Classical swine fever virus non-structural protein 5B hijacks host METTL14-mediated m6A modification to counteract host antiviral immune response.

Classical Swine Fever (CSF), caused by the Classical Swine Fever Virus (CSFV), inflicts significant economic losses on the global pig industry. A key factor in the challenge of eradicating this virus is its ability to evade the host's innate immune response, leading to persistent infections. In our study, we elucidate the molecular mechanism through which CSFV exploits m6A modifications to circumvent host immune surveillance, thus facilitating its proliferation. We initially discovered that m6A modifications were elevated both in vivo and in vitro upon CSFV infection, particularly noting an increase in the expression of the methyltransferase METTL14. CSFV non-structural protein 5B was found to hijack HRD1, the E3 ubiquitin ligase for METTL14, preventing METTL14 degradation. MeRIP-seq analysis further revealed that METTL14 specifically targeted and methylated TLRs, notably TLR4. METTL14-mediated regulation of TLR4 degradation, facilitated by YTHDF2, led to the accelerated mRNA decay of TLR4. Consequently, TLR4-mediated NF-κB signaling, a crucial component of the innate immune response, is suppressed by CSFV. Collectively, these data effectively highlight the viral evasion tactics, shedding light on potential antiviral strategies targeting METTL14 to curb CSFV infection.

Two novel compounds inhibit Flavivirus infection in vitro and in vivo by targeting lipid metabolism.

Flavivirus infection capitalizes on cellular lipid metabolism to remodel the cellular intima, creating a specialized lipid environment conducive to viral replication, assembly, and release. The Japanese encephalitis virus (JEV), a member of the Flavivirus genus, is responsible for significant morbidity and mortality in both humans and animals. Currently, there are no effective antiviral drugs available to combat JEV infection. In this study, we embarked on a quest to identify anti-JEV compounds within a lipid compound library. Our research led to the discovery of two novel compounds, isobavachalcone (IBC) and corosolic acid (CA), which exhibit dose-dependent inhibition of JEV proliferation. Time-of-addition assays indicated that IBC and CA predominantly target the late stage of the viral replication cycle. Mechanistically, JEV nonstructural proteins 1 and 2A (NS1 and NS2A) impede 5'-adenosine monophosphate (AMP)-activated protein kinase (AMPK) activation by obstructing the liver kinase B1 (LKB1)-AMPK interaction, resulting in decreased p-AMPK expression and a consequent upsurge in lipid synthesis. In contrast, IBC and CA may stimulate AMPK by binding to its active allosteric site, thereby inhibiting lipid synthesis essential for JEV replication and ultimately curtailing viral infection. Most importantly, in vivo experiments demonstrated that IBC and CA protected mice from JEV-induced mortality, significantly reducing viral loads in the brain and mitigating histopathological alterations. Overall, IBC and CA demonstrate significant potential as effective anti-JEV agents by precisely targeting AMPK-associated signaling pathways. These findings open new therapeutic avenues for addressing infections caused by Flaviviruses. IMPORTANCE: This study is the inaugural utilization of a lipid compound library in antiviral drug screening. Two lipid compounds, isobavachalcone (IBC) and corosolic acid (CA), emerged from the screening, exhibiting substantial inhibitory effects on the Japanese encephalitis virus (JEV) proliferation in vitro. In vivo experiments underscored their efficacy, with IBC and CA reducing viral loads in the brain and mitigating JEV-induced histopathological changes, effectively shielding mice from fatal JEV infection. Intriguingly, IBC and CA may activate 5'-adenosine monophosphate (AMP)-activated protein kinase (AMPK) by binding to its active site, curtailing the synthesis of lipid substances, and thus suppressing JEV proliferation. This indicates AMPK as a potential antiviral target. Remarkably, IBC and CA demonstrated suppression of multiple viruses, including Flaviviruses (JEV and Zika virus), porcine herpesvirus (pseudorabies virus), and coronaviruses (porcine deltacoronavirus and porcine epidemic diarrhea virus), suggesting their potential as broad-spectrum antiviral agents. These findings shed new light on the potential applications of these compounds in antiviral research.

The type-B response regulators ARR10, ARR12, and ARR18 specify the central cell in Arabidopsis.

In Arabidopsis thaliana, the female gametophyte consists of two synergid cells, an egg cell, a diploid central cell, and three antipodal cells. CYTOKININ INDEPENDENT 1 (CKI1), a histidine kinase constitutively activating the cytokinin signaling pathway, specifies the central cell and restricts the egg cell. However, the mechanism regulating CKI1-dependent central cell specification is largely unknown. Here, we showed that the type-B ARABIDOPSIS RESPONSE REGULATORS10, 12, and 18 (ARR10/12/18) localize at the chalazal pole of the female gametophyte. Phenotypic analysis showed that the arr10 12 18 triple mutant is female sterile. We examined the expression patterns of embryo sac marker genes and found that the embryo sac of arr10 12 18 plants had lost central cell identity, a phenotype similar to that of the Arabidopsis cki1 mutant. Genetic analyses demonstrated that ARR10/12/18, CKI1, and ARABIDOPSIS HISTIDINE PHOSPHOTRANSFER PROTEIN2, 3, and 5 (AHP2/3/5) function in a common pathway to regulate female gametophyte development. In addition, constitutively activated ARR10/12/18 in the cki1 embryo sac partially restored the fertility of cki1. Results of transcriptomic analysis supported the conclusion that ARR10/12/18 and CKI1 function together to regulate the identity of the central cell. Our results demonstrated that ARR10/12/18 function downstream of CKI1-AHP2/3/5 as core factors to determine cell fate of the female gametophyte.

Temporal analysis of lung injury induced by real-ambient PM2 .5 exposure in mice.

Fine particulate matter (PM2.5 ) has been shown to induce lung injury. However, the pathophysiological mechanisms of PM2.5 -induced pulmonary injury after different exposure times are poorly understood. In this study, we exposed male ICR mice to a whole-body PM2.5 inhalation system at daily mean concentration range from 92.00 to 862.00 µg/m3 for 30, 60, and 90 days. We found that following prolonged exposure to PM2.5 , pulmonary injury was increasingly evident with significant histopathological alterations. Notably, the pulmonary inflammatory response and fibrosis caused by PM2.5 after different exposure times were closely associated with histopathological changes. In addition, PM2.5 exposure caused oxidative stress, DNA damage and impairment of DNA repair in a time-dependent manner in the lung. Importantly, exposure to PM2.5 eventually caused apoptosis in the lung through upregulation of cleaved-caspase-3 and downregulation of Bcl-2. Overall, our data demonstrated that PM2.5 led to pulmonary injury in a time-dependent manner via upregulation of proinflammatory and fibrosis-related genes, and activation of the DNA damage response. Our findings provided a novel perspective on the pathophysiology of respiratory diseases caused by airborne pollution.

The EPFL-ERf-SERK signaling controls integument development in Arabidopsis.

As the seed precursor, the ovule produces the female gametophyte (or embryo sac), and the subsequent double fertilization occurs in it. The integuments emerge sequentially from the integument primordia at the early stages of ovule development and finally enwrap the embryo sac gradually during gametogenesis, protecting and nursing the embryo sac. However, the mechanisms regulating integument development are still obscure. In this study, we show that SOMATIC EMBRYOGENESIS RECEPTOR-LIKE KINASES (SERKs) play essential roles during integument development in Arabidopsis thaliana. The serk1/2/3 triple mutant shows arrested integuments and abnormal embryo sacs, similar defects also found in the triple loss-of-function mutants of ERECTA family (ERf) genes. Ovules of serk1/2/3 er erl1/2 show defects similar to er erl1/2 and serk1/2/3. Results of yeast two-hybrid analyses, bimolecular fluorescence complementation (BiFC) analyses, and co-immunoprecipitation assays demonstrated that SERKs interact with ERf, which depends on EPIDERMAL PATTERNING FACTOR-LIKE (EPFL) family small peptides. The sextuple mutant epfl1/2/3/4/5/6 shows integument defects similar to both of er erl1/2 and serk1/2/3. Our results demonstrate that ERf-SERK-mediated EPFL signaling orchestrates the development of the female gametophyte and the surrounding sporophytic integuments.

Essential roles of SERKs in the ROOT MERISTEM GROWTH FACTOR-mediated signaling pathway.

ROOT MERISTEM GROWTH FACTORs (RGFs), a group of peptide hormones, play key roles in root apical meristem development. In Arabidopsis (Arabidopsis thaliana), there are 11 members of RGFs, in which at least RGF1, RGF2, and RGF3 are expressed at the root tip and are involved in root stem cell niche maintenance. RGFs are perceived by five functionally redundant receptor-like protein kinases, RGF1 INSENSITIVE 1 (RGI1) to RGI5, to maintain the expression of two downstream APETALA 2 (AP2) transcription factor genes, PLETHORA 1 (PLT1) and PLT2, and to stabilize PLT2. RGI1 to RGI3 were also named RGF RECEPTOR 1 (RGFR1) to RGFR3, respectively. Although previous studies have suggested that BRI1-ASSOCIATED RECEPTOR KINASE 1 (BAK1) and its paralogs, SOMATIC EMBRYOGENESIS RECEPTOR-LIKE KINASEs (SERKs), may act as coreceptors of RGIs, comprehensive genetic and biochemical analyses have not been well documented. Here, we report that single, double, and triple mutants of SERKs show various degrees of short root phenotypes and insensitivity to exogenously applied RGF1. The interaction between RGIs and BAK1 and their mutual phosphorylation are RGF1 dependent. We also found that RGF1-induced MAPK activation relies on both RGIs and SERKs. We demonstrate that RGIs play redundant roles in regulating root apical meristem development. Therefore, we genetically and biochemically substantiated that SERKs, as coreceptors, play essential roles in the RGF1-mediated signaling pathway.

Association of DLT versus SLT with postoperative pneumonia during esophagectomy in China: a retrospective comparison study.

BACKGROUND: Double lumen tube (DLT) and single lumen tube (SLT) are two common endotracheal tube (ETT) types in esophageal cancer surgery. Evidence of the relationship between two ETT types and postoperative pneumonia (PP) remains unclear. We aimed to determine the association between two types of ETT (DLT and SLT) and PP and assess the perioperative risk-related parameters that affect PP. METHODS: This study included 680 patients who underwent esophageal cancer surgery from January 01, 2010 through December 31, 2020. The primary outcome was PP, and the secondary outcome was perioperative risk-related parameters that affect PP. The independent variable was the type of ETT: DLT or SLT. The dependent variable was PP. To determine the relationship between variables and PP, univariate and multivariate analyses were performed. The covariables included baseline demographic characteristics, comorbidity disease, neoadjuvant chemotherapy, tumor location, laboratory parameters, intraoperative related variables. RESULTS: In all patients, the incidence of postoperative pneumonia in esophagectomy was 32.77% (36.90% in DLT group and 26.38% in SLT group). After adjusting for potential risk factors, we found that using an SLT in esophagectomy was associated with lower risk of postoperative pneumonia compared to using a DLT (Odd ratio = 0.41, 95% confidence interval (CI): 0.22, 0.77, p = 0.0057). Besides DLT, smoking history, combined intravenous and inhalation anesthesia (CIIA) and vasoactive drug use were all significant and independent risk factors for postoperative pneumonia in esophagectomy. These results remained stable and reliable after subgroup analysis. CONCLUSIONS: During esophagectomy, there is significant association between the type of ETT (DLT or SLT) and PP. Patients who were intubated with a single lumen tube may have a lower rate of postoperative pneumonia than those who were intubated with a double lumen tube. This finding requires verification in follow-up studies.

Circular RNA circNIPBL promotes NNK-induced DNA damage in bronchial epithelial cells via the base excision repair pathway.

Environmental chemical exposure often causes DNA damage, which leads to cellular dysfunction and the development of diseases. 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), a tobacco-specific carcinogen that is known to cause DNA damage, while remains unknown about the underlying mechanism. In this study, simulated doses of NNK exposure in smokers, ranging from 50 to 300 µM, were used to detect the DNA damage effects of NNK in two human bronchial epithelial cells, 16HBE and BEAS-2B. The comet assay revealed increased DNA damage in response to NNK treatment, as measured by increased Olive tail moment (OTM). NNK treatment also led to elevated foci formation and protein expression of γ-H2AX, a DNA damage sensor. Dysregulation of proliferation, cell cycle arrest and apoptosis, was also observed in NNK-treated cells. Furthermore, the most effective dose of NNK (300 µM) was used in subsequent mechanistic studies. A circular RNA circNIPBL was identified to be significantly up-regulated in NNK-treated cells, circNIPBL knockdown successfully alleviated NNK-induced DNA damage and reversed the cellular dysregulation, while circNIPBL overexpression had the opposite effect. Mechanistically, we identified an interaction between circNIPBL and PARP1, a critical enzyme of the base excision repair (BER) pathway. CircNIPBL silencing successfully alleviated the NNK-induced inhibition of BER pathway proteins, including PARP1, XRCC1, PCNA and FEN1, while overexpression of circNIPBL had the opposite effect. In summary, our study shows for the first time that circNIPBL promotes NNK-induced DNA damage and cellular dysfunction through the BER pathway. In addition, our findings reveal the crucial role of epigenetic regulation in carcinogen-induced genetic lesions and further our understanding of environmental carcinogenesis.

Effect of intravenous lidocaine on propofol consumption in elderly patients undergoing colonoscopy: a double-blinded, randomized, controlled trial.

BACKGROUND: Elderly patients undergoing colonoscopy with propofol as sedation are prone to respiratory or cardiovascular complications. Intravenous lidocaine has analgesic efficacy and reduces propofol consumption during surgery. Here, the effect of intravenous lidocaine on propofol consumption was evaluated in elderly patients undergoing colonoscopy. METHODS: Patients were randomly allocated to receive intravenous lidocaine (1.5 mg/kg bolus dose, followed by a 2 mg/kg/h continuous infusion during the procedure; Group L) or a placebo (saline; Group N). During the procedure, sedation was achieved by propofol. The following outcomes were recorded: total propofol consumption; time to loss of consciousness; number of airway modifications; time to the first airway intervention; incidence of sedation-related events; pain score after awakening; endoscopists' and patients' satisfaction scores; memory level of the procedure; and adverse events within 24 h postoperatively. RESULTS: Compared with Group N, propofol consumption was reduced by 13.2% in Group L (100.30 ± 25.29 mg vs. 115.58 ± 27.52 mg, respectively, p = 0.008). Kaplan-Meier curves showed that the median time to the loss of consciousness episode was shorter in Group L than in Group N (40 s vs. 55 s, respectively, log rank p < 0.0001). The number of airway modifications, time to the first airway intervention, incidence of sedation-related events, time to awakening, pain score after awakening, endoscopists' and patients' satisfaction scores, memory level of the procedure and adverse events within 24 h postoperatively did not differ between the two groups (p > 0.05). CONCLUSIONS: Intravenous lidocaine can reduce propofol consumption in elderly patients undergoing colonoscopy, with quicker time to loss of consciousness. TRIAL REGISTRATION: The clinical trial was registered at (12/01/2021, ChiCTR2100042001 ).

Circular RNA circ_Cabin1 promotes DNA damage in multiple mouse organs via inhibition of non-homologous end-joining repair upon PM2.5 exposure.

Fine particulate matter (PM2.5) has been shown to induce DNA damage. Circular RNAs (circRNAs) have been implicated in various disease processes related to environmental chemical exposure. However, the role of circRNAs in the regulation of DNA damage response (DDR) after PM2.5 exposure remains unclear. In this study, male ICR mice were exposed to PM2.5 at a daily mean concentration of 382.18 µg/m3 for 3 months in an enriched-ambient PM2.5 exposure system in Shijiazhuang, China, and PM2.5 collected form Shijiazhuang was applied to RAW264.7 cells at 100 µg/mL for 48 h. The results indicated that exposure to PM2.5 induced histopathological changes and DNA damage in the lung, kidney and spleen of male ICR mice, and led to decreased cell viability, increased LDH activity and DNA damage in RAW264.7 cells. Furthermore, circ_Cabin1 expression was significantly upregulated in multiple mouse organs as well as in RAW264.7 cells upon exposure to PM2.5. PM2.5 exposure also resulted in impairment of non-homologous end joining (NHEJ) repair via the downregulation of Lig4 or Dclre1c expression in vivo and in vitro. Importantly, circ_Cabin1 promoted PM2.5-induced DNA damage via inhibiting of NHEJ repair. Moreover, the expression of circ_Cabin1 and Lig4 or Dclre1c was strongly correlated in multiple mouse organs, as well as in the blood. In summary, our study provides a new perspective on circRNAs in the regulation of DDR after environmental chemical exposure.

Characteristics of Cd accumulation and distribution in two sweet potato cultivars.

In this study, we compared the chemical forms and subcellular distribution of Cd in high-Cd (X16) and low-Cd (N88) sweet potato cultivars through hydroponic experiments and examined the Cd distribution in their roots by histochemical staining. The results showed that inorganic and pectate/protein-integrated Cd predominated in the leaves, and Cd concentrations were significantly higher in X16 than in N88. However, in the roots, Cd was mostly integrated with pectate and protein, and Cd concentration was higher in N88 than in X16. It was mainly stored through vacuolar sequestration and cell wall binding. In the leaves and stems, Cd concentrations in all subcellular fractions were higher in X16 than in N88; the opposite was observed in the roots. In X16, Cd was mostly accumulated in the root stele, and its Cd translocation factor was higher than that of N88. Overall, the subcellular fractions of X16 roots retained less Cd than N88 roots, and more Cd entered the root stele of X16 and subsequently moved to the shoots. The higher amounts of inorganic, water-soluble, and pectate/protein-integrated Cd with high mobility in the shoots of X16 than in N88 might facilitate Cd remobilization to other tissues, but this needs to be further studied.

The genomic features of parasitism, Polyembryony and immune evasion in the endoparasitic wasp Macrocentrus cingulum.

BACKGROUND: Parasitoid wasps are well-known natural enemies of major agricultural pests and arthropod borne diseases. The parasitoid wasp Macrocentrus cingulum (Hymenoptera: Braconidae) has been widely used to control the notorious insect pests Ostrinia furnacalis (Asian Corn Borer) and O. nubilalis (European corn borer). One striking phenomenon exhibited by M. cingulum is polyembryony, the formation of multiple genetically identical offspring from a single zygote. Moreover, M. cingulum employs a passive parasitic strategy by preventing the host's immune system from recognizing the embryo as a foreign body. Thus, the embryos evade the host's immune system and are not encapsulated by host hemocytes. Unfortunately, the mechanism of both polyembryony and immune evasion remains largely unknown. RESULTS: We report the genome of the parasitoid wasp M. cingulum. Comparative genomics analysis of M. cingulum and other 11 insects were conducted, finding some gene families with apparent expansion or contraction which might be linked to the parasitic behaviors or polyembryony of M. cingulum. Moreover, we present the evidence that the microRNA miR-14b regulates the polyembryonic development of M. cingulum by targeting the c-Myc Promoter-binding Protein 1 (MBP-1), histone-lysine N-methyltransferase 2E (KMT2E) and segmentation protein Runt. In addition, Hemomucin, an O-glycosylated transmembrane protein, protects the endoparasitoid wasp larvae from being encapsulated by host hemocytes. Motif and domain analysis showed that only the hemomucin in two endoparasitoids, M. cingulum and Venturia canescens, possessing the ability of passive immune evasion has intact mucin domain and similar O-glycosylation patterns, indicating that the hemomucin is a key factor modulating the immune evasion. CONCLUSIONS: The microRNA miR-14b participates in the regulation of polyembryonic development, and the O-glycosylation of the mucin domain in the hemomucin confers the passive immune evasion in this wasp. These key findings provide new insights into the polyembryony and immune evasion.

Metatranscriptome analysis reveals environmental and diel regulation of a Heterosigma akashiwo (raphidophyceae) bloom.

Despite numerous laboratory studies on physiologies of harmful algal bloom (HAB) species, physiologies of these algae during a natural bloom are understudied. Here, we investigated a bloom of the raphidophyte Heterosigma akashiwo in the East China Sea in 2014 using metabarcode (18S rDNA) and metatranscriptome sequencing. Based on 18S rDNA analyses, the phytoplankton community shifted from high diversity in the pre-bloom stage to H. akashiwo predominance during the bloom. A sharp decrease in ambient dissolved inorganic phosphate and strong up-regulation of phosphate and dissolved organic phosphorus (DOP) uptake genes, including the rarely documented (ppGpp)ase, in H. akashiwo from pre-bloom to bloom was indicative of rapid phosphorus uptake and efficient utilization of DOP that might be a driver of the H. akashiwo bloom. Furthermore, observed up-regulated expression of mixotrophy-related genes suggests potential contribution of mixotrophy to the bloom. Accelerating photosynthetic carbon fixation was also implied by the up-regulation of carbonic anhydrase genes during the bloom. Notably, we also observed a strong morning-to-afternoon shift in the expression of many genes. Our findings provide insights into metabolic processes likely important for H. akashiwo bloom formation, and suggest the need to consider timing of sampling in field studies on this alga.

Circ_0008657 regulates lung DNA damage induced by hexavalent chromium through the miR-203a-3p/ATM axis.

Hexavalent chromium [Cr (VI)] is an important environmental pollutant and may cause lung injury when inhaled into the human body. Cr (VI) is genotoxic and can cause DNA damage, although the underlying epigenetic mechanisms remain unclear. To simulate the real-life workplace exposure to Cr (VI), we used a novel exposure dose calculation method. We evaluated the effect of Cr (VI) on DNA damage in human bronchial epithelial cells (16HBE and BEAS-2B) by calculating the equivalent real-time exposure dose of Cr (VI) (0 to 10 µM) in an environmental population. Comet experiments and olive tail moment measurements revealed increased DNA damage in cells exposed to Cr (VI). Cr (VI) treatment increased nuclear γ-H2AX foci and γ-H2AX protein expression, and caused DNA damage in the lung tissues of mice. An effective Cr (VI) dose (6 µM) was determined and used for cell treatment. Cr (VI) exposure upregulated circ_0008657, and knockdown of circ_0008657 decreased Cr (VI)-induced DNA damage, whereas circ_0008657 overexpression had the opposite effect. Mechanistically, we found that circ_0008657 binds to microRNA (miR)-203a-3p and subsequently regulates ATM serine/threonine kinase (ATM), a key protein involved in homologous recombination repair downstream of miR-203a-3p, thereby regulating DNA damage induced by Cr (VI). The present findings suggest that circ_0008657 competitively binds to miR-203a-3p to activate the ATM pathway and regulate the DNA damage response after environmental chemical exposure in vivo and in vitro.

Essential roles of histone lysine methyltransferases EZH2 and EHMT1 in male embryo development of Phenacoccus solenopsis.

Paternal genome elimination (PGE) is an intriguing but poorly understood reproductive strategy in which females are typically diploid, but males lose paternal genomes. Paternal genome heterochromatin (PGH) occurs in arthropods with germline PGE, such as the mealybug, coffee borer beetles, and booklice. Here, we present evidence that PGH initially occurs during early embryo development at around 15 h post-mating (hpm) in the cotton mealybug, Phenacoccus solenopsis Tinsley. Transcriptome analysis followed by qPCR validation indicated that six histone lysine methyltransferase (KMT) genes are predominantly expressed in adult females. We knocked down these five genes through dsRNA microinjection. We found that downregulation of two KMT genes, PsEZH2-X1 and PsEHMT1, resulted in a decrease of heterochromatin-related methylations, including H3K27me1, H3K27me3, and H3K9me3 in the ovaries, fewer PGH male embryos, and reduced male offspring. For further confirmation, we obtained two strains of transgenic tobacco highly expressing dsRNA targeting PsEZH2-X1 and PsEHMT1, respectively. Similarly, fewer PGH embryos and fewer male offspring were observed when feeding on these transgenic tobacco plants. Overall, we present evidence that PsEZH2-X1 and PsEHMT1 have essential roles in male embryo survival by regulating PGH formation in cotton mealybugs.

Endosymbiont Tremblaya phenacola influences the reproduction of cotton mealybugs by regulating the mechanistic target of rapamycin pathway.

The intricate evolutionary dynamics of endosymbiotic relationships result in unique characteristics among the genomes of symbionts, which profoundly influence host insect phenotypes. Here, we investigated an endosymbiotic system in Phenacoccus solenopsis, a notorious pest of the subfamily Phenacoccinae. The endosymbiont, "Candidatus Tremblaya phenacola" (T. phenacola PSOL), persisted throughout the complete life cycle of female hosts and was more active during oviposition, whereas there was a significant decline in abundance after pupation in males. Genome sequencing yielded an endosymbiont genome of 221.1 kb in size, comprising seven contigs and originating from a chimeric arrangement between betaproteobacteria and gammaproteobacteria. A comprehensive analysis of amino acid metabolic pathways demonstrated complementarity between the host and endosymbiont metabolism. Elimination of T. phenacola PSOL through antibiotic treatment significantly decreased P. solenopsis fecundity. Weighted gene coexpression network analysis demonstrated a correlation between genes associated with essential amino acid synthesis and those associated with host meiosis and oocyte maturation. Moreover, altering endosymbiont abundance activated the host mechanistic target of rapamycin pathway, suggesting that changes in the amino acid abundance affected the host reproductive capabilities via this signal pathway. Taken together, these findings demonstrate a mechanism by which the endosymbiont T. phenacola PSOL contributed to high fecundity in P. solenopsis and provide new insights into nutritional compensation and coevolution of the endosymbiotic system.

Characterization of gut microbiota in patients with stage 3-4 chronic kidney disease: a retrospective cohort study.

PURPOSE: Multiple factors, such as dietary patterns, pharmaceutical interventions, and exposure to harmful substances, possess the capacity to influence gut microbiota composition. Gut microbiota dysbiosis has emerged as a significant contributor to the progression of chronic kidney disease (CKD) and its associated complications. By comprehending the intricacies of the intestinal microbiota, this research endeavor holds the potential to offer novel perspectives on potential strategies for mitigating CKD progression. METHODS: In this retrospective analysis, we assessed gut microbiota composition in CKD patients. Fecal samples were collected from a cohort of 44 patients with stage 3-4 CKD, alongside a control group consisting of 132 healthy volunteers. Subsequently, 16 s rDNA sequencing was conducted to examine the composition of the gut microbiota. RESULTS: Our findings revealed significant alterations in the diversity of intestinal microbiota in fecal samples between patients with stage 3-4 CKD and healthy subjects. Among the 475 bacterial genera, 164 were shared, while 242 dominant genera were exclusive to healthy subjects and 69 to CKD stages 3-4 samples. Notably, healthy volunteers exhibited a prevalence of intestinal Firmicutes and Bacteroidetes, whereas stage 3-4 CKD patients displayed higher abundance of Proteobacteria and Actinobacteria. The presence of uncultured Coprobacillus sp. notably contributed to distinguishing between the two groups. ROC curve analysis identified distinct microbiota with superior diagnostic efficacy for discriminating stage 3-4 CKD patients from healthy individuals. Metabolic pathway analysis revealed differing dominant pathways between the two groups-the NADH dehydrogenase pathway in healthy individuals and the phosphate acetyltransferase pathway in stage 3-4 CKD patients. Moreover, the CKD cohort displayed a higher proportion of Gram-negative bacteria and facultative anaerobes. CONCLUSIONS: In conclusion, our study underscores the profound influence of gut microbiota dysbiosis on CKD progression. The distinct microbial profiles observed in CKD patients highlight the potential efficacy of microbiota-based interventions in mitigating CKD advancement.

Recent Molecular Characterization of Porcine Rotaviruses Detected in China and Their Phylogenetic Relationships with Human Rotaviruses.

Porcine rotavirus A (PoRVA) is an enteric pathogen capable of causing severe diarrhea in suckling piglets. Investigating the prevalence and molecular characteristics of PoRVA in the world, including China, is of significance for disease prevention. In 2022, a total of 25,768 samples were collected from 230 farms across China, undergoing porcine RVA positivity testing. The results showed that 86.52% of the pig farms tested positive for porcine RVA, with an overall positive rate of 51.15%. Through the genetic evolution analysis of VP7, VP4 and VP6 genes, it was revealed that G9 is the predominant genotype within the VP7 segment, constituting 56.55%. VP4 genotypes were identified as P[13] (42.22%), P[23] (25.56%) and P[7] (22.22%). VP6 exhibited only two genotypes, namely I5 (88.81%) and I1 (11.19%). The prevailing genotype combination for RVA was determined as G9P[23]I5. Additionally, some RVA strains demonstrated significant homology between VP7, VP4 and VP6 genes and human RV strains, indicating the potential for human RV infection in pigs. Based on complete genome sequencing analysis, a special PoRVA strain, CHN/SD/LYXH2/2022/G4P[6]I1, had high homology with human RV strains, revealing genetic reassortment between human and porcine RV strains in vivo. Our data indicate the high prevalence, major genotypes, and cross-species transmission of porcine RVA in China. Therefore, the continuous monitoring of porcine RVA prevalence is essential, providing valuable insights for virus prevention and control, and supporting the development of candidate vaccines against porcine RVA.

Long non-coding RNAs mediate the association between short-term PM2.5 exposure and circulating biomarkers of systemic inflammation.

Although short-term fine particulate matter (PM2.5) exposure is associated with systemic inflammation, the effect of lncRNA on these association remains unknown. This study aims to investigate whether the plasma lncRNA mediate the effect of short-term PM2.5 exposure on systemic inflammation. In this cross-sectional study, plasma Clara cell protein 16 (CC16), interleukin 6 (IL-6), IL-8, tumor necrosis factor-α (TNF-α) and lncRNA expression levels were measured in 161 adults between March and April in 2018 in Shijiazhuang, China. PM2.5 concentrations were estimated 0-3 days prior to the examination date and the moving averages were calculated. Multiple linear regressions were used to evaluate the associations between PM2.5, the four biomarkers and lncRNA expression levels. Mediation analyses were performed to explore the potential roles of lncRNA expression in these associations. The median concentration of PM2.5 ranged from 39.65 to 60.91 mg/m3 across different lag days. The most significant effects on IL-6 and TNF-α per interquartile range increase in PM2.5 were observed at lag 0-3 days, with increases of 0.70 pg/mL (95% CI: 0.33, 1.07) and 0.21 pg/mL (95% CI: 0.06, 0.36), respectively. While the associations between PM2.5 and IL-8 (0.68 pg/mL, 95% CI: 0.34, 1.02) and CC16 (3.86 ng/mL, 95% CI: 1.60, 6.13) were stronger at lag 0 day. Interestingly, a negative association between PM2.5 and the expression of four novel lncRNAs (lnc-ACAD11-1:1, lnc-PRICKLE1-4:1, lnc-GPR39-7:2, and lnc-MTRNR2L12-3:6) were observed at each lag days. Furthermore, these lncRNAs mediated the effects of PM2.5 on the four biomarkers, with proportions of mediation ranged from 2.27% (95% CI: 1.19%, 9.82%) for CC16 to 35.60% (95% CI: 17.16%, 175.45%) for IL-6. Our findings suggested that plasma lncRNA expression mediat the acute effects of PM2.5 exposure on systematic inflammation. These highlight a need to consider circulating lncRNA expression as biomarkers to reduce health risks associated with PM2.5.

circCIMT Silencing Promotes Cadmium-Induced Malignant Transformation of Lung Epithelial Cells Through the DNA Base Excision Repair Pathway.

Changes in gene expression in lung epithelial cells are detected in cancer tissues during exposure to pollutants, highlighting the importance of gene-environmental interactions in disease. Here, a Cd-induced malignant transformation model in mouse lungs and bronchial epithelial cell lines is constructed, and differences in the expression of non-coding circRNAs are analyzed. The migratory and invasive abilities of Cd-transformed cells are suppressed by circCIMT. A significant DNA damage response is observed after exposure to Cd, which increased further following circCIMT-interference. It is found that APEX1 is significantly down-regulated following Cd exposure. Furthermore, it is demonstrated that circCIMT bound to APEX1 during Cd exposure to mediate the DNA base excision repair (BER) pathway, thereby reducing DNA damage. In addition, simultaneous knockdown of both circCIMT and APEX1 promotes the expression of cancer-related genes and malignant transformation after long-term Cd exposure. Overall, these findings emphasis the importance of genetic-epigenetic interactions in chemical-induced cancer transformation.