A novel biomarker associated with EBV infection improves response prediction of immunotherapy in gastric cancer.

BACKGROUND: Novel biomarkers are required in gastric cancer (GC) treated by immunotherapy. Epstein-Barr virus (EBV) infection induces an immune-active tumor microenvironment, while its association with immunotherapy response is still controversial. Genes underlying EBV infection may determine the response heterogeneity of EBV + GC. Thus, we screened hub genes associated with EBV infection to predict the response to immunotherapy in GC. METHODS: Prognostic hub genes associated with EBV infection were screened using multi-omic data of GC. EBV + GC cells were established and confirmed by EBV-encoded small RNA in situ hybridization (EBER-ISH). Immunohistochemistry (IHC) staining of the hub genes was conducted in GC samples with EBER-ISH assay. Infiltrating immune cells were stained using immunofluorescence. RESULTS: CHAF1A was identified as a hub gene in EBV + GC, and its expression was an independent predictor of overall survival (OS). EBV infection up-regulated CHAF1A expression which also predicted EBV infection well. CHAF1A expression also predicted microsatellite instability (MSI) and a high tumor mutation burden (TMB). The combined score (CS) of CHAF1A expression with MSI or TMB further improved prognostic stratification. CHAF1A IHC score positively correlated with the infiltration of NK cells and macrophages M1. CHAF1A expression alone could predict the immunotherapy response, but its CS with EBV infection, MSI, TMB, or PD-L1 expression showed better effects and improved response stratification based on current biomarkers. CONCLUSIONS: CHAF1A could be a novel biomarker for immunotherapy of GC, with the potential to improve the efficacy of existing biomarkers.

A Cu/MnOx Composite with Copper-Doping-Induced Oxygen Vacancies as a Cathode for Aqueous Zinc-Ion Batteries.

Aqueous zinc-ion batteries are anticipated to be the next generation of important energy storage devices to replace lithium-ion batteries due to the ongoing use of lithium resources and the safety hazards associated with organic electrolytes in lithium-ion batteries. Manganese-based compounds, including MnOx materials, have prominent places among the many zinc-ion battery cathode materials. Additionally, Cu doping can cause the creation of an oxygen vacancy, which increases the material's internal electric field and enhances cycle stability. MnOx also has great cyclic stability and promotes ion transport. At a current density of 0.2 A g-1, the Cu/MnOx nanocomposite obtained a high specific capacitance of 304.4 mAh g-1. In addition, Cu/MnOx nanocomposites showed A high specific capacity of 198.9 mAh g-1 after 1000 cycles at a current density of 0.5 A g-1. Therefore, Cu/MnOx nanocomposites are expected to be a strong contender for the next generation of zinc-ion battery cathode materials in high energy density storage systems.

Advances in herbal polysaccharides-based nano-drug delivery systems for cancer immunotherapy.

The boom in cancer immunotherapy has provided many patients with a better chance of survival, but opportunities often come with challenges. Single immunotherapy is not good enough to eradicate tumours, and often fails to achieve the desired therapeutic effect because of the low targeting of immunotherapy drugs, and causes more side effects. As a solution to this problem, researchers have developed several nano Drug Delivery Systems (NDDS) to deliver immunotherapeutic agents to achieve good therapeutic outcomes. However, traditional drug delivery systems (DDS) have disadvantages such as poor bioavailability, high cytotoxicity, and difficulty in synthesis, etc. Herbal Polysaccharides (HPS), derived from natural Chinese herbs, inherently possess low toxicity. Furthermore, the biocompatibility, biodegradability, hydrophilicity, ease of modification, and immunomodulatory activities of HPS offer unique advantages in substituting traditional DDS. This review initially addresses the current developments and challenges in immunotherapy. Subsequently, it focuses on the immunomodulatory mechanisms of HPS and their design as nanomedicines for targeted drug delivery in tumour immunotherapy. Our findings reveal that HPS-based nanomedicines exhibit significant potential in enhancing the efficacy of cancer immunotherapy, providing crucial theoretical foundations and practical guidelines for future clinical applications.

Constructing a New Biomass-Based Bistatic Window for Solar Regulation.

Smart windows effectively respond to the ever-changing climatic conditions, offering a smart solution for low-carbon buildings. However, current smart windows derived from chromic materials often have inferior solar modulation ability, or showcase high haze that obstructs outdoor views. Here, instead of developing new chromic materials, a new bistatic window is proposed for ultra-high solar modulation and luminous transmission. The new developed window can reduce the indoor surface temperature for ≈11 °C, and reduce the building space cooling and heating energy consumption by 30% to 40%, providing significant energy-related advances over traditional smart windows. In detail, the bistatic window exhibits excellent solar modulation ability (ΔTsol = 61%), high visible transmittance in both bleached (Tlum,bleached = 91%) and colored (Tlum,colored = 56%) states, low haze (< 1%), rapid switching response (switching time < 1 min), high color rendering index (CRI > 80), and long-cyclic stability after 1000 cycles. With the advantages of facile fabrication and scalability, it is foreseen the developed bistatic window holds promising prospect for the next-generation low-carbon buildings, paving a new way for future advancements in the fields of smart windows.

How and when is academic stress associated with mobile phone addiction? The roles of psychological distress, peer alienation and rumination.

BACKGROUND: Mobile phone addiction has a high detection rate among adolescents and is thought to be related to academic stress. However, the underlying mechanisms in this relation were still unclear. The present study tested the mediating role of psychological distress and the moderating roles of peer alienation and rumination in the relationship between academic stress and mobile phone addiction. METHODS: A total of 742 middle school students were recruited to complete measures of academic stress, psychological distress, mobile phone addiction, peer alienation, rumination, and demographic variables. Regression-based statistical mediation and moderation were conducted using the PROCESS macro for SPSS. RESULTS: The results indicated that academic stress was significantly and positively associated with mobile phone addiction, and this link could be mediated by psychological distress. Moreover, this indirect effect was moderated by both peer alienation and rumination. Specifically, the mediating effect of psychological distress was stronger for adolescents with higher levels of peer alienation or adolescents with higher levels of rumination, as well as those with both higher levels of peer alienation and rumination. CONCLUSION: The findings of this study enrich our understanding of how and for whom academic stress is correlated with mobile phone addiction. Education experts and parents should pay special attention to adolescents suffering from academic stress, especially those with higher peer alienation and rumination, and help them get rid of mobile phone addiction.

A photothermal assisted zinc-air battery cathode based on pyroelectric and photocatalytic effect.

Zinc-air battery as one of the new generations of battery system, its theoretical specific energy is as high as 1086 Wh kg-1, specific capacity up to 820 mAh/g, and zinc has the advantages of environmental friendliness, resource abundance, low cost and good safety, so it has attracted much attention. However, due to its slow reaction kinetic process, zinc-air battery will produce a large charging overpotential usually up to 2 V, it is far beyond the theoretical voltage of 1.65 V, so reducing the overpotential of zinc-air batteries is extremely necessary, and the most common way to solve this problem is to use excellent catalyst cathode to improve the oxygen reduction and oxygen evolution kinetics of zinc-air batteries. So we developed a new photothermal assisted zinc-air battery system with Hollow carbon nanosphere@poly (vinylidene fluoride-trifluoroethylene-chlorofluoroethylene)@CdS(HCN@PVTC@CdS) photocathode, the pyroelectric and photocatalysis effect can effectively promote the reaction kinetics and reduce the reaction overpotential. With the pyroelectric and photocatalysis synergistic effect, the zinc-air has displayed a high discharge potential of 1.33 V and a low charging potential of 1.5 V with good cycle stability. This multi-assist technology with built-in electric and light fields paves the way for the development of high-performance zinc-air batteries and other energy storage systems.

SPARC overexpression in allogeneic adipose-derived mesenchymal stem cells in dog dry eye model induced by benzalkonium chloride.

BACKGROUND: Nowadays, companion and working dogs hold significant social and economic importance. Dry eye, also known as dry keratoconjunctivitis (KCS), a common disease in ophthalmology, can readily impact a dog's working capacity and lead to economic losses. Although there are several medications available for this disease, all of them only improve the symptoms on the surface of the eye, and they are irritating and not easy to use for long periods of time. Adipose-derived mesenchymal stem cells (ADMSC) are promising candidates for tissue regeneration and disease treatment. However, long-term in vitro passaging leads to stemness loss of ADMSC. Here, we aimed to use ADMSC overexpressing Secreted Protein Acidic and Rich in Cysteine (SPARC) to treat 0.25% benzalkonium chloride-treated dogs with dry eye to verify its efficacy. For in vitro validation, we induced corneal epithelial cell (HCECs) damage using 1 µg/mL benzalkonium chloride. METHODS: Fifteen male crossbred dogs were randomly divided into five groups: normal, dry eye self-healing control, cyclosporine-treated, ADMSC-CMV-treated and ADMSC-OESPARC-treated. HCECs were divided into four groups: normal control group, untreated model group, ADMSC-CMV supernatant culture group and ADMSC-OESRARC supernatant culture group. RESULTS: SPARC-modified ADMSC had the most significant effect on canine ocular surface inflammation, corneal injury, and tear recovery, and the addition of ADMSC-OESPARC cell supernatant also had a salvage effect on HCECs cellular damage, such as cell viability and cell proliferation ability. Moreover, analysis of the co-transcriptome sequencing data showed that SPARC could promote corneal epithelial cell repair by enhancing the in vitro viability, migration and proliferation and immunosuppression of ADMSC. CONCLUSION: The in vitro cell test and in vivo model totally suggest that the combination of SPARC and ADMSC has a promising future in novel dry eye therapy.

High-Voltage Na0.76Ni0.25-x/2Mgx/2Mn0.75O2-xFx Cathode Improved by One-Step In Situ MgF2 Doping with Superior Low-Temperature Performance and Extra-Stable Air Stability.

P2-NaxMnO2 has garnered significant attention due to its favorable Na+ conductivity and structural stability for large-scale energy storage fields. However, achieving a balance between high energy density and extended cycling stability remains a challenge due to the Jahn-Teller distortion of Mn3+ and anionic activity above 4.1 V. Herein, we propose a one-step in situ MgF2 strategy to synthesize a P2-Na0.76Ni0.225Mg0.025Mn0.75O1.95F0.05 cathode with improved Na-storage performance and decent water/air stability. By partially substituting cost-effective Mg for Ni and incorporating extra F for O, the optimized material demonstrates both enhanced capacity and structure stability via promoting Ni2+/Ni4+ and oxygen redox activity. It delivers a high capacity of 132.9 mA h g-1 with an elevated working potential of ≈3.48 V and maintains ≈83.0% capacity retention after 150 cycles at 100 mA g-1 within 2-4.3 V, compared to the 114.9 mA h g-1 capacity and 3.32 V discharging potential of the undoped Na0.76Ni0.25Mn0.75O2. While increasing the charging voltage to 4.5 V, 133.1 mA h g-1 capacity and 3.55 V discharging potential (vs Na/Na+) were achieved with 72.8% capacity retention after 100 cycles, far beyond that of the pristine sample (123.7 mA h g-1, 3.45 V, and 43.8%@100 cycles). Moreover, exceptional low-temperature cycling stability is achieved, with 95.0% after 150 cycles. Finally, the Na-storage mechanism of samples employing various doping strategies was investigated using in situ EIS, in situ XRD, and ex situ XPS techniques.

An oncogene regulating chromatin favors response to immunotherapy: Oncogene CHAF1A and immunotherapy outcomes.

Many biological processes related to cell function and fate begin with chromatin alterations, and many factors associated with the efficacy of immune checkpoint inhibitors (ICIs) are actually downstream events of chromatin alterations, such as genome changes, neoantigen production, and immune checkpoint expression. However, the influence of genes as chromatin regulators on the efficacy of ICIs remains elusive, especially in gastric cancer (GC). In this study, thirty out of 1593 genes regulating chromatin associated with a favorable prognosis were selected for GC. CHAF1A, a well-defined oncogene, was identified as the highest linkage hub gene. High CHAF1A expression were associated with microsatellite instability (MSI), high tumor mutation burden (TMB), high tumor neoantigen burden (TNB), high expressions of PD-L1 and immune effector genes, and live infiltration of immune cells. High CHAF1A expression indicated a favorable response and prognosis in immunotherapy of several cohorts, which was independent of MSI, TMB, TNB, PD-L1 expression, immune phenotype and transcriptome scoring, and improved patient selection based on these classic biomarkers. In vivo, CHAF1A knockdown alone inhibited tumor growth but it impaired the effect of an anti-PD-1 antibody by increasing the relative tumor proliferation rate and decreasing the survival benefit, potentially through the activation of TGF-ß signaling. In conclusion, CHAF1A may be a novel biomarker for improving patient selection in immunotherapy.

Electrically Conductive Polymers for Additive Manufacturing.

The use of electrically conductive polymers (CPs) in the development of electronic devices has attracted significant interest due to their unique intrinsic properties, which result from the synergistic combination of physicochemical properties in conventional polymers with the electronic properties of metals or semiconductors. Most conventional methods adopted for the fabrication of devices with nonplanar morphologies are still challenged by the poor ionic/electronic mobility of end products. Additive manufacturing (AM) brings about exciting prospects to the realm of CPs by enabling greater design freedom, more elaborate structures, quicker prototyping, relatively low cost, and more environmentally friendly electronic device creation. A growing variety of AM technologies are becoming available for three-dimensional (3D) printing of conductive devices, i.e., vat photopolymerization (VP), material extrusion (ME), powder bed fusion (PBF), material jetting (MJ), and lamination object manufacturing (LOM). In this review, we provide an overview of the recent research progress in the area of CPs developed for AM, which advances the design and development of future electronic devices. We consider different AM techniques, vis-à-vis, their development progress and respective challenges in printing CPs. We also discuss the material requirements and notable advances in 3D printing of CPs, as well as their potential electronic applications including wearable electronics, sensors, energy storage and conversion devices, etc. This review concludes with an outlook on AM of CPs.

Novel glucomannan-like polysaccharide from Lycium barbarum L. ameliorates renal fibrosis via blocking macrophage-to-myofibroblasts transition.

The macrophage to myofibroblasts transition (MMT) has been reported as a newly key target in renal fibrosis. Lycium barbarum L. is a traditional Chinese medicine for improving renal function, in which its polysaccharides (LBPs) are the mainly active components. However, whether the role of LBPs in treating renal fibrosis is related to MMT process remain unclear. The purpose of this study was to explore the relationship between the regulating effect on MMT process and the anti-fibrotic effect of LBPs. Initially, small molecular weight LBPs fractions (LBP-S) were firstly isolated via Sephadex G-100 column. Then, the potent inhibitory effect of LBP-S on MMT process was revealed on bone marrow-derived macrophages (BMDM) model induced by TGF-ß. Subsequently, the chemical structure of LBP-S was elucidated through monosaccharide, methylation and NMR spectrum analysis. In vivo biodistribution characteristics studies demonstrated that LBP-S exhibited effectively accumulation in kidney via intraperitoneal administration. Finally, LBP-S showed a satisfactory anti-renal fibrotic effect on unilateral ureteral obstruction operation (UUO) mice, which was significantly reduced following macrophage depletion. Overall, our findings indicated that LPB-S could alleviate renal fibrosis through regulating MMT process and providing new candidate agents for chronic kidney disease (CKD) related fibrosis treatment.

m6A methylation modification and immune cell infiltration: implications for targeting the catalytic subunit m6A-METTL complex in gastrointestinal cancer immunotherapy.

N6-methyladenosine (m6A) methylation modification is a ubiquitous RNA modification involved in the regulation of various cellular processes, including regulation of RNA stability, metabolism, splicing and translation. Gastrointestinal (GI) cancers are some of the world's most common and fatal cancers. Emerging evidence has shown that m6A modification is dynamically regulated by a complex network of enzymes and that the catalytic subunit m6A-METTL complex (MAC)-METTL3/14, a core component of m6A methyltransferases, participates in the development and progression of GI cancers. Furthermore, it has been shown that METTL3/14 modulates immune cell infiltration in an m6A-dependent manner in TIME (Tumor immune microenvironment), thereby altering the response of cancer cells to ICIs (Immune checkpoint inhibitors). Immunotherapy has emerged as a promising approach for treating GI cancers. Moreover, targeting the expression of METTL3/14 and its downstream genes may improve patient response to immunotherapy. Therefore, understanding the role of MAC in the pathogenesis of GI cancers and its impact on immune cell infiltration may provide new insights into the development of effective therapeutic strategies for GI cancers.

[BLOC1S1 promotes proliferation of goat spermatogonial stem cells].

With the rapid development of gene editing technology, the study of spermatogonial stem cells (SSCs) holds great significance in understanding spermatogenesis and its regulatory mechanism, developing transgenic animals, gene therapy, infertility treatment and protecting rare species. Biogenesis of lysosome-related organelles complex 1 subunit 1 (BLOC1S1) is believed to have anti-brucella potential. Exploring the impack of BLOC1S1 on goat SSCs not only helps investigate the ability of BLOC1S1 to promote SSCs proliferation, but also provides a cytological basis for disease-resistant breeding research. In this study, a BLOC1S1 overexpression vector was constructed by homologous recombination. The BLOC1S1 overexpression cell line of goat spermatogonial stem cells was successfully constructed by lentivirus packaging, transfection and puromycin screening. The overexpression efficiency of BLOC1S1 was found to be 18 times higher using real time quantitative PCR (RT-qPCR). Furthermore, the results from cell growth curve analysis, flow cytometry for cell cycle detection, and 5-ethynyl-2'-deoxyuridine (EdU) staining showed that BLOC1S1 significantly increased the proliferation activity of goat SSCs. The results of RT-qPCR, immunofluorescence staining and Western blotting analyses revealed up-regulation of proliferation-related genes (PCNA, CDK2, CCND1), and EIF2S3Y, a key gene regulating the proliferation of spermatogonial stem cells. These findings strongly suggest that the proliferative ability of goat SSCs can be enhanced through the EIF2S3Y/ERK pathway. In summary, this study successfully created a goat spermatogonial stem cell BLOC1S1 overexpression cell line, which exhibited improved proliferation ability. This research laid the groundwork for exploring the regulatory role of BLOC1S1 in goat spermatogonia and provided a cell platform for further study into the biological function of BLOC1S1. These findings also establish a foundation for breeding BLOC1S1 overexpressing goats.