Identification of the effects of alkalinity exposure on the gills of oriental river prawns, Macrobrachium nipponense.

Macrobrachium nipponense is an important commercial freshwater species in China. However, the ability of alkali tolerance of M. nipponense is insufficient to culture in the major saline-alkali water source in China. Thus, it is urgently needed to perform the genetic improvement of alkali tolerance in this species. In the present study, we aimed to analyse the effects of alkali treatment on gills in this species after 96 h alkalinity exposure under the alkali concentrations of 0 mmol/L, 4 mmol/L, 8 mmol/L, and 12 mmol/L through performing the histological observations, measurement of antioxidant enzymes, metabolic profiling analysis, and transcriptome profiling analysis. The results of the present study revealed that alkali treatment stimulated the contents of malondialdehyde, glutathione, glutathione peroxidase in gills, indicating these antioxidant enzymes plays essential roles in the protection of body from the damage, caused by the alkali treatment. In addition, high concentration of alkali treatment (> 8 mmol/L) resulted in the damage of gill membrane and haemolymph vessel, affecting the normal respiratory function of gill. Metabolic profiling analysis revealed that Metabolic pathways, Biosynthesis of secondary metabolites, Biosynthesis of plant secondary metabolites, Microbial metabolism in diverse environments, Biosynthesis of amino acids were identified as the main enriched metabolic pathways of differentially expressed metabolites, which are consistent with the previous publications, treated by the various environmental factors. Transcriptome profiling analyses revealed that the alkali concentration of 12 mmol/L has more regulatory effects on the changes of gene expression than the other alkali concentrations. KEGG analysis revealed that Phagosome, Lysosome, Glycolysis/Gluconeogenesis, Purine Metabolism, Amino sugar and nucleotide sugar metabolism, and Endocytosis were identified as the main enriched metabolic pathways in the present study, predicting these metabolic pathways may be involved in the adaption of alkali treatment in M. nipponense. Phagosome, Lysosome, Purine Metabolism, and Endocytosis are immune-related metabolic pathways, while Glycolysis/Gluconeogenesis, and Amino sugar and nucleotide sugar metabolism are energy metabolism-related metabolic pathways. Quantitative PCR analyses of differentially expressed genes (DEGs) verified the accuracy of the RNA-Seq. Alkali treatment significantly stimulated the expressions of DEGs from the metabolic pathways of Phagosome and Lysosome, suggesting Phagosome and Lysosome play essential roles in the regulation of alkali tolerance in this species, as well as the genes from these metabolic pathways. The present study identified the effects of alkali treatment on gills, providing valuable evidences for the genetic improvement of alkali tolerance in M. nipponense.

Studies on the Relationships between Growth and Gonad Development during First Sexual Maturation of Macrobrachium nipponense and Associated SNPs Screening.

In this study, we used full-sib families to investigate the association between growth and gonad development during first sexual maturation of M. nipponense. We found that male GSI was significantly negatively correlated with growth traits (p < 0.01) and there were no significant correlations between female GSI (Gonadosomatic index) and growth traits (p > 0.05). HSI (Hepatopancreas index) in both males and females showed no significant correlations with growth traits (p > 0.05). We furthermore investigated the association between the specific allele of Mn-CTS L1 polymorphism and gonad development and growth traits. In total, 35 mutation loci were screened and 16 high-quality single-nucleotide polymorphisms (SNPs) loci were obtained after validation. Four and two SNPs proved to be strongly associated with all growth traits in female and male M. nipponense separately, among which A+118T might be a candidate SNP positively associated with large growth traits. Two and one SNPs were screened, respectively, in males and females to associate with GSI, while three SNPs were detected to associate with female HSI, among which A+1379C may be applied as a potential molecular marker for gene-assisted selection to improve both reproduction speed and growth traits in M. nipponense.

New Strategies for Responding to SARS-CoV-2: The Present and Future of Dual-Target Drugs.

The 2019 coronavirus disease (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in millions of deaths, posing a serious threat to public health and safety. Rapid mutations of SARS-CoV-2 and complex interactions among multiple targets during infection pose a risk of expiry for small molecule inhibitors. This suggests that the traditional concept of "one bug, one drug" could be ineffective in dealing with the coronavirus. The dual-target drug strategy is expected to be the key to ending coronavirus infections. However, the lack of design method and improper combination of dual-targets poses obstacle to the discovery of new dual-target drugs. In this Perspective, we summarized the profiles concerning drug design methods, structure-activity relationships, and pharmacological parameters of dual-target drugs for the treatment of COVID-19. Importantly, we underscored how target combination and rational drug design illuminate the development of dual-target drugs for SARS-CoV-2.

Sarcopenic obesity and falls in older adults: A validation study of ESPEN/EASO criteria and modifications in Western China communities.

OBJECTIVES: The ESPEN and the EASO recently developed consensus criteria for sarcopenic obesity (SO), employing the skeletal muscle mass to weight (SMM/W) ratio. Emerging evidence suggests that adjusting skeletal muscle mass for body mass index (SMM/BMI) could enhance the predictive accuracy for health outcomes. We aimed to validate the ESPEN/EASO criteria and explore the potential benefits of the SMM/BMI adjustment in predicting falls among older adults in Western China. METHODS: We conducted a multicenter, cross-sectional study and included community-dwelling older adults. The diagnosis of SO was determined using the standard ESPEN/EASO consensus criteria (SOESPEN) and a modified version adjusting SMM/BMI (SOESPEN-M). The associations of SOESPEN, SOESPEN-M, and their components with falls were analyzed. RESULTS: Among the 1353 participants, the prevalence of SO was 13.2 % (SOESPEN) and 11.4 % (SOESPEN-M), which increased with age and higher BMI levels. Within participants with a normal BMI, 4.2 % and 6.2 % were found to have SOESPEN and SOESPEN-M, respectively. SMM/W and SMM/BMI negatively correlated with fall risk (p=0.042 and p=0.021, respectively). Upon adjusting for confounders, only SOESPEN was significantly associated with falls (odds ratios [OR] 1.61, 95 % confidence interval [CI] 1.08 to 2.40), whereas the association for SOESPEN-M did not achieve significance (OR 1.55, 95 % CI 0.99 to 2.43). CONCLUSIONS: This research validated the ESPEN/EASO criteria (SOESPEN) and their modified version (SOESPEN-M) among community-dwelling older adults in Western China. The SMM/BMI adjustment appears to offer a lower estimate of SO prevalence, with only SOESPEN showing a significant association with falls.

Functional Study of the Role of the Methyl Farnesoate Epoxidase Gene in the Ovarian Development of Macrobrachium nipponense.

Methyl farnesoate epoxidase (MFE) is a gene encoding an enzyme related to the last step of juvenile hormone biosynthesis. Mn-MFE cDNA has a total length of 1695 bp and an open reading frame (ORF) length of 1482 bp, encoding 493 amino acids. Sequence analysis showed that its amino acid sequence has a PPGP hinge, an FGCG structural domain, and other structural domains specific to the P450 family of enzymes. Mn-MFE was most highly expressed in the hepatopancreas, followed by the ovary and gill, weakly expressed in heart and muscle tissue, and barely expressed in the eyestalk and cranial ganglion. Mn-MFE expression remained stable during the larval period, during which it mainly played a critical role in gonadal differentiation. Expression in the ovary was positively correlated and expression in the hepatopancreas was negatively correlated with ovarian development. In situ hybridization (ISH) showed that the signal was expressed in the oocyte, nucleus, cell membrane and follicular cells, and the intensity of expression was strongest at stage O-IV. The knockdown of Mn-MFE resulted in a significantly lower gonadosomatic index and percentage of ovaries past stage O-III compared to the control group. However, no differences were found in the cumulative frequency of molting between the experimental and control groups. Moreover, the analysis of ovarian tissue sections at the end of the experiment showed differences between groups in development speed but not in subcellular structure. These results demonstrate that Mn-MFE promotes the ovarian development of Macrobrachium nipponense adults but has no effect on molting.

HMMR triggers immune evasion of hepatocellular carcinoma by inactivation of phagocyte killing.

Hepatocellular carcinoma (HCC) acquires an immunosuppressive microenvironment, leading to unbeneficial therapeutic outcomes. Hyaluronan-mediated motility receptor (HMMR) plays a crucial role in tumor progression. Here, we found that aberrant expression of HMMR could be a predictive biomarker for the immune suppressive microenvironment of HCC, but the mechanism remains unclear. We established an HMMR-/- liver cancer mouse model to elucidate the HMMR-mediated mechanism of the dysregulated "don't eat me" signal. HMMR knockout inhibited liver cancer growth and induced phagocytosis. HMMRhigh liver cancer cells escaped from phagocytosis via sustaining CD47 signaling. Patients with HMMRhighCD47high expression showed a worse prognosis than those with HMMRlowCD47low expression. HMMR formed a complex with FAK/SRC in the cytoplasm to activate NF-κB signaling, which could be independent of membrane interaction with CD44. Notably, targeting HMMR could enhance anti-PD-1 treatment efficiency by recruiting CD8+ T cells. Overall, our data revealed a regulatory mechanism of the "don't eat me" signal and knockdown of HMMR for enhancing anti-PD-1 treatment.

Federated Graph Anomaly Detection via Contrastive Self-Supervised Learning.

Attribute graph anomaly detection aims to identify nodes that significantly deviate from the majority of normal nodes, and has received increasing attention due to the ubiquity and complexity of graph-structured data in various real-world scenarios. However, current mainstream anomaly detection methods are primarily designed for centralized settings, which may pose privacy leakage risks in certain sensitive situations. Although federated graph learning offers a promising solution by enabling collaborative model training in distributed systems while preserving data privacy, a practical challenge arises as each client typically possesses a limited amount of graph data. Consequently, naively applying federated graph learning directly to anomaly detection tasks in distributed environments may lead to suboptimal performance results. We propose a federated graph anomaly detection framework via contrastive self-supervised learning (CSSL) federated CSSL anomaly detection framework (FedCAD) to address these challenges. FedCAD updates anomaly node information between clients via federated learning (FL) interactions. First, FedCAD uses pseudo-label discovery to determine the anomaly node of the client preliminarily. Second, FedCAD employs a local anomaly neighbor embedding aggregation strategy. This strategy enables the current client to aggregate the neighbor embeddings of anomaly nodes from other clients, thereby amplifying the distinction between anomaly nodes and their neighbor nodes. Doing so effectively sharpens the contrast between positive and negative instance pairs within contrastive learning, thus enhancing the efficacy and precision of anomaly detection through such a learning paradigm. Finally, the efficiency of FedCAD is demonstrated by experimental results on four real graph datasets.

Quantum criticality of generalized Aubry-André models with exact mobility edges using fidelity susceptibility.

In this study, we explore the quantum critical phenomena in generalized Aubry-André models, with a particular focus on the scaling behavior at various filling states. Our approach involves using quantum fidelity susceptibility to precisely identify the mobility edges in these systems. Through a finite-size scaling analysis of the fidelity susceptibility, we are able to determine both the correlation-length critical exponent and the dynamical critical exponent at the critical point of the generalized Aubry-André model. Based on the Diophantine equation conjecture, we can determines the number of subsequences of the Fibonacci sequence and the corresponding scaling functions for a specific filling fraction, as well as the universality class. Our findings demonstrate the effectiveness of employing the generalized fidelity susceptibility for the analysis of unconventional quantum criticality and the associated universal information of quasiperiodic systems in cutting-edge quantum simulation experiments.

NPC Intracellular Cholesterol Transporter 1 Regulates Ovarian Maturation and Molting in Female Macrobrachium nipponense.

NPC intracellular cholesterol transporter 1 (NPC1) plays an important role in sterol metabolism and transport processes and has been studied in many vertebrates and some insects, but rarely in crustaceans. In this study, we characterized NPC1 from Macrobrachium nipponense (Mn-NPC1) and evaluated its functions. Its total cDNA length was 4283 bp, encoding for 1344 amino acids. It contained three conserved domains typical of the NPC family (NPC1_N, SSD, and PTC). In contrast to its role in insects, Mn-NPC1 was mainly expressed in the adult female hepatopancreas, with moderate expression in the ovary and heart. No expression was found in the embryo (stages CS-ZS) and only weak expression in the larval stages from hatching to the post-larval stage (L1-PL15). Mn-NPC1 expression was positively correlated with ovarian maturation. In situ hybridization showed that it was mainly located in the cytoplasmic membrane and nucleus of oocytes. A 25-day RNA interference experiment was employed to illustrate the Mn-NPC1 function in ovary maturation. Experimental knockdown of Mn-NPC1 using dsRNA resulted in a marked reduction in the gonadosomatic index and ecdysone content of M. nipponense females. The experimental group showed a significant delay in ovarian maturation and a reduction in the frequency of molting. These results expand our understanding of NPC1 in crustaceans and of the regulatory mechanism of ovarian maturation in M. nipponense.

Prevention and treatment of antibiotics-associated adverse effects through the use of probiotics: A review.

BACKGROUND: The human gut hosts a diverse microbial community, essential for maintaining overall health. However, antibiotics, commonly prescribed for infections, can disrupt this delicate balance, leading to antibiotic-associated diarrhea, inflammatory bowel disease, obesity, and even neurological disorders. Recognizing this, probiotics have emerged as a promising strategy to counteract these adverse effects. AIM OF REVIEW: This review aims to offer a comprehensive overview of the latest evidence concerning the utilization of probiotics in managing antibiotic-associated side effects. KEY SCIENTIFIC CONCEPTS OF REVIEW: Probiotics play a crucial role in preserving gut homeostasis, regulating intestinal function and metabolism, and modulating the host immune system. These mechanisms serve to effectively alleviate antibiotic-associated adverse effects and enhance overall well-being.

Distinctive hydrodynamic properties and ecological responses of multi-thread rivers under different degrees of multiplicity in the Upper Yellow River.

Alluvial rivers that exhibit multi-thread patterns are common in nature and can be the dominant channel morphology in large rivers. However, their ecological properties in response to diverse and dynamic channel morphology has gained limited attention and remained poorly understood. In this study, we adopted an eco-hydraulic model by integrating a hydrodynamic, a sediment-transport, and a habitat-suitability model to assess habitat quality for fish species (Schizopygopsis pylzovi and Platypharodon extremus) in three anabranching reaches with each exhibiting a distinct anabranching morphology in the Upper Yellow River, eastern Qinghai-Tibet Plateau. Based on the hydrologic data and actual channel morphology, we modeled the hydrodynamic and sediment-transport conditions for a period spanning ten years, and simulated habitat conditions under a potentially changing environment with different flow magnitudes and frequencies. The results indicated that the average flow velocity in the low and mid-order anabranching reaches is higher than that in the high-order, complex anabranching reaches. Meanwhile, the bedload transport rate was higher in the high and mid-order anabranching reaches than that in the low-order anabranching reach, demonstrating a greater transport efficiency of multi-thread systems with a greater multiplicity. Consequently, the habitat suitability shows a deteriorating trend over the ten-year modeling period and Schizopygopsis pylzovi shows better habitat status than Platypharodon extremus. The flow magnitudes and frequency also have a significant impact on the distribution of high habitat suitability index among the different river patterns in Upper Yellow River. This study can provide valuable information to optimize ecological outcomes and provide valuable insights for future dam operation strategies and consideration efforts aimed at preserving and restoring riverine ecosystems.

Human Breast Milk: The Role of Its Microbiota and Metabolites in Infant Health.

This review explores the role of microorganisms and metabolites in human breast milk and their impact on neonatal health. Breast milk serves as both a primary source of nutrition for newborns and contributes to the development and maturation of the digestive, immunological, and neurological systems. It has the potential to reduce the risks of infections, allergies, and asthma. As our understanding of the properties of human milk advances, there is growing interest in incorporating its benefits into personalized infant nutrition strategies, particularly in situations in which breastfeeding is not an option. Future infant formula products are expected to emulate the composition and advantages of human milk, aligning with an evolving understanding of infant nutrition. The long-term health implications of human milk are still under investigation.

EPAS1, a hypoxia- and ferroptosis-related gene, promotes malignant behaviour of cervical cancer by ceRNA and super-enhancer.

Hypoxia and Ferroptosis are associated with the malignant behaviour of cervical cancer. Endothelial PAS domain-containing protein 1 (EPAS1) contributes to the progression of cervical cancer. EPAS1 plays important roles in hypoxia and ferroptosis. Using the GEO dataset, machine-learning algorithms were used to screen for hypoxia- and ferroptosis-related genes (HFRGs) in cervical cancer. EPAS1 was identified as the hub gene. qPCR and WB were used to investigate the expression of EPAS1 in normal and cervical cancer tissues. The proliferation, invasion and migration of EPAS1 cells in HeLa and SiHa cell lines were detected using CCK8, transwell and wound healing assays, respectively. Apoptosis was detected by flow cytometry. A dual-luciferase assay was used to analyse the MALAT1-miR-182-5P-EPAS1 mRNA axis and core promoter elements of the super-enhancer. EPAS1 was significantly overexpressed in cervical cancer tissues. EPAS1 could increase the proliferation, invasion, migration of HeLa and SiHa cells and reduce the apoptosis of HeLa and SiHa cell. According to the double-luciferase assay, EPAS1 expression was regulated by the MALAT1-Mir-182-5p-EPAS1 mRNA axis. EPAS1 is associated with super-enhancers. Double-luciferase assay showed that the core elements of the super-enhancer were E1 and E3. EPAS1, an HFRG, is significantly overexpressed in cervical cancer. EPAS1 promotes malignant behaviour of cervical cancer cells. EPAS1 expression is regulated by super-enhancers and the MALAT1-miR-182-5P- EPAS1 mRNA axis. EPAS1 may be a target for the diagnosis and treatment of cervical cancer.

Nanoplastic pollution changes the intestinal microbiome but not the morphology or behavior of a freshwater turtle.

Humans produce 350 million metric tons of plastic waste per year, leading to microplastic pollution and widespread environmental contamination, particularly in aquatic environments. This subsequently impacts aquatic organisms in myriad ways, yet the vast majority of research is conducted in marine, rather than freshwater systems. In this study, we exposed eggs and hatchlings of the Chinese soft-shelled turtle (Pelodiscus sinensis) to 80-nm polystyrene nanoplastics (PS-NPs) and monitored the impacts on development, behavior and the gut microbiome. We demonstrate that 80-nm PS-NPs can penetrate the eggshell and move into developing embryos. This led to metabolic impairments, as evidenced by bradycardia (a decreased heart rate), which persisted until hatching. We found no evidence that nanoplastic exposure affected hatchling morphology, growth rates, or levels of boldness and exploration, yet we discuss some potential caveats here. Exposure to nanoplastics reduced the diversity and homogeneity of gut microbiota in P. sinensis, with the level of disruption correlating to the length of environmental exposure (during incubation only or post-hatching also). Thirteen core genera (with an initial abundance >1 %) shifted after nanoplastic treatment: pathogenic bacteria increased, beneficial probiotic bacteria decreased, and there was an increase in the proportion of negative correlations between bacterial genera. These changes could have profound impacts on the viability of turtles throughout their lives. Our study highlights the toxicity of environmental NPs to the embryonic development and survival of freshwater turtles. We provide insights about population trends of P. sinensis in the wild, and future directions for research.

Chitosan Phytate Nanoparticles: A Synergistic Strategy for Effective Dental Caries Prevention.

Dental caries is a widespread oral disease that poses a significant medical challenge. Traditional caries prevention methods, primarily the application of fluoride, often fall short in effectively destroying biofilms and preventing enamel demineralization, thereby providing limited efficacy in halting the progression of caries over time. To address this issue, we have developed a green and cost-effective synergistic strategy for the prevention of dental caries. By combining natural sodium phytate and chitosan, we have created chitosan-sodium phytate nanoparticles that offer both the antimicrobial properties of chitosan and the enamel demineralization-inhibiting capabilities of sodium phytate. In an ex vivo biofilm model of human teeth, we found that these nanoparticles effectively prevent biofilm buildup and acid damage to the mineralized tissue. Additionally, topical treatment of dental caries in rodent models has shown that these nanoparticles effectively suppress disease progression without negatively impacting oral microbiota diversity or causing harm to the gingival-mucosal tissues, unlike traditional prevention methods.

Lag effect of ambient temperature on respiratory emergency department visits in Beijing: a time series and pooled analysis.

BACKGROUND: Although the association between ambient temperature and mortality of respiratory diseases was numerously documented, the association between various ambient temperature levels and respiratory emergency department (ED) visits has not been well studied. A recent investigation of the association between respiratory ED visits and various levels of ambient temperature was conducted in Beijing, China. METHODS: Daily meteorological data, air pollution data, and respiratory ED visits data from 2017 to 2018 were collected in Beijing. The relationship between ambient temperature and respiratory ED visits was explored using a distributed lagged nonlinear model (DLNM). Then we performed subgroup analysis based on age and gender. Finally, meta-analysis was utilized to aggregate the total influence of ambient temperature on respiratory ED visits across China. RESULTS: The single-day lag risk for extreme cold peaked at a relative risk (RR) of 1.048 [95% confidence interval (CI): 1.009, 1.088] at a lag of 21 days, with a long lag effect. As for the single-day lag risk for extreme hot, a short lag effect was shown at a lag of 7 days with an RR of 1.076 (95% CI: 1.038, 1.114). The cumulative lagged effects of both hot and cold effects peaked at lag 0-21 days, with a cumulative risk of the onset of 3.690 (95% CI: 2.133, 6.382) and 1.641 (95% CI: 1.284, 2.098), respectively, with stronger impact on the hot. Additionally, the elderly were more sensitive to ambient temperature. The males were more susceptible to hot weather than the females. A longer cold temperature lag effect was found in females. Compared with the meta-analysis, a pooled effect of ambient temperature was consistent in general. In the subgroup analysis, a significant difference was found by gender. CONCLUSIONS: Temperature level, age-specific, and gender-specific effects between ambient temperature and the number of ED visits provide information on early warning measures for the prevention and control of respiratory diseases.

Metabolomics analysis revealed the neuroprotective role of 2-phosphoglyceric acid in hypoxic-ischemic brain damage through GPX4/ACSL4 axis regulation.

Hypoxic-ischemic brain damage (HIBD) is a cerebral injury resulting from the combination of ischemia and hypoxia in neonatal brain tissue. Presently, there exists no efficacious remedy for HIBD. A mounting body of evidence indicates that dynamic metabolites formed during metabolic procedures assume a vital role in neuronal maturation and recuperation. However, it remains unclear whether any endogenous metabolites are involved in the pathogenesis of HIBD. Here, an untargeted metabolomics analysis was conducted by gas chromatography-mass spectrometry and liquid chromatography-mass spectrometry (GC/LC-MS) in OGD/R (oxygen-glucose deprivation/reoxygenation)-induced HT-22 cells. We observed that ferroptosis signaling plays an essential role in HI-induced neuronal injury. Interestingly, we also found that the differentially expressed metabolite, 2-phosphoglyceric acid, significantly improved the neuronal cell survival of OGD/R HT-22 cells by inhibiting ferroptosis. Moreover, 2-phosphoglyceric acid effectively rescued the cell activity of HT-22 cells treated with the ferroptosis inducer RSL-3. Furthermore, 2-phosphoglyceric acid alleviated cerebral infarction and reduced HIBD-induced neuronal cell loss of the central nervous system in neonatal rats by regulating GPX4 expression. Taken together, we found that 2-phosphoglyceric acid, which was downregulated in HT-22 cells induced by OGD/R, exerted neuronal protective effects on OGD/R-treated HT-22 cells and HIBD-induced neonatal rats by inhibiting hypoxic-ischemic-induced ferroptosis through the regulation of the GPX4/ACSL4 axis.

Identifying Relationships between Glutathione S-Transferase-2 Single Nucleotide Polymorphisms and Hypoxia Tolerance and Growth Traits in Macrobrachium nipponense.

Investigating hypoxia tolerance and growth trait single nucleotide polymorphisms (SNPs) in Macrobrachium nipponense is conducive to cultivating prawns with hypoxia tolerance and good growth characteristics. The glutathione S-transferase-2 gene (GST-2) has been shown to regulate hypoxia responses in M. nipponense. In this study, we identified a single GST-2 SNP in M. nipponense, and analyzed its regulatory relationship with hypoxia tolerance and growth. The GST-2 sequence was amplified with a polymerase chain reaction from 197 "Taihu Lake No. 3", "Taihu Lake No. 2", and Pearl River population samples to identify SNP loci. The full-length Mn-GST2 sequence was 2317 bp, including three exons and two introns. In total, 38 candidate SNP loci were identified from GST-2 using Mega11.0 comparisons, with most loci moderately polymorphic in terms of genetic diversity. Locus genotypes were also analyzed, and basic genetic parameters for loci were calculated using Popgene32 and PIC_CALC. The expected heterozygosity of the 38 SNP loci ranged from 0.2334 to 0.4997, with an average of 0.4107, while observed heterozygosity ranged from 0.1929 to 0.4721, with an average of 0.3401. The polymorphic information content ranged from 0.21 to 0.37. From SPSS analyses, the G+256A locus was significantly correlated with hypoxia tolerance across all three M. nipponense populations, while the SNP loci A+261C, C+898T, A+1370C, and G+1373T were significantly associated with growth traits. Further analyses revealed that the T+2017C locus was significantly correlated with hypoxia tolerance in "Taihu Lake No. 2" populations, G+256A, A+808T, C+1032T, and A+1530G loci were significantly correlated with hypoxia tolerance in "Taihu Lake No. 3" populations, while no SNP loci were correlated with hypoxia tolerance in Pearl River populations. A+1370C and G+1373T loci, which were associated with growth traits, exhibited a high degree of linkage disequilibrium (r2 = 0.89 and r2 > 0.8), suggesting potential genetic linkage. Our data suggest associations between hypoxia tolerance and growth trait SNP loci in M. nipponense, and provide valuable evidence for the genetic improvement of growth and hypoxia tolerance in this prawn species.

Medium-term exposure to size-fractioned particulate matter and asthma exacerbations in China: A longitudinal study of asthmatics with poor medication adherence.

BACKGROUND: Studies have shown that short- and long-term exposure to particulate matter (PM) can increase the risk of asthma morbidity and mortality. However, the effect of medium-term exposure remains unknown. We aim to examine the effect of medium-term exposure to size-fractioned PM on asthma exacerbations among asthmatics with poor medication adherence. METHODS: We conducted a longitudinal study in China based on the National Mobile Asthma Management System Project that specifically and routinely followed asthma exacerbations in asthmatics with poor medication adherence from April 2017 to May 2019. High-resolution satellite remote-sensing data were used to estimate each participant's medium-term exposure (on average 90 days) to size-fractioned PM (PM1, PM2.5, and PM10) based on the residential address and the date of the follow-up when asthma exacerbations (e.g., hospitalizations and emergency room visits) occurred or the end of the follow-up. The Cox proportional hazards model was employed to examine the hazard ratio of asthma exacerbations associated with each PM after controlling for sex, age, BMI, education level, geographic region, and temperature. RESULTS: Modelling results revealed nonlinear exposure-response associations of asthma exacerbations with medium-term exposure to PM1, PM2.5, and PM10. Specifically, for emergency room visits, we found an increased hazard ratio for PM1 above 22.8 µg/m3 (1.060, 95 % CI: 1.025-1.096, per 1 µg/m3 increase), PM2.5 above 38.2 µg/m3 (1.032, 95 % CI: 1.010-1.054), and PM10 above 78.6 µg/m3 (1.019, 95 % CI: 1.006-1.032). For hospitalizations, we also found an increased hazard ratio for PM1 above 20.3 µg/m3 (1.055, 95 % CI: 1.001-1.111) and PM2.5 above 39.2 µg/m3 (1.038, 95 % CI: 1.003-1.074). Furthermore, the effects of PM were greater for a longer exposure window (90-180 days) and among participants with a high BMI. CONCLUSION: This study suggests that medium-term exposure to PM is associated with an increased risk of asthma exacerbations in asthmatics with poor medication adherence, with a higher risk from smaller PM.

Vulnerability to APOBEC3G linked to the pathogenicity of deltaretroviruses.

Human retroviruses are derived from simian ones through cross-species transmission. These retroviruses are associated with little pathogenicity in their natural hosts, but in humans, HIV causes AIDS, and human T-cell leukemia virus type 1 (HTLV-1) induces adult T-cell leukemia-lymphoma (ATL). We analyzed the proviral sequences of HTLV-1, HTLV-2, and simian T-cell leukemia virus type 1 (STLV-1) from Japanese macaques (Macaca fuscata) and found that APOBEC3G (A3G) frequently generates G-to-A mutations in the HTLV-1 provirus, whereas such mutations are rare in the HTLV-2 and STLV-1 proviruses. Therefore, we investigated the mechanism of how HTLV-2 is resistant to human A3G (hA3G). HTLV-1, HTLV-2, and STLV-1 encode the so-called antisense proteins, HTLV-1 bZIP factor (HBZ), Antisense protein of HTLV-2 (APH-2), and STLV-1 bZIP factor (SBZ), respectively. APH-2 efficiently inhibits the deaminase activity of both hA3G and simian A3G (sA3G). HBZ and SBZ strongly suppress sA3G activity but only weakly inhibit hA3G, suggesting that HTLV-1 is incompletely adapted to humans. Unexpectedly, hA3G augments the activation of the transforming growth factor (TGF)-ß/Smad pathway by HBZ, and this activation is associated with ATL cell proliferation by up-regulating BATF3/IRF4 and MYC. In contrast, the combination of APH-2 and hA3G, or the combination of SBZ and sA3G, does not enhance the TGF-ß/Smad pathway. Thus, HTLV-1 is vulnerable to hA3G but utilizes it to promote the proliferation of infected cells via the activation of the TGF-ß/Smad pathway. Antisense factors in each virus, differently adapted to control host cellular functions through A3G, seem to dictate the pathogenesis.