Science China Life Sciences最新文献

Lignin, an energy-rich and adaptable polymer comprising phenylpropanoid monomers utilized by plants for structural reinforcement, water conveyance, and defense mechanisms, ranks as the planet's second most prevalent biopolymer, after cellulose. Despite its prevalence, lignin is frequently underused in the process of converting biomass into fuels and chemicals. Instead, it is commonly incinerated for industrial heat due to its intricate composition and resistance to decomposition, presenting obstacles for targeted valorization. In contrast to chemical catalysts, biological enzymes show promise not only in selectively converting lignin components but also in seamlessly integrating into cellular structures, offering biocatalysis as a potentially efficient pathway for lignin enhancement. This review comprehensively summarizes cutting-edge biostrategies, ligninolytic enzymes, metabolic pathways, and lignin-degrading strains or consortia involved in lignin degradation, while critically evaluating the underlying mechanisms. Metabolic and genetic engineering play crucial roles in redirecting lignin and its derivatives towards metabolic pathways like the tricarboxylic acid cycle, opening up novel avenues for its valorization. Recent advancements in lignin valorization are scrutinized, highlighting key challenges and promising solutions. Furthermore, the review underscores the importance of innovative approaches, such as leveraging digital systems and synthetic biology, to unlock the commercial potential of lignin-derived raw materials as sustainable feedstocks. Artificial intelligence-driven technologies offer promise in overcoming current challenges and driving widespread adoption of lignin valorization, presenting an alternative to sugar-based feedstocks for bio-based manufacturing in the future. The utilization of available lignin residue for synthesis of high-value chemicals or energy, even alternative food, addresses various crises looming in the food-energy-water nexus.

Ruminant livestock provide a rich source of products, such as meat, milk, and wool, and play a critical role in global food security and nutrition. Over the past few decades, genomic studies of ruminant livestock have provided valuable insights into their domestication and the genetic basis of economically important traits, facilitating the breeding of elite varieties. In this review, we summarize the main advancements for domestic ruminants in reference genome assemblies, population genomics, and the identification of functional genes or variants for phenotypic traits. These traits include meat and carcass quality, reproduction, milk production, feed efficiency, wool and cashmere yield, horn development, tail type, coat color, environmental adaptation, and disease resistance. Functional genomic research is entering a new era with the advancements of graphical pangenomics and telomere-to-telomere (T2T) gap-free genome assembly. These advancements promise to improve our understanding of domestication and the molecular mechanisms underlying economically important traits in ruminant livestock. Finally, we provide new perspectives and future directions for genomic research on ruminant genomes. We suggest how ever-increasing multiomics datasets will facilitate future studies and molecular breeding in livestock, including the potential to uncover novel genetic mechanisms underlying phenotypic traits, to enable more accurate genomic prediction models, and to accelerate genetic improvement programs.

Although disturbances in the gut microbiome have been implicated in multiple sclerosis (MS), little is known about the changes and interactions between the gut microbiome and blood metabolome, and how these changes affect disease-modifying therapy (DMT) in preventing the progression of MS. In this study, the structure and composition of the gut microbiota were evaluated using 16S rRNA gene sequencing and an untargeted metabolomics approach was used to compare the serum metabolite profiles from patients with relapsing-remitting MS (RRMS) and healthy controls (HCs). Results indicated that RRMS was characterized by phase-dependent α-phylogenetic diversity and significant disturbances in serum glycerophospholipid metabolism. Notably, α-phylogenetic diversity was significantly decreased in RRMS patients during the chronic phase (CMS) compared with those in the acute phase (AMS). A distinctive combination of two elevated genera (Slackia, Lactobacillus) and five glycerophospholipid metabolism-associated metabolites (four increased: GPCho(22:5/20:3), PC(18:2(9Z,12Z)/16:0), PE(16:0/18:2(9Z,12Z)), PE(18:1(11Z)/18:2(9Z,12Z)); one decreased: PS(15:0/22:1(13Z))) in RRMS patients when comparing to HCs. Moreover, a biomarker panel consisting of four microbial genera (three decreased: Lysinibacillus, Parabacteroides, UBA1819; one increased: Lachnoanaerobaculum) and two glycerophospholipid metabolism-associated metabolites (one increased: PE(P-16:0/22:6); one decreased: CL(i-12:0/i-16:0/i-17:0/i-12:0)) effectively discriminated CMS patients from AMS patients, which indicate correlation with higher disability. Additionally, DMTs appeared to attenuate MS progression by reducing UBA1819 and upregulating CL(i-12:0/i-16:0/i-17:0/i-12:0). These findings expand our understanding of the microbiome and metabolome roles in RRMS and may contribute to identifying novel diagnostic biomarkers and promising therapeutic targets.

China, with its large geographic span, possesses rich genetic diversity across vast frontier regions in addition to the Han Chinese majority. Importantly, demographic events and various natural and cultural environments in Chinese frontier regions have shaped the genomic diversity of ethnic minorities via local adaptations. Thus, insights into the genetic diversity and adaptive evolution of these under-represented ethnic groups are crucial for understanding evolutionary scenarios and biomedical implications in East Asian populations. Here, we focus on ethnic minorities in Chinese frontier regions and review research advances regarding genomic diversity, genetic structure, population history, genetic admixture, and local adaptation. We first provide an overview of the extensive genetic diversity across populations in different Chinese frontier regions. Next, we summarize research progress regarding genetic ancestry, demographic history, the adaptive process, and the archaic identification of multiple ethnic minorities in different Chinese frontier regions. Finally, we discuss the gaps and opportunities in genomic studies of Chinese populations and the need for a more comprehensive understanding of genomic diversity and the evolution of populations of East Asian ancestry in the post-genomic era.

Despite considerable research underscoring the importance of carbohydrate intake in relation to the risk of type 2 diabetes (T2D), a comprehensive assessment of this relationship is currently lacking. We aimed to examine the associations of various types and food sources of dietary carbohydrate intake with the risk of T2D, to evaluate potential effect modification by other factors, including genetic susceptibility, and to explore the potential mediators for such associations. The present study included 161,872 participants of the UK Biobank who were free of prevalent cancer, cardiovascular disease, or diabetes, and had at least one validated 24-h dietary recall assessment. Multivariable-adjusted age-stratified Cox proportional hazard regression models were applied to estimate hazard ratios (HRs) and 95% confidence intervals (CI) for the associations of various types and food sources of dietary carbohydrate intake with risk of T2D. During a median follow-up of 13.6 years, 4,176 incident cases of T2D were identified. In the multivariable-adjusted models, a greater intake of fiber, carbohydrates from whole grains, and carbohydrates from non-starchy vegetables was significantly associated with a lower risk of T2D (highest vs. lowest quantile, HR [95% CI]=0.70 [0.62-0.79], 0.74 [0.67-0.82], and 0.83 [0.75-0.92], respectively, all P for trend <0.005). In contrast, a higher intake of starch and carbohydrate from starchy vegetables was associated with an increased risk of T2D (highest vs. lowest quantile, HR [95% CI]=1.31 [1.16-1.48] and 1.19 [1.09-1.31], respectively, both P for trend <0.005). Replacing one serving of refined grains or starchy vegetables with an equal amount of whole grains or non-starchy vegetables was associated with 4% to 10% lower risk of T2D (all P values <0.001). The observed associations were generally similar across population subgroups, including individuals with different genetic susceptibility to T2D. Mediation analyses of the inverse association between T2D risk and isocaloric substitution of carbohydrates from refined grains with carbohydrate from whole grains demonstrated that 39.6%, 43.4%, 44.0%, 27.8%, and 34.9% were mediated through body mass index, waist-to-hip ratio, glycosylated hemoglobin, high-density lipoprotein cholesterol, and C-reactive protein, respectively. In addition, the inverse association between the isocaloric substitution of carbohydrates from starchy vegetables with carbohydrates from non-starchy vegetables and T2D was partially mediated through high-density lipoprotein cholesterol (15.9%). These findings underscore the importance of dietary modifications of carbohydrates, particularly considering types and food sources of carbohydrate intake, in the primary prevention of T2D.

Innate immunity serves as a crucial defense mechanism against invading pathogens, yet its negative regulatory network remains under explored. In this study, we identify BEN domain-containing protein 6 (BEND6) as a novel negative regulator of innate immunity through a genome-scale CRISPR knockout screen for host factors essential for viral replication. We show that BEND6 exhibits characteristics of an interferon-stimulated gene (ISG), with its mRNA and protein levels upregulated by RNA virus-induced IFN-β. BEND6 targets IRF3 and inhibits its recruitment by TBK1, thus preventing IRF3 phosphorylation and dimerization. Additionally, BEND6 directly binds to ISRE, thereby hindering the DNA binding activity of IRF3 and blocking the subsequent activation of IFN-β transcription. Taken together, our study reveals the mechanism of BEND6 in promoting the replication of various RNA viruses and provides a potential therapeutic target for RNA virus infection.

The m⁶A modification is an RNA modification that impacts various processes of RNA molecules, including transcription, splicing, stability, and translation. Recently, researchers have discovered that the presence of m⁶A modification can influence the interaction between tumor cells and immune cells and also play a role in regulating the expression of immune response-related genes. Additionally, m⁶A modification is intricately involved in the regulation of tumor immune evasion and drug resistance. Specifically, certain tumor cells can manipulate the gene expression through m⁶A modification to evade immune system attacks. Therefore, it might be possible to enhance tumor immune surveillance and improve the effectiveness of immune-based therapies by manipulating m⁶A modification. This review systematically discusses the role of m⁶A modification in tumor immunity, specifically highlighting its regulation of immune cells and immune-related genes in tumor cells. Furthermore, we explore the potential of m⁶A modification inhibitors as anti-cancer therapies and the significance of m⁶A regulatory factors in predicting the efficacy of tumor immune therapy.

Delayed tooth extraction socket (TES) healing can cause failure of subsequent oral implantation and increase socioeconomic burden on patients. Excessive amounts of M1 macrophages, apoptotic neutrophils (ANs), and neutrophil extracellular traps (NETs) impair alveolar bone regeneration during TES healing. In the present study, we first discovered that conditioned medium (CM) collected from berberine-treated human bone marrow mesenchymal stem cells (BBR-HB-CM) accelerated TES healing. BBR-HB-CM contained bioactive materials that promoted the polarization of macrophages from M1 to M2, impeded the formation of ANs and NETs, and modulated M2 macrophage efferocytosis in vivo and in vitro. Mechanistically, BBR-HB-CM promoted bone formation by inhibiting macrophage-myofibroblast transition and reprogrammed macrophage polarization through p85/AKT/mTOR pathway-dependent autophagy. The 3-methyladenine abolished the therapeutic effects of BBR-HB-CM. Further studies revealed that BBR-HB-CM accelerated TES healing in rats with type 2 diabetes mellitus. Overall, our results demonstrated that BBR-HB-CM had high potential to promote rapid TES healing.

Genomic sources from China are underrepresented in the population-specific reference database. We performed whole-genome sequencing or genome-wide genotyping on 1,207 individuals from four linguistically diverse groups (1,081 Sinitic, 56 Mongolic, 40 Turkic, and 30 Tibeto-Burman people) living in North China included in the 10K Chinese People Genomic Diversity Project (10K_CPGDP) to characterize the genetic architecture and adaptative history of ethnic groups in the Silk Road Region of China. We observed a population split between Northwest Chinese minorities (NWCMs) and Han Chinese since the Upper Paleolithic and later Neolithic genetic differentiation within NWCMs. The observed population substructures among ethnically/linguistically diverse NWCMs suggested that differentiated admixture events contributed to the differences in their genomic and phenotypic diversity. We estimated that the Dongxiang, Tibetan, and Yugur people inherited more than 10% of the Western Eurasian ancestry, which is much greater than that of the Salar and Tu people (<7%), while Han neighbors showed less West Eurasian ancestry (∼1%-3%). Male-biased admixture introduced Western Eurasian ancestry in the Dongxiang, Tibetan, and Yugur populations. We found that the eastern-western admixture in NWCMs occurred ∼800-1,100 years ago, coinciding with intensive economic and cultural exchanges during the Tang and Song dynasties. Additionally, we identified the signatures of natural selection associated with cardiovascular system diseases or lipid metabolism and developmental/neurogenetic disorders. Moreover, the EPAS1 gene showed relatively high population branch statistic values in NWCMs. The well-fitted demographical models presented the vast landscape of complex admixture processes of the Silk Road people, and the newly reported functionally important variations suggested the importance of including ethnolinguistically diverse populations in Chinese genetic studies for uncovering the genetic basis of complex traits/diseases.