The episodic resurgence of highly pathogenic avian influenza H5 virus.

Highly pathogenic avian influenza (HPAI) H5N1 activity has intensified globally since 2021, increasingly causing mass mortality in wild birds and poultry and incidental infections in mammals1-3. However, the ecological and virological properties that underscore future mitigation strategies still remain unclear. Using epidemiological, spatial and genomic approaches, we demonstrate changes in the origins of resurgent HPAI H5 and reveal significant shifts in virus ecology and evolution. Outbreak data show key resurgent events in 2016-2017 and 2020-2021, contributing to the emergence and panzootic spread of H5N1 in 2021-2022. Genomic analysis reveals that the 2016-2017 epizootics originated in Asia, where HPAI H5 reservoirs are endemic. In 2020-2021, 2.3.4.4b H5N8 viruses emerged in African poultry, featuring mutations altering HA structure and receptor binding. In 2021-2022, a new H5N1 virus evolved through reassortment in wild birds in Europe, undergoing further reassortment with low-pathogenic avian influenza in wild and domestic birds during global dissemination. These results highlight a shift in the HPAI H5 epicentre beyond Asia and indicate that increasing persistence of HPAI H5 in wild birds is facilitating geographic and host range expansion, accelerating dispersion velocity and increasing reassortment potential. As earlier outbreaks of H5N1 and H5N8 were caused by more stable genomic constellations, these recent changes reflect adaptation across the domestic-bird-wild-bird interface. Elimination strategies in domestic birds therefore remain a high priority to limit future epizootics.

msBERT-Promoter: a multi-scale ensemble predictor based on BERT pre-trained model for the two-stage prediction of DNA promoters and their strengths.

BACKGROUND: A promoter is a specific sequence in DNA that has transcriptional regulatory functions, playing a role in initiating gene expression. Identifying promoters and their strengths can provide valuable information related to human diseases. In recent years, computational methods have gained prominence as an effective means for identifying promoter, offering a more efficient alternative to labor-intensive biological approaches. RESULTS: In this study, a two-stage integrated predictor called "msBERT-Promoter" is proposed for identifying promoters and predicting their strengths. The model incorporates multi-scale sequence information through a tokenization strategy and fine-tunes the DNABERT model. Soft voting is then used to fuse the multi-scale information, effectively addressing the issue of insufficient DNA sequence information extraction in traditional models. To the best of our knowledge, this is the first time an integrated approach has been used in the DNABERT model for promoter identification and strength prediction. Our model achieves accuracy rates of 96.2% for promoter identification and 79.8% for promoter strength prediction, significantly outperforming existing methods. Furthermore, through attention mechanism analysis, we demonstrate that our model can effectively combine local and global sequence information, enhancing its interpretability. CONCLUSIONS: msBERT-Promoter provides an effective tool that successfully captures sequence-related attributes of DNA promoters and can accurately identify promoters and predict their strengths. This work paves a new path for the application of artificial intelligence in traditional biology.

Enzyme enhanced lactic acid fermentation of swine manure and apple waste: Insights from organic matter transformation and functional bacteria.

Anaerobic co-fermentation is a favorable way to convert agricultural waste, such as swine manure (SM) and apple waste (AW), into lactic acid (LA) through microbial action. However, the limited hydrolysis of organic matter remains a main challenge in the anaerobic co-fermentation process. Therefore, this work aims to deeply understand the impact of cellulase (C) and protease (P) ratios on LA production during the anaerobic co-fermentation of SM with AW. Results showed that the combined use of cellulase and protease significantly improved the hydrolysis during the enzymatic pretreatment, thus enhancing the LA production in anaerobic acidification. The highest LA reached 41.02 ± 2.09 g/L within 12 days at the ratio of C/P = 1:3, which was approximately 1.26-fold of that in the control. After a C/P = 1:3 pretreatment, a significant SCOD release of 45.34 ± 2.87 g/L was achieved, which was 1.13 times the amount in the control. Moreover, improved LA production was also attributed to the release of large amounts of soluble carbohydrates and proteins with enzymatic pretreated SM and AW. The bacterial community analysis revealed that the hydrolytic bacteria Romboutsia and Clostridium_sensu_stricto_1 were enriched after enzyme pretreatment, and Lactobacillus was the dominant bacteria for LA production. This study provides an eco-friendly technology to enhance hydrolysis by enzymatic pretreatment and improve LA production during anaerobic fermentation.

Detection of Clade 2.3.4.4b Avian Influenza A(H5N8) Virus in Cambodia, 2021.

In late 2021, highly pathogenic avian influenza A(H5N8) clade 2.3.4.4b viruses were detected in domestic ducks in poultry markets in Cambodia. Surveillance, biosafety, and biosecurity efforts should be bolstered along the poultry value chain to limit spread and infection risk at the animal-human interface.

Multiple Infiltration and Cross-Species Transmission of Foamy Viruses across the Paleozoic to the Cenozoic Era.

Foamy viruses (FVs) are complex retroviruses that can infect humans and other animals. In this study, by integrating transcriptomic and genomic data, we discovered 412 FVs from 6 lineages in amphibians, which significantly increased the known set of FVs in amphibians. Among these lineages, salamander FVs maintained a coevolutionary pattern with their hosts that could be dated back to the Paleozoic era, while in contrast, frog FVs were much more likely acquired from cross-species (class-level) transmission in the Cenozoic era. In addition, we found that three distinct FV lineages had integrated into the genome of a salamander. Unexpectedly, we identified a lineage of endogenous FVs in caecilians that expressed all complete major genes, demonstrating the potential existence of an exogenous form of FV outside of mammals. Our discovery of rare phenomena in amphibian FVs has significantly increased our understanding of the macroevolution of the complex retrovirus. IMPORTANCE Foamy viruses (FVs) represent, more so than other viruses, the best model of coevolution between a virus and a host. This study represents the largest investigation so far of amphibian FVs and reveals 412 FVs of 6 distinct lineages from three major orders of amphibians. Besides a coevolutionary pattern, cross-species and repeated infections were also observed during the evolution of amphibian FVs. Remarkably, expressed FVs including a potential exogenous form were discovered, suggesting that active FVs might be underestimated in nature. These findings revealed that the multiple origins and complex evolution of amphibian FVs started from the Paleozoic era.

Co-circulation of multiple reassortant H6 subtype avian influenza viruses in wild birds in eastern China, 2016-2017.

BACKGROUND: H6 subtype influenza viruses were prevalent in domestic poultry and wild birds, which also could pose potential threat to humans. However, little is known about the prevalence of H6 subtype viruses in wild birds in eastern China, a crucial stopover or wintering site for migratory wild birds along the East Asian-Australasian Flyway. METHODS: During the routine surveillance in 2016-2017, H6 subtype AIVs positive samples were identified, and the representative strains were selected for further sequence and phylogenetic analysis and the pathogenicity in mice were evaluated. RESULTS: Among the 30 H6 positive samples, there were at least four subtypes H6N1, H6N2, H6N5 and H6N8 co-circulated in Shanghai, China. Genetic analysis showed the 8 representative isolates shared homology with different AIV sub-lineages isolated from domestic ducks or wild birds in different countries along the East Asian-Australasian flyways, and were classified into 7 new genotypes. The pathogenicity to mice showed that these H6 viruses could replicate efficiently in the lungs without prior adaptation, but could not cause mice death. CONCLUSIONS: Eight novel strains belonged to H6N1, H6N2, H6N5 and H6N8 subtypes were isolated. Phylogenetic analyses revealed multiple origins of internal genes indicative of robust reassortment events and frequent wild birds-poultry interaction encouraging the evolution and emergence of new genotypes. The pathogenicity to mammals should be closely monitored to prevent the emergence of novel pandemic viruses.

Emergence and Adaptation of a Novel Highly Pathogenic H7N9 Influenza Virus in Birds and Humans from a 2013 Human-Infecting Low-Pathogenic Ancestor.

Since its emergence in 2013, the H7N9 low-pathogenic avian influenza virus (LPAIV) has been circulating in domestic poultry in China, causing five waves of human infections. A novel H7N9 highly pathogenic avian influenza virus (HPAIV) variant possessing multiple basic amino acids at the cleavage site of the hemagglutinin (HA) protein was first reported in two cases of human infection in January 2017. More seriously, those novel H7N9 HPAIV variants have been transmitted and caused outbreaks on poultry farms in eight provinces in China. Herein, we demonstrate the presence of three different amino acid motifs at the cleavage sites of these HPAIV variants which were isolated from chickens and humans and likely evolved from the preexisting LPAIVs. Animal experiments showed that these novel H7N9 HPAIV variants are both highly pathogenic in chickens and lethal to mice. Notably, human-origin viruses were more pathogenic in mice than avian viruses, and the mutations in the PB2 gene associated with adaptation to mammals (E627K, A588V, and D701N) were identified by next-generation sequencing (NGS) and Sanger sequencing of the isolates from infected mice. No polymorphisms in the key amino acid substitutions of PB2 and HA in isolates from infected chicken lungs were detected by NGS. In sum, these results highlight the high degree of pathogenicity and the valid transmissibility of this new H7N9 variant in chickens and the quick adaptation of this new H7N9 variant to mammals, so the risk should be evaluated and more attention should be paid to this variant.IMPORTANCE Due to the recent increased numbers of zoonotic infections in poultry and persistent human infections in China, influenza A(H7N9) virus has remained a public health threat. Most of the influenza A(H7N9) viruses reported previously have been of low pathogenicity. Now, these novel H7N9 HPAIV variants have caused human infections in three provinces and outbreaks on poultry farms in eight provinces in China. We analyzed the molecular features and compared the relative characteristics of one H7N9 LPAIV and two H7N9 HPAIVs isolated from chickens and two human-origin H7N9 HPAIVs in chicken and mouse models. We found that all HPAIVs both are highly pathogenic and have valid transmissibility in chickens. Strikingly, the human-origin viruses were more highly pathogenic than the avian-origin viruses in mice, and dynamic mutations were confirmed by NGS and Sanger sequencing. Our findings offer important insight into the origin, adaptation, pathogenicity, and transmissibility of these viruses to both poultry and mammals.

Genetic Analysis of Reemerging GII.P16-GII.2 Noroviruses in 2016-2017 in China.

Background: During 2016-2017, the previously rare GII.P16-GII.2 norovirus suddenly emerged as the predominant genotype causing gastroenteritis outbreaks in China and other countries. Its origin, phylodynamics, and mechanism behind the predominance remain unclear. Methods: Bayesian phylogenetic analyses were performed on 180 full capsid and 150 polymerase sequences of 2016-2017 GII.P16-GII.2 noroviruses in China, and those for all publicly available GII.P16 and GII.2 sequences. Saliva-based histo-blood group antigen (HBGA) binding assays and crystal structural analysis were conducted by using the P proteins of 2016-2017 GII.P16-GII.2 noroviruses. Results: The reemerging GII.P16-GII.2 norovirus showed a rapid genetic diversification after its emergence in 2012-2013. The antigenicity and HBGA binding profile of the early 2016-2017 and pre-2016 GII.2 noroviruses were similar. A further variant with a single Val256Ile mutation and the conventionally orientated Asp382 in the VP1 protein showed an expanded HBGA-binding spectrum. Mutations on the surface of polymerase that could alter its function were seen, which may help to accelerate the VP1 gene evolution to 5.5 × 10-3 substitutions per site per year. This virus can be traced back to Pearl River Delta, China. Conclusions: Our findings provide new insights into GII.2 norovirus epidemics and highlight the necessity of enhanced global surveillance for potential epidemics of rare-genotype noroviruses.

[Immunoreactivity and immunogenicity analysis of the recombinant cathepsin L-like protease of Fasciola hepatica in SD rats].

OBJECTIVE: To analyze the immunoreactivity of recombinant cathepsin L-like proteases (CatL) protein of Fasciola hepatica and its immunogenicity in SD rats. METHODS: The E. coli BL21(DE3) cells harbouring recombinant plasmid pET30a-FhCatL were inoculated in LB medium, and the protein expression was induced with IPTG. The recombinant protein FhCatL was analyzed by SDS-PAGE and the immunoreactivity was identified by Western blotting with sera from Fasciola hepatica-infected goat as the primary antibody. Twenty SD rats were randomly divided into immunized group and adjuvant control group. SD rats in immunized group were injected subcutaneously with 200 microg of purified FhCatL protein. All the rats received three immunizations at 3-week intervals. The adjuvant control group with 10 SD rats received only adjuvants emulsified with the same amount of PBS. Serum samples were collected at the day before the second and final immunization, 3, 6, and 9 weeks after the final immunization. The IgG antibody of rats' sera was examined by indirect ELISA and spleen lymphocyte proliferation (SLP) was tested by methyl thiazolyl tetrazolium (MTT). RESULTS: The molecular weight of purified FhCatL was about Mr 42,000. The recombinant FhCatL was recognized by pool sera of goats naturally infected with F. hepatica. The titer of specific antibody IgG in SD rats induced by the recombinant protein against CatL protein was significantly higher than that of the control, and the antibody titer reached the peak at three weeks after the final immunization (1 : 102,400). The stimulation index of splenocytes in immunized group was 2.176 +/- 0.047, which was significantly higher than that of the control (1.171 +/- 0.032) (P<0.05). CONCLUSION: The recombinant FhCatL protein bears stronger immnoreactivity and immunogenicity.

A Multi-dimensional Data Mining-based Study on the Prescriptions Developed by Professor Xu Zhiyin in Treating Thyroid Nodules.

OBJECTIVES: In this study, we employed a multi-dimensional data mining approach to examine the clinical instances where Professor Xu Zhiyin treated thyroid nodules. Our aim is to understand the patterns of symptoms, underlying causes, and treatment approaches used for thyroid nodules. By doing so, the intention is to distill the essential aspects, compile Professor Xu Zhiyin's clinical insights, and investigate his scholarly perspectives. METHODS: Professor Xu Zhiyin's clinical diagnoses and treatments spanning from 2009 to 2019 were entered into Microsoft Excel. Subsequently, the collected data was imported into the Medcase V5.2 system to facilitate data mining. Various techniques, such as frequency-based method, association rule analysis, and clustering, including a decentralized system clustering approach, were employed on a set of 346 cases involving patients with thyroid nodules that conformed to the specified criteria. The primary focus was on extracting insights regarding symptoms and the underlying causes from the medical records. By integrating these findings with Professor Xu Zhiyin's clinical expertise, we examined and summarized the outcomes of the data mining process. RESULTS: The fundamental prescriptions were successfully extracted using the techniques for mining across multiple dimensions. Utilizing the scattered grouping of these prescriptions and with reference to the cluster analysis of the frequency-linked system, the fundamental prescriptions proposed by Professor Xu Zhiyin for addressing thyroid nodules encompass the following ingredients: Glycyrrhiza uralensis Fisch, Cortex Moutan, Paeoniae radix rubra, Curcuma longa L., Radix Curcumae, persica seed, Citri Reticulatae Viride Pericarpium, Pinellia ternata, Spica Prunellae, Ostreae concha, Gleditsia sinensis spine, Tuckahoe and Radix Codonopsis. CONCLUSION: The fundamental prescriptions were acquired using the frequency approach, association rule technique, k-means clustering approach, and systematic clustering approach. The research findings corroborate one another, demonstrating that Professor Xu Zhiyin's approach to distinguishing and treating thyroid nodules is embodied in distinct prescriptions tailored to specific diseases.

Lactic acid production with two types of feedstocks from food waste: Effect of inoculum, temperature, micro-oxygen, and initial pH.

Lactic acid (LA) is an important chemical with broad market applications. To optimize LA production, food waste has been explored as feedstock. Due to the wide variety of food waste types, most current research studies have obtained different conclusions. This study focuses on carbohydrate-rich fruit and vegetable waste (FVW) and lipid-rich kitchen waste (KW), and the effect of inoculum, temperature, micro-oxygen, and initial pH were compared. FVW has a greater potential for LA production than KW. As an inoculum, lactic acid bacteria (LAB) significantly increased the maximum LA concentration (27.6 g/L) by 50.8 % compared with anaerobic sludge (AS). FVW exhibited optimal LA production at 37 °C with micro-oxygen. Adjustment of initial pH from 4 to 8 alleviated the inhibitory effect of accumulated LA, resulting in a 46.2 % increase in maximum LA production in FVW. The expression of functional genes associated with metabolism, genetic information processing, and environmental information processing was higher at 37 °C compared to 50 °C.

[Immunogenicity analysis of recombinant GST protein of Fasciola hepatica in SD rats].

OBJECTIVE: To analyze the immunogenicity of recombinant glutathione S-transferase protein of Fasciola hepatica (FhGST) in SD rats. METHODS: The recombinant expression plasmid pET30a-FhGST was transformed into E. coli BL21 (DE3) cells and induced with IPTG for protein expression. The recombinant protein FhGST was analyzed by SDS-PAGE and identified by Western blotting. Twenty SD rats were randomly divided into two groups: immunized group and adjuvant control group. SD rats in immunized group were injected subcutaneously with 200 microg of purified FhGST protein. The adjuvant control group with 10 SD rats received only adjuvants emulsified with PBS. All the rats received three immunizations at 3-week intervals. Serum samples were collected at pre-immunization, the day after each immunization, 3 weeks and 6 weeks after the final immunization. The IgG antibody of rats' sera was examined by indirect ELISA and spleen lymphocyte proliferation (SLP) was tested by MTT. RESULTS: The molecular weight of purified FhGST was about M(r) 31 300. The recombinant FhGST was recognized by pool sera of goats naturally infected with F. hepatica. The recombinant protein induced specific antibody IgG against GST protein in SD rats significantly higher than that of the control, and the antibody titer reached the peak at 9 weeks after the first immunization (GMT 1:89 144). FhGST protein significantly enhanced the growth and proliferation of rat splenocytes. CONCLUSION: The recombinant FhGST protein induces specific immune response in SD rats.

Effect of short-term exposure to high temperatures on the reproductive behavior and physiological enzyme activities in the fruit fly Zeugodacus tau (Walker).

Zeugodacus tau is an economically important invasive pest of various vegetables and fruits. In this study, we evaluated the effects of short-term (12 h) exposure to high temperatures on the reproductive behaviors and physiological enzyme activities of adult Z. tau flies. When compared to the control group, the mating rate in the treated group increased significantly after exposure to 34°C and 38°C. After 34°C exposure, the mating rate of the control♀-treated♂ mating was the highest (60.0%). The use of high temperatures for a short period reduced the pre-mating period and lengthened the duration of copulation. After 38°C exposure, the mating between treated♀ and treated♂ had the shortest pre-mating period of 39.0 min and the longest copulation duration of 67.8 min. Mating after a brief exposure to high temperatures had a negative impact on female reproduction, whereas mating with males who previously had a brief exposure to 34°C and 38°C significantly increased female fecundity. After 40 °C exposure, the mating between treated♀ and control♂ showed the lowest fecundity and hatching rate of 293.25 eggs and 25.71%, respectively. The mating between control♀ and treated♂ showed the highest fecundity of 1,016.75 eggs after exposure to 38°C. The SOD, POD, and CAT activities exhibited significant changes (increase or decrease) after the short-term exposure of Z. tau adults to high temperatures. After being exposed to 38°C, SOD activity increased by 2.64 and 2.10 times in females and males in the treated group, respectively, compared to the SOD activity in the control group. The AchE, CarE, and GST activities first increased and then decreased with the increase in temperature. CarE activity changed the most after exposure to 38°C, with females and males in the treated group increasing by 7.81 and 1.69 times, respectively, compared to the activity in the control group. In conclusion, mating strategy and physiological stress are important adaptive mechanisms of Z. tau for adapting to short-term heat stress in a sex-specific manner.

An Analysis of the Clinical Medication Rules of Traditional Chinese Medicine for Polycystic Ovary Syndrome Based on Data Mining.

Objective: The aim of the present study is to investigate the rules and characteristics of the clinical administration of traditional Chinese medicine (TCM) in the treatment of polycystic ovary syndrome (PCOS) using data mining methods. Method: Medical cases of well-known contemporary TCM doctors treating PCOS were collected from the China National Knowledge Infrastructure, Chinese Biomedical Literature Service System, Wanfang, Chinese Scientific Journals Database, and PubMed; the data were then characterized, and a standardized database of medical cases was built. This database was used to (1) count the frequency of syndrome types and the herbs used in medical cases by data mining methods and (2) analyze drug association rules and systematic clustering methods. Results: A total of 330 papers were included, involving 382 patients and a total of 1,427 consultations. The most common syndrome type was kidney deficiency; sputum stasis was the core pathological product and causative factor. A total of 364 herbs were used. Among them, 22 herbs were used >300 times, including Danggui (Angelicae Sinensis Radix), Tusizi (Semen Cuscutae), Fuling (Poria), Xiangfu (Nutgrass Galingale Rhizome), and Baizhu (Atractylodis Macrocephalae Rhizoma). Additionally, 22 binomial associations were obtained from the analysis of association rules; five clustering formulae were obtained via the analysis of high-frequency drug clusters; and 27 core combinations were obtained by k-means clustering of formula. Conclusion: In the treatment of PCOS, TCM is primarily employed as a combination approach involving tonifying the kidneys, strengthening the spleen, eliminating damp and dissolving phlegm, activating blood circulation, and resolving blood stasis. The core prescription is primarily a compound intervention based on the Cangfu Daotan pill, Liuwei Dihuang pill, and Taohong Siwu decoction.

Overview of research progress and application of experimental models of colorectal cancer.

Colorectal cancer (CRC) is the third most common malignancy in terms of global tumor incidence, and the rates of morbidity and mortality due to CRC are rising. Experimental models of CRC play a vital role in CRC research. Clinical studies aimed at investigating the evolution and mechanism underlying the formation of CRC are based on cellular and animal models with broad applications. The present review classifies the different experimental models used in CRC research, and describes the characteristics and limitations of these models by comparing the research models with the clinical symptoms. The review also discusses the future prospects of developing new experimental models of CRC.

Resurgence of Omicron BA.2 in SARS-CoV-2 infection-naive Hong Kong.

Hong Kong experienced a surge of Omicron BA.2 infections in early 2022, resulting in one of the highest per-capita death rates of COVID-19. The outbreak occurred in a dense population with low immunity towards natural SARS-CoV-2 infection, high vaccine hesitancy in vulnerable populations, comprehensive disease surveillance and the capacity for stringent public health and social measures (PHSMs). By analyzing genome sequences and epidemiological data, we reconstructed the epidemic trajectory of BA.2 wave and found that the initial BA.2 community transmission emerged from cross-infection within hotel quarantine. The rapid implementation of PHSMs suppressed early epidemic growth but the effective reproduction number (Re) increased again during the Spring festival in early February and remained around 1 until early April. Independent estimates of point prevalence and incidence using phylodynamics also showed extensive superspreading at this time, which likely contributed to the rapid expansion of the epidemic. Discordant inferences based on genomic and epidemiological data underscore the need for research to improve near real-time epidemic growth estimates by combining multiple disparate data sources to better inform outbreak response policy.

School Belonging and Reading Literacy: A Multilevel Moderated Mediation Model.

School belonging is of great significance to students' physical and mental health development, especially academic improvement. However, the mechanism of the influence of school belonging on student academic achievement should be further explored, especially reading performance. Based on ecological systems theory and self-determination theory, the present research constructs a multilevel design to examine a moderated mediation model in which school belonging as a level-1 predictor, mastery goal orientation as a level-1 mediator and school disciplinary climate as a level-2 moderator jointly impact reading literacy. Results of the study were based on the questionnaires from 11,364 (5,455 girls and 5,909 boys) 15-year-olds nested in 332 schools in mainland China that participated in PISA 2018. The cross-sectional analysis indicated that: (1) school belonging had a direct and positive effect on student reading literacy; (2) the relationship between school belonging and reading literacy was prominently mediated by mastery goal orientation; (3) both school disciplinary climate level and strength could negatively moderate the latter half path of "school belonging → mastery goal orientation → reading literacy." Implications, limitations, and future research directions are discussed.

Viromes in marine ecosystems reveal remarkable invertebrate RNA virus diversity.

Little is known about ocean viromes and the ecological drivers of the evolution of aquatic RNA viruses. This study employed a meta-transcriptomic approach to characterize the viromes of 58 marine invertebrate species across three seas. This revealed the presence of 315 newly identified RNA viruses in nine viral families or orders (Durnavirales, Totiviridae, Bunyavirales, Hantaviridae, Picornavirales, Flaviviridae, Hepelivirales, Solemoviridae, and Tombusviridae), with most of them being sufficiently divergent to the already documented viruses. Notably, this study revealed three marine invertebrate hantaviruses that are rooted to vertebrate hantaviruses, further supporting that hantaviruses may have a marine origin. We have also found evidence for possible host sharing and switch events during virus evolution. Overall, we have revealed the hidden diversity of marine invertebrate RNA viruses.

Revealing mechanism of micro-aeration for enhancing volatile fatty acids production from swine manure.

Micro-aeration is considered a new strategy for improving volatile fatty acids (VFAs) production of agricultural waste. This study investigated the effect and mechanism of micro-aeration of air and oxygen (O2) on VFAs production from swine manure. The results showed that Air-micro-aeration had the most significant improvement effect, with the highest VFAs of 8.21 g/L, which was increased by 22.4%. Moreover, the mixing effects of different micro-aeration were limited, and the microbial communities significantly varied. Firmicutes and Bacteroidota were the dominant hydrolytic and acidogenic bacteria, and Air-micro-aeration preferentially promoted electron transfer activity and energy generation. Methanosarcina, Methanocorpusculum, and Methanobrevibacter can adapt to environmental changes according to their different oxygen tolerance, and the consumption and conversion of VFAs by methanogens were slow under Air-micro-aeration condition. This study revealed mechanism of micro-aeration for improving VFAs production from swine manure, providing a theoretical basis for micro-aeration regulation optimization.

A novel tRNA-derived fragment tRF-3022b modulates cell apoptosis and M2 macrophage polarization via binding to cytokines in colorectal cancer.

tRNA-derived fragments (tRFs) are a class of small RNAs that occur when tRNAs are broken down by enzymes due to stress. Increasing reports have shown that tRFs are associated with multiple physiological and pathological processes, especially in cancers; however, very little is known of the effects and mechanisms of tRFs. Therefore, further investigation on the biological roles and clinical value of tRFs is required. In this study, we utilized whole-transcriptome sequencing to profile tRFs expression in the tissues and plasma exosomes of patients with colorectal cancer (CRC). Three tRFs (tRF-3022b, tRF-3030b and tRF-5008b) showed an increasing trend in CRC tissues compared to adjacent normal tissues. They also tended to be elevated in plasma exosomes of CRC patients compared to healthy controls. These results indicated that they may be upregulated in cancer cells and then secreted by exosomes. The knockdown of tRF-regulated factors such as AlkB homolog 3 (ALKBH3), tRNA aspartic acid methyltransferase 1 (DNMT2), angiogenin (ANG), and argonaute RISC catalytic component 2 (AGO2) could affect the expression of tRFs. Notably, we found that the decrease in the three tRFs arrests the progression of the CRC cell cycle and induces cell apoptosis. Silencing tRF-3022b could facilitate M2 macrophage polarization. Mechanistically, we found that tRF-3022b binds to galectin 1 (LGALS1) and macrophage migration inhibitory factor (MIF) in CRC cells and reduces polarization by regulating MIF in M2 macrophages. In conclusion, our study revealed the expression pattern of tRFs in both tissue and plasma exosomes and identified a novel tRF, tRF-3022b, which may affect CRC tumor growth and M2 macrophage polarization by binding to LGALS1 and MIF.