Photodynamic Therapy Synergizes CD47 Blockade Strategy for Enhanced Antitumor Therapy.

The antitumor strategies based on innate immunity activation have become favored by researchers in recent years. In particular, strategies targeting antiphagocytic signaling blockade to enhance phagocytosis have been widely reported. For example, the addition of prophagocytic signals such as calreticulin could make the strategy significantly more effective. In this study, an antitumor strategy that combines photodynamic therapy (PDT) with CD47 blockade has been reported. This approach promotes the maturation of dendritic cells and the presentation of tumor antigens by PDT-mediated tumor immunogenic cell death, as well as the enhancement of cytotoxic T lymphocyte infiltration in tumor areas and the phagocytic activity of phagocytes. Furthermore, the downregulation and blockage of CD47 protein could further promote phagocytic activity, strengthen the innate immune system, and ultimately elevate the antitumor efficacy and inhibit tumor metastasis.

Efficacy, immunogenicity, and safety of a monovalent mRNA vaccine, ABO1020, in adults: A randomized, double-blind, placebo-controlled, phase 3 trial.

BACKGROUND: ABO1020 is a monovalent COVID-19 mRNA vaccine. Results from a phase 1 trial showed ABO1020 was safe and well tolerated, and phase 3 trials to evaluate the efficacy, immunogenicity, and safety of ABO1020 in healthy adults are urgently needed. METHODS: We conducted a multinational, randomized, placebo-controlled, double-blind, phase 3 trial among healthy adults (ClinicalTrials.gov: NCT05636319). Participants were randomly assigned (1:1) to receive either 2 doses of ABO1020 (15 µg per dose) or placebo, administered 28 days apart. The primary endpoint was the vaccine efficacy in preventing symptomatic COVID-19 cases that occurred at least 14 days post-full vaccination. The second endpoint included the neutralizing antibody titers against Omicron BA.5 and XBB and safety assessments. FINDINGS: A total of 14,138 participants were randomly assigned to receive either vaccine or placebo (7,069 participants in each group). A total of 366 symptomatic COVID-19 cases were confirmed 14 days after the second dose among 93 participants in the ABO1020 group and 273 participants in the placebo group, yielding a vaccine efficacy of 66.18% (95% confidence interval: 57.21-73.27, p < 0.0001). A single dose or two doses of ABO1020 elicited potent neutralizing antibodies against both BA.5 and XBB.1.5. The safety profile of ABO1020 was characterized by transient, mild-to-moderate fever, pain at the injection site, and headache. CONCLUSION: ABO1020 was well tolerated and conferred 66.18% protection against symptomatic COVID-19 in adults. FUNDING: National Key Research and Development Project of China, Innovation Fund for Medical Sciences from the CAMS, National Natural Science Foundation of China.

"Top-down" overexpression optimization of Butelase 1 in Escherichia coli and its application in anti-tumor peptides.

Butelase 1, the fastest known Asn/Asp-specific peptide ligase capable of catalyzing peptide ligation and cyclization, holds promising application prospects in the fields of food and biology. However, limited research exists on its recombinant expression and potential applications in peptide drugs. In this study, the activity of recombinantly-produced butelase 1 was enhanced by co-expressing it with a molecular chaperone in the SHuffle T7 strain. By introducing single or multiple synonymous rare codons at the beginning of the coding regions of beta-strand or alpha-helix, in combination with ribosomal binding site engineering, the activity of butelase 1 could be further improved. Consequently, the butelase 1 with a specific activity of 386.93 U/mg and a catalytic efficiency of 11,048 M-1 s-1 was successfully prepared in E. coli, resulting in a total activity of 8183.54 U/L and a yield of about 100 mg/L. This optimized butelase 1 was then used to efficiently cyclize the redesigned anti-cancer peptide lunasin, leading to enhanced bioavailability and anti-cancer effects. Overall, this study not only provided valuable biotechnology strategies for improving the recombinant expression of butelase 1 but also demonstrated a successful application for enhancing the biological efficacy of anti-cancer peptides.

Exserolide J ameliorates lipid accumulation in vitro by regulating liver X receptor alpha and peroxisome proliferator-activated receptor alpha proteins.

Exserolides are isocoumarin derivatives containing lactone moiety. Recently, some isocoumarins have been demonstrated to ameliorate hyperlipidemia, a major factor for inducing cardiovascular diseases. However, the effects and mechanisms of action of exserolides on hyperlipidemia are not known. The aim of this study is to investigate whether the marine fungus Setosphaeria sp.-derived exserolides (compounds I, J, E, and F) exert lipid-lowering effects via improving reverse cholesterol transport (RCT) in vitro. RAW264.7 macrophages and HepG2 cells were used to establish lipid-laden models, and the levels of intracellular lipids and RCT-related proteins were determined by assay kits and Western blotting, respectively. We observed that exserolides (at a 5 µM concentration) significantly decreased intracellular cholesterol and triglyceride levels in oxidized low-density lipoprotein-laden RAW264.7 cells and markedly improved [3H]-cholesterol efflux. Among the four tested compounds, exserolide J increased the protein levels of ATP-binding cassette transporter A1, peroxisome proliferator-activated receptor α (PPARα), and liver X receptor α (LXRα). Furthermore, treatment with exserolides significantly decreased oleic acid-laden lipid accumulation in HepG2 hepatocytes. Mechanistically, exserolides enhance PPARα protein levels; furthermore, compound J increases cholesterol 7 alpha-hydroxylase A1 and LXRα protein levels. Molecular docking revealed that exserolides, particularly compound J, can interact with PPARα and LXRα proteins. These data suggest that the terminal carboxyl group of compound J plays a key role in lowering lipid levels by stimulating LXRα and PPARα proteins. In conclusion, compound J exhibits powerful lipid-lowering effects in vitro. However, its hypolipidemic effects in vivo should be investigated in the future.

Secondary diabetes due to different etiologies: Four case reports.

BACKGROUND: As research on diabetes continues to advance, more complex classifications of this disease have emerged, revealing the existence of special types of diabetes, and many of these patients are prone to misdiagnosis and underdiagnosis, leading to treatment delays and increased health care costs. The purpose of this study was to identify four causes of secondary diabetes. CASE SUMMARY: Secondary diabetes can be caused by various factors, some of which are often overlooked. These factors include genetic defects, autoimmune disorders, and diabetes induced by tumours. This paper describes four types of secondary diabetes caused by Williams-Beuren syndrome, Prader-Willi syndrome, pituitary adenoma, and IgG4-related diseases. These cases deviate significantly from the typical progression of the disease due to their low incidence and rarity, often leading to their neglect in clinical practice. In comparison to regular diabetes patients, the four individuals described here exhibited distinct characteristics. Standard hypoglycaemic treatments failed to effectively control the disease. Subsequently, a series of examinations and follow-up history confirmed the diagnosis and underlying cause of diabetes. Upon addressing the primary condition, such as excising a pituitary adenoma, providing glucocorticoid supplementation, and implementing symptomatic treatments, all patients experienced a considerable decrease in blood glucose levels, which were subsequently maintained within a stable range. Furthermore, other accompanying symptoms improved. CONCLUSION: Rare diseases causing secondary diabetes are often not considered in the diagnosis of diabetes. Therefore, it is crucial to conduct genetic tests, antibody detection and other appropriate diagnostic measures when necessary to facilitate early diagnosis and intervention through proactive and efficient management of the underlying condition, ultimately improving patient outcomes.

Conversion therapy of a giant hepatocellular carcinoma with portal vein thrombus and inferior vena cava thrombus: A case report and review of literature.

BACKGROUND: The prognosis of hepatocellular carcinoma (HCC) combined with portal and hepatic vein cancerous thrombosis is poor, for unresectable patients the combination of targeted therapy and immune therapy was the first-line recommended treatment for advanced HCC, with a median survival time of only about 2.7-6 months. In this case report, we present the case of a patient with portal and hepatic vein cancerous thrombosis who achieved pathologic complete response after conversion therapy. CASE SUMMARY: In our center, a patient with giant HCC combined with portal vein tumor thrombus and hepatic vein tumor thrombus was treated with transcatheter arterial chemoembolization (TACE), radiotherapy, targeted therapy and immunotherapy, and was continuously given icaritin soft capsules for oral regulation. After 7 months of conversion therapy, the patient's tumor shrank and the tumor thrombus subsided significantly. The pathology of surgical resection was in complete remission, and there was no progression in the postoperative follow-up for 7 months, which provided a basis for the future strategy of combined conversion therapy. CONCLUSION: In this case, atezolizumab, bevacizumab, icaritin soft capsules combined with radiotherapy and TACE had a good effect. For patients with hepatocellular carcinoma combined with hepatic vein/inferior vena cava tumor thrombus, adopting a high-intensity, multimodal proactive strategy under the guidance of multidisciplinary team (MDT) is an important attempt to break through the current treatment dilemma.

[Effects of Biochar-loaded Ammonia Nitrogen on Soil Carbon Emissions, Enzyme Activity, and Microbial Communities].

The form of soil nitrogen input significantly affects soil CO2 emission. As a new form of nitrogen input, biochar-loaded ammonia nitrogen not only reduces the input of chemical nitrogen fertilizer in farmland but also reduces the cost of environmental treatment. It is of great significance to promote the zero growth of national chemical fertilizer, the prevention and control of farmland non-point source pollution, and the realization of the national goal of "carbon peak" and "carbon neutralization." Through an indoor culture experiment, the effects of different nitrogen input forms on soil carbon emission, enzyme activity, and microbial community were studied through four treatments:no fertilization (CK), single application of chemical nitrogen fertilizer (CF), biochar combined application of chemical nitrogen fertilizer (BF), and biochar-loaded ammonia nitrogen (BN). The results showed that compared with that in CF, BF significantly increased cumulative carbon emissions (66.24 %), whereas BN had no significant difference. It is worth noting that the cumulative carbon emissions were significantly reduced by 35.28 % compared with that in BF and BN. Compared with those in CF and BF, the activities of ß-glucosidase, peroxidase, and polyphenol oxidase treated with BN significantly increased by 20.25 % and 5.20 %, respectively. Compared with that in CF, the BF treatment increased microbial community richness and community diversity, whereas the BN treatment decreased microbial community richness. Compared with that in BF, the relative abundance of Proteobacteria decreased by 11.16 %, and the relative abundance of Actinobacteria and Bacteroidota increased by 8.12 % and 5.83 %, respectively, in which xylosidase activity was the most important soil factor affecting microbial community structure. The relative abundance of Chloroflexi was significantly correlated with cellobiose hydrolase activity, and the relative abundance of Gemmatimonadetes was significantly correlated with ß-glucosidase activity. There was a very significant correlation between the relative abundance of Proteobacteria and cumulative carbon emissions. To summarize, compared with those under biochar combined with chemical nitrogen fertilizer, biochar loaded with ammonia nitrogen significantly reduced cumulative carbon emissions, and its emission reduction effect was better. The results of this study will be beneficial to the landing of the national "double carbon strategy," the healthy development of the biological natural gas industry, the construction of the national green cultivation circular agriculture system, and the realization of the national zero growth strategy of chemical fertilizer.

Taxonomy and phylogeny of three species in Perichaena sensu lato (Myxomycetes = Myxogastria) from China.

After Gulielmina was erected and Ophiotheca was resurrected based on some species originally included in Perichaena (Trichiaceae, Trichiales, Myxomyxetes), some specimens from the Herbarium of Fungi of Nanjing Normal University previously identified as Perichaena species were reexamined from morphological and two-gene (nuclear 18S rDNA and elongation factor-1 alpha) phylogenetic perspectives. In this study, two new myxomycete species, Gulielmina subreticulospora and Ophiotheca dictyospora, are described. Gulielmina subreticulospora shows the following character combination: branched plasmodiocarps, single peridium with circular protrusions in the inner surface, capillitium (2.4-)2.8-3.0(-3.4) µm in diameter, spores (7.4-)8.0-8.5(-9.0) µm in diameter and sub-reticulated. Ophiotheca dictyospora shows the following character combination: sessile sporocarps to short plasmodiocarps, single peridium with a densely irregular network and protrusions in the inner surface, capillitium (2.7-)3.5-5.0(-7.1) µm in diameter, uneven, decorated with spines of uneven size, spores (7.7-)8.2-8.6(-9.4) µm in diameter including obviously complete cristate reticulation with serrated edges, with deep and clear grids. Both new taxa were compared with related species and their genetic isolation was statistically tested. Moreover, a comprehensive morphological description and a detailed figure plate are provided for Perichaena verrucifera, and its phylogenetic position is determined.

Temporal turnover of viral biodiversity and functional potential in intertidal wetlands.

As the central members of the microbiome networks, viruses regulate the composition of microbial communities and drive the nutrient cycles of ecosystems by lysing host cells. Therefore, uncovering the dynamic patterns and the underlying ecological mechanisms mediating the tiniest viral communities across space and through time in natural ecosystems is of crucial importance for better understanding the complex microbial world. Here, the temporal dynamics of intertidal viral communities were investigated via a time-series sampling effort. A total of 1911 viral operational taxonomic units were recovered from 36 bimonthly collected shotgun metagenomes. Functionally important auxiliary metabolic genes involved in carbohydrate, sulfur, and phosphorus metabolism were detected, some of which (e.g., cysH gene) were stably present within viral genomes over time. Over the sampling period, strong and comparable temporal turnovers were observed for intertidal viromes and their host microbes. Winter was determined as the pivotal point for the shifts in viral diversity patterns. Notably, the viral micro-diversity covaried with the macro-diversity, following similar temporal patterns. The relative abundances of viral taxa also covaried with their host prokaryotes. Meanwhile, the virus-host relationships at the whole community level were relatively stable. Further statistical analyses demonstrated that the dynamic patterns of viral communities were highly deterministic, for which temperature was the major driver. This study provided valuable mechanistic insights into the temporal turnover of viral communities in complex ecosystems such as intertidal wetlands.

YTHDF2 regulates MSS51 expression contributing to mitochondria dysfunction of granulosa cells in polycystic ovarian syndrome patients.

RESEARCH QUESTION: Granulosa cells (GCs) dysfunction plays a crucial role in the pathogenesis of polycystic ovary syndrome (PCOS). It is reported that YTH domain-containing family protein 2 (YTHDF2) is upregulated in mural GCs of PCOS patients. What effect does the differential expression of YTHDF2 have in PCOS patients? DESIGN: Mural GCs and cumulus GCs from 15 patients with PCOS and 15 ovulatory controls and 4 cases of pathological sections in each group were collected. Real-time PCR, Western Blot, immunohistochemistry, and immunofluorescence experiments were conducted to detect gene and protein expression. RNA immunoprecipitation assay was performed to evaluate the binding relationship between YTHDF2 and MSS51. Mitochondrial morphology, cellular ATP and ROS levels and glycolysis-related gene expression were detected after YTHDF2 overexpression or MSS51 inhibition. RESULTS: In the present study, we found that YTHDF2 was upregulated in GCs of PCOS patients while MSS51 was downregulated. YTHDF2 protein can bind to MSS51 mRNA and affect MSS51 expression. The reduction of MSS51 expression or the increase in YTHDF2 expression can lead to mitochondrial damage, reduced ATP levels, increased ROS levels and reduced expression of LDHA, PFKP and PKM. CONCLUSIONS: YTHDF2 may regulate the expression of MSS51, affecting the structure and function of mitochondria in GCs and interfering with cellular glycolysis, which may disturb the normal biological processes of GCs and follicle development in PCOS patients.

Merging Quinoxalin-2(1H)-ones Excitation with Cobaloxime Catalysis: C3 Alkylation of Quinoxalin-2(1H)-ones with Unactivated Alkyl Iodides and Carboxylic Acids under Light.

Reported herein is a practical, economical, and efficient construction of 3-alkylated quinoxalin-2(1H)-ones with alkyl carboxylic acids and alkyl iodides by quinoxalin-2(1H)-one excitation and cobaloxime catalysis. Primary, secondary, and tertiary alkyl iodides and carboxylic acids all could be efficiently transferred into target products with excellent functional group tolerance. Mechanism studies reveal that the quinoxalin-2(1H)-one derivatives could be directly excited and yield alkyl carbon radicals from alkyl carboxylic acids and alkyl iodides with the aid of the cobaloxime complex.

Bioinformatic Analysis of the Significance of the KIR2DL4 Gene in Recurrent Implantation Failure.

Related studies have pointed out that Killer immunoglobulin-like receptor 2DL4 (KIR2DL4) was associated with vascular remodeling in early pregnancy, and it might play an important role in immunity. In this study, recurrent implantation failure (RIF)-related GSE58144 dataset was extracted from the Gene Expression Omnibus (GEO) database. Firstly, the immune micro-environment analyses were conducted to analyze the pathogenesis of KIR2DL4 in RIF. Then, the gene set enrichment analysis (GSEA) was performed to investigate the function of KIR2DL4. Moreover, the TF-mRNA-miRNA and the co-expression networks were constructed to reveal the potential regulation of KIR2DL4. Furthermore, the genes that were associated with KIR2DL4 and differentially expressed in RIF were obtained and defined as key genes, and the functions of these genes were further explored. KIR2DL4 could be used for clinical diagnosis of RIF, and it was correlated with the changes in the immune micro-environment in RIF. From the perspective of function, KIR2DL4 was associated with complement and coagulation cascades, natural killer cell-mediated cytotoxicity, etc. Moreover, the TF-mRNA-miRNA regulatory network was constructed with KIR2DL4, 9 TFs, and 29 miRNAs. Furthermore, KIR2DL4, ACSM1, IL2RB, and PTPN11 were screened as key genes, which were associated with immune-related functions. This study deeply analyzed the function of KIR2DL4 and its role in RIF, and we found that STAT1 might up-regulate KIR2DL4 by INF-γ/JAK2/STAT1 signaling pathway. Besides, over-expressed KIR2DL4 in the mid-luteal endometrium might influence embryo implantation by affecting the embryo implantation microenvironment, which might help deepen the understanding of the molecular mechanism of RIF.

A new cassane diterpenoid from the seed of Caesalpinia sappan.

In this study, a previously undescribed cassane diterpenoid, named caesalpinin JF (1), along with two known cassane diterpenoids caesanine C (2) and tomocinol B (3), was isolated from 95% EtOH extract of the seeds of Caesalpinia sappan Linn. Additionally, three known compounds including pulcherrin R (4), syringaresinol-4'-O-ß-D-glucopyranoside (5) and kaempferol (6) were also identified. The structures of the isolated compounds were elucidated by comprehensive 1D and 2D NMR spectroscopic analyses. Additionally, electronic circular dichroism (ECD) calculation was used to identify the absolute structure of compound 1. Among the isolated compounds, compound 1 displayed a potent anti-neuroinflammation with an IC50 value of 9.87 ± 1.71 µM.

RHC genotyping in Chinese Han population.

BACKGROUND: The Rh blood group system is characterized by its complexity and polymorphism, encompassing 56 different antigens. Accurately predicting the presence of the C antigen using genotyping methods has been challenging. The objective of this study was to evaluate the accuracy of various genotyping methods for predicting the Rh C and to identify a suitable method for the Chinese Han population. METHODS: In total, 317 donors, consisting 223 D+ (including 20 with the Del phenotype) and 94 D- were randomly selected. For RHC genotyping, 48C and 109bp insertion were detected on the Real-time PCR platform and -292 substitution was analyzed via restriction fragment length polymorphism (RFLP). Moreover, the promoter region of the RHCE gene was sequenced to search for other nucleotide substitutions between RHC and RHc. Agreement between prediction methods was evaluated using the Kappa statistic, and comparisons between methods were conducted via the χ2 test. RESULTS: The analysis revealed that the 48C allele, 109bp insertion, a specific pattern observed in RFLP results, and wild-type alleles of seven single nucleotide polymorphisms (SNPs) were in strong agreement with the Rh C, with Kappa coefficients exceeding 0.8. However, there were instances of false positives or false negatives (0.6% false negative rate for 109bp insertion and 5.4-8.2% false positive rates for other methods). The 109bp insertion method exhibited the highest accuracy in predicting the Rh C, at 99.4%, compared to other methods (P values≤0.001). Although no statistical differences were found among other methods for predicting Rh C (P values>0.05), the accuracies in descending order were 48C (94.6%) > rs586178 (92.7%) > rs4649082, rs2375313, rs2281179, rs2072933, rs2072932, and RFLP (92.4%) > rs2072931 (91.8%). CONCLUSIONS: None of the methods examined can independently and accurately predict the Rh C. However, the 109bp insertion test demonstrated the highest accuracy for predicting the Rh C in the Chinese Han population. Utilizing the 109bp insertion test in combination with other methods may enhance the accuracy of Rh C prediction.

Associations between immune cell phenotypes and lung cancer subtypes: insights from mendelian randomization analysis.

INTRODUCTION: Lung cancer is a common malignant tumor, and different types of immune cells may have different effects on the occurrence and development of lung cancer subtypes, including lung squamous cell carcinoma (LUSC) and lung adenocarcinoma (LUAD). However, the causal relationship between immune phenotype and lung cancer is still unclear. METHODS: This study utilized a comprehensive dataset containing 731 immune phenotypes from the European Bioinformatics Institute (EBI) to evaluate the potential causal relationship between immune phenotypes and LUSC and LUAD using the inverse variance weighted (IVW) method in Mendelian randomization (MR). Sensitivity analyses, including MR-Egger intercept, Cochran Q test, and others, were conducted for the robustness of the results. The study results were further validated through meta-analysis using data from the Transdisciplinary Research Into Cancer of the Lung (TRICL) data. Additionally, confounding factors were excluded to ensure the robustness of the findings. RESULTS: Among the final selection of 729 immune cell phenotypes, three immune phenotypes exhibited statistically significant effects with LUSC. CD28 expression on resting CD4 regulatory T cells (OR 1.0980, 95% CI: 1.0627-1.1344, p < 0.0001) and CD45RA + CD28- CD8 + T cell %T cell (OR 1.0011, 95% CI: 1.0007; 1.0015, p < 0.0001) were associated with increased susceptibility to LUSC. Conversely, CCR2 expression on monocytes (OR 0.9399, 95% CI: 0.9177-0.9625, p < 0.0001) was correlated with a decreased risk of LUSC. However, no significant causal relationships were established between any immune cell phenotypes and LUAD. CONCLUSION: This study demonstrates that specific immune cell types are associated with the risk of LUSC but not with LUAD. While these findings are derived solely from European populations, they still provide clues for a deeper understanding of the immunological mechanisms underlying lung cancer and may offer new directions for future therapeutic strategies and preventive measures.

Natural products in atherosclerosis therapy by targeting PPARs: a review focusing on lipid metabolism and inflammation.

Inflammation and dyslipidemia are critical inducing factors of atherosclerosis. Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors and control the expression of multiple genes that are involved in lipid metabolism and inflammatory responses. However, synthesized PPAR agonists exhibit contrary therapeutic effects and various side effects in atherosclerosis therapy. Natural products are structural diversity and have a good safety. Recent studies find that natural herbs and compounds exhibit attractive therapeutic effects on atherosclerosis by alleviating hyperlipidemia and inflammation through modulation of PPARs. Importantly, the preparation of natural products generally causes significantly lower environmental pollution compared to that of synthesized chemical compounds. Therefore, it is interesting to discover novel PPAR modulator and develop alternative strategies for atherosclerosis therapy based on natural herbs and compounds. This article reviews recent findings, mainly from the year of 2020 to present, about the roles of natural herbs and compounds in regulation of PPARs and their therapeutic effects on atherosclerosis. This article provides alternative strategies and theoretical basis for atherosclerosis therapy using natural herbs and compounds by targeting PPARs, and offers valuable information for researchers that are interested in developing novel PPAR modulators.

Simplified Protocol to Demonstrate Gene Expression in Nicotiana benthamiana Using an Agrobacterium-Mediated Transient Assay.

Agrobacterium-mediated transient gene expression in Nicotiana benthamiana is widely used to study gene function in plants. One dramatic phenotype that is frequently screened for is cell death. Here, we present a simplified protocol for Agrobacterium-mediated transient gene expression by infiltration. Compared with current methods, the novel protocol can be done without a centrifuge or spectrometer, thereby suitable for K-12 outreach programs as well as rapidly identifying genes that induce cell death. Key features • The protocol simplifies the widely used Agrobacterium-mediated transient gene expression assay [1] and can be completed within one week when plants are available. • Rice XB3 gene can induce a dramatic and easily identifiable cell death phenotype in Nicotiana benthamiana. • Allows identification of cell death-inducing genes and is suitable for teaching. • Compared to the currently used methods, our protocol omits the use of agroinfiltration buffer, pH meter, temperature-controlled growth chamber, centrifuge, and spectrophotometer. Graphical overview Agrobacterium infiltration (agroinfiltration) of Nicotiana benthamiana. The photo demonstrates the method of agroinfiltration into the abaxial side of leaves using a needleless syringe.

Spatial ecology and microhabitat selection of the nocturnal pitviper Viridovipera stejnegeri (Squamata: Viperidae) in relation to prey.

Habitat is fundamental for facilitating various life activities in animals, for instance, snakes procure essential energy for survival and reproduction by selecting ambush microhabitats. While there has been extensive research on the selection of microhabitat for feeding in terrestrial and aquatic snakes, little is known about arboreal snakes. In the present study, we analyzed the ambush microhabitat preferences of Viridovipera stejnegeri, a widely distributed Asian pitviper in China, conducted association analysis between snake microhabitat and prey microhabitat and abundance to determine the ro5le of microhabitat selection in feeding. Employing random forest analysis and habitat selection functions, we further constructed a predictive framework for assessing the probability of ambush site selection by V. stejnegeri. Our results revealed that V. stejnegeri exhibited a distinct microhabitat preference for ambush prey. Among the 13 environmental factors assessed, V. stejnegeri showed pronounced preferences towards 12 of these factors, including climatic factors, geographical factors, and vegetation factors. Furthermore, although the preferences of V. stejnegeri overlapped substantially with those of its prey across multiple habitat factors, food abundance shows no significant association with various habitat factors of V. stejnegeri, and does not have significant predictive effect on habitat selection of V. stejnegeri. Therefore, we infer that V. stejnegeri does not preferentially select microhabitats with the highest food abundance, which does not support the hypothesis that "snakes select habitats based on the spatial distribution of prey abundance." By analyzing the characteristics of vegetation, geography, and climate, we conclude that V. stejnegeri tends to choose microhabitats with better ambush conditions to increase attack success rate, thereby achieving the optimal feeding success rate at the microhabitat scale, which is in line with the predictions of optimal foraging theory. This study provides new insights into the predation ecology and habitat selection of snakes.

Zixue Powder attenuates septic thrombosis via reducing neutrophil extracellular trap through blocking platelet STING activation.

ETHNOPHARMACOLOGICAL RELEVANCE: Microthrombosis is commonly seen in sepsis and COVID-19. Zixue Powder (ZXP) is a traditional Chinese herbal formula with the potential to treat microvascular and infectious diseases. However, the role and mechanism of ZXP in sepsis-associated thrombosis remain unclear. AIM OF THE STUDY: Investigating the therapeutic effectiveness and underlying mechanisms of ZXP in septic thrombosis. MATERIALS AND METHODS: ZXP's compositions were examined with UPLC-QTOF-MS. The efficacy of ZXP on sepsis-induced thrombosis was assessed through various methods: liver tissue pathology was examined using hematoxylin-eosin staining, platelet count was determined by a blood cell analyzer, and an enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of serum tissue factor (TF), thromboxane B2 (TXB2), D-Dimer, and plasminogen activator inhibitor-1 (PAI-1). Neutrophil extracellular traps (NETs) were localized and expressed in liver tissues by immunofluorescence, and the number of NETs in peripheral blood was evaluated by ELISA, which measured the quantity of cf-DNA and MPO-DNA in serum. Platelet P-selectin expression and platelet-neutrophil aggregation were measured by flow cytometry, and plasma P-selectin expression was measured by ELISA. Furthermore, the mechanism of the stimulator of interferon genes (STING) signaling pathway in ZXP's anti-sepsis thrombosis effect was investigated using the STING agonist, Western blot experiments, and immunoprecipitation experiments. RESULTS: UPLC-QTOF-MS identified 40 chemical compositions of ZXP. Administration of ZXP resulted in significant improvements in liver thrombosis, platelet counts, and levels of TXB2, TF, PAI-1, and D-Dimer in septic rats. Moreover, ZXP inhibited NETs formation in both liver tissue and peripheral blood. Additionally, ZXP decreased the levels of P-selectin in both platelets and plasma, as well as the formation of platelet-neutrophil aggregates, thereby suppressing P-selectin-mediated NETs release. Immunoprecipitation and immunofluorescence staining experiments revealed that ZXP attenuated P-selectin secretion by inhibiting STING-mediated assembly of platelet soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) complex, ultimately preventing inhibition of NETs formation. CONCLUSION: Our study showed that ZXP effectively mitigates platelet granule secretion primarily through modulation of the STING pathway, consequently impeding NET-associated thrombosis in sepsis. These findings offer valuable insights for future research on the development and application of ZXP.

Bacterial Biohybrids for Invasion of Tumor Cells Promote Antigen Cross-Presentation Through Gap Junction.

Due to inherent differences in cellular composition and metabolic behavior with host cells, tumor-harbored bacteria can discriminatorily affect tumor immune landscape. However, the mechanisms by which intracellular bacteria affect antigen presentation process between tumor cells and antigen-presenting cells (APCs) are largely unknown. The invasion behavior of attenuated Salmonella VNP20009 (VNP) into tumor cells is investigated and an attempt is made to modulate this behavior by modifying positively charged polymers on the surface of VNP. It is found that non-toxic chitosan oligosaccharide (COS) modified VNP (VNP@COS) bolsters the formation of gap junction between tumor cells and APCs by enhancing the ability of VNP to infect tumor cells. On this basis, a bacterial biohybrid is designed to promote in situ antigen cross-presentation through intracellular bacteria induced gap junction. This bacterial biohybrid also enhances the expression of major histocompatibility complex class I molecules on the surface of tumor cells through the incorporation of Mdivi-1 coupled with VNP@COS. This strategic integration serves to heighten the immunogenic exposure of tumor antigens; while, preserving the cytotoxic potency of T cells. A strategy is proposed to precisely controlling the function and local effects of microorganisms within tumors.