DIS3 ribonuclease is essential for spermatogenesis and male fertility in mice.

Spermatogonial stem cell (SSC) self-renewal and differentiation provide foundational support for long-term, steady-state spermatogenesis in mammals. Here, we have investigated the essential role of RNA exosome associated DIS3 ribonuclease in maintaining spermatogonial homeostasis and facilitating germ cell differentiation. We have established male germ-cell Dis3 conditional knockout (cKO) mice in which the first and subsequent waves of spermatogenesis are disrupted. This leads to a Sertoli cell-only phenotype and sterility in adult male mice. Bulk RNA-seq documents that Dis3 deficiency partially abolishes RNA degradation and causes significant increases in the abundance of transcripts. This also includes pervasively transcribed PROMoter uPstream Transcripts (PROMPTs), which accumulate robustly in Dis3 cKO testes. In addition, scRNA-seq analysis indicates that Dis3 deficiency in spermatogonia significantly disrupts RNA metabolism and gene expression, and impairs early germline cell development. Overall, we document that exosome-associated DIS3 ribonuclease plays crucial roles in maintaining early male germ cell lineage in mice.

Functional Analysis of Type III Effectors in Xanthomonas campestris pv. campestris Reveals Distinct Roles in Modulating Arabidopsis Innate Immunity.

Xanthomonas campestris pv. campestris (Xcc) is a significant phytopathogen causing black rot disease in crucifers. Its virulence relies heavily on the type III secretion system (T3SS), facilitating effector translocation into plant cells. The type III effectors (T3Es) disrupt cellular processes, promoting pathogen proliferation. However, only a few T3Es from Xcc have been thoroughly characterized. In this study, we further investigated two effectors using the T3Es-deficient mutant and the Arabidopsis protoplast system. XopE2Xcc triggers Arabidopsis immune responses via an unidentified activator of the salicylic acid (SA) signaling pathway, whereas XopLXcc suppresses the expression of genes associated with patterns-triggered immunity (PTI) and the SA signaling pathway. These two effectors exert opposing effects on Arabidopsis immune responses. Additionally, we examined the relationship between the specific domains and functions of these two effector proteins. Our findings demonstrate that the N-myristoylation motif and N-terminal domain are essential for the subcellular localization and virulence of XopE2Xcc and XopLXcc, respectively. These novel insights enhance our understanding of the pathogenic mechanisms of T3Es and contribute to developing effective strategies for controlling bacterial disease.

Loss of DIS3L in the initial segment is dispensable for sperm maturation in the epididymis and male fertility.

DIS3L, a catalytic exoribonuclease associated with the cytoplasmic exosome complex, degrades cytoplasmic RNAs and is implicated in cancers and certain other diseases in humans. Epididymis plays a pivotal role in the transport, maturation, and storage of sperm required for male fertility. However, it remains unclear whether DIS3L-mediated cytoplasmic RNA degradation plays a role in epididymis biology and functioning. Herein, we fabricated a Dis3l conditional knockout (Dis3l cKO) mouse line in which DIS3L was ablated from the principal cells of the initial segment (IS). Morphological analyses showed that spermatogenesis and IS differentiation occurred normally in Dis3l cKO mice. Additionally, the absence of DIS3L had no dramatic influence on the transcriptome of IS. Moreover, the sperm count, morphology, motility, and acrosome reaction frequency in Dis3l cKO mice were comparable to that of the control, indicating that the Dis3l cKO males had normal fertility. Collectively, our genetic model demonstrates that DIS3L inactivation in the IS is nonessential for sperm maturation and male fertility.

Effect of Different Selenium Species on Indole-3-Acetic Acid Activity of Selenium Nanoparticles Producing Strain Bacillus altitudinis LH18.

Acting as a growth regulator, Indole-3-acetic acid (IAA) is an important phytohormone that can be produced by several Bacillus species. However, few studies have been published on the comprehensive evaluation of the strains for practical applications and the effects of selenium species on their IAA-producing ability. The present study showed the selenite reduction strain Bacillus altitudinis LH18, which is capable of producing selenium nanoparticles (SeNPs) at a high yield in a cost-effective manner. Bio-SeNPs were systematically characterized by using DLS, zeta potential, SEM, and FTIR. The results showed that these bio-SeNPs were small in particle size, homogeneously dispersed, and highly stable. Significantly, the IAA-producing ability of strain was differently affected under different selenium species. The addition of SeNPs and sodium selenite resulted in IAA contents of 221.7 µg/mL and 91.01 µg/mL, respectively, which were 3.23 and 1.33 times higher than that of the control. This study is the first to examine the influence of various selenium species on the IAA-producing capacity of Bacillus spp., providing a theoretical foundation for the enhancement of the IAA-production potential of microorganisms.

The maternal drug exposure birth cohort (DEBC) in China.

Drug exposure during pregnancy lacks global fetal safety data. The maternal drug exposure birth cohort (DEBC) study, a prospective longitudinal investigation, aims to explore the correlation of maternal drug exposure during pregnancy with pregnancy outcomes, and establish a human biospecimen biobank. Here we describe the process of establishing DEBC and show that the drug exposure rate in the first trimester of pregnant women in DEBC (n = 112,986) is 30.70%. Among the drugs used, dydrogesterone and progesterone have the highest exposure rates, which are 11.97% and 10.82%, respectively. The overall incidence of adverse pregnancy outcomes is 13.49%. Dydrogesterone exposure during the first trimester is correlated with higher incidences of stillbirth, preterm birth, low birth weight, and birth defects, along with a lower incidence of miscarriage/abortion. Due to the limitations of this cohort study, causative conclusions cannot be drawn. Further follow-up and in-depth data analysis are planned for future studies.

The Modulation of Compositional Heterogeneity for Controlling Shear Banding in Co-P Metallic Nanoglasses.

Shear banding is much dependent on the glass-glass interfaces (GGIs) in metallic nanoglasses (NGs). Nevertheless, the current understanding of the glass phase of GGIs is not well established for controlling the shear banding in NGs. In this study, Co-P NGs are investigated by molecular dynamics simulations to reveal the phenomenon of elemental segregation in the GGI regions where the content of Co is dominant. Specifically, Co segregation results in the formation of GGIs, whose atomic structures are comparatively less dense than those present in the interiors of glassy grains. It is suggested that the Co segregation significantly reduces the shear resistance of GGIs. Thus, such compositional heterogeneity influences the mechanical properties of Co-P NGs. Particularly, shear banding is much altered through enhancing the Co segregation in the GGI regions, which leads to improvements in the ductility of Co-P NGs. This study advances knowledge of the formation of the GGI phase in NGs, which could enable GGI engineering in enhancing the mechanical properties of NGs.

Chemical Flexibility of Atomically Precise Metal Clusters.

Ligand-protected metal clusters possess hybrid properties that seamlessly combine an inorganic core with an organic ligand shell, imparting them exceptional chemical flexibility and unlocking remarkable application potential in diverse fields. Leveraging chemical flexibility to expand the library of available materials and stimulate the development of new functionalities is becoming an increasingly pressing requirement. This Review focuses on the origin of chemical flexibility from the structural analysis, including intra-cluster bonding, inter-cluster interactions, cluster-environments interactions, metal-to-ligand ratios, and thermodynamic effects. In the introduction, we briefly outline the development of metal clusters and explain the differences and commonalities of M(I)/M(I/0) coinage metal clusters. Additionally, we distinguish the bonding characteristics of metal atoms in the inorganic core, which give rise to their distinct chemical flexibility. Section 2 delves into the structural analysis, bonding categories, and thermodynamic theories related to metal clusters. In the following sections 3 to 7, we primarily elucidate the mechanisms that trigger chemical flexibility, the dynamic processes in transformation, the resultant alterations in structure, and the ensuing modifications in physical-chemical properties. Section 8 presents the notable applications that have emerged from utilizing metal clusters and their assemblies. Finally, in section 9, we discuss future challenges and opportunities within this area.

Throat microbiota drives alterations in pulmonary alveolar microbiota in patients with septic ARDS.

OBJECTIVES: The translocation of intestinal flora has been linked to the colonization of diverse and heavy lower respiratory flora in patients with septic ARDS, and is considered a critical prognostic factor for patients. METHODS: On the first and third days of ICU admission, BALF, throat swab, and anal swab were collected, resulting in a total of 288 samples. These samples were analyzed using 16S rRNA analysis and the traceability analysis of new generation technology. RESULTS: On the first day, among the top five microbiota species in abundance, four species were found to be identical in BALF and throat samples. Similarly, on the third day, three microbiota species were found to be identical in abundance in both BALF and throat samples. On the first day, 85.16% of microorganisms originated from the throat, 5.79% from the intestines, and 9.05% were unknown. On the third day, 83.52% of microorganisms came from the throat, 4.67% from the intestines, and 11.81% were unknown. Additionally, when regrouping the 46 patients, the results revealed a significant predominance of throat microorganisms in BALF on both the first and third day. Furthermore, as the disease progressed, the proportion of intestinal flora in BALF increased in patients with enterogenic ARDS. CONCLUSIONS: In patients with septic ARDS, the main source of lung microbiota is primarily from the throat. Furthermore, the dynamic trend of the microbiota on the first and third day is essentially consistent.It is important to note that the origin of the intestinal flora does not exclude the possibility of its origin from the throat.

Multiple primary tumors in patients with surgically treated pancreatic cancer: a SEER population-based study.

Background: With improving survival after pancreatic cancer (PC) resection, questions emerge concerning risk and patterns of metachronous tumors. We aimed to determine the incidence of multiple primary cancers among postoperative PC survivors. Methods: Patients undergoing PC surgery from 1975 to 2020 were identified in the Surveillance, Epidemiology, and End Results (SEER) registry. Standardized incidence ratios (SIRs) compared observed-to-expected cancers based on U.S. population rates. Cumulative incidence of secondary tumors was analyzed with Cox regression and cancer-specific survival with Kaplan-Meier curves. Results: Of 6,100 resected PC patients, 267 (4.38%) developed multiple cancers over 6.2 years median follow-up period. Subsequent malignancies showed a rising cumulative incidence extending beyond 5 years. Lung cancer was the predominant second primary in both males (n=36, SIR 1.87) and females (n=32, SIR 2.17). Prostate (n=33) and breast (n=25) cancers were also common. Risk varied by latency period and gender. Conclusions: Postoperative PC patients face a measurable risk for secondary cancers. Enhanced long-term surveillance has the potential to improve early detection and outcomes in this survivor population. Our data provides real-world evidence which could help inform surveillance guidelines in the future.

A Bayesian Change Point Model for Dynamic Alternative Transcription Start Site Usage During Cellular Differentiation.

ABSTRACT An alternative transcription start site (ATSS) is a major driving force for increasing the complexity of transcripts in human tissues. As a transcriptional regulatory mechanism, ATSS has biological significance. Many studies have confirmed that ATSS plays an important role in diseases and cell development and differentiation. However, exploration of its dynamic mechanisms remains insufficient. Identifying ATSS change points during cell differentiation is critical for elucidating potential dynamic mechanisms. For relative ATSS usage as percentage data, the existing methods lack sensitivity to detect the change point for ATSS longitudinal data. In addition, some methods have strict requirements for data distribution and cannot be applied to deal with this problem. In this study, the Bayesian change point detection model was first constructed using reparameterization techniques for two parameters of a beta distribution for the percentage data type, and the posterior distributions of parameters and change points were obtained using Markov Chain Monte Carlo (MCMC) sampling. With comprehensive simulation studies, the performance of the Bayesian change point detection model is found to be consistently powerful and robust across most scenarios with different sample sizes and beta distributions. Second, differential ATSS events in the real data, whose change points were identified using our method, were clustered according to their change points. Last, for each change point, pathway and transcription factor motif analyses were performed on its differential ATSS events. The results of our analyses demonstrated the effectiveness of the Bayesian change point detection model and provided biological insights into cell differentiation.

Double Superconducting Dome of Quasi Two-Dimensional TaS2 in Non-Centrosymmetric van der Waals Heterostructure.

Two-dimensional van der Waals heterostructures (2D-vdWHs) based on transition metal dichalcogenides (TMDs) provide unparalleled control over electronic properties. However, the interlayer coupling is challenged by the interfacial misalignment and defects, which hinders a comprehensive understanding of the intertwined electronic orders, especially superconductivity and charge density wave (CDW). Here, by using pressure to regulate the interlayer coupling of non-centrosymmetric 6R-TaS2 vdWHs, we observe an unprecedented phase diagram in TMDs. This phase diagram encompasses successive suppression of the original CDW states from alternating H-layer and T-layer configurations, the emergence and disappearance of a new CDW-like state, and a double superconducting dome induced by different interlayer coupling effects. These results not only illuminate the crucial role of interlayer coupling in shaping the complex phase diagram of TMD systems but also pave a new avenue for the creation of a novel family of bulk heterostructures with customized 2D properties.

Epidemiological, Virulence, and Antibiotic Resistance Analysis of Klebsiella pneumoniae, a Major Source of Threat to Livestock and Poultry in Some Regions of Xinjiang, China.

Klebsiella pneumoniae (K. pneumoniae) is recognized as a zoonotic pathogen with an increasing threat to livestock and poultry. However, research on K. pneumoniae of animal origin remains limited. To address the gap, a comprehensive investigation was carried out by collecting a total of 311 samples from the farms of four animal species (dairy cow, chicken, sheep, and pig) in selected areas of Xinjiang, China. Isolates were identified by khe gene amplification and 16S rRNA gene sequencing. Genotyping of K. pneumonia isolates was performed using wzi typing and multilocus sequence typing (MLST). PCR was employed to identify virulence and resistance genes. An antibiotic susceptibility test was conducted using the Kirby-Bauer method. The findings revealed an isolation of 62 K. pneumoniae strains, with an average isolation rate of 19.94%, with the highest proportion originating from cattle sources (33.33%). Over 85.00% of these isolates harbored six virulence genes (wabG, uge, fimH, markD, entB, and ureA); while more than 75.00% of isolates possessed four resistance genes (blaTEM, blaSHV, oqxA, and gyrA). All isolates exhibited complete resistance to ampicillin and demonstrated substantial resistance to sulfisoxazole, amoxicillin/clavulanic acid, and enrofloxacin, with an antibiotic resistance rate of more than 50%. Furthermore, 48.39% (30/62) of isolates were classified as multidrug-resistant (MDR) strains, with a significantly higher isolation rate observed in the swine farms (66.67%) compared to other farms. Genetic characterization revealed the classification of the 62 isolates into 30 distinct wzi allele types or 35 different sequence types (STs). Notably, we identified K. pneumoniae strains of dairy and swine origin belonging to the same ST42 and wzi33-KL64 types, as well as strains of dairy and chicken origin belonging to the same wzi31-KL31-K31 type. These findings emphasize the widespread occurrence of drug-resistant K. pneumoniae across diverse animal sources in Xinjiang, underscoring the high prevalence of multidrug resistance. Additionally, our results suggest the potential for animal-to-animal transmission of K. pneumoniae and there was a correlation between virulence genes and antibiotic resistance genes. Moreover, the current study provides valuable data on the prevalence, antibiotic resistance, and genetic diversity of K. pneumoniae originating from diverse animal sources in Xinjiang, China.

Coxiella burnetii effector CvpE maintains biogenesis of Coxiella-containing vacuoles by suppressing lysosome tubulation through binding PI(3)P and perturbing PIKfyve activity on lysosomes.

Coxiella burnetii (C. burnetii) is the causative agent of Q fever, a zoonotic disease. Intracellular replication of C. burnetii requires the maturation of a phagolysosome-like compartment known as the replication permissive Coxiella-containing vacuole (CCV). Effector proteins secreted by the Dot/Icm secretion system are indispensable for maturation of a single large CCV by facilitating the fusion of promiscuous vesicles. However, the mechanisms of CCV maintenance and evasion of host cell clearance remain to be defined. Here, we show that C. burnetii secreted Coxiella vacuolar protein E (CvpE) contributes to CCV biogenesis by inducing lysosome-like vacuole (LLV) enlargement. LLV fission by tubulation and autolysosome degradation is impaired in CvpE-expressing cells. Subsequently, we found that CvpE suppresses lysosomal Ca2+ channel transient receptor potential channel mucolipin 1 (TRPML1) activity in an indirect manner, in which CvpE binds phosphatidylinositol 3-phosphate [PI(3)P] and perturbs PIKfyve activity in lysosomes. Finally, the agonist of TRPML1, ML-SA5, inhibits CCV biogenesis and C. burnetii replication. These results provide insight into the mechanisms of CCV maintenance by CvpE and suggest that the agonist of TRPML1 can be a novel potential treatment that does not rely on antibiotics for Q fever by enhancing Coxiella-containing vacuoles (CCVs) fission.

Transcriptomic analysis of hub genes regulating albinism in light- and temperature-sensitive albino tea cultivars 'Zhonghuang 1' and 'Zhonghuang 2'.

Albino tea cultivars have high economic value because their young leaves contain enhanced free amino acids that improve the quality and properties of tea. Zhonghuang 1 (ZH1) and Zhonghuang 2 (ZH2) are two such cultivars widely planted in China; however, the environmental factors and molecular mechanisms regulating their yellow-leaf phenotype remain unclear. In this study, we demonstrated that both ZH1 and ZH2 are light- and temperature-sensitive. Under natural sunlight and low-temperature conditions, their young shoots were yellow with decreased chlorophyll and an abnormal chloroplast ultrastructure. Conversely, young shoots were green with increased chlorophyll and a normal chloroplast ultrastructure under shading and high-temperature conditions. RNA-seq analysis was performed for high light and low light conditions, and pairwise comparisons identified genes exhibiting different light responses between albino and green-leaf cultivars, including transcription factors, cytochrome P450 genes, and heat shock proteins. Weighted gene coexpression network analyses of RNA-seq data identified the modules related to chlorophyll differences between cultivars. Genes involved in chloroplast biogenesis and development, light signaling, and JA biosynthesis and signaling were typically downregulated in albino cultivars, accompanied by a decrease in JA-ILE content in ZH2 during the albino period. Furthermore, we identified the hub genes that may regulate the yellow-leaf phenotype of ZH1 and ZH2, including CsGDC1, CsALB4, CsGUN4, and a TPR gene (TEA010575.1), which were related to chloroplast biogenesis. This study provides new insights into the molecular mechanisms underlying leaf color formation in albino tea cultivars.

Sequence-dependent effects of hematoporphyrin derivatives (HPD) photodynamic therapy and cisplatin on lung adenocarcinoma cells.

BACKGROUND: Hematoporphyrin derivatives (HPD)-Photodynamic therapy (PDT) in combination with cisplatin (DDP) is an effective anticancer strategy. However, whether the order of combination affects efficacy has not been studied. METHODS: The human lung adenocarcinoma (LUAD) A549 cells were used as the study subjects. After A549 cells were treated with a single medication (PDT/DDP) or a sequential combination (PDT + DDP / DDP + PDT), the cell viability was assayed using the cell counting kit-8 method. Hoechst staining, Annexin-V/propidium iodide (PI) double staining, western blotting, and a real-time quantitative polymerase chain reaction (RT-qPCR) were performed to examine the mechanisms behind the combined effects. RESULTS: A synergistic impact between HPD-PDT and DDP was found. The cell viability in the PDT+DDP group was significantly lower than in the DDP+PDT group. A significant apoptotic profile and a high apoptotic rate were seen in the PDT + DDP group. The western blot showed that the expression levels of Bcl2-associated x(Bax) and cleaved-poly ADP-ribose polymerase (PARP) increased, and those of B-cell lymphoma-2 (Bcl-2) and Caspase-9 decreased in the PDT + DDP group. At the same time, the RT-qPCR revealed the upregulation of Bax and PARP mRNA and the downregulation of Bcl-2 and Caspase-9 mRNA. CONCLUSION: The order of the combination therapy (PDT + DDP / DDP + PDT) was important. The HPD-PDT followed by DDP significantly inhibited LUAD cell viability, which may be related to the mitochondrial apoptotic pathway.

Differential impact of intermittent versus continuous treatment with clozapine on fatty acid metabolism in the brain of an MK-801-induced mouse model of schizophrenia.

Continuous antipsychotic treatment is often recommended to prevent relapse in schizophrenia. However, the efficacy of antipsychotic treatment appears to diminish in patients with relapsed schizophrenia and the underlying mechanisms are still unknown. Moreover, though the findings are inconclusive, several recent studies suggest that intermittent versus continuous treatment may not significantly differ in recurrence risk and therapeutic efficacy but potentially reduce the drug dose and side effects. Notably, disturbances in fatty acid (FA) metabolism are linked to the onset/relapse of schizophrenia, and patients with multi-episode schizophrenia have been reported to have reduced FA biosynthesis. We thus utilized an MK-801-induced animal model of schizophrenia to evaluate whether two treatment strategies of clozapine would affect drug response and FA metabolism differently in the brain. Schizophrenia-related behaviors were assessed through open field test (OFT) and prepulse inhibition (PPI) test, and FA profiles of prefrontal cortex (PFC) and hippocampus were analyzed by gas chromatography-mass spectrometry. Additionally, we measured gene expression levels of enzymes involved in FA synthesis. Both intermittent and continuous clozapine treatment reversed hypermotion and deficits in PPI in mice. Continuous treatment decreased total polyunsaturated fatty acids (PUFAs), saturated fatty acids (SFAs) and FAs in the PFC, whereas the intermittent administration increased n-6 PUFAs, SFAs and FAs compared to continuous administration. Meanwhile, continuous treatment reduced the expression of Fads1 and Elovl2, while intermittent treatment significantly upregulated them. This study discloses the novel findings that there was no significant difference in clozapine efficacy between continuous and intermittent administration, but intermittent treatment showed certain protective effects on phospholipid metabolism in the PFC.

Effectiveness of trans-nasal humidified rapid insufflation ventilatory exchange compared with standard facemask oxygenation for pre- and apneic oxygenation during anesthesia induction: A meta-analysis based on randomized controlled trials.

PURPOSE: To further identify the effectiveness of trans-nasal humidified rapid insufflation ventilatory exchange (THRIVE) for pre- and apneic oxygenation during the anesthesia induction by comparison to facemask ventilation (FMV) based on current available evidence. METHODS: Medline, EMBASE, Web of Science, Cochrane Library and CNKI databases were searched from inception to December 22, 2023 for available randomized controlled trials (RCTs). Primary outcomes were PaO2 and PaCO2 after intubation and safe apnoea time. Secondary outcomes included the O2 desaturation, end expiratory carbon dioxide (EtCO2) and complications. The effect measures for continuous and categorical outcomes were separately the mean difference (MD) and relative risk (RR) with 95% confidence interval. RESULTS: Twelve RCTs with 403 patients in the THRIVE group and 401 patients in th FMV group were included. Pooled results demonstrated that the PaO2 after intubation was significantly higher (MD = 82.90mmHg, 95% CI: 12.25~153.54mmHg, P = 0.02) and safe apnoea time (MD = 103.81s, 95% CI: 42.07~165.56s, P = 0.001) was longer in the THRIVE group. Besides, the incidence rate of O2 desaturation (RR = 0.28, 95% CI: 0.12-0.66, P = 0.004) and gastric insufflation (RR = 0.26, 95% CI: 0.13-0.49, P<0.001) was significantly lower in the THRIVE group. CONCLUSION: Based on current evidence, THRIVE manifested better effectiveness representing as improved oxygenation, prolonged safe apnoea time and decreased risk of complications compared to standard FMV in surgical patients. Therefore, THRIVE could be served as a novel and valuable oxygenation technology for patients during anesthesia induction.

Dissecting the Mechanisms of Intestinal Immune Homeostasis by Analyzing T-Cell Immune Response in Crohn's Disease and Colorectal Cancer.

INTRODUCTION: Crohn's disease (CD) and colorectal cancer (CRC) represent a group of intestinal disorders characterized by intricate pathogenic mechanisms linked to the disruption of intestinal immune homeostasis. Therefore, comprehending the immune response mechanisms in both categories of intestinal disorders is of paramount significance in the prevention and treatment of these debilitating intestinal ailments. METHOD: IIn this study, we conducted single-cell analysis on paired samples obtained from primary colorectal tumors and individuals with Crohn's disease, which was aimed at deciphering the factors influencing the composition of the intestinal immune microenvironment. By aligning T cells across different tissues, we identified various T cell subtypes, such as γδ T cell, NK T cell, and regulatory T (Treg) cell, which maintained immune system homeostasis and were confirmed in enrichment analyses. Subsequently, we generated pseudo-time trajectories for subclusters of T cells in both syndromes to delineate their differentiation patterns and identify key driver genes Result: Furthermore, cellular communication and transcription factor regulatory networks are all essential components of the intricate web of mechanisms that regulate intestinal immune homeostasis. The identified complex cellular interaction suggested potential T-lineage immunotherapeutic targets against epithelial cells with high copy number variation (CNV) levels in CD and CRC. CONCLUSION: Finally, the analysis of regulon networks revealed several promising candidates for cell-specific transcription factors (TFs). This study focused on the immune molecular mechanism under intestinal diseases. It contributed to the novel insight of depicting a detailed immune landscape and revealing T-cell responding mechanisms in CD and CRC.

The efficacy and safety of continuous intravenous tirofiban for acute ischemic stroke patients treated by endovascular therapy: a meta-analysis.

Introduction: Tirofiban is a non-peptide selective glycoprotein IIb/IIIa receptor inhibitor with a short half-life. The research assesses the efficacy and safety of continuous intravenous tirofiban in patients with acute ischemic stroke (AIS) undergoing endovascular therapy (ET). Methods: A systematic search of Pubmed, Embase, Web of Science, and Cochrane Library databases is conducted from inception until January 26, 2024. Eligible studies are included based on predefined selection criteria. Efficacy outcomes (favorable functional outcome and excellent functional outcome) and safety outcomes (symptomatic intracranial hemorrhage [sICH], any intracranial hemorrhage [ICH], and 90-day mortality) are calculated using odds ratios (OR) and 95% confidence intervals (CI). Results: A total of 4,329 patients from 15 studies are included in the analysis. The results indicate a significant trend toward favorable functional outcomes in the tirofiban group (OR, 1.24; 95% CI, 1.09-1.42; p = 0.001). In terms of safety outcomes, tirofiban does not increase the risk of sICH (OR, 0.90; 95% CI, 0.71-1.13; p = 0.35) or any ICH (OR, 0.97; 95% CI, 0.70-1.34; p = 0.85), but it significantly decreases 90-day mortality (OR, 0.75; 95% CI, 0.64-0.88; p = 0.0006). A subgroup analysis suggests that continuous intravenous tirofiban demonstrates better efficacy (OR, 1.24; 95% CI, 1.09-1.42; p = 0.001) for patients with AIS undergoing rescue ET with even better results when used in combination with intra-arterial and intravenous administration (OR, 1.25; 95% CI, 1.07-1.451; p = 0.005). Conclusion: Continuous intravenous tirofiban is effective and safe for patients with AIS undergoing rescue ET, particularly when combined with intra-arterial tirofiban. Systematic review registration: PROSPERO, identifier CRD42023385695.