Science China Life Sciences最新文献

Recurrent implantation failure (RIF) poses a substantial challenge in assisted reproductive technologies, causing serious psychological burden and economic pressure to patients with infertility. However, the pathogenesis of RIF remains unclear; therefore, in-depth research on RIF is crucial for guiding clinical treatment. Recent studies have indicated that reproductive tract microbiota imbalance is closely related to RIF, making it a new and promising research direction to explore. The present study shows that during the secretory phase, alpha diversity of the endometrial microbiota (EnM) significantly differed (P=0.022) between the RIF and control groups. Moreover, beta diversity analysis found significant differences in both the EnM and uterine lavage fluid microbiota (UfM) (both P<0.05). Further comparing the endometrial tissue metabolites of the RIF and control groups in the secretory phase, 34 metabolites were significantly increased, while 19 others, such as dimethylglycine (DMG), were significantly decreased in the RIF group. Correlation analysis revealed significant correlations between differentially abundant microbiota and metabolites in the endometrium. Furthermore, transplantation of EnM from the RIF group into the uterine cavity of SD rats significantly altered the microecological environment of the uterine cavity, decreasing Hoxa-10 and Lif and reducing embryonic implantation sites. Further exploration of the mechanism revealed that this transplantation decreased the proportion of uterine regulatory T (Treg) cells and the expression of DMG. Additionally, DMG supplementation is expected to mitigate the reduction in Treg and the impairment of endometrial receptivity caused by endometrial tissue microbiota disorders. Therefore, alterations in EnM in patients with RIF may alter endometrial metabolites, decrease Treg-cell proportions, affect endometrial receptivity, and ultimately induce recurrent implantation failure.

Why some flowers are so fragrant remains mysterious. The hypothesis of pollinator-mediated selection suggests that floral scent offers olfactory signals attracting pollen vectors, but it may be susceptible to pollen consumers. To explore the filtering hypothesis of floral scent that lures potential pollinators but repels pollinivores, here we provide the first report that thrips were the only effective pollinators for Osmanthus fragrans (Oleaceae), a famous fragrant tree whose flowers produce no nectar, although co-flowering species were pollinated by diverse insects, including honeybees, in both wild and cultivated populations. A series of experimental tests of ecological functions in floral scent demonstrate that two major aromatic compounds, β-ionone and linalool, both deter honeybee visits, but β-ionone attracts thrips. Honeybees obviously avoided O. fragrans, and ceased re-visiting Hibiscus mutabilis flowers that were artificially added linalool or β-ionone, illustrating a push-pull strategy using floral scent to recruit thrips pollinators but repel pollen feeders to reduce pollen consumption. The finding of β-ionone as an olfactory signal filtering pollen vectors highlights that the diversity of floral volatiles could also be selected by antagonists via pollen protection from pollinivore repellence.

Schizophrenia is a multifaceted psychiatric disorder characterized by hallucinations, delusions, cognitive deficits, and social dysfunction. Its etiology involves a complex interplay of neurochemical, neurodevelopmental, genetic, and immune responses. Despite extensive research, its precise etiology remains elusive. Multiple hypotheses have been proposed to explain its onset and progression. Neurochemical hypotheses focus on dysregulation of the dopamine and glutamate systems, leading to characteristic symptoms. Neurodevelopmental theories suggest that prenatal and perinatal insults contribute to abnormal brain development, affecting regions such as the prefrontal cortex and the hippocampus. Genetic predispositions play a crucial role, as evidenced by familial aggregation and genome-wide association studies that identified risk genes. Additionally, emerging research has implicated immune system dysfunction and inflammation in the pathophysiology of schizophrenia. Current therapeutic strategies primarily focus on antipsychotic medications targeting dopamine receptors. The efficacy of these medications varies and often fails to address negative and cognitive symptoms. Advances in the understanding of the multifactorial mechanisms underlying schizophrenia are essential for developing more effective and comprehensive treatment approaches, such as early intervention, personalized medicine, and novel pharmacological and psychosocial therapies. The study reviewed the latest findings on the neurobiology of schizophrenia and the implications of these findings for the development of new mechanistically based treatments and precision medicine for psychotic symptoms.

Elevated blood low-density lipoprotein (LDL) levels are a major risk factor for cardiovascular disease. Increasing LDL receptor (LDLR) expression effectively reduces blood LDL and serves as a key therapeutic strategy for preventing and treating cardiovascular disease. However, it remains unclear how LDLR in different aortic cells contributes to atherosclerosis progression. In this study, we found that hepatocyte-specific deletion of Ldlr in combination with high-fat, high-cholesterol diet feeding induced hypercholesterolemia and atherosclerosis in mice. On this background, further deletion of Ldlr in endothelial cells or smooth muscle cells had no significant effects on atherosclerosis, whereas myeloid-selective ablation of Ldlr markedly attenuated atherosclerotic plaque formation. The decreased percentages of T cells and natural killer T cells in the aorta of mice lacking Ldlr in myeloid cells partially explained the reduced atherosclerotic burden, despite that bone marrow-derived macrophages from Ldlr knockout mice could still be induced to form foam cells in vitro. Therefore, LDLR is better to be elevated in a cell-specific manner for cardiovascular disease prevention and treatment.

Esophageal squamous cell carcinoma (ESCC) is a prevalent malignancy worldwide with limited therapeutic options. Emerging evidence implicates intratumoral bacteria in ESCC pathogenesis. Here, we identified enriched levels of the Gram-positive bacterium Streptococcus mitis (S. mitis) in ESCC patient tumor tissues, which facilitated ESCC progression both in vitro and in vivo. Mechanistically, mitilysin (MLY), a virulence factor secreted by S. mitis, interacted with zinc finger protein 460 (ZNF460) and promoted its proteasomal degradation. Downregulation of this transcription factor suppressed the transcription of circular RNA circAAGAB, subsequently activating the miR-671-5p/GAS7c and PABP1/TNFAIP2 pathways to enhance ESCC cell proliferation and metastasis. Furthermore, we developed an S. mitis-targeted, mesoporous silica nanoparticle (MSN)-based drug delivery system, in which the MSN surface was decorated with an antibody against lipoteichoic acid (LTA), a major cell wall component of Gram-positive bacteria (LTA-MSNs). When loaded with penicillin, circAAGAB, or both, LTA-MSNs precisely targeted intratumoral S. mitis in ESCC patient-derived xenograft (PDX) models, demonstrating potent tumor-suppressive efficacy. Collectively, our findings reveal that intratumoral S. mitis critically drives ESCC tumorigenesis and represents a promising therapeutic target.

Climate change has intensified the frequency and severity of urban droughts, exposing urban green spaces to abrupt and extreme water shortage that disrupts plant-microbe interactions and microbial multifunctionality. Understanding how rhizosphere and phyllosphere microbial communities respond to drought and how these shifts influence urban microbial functions is crucial for developing strategies to enhance the resilience of urban ecosystems under climate change. In this study, we conducted microcosm experiments simulating four drought intensities, integrating omics technologies with soil enzyme stoichiometry to investigate the effects of drought on microbial communities associated with Zoysia japonica (Steud) and urban microbial multifunctionality. Our results demonstrate that drought intensities significantly altered the compositions of bacterial and fungal communities in both the rhizosphere and phyllosphere. Moreover, drought enhanced microbial multifunctionality by significantly affecting 21 microbial functional potentials, including carbon fixation and denitrification. Although urban microbial multifunctionality largely returned to the control level after rehydration, five functions remained altered, including phyllosphere organic nitrogen mineralization and soil polyphenol oxidase activity. Biotic factors, particularly rhizosphere bacteria and fungi, directly influenced microbial multifunctionality during drought, whereas abiotic factors, such as electrical conductivity, dissolved organic carbon, and ammonium-nitrogen (NH₄⁺-N), had indirect effects. After rehydration, abiotic factors, especially pH and NH₄⁺-N, emerged as the main direct drivers. These findings underscore a shift from biotic to abiotic regulation of urban microbial multi-functionality across drought and rehydration, emphasizing the vital role of microbial communities in ecosystem resilience and the need to consider both biotic and abiotic factors in urban drought management.

The co-occurrence of KPC and NDM carbapenemases in Gram-negative bacteria presents a serious and expanding global health threat. This study characterized 338 KPC-2/NDM-1 dual-positive isolates from 23 countries, including 41 clinical strains sequenced through hybrid second- and third-generation platforms from China's national surveillance network. These isolates spanned six genera, 58 species, and 138 sequence types, reflecting substantial taxonomic and geographic diversity. Molecular analysis identified IncFII(p14) plasmids as the principal vectors for cross-genus dissemination of KPC-2, while IncX3, IncN, and IncFIB(pB171)/IncFII(Yp) plasmids were dominant carriers of NDM-1 among the studied strains. Codon usage analysis indicated stronger bias in KPC-2 plasmids (effective codon number: 39.17, optimal codons: 17) compared to NDM-1 plasmids (effective codon number: 41.25, optimal codons: 12), indicating differential evolutionary pressures. Dual-positive strains exhibited significantly higher virulence scores and broader resistance profiles than reference strains (P<0.001). Notably, only 14.6% of isolates harbored Type I-E CRISPR-Cas systems, all of which encoded the anti-CRISPR protein AcrIE10. Furthermore, Type II methyltransferase numbers were significantly enriched in dual-positive strains (P<0.005), suggesting a potential role in modulating host defense evasion. We propose that in Klebsiella spp., KPC-2 plasmids are typically acquired prior to NDM-1 plasmids and can form hybrid plasmids. In non-Klebsiella genera, dual resistance is primarily driven by independent acquisition of high-risk plasmids such as IncFII(p14) and IncX3, without a fixed temporal order. These findings highlight the convergence of global plasmid-mediated resistance, host-pathogen immune interplay, and pan-resistance evolution. Targeting high-risk plasmid lineages and host defense-modulating elements may be key to forecasting resistance emergence and guiding early interventions against dual-carbapenemase-producing pathogens.