The demise of the giant ape Gigantopithecus blacki.

The largest ever primate and one of the largest of the southeast Asian megafauna, Gigantopithecus blacki1, persisted in China from about 2.0 million years until the late middle Pleistocene when it became extinct2-4. Its demise is enigmatic considering that it was one of the few Asian great apes to go extinct in the last 2.6 million years, whereas others, including orangutan, survived until the present5. The cause of the disappearance of G. blacki remains unresolved but could shed light on primate resilience and the fate of megafauna in this region6. Here we applied three multidisciplinary analyses-timing, past environments and behaviour-to 22 caves in southern China. We used 157 radiometric ages from six dating techniques to establish a timeline for the demise of G. blacki. We show that from 2.3 million years ago the environment was a mosaic of forests and grasses, providing ideal conditions for thriving G. blacki populations. However, just before and during the extinction window between 295,000 and 215,000 years ago there was enhanced environmental variability from increased seasonality, which caused changes in plant communities and an increase in open forest environments. Although its close relative Pongo weidenreichi managed to adapt its dietary preferences and behaviour to this variability, G. blacki showed signs of chronic stress and dwindling populations. Ultimately its struggle to adapt led to the extinction of the greatest primate to ever inhabit the Earth.

Last appearance of Homo erectus at Ngandong, Java, 117,000-108,000 years ago.

Homo erectus is the founding early hominin species of Island Southeast Asia, and reached Java (Indonesia) more than 1.5 million years ago1,2. Twelve H. erectus calvaria (skull caps) and two tibiae (lower leg bones) were discovered from a bone bed located about 20 m above the Solo River at Ngandong (Central Java) between 1931 and 19333,4, and are of the youngest, most-advanced form of H. erectus5-8. Despite the importance of the Ngandong fossils, the relationship between the fossils, terrace fill and ages have been heavily debated9-14. Here, to resolve the age of the Ngandong evidence, we use Bayesian modelling of 52 radiometric age estimates to establish-to our knowledge-the first robust chronology at regional, valley and local scales. We used uranium-series dating of speleothems to constrain regional landscape evolution; luminescence, 40argon/39argon (40Ar/39Ar) and uranium-series dating to constrain the sequence of terrace evolution; and applied uranium-series and uranium series-electron-spin resonance (US-ESR) dating to non-human fossils to directly date our re-excavation of Ngandong5,15. We show that at least by 500 thousand years ago (ka) the Solo River was diverted into the Kendeng Hills, and that it formed the Solo terrace sequence between 316 and 31 ka and the Ngandong terrace between about 140 and 92 ka. Non-human fossils recovered during the re-excavation of Ngandong date to between 109 and 106 ka (uranium-series minimum)16 and 134 and 118 ka (US-ESR), with modelled ages of 117 to 108 thousand years (kyr) for the H. erectus bone bed, which accumulated during flood conditions3,17. These results negate the extreme ages that have been proposed for the site and solidify Ngandong as the last known occurrence of this long-lived species.

O-GlcNAcylation stimulates the deubiquitination activity of USP16 and regulates cell cycle progression.

Histone 2A monoubiquitination (uH2A) underscores a key epigenetic regulation of gene expression. In this report, we show that the deubiquitinase for uH2A, ubiquitin-specific peptidase 16 (USP16), is modified by O-linked N-acetylglucosamine (O-GlcNAc). O-GlcNAcylation involves the installation of the O-GlcNAc moiety to Ser/Thr residues. It crosstalks with Ser/Thr phosphorylation, affects protein-protein interaction, alters enzyme activity or protein folding, and changes protein subcellular localization. In our study, we first confirmed that USP16 is glycosylated on Thr203 and Ser214, as reported in a previous chemoenzymatic screen. We then discovered that mutation of the O-GlcNAcylation site Thr203, which is adjacent to deubiquitination-required Cys204, reduces the deubiquitination activity toward H2AK119ub in vitro and in cells, while mutation on Ser214 had the opposite effects. Using USP16 Ser552 phosphorylation-specific antibodies, we demonstrated that O-GlcNAcylation antagonizes cyclin-dependent kinase 1-mediated phosphorylation and promotes USP16 nuclear export. O-GlcNAcylation of USP16 is also required for deubiquitination of Polo-like kinase 1, a mitotic master kinase, and the subsequent chromosome segregation and cytokinesis. In summary, our study revealed that O-GlcNAcylation of USP16 at Thr203 and Ser214 coordinates deubiquitination of uH2A and Polo-like kinase 1, thus ensuring proper cell cycle progression.

Earliest hunting scene in prehistoric art.

Humans seem to have an adaptive predisposition for inventing, telling and consuming stories1. Prehistoric cave art provides the most direct insight that we have into the earliest storytelling2-5, in the form of narrative compositions or 'scenes'2,5 that feature clear figurative depictions of sets of figures in spatial proximity to each other, and from which one can infer actions taking place among the figures5. The Upper Palaeolithic cave art of Europe hosts the oldest previously known images of humans and animals interacting in recognizable scenes2,5, and of therianthropes6,7-abstract beings that combine qualities of both people and animals, and which arguably communicated narrative fiction of some kind (folklore, religious myths, spiritual beliefs and so on). In this record of creative expression (spanning from about 40 thousand years ago (ka) until the beginning of the Holocene epoch at around 10 ka), scenes in cave art are generally rare and chronologically late (dating to about 21-14 ka)7, and clear representations of therianthropes are uncommon6-the oldest such image is a carved figurine from Germany of a human with a feline head (dated to about 40-39 ka)8. Here we describe an elaborate rock art panel from the limestone cave of Leang Bulu' Sipong 4 (Sulawesi, Indonesia) that portrays several figures that appear to represent therianthropes hunting wild pigs and dwarf bovids; this painting has been dated to at least 43.9 ka on the basis of uranium-series analysis of overlying speleothems. This hunting scene is-to our knowledge-currently the oldest pictorial record of storytelling and the earliest figurative artwork in the world.

Progress on network modeling and analysis of gut microecology: a review.

The gut microecological network is a complex microbial community within the human body that plays a key role in linking dietary nutrition and host physiology. To understand the complex relationships among microbes and their functions within this community, network analysis has emerged as a powerful tool. By representing the interactions between microbes and their associated omics data as a network, we can gain a comprehensive understanding of the ecological mechanisms that drive the human gut microbiota. In addition, the network-based approach provides a more intuitive analysis of the gut microbiota, simplifying the study of its complex dynamics and interdependencies. This review provides a comprehensive overview of the methods used to construct and analyze networks in the context of gut microecological background. We discuss various types of network modeling approaches, including co-occurrence networks, causal networks, dynamic networks, and multi-omics networks, and describe the analytical techniques used to identify important network properties. We also highlight the challenges and limitations of network modeling in this area, such as data scarcity and heterogeneity, and provide future research directions to overcome these limitations. By exploring these network-based methods, researchers can gain valuable insights into the intricate relationships and functional roles of microbial communities within the gut, ultimately advancing our understanding of the gut microbiota's impact on human health.

Harnessing the endogenous Type I-C CRISPR-Cas system for genome editing in Bifidobacterium breve.

Bifidobacterium breve, one of the main bifidobacterial species colonizing the human gastrointestinal tract in early life, has received extensive attention for its purported beneficial effects on human health. However, exploration of the mode of action of such beneficial effects exerted by B. breve is cumbersome due to the lack of effective genetic tools, which limits its synthetic biology application. The widespread presence of CRISPR-Cas systems in the B. breve genome makes endogenous CRISPR-based gene editing toolkits a promising tool. This study revealed that Type I-C CRISPR-Cas systems in B. breve can be divided into two groups based on the amino acid sequences encoded by cas gene clusters. Deletion of the gene coding uracil phosphoribosyl-transferase (upp) was achieved in five B. breve strains from both groups using this system. In addition, translational termination of uracil phosphoribosyl-transferase was successfully achieved in B. breve FJSWX38M7 by single-base substitution of the upp gene and insertion of three stop codons. The gene encoding linoleic acid isomerase (bbi) in B. breve, being a characteristic trait, was deleted after plasmid curing, which rendered it unable to convert linoleic acid into conjugated linoleic acid, demonstrating the feasibility of successive editing. This study expands the toolkit for gene manipulation in B. breve and provides a new approach toward functional genome editing and analysis of B. breve strains.IMPORTANCEThe lack of effective genetic tools for Bifidobacterium breve is an obstacle to studying the molecular mechanisms of its health-promoting effects, hindering the development of next-generation probiotics. Here, we introduce a gene editing method based on the endogenous CRISPR-Cas system, which can achieve gene deletion, single-base substitution, gene insertion, and successive gene editing in B. breve. This study will facilitate discovery of functional genes and elucidation of molecular mechanisms of B. breve pertaining to health-associated benefits.

Gut microbiota: a superior operator for dietary phytochemicals to improve atherosclerosis.

Mounting evidence implicates the gut microbiota as a possible key susceptibility factor for atherosclerosis (AS). The employment of dietary phytochemicals that strive to target the gut microbiota has gained scientific support for treating AS. This study conducted a general overview of the links between the gut microbiota and AS, and summarized available evidence that dietary phytochemicals improve AS via manipulating gut microbiota. Then, the microbial metabolism of several dietary phytochemicals was summarized, along with a discussion on the metabolites formed and the biotransformation pathways involving key gut bacteria and enzymes. This study additionally focused on the anti-atherosclerotic potential of representative metabolites from dietary phytochemicals, and investigated their underlying molecular mechanisms. In summary, microbiota-dependent dietary phytochemical therapy is a promising strategy for AS management, and knowledge of "phytochemical-microbiota-biotransformation" may be a breakthrough in the search for novel anti-atherogenic agents.

Fossil dermal denticles reveal the preexploitation baseline of a Caribbean coral reef shark community.

Preexploitation shark baselines and the history of human impact on coral reef-associated shark communities in the Caribbean are tpoorly understood. We recovered shark dermal denticles from mid-Holocene (∼7 ky ago) and modern reef sediments in Bocas del Toro, Caribbean Panama, to reconstruct an empirical shark baseline before major human impact and to quantify how much the modern shark community in the region had shifted from this historical reference point. We found that denticle accumulation rates, a proxy for shark abundance, declined by 71% since the mid-Holocene. All denticle morphotypes, which reflect shark community composition, experienced significant losses, but those morphotypes found on fast-swimming, pelagic sharks (e.g., families Carcharhinidae and Sphyrnidae) declined the most. An analysis of historical records suggested that the steepest decline in shark abundance occurred in the late 20th century, coinciding with the advent of a targeted shark fishery in Panama. Although the disproportionate loss of denticles characterizing pelagic sharks was consistent with overfishing, the large reduction in denticles characterizing demersal species with low commercial value (i.e., the nurse shark Ginglymostoma cirratum) indicated that other stressors could have exacerbated these declines. We demonstrate that the denticle record can reveal changes in shark communities over long ecological timescales, helping to contextualize contemporary abundances and inform shark management and ecology.

Lactobacillus-derived components for inhibiting biofilm formation in the food industry.

Biofilm, a microbial community formed by especially pathogenic and spoilage bacterial species, is a critical problem in the food industries. It is an important cause of continued contamination by foodborne pathogenic bacteria. Therefore, removing biofilm is the key to solving the high pollution caused by foodborne pathogenic bacteria in the food industry. Lactobacillus, a commonly recognized probiotic that is healthy for consumer, have been proven useful for isolating the potential biofilm inhibitors. However, the addition of surface components and metabolites of Lactobacillus is not a current widely adopted biofilm control strategy at present. This review focuses on the effects and preliminary mechanism of action on biofilm inhibition of Lactobacillus-derived components including lipoteichoic acid, exopolysaccharides, bacteriocins, secreted protein, organic acids and some new identified molecules. Further, the review discusses several modern biofilm identification techniques and particularly interesting new technology of biofilm inhibition molecules. These molecules exhibit stronger inhibition of biofilm formation, playing a pivotal role in food preservation and storage. Overall, this review article discusses the application of biofilm inhibitors produced by Lactobacillus, which would greatly aid efforts to eradicate undesirable bacteria from environment in the food industries.

Middle Pleistocene Pongo from Ganxian Cave in southern China with implications for understanding dental size evolution in orangutans.

The Pongo fossil record of China extends from the Early Pleistocene to the Late Pleistocene, but to date, no late Middle Pleistocene samples of Pongo with precise absolute dating have been identified in southern China. Here, we report the recovery of 106 fossil teeth of Pongo from Ganxian Cave in the Bubing Basin, Guangxi, southern China. We dated the speleothems using Uranium-series and dated the two rhinoceros teeth using coupled electron spin resonance/Uranium-series dating methods to between 168.9 ± 2.4 ka and 362 ± 78 ka, respectively. These dates are consistent with the biostratigraphic and magnetostratigraphic age estimates. We further describe the fossil teeth from Ganxian Cave and compare them metrically to samples of fossil Pongo (i.e., Pongo weidenreichi, Pongo duboisi, Pongo palaeosumatrensis, Pongo javensis, and Pongo sp.) from the Early, Middle, and Late Pleistocene and to extant Pongo (i.e., Pongo pygmaeus and Pongo abelii) from Southeast Asia. Based on overall dental size, a high frequency of lingual cingulum remnants on the upper molars, and a low frequency of moderate to heavy wrinkling on the molars, we attribute the Ganxian fossils to P. weidenreichi. Compared with Pongo fossils from other mainland Southeast Asia sites, those from Ganxian confirm that dental size reduction of Pongo occurred principally during the Early and Middle Pleistocene. From the Middle to Late Pleistocene, all teeth except the P3 show little change in occlusal area, indicating that the size of these teeth remained relatively stable over time. The evolutionary trajectory of the Pongo dentition through time may be more complex than previously thought. More orangutan fossils with precise dating constraints are the keys to solving this issue.

Food and drug design for gut microbiota-directed regulation: Current experimental landscape and future innovation.

Most diets and medications enhance host health via microbiota-dependent ways, but it is in the present situation of untargeted regulation. Non-targeted regulation may lead to the ineffectiveness of dietary supplements or drug treatment. Microbiota-directed food, aiming to improve diseases by targeting specific microbes without affecting other bacteria, have been proposed to deal with this problem. However, there is currently no universally applicable method to explore such foods or drugs. In this review, thirty studies on recent efforts in microbiota directed diets and medications are summarized from various databases. The methods used to find new foods and medications are primarily divided into four groups depending on the experimental models: in vivo and in vitro, as well as predictions based on bioinformatics. We also discuss their implementation, interpretation, and respective limitations, and describe the present situation. We further put forward a framework for microbiota-directed foods and medicine according to above methods and other microbiome manipulation, which will spur precision medicine.

The recent advances of glucosinolates and their metabolites: Metabolism, physiological functions and potential application strategies.

Glucosinolates and their metabolites from Brassicaceae plants have received widespread attention due to their anti-inflammatory effects. Glucosinolates occurs an "enterohepatic circulation" in the body, and the glucosinolates metabolism mainly happens in the intestine. Glucosinolates can be converted into isothiocyanates by intestinal bacteria, which are active substances with remarkable anti-inflammatory, anti-cancer, anti-obesity and neuroprotective properties. This biotransformation can greatly improve the bioactivities of glucosinolates. However, multiple factors in the environment can affect the biotransformation to isothiocyanates, including acidic pH, ferrous ions and thiocyanate-forming protein. The derivatives of glucosinolates under those conditions are usually nitriles and thiocyanates, which may impair the potential health benefits. In addition, isothiocyanates are extremely unstable because of an active sulfhydryl group, which limits their applications. This review mainly summarizes the classification, synthesis, absorption, metabolism, physiological functions and potential application strategies of glucosinolates and their metabolites.

Ellagic acid and intestinal microflora metabolite urolithin A: A review on its sources, metabolic distribution, health benefits, and biotransformation.

Foods rich in ellagic tannins are first hydrolyzed into ellagic acid in the stomach and small intestine, and then converted into urolithins with high bioavailability by the intestinal flora. Urolithin has beneficially biological effects, it can induce adipocyte browning, improve cholesterol metabolism, inhibit graft tumor growth, relieve inflammation, and downregulate neuronal amyloid protein formation via the ß3-AR/PKA/p38MAPK, ERK/AMPKα/SREBP1, PI3K/AKT/mTOR signaling pathways, and TLR4, AHR receptors. But differences have been reported in urolithin production capacity among different individuals. Thus, it is of great significance to explore the biological functions of urolithin, screen the strains responsible for biotransformation of urolithin, and explore the corresponding functional genes. Tannin acyl hydrolase can hydrolyze tannins into ellagic acid, and the genera Gordonibacter and Ellagibacter can metabolize ellagic acid into urolithins. Therefore, application of "single bacterium", "single bacterium + enzyme", and "microflora" can achieve biotransformation of urolithin A. In this review, the source and metabolic pathway of ellagic tannins, and the mechanisms of the biological function of a metabolite, urolithin A, are discussed. The current strategies of biotransformation to obtain urolithin A are expounded to provide ideas for further studies on the relationship between urolithin and human health.

Absorption, metabolism, bioactivity, and biotransformation of epigallocatechin gallate.

Epigallocatechin gallate (EGCG), a typical flavone-3-ol polyphenol containing eight free hydroxyl groups, is associated with a variety of bioactivities, such as antioxidant, anti-inflammatory, anti-cancer, and antibacterial activities. However, the poor bioavailability of EGCG restricts its use. In this review, we discuss the processes involved in the absorption and metabolism of EGCG, with a focus on its metabolic interactions with the gut microbiota. Next, we summarize the bioactivities of some key metabolites, describe the biotransformation of EGCG by different microorganisms, and discuss its catabolism by specific bacteria. A deeper understanding of the absorption, metabolism, and biotransformation of EGCG may enable its disease-preventive and therapeutic properties to be better utilized. This review provides a theoretical basis for further development and utilization of EGCG and its metabolites for improving the gut microbiota and physiological health.

Recent updates in anti-glycation strategies: selection of natural products and lactic acid bacteria as potential inhibitors based on the multi-pathway anti-glycation targets.

The prevalence of high-sugar diets and unhealthy habits exacerbates the production of advanced glycation end products (AGEs) in the body. When AGEs excessively accumulate in the body, they accelerate the aging process while directly or indirectly causing other complications that can seriously damage the body. Prevention of glycation damage is gaining increasing attention; however, a systematic strategy to combat glycation and specific glycation inhibitors is still lacking. By analyzing the process of glycation damage, we suggest that glycation damage can be mitigated by the inhibition of AGEs production, binding to proteins, and binding to receptors for advanced glycation end products, as well as the attenuation of downstream linkage reactions. This review summarizes the process of glycation damage. According to each step of the process, the review presents the corresponding anti-glycation strategies. Based on recent anti-glycation studies, we support the fabrication of glycation inhibitors by using natural plant products and fermentation products of lactic acid bacteria that partially exhibit anti-glycation properties. This review summarizes the mechanisms by which these dietary ingredients perform anti-glycation functions, providing relevant research evidence. We hope that this review will support and assist subsequent investigations in the development of anti-glycation inhibitors.

Recent advance in quality preservation of non-thermal preservation technology of fresh mushroom: a review.

Fresh mushrooms have a long history of cultivation and consumption, but high postharvest losses are a concern in the commercial production of mushrooms worldwide. Thermal dehydration is widely used in the preservation of commercial mushrooms, but the flavor and taste of mushrooms are significantly altered after dehydration. Non-thermal preservation technology, which effectively maintains the characteristics of mushrooms, is a viable alternative to thermal dehydration. The objective of this review was to critically assess the factors affecting fresh mushroom quality after preservation is remarkable, with the ultimate goal of developing and promoting non-thermal preservation technology for preserving fresh mushroom quality, effectively extending the shelf life of fresh mushrooms. The factors influencing the quality degradation process of fresh mushrooms discussed herein include the internal factors associated with the mushroom itself and the external factors associated with the storage environment. We present a comprehensive discussion of the effects of different non-thermal preservation technologies on the quality and shelf life of fresh mushrooms. To prevent quality loss and extend the shelf life after postharvest, hybrid methods, such as physical or chemical techniques combined with chemical techniques, and novel nonthermal technologies are highly recommended.

Improvement of inflammatory bowel disease by lactic acid bacteria-derived metabolites: a review.

Lactic acid bacteria (LAB) plays a crucial role in the establishment and maintenance of host health, as well as the improvement of some diseases. One of the major modes is the secretion of metabolites that may be intermediate or end products of the LAB's metabolism. In this review, we summarized some common metabolites (particularly short-chain fatty acids [SCFAs], bacteriocin, and exopolysaccharide [EPS]) from LAB in fermented foods and the gut for the first time. The effects of LAB-derived metabolites (LABM) on inflammation, oxidative stress, the intestinal barrier, and gut microbiota in inflammatory bowel disease (IBD) model are also discussed. The discovery of LABM and identification of IBD biomarkers are mainly attributed to the development of metabolomics technologies, especially nuclear magnetic resonance (NMR), gas chromatography-mass spectrometry (GC-MS), and liquid chromatography tandem mass spectrometry (LC-MS). The application of these metabolomics technologies in identification of LABM and IBD biomarkers are also summarized and analyzed. Although the beneficial effects of some LABM have been explored, undiscovered metabolites and their functions still need further investigations.

Interaction of beta-glucans with gut microbiota: Dietary origins, structures, degradation, metabolism, and beneficial function.

Beta-glucan (BG), a polysaccharide comprised of interfacing glucose monomers joined via beta-glycosidic linkages, can be defined as a type of dietary fiber with high specificity based on its interaction with the gut microbiota. It can induce similar interindividual microbiota responses, thereby having beneficial effects on the human body. In this paper, we review the four main sources of BG (cereals, fungi, algae, and bacteria) and their differences in structure and content. The interaction of BG with gut microbiota and the resulting health effects have been highlighted, including immune enhancement, regulation of serum cholesterol and insulin levels, alleviation of obesity and improvement of cognitive disorders. Finally, the application of BG in food products and its beneficial effects on the gut microbiota of consumers were discussed. Although some of the mechanisms of action remain unclear, revealing the beneficial functions of BG from the perspective of gut microbiota can help provide theoretical support for the development of diets that target the regulation of microbiota.

Microbiota-assisted therapy for systemic inflammatory arthritis: advances and mechanistic insights.

Research on the influence of gut microbiota on systemic inflammatory arthritis has exploded in the past decade. Gut microbiota changes may be a crucial regulatory component in systemic inflammatory arthritis. As a result of advancements in the field, microbiota-assisted therapy has evolved, but this discipline is still in its infancy. Consequently, we review the limitations of current systemic inflammatory arthritis treatment, analyze the connection between the microbiota and arthritis, and summarize the research progress of microbiota regulating systemic inflammatory arthritis and the further development aspects of microbiota-assisted therapy. Finally, the partial mechanisms of microbiota-assisted therapy of systemic inflammatory arthritis are being discussed. In general, this review summarizes the current progress, challenges, and prospects of microbiota-assisted therapy for systemic inflammatory arthritis and points out the direction for the development of microbiota-assisted therapy in the future.

Anti-Inflammatory, Barrier Maintenance, and Gut Microbiome Modulation Effects of Saccharomyces cerevisiae QHNLD8L1 on DSS-Induced Ulcerative Colitis in Mice.

The use of probiotics has been considered as a new therapy option for ulcerative colitis (UC), and yeast has recently received widespread recommendation for human health. In this study, the probiotic characteristics of four yeast strains, Saccharomyces boulardii CNCMI-745, Kluyveromyces marxianus QHBYC4L2, Saccharomyces cerevisiae QHNLD8L1, and Debaryomyces hansenii QSCLS6L3, were evaluated in vitro; their ability to ameliorate dextran sulfate sodium (DSS)-induced colitis was investigated. Among these, S. cerevisiae QHNLD8L1 protected against colitis, which was reflected by increased body weight, colon length, histological injury relief, decreased gut inflammation markers, and intestinal barrier restoration. The abundance of the pathogenic bacteria Escherichia-Shigella and Enterococcaceae in mice with colitis decreased after S. cerevisiae QHNLD8L1 treatment. Moreover, S. cerevisiae QHNLD8L1 enriched beneficial bacteria Lactobacillus, Faecalibaculum, and Butyricimonas, enhanced carbon metabolism and fatty acid biosynthesis function, and increased short chain fatty acid (SCFAs) production. Taken together, our results indicate the great potential of S. cerevisiae QHNLD8L1 supplementation for the prevention and alleviation of UC.