin-coating technique without the need for any anti-solvent so far. Furthermore, the NEAI-treated device can maintain ≈87% of its initial PCE after 2000 h in ambient air with a relative humidity of 30% ± 5%.

Culture-free detection of ß-lactamase-Producing bacteria in urinary tract infections using a paper sensor.

Developing simple, inexpensive, fast, sensitive, and specific probes for antibiotic-resistant bacteria is crucial for the management of urinary tract infections (UTIs). We here propose a paper-based sensor for the rapid detection of ß-lactamase-producing bacteria in the urine samples of UTI patients. By conjugating a strongly electronegative group -N+(CH3)3 with the core structures of cephalosporin and carbapenem antibiotics, two visual probes were achieved to respectively target the extended-spectrum/AmpC ß-lactamases (ESBL/AmpC) and carbapenemase, the two most prevalent factors causing antibiotic resistance. By integrating these probes into a portable paper sensor, we confirmed 10 and 8 cases out of 30 clinical urine samples as ESBL/AmpC- and carbapenemase-positive, respectively, demonstrating 100% clinical sensitivity and specificity. This paper sensor can be easily conducted on-site, without resorting to bacterial culture, providing a solution to the challenge of rapid detection of ß-lactamase-producing bacteria, particularly in resource-limited settings.

Reducing Indoor Particulate Air Pollution Improves Student Test Scores: A Randomized Double-Blind Crossover Study.

Short-term exposure to air pollution is associated with a decline in cognitive function. Standardized test scores have been employed to evaluate the effects of air pollution exposure on cognitive performance. Few studies aimed to prove whether air pollution is responsible for reduced test scores; none have implemented a "gold-standard" method for assessing the association such as a randomized, double-blind intervention. This study used a "gold-standard" method─randomized, double-blind crossover─to assess whether reducing short-term indoor particle concentrations results in improved test scores in college students in Tianjin, China. Participants (n = 162) were randomly assigned to one of two similar classrooms and completed a standardized English test on two consecutive weekends. Air purifiers with active or sham (i.e., filter removed) particle filtration were placed in each classroom. The filtration mode was switched between the two test days. Linear mixed-effect models were used to evaluate the effect of the intervention mode on the test scores. The results show that air purification (i.e., reducing PM) was significantly associated with increases in the z score for combined (0.11 [95%CI: 0.02, 0.21]) and reading (0.11 [95%CI: 0.00, 0.22]) components. In conclusion, a short-term reduction in indoor particle concentration led to improved test scores in students, suggesting an improvement in cognitive function.

Using Machine Learning to Construct the Blood-Follicle Distribution Models of Various Trace Elements and Explore the Transport-Related Pathways with Multiomics Data.

Permeabilities of various trace elements (TEs) through the blood-follicle barrier (BFB) play an important role in oocyte development. However, it has not been comprehensively described as well as its involved biological pathways. Our study aimed to construct a blood-follicle distribution model of the concerned TEs and explore their related biological pathways. We finally included a total of 168 women from a cohort of in vitro fertilization-embryo transfer conducted in two reproductive centers in Beijing City and Shandong Province, China. The concentrations of 35 TEs in both serum and follicular fluid (FF) samples from the 168 women were measured, as well as the multiomics features of the metabolome, lipidome, and proteome in both plasma and FF samples. Multiomics features associated with the transfer efficiencies of TEs through the BFB were selected by using an elastic net model and further utilized for pathway analysis. Various machine learning (ML) models were built to predict the concentrations of TEs in FF. Overall, there are 21 TEs that exhibited three types of consistent BFB distribution characteristics between Beijing and Shandong centers. Among them, the concentrations of arsenic, manganese, nickel, tin, and bismuth in FF were higher than those in the serum with transfer efficiencies of 1.19-4.38, while a reverse trend was observed for the 15 TEs with transfer efficiencies of 0.076-0.905, e.g., mercury, germanium, selenium, antimony, and titanium. Lastly, cadmium was evenly distributed in the two compartments with transfer efficiencies of 0.998-1.056. Multiomics analysis showed that the enrichment of TEs was associated with the synthesis and action of steroid hormones and the glucose metabolism. Random forest model can provide the most accurate predictions of the concentrations of TEs in FF among the concerned ML models. In conclusion, the selective permeability through the BFB for various TEs may be significantly regulated by the steroid hormones and the glucose metabolism. Also, the concentrations of some TEs in FF can be well predicted by their serum levels with a random forest model.

NUP85 alleviates lipid metabolism and inflammation by regulating PI3K/AKT signaling pathway in nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) is one of the common causes of chronic liver disease in the world. The problem of NAFLD had become increasingly prominent. However, its pathogenesis is still indistinct. As we all know, NAFLD begins with the accumulation of triglyceride (TG), leading to fatty degeneration, inflammation and other liver tissues damage. Notably, structure of nucleoporin 85 (NUP85) is related to lipid metabolism and inflammation of liver diseases. In this study, the results of researches indicated that NUP85 played a critical role in NAFLD. Firstly, the expression level of NUP85 in methionine-choline-deficient (MCD)-induced mice increased distinctly, as well as the levels of fat disorder and inflammation. On the contrary, knockdown of NUP85 had the opposite effects. In vitro, AML-12 cells were stimulated with 2 mm free fatty acids (FFA) for 24 h. Results also proved that NUP85 significantly increased in model group, and increased lipid accumulation and inflammation level. Besides, NUP85 protein could interact with C-C motif chemokine receptor 2 (CCR2). Furthermore, when NUP85 protein expressed at an extremely low level, the expression level of CCR2 protein also decreased, accompanied with an inhibition of phosphorylation of phosphoinositol-3 kinase (PI3K)-protein kinase B (AKT) signaling pathway. What is more, trans isomer (ISRIB), a targeted inhibitor of NUP85, could alleviate NAFLD. In summary, our findings suggested that NUP85 functions as an important regulator in NAFLD through modulation of CCR2.

Fabrication and Characterization of a Lead-Free Cesium Bismuth Iodide Perovskite through Antisolvent-Assisted Crystallization.

Cesium bismuth iodide perovskite material offers good stability toward ambient conditions and has potential optoelectronic characteristics. However, wide bandgap, absorber surface roughness, and poor surface coverage with pinholes are among the key impediments to its adoption as a photovoltaic absorber material. Herein, bandgap modification and the tailoring of surface morphology have been performed through molar ratio variation and antisolvent treatment, whereby type III antisolvent (toluene) based on Hansen space has been utilized. XRD and Raman spectroscopy analyses confirm the formation of a 0D/2D mixed dimensional structure with improved optoelectronic properties when the molar ratio of CsI/BiI3 was adjusted from 1.5:1 to 1:1.5. The absorption results and Tauc plot determination show that the fabricated film has a lower bandgap of 1.80 eV. TRPL analysis reveals that the film possesses a very low charge carrier lifetime of 0.94 ns, suggesting deep defects. Toluene improves the charge carrier lifetime to 1.89 ns. The average grain size also increases from 323.26 nm to 444.3 nm upon toluene addition. Additionally, the inclusion of toluene results in a modest improvement in PCE, from 0.23% to 0.33%.

Semaphorin3C identified as mediator of neuroinflammation and microglia polarization after spinal cord injury.

Excessive neuroinflammation after spinal cord injury (SCI) is a major hurdle during nerve repair. Although proinflammatory macrophage/microglia-mediated neuroinflammation plays important roles, the underlying mechanism that triggers neuroinflammation and aggravating factors remain unclear. The present study identified a proinflammatory role of semaphorin3C (SEMA3C) in immunoregulation after SCI. SEMA3C expression level peaked 7 days post-injury (dpi) and decreased by 14 dpi. In vivo and in vitro studies revealed that macrophages/microglia expressed SEMA3C in the local microenvironment, which induced neuroinflammation and conversion of proinflammatory macrophage/microglia. Mechanistic experiments revealed that RAGE/NF-κB was downstream target of SEMA3C. Inhibiting SEMA3C-mediated RAGE signaling considerably suppressed proinflammatory cytokine production, reversed polarization of macrophages/microglia shortly after SCI. In addition, inhibition of SEMA3C-mediated RAGE signaling suggested that the SEMA3C/RAGE axis is a feasible target to preserve axons from neuroinflammation. Taken together, our study provides the first experimental evidence of an immunoregulatory role for SEMA3C in SCI via an autocrine mechanism.

Circulating microRNA-33b levels are associated with the presence and severity of coronary heart disease.

MicroRNA-33b (miR-33b) affected various biological pathways in regulating cholesterol homeostasis which may link to the pathogenesis of atherosclerotic lesions. However, whether this marker is associated with the presence and severity of coronary heart disease (CHD) is undetermined. We aim to explore the diagnostic value of circulating miR-33b level in the presence and severity of CHD. Altogether 320 patients were enrolled, including 240 patients diagnosed with CHD while 80 were classified as controls after CAG examination. Circulating miR-33b level was analyzed in all subjects, the Gensini score was calculated to assess the severity of stenotic lesions. The association between miR-33b and the presence and severity of CHD was analyzed, and the diagnostic potential of miR-33b of CHD was performed by the receiver operating characteristic (ROC) analysis. The CHD group had higher miR-33b levels (p < 0.001), and the miR-33b content significantly elevated following an increasing Gensini score (p for trend < 0.001). After adjustments for potential risk factors, such as several blood lipid markers, miR-33b remained a significant determinant for CHD (p < 0.001). ROC analysis disclosed that the AUC was 0.931. The optimal cutoff value of miR-33b was with a sensitivity of 81.3% and a specificity of 98.7% in differentiating CHD. It can prognosticate that the higher level of miR-33b was linked to increased severity of disease in CHD patients. Thus, the application of this marker might assist in the diagnosis and classification of CHD patients. Nevertheless, additional studies with larger sample sizes will be required to verify these results.

Role of non-coding RNAs mediated pyroptosis on cancer therapy: a review.

INTRODUCTION: Non-coding RNAs (ncRNAs), which are incapable of encoding proteins, are involved in the progression of numerous tumors by altering transcriptional and post-transcriptional processing. Recent studies have revealed prominent features of ncRNAs in pyroptosis, a type of non-apoptotic programmed cellular destruction linked to an inflammatory reaction. Drug resistance has arisen gradually as a result of anti-apoptotic proteins, therefore strategies based on pyroptotic cell death have attracted increasing attention. We have observed that ncRNAs may exert significant influence on cancer therapy, chemotherapy, radio- therapy, targeted therapy and immunotherapy, by regulating pyroptosis. AREAS COVERED: Literatures were searched (December 2023) for studies on cancer therapy for ncRNAs-mediated pyroptotic cell death. EXPERT OPINION: The most universal mechanical strategy for ncRNAs to regulate target genes is competitive endogenous RNAs (ceRNA). Besides, certain ncRNAs could directly interact with proteins and modulate downstream genes to induce pyroptosis, resulting in tumor growth or inhibition. In this review, we aim to display that ncRNAs, predominantly long non-coding RNAs (lncRNAs), microRNAs (miRNAs) and circular RNAs (circRNAs), could function as potential biomarkers for diagnosis and prognosis and produce new insights into anti-cancer strategies modulated by pyroptosis for clinical applications.

Long-Term Satisfaction of Oral Sedation versus Standard-of-Care Intravenous Sedation for Ocular Surgery.

Purpose: Long-term patient satisfaction may influence patients' perspectives of the quality of care and their relationship with their providers. This is a follow up to a comparative effectiveness study investigating oral to intravenous sedation (OIV study). The OIV study found that oral sedation was noninferior in patient satisfaction to standard intravenous (IV) sedation for anterior segment and vitreoretinal surgeries. This study aims to determine if patient satisfaction with oral sedation remained noninferior long term. Patients and Methods: Patients were re-interviewed using the same satisfaction survey given during the OIV study. Statistical analysis involved t-tests for noninferiority of the long-term mean satisfaction score of oral and IV sedation. We also compared the original mean satisfaction score and the follow-up mean satisfaction score for each type of sedation and for both groups combined. Results: Participants were interviewed at a median of 1225.5 days (range 754-1675 days) from their surgery. The original mean satisfaction score was 5.26 ± 0.79 for the oral treatment group (n = 52) and 5.27 ± 0.64 for the intravenous treatment group (n = 46), demonstrating noninferiority with a difference in mean satisfaction score of 0.015 (p < 0.0001). The follow-up mean satisfaction score was 5.23 ± 0.90 for oral sedation and 5.60 ± 0.61 for IV sedation, with a difference in the mean satisfaction score of 0.371 (p = 0.2071). Satisfaction scores did not differ between the original mean satisfaction score and the follow-up mean satisfaction score for the oral treatment group alone (p = 0.8367), but scores in the intravenous treatment group increased longitudinally (p = 0.0004). Conclusion: In this study, long-term patient satisfaction with oral sedation was not noninferior to satisfaction with IV sedation, unlike our findings with short-term patient satisfaction in our original study. Patient satisfaction also remained unchanged over time for the oral treatment group, but patients in the intravenous treatment group reported higher long-term satisfaction with their anesthesia experience compared to the immediate post-operative period.

m6A methyltransferase METTL14­mediated RP1­228H13.5 promotes the occurrence of liver cancer by targeting hsa­miR­205/ZIK1.

The aim of the present study was to explore the association between N6­methyladenosine (m6A) modification regulatory gene­related long noncoding (lnc)RNA RP1­228H13.5 and cancer prognosis through bioinformatics analysis, as well as the impact of RP1­228H13.5 on cell biology­related behaviors and specific molecular mechanisms. Bioinformatics analysis was used to construct a risk model consisting of nine genes. This model can reflect the survival time and differentiation degree of cancer. Subsequently, a competing endogenous RNA network consisting of 3 m6A­related lncRNAs, six microRNAs (miRs) and 201 mRNAs was constructed. A cell assay confirmed that RP1­228H13.5 is significantly upregulated in liver cancer cells, which can promote liver cancer cell proliferation, migration and invasion, and inhibit liver cancer cell apoptosis. The specific molecular mechanism may be the regulation of the expression of zinc finger protein interacting with K protein 1 (ZIK1) by targeting the downstream hsa­miR­205. Further experiments found that the m6A methyltransferase 14, N6­adenosine­methyltransferase subunit mediates the regulation of miR­205­5p expression by RP1­228H13.5. m6A methylation regulatory factor­related lncRNA has an important role in cancer. The targeting of hsa­miR­205 by RP1­228H13.5 to regulate ZIK1 may serve as a potential mechanism in the occurrence and development of liver cancer.

Pharmacological suppression of HHLA2 glycosylation restores anti-tumor immunity in colorectal cancer.

Immunotherapy aimed at inhibiting the negative co-stimulatory molecule programmed cell death-ligand 1 (PD-L1) has limited effectiveness, with clinical response rates remaining below 10%-15%. Therefore, new immune checkpoints need to be explored. Our study focused on human endogenous retrovirus H long terminal repeat-associating protein 2 (HHLA2), a highly glycosylated member of the B7 family that is widely expressed in colorectal cancer. HHLA2 expression negatively correlates with the prognosis of colorectal cancer. Glycosylation of HHLA2, which is regulated by the glycosyltransferase STT3 oligosaccharyltransferase complex catalytic subunit A (STT3A), is crucial for protein stability and expression in cell membranes. Additionally, the binding of HHLA2 to the receptors killer cell immunoglobulin-like receptor, three immunoglobulin domains and long cytoplasmic tail 3 (KIR3DL3) and transmembrane and immunoglobulin (Ig) domain containing 2 (TMIGD2) is dependent on N-glycosylation. Moreover, N-glycosylation of HHLA2 promotes immune evasion in colorectal cancer by suppressing the immune response of NK cells. Notably, the STT3A inhibitor NGI-1 enhances the anti-tumor immune response of NK cells. Our findings provide new insights and a molecular basis for targeting HHLA2 in immunotherapy for colorectal cancer.