Ferroptosis is a recently identified iron-dependent form of nonapoptotic cell death characterized by reactive oxygen species (ROS) generation and lipid peroxidation. Here, we report a novel iron-dependent form of ferroptosis induced by labile iron and investigate the mechanism underlying this process. We find that labile iron-induced ferroptosis is distinct from canonical ferroptosis and is linked to the mitochondrial pathway. Specifically, the mitochondrial calcium uniporter mediates the ferroptosis induced by labile iron. Interestingly, cells undergoing labile iron-induced ferroptosis exhibit cytoplasmic features of oncosis and nuclear features of apoptosis. Furthermore, labile iron-induced ferroptosis involves a unique set of genes. Finally, labile iron-induced ferroptosis was observed in liver subjected to acute iron overload in vivo. Our study reveals a novel form of ferroptosis that may be implicated in diseases caused by acute injury.

UPR is a conserved response in eukaryotes and can alleviate endoplasmic reticulum (ER) stresses induced by abiotic and biotic stresses. The interactions between UPR and plant RNA viruses have been documented, while the interplays between UPR and plant DNA viruses remain unknown. Using tomato yellow leaf curl China virus (TYLCCNV) and its associated betasatellite (TYLCCNB) as a model, we indicate that TYLCCNB βC1 is a major inducer of UPR and can upregulate the expression of bZIP60, a transcription factor in Nicotiana benthamiana plants. Treatment using ER stress inducers or overexpression of NbbZIP60 increases βC1 accumulation and benefits TYLCCNV/TYLCCNB infection in N. benthamiana plants, and vice versa. In the TYLCCNV/TYLCCNB-infected or the βC1-expressing cells, NbbZIP60 is exported from the nucleus to the nuclear periphery via the XPO1 pathway, and blocking the XPO1 pathway inhibited TYLCCNV/TYLCCNB infection. We have found that the NbbZIP60-regulated pro-survival genes could promote virus infection, and the pro-death gene plays a contrasting role in virus infection. This study reveals that geminivirus infection activates UPR and utilizes the up-regulated molecular chaperons to promote viral infection, and then induces the nuclear export of NbbZIP60 to evade plant defense response, which is a distinct virulence strategy exploited by plant pathogens.

Vegetable crops provide a rich source of essential nutrients for humanity and represent critical economic values to global rural societies. However, genetic studies of vegetable crops have lagged behind major food crops, such as rice, wheat and maize, thereby limiting the application of molecular breeding. In the past decades, genome sequencing technologies have been increasingly applied in genetic studies and breeding of vegetables. In this review, we recapitulate recent progress on reference genome construction, population genomics and the exploitation of multi-omics datasets in vegetable crops. These advances have enabled an in-depth understanding of their domestication and evolution, and facilitated the genetic dissection of numerous agronomic traits, which jointly expedites the exploitation of state-of-the-art biotechnologies in vegetable breeding. We further provide perspectives of further directions for vegetable genomics and indicate how the ever-increasing omics data could accelerate genetic, biological studies and breeding in vegetable crops.

Multivalent vaccines combining crucial mutations from phylogenetically divergent variants could be an effective approach to defend against existing and future SARS-CoV-2 variants. In this study, we developed a tetravalent COVID-19 vaccine SCTV01E, based on the trimeric Spike protein of SARS-CoV-2 variants Alpha, Beta, Delta, and Omicron BA.1, with a squalene-based oil-in-water adjuvant SCT-VA02B. In the immunogenicity studies in naïve BALB/c and C57BL/6J mice, SCTV01E exhibited the most favorable immunogenic characteristics to induce balanced and broad-spectrum neutralizing potencies against pre-Omicron variants (D614G, Alpha, Beta, and Delta) and newly emerging Omicron subvariants (BA.1, BA.1.1, BA.2, BA.3, and BA.4/5). Booster studies in C57BL/6J mice previously immunized with D614G monovalent vaccine demonstrated superior neutralizing capacities of SCTV01E against Omicron subvariants, compared with the D614G booster regimen. Furthermore, SCTV01E vaccination elicited naïve and central memory T cell responses to SARS-CoV-2 ancestral strain and Omicron spike peptides. Together, our comprehensive immunogenicity evaluation results indicate that SCTV01E could become an important COVID-19 vaccine platform to combat surging infections caused by the highly immune evasive BA.4/5 variants. SCTV01E is currently being studied in a head-to-head immunogenicity comparison phase 3 clinical study with inactivated and mRNA vaccines (NCT05323461).

Intensive livestock and poultry farming in China largely relied on the use of in-feed antibiotics until July 2020. The consequences of antibiotic overuse in animal feed include accumulation in animal products and the development of bacterial antibiotic resistance, both of which threaten food safety and human health. China has now completely banned the circulation of commercial feed containing growth-promoting drug additives (except Chinese herbal medicine). Therefore, alternatives to in-feed antibiotics in animal production are greatly needed. Natural phenolic compounds (NPCs) exist widely in plants and are non-toxic, non-polluting, highly reproducible, and leave little residue. Many natural flavonoids, phenolic acids, lignans, and stilbenes have polyphenol chemical structures and exhibit great potential as alternatives to antibiotics. In this review we delineate the characteristics of plant-derived NPCs and summarize their current applications as alternatives to in-feed antibiotics, aiming to provide new strategies for antibiotic-free feeding and promote the development of more sustainable animal husbandry practices.

Maintainance of sulfomucin is a key end point in the treatment of diarrhea and inflammatory bowel disease (IBD). However, the mechanisms underlying the microbial sense to sulfomucin are poorly understood, and to date, there are no therapies targeting the secretion and maturation of sulfomucin in IBD. Herein, we biosynthesized poly-β-hydroxybutyrate (PHB) and found that PHB could alleviate inflammation caused by diarrhea and colitis by enhancing the differentiation of sulfomucin. Microbiota transplantation and clearance together demonstrate that PHB promoting sulfomucin is mediated by Lactobacillus johnsonii (L. johnsonii). Further studies revealed that PHB provides a favorable niche for L. johnsonii biofilm formation to resist disturbance and support its growth. L. johnsonii-biofilm alleviates colitis by regulating fucose residues to promote goblet cell differentiation and subsequent sulfomucin maturation. Importantly, PHB alleviates colitis by enhancing sulfomucin secretion and maturation in a L. johnsonii-dependent manner. PHB represents a class of guardians, acting as a safe probiotic-biofilm delivery system that significantly promotes probiotic proliferation. Altogether, this study adds weight to the possible role of probiotics and functional materials in the treatment of intestinal inflammation. The application of PHB and biofilm self-coating L. johnsonii carries high translational potential and may be of clinical relevance.

Pork meat is closely related to physicochemical alterations during growth and development, resulting in differences in nutritional value and meat flavor. This study aimed to evaluate the composition of amino acids, fatty acids, and metabolic profiles in the longissimus thoracis muscle (LM) of Shaziling pigs aged 30, 90, 150, 210, and 300 days. The results showed that the predominant fatty acids identified in the LM of Shaziling pigs were C16:0, C16:1, C18:0, C18:1n9c, and C18:2n6c. An opposite correlation was observed for C18:2n6c and n6/n3 polyunsaturated fatty acids (P<0.05). Alanine, aspartate, glutamate, D-glutamine, and D-glutamate metabolism were the main metabolic pathways for the Shaziling pig meat flavor (P<0.05). Moreover, the correlation coefficients revealed that the contents of anserine, C16:0, C16:1, and C18:1n9c were positively correlated with intramuscular fat and/or pH24h and were negatively correlated with the values of L* (lightness) and b* (yellowness) (P<0.05). In conclusion, age greatly affected the meat quality of Shaziling pigs, and the contents of muscular anserine, C16:0, C16:1, and C18:1n9c might be promising indicators for better meat quality.

Vaccines are essential public health tools and play an important role in reducing the burden of infectious diseases in the population. Emerging infectious diseases and outbreaks pose new challenges for vaccine development, requiring the rapid design and production of safe and effective vaccines against diseases with limited resources. Here, we focus on the development of vaccines in broad fields ranging from conventional prophylactic vaccines against infectious diseases to therapeutic vaccines against chronic diseases and cancer providing a comprehensive overview of recent advances in eight different vaccine forms (live attenuated vaccines, inactivated vaccines, polysaccharide and polysaccharide conjugate vaccines, recombinant subunit vaccines, virus-like particle and nanoparticle vaccines, polypeptide vaccines, DNA vaccines, and mRNA vaccines) and the therapeutic vaccines against five solid tumors (lung cancer breast cancer colorectal cancer liver cancer and gastric cancer), three infectious diseases (human immunodeficiency virus, hepatitis B virus and human papillomavirus-induced diseases) and three common chronic diseases (hypertension, diabetes mellitus and dyslipidemia). We aim to provide new insights into vaccine technologies, platforms, applications and understanding of potential next-generation preventive and therapeutic vaccine technologies paving the way for the vaccines design in the future.

One factor that shapes the establishment of early neonatal intestinal microbiota is environmental microbial exposure, and probiotic application has been shown to promote health and growth of piglets. Thus, this study hypothesized that environmental probiotic application in early days of life would be beneficial to newborn piglets. This study aimed to investigate the effect of spraying a compound probiotic fermented liquid (CPFL) into the living environment of piglets on their early growth performance and immunity. This work included 68 piglets, which were randomized into probiotic and control groups. Blood and fecal samples were collected at 0, 3, 7, 14, and 21 days of age. Spraying CPFL significantly reshaped the microbiota composition of the delivery room environment, increased piglets' daily weight gain and weaning weight (P<0.001), and modulated piglets' serum cytokine levels (increases in IgA, IgG, and IL-10; decrease in IFN-γ; P<0.05 in each case) in piglets. Additionally, spraying CPFL during early days of life modified piglets' gut microbiota structure and diversity, increased the abundance of some potentially beneficial bacteria (such as Bacteroides uniformis, Butyricimonas virosa, Parabacteroides distasonis, and Phascolarctobacterium succinatutens) and decreased the abundance of Escherichia coli (P<0.05). Interestingly, CPFL application also significantly enhanced the gut microbial bioactive potential and levels of several serum metabolites involved in the metabolism of vitamins (B2, B3, B6, and E), medium/long-chain fatty acids (caproic, tetradecanoic, and peptadecanoic acids), and dicarboxylic acids (azelaic and sebacic acids). Our study demonstrated that spraying CPFL significantly could improve piglets' growth performance and immunity, and the beneficial effects are associated with changes in the gut microbiota and host metabolism. Our study has provided novel data for future development of probiotic-based health-promoting strategies and expanded our knowledge of probiotic application in animal husbandry.

The rapid accumulation of large-scale single-cell RNA-seq datasets from multiple institutions presents remarkable opportunities for automatically cell annotations through integrative analyses. However, the privacy issue has existed but being ignored, since we are limited to access and utilize all the reference datasets distributed in different institutions globally due to the prohibited data transmission across institutions by data regulation laws. To this end, we present scPrivacy, which is the first and generalized automatically single-cell type identification prototype to facilitate single cell annotations in a data privacy-preserving collaboration manner. We evaluated scPrivacy on a comprehensive set of publicly available benchmark datasets for single-cell type identification to stimulate the scenario that the reference datasets are rapidly generated and distributed in multiple institutions, while they are prohibited to be integrated directly or exposed to each other due to the data privacy regulations, demonstrating its effectiveness, time efficiency and robustness for privacy-preserving integration of multiple institutional datasets in single cell annotations.

Largely due to population ageing, the cancer burden from older people has been rising, which imposed considerable pressure on current Chinese healthcare system. We provide comprehensive information about cancer burden of Chinese older people based on the most recent data from National Central Cancer Registry of China. The logarithmic linear regression was used to project the current cancer burden in 2022, and Joinpoint regression was used for temporal trend analysis from 2000 to 2017. We also estimated cancer statistics of older people in the US, Japan and the Republic of Korea for comparisons. It is estimated that 2.79 million cases and 1.94 million deaths occur for Chinese older people, representing 55.8% and 68.2% of cases and deaths in all population in 2022. The overall cancer incidence rate gradually increased among older women, while the mortality rates declined for both sexes. Notably, approximately 10.0% of all cases and 17.7% of all deaths are from people aged over 80 years, and cancer incidence and mortality in this age group showed upward trends for women. Lung cancer and digestive cancers are the leading cancer types for Chinese older people. Compared with other countries, China has lower incidence rates but higher mortality rates for older people. The rapidly growing burden of prostate cancer, breast cancer, colorectal cancer, and declines in esophageal cancer, stomach cancer, and liver cancer among older people indicate the cancer pattern in China is being in a transition stage to that in developed countries. Our findings imply that it should be the national health priority to meet the growing demands for cancer diagnosis, treatment and care services from the older people as the rapid population ageing in next few decades.

Erratum for Sci China Life Sci. 2020 Jul;63(7):1093-1095.

The sesquiterpene alpha-bisabolol is the predominant active ingredient in essential oils that are highly valued in the cosmetics industry due to its wound healing, anti-inflammatory, and skin-soothing properties. Alpha-bisabolol was thought to be restricted to Compositae plants. Here we reveal that alpha-bisabolol is also synthesized in rice, a non-Compositae plant, where it acts as a novel sesquiterpene phytoalexin. Overexpressing the gene responsible for the biosynthesis of alpha-bisabolol, OsTPS1, conferred bacterial blight resistance in rice. Phylogenomic analyses revealed that alpha-bisabolol-synthesizing enzymes in rice and Compositae evolved independently. Further experiments demonstrated that the natural variation in the disease resistance level was associated with differential transcription of OsTPS1 due to polymorphisms in its promoter. We demonstrated that OsTPS1 was regulated at the epigenetic level by JMJ705 through the methyl jasmonate pathway. These data reveal the cross-family accumulation and regulatory mechanisms of alpha-bisabolol production.

Plant and fungal species interactions drive many essential ecosystem properties and processes; however, how these interactions differ between aboveground and belowground habitats remains unclear at large spatial scales. Here, we surveyed 494 pairwise fungal communities in leaves and soils by Illumina sequencing, which were associated with 55 woody plant species across more than 2,000-km span of mountain forests in eastern China. The relative contributions of plant, climate, soil and space to the variation of fungal communities were assessed, and the plant-fungus network topologies were inferred. Plant phylogeny was the strongest predictor for fungal community composition in leaves, accounting for 19.1% of the variation. In soils, plant phylogeny, climatic factors and soil properties explained 9.2%, 9.0% and 8.7% of the variation in soil fungal community, respectively. The plant-fungus networks in leaves exhibited significantly higher specialization, modularity and robustness (resistance to node loss), but less complicated topology (e.g., significantly lower linkage density and mean number of links) than those in soils. In addition, host/fungus preference combinations and key species, such as hubs and connectors, in bipartite networks differed strikingly between aboveground and belowground samples. The findings provide novel insights into cross-kingdom (plant-fungus) species co-occurrence at large spatial scales. The data further suggest that community shifts of trees due to climate change or human activities will impair aboveground and belowground forest fungal diversity in different ways.