Effects of Simulated Presence Therapy on Agitated Behavior, Cognition, and Use of Protective Constraint among Patients with Senile Dementia.

The research was conducted to investigate the improvement of agitated behaviors, cognitive functions, and negative emotions among patients with senile dementia and the burden of caregivers after simulated presence therapy (SPT) intervention. 85 patients with senile dementia were included as the research subjects and divided into control group (40 cases performed with routine nursing) and observation group (45 cases undergoing routine nursing combined with SPT) via a random number table method. Cohen-Mansfield agitation inventory (CAMI) and protective constraint were used to assess the improvement of agitated behaviors among patients. Besides, apathy evaluation scale-informant (AES-I), functional independence measure (FIM), self-rating depression scale (SDS), self-rating anxiety scale (SAS), clock drawing test, and caregiver burden inventory (CBI) were adopted to evaluate the differences in apathy, daily living and sociability, depression, anxiety, cognitive functions, and caregiver burden between the two groups. It was demonstrated that CAMI score, the duration of protective constraint use, AES-I score, SDS score, SAS score, and CBI score among patients in observation group all apparently decreased compared with those in control group after the intervention. In contrast, FIM and clock drawing test scores both notably increased (P < 0.05). The above findings suggested that SPT could obviously reduce the incidence of agitated behaviors, improve the level of apathy, daily living and sociability, depression, anxiety, and cognitive functions, and relieve caregiver burden among patients with senile dementia during SPT intervention for patients with senile dementia.

Small but powerful: RALF peptides in plant adaptive and developmental responses.

Plants live in a highly dynamic environment and require to rapidly respond to a plethora of environmental stimuli, so that to maintain their optimal growth and development. A small plant peptide, rapid alkalization factor (RALF), can rapidly increase the pH value of the extracellular matrix in plant cells. RALFs always function with its corresponding receptors. Mechanistically, effective amount of RALF is induced and released at the critical period of plant growth and development or under different external environmental factors. Recent studies also highlighted the role of RALF peptides as important regulators in plant intercellular communications, as well as their operation in signal perception and as ligands for different receptor kinases on the surface of the plasma membrane, to integrate various environmental cues. In this context, understanding the fine-print of above processes may be essential to solve the problems of crop adaptation to various harsh environments under current climate trends scenarios, by genetic means. This paper summarizes the current knowledge about the structure and diversity of RALF peptides and their roles in plant development and response to stresses, highlighting unanswered questions and problems to be solved.

Activation of RIG-I signaling in the early stage of Paragonimus proliferus infection causes lung injury via type I immune response in rat.

Paragonimiasis is a common zoonotic parasitic disease. The retinoic acid-inducible gene I (RIG-I) signaling is very important for the host to recognize invading pathogens (especially viruses and bacteria). However, the role of RIG-I signaling in the early stages of P. proliferus infection remains unclear. Therefore, in this study, Sprague-Dawley (SD) rat models with lung damage caused by P. proliferus were established. Experimental methods including Enzyme-linked Immuno Sorbent Assay (ELISA), real-time fluorescent quantitative polymerase chain reaction (PCR), western blotting, and hematoxylin and eosin (HE) staining were used to explore the mechanisms of lung injury caused by P. proliferus. As a result, the expression of the mRNA and proteins of RIG-I signal-related key target molecules, including RIG-I, tumor necrosis factor (TNF) receptor associated factor 6 (TRAF6), interferon regulatory Factor 7 (IRF7), IPS-1, and downstream C-X-C chemokine ligand 10 (CXCL10), were significantly up-regulated immediately after infection, peaked at 3 or 7 days, and showed a downward trend on after 14 days. The levels of pro-inflammatory cytokines interleukin-1 (IL-1), interferon (IFN)-α, -ß, and -γ, which represent type 1 immune response, gradually increased and reached a peak by 14 days, which was consistent with the changes in the degree of inflammatory damage observed under HE staining of lung tissues. In conclusion, RIG-I signaling is activated in the early stage (before 14 days) of P. proliferus infection, it is inferred that the lung injury of the host may be related to the activation of RIG-I like signaling to induce type I immune response.

Dual modifying of MAVS at lysine 7 by SIRT3-catalyzed deacetylation and SIRT5-catalyzed desuccinylation orchestrates antiviral innate immunity.

To effectively protect the host from viral infection while avoiding excessive immunopathology, the innate immune response must be tightly controlled. However, the precise regulation of antiviral innate immunity and the underlying mechanisms remain unclear. Here, we find that sirtuin3 (SIRT3) interacts with mitochondrial antiviral signaling protein (MAVS) to catalyze MAVS deacetylation at lysine residue 7 (K7), which promotes MAVS aggregation, as well as TANK-binding kinase I and IRF3 phosphorylation, resulting in increased MAVS activation and enhanced type I interferon signaling. Consistent with these findings, loss of Sirt3 in mice and zebrafish renders them more susceptible to viral infection compared to their wild-type (WT) siblings. However, Sirt3 and Sirt5 double-deficient mice exhibit the same viral susceptibility as their WT littermates, suggesting that loss of Sirt5 in Sirt3-deficient mice may counteract the increased viral susceptibility displayed in Sirt3-deficient mice. Thus, we not only demonstrate that SIRT3 positively regulates antiviral immunity in vitro and in vivo, likely via MAVS, but also uncover a previously unrecognized mechanism by which SIRT3 acts as an accelerator and SIRT5 as a brake to orchestrate antiviral innate immunity.

WAV E3 ubiquitin ligases mediate degradation of IAA32/34 in the TMK1-mediated auxin signaling pathway during apical hook development.

Auxin regulates plant growth and development through downstream signaling pathways, including the best-known SCFTIR1/AFB-Aux/IAA-ARF pathway and several other less characterized "noncanonical" pathways. Recently, one SCFTIR1/AFB-independent noncanonical pathway, mediated by Transmembrane Kinase 1 (TMK1), was discovered through the analyses of its functions in Arabidopsis apical hook development. Asymmetric accumulation of auxin on the concave side of the apical hook triggers DAR1-catalyzed release of the C-terminal of TMK1, which migrates into the nucleus, where it phosphorylates and stabilizes IAA32/34 to inhibit cell elongation, which is essential for full apical hook formation. However, the molecular factors mediating IAA32/34 degradation have not been identified. Here, we show that proteins in the CYTOKININ INDUCED ROOT WAVING 1 (CKRW1)/WAVY GROWTH 3 (WAV3) subfamily act as E3 ubiquitin ligases to target IAA32/34 for ubiquitination and degradation, which is inhibited by TMK1c-mediated phosphorylation. This antagonistic interaction between TMK1c and CKRW1/WAV3 subfamily E3 ubiquitin ligases regulates IAA32/34 levels to control differential cell elongation along opposite sides of the apical hook.

A radiomics signature derived from CT imaging to predict MSI status and immunotherapy outcomes in gastric cancer: a multi-cohort study.

BACKGROUND: Accurate microsatellite instability (MSI) testing is essential for identifying gastric cancer (GC) patients eligible for immunotherapy. We aimed to develop and validate a CT-based radiomics signature to predict MSI and immunotherapy outcomes in GC. METHODS: This retrospective multicohort study included a total of 457 GC patients from two independent medical centers in China and The Cancer Imaging Archive (TCIA) databases. The primary cohort (n = 201, center 1, 2017-2022), was used for signature development via Least Absolute Shrinkage and Selection Operator (LASSO) and logistic regression analysis. Two independent immunotherapy cohorts, one from center 1 (n = 184, 2018-2021) and another from center 2 (n = 43, 2020-2021), were utilized to assess the signature's association with immunotherapy response and survival. Diagnostic efficiency was evaluated using the area under the receiver operating characteristic curve (AUC), and survival outcomes were analyzed via the Kaplan-Meier method. The TCIA cohort (n = 29) was included to evaluate the immune infiltration landscape of the radiomics signature subgroups using both CT images and mRNA sequencing data. RESULTS: Nine radiomics features were identified for signature development, exhibiting excellent discriminative performance in both the training (AUC: 0.851, 95%CI: 0.782, 0.919) and validation cohorts (AUC: 0.816, 95%CI: 0.706, 0.926). The radscore, calculated using the signature, demonstrated strong predictive abilities for objective response in immunotherapy cohorts (AUC: 0.734, 95%CI: 0.662, 0.806; AUC: 0.724, 95%CI: 0.572, 0.877). Additionally, the radscore showed a significant association with PFS and OS, with GC patients with a low radscore experiencing a significant survival benefit from immunotherapy. Immune infiltration analysis revealed significantly higher levels of CD8 + T cells, activated CD4 + B cells, and TNFRSF18 expression in the low radscore group, while the high radscore group exhibited higher levels of T cells regulatory and HHLA2 expression. CONCLUSION: This study developed a robust radiomics signature with the potential to serve as a non-invasive biomarker for GC's MSI status and immunotherapy response, demonstrating notable links to post-immunotherapy PFS and OS. Additionally, distinct immune profiles were observed between low and high radscore groups, highlighting their potential clinical implications.

Quercetin inhibition of porcine intestinal alpha coronavirus in vitro and in vivo.

BACKGROUND: Porcine acute diarrhea syndrome coronavirus (SADS-CoV) is one of the novel pathogens responsible for piglet diarrhea, contributing to substantial economic losses in the farming sector. The broad host range of SADS-CoV raises concerns regarding its potential for cross-species transmission. Currently, there are no effective means of preventing or treating SADS-CoV infection, underscoring the urgent need for identifying efficient antiviral drugs. This study focuses on evaluating quercetin as an antiviral agent against SADS-CoV. RESULTS: In vitro experiments showed that quercetin inhibited SADS-CoV proliferation in a concentration-dependent manner, targeting the adsorption and replication stages of the viral life cycle. Furthermore, quercetin disrupts the regulation of the P53 gene by the virus and inhibits host cell cycle progression induced by SADS-CoV infection. In vivo experiments revealed that quercetin effectively alleviated the clinical symptoms and intestinal pathological damage caused by SADS-CoV-infected piglets, leading to reduced expression levels of inflammatory factors such as TLR3, IL-6, IL-8, and TNF-α. CONCLUSIONS: Therefore, this study provides compelling evidence that quercetin has great potential and promising applications for anti- SADS-CoV action.

Innexin hemichannel activation by Microplitis bicoloratus ecSOD monopolymer reduces ROS.

The extracellular superoxide dismutases (ecSODs) secreted by Microplitis bicoloratus reduce the reactive oxygen species (ROS) stimulated by the Microplitis bicoloratus bracovirus. Here, we demonstrate that the bacterial transferase hexapeptide (hexapep) motif and bacterial-immunoglobulin-like (BIg-like) domain of ecSODs bind to the cell membrane and transiently open hemichannels, facilitating ROS reductions. RNAi-mediated ecSOD silencing in vivo elevated ROS in host hemocytes, impairing parasitoid larva development. In vitro, the ecSOD-monopolymer needed to be membrane bound to open hemichannels. Furthermore, the hexapep motif in the beta-sandwich of ecSOD49 and ecSOD58, and BIg-like domain in the signal peptides of ecSOD67 were required for cell membrane binding. Hexapep motif and BIg-like domain deletions induced ecSODs loss of adhesion and ROS reduction failure. The hexapep motif and BIg-like domain mediated ecSOD binding via upregulating innexins and stabilizing the opened hemichannels. Our findings reveal a mechanism through which ecSOD reduces ROS, which may aid in developing anti-redox therapy.

circular RNA circ-231 promotes protein biogenesis of TPI1 and PRDX6 through mediating the interaction of eIF4A3 with STAU1 to facilitate unwinding of secondary structure in 5' UTR, enhancing progression of human esophageal squamous cell carcinoma (ESCC).

Background: The nuclear cap-binding complex (CBC)-dependent translation (CT) is an important initial translation pathway for 5'-cap-dependent translation in normal mammal cells. Eukaryotic translation initiation factor 4A-III (eIF4A3), as an RNA helicase, is recruited to CT complex and enhances CT efficiency through participating in unwinding of secondary structure in the 5' UTR. However, the detailed mechanism for eIF4A3 implicated in unwinding of secondary structure in the 5' UTR in normal mammal cells is still unclear. Specially, we need to investigate whether the kind of mechanism in normal mammal cells extrapolates to cancer cells, e.g. ESCC, and further interrogate whether and how the mechanism triggers malignant phenotype of ESCC, which are important for identifying a potential therapeutic target for patients with ESCC. Methods: Bioinformatics analysis, RNA immunoprecipitation and RNA pulldown assays were performed to detect the interaction of circular RNA circ-231 with eIF4A3. In vitro and in vivo assays were performed to detect biological roles of circ-231 in ESCC. RNA immunoprecipitation, RNA pulldown, mass spectrometry analysis and co-immunoprecipitation assays were used to measure the interaction of circ-231, eIF4A3 and STAU1 in HEK293T and ESCC. In vitro EGFP reporter and 5' UTR of mRNA pulldown assays were performed to probe for the binding of circ-231, eIF4A3 and STAU1 to secondary structure of 5' UTR. Results: RNA immunoprecipitation assays showed that circ-231 interacted with eIF4A3 in HEK293T and ESCC. Further study confirmed that circ-231 orchestrated with eIF4A3 to control protein expression of TPI1 and PRDX6, but not for mRNA transcripts. The in-depth mechanism study uncovered that both circ-231 and eIF4A3 were involved in unwinding of secondary structure in 5' UTR of TPI1 and PRDX6. More importantly, circ-231 promoted the interaction between eIF4A3 and STAU1. Intriguingly, both circ-231 and eIF4A3 were dependent on STAU1 binding to secondary structure in 5' UTR. Biological function assays revealed that circ-231 promoted the migration and proliferation of ESCC via TPI1 and PRDX6. In ESCC, the up-regulated expression of circ-231 was observed and patients with ESCC characterized by higher expression of circ-231 have concurrent lymph node metastasis, compared with control. Conclusions: Our data unravels the detailed mechanism by which STAU1 binds to secondary structure in 5' UTR of mRNAs and recruits eIF4A3 through interacting with circ-231 and thereby eIF4A3 is implicated in unwinding of secondary structure, which is common to HEK293T and ESCC. However, importantly, our data reveals that circ-231 promotes migration and proliferation of ESCC and the up-regulated circ-231 greatly correlates with tumor lymph node metastasis, insinuating that circ-231 could be a therapeutic target and an indicator of risk of lymph node metastasis for patients with ESCC.

Research on the Application of Molecular Image Processing in Rice Quality Inspection.

Objective: With the improvement of living standards, consumers are paying more and more attention to the quality of rice. Traditional rice quality detection relies on human sensory judgment, which is inaccurate and inefficient. With the continuous development of molecular imaging technology, more and more scholars at home and abroad have begun to pay attention to its application in the nondestructive testing of agricultural products. Molecular imaging technology combines the advantages of spectral technology and image technology, which can achieve rapid, nondestructive and accurate detection of rice quality. In this paper, taking rice as the research object, we carried out nondestructive detection research on rice varieties, moisture and starch content using molecular imaging technology. We proposed a rapid detection method based on molecular imaging technology for rice variety identification, moisture content and starch content. Molecular images of the rice samples from four origins were obtained using a molecular imaging system, the regions of interest of the rice were identified and, spectral data, textural features and morphological features of the rice were extracted. Spectral, textural and morphological features were selected by principal component analysis (PCA), and nine feature wavelengths were obtained and an optimal model was established with an accuracy of 91.67%, which demonstrated the feasibility of molecular imaging. By comparing the models, the BCC-LS-SVR model based on the RB function had the highest accuracy with R2 of 0.989, RMSEP of 0.767%, R2 of 0.985, and RMSEC of 0.591%. Moreover, starchy rice was detected using molecular imaging. The PCA-SVR model based on the RBF kernel function had the highest accuracy with R2 of 0.989, RMSEC of 0.445%, R2 of 0.991, and RMSEP of 0.669%. Our models demonstrated high accuracy in identifying rice varieties, as well as quantifying moisture and starch content, showcasing the feasibility of molecular imaging technology in rice quality assessment. This research offers a rapid, nondestructive, and accurate method for rice quality assessment, promising significant benefits for agricultural producers and consumers.

Pathway-based stratification of gliomas uncovers four subtypes with different TME characteristics and prognosis.

Increasing evidences have found that the interactions between hypoxia, immune response and metabolism status in tumour microenvironment (TME) have clinical importance of predicting clinical outcomes and therapeutic efficacy. This study aimed to develop a reliable molecular stratification based on these key components of TME. The TCGA data set (training cohort) and two independent cohorts from CGGA database (validation cohort) were enrolled in this study. First, the enrichment score of 277 TME-related signalling pathways was calculated by gene set variation analysis (GSVA). Then, consensus clustering identified four stable and reproducible subtypes (AFM, CSS, HIS and GLU) based on TME-related signalling pathways, which were characterized by differences in hypoxia and immune responses, metabolism status, somatic alterations and clinical outcomes. Among the four subtypes, HIS subtype had features of immunosuppression, oxygen deprivation and active energy metabolism, resulting in a worst prognosis. Thus, for better clinical application of this acquired stratification, we constructed a risk signature by using the LASSO regression model to identify patients in HIS subtype accurately. We found that the risk signature could accurately screen out the patients in HIS subtype and had important reference value for individualized treatment of glioma patients. In brief, the definition of the TME-related subtypes was a valuable tool for risk stratification in gliomas. It might serve as a reliable prognostic classifier and provide rational design of individualized treatment, and follow-up scheduling for patients with gliomas.

Two new species of the mealybug genus Paracoccus from Jiangxi, South China (Hemiptera, Coccomorpha, Pseudococcidae).

Two new mealybug species, Paracoccusgillianwatsonae Zhang, sp. nov. and P.wui Zhang, sp. nov., collected from Jiangxi, South China, are described and illustrated based on the morphology of adult females. Paracoccusgillianwatsonae is similar to P.burnerae (Brain, 1915), but it differs in having fewer pairs of cerarii, and in lacking both ventral oral collar tubular ducts on the margins of the head and translucent pores on the hind femur. Paracoccuswui resembles P.keralae Williams, 2004 and P.neocarens (Lit, 1992), but it differs in lacking ventral oral collar tubular ducts on the margins of the head and in having multilocular disc-pores usually in double rows at the posterior edges of abdominal segments V and VI. A key to the Paracoccus species found in China is provided.

Analysis of endophytic bacterial diversity in seeds of different genotypes of cotton and the suppression of Verticillium wilt pathogen infection by a synthetic microbial community.

BACKGROUND: In agricultural production, fungal diseases significantly impact the yield and quality of cotton (Gossypium spp.) with Verticillium wilt posing a particularly severe threat. RESULTS: This study is focused on investigating the effectiveness of endophytic microbial communities present in the seeds of disease-resistant cotton genotypes in the control of cotton Verticillium wilt. The technique of 16S ribosomal RNA (16S rRNA) amplicon sequencing identified a significant enrichment of the Bacillus genus in the resistant genotype Xinluzao 78, which differed from the endophytic bacterial community structure in the susceptible genotype Xinluzao 63. Specific enriched strains were isolated and screened from the seeds of Xinluzao 78 to further explore the biological functions of seed endophytes. A synthetic microbial community (SynCom) was constructed using the broken-rod model, and seeds of the susceptible genotype Xinluzao 63 in this community that had been soaked with the SynCom were found to significantly control the occurrence of Verticillium wilt and regulate the growth of cotton plants. Antibiotic screening techniques were used to preliminarily identify the colonization of strains in the community. These techniques revealed that the strains can colonize plant tissues and occupy ecological niches in cotton tissues through a priority effect, which prevents infection by pathogens. CONCLUSION: This study highlights the key role of seed endophytes in driving plant disease defense and provides a theoretical basis for the future application of SynComs in agriculture.

Flexible, scalable and simple-fabricated silver nanorod-decorated bacterial nanocellulose SERS substrates cooperated with portable Raman spectrometer for on-site detection of pesticide residues.

Owing to good flexibility, prominent mechanical properties, three-dimensional (3D) nanofibrous structure and low background interference, sustainable bacterial nanocellulose (BNC) is a highly attractive matrix material for surface-enhanced Raman scattering (SERS) sensor. Herein, a highly sensitive, flexible and scalable silver nanorod-decorated BNC (AgNRs@BNC) SERS sensor is developed by a simple vacuum-assisted filtration. The AgNRs were firmly locked in the 3D nanofibrous network of cellulose nanofibers upon vacuum drying process, resulting in the formation of 3D SERS hotspots with a depth of more than 10 µm on the sensor. With 4-aminothiophenol (4-ATP) as a target molecule, a lowest distinguishable level of 10-12 M and a high enhancement factor of 1.1 × 109 were realized by the optimal AgNRs1.5@BNC SERS sensor. Moreover, the AgNRs@BNC SERS sensor exhibits high detectable level of 10-9 M for thiram molecules by integrating with a portable Raman spectrometer. Besides, toxic thiram residues on grape surface could be directly on-site identified by the combination of AgNRs@BNC SERS sensors and a portable Raman spectrometer through a feasible press-and-peel method. The flexible AgNRs@BNC SERS sensor cooperated with portable Raman system demonstrates great potential for on-site detection of pesticide residues on irregular food surfaces.

Plant-derived flavonoids are a potential source of drugs for the treatment of liver fibrosis.

Liver fibrosis is a dynamic pathological process that can be triggered by any chronic liver injury. If left unaddressed, it will inevitably progress to the severe outcomes of liver cirrhosis or even hepatocellular carcinoma. In the past few years, the prevalence and fatality of hepatic fibrosis have been steadily rising on a global scale. As a result of its intricate pathogenesis, the quest for pharmacological interventions targeting liver fibrosis has remained a formidable challenge. Currently, no pharmaceuticals are exhibiting substantial clinical efficacy in the management of hepatic fibrosis. Hence, it is of utmost importance to expedite the development of novel therapeutics for the treatment of this condition. Various research studies have revealed the ability of different natural flavonoid compounds to alleviate or reverse hepatic fibrosis through a range of mechanisms, which are related to the regulation of liver inflammation, oxidative stress, synthesis and secretion of fibrosis-related factors, hepatic stellate cells activation, and proliferation, and extracellular matrix synthesis and degradation by these compounds. This review summarizes the progress of research on different sources of natural flavonoids with inhibitory effects on liver fibrosis over the last decades. The anti-fibrotic effects of natural flavonoids have been increasingly studied, making them a potential source of drugs for the treatment of liver fibrosis due to their good efficacy and biosafety.

Two novel Fe(III)-reducing bacteria, Geothrix campi sp. nov. and Geothrix mesophila sp. nov., isolated from paddy soils.

In this research, two novel Fe(III)-reducing bacteria, SG10T and SG198T of genus Geothrix, were isolated from the rice field of Fujian Agriculture and Forestry University in Fuzhou, Fujian Province, China. Strains SG10T and SG198T were strictly anaerobic, rod-shaped and Gram-stain-negative. The two novel strains exhibited iron reduction ability, utilizing various single organic acid as the elector donor and Fe(III) as a terminal electron acceptor. Strains SG10T and SG198T showed the highest 16S rRNA sequences similarities to the type strains of Geothrix oryzisoli SG189T (99.0-99.5%) and Geothrix paludis SG195T (99.0-99.7%), respectively. The phylogenetic trees based on the 16S rRNA gene and genome 120 conserved core genes showed that strains SG10T and SG198T belong to the genus Geothrix. Average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH) values between the phylogenetic neighbors and the two isolated strains were 86.1-94.3% and 30.7-59.5%, respectively. The major fatty acids were iso-C15:0, anteiso-C15:0, C16:0 and iso-C13:0 3OH, and MK-8 was the main respiratory quinone. According to above results, the two strains were assigned to the genus Geothrix with the names Geothrix campi sp. nov. and Geothrix mesophila sp. nov. Type strains are SG10T (= GDMCC 1.3406 T = JCM 39331 T) and SG198T (= GDMCC 62910 T = KCTC 25635 T), respectively.

Spatiotemporal characteristics of tissue derived small extracellular vesicles is associated with tumor relapse and anti-PD-1 response.

Small extracellular vesicles (sEVs) residing at tumor tissues are valuable specimens for biopsy. Tumor heterogeneity is common across all cancer types, but the heterogeneity of tumor tissue-derived sEVs (Ti-sEVs) is undefined. This study aims to discover the spatial distributions of Ti-sEVs in oral squamous cell carcinoma (OSCC) tissues and explore how these vesicle distributions affect the patients' prognosis. Multi-regional sampling enabled us to uncover that Ti-sEVs' accumulation at peritumoral sites correlates with a higher disease-free survival rate, and conversely, sparse peritumoral Ti-sEVs tend to forecast a higher risk of relapse. Of those relapsed patients, Ti-sEVs strongly bind to extracellular matrix and subsequently degrade it for allowing themselves enter the bloodstream rather than staying in situ. In advanced OSCC patients, the quantity and spatial distribution of Ti-sEVs prior to anti-PD-1 treatment, as well as the temporal variance of Ti-sEVs before and after immunotherapy, strongly map the clinical response and can help to distinguish the patients with shrinking tumors from those with growing tumors. Our work elucidates the correlation of spatiotemporal features of Ti-sEVs with patients' therapeutic outcomes and exhibit the potential for using Ti-sEVs as a predictor to forecast prognosis and screen the responders to anti-PD-1 therapy.

CXXC5 drove inflammation and ovarian cancer proliferation via transcriptional activation of ZNF143 and EGR1.

CXXC5, a zinc-finger protein, is known for its role in epigenetic regulation via binding to unmethylated CpG islands in gene promoters. As a transcription factor and epigenetic regulator, CXXC5 modulates various signaling processes and acts as a key coordinator. Altered expression or activity of CXXC5 has been linked to various pathological conditions, including tumorigenesis. Despite its known role in cancer, CXXC5's function and mechanism in ovarian cancer are unclear. We analyzed multiple public databases and found that CXXC5 is highly expressed in ovarian cancer, with high expression correlating with poor patient prognosis. We show that CXXC5 expression is regulated by oxygen concentration and is a direct target of HIF1A. CXXC5 is critical for maintaining the proliferative potential of ovarian cancer cells, with knockdown decreasing and overexpression increasing cell proliferation. Loss of CXXC5 led to inactivation of multiple inflammatory signaling pathways, while overexpression activated these pathways. Through in vitro and in vivo experiments, we confirmed ZNF143 and EGR1 as downstream transcription factors of CXXC5, mediating its proliferative potential in ovarian cancer. Our findings suggest that the CXXC5-ZNF143/EGR1 axis forms a network driving ovarian cell proliferation and tumorigenesis, and highlight CXXC5 as a potential therapeutic target for ovarian cancer treatment.