Unveiling the intricacies of COVID-19: Autoimmunity, multi-organ manifestations and the role of autoantibodies.

COVID-19 is a severe infectious disease caused by a SARS-CoV-2 infection. It has caused a global pandemic and can lead to acute respiratory distress syndrome (ARDS). Beyond the respiratory system, the disease manifests in multiple organs, producing a spectrum of clinical symptoms. A pivotal factor in the disease's progression is autoimmunity, which intensifies its severity and contributes to multi-organ injuries. The intricate interaction between the virus' spike protein and human proteins may engender the generation of autoreactive antibodies through molecular mimicry. This can further convolute the immune response, with the potential to escalate into overt autoimmunity. There is also emerging evidence to suggest that COVID-19 vaccinations might elicit analogous autoimmune responses. Advanced technologies have pinpointed self-reactive antibodies that target diverse organs or immune-modulatory proteins. The interplay between autoantibody levels and multi-organ manifestations underscores the importance of regular monitoring of serum antibodies and proinflammatory markers. A combination of immunosuppressive treatments and antiviral therapy is crucial for managing COVID-19-associated autoimmune diseases. The review will focus on the generation of autoantibodies in the context of COVID-19 and their impact on organ health.

Revolutionizing aquatic eco-environmental monitoring: Utilizing the RPA-Cas-FQ detection platform for zooplankton.

The integration of recombinase polymerase amplification (RPA) with CRISPR/Cas technology has revolutionized molecular diagnostics and pathogen detection due to its unparalleled sensitivity and trans-cleavage ability. However, its potential in the ecological and environmental monitoring scenarios for aquatic ecosystems remains largely unexplored, particularly in accurate qualitative/quantitative detection, and its actual performance in handling complex real environmental samples. Using zooplankton as a model, we have successfully optimized the RPA-CRISPR/Cas12a fluorescence detection platform (RPA-Cas-FQ), providing several crucial "technical tips". Our findings indicate the sensitivity of CRISPR/Cas12a alone is 5 × 109 copies/reaction, which can be dramatically increased to 5 copies/reaction when combined with RPA. The optimized RPA-Cas-FQ enables reliable qualitative and semi-quantitative detection within 50 min, and exhibits a good linear relationship between fluorescence intensity and DNA concentration (R2 = 0.956-0.974***). Additionally, we developed a rapid and straightforward identification procedure for single zooplankton by incorporating heat-lysis and DNA-barcode techniques. We evaluated the platform's effectiveness using real environmental DNA (eDNA) samples from the Three Gorges Reservoir, confirming its practicality. The eDNA-RPA-Cas-FQ demonstrated strong consistency (Kappa = 0.43***) with eDNA-Metabarcoding in detecting species presence/absence in the reservoir. Furthermore, the two semi-quantitative eDNA technologies showed a strong positive correlation (R2 = 0.58-0.87***). This platform also has the potential to monitor environmental pollutants by selecting appropriate indicator species. The novel insights and methodologies presented in this study represent a significant advancement in meeting the complex needs of aquatic ecosystem protection and monitoring.

Presence of humic acid in the environment holds promise as a potential mitigating factor for the joint toxicity of polystyrene nanoplastics and herbicide atrazine to Chlorella vulgaris: 96-H acute toxicity.

Increasing amounts of amino-functionalized polystyrene nanoplastics (PS-NH2) are entering aquatic ecosystems, raising concerns. Hence, this study investigated 96-h acute toxicity of PS-NH2 and its combination with the pesticide atrazine (ATZ) in the absence/presence of humic acid (HA) on the microalgae Chlorella vulgaris (C. vulgaris). Results showed that both PS-NH2 and PS-NH2+ATZ reduced algal growth, photosynthetic pigments, protein content, and antioxidant capacity, while increasing enzymatic activities. Gene expression related to oxidative stress was altered in C. vulgaris exposed to these treatments. Morphological and intracellular changes were also observed. The combined toxicity of PS-NH2+ATZ demonstrated a synergistic effect, but the addition of environmentally relevant concentration of HA significantly alleviated its toxicity to C. vulgaris, indicating an antagonistic effect due to the emergence of an eco-corona, and entrapment and sedimentation of PS-NH2+ATZ particles by HA. This study firstly highlights the role of HA in mitigating the toxicity of PS-NH2 when combined with other harmful compounds, enhancing our understanding of HA's presence in the environment.

Developmental Toxicity of PEDOT:PSS in Zebrafish: Effects on Morphology, Cardiac Function, and Intestinal Health.

Poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) is a conductive polymer commonly used in various technological applications. However, its impact on aquatic ecosystems remains largely unexplored. In this study, we investigated the toxicity effects of PEDOT:PSS on zebrafish. We first determined the lethal concentration (LC50) of PEDOT:PSS in zebrafish and then exposed AB-type zebrafish embryos to different concentrations of PEDOT:PSS for 120 h. Our investigation elucidated the toxicity effects of zebrafish development, including morphological assessments, heart rate measurements, behavioral analysis, transcriptome profiling, and histopathological analysis. We discovered that PEDOT:PSS exhibited detrimental effects on the early developmental stages of zebrafish, exacerbating the oxidative stress level, suppressing zebrafish activity, impairing cardiac development, and causing intestinal cell damage. This study adds a new dimension to the developmental toxicity of PEDOT:PSS in zebrafish. Our findings contribute to our understanding of the ecological repercussions of PEDOT:PSS and highlight the importance of responsible development and application of novel materials in our rapidly evolving technological landscape.

Biogeographic patterns of meio- and micro-eukaryotic communities in dam-induced river-reservoir systems.

Although the Three Gorges Dam (TGD) is the world's largest hydroelectric dam, little is known about the spatial-temporal patterns and community assembly mechanisms of meio- and micro-eukaryotes and its two subtaxa (zooplankton and zoobenthos). This knowledge gap is particularly evident across various habitats and during different water-level periods, primarily arising from the annual regular dam regulation. To address this inquiry, we employed mitochondrial cytochrome c oxidase I (COI) gene-based environmental DNA (eDNA) metabarcoding technology to systematically analyze the biogeographic pattern of the three communities within the Three Gorges Reservoir (TGR). Our findings reveal distinct spatiotemporal characteristics and complementary patterns in the distribution of meio- and micro-eukaryotes. The three communities showed similar biogeographic patterns and assembly processes. Notably, the diversity of these three taxa gradually decreased along the river. Their communities were less shaped by stochastic processes, which gradually decreased along the longitudinal riverine-transition-lacustrine gradient. Hence, deterministic factors, such as seasonality, environmental, and spatial variables, along with species interactions, likely play a pivotal role in shaping these communities. Environmental factors primarily drive seasonal variations in these communities, while hydrological conditions, represented as spatial distance, predominantly influence spatial variations. These three communities followed the distance-decay pattern. In winter, compared to summer, both the decay and species interrelationships are more pronounced. Taken together, this study offers fresh insights into the composition and diversity patterns of meio- and micro-eukaryotes at the spatial-temporal level. It also uncovers the mechanisms behind community assembly in various environmental niches within the dam-induced river-reservoir systems. KEY POINTS: • Distribution and diversity of meio- and micro-eukaryotes exhibit distinct spatiotemporal patterns in the TGR. • Contribution of stochastic processes in community assembly gradually decreases along the river. • Deterministic factors and species interactions shape meio- and micro-eukaryotic community.

Supervised machine learning improves general applicability of eDNA metabarcoding for reservoir health monitoring.

Effective and standardized monitoring methodologies are vital for successful reservoir restoration and management. Environmental DNA (eDNA) metabarcoding sequencing offers a promising alternative for biomonitoring and can overcome many limitations of traditional morphological bioassessment. Recent attempts have even shown that supervised machine learning (SML) can directly infer biotic indices (BI) from eDNA metabarcoding data, bypassing the cumbersome calculation process of BI regardless of the taxonomic assignment of eDNA sequences. However, questions surrounding the general applicability of this taxonomy-free approach to monitoring reservoir health remain unclear, including model stability, feature selection, algorithm choice, and multi-season biomonitoring. Here, we firstly developed a novel biological integrity index (Me-IBI) that integrates multitrophic interactions and environmental information, based on taxonomy-assigned eDNA metabarcoding data. The Me-IBI can better distinguish the actual health status of the Three Gorges Reservoir (TGR) than physicochemical assessments and have a clear response to human activity. Then, taking this reliable Me-IBI as a supervised label, we compared the impact of selecting different numbers of features and SML algorithms on the stability and predictive performance of the model for predicting ecological conditions in multiple seasons using taxonomy-free eDNA metabarcoding data. We discovered that even with a small number of features, different SML algorithms can establish a stable model and obtain excellent predictive performance. Finally, we proposed a four-step strategy for standardized routine biomonitoring using SML tools. Our study firstly explores the general applicability problem of the taxonomy-free eDNA-SML approach and establishes a solid foundation for the large-scale and standardized biomonitoring application.

Multi-omics reveal mechanisms underlying chronic kidney disease of unknown etiology (CKDu) pathogenesis using zebrafish.

Chronic kidney disease of unknown etiology (CKDu) is an endemic disease in the dry zone of farming communities, Sri Lanka. The drinking water in a CKDu prevalent area contains a high concentration of F-, hardness and other environmental pollutants, including heavy metals and microcystin, which are considered possible etiology of CKDu in these areas. Here, multi-omics data with host transcriptome, metabolome and gut microbiomes were obtained using simulated local drinking water of Sri Lanka after their exposure to adult zebrafish. Based on an integrated multi-omics analysis in the context of host physiology in the kidney injury samples with different pathologic grades, two common pathways necroptosis and purine metabolism were identified as potentially important pathways that affect kidney injury. The key metabolite acetyl adenylate in the purine metabolism pathway was significantly positively correlated with Comamonas (rho = 0.72) and significantly negatively correlated with Plesiomonas (rho = -0.58). This crucial metabolite and two key gut bacteria genera may not only be potential markers but also potential therapeutic targets in the uric acid metabolic pathway, which is an important factor in the pathogenesis of acute kidney injury (AKI) in general, as well as of chronic kidney disease (CKD). Based on this, we revealed the urea metabolism pathway of kidney injury in zebrafish and provided a new avenue for the treatment of CKDu in Sri Lanka.

Ultra-sensitive detection of ecologically rare fish from eDNA samples based on the RPA-CRISPR/Cas12a technology.

Environmental DNA (eDNA) research holds great promise for improving biodiversity science and conservation efforts by enabling worldwide species censuses in near real-time. Current eDNA methods face challenges in detecting low-abundance ecologically important species. In this study, we used isothermal recombinase polymerase amplification (RPA)-CRISPR/Cas detection to test Ctenopharyngodon idella. RPA-CRISPR-Cas12a detected 6.0 eDNA copies/µL within 35 min. Ecologically rare species were identified in the Three Gorges Reservoir Area (TGRA) using functional distinctiveness and geographical restrictiveness, with seven fish species (9%) classified as potentially ecologically rare including three species in this investigation. RPA-CRISPR/Cas12a-FQ outperformed high-throughput sequencing (HTS) and qPCR in detecting low-abundance eDNA (AUC = 0.883∗∗). A significant linear correlation (R2 = 0.682∗∗) between RPA-CRISPR/Cas12a-FQ and HTS quantification suggests its potential for predicting species abundance and enhancing eDNA-based fish biodiversity monitoring. This study highlights the value of RPA-CRISPR/Cas12a-FQ as a tool for advancing eDNA research and conservation efforts.

Elucidating environmental factors and their combined effects on CKDu in Sri Lanka using zebrafish.

Chronic kidney disease with uncertain etiology (CKDu) in Sri Lanka has attracted much attention as a global health issue. However, how environmental factors in local drinking water induce kidney damage in organisms is still elusive. We investigated multiple environmental factors including water hardness and fluoride (HF), heavy metals (HM), microcystin-LR (MC-LR), and their combined exposure (HFMM) to elucidate their toxic effects on CKDu risk in zebrafish. Acute exposure affected renal development and inhibited the fluorescence of Na, K-ATPase alpha1A4:GFP zebrafish kidney. Chronic exposure influenced the body weight of both genders of adult fish and induced kidney damage by histopathological analyses. Furthermore, the exposure significantly disturbed differential expression genes (DEGs), diversity and richness of gut microbiota, and critical metabolites related to renal functions. The transcriptomic analysis revealed that kidney-related DEGs were linked with renal cell carcinoma, proximal tubule bicarbonate reclamation, calcium signaling pathway, and HIF-1 signaling pathway. The significantly disrupted intestinal microbiota was closely related to the environmental factors and H&E score, which demonstrated the mechanisms of kidney risks. Notably, the Spearman correlation analysis indicated that the changed bacteria such as Pseudomonas, Paracoccus, and ZOR0006, etc were significantly connected to the DEGs and metabolites. Therefore, the assessment of multiple environmental factors provided new insights on "bio-markers" as potential therapies of the target signaling pathways, metabolites, and gut bacteria to monitor or protect residents from CKDu.

Exercise Rehabilitation and Chronic Respiratory Diseases: Effects, Mechanisms, and Therapeutic Benefits.

Chronic respiratory diseases (CRD), is a group of disorders, primarily chronic obstructive pulmonary disease and asthma, which are characterized by high prevalence and disability, recurrent acute exacerbations, and multiple comorbidities, resulting in exercise limitations and reduced health-related quality of life. Exercise training, an important tool in pulmonary rehabilitation, reduces adverse symptoms in patients by relieving respiratory limitations, increasing gas exchange, increasing central and peripheral hemodynamic forces, and enhancing skeletal muscle function. Aerobic, resistance, and high-intensity intermittent exercises, and other emerging forms such as aquatic exercise and Tai Chi effectively improve exercise capacity, physical fitness, and pulmonary function in patients with CRD. The underlying mechanisms include enhancement of the body's immune response, better control of the inflammatory response, and acceleration of the interaction between the vagus and sympathetic nerves to improve gas exchange. Here, we reviewed the new evidence of benefits and mechanisms of exercise intervention in the pulmonary rehabilitation of patients with chronic obstructive pulmonary disease, bronchial asthma, bronchiectasis, interstitial lung disease, and lung cancer.

Effects of High-Intensity Interval Training and Combined High-Intensity Interval Training Programs on Cancer-Related Fatigue and Cancer Pain: A Systematic Review and Meta-analysis.

PURPOSE: This systematic review and meta-analysis assessed the effectiveness of high-intensity interval training (HIIT) alone and combined HIIT programs compared with usual care on cancer-related fatigue (CRF) and pain related to cancer or cancer-related treatments. METHODS: Articles published prior to January 2023 were searched in the following digital databases: PubMed, Cochrane Database of Systematic Reviews and Cochrane Controlled Clinical Trials (CENTRAL), Web of Science, Scopus and ScienceDirect. Randomized controlled trials were included that met the following criteria: (i) adult cancer patients and survivors (>18 yr old); (ii) HIIT or combined HIIT programs versus usual care; (iii) assessment of fatigue and pain. Cochrane tool was used for assessing Risk of Bias (RoB) and Review Manager (RevMan 5.2) was used for data analysis. RESULTS: Based on limited number (12) of studies included, we found HIIT and combined HIIT interventions have significant effect sizes on reducing both CRF (standardized mean difference, 0.63; 95% confidence interval, 0.42-0.84; P < 0.001) and cancer-associated pain (standardized mean difference, 0.44; 95% confidence interval, 0.25-0.63; P < 0.001). CONCLUSIONS: This systematic review and meta-analysis indicate that HIIT and combined HIIT programs can reduce CRF and pain.

Generation and application of a novel high-throughput detection based on RPA-CRISPR technique to sensitively monitor pathogenic microorganisms in the environment.

Staphylococcus aureus (S. aureus) is an important opportunistic human and animal pathogen that can cause a wide diversity of infections. Due to its environmental health risks, it is crucial to establish a time-saving, high-throughput, and highly sensitive technique for water quality surveillance. In this study, we developed a novel method to detect S. aureus in the water environment based on recombinase polymerase amplification (RPA) and CRISPR/Cas12a. This method utilizes isothermal amplification of nucleic acids and the trans-cleavage activity of the CRISPR/Cas12a system to generate fluorescence signals with a single-stranded DNA-fluorophore-quencher (ssDNA-FQ) reporter and a naked-eye detected lateral flow assay (LFA). Our RPA-CRISPR/Cas12a detection system can reduce the detection time to 35 min and enhance the high-throughput detection threshold to ≥5 copies of pathogen DNA, which is more sensitive than that of reported. Moreover, in the lower reaches of the Jialing River in Chongqing, China, 10 water samples from the mainstream and 7 ones from tributaries were successfully monitored S. aureus for less than 35 min using RPA-CRISPR/Cas12a detection system. Taken together, a novel high-throughput RPA-CRISPR detection was established and firstly applied for sensitively monitoring S. aureus in the natural water environment.

Development of molecular markers based on LTR retrotransposon in the Cleistogenes songorica genome.

Long terminal repeat retrotransposons (LTR-RTs) contribute a large fraction of many sequenced plant genomes and play important roles in genomic diversity and phenotypic variations. LTR-RTs are abundantly distributed in plant genomes, facilitating the development of markers based on LTR-RTs for a variety of genotyping purposes. Whole-genome analysis of LTR-RTs was performed in Cleistogenes songorica. A total of 299,079 LTR-RTs were identified and classified as Gypsy type, Copia type, or other type. LTR-RTs were widely distributed in the genome, enriched in the heterochromatic region of the chromosome, and negatively correlated with gene distribution. However, approximately one-fifth of genes were still interrupted by LTR-RTs, and these genes are annotated. Furthermore, four types of primer pairs (PPs) were designed, namely, retrotransposon-based insertion polymorphisms, inter-retrotransposon amplified polymorphisms, insertion site-based polymorphisms, and retrotransposon-microsatellite amplified polymorphisms. A total of 350 PPs were screened in 23 accessions of the genus Cleistogenes, of which 80 PPs showed polymorphism, and 72 PPs showed transferability among Gramineae and non-Gramineae species. In addition, a comparative analysis of homologous LTR-RTs was performed with other related grasses. Taken together, the study will serve as a valuable resource for genotyping applications for C. songorica and related grasses.

Role of manganese superoxide dismutase (Mn-SOD) against Cr(III)-induced toxicity in bacteria.

The toxicity of Cr(VI) was widely investigated, but the defense mechanism against Cr(III) in bacteria are seldom reported. Here, we found that Cr(III) inhibited bacterial growth and induced reactive oxygen species (ROS). After exposure to Cr(III), loss of sodA not only led to the excessive generation of ROS, but also enhanced the level of lipid peroxidation and reduced the GSH level, indicating that the deficiency of Mn-SOD decreased the bacterial resistance ability against Cr(III). The adverse effects of oxidative stress caused by Cr(III) could be recovered by the rescue of Mn-SOD in the sodA-deficient strain. Besides the oxidative stress, Cr(III) could cause the bacterial morphology variation, which was distinct between the wild-type and the sodA-deficient strains due to the differential expressions of Z-ring division genes. Moreover, Mn-SOD might prevent Cr(III) from oxidation on the bacterial surface by combining with Cr(III). Taken together, our results indicated that the Mn-SOD played a vital role in regulating the stress resistance, expression of cell division-related genes, bacterial morphology, and chemistry valence state of Cr. Our findings firstly provided a more in-depth understanding of Cr(III) toxicity and bacterial defense mechanism against Cr(III).

Transcriptome-Wide Characterization and Functional Identification of the Aquaporin Gene Family During Drought Stress in Common Vetch.

Aquaporins (AQPs) are transmembrane channels that are essential for the movement of water and other small molecules between biofilms in various physiological processes in plants. In this study, based on transcriptome-wide data, we identified and described a total of 21 AQP genes in common vetch (Vicia sativa subsp. sativa), which is an economically important pasture legume worldwide. Based on phylogenetic analyses, the VsAQPs were sorted into four subfamilies, including four plasma membrane intrinsic proteins (PIPs), six tonoplast intrinsic proteins (TIPs), seven NOD26-like intrinsic proteins, and four small basic intrinsic proteins. Furthermore, chemical and physical properties of these VsAQPs, including the isoelectric point and theoretical molecular weight, were analyzed. Analyses of the AQP signature sequences and key residues indicated the substrate specificity of each VsAQP. A set of VsAQPs was selected for gene expression analysis in a number of tissues and after drought stress treatments using real-time quantitative reverse transcription/polymerase chain reaction assays. Most of the PIPs and TIPs were proposed to have critical roles in regulating the flow of water during drought stress. Heterologous expression experiments in yeast indicated that VsPIP1;2 and VsPIP2;2 are key candidate genes for improving drought stress tolerance. The results reported in this study could be a crucial resource for further practical analyses and for genetic improvement of drought stress tolerance in common vetch.

Transcriptome-wide characterization and functional analysis of MATE transporters in response to aluminum toxicity in Medicago sativa L.

Multidrug and toxic compound extrusion (MATE) transporters contribute to multidrug resistance and play major determinants of aluminum (Al) tolerance in plants. Alfalfa (Medicago sativa L.) is the most extensively cultivated forage crop in the world, yet most alfalfa cultivars are not Al tolerant. The basic knowledge of the MATE transcripts family and the characterisation of specific MATE members involved in alfalfa Al stress remain unclear. In this study, 88 alfalfa MATE (MsMATE) transporters were identified at the whole transcriptome level. Phylogenetic analysis classified them into four subfamilies comprising 11 subgroups. Generally, five kinds of motifs were found in group G1, and most were located at the N-terminus, which might confer these genes with Al detoxification functions. Furthermore, 10 putative Al detoxification-related MsMATE genes were identified and the expression of five genes was significantly increased after Al treatment, indicating that these genes might play important roles in conferring Al tolerance to alfalfa. Considering the limited functional understanding of MATE transcripts in alfalfa, our findings will be valuable for the functional investigation and application of this family in alfalfa.

Genome-wide identification and expression analysis of the fatty acid desaturase genes in Medicago truncatula.

Fatty acid desaturases (FADs) are of great importance and play critical roles in regulating plant fatty acid (FA) compositions. But to date, no reports about characterization of the FAD genes have been reported in the model dicotyledonous grass species Medicago truncatula. In this study, using database searches, 20 full-length FAD genes were identified in M. truncatula. These FAD genes were unevenly distributed on six chromosomes except the chromosome 6 and 8. Phylogenetic analysis showed the FAD genes in M. truncatula were clustered into six subfamilies and had similar exon number and intron phase in the same subfamily. Moreover, expression analysis based on qRT-PCR indicated these FAD genes were extensively involved in cold and heat responses. This study would provide an important foundation for future cloning and functional studies of FAD genes in M. truncatula and other related legume species.

Genome-Wide Development of MicroRNA-Based SSR Markers in Medicago truncatula with Their Transferability Analysis and Utilization in Related Legume Species.

Microsatellite (simple sequence repeats, SSRs) marker is one of the most widely used markers in marker-assisted breeding. As one type of functional markers, MicroRNA-based SSR (miRNA-SSR) markers have been exploited mainly in animals, but the development and characterization of miRNA-SSR markers in plants are still limited. In the present study, miRNA-SSR markers for Medicago truncatula (M. truncatula) were developed and their cross-species transferability in six leguminous species was evaluated. A total of 169 primer pairs were successfully designed from 130 M. truncatula miRNA genes, the majority of which were mononucleotide repeats (70.41%), followed by dinucleotide repeats (14.20%), compound repeats (11.24%) and trinucleotide repeats (4.14%). Functional classification of SSR-containing miRNA genes showed that all targets could be grouped into three Gene Ontology (GO) categories: 17 in biological process, 11 in molecular function, and 14 in cellular component. The miRNA-SSR markers showed high transferability in other six leguminous species, ranged from 74.56% to 90.53%. Furthermore, 25 Mt-miRNA-SSR markers were used to evaluate polymorphisms in 20 alfalfa accessions, and the polymorphism information content (PIC) values ranged from 0.39 to 0.89 with an average of 0.71, the allele number per marker varied from 3 to 18 with an average of 7.88, indicating a high level of informativeness. The present study is the first time developed and characterized of M. truncatula miRNA-SSRs and demonstrated their utility in transferability, these novel markers will be valuable for genetic diversity analysis, marker-assisted selection and genotyping in leguminous species.