The dynamic molecular characteristics of neutrophils are associated with disease progression in dengue patients.

Dengue, the most prevalent mosquito-borne disease worldwide, poses a significant health burden. This study integrates clinical data and transcriptomic datasets from different phases of dengue to investigate distinctive and shared cellular and molecular features. Clinical data from 29 dengue patients were collected and analyzed alongside a public transcriptomic data set (GSE28405) to perform differential gene expression analysis, functional enrichment, immune landscape assessment, and development of machine learning model. Neutropenia was observed in 54.79% of dengue patients, particularly during the defervescence phase (65.79%) in clinical cohorts. Bioinformatics analyses corroborated a significant reduction in neutrophil immune infiltration in dengue patients. Receiver operating characteristic curve analysis demonstrated that dynamic changes in neutrophil infiltration levels could predict disease progression, especially during the defervescence phase, with the area under the curve of 0.96. Three neutrophil-associated biomarkers-DHRS12, Transforming growth factor alpha, and ZDHHC19-were identified as promising for diagnosing and predicting dengue progression. In addition, the activation of neutrophil extracellular traps was significantly enhanced and linked to FcγR-mediated signaling pathways and Toll-like receptor signaling pathways. Neutrophil activation and depletion play a critical role in dengue's immune response. The identified biomarkers and their associated pathways offer potential for improved diagnosis and understanding of dengue pathogenesis and progression.

Evolving immune evasion and transmissibility of SARS-CoV-2: The emergence of JN.1 variant and its global impact.

The continuous evolution of SARS-CoV-2 variants constitutes a significant impediment to the public health. The World Health Organization (WHO) has designated the SARS-CoV-2 variant JN.1, which has evolved from its progenitor BA.2.86, as a Variant of Interest (VOI) in light of its enhanced immune evasion and transmissibility. The proliferating dissemination of JN.1 globally accentuates its competitive superiority and the potential to instigate fresh surges of infection, notably among cohorts previously infected by antecedent variants. Notably, prevailing evidence does not corroborate an increase in pathogenicity associated with JN.1, and antiviral agents retain their antiviral activity against both BA.2.86 and JN.1. The sustained effectiveness of antiviral agents offers a beacon of hope. Nonetheless, the variant's adeptness at eluding the immunoprotective effects conferred by extant vaccines highlights the imperative for the development of more effective vaccines and therapeutic approaches. Overall, the distinct evolutionary trajectories of BA.2.86 and JN.1 underscore the necessity for ongoing surveillance and scholarly inquiry to elucidate their implications for the pandemic's evolution, which requires the international communities to foster collaboration through the sharing of data, exchange of insights, and collective scientific endeavors.

Leaching behavior of microplastics during sludge mechanical dewatering and its effect on activated sludge.

Dewatering is an indispensable link in sludge treatment, but its effect on the microplastics (MPs) remains inadequately understood. This study investigated the physicochemical changes and leaching behavior of MPs during the mechanical dewatering of sludge, as well as the impact of MP leachates on activated sludge (AS). After sludge dewatering, MPs exhibit rougher surfaces, decreased sizes and altered functional groups due to the addition of dewatering agents and the application of mechanical force. Meanwhile, plastic additives, depolymerization products, and derivatives of their interactions are leached from MPs during sludge dewatering process. The concentration of MP-based leachates in sludge is 2-25 times higher than that in water. The enhancement of pH and ionic strength caused by dewatering agents induces the release of MP leachates enriched with protein-like, fulvic acid-like, and soluble microbial by-product-like substances. The reflux of MP leachates in sludge dewatering liquor to the wastewater treatment system negatively impacts AS, leading to a decrease in COD removal rate and inhibition of the extracellular polymeric substances secretion. More importantly, MP leachates cause oxidative stress to microbial cells and alter the microbial community structure of AS at the phylum and genus levels. These findings confirm that MPs undergo aging and leaching during sludge dewatering process, and MP leachates may negatively affect the wastewater treatment system.

Aging and mitigation of microplastics during sewage sludge treatments: An overview.

Wastewater treatment plants (WWTPs) receive large quantities of microplastics (MPs) from raw wastewater, but many MPs are trapped in the sludge. Land application of sludge is a significant source of MP pollution. Existing reviews have summarized the analysis methods of MPs in sludge and the effect of MPs on sludge treatments. However, MP aging and mitigation during sludge treatment processes are not fully reviewed. Treatment processes used to remove water, pathogenic microorganisms, and other pollutants in sewage sludge also cause surface changes and degradation in the sludge MPs, affecting the potential risk of MPs. This study integrates MP abundance and distribution in sludge and their aging and mitigation characteristics during sludge treatment processes. The abundance, composition, and distribution of sludge MPs vary significantly with WWTPs. Furthermore, MPs exhibit variable degrees of aging, including rough surfaces, enhanced adsorption potentials for pollutants, and increased leaching behavior. Various sludge treatment processes further intensify these aging characteristics. Some sludge treatments, such as hydrothermal treatment, have efficiently removed MPs from sewage sludge. It is crucial to understand the potential risk of MP aging in sludge and the degradation properties of the MP-derived products from MP degradation in-depth and develop novel MP mitigation strategies in sludge, such as combining hydrothermal treatment and biological processes.

Repeated Omicron infection dampens immune imprinting from previous vaccination and induces broad neutralizing antibodies against Omicron sub-variants.

OBJECTIVE: Similar with influenza virus, antigenic drift is highly relevant to SARS-CoV-2 evolution, and immune imprinting has been found to limit the performance of updated vaccines based on the emerging variants of SARS-CoV-2. We aimed to investigate whether repeated exposure to Omicron variant could reduce the immune imprinting from previous vaccination. METHODS: A total of 194 participants with different status of vaccination (unvaccinated, regular vaccination and booster vaccination) confirmed for first infection and re-infection with BA.5, BF.7 and XBB variants were enrolled, and the neutralizing profiles against wild type (WT) SARS-CoV-2 and Omicron sub-variants were analyzed. RESULTS: Neutralizing potency against the corresponding infected variant is significantly hampered along with the doses of vaccination during first infection. However, for the participants with first infection of BA.5/BF.7 variants and re-infection of XBB variant, immune imprinting was obviously alleviated, indicated as significantly increased ratio of the corresponding infected variant/WT ID50 titers and higher percentage of samples with high neutralizing activities (ID50 > 500) against BA.5, BF.7 and XBB variants. Moreover, repeated Omicron infection could induce strong neutralizing potency with broad neutralizing profiles against a series of other Omicron sub-variants, both in the vaccine naive and vaccine experienced individuals. CONCLUSIONS: Our results demonstrate that repeated Omicron infection dampens immune imprinting from vaccination with WT SARS-CoV-2 and induces broad neutralizing profiles against Omicron sub-variants.

Longitudinal viral shedding and antibody response characteristics of men with acute infection of monkeypox virus: a prospective cohort study.

Understanding of infection dynamics is important for public health measures against monkeypox virus (MPXV) infection. Herein, samples from multiple body sites and environmental fomites of 77 acute MPXV infections (HIV co-infection: N = 42) were collected every two to three days and used for detection of MPXV DNA, surface protein specific antibodies and neutralizing titers. Skin lesions show 100% positivity rate of MPXV DNA, followed by rectum (88.16%), saliva (83.78%) and oropharynx (78.95%). Positivity rate of oropharynx decreases rapidly after 7 days post symptom onset (d.p.o), while the rectum and saliva maintain a positivity rate similar to skin lesions. Viral dynamics are similar among skin lesions, saliva and oropharynx, with a peak at about 6 d.p.o. In contrast, viral levels in the rectum peak at the beginning of symptom onset and decrease rapidly thereafter. 52.66% of environmental fomite swabs are positive for MPXV DNA, with highest positivity rate (69.89%) from air-conditioning air outlets. High seropositivity against A29L (100%) and H3L (94.74%) are detected, while a correlation between IgG endpoint titers and neutralizing titers is only found for A29L. Most indexes are similar between HIV and Non-HIV participants, while HIV and rectitis are associated with higher viral loads in rectum.

Evolutionary trajectory and characteristics of Mpox virus in 2023 based on a large-scale genomic surveillance in Shenzhen, China.

The global epidemic of Mpox virus (MPXV) continues, and a local outbreak has occurred in Shenzhen city since June 2023. Herein, the evolutionary trajectory and characteristics of MPXV in 2023 were analyzed using 92 MPXV sequences from the Shenzhen outbreak and the available genomes from GISAID and GenBank databases. Phylogenetic tracing of the 92 MPXVs suggests that MPXVs in Shenzhen may have multiple sources of importation, and two main transmission chains have been established. The combination of phylogenetic relationships, epidemiological features, and mutation characteristics supports the emergence of a new lineage C.1.1. Together with the B.1 lineage diverging from the A.1 lineage, C.1.1 lineage diverging from the C.1 lineage may serve as another significant evolutionary events of MPXV. Moreover, increasing apolipoprotein B mRNA-editing catalytic polypeptide-like 3 (APOBEC3) related mutations, higher rate of missense mutations, and less mutations in the non-coding regions have been shown during MPXV evolution. Host regulation proteins of MPXV have accumulated considerable amino acid mutations since the B.1 lineage, and a lineage-defining APOBEC3-related mutation that disrupts the N2L gene encoding a viral innate immune modulator has been identified in the C.1.1 lineage. In summary, our study provides compelling evidence for the ongoing evolution of MPXV with specific features.

Identification of mpox M1R and B6R monoclonal and bispecific antibodies that efficiently neutralize authentic mpox virus.

In 2022, the monkeypox virus (mpox virus, MPXV) exhibited global dissemination across six continents, representing a notable challenge owing to the scarcity of targeted antiviral interventions. Passive immunotherapy, such as the use of monoclonal antibodies (mAbs) and bispecific antibodies (bsAbs), has emerged as a promising option for antiviral regimens. Here, we generated several mAbs against M1R and B6R of MPXV, and subsequently characterized the antiviral activity of these antibodies both in vitro and in vivo. Two neutralizing mAbs, M1H11 and M3B2, targeting M1R, and one B6R-specific mAb, B7C9, were identified. They exhibited varying antiviral efficacy against vaccinia virus (VACV) in vitro and in vivo. A cocktail comprising M1H11 and M3B2 demonstrated a superior protective effect in vivo. A bsAb, Bis-M1M3, was engineered by conjugating the fragment crystallizable (Fc) region of the human-mouse chimeric engineered M1H11 with the single-chain fragment variable (scFv) of M3B2. In mice challenged with MPXV, Bis-M1M3 showed a notable protective effects. Analysis of neutralization mechanism showed that these mAbs and Bis-M1M3 exerted virus-neutralizing effects before the virus infects cells. In vivo pharmacokinetic experiments showed that Bis-M1M3 has a long half-life in rhesus macaques. This study provides crucial insights for further research on broad-spectrum antiviral drugs against MPXV and other orthopoxviruses.

Treatment of obesity by acupuncture combined with medicine based on pathophysiological mechanism: A review.

Obesity is a complex, multifactorial disease. The incidence of overweight and obesity has doubled worldwide since 1980, and nearly one-third of the world population is now classified as overweight or obese. Obesity rates are increasing in all age groups and for both sexes, regardless of geographic region, race, or socioeconomic status, although they are generally higher in older adults and women. Although the absolute prevalence of overweight and obesity varies widely, this trend is similar across different regions and countries. In some developed countries, the prevalence of obesity has levelled off over the past few years. However, obesity has become a health problem that cannot be ignored in low- and middle-income countries. Although the drug treatment model of modern medicine has a significant therapeutic effect in the treatment of obesity, its adverse effects are also obvious. Acupuncture combined with Chinese medicine treatment of obesity has prominent advantages in terms of clinical efficacy, and its clinical safety is higher, with fewer adverse reactions. The combination of acupuncture and medicine in the treatment of obesity is worth exploring.

Wastewater surveillance and an automated robot: effectively tracking SARS-CoV-2 transmission in the post-epidemic era.

Wastewater-based epidemiology (WBE) has exhibited great utility in the early and rapid identification of SARS-CoV-2. However, the efficacy of wastewater surveillance under China's previous strict epidemic prevention policy remains to be described. We collected the WBE data of wastewater treatment plants (WWTPs) in the Third People's Hospital of Shenzhen and several communities to determine the significant effectiveness of routine wastewater surveillance in monitoring the local spread of SARS-CoV-2 under tight containment of the epidemic. The results of 1 month of continuous wastewater surveillance showed that positive signals for SARS-CoV-2 RNA were detected in the wastewater samples, and a significant positive correlation was observed between the virus concentration and the number of daily cases. In addition, the community's domestic wastewater surveillance results were confirmed even 3 days before, or simultaneously with, the infected patient being confirmed as having the virus. Meanwhile, an automated sewage virus detection robot, ShenNong No.1 robot, was developed, showing a high degree of agreement with experimental data, offering the possibility of large-scale multi-point surveillance. Overall, our results illustrated the clear indicative role of wastewater surveillance in combating COVID-19 and provided a practical basis for rapidly expanding the feasibility and value of routine wastewater surveillance for future emerging infectious diseases.

Differences in nitrogen and phosphorus sinks between the harvest and non-harvest of Miscanthus lutarioriparius in the Dongting Lake wetlands.

Plant non-harvest changes element circulation and has a marked effect on element sinks in the ecosystem. In this study, a field investigation was conducted on the fixation of nitrogen and phosphorus in Miscanthus lutarioriparius, the most dominant plant species in the Dongting Lake wetlands. Further, to quantitatively compare the difference in nitrogen and phosphorus sinks between harvest and non-harvest, an in situ experiment on the release of the two elements from two types of litters (leaves and stems) was studied. The nitrogen concentrations in the plant had no significant relationship with the environmental parameters. The phosphorus concentrations were positively related to the plot elevation, soil organic matter, and soil total potassium and were negatively related to the soil moisture. The leaves demonstrated a higher decomposition coefficient than that of the stems in the in situ experiment. The half decomposition time was 0.61 years for leaves and 1.12 years for stems, and the complete decomposition time was 2.83 years for leaves and 4.95 years for stems. Except for the nitrogen concentration in the leaves, all the concentrations increased during the flood period. All concentrations unsteadily changed in the backwater period. Similarly, except for the relative release index of nitrogen in the leaves, all the relative release indices decreased in the flood period. At the end of the in situ decomposition experiment, the relative release indices of both the nitrogen and phosphors were greater than zero, indicating that there was a net release of nitrogen and phosphorus. Under the harvest scenario, the aboveground parts of the plant were harvested and moved from the wetlands, thus increasing the nitrogen and phosphorus sinks linearly over time. The fixed nitrogen and phosphorus in the aboveground parts were released under the non-harvest scenario, gradually accumulating the nitrogen and phosphorus sinks from the first year to the fifth year after non-harvest, reaching a maximum value after the fifth year. This study showed that the nitrogen and phosphorus sinks greatly decreased after the non-harvest of M. lutarioriparius compared to that after harvest. It is recommended to continue harvesting the plant for enhancing the capacity of element sinks.

Aging microplastics in wastewater pipeline networks and treatment processes: Physicochemical characteristics and Cd adsorption.

Despite a wealth of information on removal of the microplastics (MPs) in wastewater treatment plants (WWTPs), little attention has been paid to how wastewater treatment process affect the MP physicochemical and adsorption characteristics. In this study, changes in physicochemical property of three MPs, i.e. polyamide (PA), polyethylene (PE) and polystyrene (PS) through the wastewater pipeline, grit and biological aeration tanks were investigated. The results show that compared with virgin MPs, the treated MPs have higher specific surface area and O content, and lower C and H contents, and glass transition temperature, implying that the three treatments cause the chain scission and oxidation of the MPs. Cd adsorption capacities of the MPs are higher than the corresponding virgin MPs after sulfidation in the pipeline (SWPN) and biological treatment in aeration tank (BTAT). Pearson correlation analysis shows that the increase is mainly resulted from the enhancement of the O-containing groups on the MPs. However, Cd adsorption capacities of the MPs decrease after mechanical abrasion in grit tank (MAGT), corresponding to the decrease in carbonyl index. Two dimensional FTIR correlation spectroscopy demonstrates that the NH bond in the PA plays a more important role than CH bond in the adsorption of Cd, but only change of the CH bond is found in the PE and PS. The findings provide new insights into the effect of WWTPs on the MP aging and physicochemical characteristics.