Progestogen-driven B7-H4 contributes to onco-fetal immune tolerance.

Immune tolerance mechanisms are shared in cancer and pregnancy. Through cross-analyzing single-cell RNA-sequencing data from multiple human cancer types and the maternal-fetal interface, we found B7-H4 (VTCN1) is an onco-fetal immune tolerance checkpoint. We showed that genetic deficiency of B7-H4 resulted in immune activation and fetal resorption in allogeneic pregnancy models. Analogously, B7-H4 contributed to MPA/DMBA-induced breast cancer progression, accompanied by CD8+ T cell exhaustion. Female hormone screening revealed that progesterone stimulated B7-H4 expression in placental and breast cancer cells. Mechanistically, progesterone receptor (PR) bound to a newly identified -58 kb enhancer, thereby mediating B7-H4 transcription via the PR-P300-BRD4 axis. PR antagonist or BRD4 degrader potentiated immunotherapy in a murine B7-H4+ breast cancer model. Thus, our work unravels a mechanistic and biological connection of a female sex hormone (progesterone) to onco-fetal immune tolerance via B7-H4 and suggests that the PR-P300-BRD4 axis is targetable for treating B7-H4+ cancer.

The ubiquitin ligase MDM2 sustains STAT5 stability to control T cell-mediated antitumor immunity.

Targeting the p53-MDM2 pathway to reactivate tumor p53 is a chemotherapeutic approach. However, the involvement of this pathway in CD8+ T cell-mediated antitumor immunity is unknown. Here, we report that mice with MDM2 deficiency in T cells exhibit accelerated tumor progression and a decrease in tumor-infiltrating CD8+ T cell survival and function. Mechanistically, MDM2 competes with c-Cbl for STAT5 binding, reduces c-Cbl-mediated STAT5 degradation and enhances STAT5 stability in tumor-infiltrating CD8+ T cells. Targeting the p53-MDM2 interaction with a pharmacological agent, APG-115, augmented MDM2 in T cells, thereby stabilizing STAT5, boosting T cell immunity and synergizing with cancer immunotherapy. Unexpectedly, these effects of APG-115 were dependent on p53 and MDM2 in T cells. Clinically, MDM2 abundance correlated with T cell function and interferon-γ signature in patients with cancer. Thus, the p53-MDM2 pathway controls T cell immunity, and targeting this pathway may treat patients with cancer regardless of tumor p53 status.

Effector T Cells Abrogate Stroma-Mediated Chemoresistance in Ovarian Cancer.

Effector T cells and fibroblasts are major components in the tumor microenvironment. The means through which these cellular interactions affect chemoresistance is unclear. Here, we show that fibroblasts diminish nuclear accumulation of platinum in ovarian cancer cells, resulting in resistance to platinum-based chemotherapy. We demonstrate that glutathione and cysteine released by fibroblasts contribute to this resistance. CD8(+) T cells abolish the resistance by altering glutathione and cystine metabolism in fibroblasts. CD8(+) T-cell-derived interferon (IFN)γ controls fibroblast glutathione and cysteine through upregulation of gamma-glutamyltransferases and transcriptional repression of system xc(-) cystine and glutamate antiporter via the JAK/STAT1 pathway. The presence of stromal fibroblasts and CD8(+) T cells is negatively and positively associated with ovarian cancer patient survival, respectively. Thus, our work uncovers a mode of action for effector T cells: they abrogate stromal-mediated chemoresistance. Capitalizing upon the interplay between chemotherapy and immunotherapy holds high potential for cancer treatment.

Oxidative stress controls regulatory T cell apoptosis and suppressor activity and PD-L1-blockade resistance in tumor.

Live regulatory T cells (Treg cells) suppress antitumor immunity, but how Treg cells behave in the metabolically abnormal tumor microenvironment remains unknown. Here we show that tumor Treg cells undergo apoptosis, and such apoptotic Treg cells abolish spontaneous and PD-L1-blockade-mediated antitumor T cell immunity. Biochemical and functional analyses show that adenosine, but not typical suppressive factors such as PD-L1, CTLA-4, TGF-ß, IL-35, and IL-10, contributes to apoptotic Treg-cell-mediated immunosuppression. Mechanistically, apoptotic Treg cells release and convert a large amount of ATP to adenosine via CD39 and CD73, and mediate immunosuppression via the adenosine and A2A pathways. Apoptosis in Treg cells is attributed to their weak NRF2-associated antioxidant system and high vulnerability to free oxygen species in the tumor microenvironment. Thus, the data support a model wherein tumor Treg cells sustain and amplify their suppressor capacity through inadvertent death via oxidative stress. This work highlights the oxidative pathway as a metabolic checkpoint that controls Treg cell behavior and affects the efficacy of therapeutics targeting cancer checkpoints.

Cancer mediates effector T cell dysfunction by targeting microRNAs and EZH2 via glycolysis restriction.

Aerobic glycolysis regulates T cell function. However, whether and how primary cancer alters T cell glycolytic metabolism and affects tumor immunity in cancer patients remains a question. Here we found that ovarian cancers imposed glucose restriction on T cells and dampened their function via maintaining high expression of microRNAs miR-101 and miR-26a, which constrained expression of the methyltransferase EZH2. EZH2 activated the Notch pathway by suppressing Notch repressors Numb and Fbxw7 via trimethylation of histone H3 at Lys27 and, consequently, stimulated T cell polyfunctional cytokine expression and promoted their survival via Bcl-2 signaling. Moreover, small hairpin RNA-mediated knockdown of human EZH2 in T cells elicited poor antitumor immunity. EZH2(+)CD8(+) T cells were associated with improved survival in patients. Together, these data unveil a metabolic target and mechanism of cancer immune evasion.

Glucose regulation of adipose tissue browning by CBP/p300- and HDAC3-mediated reversible acetylation of CREBZF.

Glucose is required for generating heat during cold-induced nonshivering thermogenesis in adipose tissue, but the regulatory mechanism is largely unknown. CREBZF has emerged as a critical mechanism for metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as nonalcoholic fatty liver disease (NAFLD). We investigated the roles of CREBZF in the control of thermogenesis and energy metabolism. Glucose induces CREBZF in human white adipose tissue (WAT) and inguinal WAT (iWAT) in mice. Lys208 acetylation modulated by transacetylase CREB-binding protein/p300 and deacetylase HDAC3 is required for glucose-induced reduction of proteasomal degradation and augmentation of protein stability of CREBZF. Glucose induces rectal temperature and thermogenesis in white adipose of control mice, which is further potentiated in adipose-specific CREBZF knockout (CREBZF FKO) mice. During cold exposure, CREBZF FKO mice display enhanced thermogenic gene expression, browning of iWAT, and adaptive thermogenesis. CREBZF associates with PGC-1α to repress thermogenic gene expression. Expression levels of CREBZF are negatively correlated with UCP1 in human adipose tissues and increased in WAT of obese ob/ob mice, which may underscore the potential role of CREBZF in the development of compromised thermogenic capability under hyperglycemic conditions. Our results reveal an important mechanism of glucose sensing and thermogenic inactivation through reversible acetylation.

An orthogonalized PYR1-based CID module with reprogrammable ligand-binding specificity.

Plants sense abscisic acid (ABA) using chemical-induced dimerization (CID) modules, including the receptor PYR1 and HAB1, a phosphatase inhibited by ligand-activated PYR1. This system is unique because of the relative ease with which ligand recognition can be reprogrammed. To expand the PYR1 system, we designed an orthogonal '*' module, which harbors a dimer interface salt bridge; X-ray crystallographic, biochemical and in vivo analyses confirm its orthogonality. We used this module to create PYR1*MANDI/HAB1* and PYR1*AZIN/HAB1*, which possess nanomolar sensitivities to their activating ligands mandipropamid and azinphos-ethyl. Experiments in Arabidopsis thaliana and Saccharomyces cerevisiae demonstrate the sensitive detection of banned organophosphate contaminants using living biosensors and the construction of multi-input/output genetic circuits. Our new modules enable ligand-programmable multi-channel CID systems for plant and eukaryotic synthetic biology that can empower new plant-based and microbe-based sensing modalities.

Cancer SLC43A2 alters T cell methionine metabolism and histone methylation.

Abnormal epigenetic patterns correlate with effector T cell malfunction in tumours1-4, but the cause of this link is unknown. Here we show that tumour cells disrupt methionine metabolism in CD8+ T cells, thereby lowering intracellular levels of methionine and the methyl donor S-adenosylmethionine (SAM) and resulting in loss of dimethylation at lysine 79 of histone H3 (H3K79me2). Loss of H3K79me2 led to low expression of STAT5 and impaired T cell immunity. Mechanistically, tumour cells avidly consumed methionine and outcompeted T cells for methionine by expressing high levels of the methionine transporter SLC43A2. Genetic and biochemical inhibition of tumour SLC43A2 restored H3K79me2 in T cells, thereby boosting spontaneous and checkpoint-induced tumour immunity. Moreover, methionine supplementation improved the expression of H3K79me2 and STAT5 in T cells, and this was accompanied by increased T cell immunity in tumour-bearing mice and patients with colon cancer. Clinically, tumour SLC43A2 correlated negatively with T cell histone methylation and functional gene signatures. Our results identify a mechanistic connection between methionine metabolism, histone patterns, and T cell immunity in the tumour microenvironment. Thus, cancer methionine consumption is an immune evasion mechanism, and targeting cancer methionine signalling may provide an immunotherapeutic approach.

Proline hydroxylation of CREB-regulated transcriptional coactivator 2 controls hepatic glucose metabolism.

Prolyl hydroxylase domain (PHD) enzymes change HIF activity according to oxygen signal; whether it is regulated by other physiological conditions remains largely unknown. Here, we report that PHD3 is induced by fasting and regulates hepatic gluconeogenesis through interaction and hydroxylation of CRTC2. Pro129 and Pro615 hydroxylation of CRTC2 following PHD3 activation is necessary for its association with cAMP-response element binding protein (CREB) and nuclear translocation, and enhanced binding to promoters of gluconeogenic genes by fasting or forskolin. CRTC2 hydroxylation-stimulated gluconeogenic gene expression is independent of SIK-mediated phosphorylation of CRTC2. Liver-specific knockout of PHD3 (PHD3 LKO) or prolyl hydroxylase-deficient knockin mice (PHD3 KI) show attenuated fasting gluconeogenic genes, glycemia, and hepatic capacity to produce glucose during fasting or fed with high-fat, high-sucrose diet. Importantly, Pro615 hydroxylation of CRTC2 by PHD3 is increased in livers of fasted mice, diet-induced insulin resistance or genetically obese ob/ob mice, and humans with diabetes. These findings increase our understanding of molecular mechanisms linking protein hydroxylation to gluconeogenesis and may offer therapeutic potential for treating excessive gluconeogenesis, hyperglycemia, and type 2 diabetes.

CD8+ T cells regulate tumour ferroptosis during cancer immunotherapy.

Cancer immunotherapy restores or enhances the effector function of CD8+ T cells in the tumour microenvironment1,2. CD8+ T cells activated by cancer immunotherapy clear tumours mainly by inducing cell death through perforin-granzyme and Fas-Fas ligand pathways3,4. Ferroptosis is a form of cell death that differs from apoptosis and results from iron-dependent accumulation of lipid peroxide5,6. Although it has been investigated in vitro7,8, there is emerging evidence that ferroptosis might be implicated in a variety of pathological scenarios9,10. It is unclear whether, and how, ferroptosis is involved in T cell immunity and cancer immunotherapy. Here we show that immunotherapy-activated CD8+ T cells enhance ferroptosis-specific lipid peroxidation in tumour cells, and that increased ferroptosis contributes to the anti-tumour efficacy of immunotherapy. Mechanistically, interferon gamma (IFNγ) released from CD8+ T cells downregulates the expression of SLC3A2 and SLC7A11, two subunits of the glutamate-cystine antiporter system xc-, impairs the uptake of cystine by tumour cells, and as a consequence, promotes tumour cell lipid peroxidation and ferroptosis. In mouse models, depletion of cystine or cysteine by cyst(e)inase (an engineered enzyme that degrades both cystine and cysteine) in combination with checkpoint blockade synergistically enhanced T cell-mediated anti-tumour immunity and induced ferroptosis in tumour cells. Expression of system xc- was negatively associated, in cancer patients, with CD8+ T cell signature, IFNγ expression, and patient outcome. Analyses of human transcriptomes before and during nivolumab therapy revealed that clinical benefits correlate with reduced expression of SLC3A2 and increased IFNγ and CD8. Thus, T cell-promoted tumour ferroptosis is an anti-tumour mechanism, and targeting this pathway in combination with checkpoint blockade is a potential therapeutic approach.

Group II metabotropic glutamate receptor activation attenuates acid-sensing ion channel currents in rat primary sensory neurons.

Acid-sensing ion channels (ASICs) play an important role in pain associated with tissue acidification. Peripheral inhibitory group II metabotropic glutamate receptors (mGluRs) have analgesic effects in a variety of pain conditions. Whether there is a link between ASICs and mGluRs in pain processes is still unclear. Herein, we show that the group II mGluR agonist LY354740 inhibited acid-evoked ASIC currents and action potentials in rat dorsal root ganglia neurons. LY354740 reduced the maximum current response to protons, but it did not change the sensitivity of ASICs to protons. LY354740 inhibited ASIC currents by activating group II mGluRs. We found that the inhibitory effect of LY354740 was blocked by intracellular application of the Gi/o protein inhibitor pertussis toxin and the cAMP analogue 8-Br-cAMP and mimicked by the protein kinase A (PKA) inhibitor H-89. LY354740 also inhibited ASIC3 currents in CHO cells coexpressing mGluR2 and ASIC3 but not in cells expressing ASIC3 alone. In addition, intraplantar injection of LY354740 dose-dependently alleviated acid-induced nociceptive behavior in rats through local group II mGluRs. Together, these results suggested that activation of peripheral group II mGluRs inhibited the functional activity of ASICs through a mechanism that depended on Gi/o proteins and the intracellular cAMP/PKA signaling pathway in rat dorsal root ganglia neurons. We propose that peripheral group II mGluRs are an important therapeutic target for ASIC-mediated pain.

Genome characteristics and the ODV proteome of a second distinct alphabaculovirus from Spodoptera litura.

BACKGROUND: Spodoptera litura is a harmful pest that feeds on more than 80 species of plants, and can be infected and killed by Spodoptera litura nucleopolyhedrovirus (SpltNPV). SpltNPV-C3 is a type C SpltNPV clone, that was observed and collected in Japan. Compared with type A or type B SpltNPVs, SpltNPV-C3 can cause the rapid mortality of S. litura larvae. METHODS: In this study, occlusion bodies (OBs) and occlusion-derived viruses (ODVs) of SpltNPV-C3 were purified, and OBs were observed by scanning electron microscopy (SEM). ODVs were observed under a transmission electron microscope (TEM). RESULTS: Both OBs and ODVs exhibit morphological characteristics typical of nucleopolyhedroviruses (NPVs).The genome of SpltNPV-C3 was sequenced and analyzed; the total length was 148,634 bp (GenBank accession 780,426,which was submitted as SpltNPV-II), with a G + C content of 45%. A total of 149 predicted ORFs were found. A phylogenetic tree of 90 baculoviruses was constructed based on core baculovirus genes. LC‒MS/MS was used to analyze the proteins of SpltNPV-C3; 34 proteins were found in the purified ODVs, 15 of which were core proteins. The structure of the complexes formed by per os infectivity factors 1, 2, 3 and 4 (PIF-1, PIF-2, PIF-3 and PIF-4) was predicted with the help of the AlphaFold multimer tool and predicted conserved sequences in PIF-3. SpltNPV-C3 is a valuable species because of its virulence, and the analysis of its genome and proteins in this research will be beneficial for pest control efforts.

Repurposing plant hormone receptors as chemically-inducible genetic switches for dynamic regulation in yeast.

Precise control of gene expression is critical for optimizing cellular metabolism and improving the production of valuable biochemicals. However, hard-wired approaches to pathway engineering, such as optimizing promoters, can take time and effort. Moreover, limited tools exist for controlling gene regulation in non-conventional hosts. Here, we develop a two-channel chemically-regulated gene expression system for the multi-stress tolerant yeast Kluyveromyces marxianus and use it to tune ethyl acetate production, a native metabolite produced at high titers in this yeast. To achieve this, we repurposed the plant hormone sensing modules (PYR1ABA/HAB1 and PYR1*MANDI/HAB1*) for high dynamic-range gene activation and repression controlled by either abscisic acid (ABA) or mandipropamid (mandi). To redirect metabolic flux towards ethyl acetate biosynthesis, we simultaneously repress pyruvate dehydrogenase (PDA1) and activate pyruvate decarboxylase (PDC1) to enhance ethyl acetate titers. Thus, we have developed new tools for chemically tuning gene expression in K. marxianus and S. cerevisiae that should be deployable across many non-conventional eukaryotic hosts.

Intrahepatic osteopontin signaling by CREBZF defines a checkpoint for steatosis-to-NASH progression.

BACKGROUND AND AIMS: NASH has emerged as a leading cause of chronic liver disease. However, the mechanisms that govern NASH fibrosis remain largely unknown. CREBZF is a CREB/ATF bZIP transcription factor that causes hepatic steatosis and metabolic defects in obesity. APPROACH AND RESULTS: Here, we show that CREBZF is a key mechanism of liver fibrosis checkpoint that promotes hepatocyte injury and exacerbates diet-induced NASH in mice. CREBZF deficiency attenuated liver injury, fibrosis, and inflammation in diet-induced mouse models of NASH. CREBZF increases HSC activation and fibrosis in a hepatocyte-autonomous manner by stimulating an extracellular matrix protein osteopontin, a key regulator of fibrosis. The inhibition of miR-6964-3p mediates CREBZF-induced production and secretion of osteopontin in hepatocytes. Adeno-associated virus -mediated rescue of osteopontin restored HSC activation, liver fibrosis, and NASH progression in CREBZF-deficient mice. Importantly, expression levels of CREBZF are increased in livers of diet-induced NASH mouse models and humans with NASH. CONCLUSIONS: Osteopontin signaling by CREBZF represents a previously unrecognized intrahepatic mechanism that triggers liver fibrosis and contributes to the severity of NASH.

Involvement of GSTP1 in low dose radiation-induced apoptosis in GM12878 cells.

BACKGROUND: Low-dose ionizing radiation-induced protection and damage are of great significance among radiation workers. We aimed to study the role of glutathione S-transferase Pi (GSTP1) in low-dose ionizing radiation damage and clarify the impact of ionizing radiation on the biological activities of cells. RESULTS: In this study, we collected peripheral blood samples from healthy adults and workers engaged in radiation and radiotherapy and detected the expression of GSTP1 by qPCR. We utilized γ-rays emitted from uranium tailings as a radiation source, with a dose rate of 14 µGy/h. GM12878 cells subjected to this radiation for 7, 14, 21, and 28 days received total doses of 2.4, 4.7, 7.1, and 9.4 mGy, respectively. Subsequent analyses, including flow cytometry, MTS, and other assays, were performed to assess the ionizing radiation's effects on cellular biological functions. In peripheral blood samples collected from healthy adults and radiologic technologist working in a hospital, we observed a decreased expression of GSTP1 mRNA in radiation personnel compared to the healthy controls. In cultured GM12878 cells exposed to low-dose ionizing radiation from uranium tailings, we noted significant changes in cell morphology, suppression of proliferation, delay in cell cycle progression, and increased apoptosis. These effects were partially reversed by overexpression of GSTP1. Moreover, low-dose ionizing radiation increased GSTP1 gene methylation and downregulated GSTP1 expression. Furthermore, low-dose ionizing radiation affected the expression of GSTP1-related signaling molecules. CONCLUSIONS: This study shows that low-dose ionizing radiation damages GM12878 cells and affects their proliferation, cell cycle progression, and apoptosis. In addition, GSTP1 plays a modulating role under low-dose ionizing radiation damage conditions. Low-dose ionizing radiation affects the expression of Nrf2, JNK, and other signaling molecules through GSTP1.

MDM2-p53 mediate a miR-181c-3p/LIF axis to regulate low dose-rate radiation-induced DNA damage in human B lymphocytes.

PURPOSE: Prolonged exposure to low dose-rate radiation (LDRR) is of growing concern to public health. Recent evidences indicates that LDRR causes deleterious health effects and is closely related to miRNAs. The aim of our study is to investigate the relationship between miRNAs and DNA damage caused by LDRR. MATERIALS AND METHODS: In this study, we irradiated C57BL/6J mice with 12.5µGy/h dose of γ ray emitted from uranium ore for 8 h a day for 120 days at a total dose of 12 mGy, and identified differentially expressed miRNAs from the mice long-term exposed to LDRR through isolating serum RNAs, constructing small RNA library, Illumina sequencing. To further investigate the role of differential miRNA under LDRR，we first built DNA damage model in Immortal B cells irradiated with 12.5µGy/h dose of γ ray for 28 days at a total dose of 9.4 mGy. Then, we chose the highly conserved miR-181c-3p among 12 miRNA and its mechanism in alleviating DNA damage induced by LDRR was studied by transfection, quantitative PCR, luciferase assay, and Western blot. RESULTS AND CONCLUSIONS: We have found that 12 differentially expressed miRNAs including miR-181c-3p in serum isolated from irradiated mice. Analysis of GO and KEGG indicated that target genes of theses 12 miRNA enriched in pathways related to membrane, protein binding and cancer. Long-term exposure to LDRR induced upregulation of gamma-H2A histone family member X (γ-H2AX) expression, a classical biomarker for DNA damage in B cells. miR-181c-3p inhibited Leukemia inhibitory factor (LIF) expression via combining its 3'UTR. LIF, MDM2, p53, and p-p53-s6 were upregulated after exposure to LDRR. In irradiated B cells, Transfection of miR-181c-3p reduced γ-H2AX expression and suppressed LIF and MDM2 protein levels, whereas p-p53-s6 expression was increased. As expected, the effect of LIF inhibition on irradiated B cells was similar to miR-181c-3p overexpression. Our results suggest that LDRR alters miRNA expression and induces DNA damage. Furthermore, miR-181c-3p can alleviate LDRR-induced DNA damage via the LIF/MDM2/p-p53-s6 pathway in human B lymphocytes. This could provide the basis for prevention and treatment of LDRR injury.

A Novel Sparse Array Configuration for Direction of Arrival Estimation with Increased Uniform Degrees of Freedom and Reduced Mutual Coupling.

Sparse arrays are widely employed in array signal processing due to their obvious advantages in array element distribution and uniform degrees of freedom (uDOFs). In this paper, a generalized augmented multi-subarray nested array (GAMSNA-I) and its variant, GAMSNA-II are proposed, with the objective of increasing uDOFs and reducing mutual coupling. Based on two subarrays of the prototype nested array (NA), GAMSNA-I is constructed by reconfiguring the dense uniform linear array (ULA) and forward-shifting the sparse ULA. GAMSNA-II is obtained by sparsifying the dense part of GAMSNA-I, ensuring constant uDOFs while further reducing mutual coupling. Subsequently, the closed-form expression for the uDOFs of GAMSNA-I with an arbitrary number of sensors is derived, and the proof is provided that the uDOFs of GAMSNA-II remain unchanged relative to that of GAMSNA-I. Compared to some existing array configurations, both GAMSNA-I and GAMSNA-II exhibit improved uDOFs, with GAMSNA-II achieving lower mutual coupling. Simulation results show the superior performance of the proposed GAMSNA-I and GAMSNA-II.

First-Principles Investigation of Phosphorus-Doped Graphitic Carbon Nitride as Anchoring Material for the Lithium-Sulfur Battery.

The utilization of lithium-sulfur battery is hindered by various challenges, including the "shuttle effect", limited sulfur utilization, and the sluggish conversion kinetics of lithium polysulfides (LiPSs). In the present work, a theoretical design for the viability of graphitic carbon nitride (g-C3N4) and phosphorus-doping graphitic carbon nitride substrates (P-g-C3N4) as promising host materials in a Li-S battery was conducted utilizing first-principles calculations. The PDOS shows that when the P atom is introduced, the 2p of the N atom is affected by the 2p orbital of the P atom, which increases the energy band of phosphorus-doping substrates. The energy bands of PC and Pi are 0.12 eV and 0.20 eV, respectively. When the lithium polysulfides are adsorbed on four substrates, the overall adsorption energy of PC is 48-77% higher than that of graphitic carbon nitride, in which the charge transfer of long-chain lithium polysulfides increase by more than 1.5-fold. It is found that there are powerful Li-N bonds between lithium polysulfides and P-g-C3N4 substrates. Compared with the graphitic carbon nitride monolayer, the anchoring effect of the LiPSs@P-g-C3N4 substrate is enhanced, which is beneficial for inhibiting the shuttle of high-order lithium polysulfides. Furthermore, the catalytic performance of the P-g-C3N4 substrate is assessed in terms of the S8 reduction pathway and the decomposition of Li2S; the decomposition energy barrier of the P-g-C3N4 substrate decrease by 10% to 18%. The calculated results show that P-g-C3N4 can promote the reduction of S8 molecules and Li-S bond cleavage within Li2S, thus improving the utilization of sulfur-active substances and the ability of rapid reaction kinetics. Therefore, the P-g-C3N4 substrates are a promising high-performance lithium-sulfur battery anchoring material.

Integrating key generation and distribution with the quantum noise stream cipher system without compromising the transmission performance.

We propose and experimentally demonstrate a secure quantum noise stream cipher transmission system that integrates key generation and distribution. At the stage of carrier phase recovery, the estimated phase noise is used to generate randomness keys without additional equipment. Based on direct sequence spread spectrum technology, we integrate the distributed keys with quantum noise stream cipher signals. The key distribution and encryption transmission can be completed simultaneously without occupying additional bandwidth or time slots. By changing the position of distributed keys in the encryption base, the BER performance of QAM/QNSC signals cannot be affected by the keys. Experimental results demonstrate that the 54.5 Mbps key distribution and 31 Gbps encryption transmission without OSNR penalty can be achieved simultaneously over a 120 km standard single-mode fiber.

Comprehensive bioinformatics analysis of the solute carrier family and preliminary exploration of SLC25A29 in lung adenocarcinoma.

According to the latest epidemiological investigation, lung adenocarcinoma (LUAD) is one of the most fatal cancer among both men and women. Despite continuous advancements in treatment approaches in recent years, the prognosis for LUAD remains relatively poor. Given the crucial role of the solute carrier (SLC) family in maintaining cellular energy metabolism stability, we conducted a comprehensive analysis of the association between SLC genes and LUAD prognosis. In the present study, we identified 71 genes among the SLC family members, of which 32 were downregulated and 39 were upregulated in LUAD samples. Based on these differentially expressed genes, a prognostic risk scoring model was established that was composed of five genes (SLC16A7, SLC16A4, SLC16A3, SLC12A8, and SLC25A15) and clinical characteristics; this model could effectively predict the survival and prognosis of patients in the cohort. Notably, SLC2A1, SLC25A29, and SLC27A4 were identified as key genes associated with survival and tumor stage. Further analysis revealed that SLC25A29 was underexpressed in LUAD tissue and regulated the phenotype of endothelial cells. Endothelial cell proliferation and migration increased and apoptosis decreased with a decrease in SLC25A29 expression. Investigation of the upstream regulatory mechanisms of SLC25A29 revealed that SLC25A29 expression gradually decreased as the lactate concentration increased. This phenomenon suggested that the expression of SLC25A29 may be related to lactylation modification. ChIP-qPCR experiments confirmed the critical regulatory role played by H3K14la and H3K18la modifications in the promoter region of SLC25A29. In conclusion, this study confirmed the role of SLC family genes in LUAD prognosis and revealed the role of SLC25A29 in regulating endothelial cell phenotypes. These study results provided important clues to further understand LUAD pathogenesis and develop appropriate therapeutic strategies.