[Simultaneous determination of 17 perfluoroalkyl substances in beef by EMR-Lipid dispersive solid-phase extraction and ultra performance liquid chromatography-tandem mass spectrometry].

The ability to accurately analyze perfluoroalkyl substance (PFAS) levels in beef is imperative in order to effectively assess food-safety risks and ensure consumer safety because PFASs are harmful and prevalent in beef. In this study, we developed a rapid and accurate method for the simultaneously determination of the 17 PFASs in beef using dispersive solid-phase extraction (d-SPE) and ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), and optimized the mobile phase system, extraction solvent, and d-SPE materials. Samples were finally extracted using 0.1% (v/v) formic acid in acetonitrile, cleaned using d-SPE with PSA, C18, GCB, and EMR-Lipid, separated using an Acquity Premier BEH C18 column (100 mm×2.1 mm, 1.7 µm) with 0.5 mmol/L ammonium fluoride aqueous solution and methanol as the mobile phases at a flow rate of 0.3 mL/min. Analytes were detected in negative ion switching mode (ESI-) with multiple reaction monitoring (MRM) scanning, and quantitatively analyzed using the internal standard method. The 17 PFASs exhibited linearity in the 0.2-20.0 µg/L range under the optimal experimental conditions, with correlation coefficients of 0.9915-0.9999. The method delivered limits of detection (LODs) of 0.003-0.007 µg/kg and limits of quantification (LOQs) of 0.01-0.02 µg/kg. The 17 PFASs exhibited recoveries of 71.1%-127.4% with RSDs of 0.6%-14.4% when spiked at three levels (0.05, 0.5, and 1.8 µg/kg). We optimized the mobile phase system, which revealed that, compared with 2.0, 5.0, and 10.0 mmol/L ammonium formate or ammonium acetate in aqueous methanol, 0.5 mmol/L ammonium fluoride in aqueous methanol exhibited higher sensitivities for all the 17 PFASs, with PFASs bearing long-chain carboxylic acids (C10-C18) showing 1-2 fold increases in sensitivity. PFASs do not dissociate in acidic environments, favoring their entry into the organic phase. Therefore, we investigated the effect of extractant acidity, which revealed that the 17 PFASs were better extracted using 0.1% (v/v) formic acid in acetonitrile. The beef matrix has a complex composition; consequently, d-SPE adsorbents were required to purify samples and reduce matrix effects. The purification effects of four adsorbents (PSA, C18, GCB, and EMR-Lipid) toward the 17 PFASs and the amount of EMR-Lipid used were investigated, which revealed that 100 mg PSA+80 mg C18+40 mg GCB+150 mg EMR-Lipid exhibited superior matrix-purification behavior. We also investigated the effects of various injection solutions and types of syringe filter, with pure methanol selected for reconstitution and high-speed supernatant centrifugation applied prior to injection. The developed method is simple, rapid, sensitive, and reproducible, and can be used to simultaneously, rapidly, and accurately determine various perfluoroalkyl compounds in beef.

Deciphering the role of CD47 in cancer immunotherapy.

BACKGROUND: Immunotherapy has emerged as a novel strategy for cancer treatment following surgery, radiotherapy, and chemotherapy. Immune checkpoint blockade and Chimeric antigen receptor (CAR)-T cell therapies have been successful in clinical trials. Cancer cells evade immune surveillance by hijacking inhibitory pathways via overexpression of checkpoint genes. The Cluster of Differentiation 47 (CD47) has emerged as a crucial checkpoint for cancer immunotherapy by working as a "don't eat me" signal and suppressing innate immune signaling. Furthermore, CD47 is highly expressed in many cancer types to protect cancer cells from phagocytosis via binding to SIRPα on phagocytes. Targeting CD47 by either interrupting the CD47-SIRPα axis or combing with other therapies has been demonstrated as an encouraging therapeutic strategy in cancer immunotherapy. Antibodies and small molecules that target CD47 have been explored in pre- and clinical trials. However, formidable challenges such as the anemia and palate aggregation cannot be avoided because of the wide presentation of CD47 on erythrocytes. AIM OF VIEW: This review summarizes the current knowledge on the regulation and function of CD47, and provides a new perspective for immunotherapy targeting CD47. It also highlights the clinical progress of targeting CD47 and discusses challenges and potential strategies. KEY SCIENTIFIC CONCEPTS OF REVIEW: This review provides a comprehensive understanding of targeting CD47 in cancer immunotherapy, it also augments the concept of combination immunotherapy strategies by employing both innate and adaptive immune responses.

CL429 enhances the renewal of intestinal stem cells by upregulating TLR2-YAP1.

Intestinal stem cells (ISCs) play a crucial role in maintaining the equilibrium and regenerative potential of intestinal tissue, thereby ensuring tissue homeostasis and promoting effective tissue regeneration following injury. It has been proven that targeting Toll-like receptors (TLRs) can help prevent radiation-induced damage to the intestine. In this study, we established an intestinal injury model using IR and evaluated the effects of CL429 on ISC regeneration both in vivo and in vitro. Following radiation exposure, mice treated with CL429 showed a significant increase in survival rates (100% survival in the treated group compared to 54.54% in the control group). CL429 also showed remarkable efficacy in inhibiting radiation-induced intestinal damage and promoting ISC proliferation and regeneration. In addition, CL429 protected intestinal organoids against IR-induced injury. Mechanistically, RNA sequencing and Western blot analysis revealed the activation of the Wnt and Hippo signaling pathways by CL429. Specifically, we observed a significant upregulation of YAP1, a key transcription factor in the Hippo pathway, upon CL429 stimulation. Furthermore, knockdown of YAP1 significantly attenuated the radioprotective effect of CL429 on intestinal organoids, indicating that CL429-mediated intestinal radioprotection is dependent on YAP1. In addition, we investigated the relationship between TLR2 and YAP1 using TLR2 knockout mice, and our results showed that TLR2 knockout abolished the activation of CL429 on YAP1. Taken together, our study provides evidence supporting the role of CL429 in promoting ISC regeneration through activation of TLR2-YAP1. And further investigation of the interaction between TLRs and other signaling pathways may enhance our understanding of ISC regeneration after injury.

Ultrasound-assisted nucleation and growth of hydroxyl-protected and ligand-free Cs3Cu2X5 nanocrystals with bright luminescence.

The commercial applications of lead halide perovskites are hindered by their negative environmental impact and inherent instability. Consequently, developing environmentally friendly copper-based perovskite materials is crucial for future solid-state lighting and display applications. In this study, an ultrafast high-power ultrasonic synthesis strategy was utilized to achieve uniform nucleation and growth of Cs3Cu2X5 (X = Cl, Br, I) nanocrystals (NCs) that possess remarkable luminescence properties, hydroxyl protection, and ligand-free characteristics. These Cs3Cu2X5 NCs exhibited a tunable spectral range spanning from 446 to 525 nm, accompanied by photoluminescence quantum yields (PLQYs) varying from 0.2% to 79.2%. The spectral attributes of the NCs were effectively controlled by modulating the halide type and composition. It is worth noting that density functional theory (DFT) calculations offer valuable insights into the synthesis of NCs and the selection of suitable alcohol solvents. Moreover, we successfully fabricated an efficient and stable white light-emitting diode (WLED) with a high luminous efficiency of 23 lm W-1 and CIE color coordinates of (0.3266, 0.3487). Our work provides a new strategy to synthesize Cs3Cu2X5 NCs and holds promise for their potential application in display and lighting devices.

Characteristics of early gastric tumors with different differentiation and predictors of long-term outcomes after endoscopic submucosal dissection.

BACKGROUND: Gastric cancer is a common malignant tumor of the digestive tract, and endoscopic submucosal dissection (ESD) is the preferred treatment for early-stage gastric cancer. The analysis of the epidemiological characteristics of gastric mucosal tumors with different differentiation degrees and the influencing factors of long-term ESD efficacy may have certain significance for revealing the development of gastric cancer and ESD. AIM: To analyze the features of gastric mucosal tumors at different differentiation levels, and to explore the prognostic factors of ESD. METHODS: We retrospectively studied 301 lesions in 285 patients at The Second Affiliated Hospital of Xi'an Jiaotong University from 2014 to 2021, according to the latest Japanese guidelines (sixth edition), and divided them into low-grade intraepithelial neoplasia (LGIN), high-grade intraepithelial neoplasia (HGIN), and differentiated and undifferentiated early carcinoma. They are followed up by endoscopy, chest and abdominal computed tomography at 3, 6 and 12 months after ESD. We compared clinicopathologic characteristics, ESD efficacy, and complications with different degrees of differentiation, and analyzed the related factors associated with ESD. RESULTS: HGIN and differentiated carcinoma patients were significantly older compared with LGIN patients (P < 0.001) and accounted for more 0-IIc (P < 0.001), atrophic gastritis was common (P < 0.001), and irregular microvascular patterns (IMVPs) and demarcation lines (DLs) were more obvious (P < 0.001). There was more infiltration in the undifferentiated carcinoma tissue (P < 0.001), more abnormal folds and poorer mucosal peristalsis (P < 0.001), and more obvious IMVPs, irregular microsurface patterns and DLs (P < 0.05) than in the LGIN and HGIN tissues. The disease-free survival rates at 2, 5, and 8 years after ESD were 95.0%, 90.1%, and 86.9%, respectively. Undifferentiated lesions (HR 5.066), white moss (HR 7.187), incomplete resection (HR 3.658), and multiple primary cancers (HR 2.462) were significantly associated with poor prognosis. CONCLUSION: Differentiations of gastric mucosal tumors have different epidemiological and endoscopic characteristics, which are closely related to the safety and efficacy of ESD.

[Develop the rural ecology in the New Era]. / 发展新时代的乡村生态学.

Rural ecology is a comprehensive field of study that takes the rural social-ecological-economic systems as the objective object and emphasizes spatial carrier governance. The development of rural ecology in the New Era embodies and implements comprehensively the core concepts of Xi Jinping Thought on Socialism with Chinese Cha-racteristics for a New Era, including harmonious coexistence between humans and nature, rural revitalization, green development, and the comprehensive construction of a socialist modernized nation. Under the goal of Chinese-style modernization, rural ecology exhibits characteristics distinct from the past, such as the integration of research objects, the intersectionality of basic theories, the computational feature of technical methods, and the orientation of exporting outcomes. To provide disciplinary support for modernization-oriented science to meet the new demands of country's rural development, effectively narrating the story of sustainable rural development in China and providing fundamental guarantees for the safety of rural systems, a number of issues such as paradigm innovation in research, improvement of data quality, and integration of comprehensive technologies, should be fully considered.

Exosome-mediated delivery of artificial circular RNAs for gene therapy of bladder cancer.

Bladder cancer (BCa) is one of the most common malignancies affecting men. Oncogenic transcription factors function as an important regulator in the progression of human cancer. In our study, we aimed to construct artificial circular non-coding RNAs (acircRNAs) consisting of three functional units that mimic the CRISPR-Cas system and elucidate its therapeutic role in bladder cancer. Additionally, the compare of the efficiency in regulating gene expression between acircRNA and CRISPR-dCas systems was performed. We connected the cDNA sequences of TFs aptamer and constructed a circRNA. To demonstrate the platform's practicality, ß-catenin and NF-κB were chosen as functional targets, while T24 and 5637 cell lines served as test models. Real-time Quantitative PCR (qPCR), double luciferase assay and related phenotype assay were used to detect the expression of related genes and the therapeutic effect. To elucidate the functionality of acircRNAs, luciferase vectors capable of detecting ß-catenin and NF-κB expression were employed to assess the inhibitory impact of acircRNA on ß-catenin and NF-κB. Consequently, the optimal combination involving acircRNA-3 was determined. Next, qPCR assay was employed to assess the relative expression levels of target downstream genes following acircRNA treatment. The expression of c-myc and cyclin D1 were used to determine the function of ß-catenin, while Bcl-XL and TRAF1 were used to determine that of NF-κB. The acircRNAs inhibited the ß-catenin and NF-κB related signaling in BCa cells specifically. CD63-HuR fusion protein was used to loading acircRNA into exosomes. The results showed that acircRNA could inhibit the activity of the target transcription factors, and the inhibitory effect was better than that of CRIPSR-dCas9-KRAB. Furthermore, functional experiments demonstrated that the transfection of acircRNA in bladder cells resulted in decreased proliferation, enhanced apoptosis, and suppressed migration. In conclusion, our synthetic gene device exhibited anti-tumor regulatory capabilities and showed greater efficiency in tumor suppression compared to the CRISPR-dCas9-KRAB system. Therefore, our device provides a new strategy for cancer treatment and could be a useful strategy for cancer cells.

Scleroglucan protects the intestine from irradiation-induced injury by targeting the IL-17 signaling pathway.

BACKGROUND: Intestinal tissue is extremely sensitive to ionizing radiation (IR), which is easy to cause intestinal radiation sickness, and the mortality rate is very high after exposure. Recent studies have found that intestinal immune cells and intestinal stem cells (ISCs) may play a key role in IR-induced intestinal injury. METHODS: C57BL6 mice matched for age, sex and weight were randomly grouped and intraperitoneal injected with PBS, Scleroglucan (125.0 mg/kg) or Anti-mouse IL-17A -InVivo (10 mg/kg), the number of mice in each group was n ≥ 3.Survival time, body weight, pathology, organoids and immune cell markers of the mice after IR (10.0 Gy) were compared, and the mechanism of action in intestinal tissues was verified by transcriptome sequencing. RESULTS: Scleroglucan has significant radiation protective effects on the intestine, including improving the survival rate of irradiated mice, inhibiting the radiation damage of intestinal tissue, and promoting the proliferation and differentiation of intestinal stem cells (ISCs). The results of RNA sequencing suggested that Scleroglucan could significantly activate the immune system and up-regulate the IL-17 and NF-κB signaling pathways. Flow cytometry showed that Scleroglucan could significantly up-regulate the number of Th17 cells and the level of IL-17A in the gut. IL-17A provides radiation protection. After intraperitoneal injection of Scleroglucan and Anti-mouse IL-17A -InVivo, mice can significantly reverse the radiation protection effect of Scleroglucan, down-regulate the molecular markers of intestinal stem cells and the associated markers of DC, Th1 and Th17 cells, and up-regulate the associated markers of Treg and Macrophage cells. CONCLUSION: Scleroglucan may promote the proliferation and regeneration of ISCs by regulating the activation of intestinal immune function mediated by IL-17 signaling pathway and play a protective role in IR-induced injury.

7-Dehydrocholesterol dictates ferroptosis sensitivity.

Ferroptosis, a form of regulated cell death that is driven by iron-dependent phospholipid peroxidation, has been implicated in multiple diseases, including cancer1-3, degenerative disorders4 and organ ischaemia-reperfusion injury (IRI)5,6. Here, using genome-wide CRISPR-Cas9 screening, we identified that the enzymes involved in distal cholesterol biosynthesis have pivotal yet opposing roles in regulating ferroptosis through dictating the level of 7-dehydrocholesterol (7-DHC)-an intermediate metabolite of distal cholesterol biosynthesis that is synthesized by sterol C5-desaturase (SC5D) and metabolized by 7-DHC reductase (DHCR7) for cholesterol synthesis. We found that the pathway components, including MSMO1, CYP51A1, EBP and SC5D, function as potential suppressors of ferroptosis, whereas DHCR7 functions as a pro-ferroptotic gene. Mechanistically, 7-DHC dictates ferroptosis surveillance by using the conjugated diene to exert its anti-phospholipid autoxidation function and shields plasma and mitochondria membranes from phospholipid autoxidation. Importantly, blocking the biosynthesis of endogenous 7-DHC by pharmacological targeting of EBP induces ferroptosis and inhibits tumour growth, whereas increasing the 7-DHC level by inhibiting DHCR7 effectively promotes cancer metastasis and attenuates the progression of kidney IRI, supporting a critical function of this axis in vivo. In conclusion, our data reveal a role of 7-DHC as a natural anti-ferroptotic metabolite and suggest that pharmacological manipulation of 7-DHC levels is a promising therapeutic strategy for cancer and IRI.

Emerging mechanisms and implications of cGAS-STING signaling in cancer immunotherapy strategies.

The intricate interplay between the human immune system and cancer development underscores the central role of immunotherapy in cancer treatment. Within this landscape, the innate immune system, a critical sentinel protecting against tumor incursion, is a key player. The cyclic GMP-AMP synthase (cGAS) and stimulator of interferon genes (STING) pathway has been found to be a linchpin of innate immunity: activation of this signaling pathway orchestrates the production of type I interferon (IFN-α/ß), thus fostering the maturation, differentiation, and mobilization of immune effectors in the tumor microenvironment. Furthermore, STING activation facilitates the release and presentation of tumor antigens, and therefore is an attractive target for cancer immunotherapy. Current strategies to activate the STING pathway, including use of pharmacological agonists, have made substantial advancements, particularly when combined with immune checkpoint inhibitors. These approaches have shown promise in preclinical and clinical settings, by enhancing patient survival rates. This review describes the evolving understanding of the cGAS-STING pathway's involvement in tumor biology and therapy. Moreover, this review explores classical and non-classical STING agonists, providing insights into their mechanisms of action and potential for optimizing immunotherapy strategies. Despite challenges and complexities, the cGAS-STING pathway, a promising avenue for enhancing cancer treatment efficacy, has the potential to revolutionize patient outcomes.

A Lysosome-Targeted Magnetic Nanotorquer Mechanically Triggers Ferroptosis for Breast Cancer Treatment.

Targeting ferroptosis has attracted exponential attention to eradicate cancer cells with high iron-dependent growth. Increasing the level of intracellular labile iron pool via small molecules and iron-containing nanomaterials is an effective approach to induce ferroptosis but often faces insufficient efficacy due to the fast drug metabolism and toxicity issues on normal tissues. Therefore, developing a long-acting and selective approach to regulate ferroptosis is highly demanded in cancer treatment. Herein, a lysosome-targeted magnetic nanotorquer (T7-MNT) is proposed as the mechanical tool to dynamically induce the endogenous Fe2+ pool outbreak for ferroptosis of breast cancer. T7-MNTs target lysosomes via the transferrin receptor-mediated endocytosis in breast cancer cells. Under the programmed rotating magnetic field, T7-MNTs generate torques to trigger endogenous Fe2+ release by disrupting the lysosomal membrane. This magneto-mechanical manipulation can induce oxidative damage and antioxidant defense imbalance to boost frequency- and time-dependent lipid peroxidization. Importantly, in vivo studies show that T7-MNTs can efficiently trigger ferroptosis under the magnetic field and play as a long-acting physical inducer to boost ferrotherapy efficacy in combination with RSL3. It is anticipated that this dynamic targeted strategy can be coupled with current ferroptosis inducers to achieve enhanced efficacy and inspire the design of mechanical-based ferroptosis inducers for cancer treatment.

A meta-analysis of adverse effects of retinopathy of prematurity on neurodevelopment in preterm infants.

BACKGROUND: Retinopathy of prematurity (ROP) increases with the survival of late preterm infants, but its relationship with neurodevelopmental outcomes in preterm infants remains controversial. To investigate the relationship between ROP and its severity and adverse neurodevelopmental outcomes in preterm infants. METHODS: We conducted a meta-analysis. All relevant literature before November 2022 were retrieved from PubMed, Embase, Cochrane Library Web of Science, CNKI, CBM, Wan fang Data, and VIP Database. According to the inclusion criteria and exclusion criteria, eligible literature were included to conduct clinical trial quality assessment, and the Newcastle-Ottawa scale was used to evaluate the quality of evidence. Meta-analysis was performed using RevMan5.3. Data extraction, quality assessment, and meta-analysis were performed independently by 2 people. Mean difference or standardized mean difference of motor, language and cognitive scores (Bayley III or Bayley II) were used as effect sizes for continuous data analysis, all of which were represented by 95% CI. For heterogeneity (I2 ≥ 50% or P < .10), a random effects model was used, otherwise a fixed effects model was used. RESULTS: A total of 6 literature were included. The results of the ROP group for motor (comprehensive motor, proportional motor, and fine motor), language and cognitive scores were -5.57 (95%CI, -1.43 to 0.04), -0.95 (95%CI, 1.4-0.50), -1.34 (95% CI, 1.77-0.92), -1.75 (95% CI, 2.26-1.24) and -5.56 (95% CI, 9.56-1.57). Additionally, the results of severe ROP group for motor (comprehensive motor, proportional motor, fine motor), language and cognitive scores were -8.32 (95%CI, -8.91 to 7.74), -1.10 (95%CI, -1.83 to -0.36), -1.08 (95%CI, -1.75 to -0.41), -7.03 (95%CI, -7.71 to 6.35), and -7.96 (95%CI, -8.5 to -7.42). CONCLUSIONS: The Bayley Scale scores of the ROP group were lower than those of the not ROP group, and the scores of the severe ROP were significantly lower than those of the not severe ROP group. These findings suggest that ROP can indeed delay motor, language and cognitive, especially in severe cases.

IL-17 in osteoarthritis: A narrative review.

Osteoarthritis (OA) is a painful joint disease that is common among the middle-aged and elderly populations, with an increasing prevalence. Therapeutic options for OA are limited, and the pathogenic mechanism of OA remains unclear. The roles of cytokines and signaling pathways in the development of OA is a current research hot spot. Interleukin (IL)-17 is a pleiotropic inflammatory cytokine produced mainly by T helper 17 cells that has established roles in host defense, tissue repair, lymphoid tissue metabolism, tumor progression, and pathological processes of immune diseases, and studies in recent years have identified an important role for IL-17 in the progression of OA. This narrative review focuses on the mechanisms by which IL-17 contributes to articular cartilage degeneration and synovial inflammation in OA and discusses how IL-17 and the IL-17 signaling pathway affect the pathological process of OA. Additionally, therapeutic targets that have been proposed in recent years based on IL-17 and its pathway in OA are summarized as well as recent advances in the study of IL-17 pathway inhibitors and the potential challenges of their use for OA treatment.

Ultrasound-assisted continuous crystallization of metastable polymorphic pharmaceutical in a slug-flow tubular crystallizer.

Metastable polymorphic pharmaceuticals have garnered significant attention in recent years due to their enhanced physicochemical properties, including solubility, bioavailability, and intellectual property considerations. However, the manufacturing of metastable form pharmaceuticals remains a formidable challenge. The stable preparation of metastable carvedilol (CVD) form Ⅱ crystals during CVD production is elusive, leading to substantial inconsistencies in product quality and regulatory compliance. In this study, we successfully prepared metastable CVD Form Ⅱ crystals using a continuous tubular crystallizer. Our findings demonstrate that the tubular crystallizer exhibits high efficiency and robustness for generating metastable crystal Form Ⅱ. We optimized the crystallization process by incorporating air bubble segments and employing ultrasonic irradiation strategies to overcome blockages and wall sticking issues encountered during operation. Ultimately, we developed an ultrasound-assisted continuous slug-flow tubular crystallization method and evaluated its performance. The results indicate that the CVD crystals produced through this process are resilient, sustainable, and uninterrupted products with promising potential for producing metastable polymorphic pharmaceuticals while effectively addressing encrustation problems associated with continuous tubular crystallization.

Stability performance analysis of Fe based MOFs for peroxydisulfates activation to effectively degrade ciprofloxacin.

Fe-based metal-organic frameworks (MOFs) show high activity toward the activation of peroxodisulfate (PDS) for the removal of organic micropollutants (OMPs) in wastewater treatment. However, there is a phenomenon of Fe ion dissolution in the Fe-based MOFs' active PDS system, and the reasons and influencing factors that cause Fe ion dissolution are poorly understood. In this study, we synthesized four types of Fe-based MOFs and confirmed their crystal structure through characterization. All types of Fe-based MOFs were found to activate PDS and form sulfate radicals (SO4 -), which effectively remove OMPs in wastewater. During the process of Fe-based MOFs activating PDS for CIP removal, activated species, oxidant reagent, and pH negatively impact the stability performance of the MOFs' structure. The coordination bond between Fe atom and O atom can be attacked by water molecules, free radicals, and H+, causing damage to the crystal structure of MOFs. Additionally, Fe (II)-MOFs exhibit the best stability performance, due to the enhanced bond energy of the coordination bond in MOFs by the F ligands. This study summarizes the influencing factors of Fe-based MOFs' damage during PDS activation processes, providing new insights for the future development of Fe-based MOFs.

Methionine restriction promotes cGAS activation and chromatin untethering through demethylation to enhance antitumor immunity.

Cyclic GMP-AMP synthase (cGAS) is the major sensor for cytosolic DNA and activates type I interferon signaling and plays an essential role in antitumor immunity. However, it remains unclear whether the cGAS-mediated antitumor activity is affected by nutrient status. Here, our study reports that methionine deprivation enhances cGAS activity by blocking its methylation, which is catalyzed by methyltransferase SUV39H1. We further show that methylation enhances the chromatin sequestration of cGAS in a UHRF1-dependent manner. Blocking cGAS methylation enhances cGAS-mediated antitumor immunity and suppresses colorectal tumorigenesis. Clinically, cGAS methylation in human cancers correlates with poor prognosis. Thus, our results indicate that nutrient stress promotes cGAS activation via reversible methylation, and suggest a potential therapeutic strategy for targeting cGAS methylation in cancer treatment.

Spatial effects of the agricultural ecosystem services based on environmental kuznets curve in Mengyin county, China.

Worldwide most agroecosystems effort to increase production and yields and leads to damages of a series of non-provisioning ecosystem services (ESs). To fill in the knowledge gaps pertaining to the understanding of complex relationship between agricultural harvests and other ESs, therefore this study aims to estimate the existence of Environmental Kuznets Curve (EKC) for agricultural ESs by incorporating the spatial factors. Based on the test of the spatial autocorrelation of agricultural ESs, the estimation results of spatial model are compared with general regression to explain the spatial effect of agricultural ESs. The results show that (1) contrary to expectation, the curve of the nonlinear relationship between agricultural ESs and annual household income is an inverted U-shape, and not an upright U-shape; (2) compared to non-spatial model, the turning point of the inverted U-shaped curve for agricultural ESs under the direct effect would happen earlier and happen later under the indirect effect; (3) years of formal education, vegetation coverage of field margin and cultivated land area have significantly impact on local agricultural ESs, and local perennial crops has significantly impact on agricultural ESs of neighboring villages. Results of this study have a promising application prospect to promote sustainable development of agriculture.

Emerging phagocytosis checkpoints in cancer immunotherapy.

Cancer immunotherapy, mainly including immune checkpoints-targeted therapy and the adoptive transfer of engineered immune cells, has revolutionized the oncology landscape as it utilizes patients' own immune systems in combating the cancer cells. Cancer cells escape immune surveillance by hijacking the corresponding inhibitory pathways via overexpressing checkpoint genes. Phagocytosis checkpoints, such as CD47, CD24, MHC-I, PD-L1, STC-1 and GD2, have emerged as essential checkpoints for cancer immunotherapy by functioning as "don't eat me" signals or interacting with "eat me" signals to suppress immune responses. Phagocytosis checkpoints link innate immunity and adaptive immunity in cancer immunotherapy. Genetic ablation of these phagocytosis checkpoints, as well as blockade of their signaling pathways, robustly augments phagocytosis and reduces tumor size. Among all phagocytosis checkpoints, CD47 is the most thoroughly studied and has emerged as a rising star among targets for cancer treatment. CD47-targeting antibodies and inhibitors have been investigated in various preclinical and clinical trials. However, anemia and thrombocytopenia appear to be formidable challenges since CD47 is ubiquitously expressed on erythrocytes. Here, we review the reported phagocytosis checkpoints by discussing their mechanisms and functions in cancer immunotherapy, highlight clinical progress in targeting these checkpoints and discuss challenges and potential solutions to smooth the way for combination immunotherapeutic strategies that involve both innate and adaptive immune responses.

Characterization of a Plant Growth-Promoting Endohyphal Bacillus subtilis in Fusarium acuminatum from Spiranthes sinensis.

Successful seed germination and seedling growth in orchids require an association with mycorrhizal fungi. An endophytic Fusarium fungal strain YZU 172038 exhibiting plant growth-promoting (PGP) ability was isolated from the roots of Spiranthes sinensis (Orchidaceae). The harboring endohyphal bacteria were detected in the hypha by SYTO-9 fluorescent nucleic acid staining, fluorescence in situ hybridization (FISH), and PCR amplification of the 16S rDNA gene's region. Consequently, one endohyphal bacterium (EHB) - a strain YZSR384 was isolated and identified as Bacillus subtilis based on morphology, phylogenetic analysis, and genomic information. The results indicated that the strain YZSR384 could significantly promote the growth of rice roots and shoots similar to its host fungus. Its indole acetic acid (IAA) production reached a maximum of 23.361 µg/ml on the sixth day after inoculation. The genome annotation revealed several genes involved in PGP traits, including the clusters of genes encoding the IAA (trpABCDEFS), the siderophores (entABCE), and the dissolving phosphate (pstABCS and phoABDHPR). As an EHB, B. subtilis was first isolated from endophytic Fusarium acuminatum from S. sinensis.