Tat-dependent conditionally replicating adenoviruses expressing diphtheria toxin A for specifically killing HIV-1-infected cells.

HIV-1 infection remains a public health problem with no cure. Although antiretroviral therapy (ART) is effective for suppressing HIV-1 replication, it requires lifelong drug administration due to a stable reservoir of latent proviruses and may cause serious side effects and drive the emergence of drug-resistant HIV-1 variants. Gene therapy represents an alternative approach to overcome the limitations of conventional treatments against HIV-1 infection. In this study, we constructed and investigated the antiviral effects of an HIV-1 Tat-dependent conditionally replicating adenovirus, which selectively replicates and expresses the diphtheria toxin A chain (Tat-CRAds-DTA) in HIV-1-infected cells both in vitro and in vivo. We found that Tat-CRAds-DTA could specifically induce cell death and inhibit virus replication in HIV-1-infected cells mediated by adenovirus proliferation and DTA expression. A low titer of progeny Tat-CRAds-DTA was also detected in HIV-1-infected cells. In addition, Tat-CRAds-DTA showed no apparent cytotoxicity to HIV-1-negative cells and demonstrated significant therapeutic efficacy against HIV-1 infection in a humanized mouse model. The findings in this study highlight the potential of Tat-CRAds-DTA as a new gene therapy for the treatment of HIV-1 infection.

Per- and polyfluoroalkyl substances (PFAS) in construction and demolition debris (CDD): discerning sources and fate during waste management.

As regulatory frameworks for per- and polyfluoroalkyl substances (PFAS) evolve, the solid waste community seeks to manage PFAS risks effectively. Despite extensive research on PFAS in municipal solid waste (MSW) and wastewater sludge, there is limited information on a major global waste stream which seldom gleans regulatory oversight - construction and demolition debris (CDD). This study sampled a CDD processing facility to provide material-specific information on the PFAS profile within CDD. The bulk CDD accepted by this facility was separated into major categories, representatively sampled, then characterized for total available PFAS (∑92PFAS). As reprocessed CDD is ultimately recycled or landfilled, often unencapsulated or in unlined landfills, the PFAS leaching potential was also examined using two leaching procedures. Among the categories assessed for total PFAS, carpeting, carpet padding, and gypsum drywall showed elevated concentrations compared to other components, with most of the PFAS mass contributed by precursor species. However, materials with the highest total PFAS, such as carpeting, did not necessarily exhibit the highest leaching, and leachate was predominantly composed of terminal species rather than precursors. Extrapolating these findings with national CDD generation and management data inventories suggests that despite MSW having higher total available PFAS concentrations, the leachability of PFAS from landfilled CDD is comparable, raising legitimate concerns with CDD disposal practices, particularly in unlined CDD landfills.

Characterization of per- and polyfluoroalkyl substances (PFAS) and other constituents in MSW landfill leachate from Puerto Rico.

Elevated per- and polyfluoroalkyl substance (PFAS) concentrations have been reported in municipal solid waste (MSW) landfill leachate with higher levels in wet and warmer subtropical climates. Information about landfill leachate characteristics is much more limited in tropical climates. In this study, 20 landfill leachate samples were collected from three MSW landfills on the tropical island of Puerto Rico and results were compared against landfills nationally and within Florida, USA. The samples collected in Puerto Rico underwent physical-chemical analysis, as well as a quantitative analysis of 92 PFAS. Samples described in this study include discrete leachate types, such as leachate, gas condensate, and leachate which has undergone on-site treatment (e.g., RO treatment, phytoremediation, lagoons). A total of 51 PFAS were detected above quantitation limits, including perfluorohexylphosphonic acid, a perfluoroalkyl acid (PFAA) which has not been reported previously in landfill leachate. ∑PFAS concentrations in this study (mean: 38,000 ng L-1), as well as concentrations of individual PFAS, are significantly higher than other reported MSW landfill leachate concentrations. The profiles of leachates collected from on-site treatment systems indicate possible transformation of precursor PFAS as a result of treatment processes - oxidizing conditions, for example, may facilitate aerobic transformation, increase the concentrations of PFAAs, and possibly increase the apparent ∑PFAS concentration. Extreme climate events, including rising temperatures and more frequent hurricanes, have placed additional strain on the solid waste management infrastructure on the island - adding complexity to an already challenging PFAS management issue. As concern grows over PFAS contamination in drinking water, these findings should inform solid waste and leachate management decisions in order to minimize PFAS emissions in island environments.

Effect of intercropping with legumes at different rates on the yield and soil physicochemical properties of Cyperus esculentus L. in arid land.

Intercropping has the potential to enhance yields and nutrient availability in resource-limited agricultural systems. However, the effects on crop yield nutrients and soil properties can vary considerably depending on the specific plant combinations and intercropping ratios used. In this study, the advantages and impacts of intercropping C. esculentus with legumes were investigated by measuring their biomass, nutrient content, and soil properties. The experiment included five intercropping treatments: monoculture of C. esculentus (MC), intercropping of C. esculentus with Medicago sativa L. (alfalfa) at row spacing ratios of 4:4 (4:4CM) and 8:4 (8:4CM), and intercropping of C. esculentus with Glycine max (L.) Merr. (soybean), also at row spacing ratios of 4:4 (4:4CG) and 8:4 (8:4CG). Our results demonstrated that all four intercropping treatments (4:4CM, 4:4CG, 8:4CM, and 8:4CG) significantly increased the biomass of C. esculentus by approximately 41.05%, 41.73%, 16.08%, and 18.43%, respectively, compared with monoculture cultivation alone, among which the 4:4CG treatment was optimum. However, no significant differences were observed in alfalfa or soybean biomass across different intercropping ratios. A notable increase was found in the total nitrogen (TN) and total phosphorus (TP) contents in the leaves, roots, and tubers of C. esculentus under intercropping, along with increased soil organic carbon (SOC), alkaline-hydrolyzed nitrogen (AN), available phosphorus (AP), microbial biomass carbon (MBC), microbial biomass nitrogen (MBN), and soil water content (SWC), and significantly reduced the soil pH. Among the intercropping treatments, the 4:4CG treatment also exhibited the most favorable soil properties. In particular, compared with MC, the 4:4CG treatment resulted in significant increases of 163.8%, 394.6%, and 716.8% in SOC, AN, and AP contents, respectively. The same treatment also led to significant increases of 48.34%, 46.40%, and 208.65% in MBC, MBN, and SWC, respectively. Overall, the findings suggest that the use of 4:4CG intercropping is an effective approach for sustainable farming management in Xinjiang.

Evaluation of per- and polyfluoroalkyl substances (PFAS) in landfill liquids from Pennsylvania, Colorado, and Wisconsin.

PER: and polyfluoroalkyl substances (PFAS) have been measured in aqueous components within landfills. To date, the majority of these studies have been conducted in Florida. This current study aimed to evaluate PFAS concentrations in aqueous components (leachate, gas condensate, stormwater, and groundwater) from four landfills located outside of Florida, in Pennsylvania, Colorado, and Wisconsin (2 landfills). The Pennsylvania landfill also provided the opportunity to assess a leachate treatment system. Sample analyses were consistent across studies including the measurements of 26 PFAS and physical-chemical parameters. For the four target landfills, average PFAS concentrations were 6,900, 22,000, 280, and 260 ng L-1 in the leachate, gas condensate, stormwater, and groundwater, respectively. These results were not significantly different than those observed for landfills in Florida except for the significantly higher PFAS concentrations in gas condensate compared to leachate. For on-site treatment at the Pennsylvania landfill, results suggest that the membrane biological bioreactor (MBBR) system performed similarly as aeration-based leachate treatment systems at Florida landfills resulting in no significant decreases in ∑26PFAS. Overall, results suggest a general consistency across US regions in PFAS concentrations within different landfill liquid types, with the few differences observed likely influenced by landfill design and local climate. Results confirm that leachate exposed to open air (e.g., in trenches or in treatment systems) have lower proportions of perfluoroalkyl acid precursors relative to leachate collected in enclosed pipe systems. Results also confirm that landfills without bottom liner systems may have relatively higher PFAS levels in adjacent groundwater and that landfills in wetter climates tend to have higher PFAS concentrations in leachate.

Comparison of Umbilical Cord Mesenchymal Stem Cells and Fibroblasts as Donor Nuclei for Handmade Cloning in Sheep Using a Single-Cell Transcriptome.

Oocytes are efficient at reprogramming terminally differentiated cells to a totipotent state. Nuclear transfer techniques can exploit this property to produce cloned animals. However, the overall efficiency is low. The use of umbilical cord mesenchymal stem cells (UC-MSCs) as donor nuclei may increase blastocyst rates, but the exact reasons for this remain unexplored. A single-cell transcriptomic approach was used to map the transcriptome profiles of eight-cell embryos that were in vitro-fertilized and handmade-cloned using umbilical cord mesenchymal stem cells and fibroblasts as nuclear donors. Differences were examined at the chromatin level, the level of differentially expressed genes, the level of histone modifications and the level of DNA methylation. This research provides critical information regarding the use of UC-MSCs as a preferred donor nucleus for nuclear transfer techniques. It also offers unique insights into the mechanism of cellular reprogramming.

Identification of a family with van der Hoeve's syndrome harboring a novel COL1A1 mutation and generation of patient-derived iPSC lines and CRISPR/Cas9-corrected isogenic iPSCs.

Van der Hoeve's syndrome, also known as osteogenesis imperfecta (OI), is a genetic connective tissue disorder characterized by fragile, fracture-prone bone and hearing loss. The disease is caused by a gene mutation in one of the two type I collagen genes COL1A1 or COL1A2. In this study, we identified a novel frameshift mutation of the COL1A1 gene (c.1607delG) in a family with OI using whole-exome sequencing, bioinformatics analysis and Sanger sequencing. This mutation may lead to the deletion of a portion of exon 23 and the generation of a premature stop codon in the COL1A1 gene. To further investigate the impact of this mutation, we established two induced pluripotent stem cell (iPSC) lines from peripheral blood mononuclear cells of OI patients carrying a novel mutation in the COL1A1 gene. Osteoblasts (OB) derived from OI-iPSCs exhibited reduced production of type I collagen and diminished ability to differentiate into osteoblasts. Using a CRISPR-based homology-directed repair strategy, we corrected the OI disease-causing COL1A1 novel mutations in iPSCs generated from an affected individual. Our results demonstrated that the diminished expression of type I collagen and osteogenic potential were enhanced in OB induced from corrected OI-iPSCs compared to those from OI-iPSCs. Overall, our results provide new insights into the genetic basis of Van der Hoeve's syndrome and highlight the potential of iPSC technology for disease modeling and therapeutic development.

Evaluation of per- and polyfluoroalkyl substances (PFAS) released from two Florida landfills based on mass balance analyses.

Per- and polyfluoroalkyl substances (PFAS) have been found at high levels within landfill environments. To assess PFAS distributions, this study aimed to evaluate PFAS mass flux leached from disposed solid waste and within landfill reservoirs by mass balance analyses for two full-scale operational Florida landfills. PFAS mass flux in different aqueous components within landfills were estimated based on PFAS concentrations and water flow rates. For PFAS concentration, 26 PFAS, including 18 perfluoroalkyl acids (PFAAs) and 8 PFAA-precursors, were measured in samples collected from the landfills or estimated based on previous studies. Flow rates of aqueous components (rainfall, evapotranspiration, runoff, stormwater, groundwater, leakage, gas condensate, and leachate) were evaluated through the Hydrologic Evaluation of Landfill Performance model, water balance, and Darcy's Law. Results showed that the average PFAS mass flux leached from the solid waste standardized by area was estimated as 36.8 g/ha-yr, which was approximately 1 % to 3 % of the total amount of PFAS within the solid waste. The majority of PFAS leached from the solid waste (95 % to 97 %) is captured by the leachate collection system, with other aqueous components representing much smaller fractions (stormwater system at 3 % to 5 %, and gas condensate and groundwater at < 1 %). Also, based on the results, we estimate that PFAS releases will likely occur at least over 40 years. Overall, these results can help prioritize components for waste management and PFAS treatment during the anticipated landfill release periods.

Recombinant neutralizing secretory IgA antibodies for preventing mucosal acquisition and transmission of SARS-CoV-2.

Passive delivery of antibodies to mucosal sites may be a valuable adjunct to COVID-19 vaccination to prevent infection, treat viral carriage, or block transmission. Neutralizing monoclonal IgG antibodies are already approved for systemic delivery, and several clinical trials have been reported for delivery to mucosal sites where SARS-CoV-2 resides and replicates in early infection. However, secretory IgA may be preferred because the polymeric complex is adapted for the harsh, unstable external mucosal environment. Here, we investigated the feasibility of producing neutralizing monoclonal IgA antibodies against SARS-CoV-2. We engineered two class-switched mAbs that express well as monomeric and secretory IgA (SIgA) variants with high antigen-binding affinities and increased stability in mucosal secretions compared to their IgG counterparts. SIgAs had stronger virus neutralization activities than IgG mAbs and were protective against SARS-CoV-2 infection in an in vivo murine model. Furthermore, SIgA1 can be aerosolized for topical delivery using a mesh nebulizer. Our findings provide a persuasive case for developing recombinant SIgAs for mucosal application as a new tool in the fight against COVID-19.

Modeling future changes in potential habitats of five alpine vegetation types on the Tibetan Plateau by incorporating snow depth and snow phenology.

Although snow cover is a major factor affecting vegetation in alpine regions, it is rarely introduced into ecological niche models in alpine regions. Snow phenology over the Tibetan Plateau (TP) was estimated using a daily passive microwave snow depth dataset, and future datasets of snow depth and snow phenology were projected based on their sensitivity to temperature and precipitation. Furthermore, the potential habitats of five alpine vegetation types on the TP were predicted under two future climate scenarios (SSP245 and SSP585) by using a model with incorporated snow variables, and the driving factors of habitat change were analyzed. The results showed that the inclusion of snow variables improved the prediction accuracy of MaxEnt model, particularly in alpine meadow habitats. By the end of the 21st century, the potential habitats of steppes, meadows, shrubs, deserts, and coniferous forests on the TP will migrate to higher latitudes and altitudes, in which the potential habitats of alpine desert will recede (replaced by alpine steppe), and the potential habitats of other four vegetation types will expand. The random forest importance analysis showed that the recession of potential habitat was mainly driven by the increase in average annual temperature, and the expansion of potential habitat was mainly driven by the increase in precipitation. With the gradual increase in temperature and precipitation in the future, the snow depth and snow cover duration days will decrease, which may further lead to the transition of vegetation types from cold-adapted to warm-adapted on the TP. Our study highlights both that the prediction accuracy of alpine vegetation was improved by incorporating snow variables into the species distribution model, and that a changing climate will likely have a powerful influence on the distribution of alpine vegetation across the TP.

Astragaloside IV Inhibits Rotenone-Induced α-syn Presentation and the CD4 T-Cell Immune Response.

The increased α-synuclein (α-syn)-dependent activation of CD4 T cells leads to the progressive loss of dopaminergic (DA) neurons in the substantia nigra (SN) in Parkinson's disease (PD). Astragaloside IV (AS-IV) protects DA neurons against neuroinflammation. The effects of AS-IV on CD4 T-cell-mediated immune responses in PD remain unknown. Rotenone (ROT) injected unilaterally into the substantia nigra pars compacta (SNc) of rats induced PD. AS-IV (20 mg/kg) was intraperitoneally injected once a day for 14 days. The limb hanging test and rotarod test were performed to evaluate the alteration of behavior at 4 and 6 weeks. Total gastrointestinal transit tests were performed at 4 weeks. Western blotting was used to detect the expression of proinflammatory cytokine proteins. Immunofluorescence staining was conducted to test the expression and localization of major histocompatibility complex class II (MHCII), cleaved caspase-1 and α-syn in astrocytes. Flow cytometry analysis, immunohistochemistry and immunofluorescence staining were used to measure the expression of CD4 T-cell subsets in the SN. The application of AS-IV protected against the loss of DA neurons and behavioral deficits in ROT-induced PD rat models. AS-IV administration inhibited the aggregation of α-syn in DA neurons and the expression of proinflammatory cytokines such as TNF-α, IL-18, IL-6 and IL-1ß. AS-IV decreased the activation of CD4 T cells and three CD4 T-cell subsets: Tfh, Treg and Th1. AS-IV interrupted the ROT-induced interaction between astrocytes and CD4 T cells and the colocalization of MHCII and α-syn in astrocytes. AS-IV inhibited the expression of α-syn in astrocytes and the colocalization of α-syn and cleaved caspase-1 in astrocytes. AS-IV prevents the loss of DA neurons in PD by inhibiting the activation of α-syn-specific CD4 T cells, which is regulated by MHCII-mediated antigen presentation in astrocytes.

Comparison of the PFAS and physical-chemical parameter fluctuations between an ash landfill and a MSW landfill.

Studies of per- and polyfluoroalkyl substances (PFAS) fluctuations at landfills have focused on municipal solid waste (MSW) leachate. Few studies exist that evaluate fluctuations (defined by the coefficient of variation, CV) in MSW incinerator ash (MSWA) landfill leachate and that evaluate PFAS fluctuations in stormwater, groundwater, and treated liquids on-site. In this study, aqueous landfill samples (leachate, treated leachate, stormwater, gas condensate, ambient groundwater, and effluent from a groundwater remediation system) were collected from a MSW and an MSWA landfill geographically located within close proximity (less than 40 km). The objective of this study was to compare the leachate compositions between these two landfill types and to evaluate temporal variations. Results indicated that the CV of total detected PFAS concentrations in leachate was higher for the MSW landfill (CV = 43 %) compared to the MSWA landfill (CV = 16 %). The total detected PFAS concentration in MSW leachate samples (mean: 9641 ng/L) was higher than in MSWA leachate samples (mean: 2621 ng/L) (p < 0.05). Within a landfill, PFAS concentrations were correlated (rs > 0.6, p < 0.05) with alkalinity, total organic carbon (TOC), and ammonia. Results from the on-site leachate treatment system at the MSW landfill indicated reductions in COD, TOC, and ammonia; however, the ∑26PFAS concentration increased 3 % after the treatment. Overall, results demonstrated that differences between landfill types and fluctuations in PFAS within landfills should be considered when designing landfill leachate collection and treatment systems to remove PFAS. The comparative analysis in this study can provide insights into optimizing leachate management for MSW and MSWA landfills.

Assessing construction and demolition wood-derived biochar for in-situ per- and polyfluoroalkyl substance (PFAS) removal from landfill leachate.

With regulations for per-and polyfluoroalkyl substances (PFAS) impending, the abundance of these chemicals of emerging concern in municipal solid waste (MSW) landfill leachate increasingly challenges landfill operators to seek on-site leachate pre-treatment options. This two-staged study explores the potential reuse of biochar derived from construction and demolition debris (CDD) wood as an in-situ PFAS sorbent for application within MSW landfill leachate collection systems. Batch leaching tests were first used to examine the feasibility of capturing PFAS from landfill leachate using two sources of CDD-wood-derived biochar. Then, columns were used to test the in-situ sorption capabilities of the same biochars under simulated landfill conditions. All leachates were characterized for pH, chemical oxygen demand, ammonia-nitrogen, and 92 PFAS. Seventeen PFAS were detected in the batch leaching experiment, and nine PFAS were detected in column leachates. In the batch leaching scenario, Biochar 1 achieved a maximum of 29% PFAS reduction compared to controls. Columns containing Biochar 1 generated leachates with PFAS concentrations 50% to 80% higher than those in control columns for the duration of the experiment. Columns containing Biochar 2 generated leachates with PFAS concentrations 44% less than controls in week 1 and similar concentrations in weeks 2, 3, and 4. In this study, PFAS removal from landfill leachate using biochar derived from CDD wood was not significant. Further research on biochar derived from CDD wood is needed before it can be recommended as an in-situ landfill leachate pre-treatment method.

Corrigendum: A case of malonyl coenzyme a decarboxylase deficiency with novel mutations and literature review.

[This corrects the article DOI: 10.3389/fped.2023.1133134.].

Medication adjustment of afatinib and combination therapy with sitagliptin for alleviating afatinib-induced diarrhea in rats.

Afatinib, as the first-line treatment for non-small cell lung cancer (NSCLC), causes severe gastrointestinal adverse reactions that greatly affect patients' quality of life and even potentially result in treatment discontinuation. Multiple dose adjustments and concomitant use of anti-diarrheal medications are commonly employed to manage diarrhea, also allowing for a recovery period between each adjustment. However, these approaches are based on empirical guidance and still have limitations. This study aims to explore reliable approaches to alleviate diarrhea by focusing on two strategies: adjusting the dosing regimen of afatinib itself and implementing combination therapy. In this study, we firstly revealed a dose-dependent relationship between afatinib-induced diarrhea and gastrointestinal epithelial damage, resulting in atrophy, reduced expression of tight junction proteins, and increased permeability. We further found that even after discontinuation of the medication, although the severity of diarrhea had improved to baseline, the tight junction proteins and permeability of the intestinal epithelium did not fully recover, and the pharmacokinetics studies showed that drug absorption significantly increased than normal. This indicated the recovery period was longer than expected and may accelerate the occurrence of subsequent episodes of diarrhea. Hence, it would be prudent to consider adjustments to the starting dose or the recovery interval. Furthermore, we initially investigated the relationship between DPP enzyme and afatinib-induced diarrhea and found a significant decrease in plasma DPP enzyme activity following afatinib-induced diarrhea. Subsequently, we conducted continuous treatment with sitagliptin and observed significant improvement in afatinib-induced diarrhea. We observed that sitagliptin can promote the production of anti-inflammatory factors, increase the expression of intestinal epithelial tight junction proteins, and improve intestinal microbiota, further validating the mechanism through the use of GLP-23-33 as GLP-2 receptor inhibitor. In conclusion, sitagliptin exhibits promising potential as a therapeutic option for managing afatinib-induced diarrhea. Taken together, our study provides valuable insights into alleviating afatinib-induced diarrhea through both afatinib medication adjustment and sitagliptin combination therapy.

Advances in saRNA Vaccine Research against Emerging/Re-Emerging Viruses.

Although conventional vaccine approaches have proven to be successful in preventing infectious diseases in past decades, for vaccine development against emerging/re-emerging viruses, one of the main challenges is rapid response in terms of design and manufacture. mRNA vaccines can be designed and produced within days, representing a powerful approach for developing vaccines. Furthermore, mRNA vaccines can be scaled up and may not have the risk of integration. mRNA vaccines are roughly divided into non-replicating mRNA vaccines and self-amplifying RNA (saRNA) vaccines. In this review, we provide an overview of saRNA vaccines, and discuss future directions and challenges in advancing this promising vaccine platform to combat emerging/re-emerging viruses.

A Nomogram Based on Consolidation Tumor Ratio Combined with Solid or Micropapillary Patterns for Postoperative Recurrence in Pathological Stage IA Lung Adenocarcinoma.

BACKGROUND: Patients with pathological stage IA lung adenocarcinoma (LUAD) are at risk of relapse. The value of the TNM staging system is limited in predicting recurrence. Our study aimed to develop a precise recurrence prediction model for stage IA LUAD. MATERIALS AND METHODS: Patients with pathological stage IA LUAD who received surgical treatment at Zhongshan Hospital Fudan University were retrospectively analyzed. Multivariate Cox proportional hazards regression models were used to create nomograms for recurrence-free survival (RFS). The predictive performance of the model was assessed using calibration plots and the concordance index (C-index). RESULTS: The multivariate Cox regression analysis revealed that CTR (0.75 < CTR ≤ 1; HR = 9.882, 95% CI: 2.036-47.959, p = 0.004) and solid/micropapillary-predominance (SMPP; >5% and the most dominant) (HR = 4.743, 95% CI: 1.506-14.933, p = 0.008) were independent prognostic factors of RFS. These risk factors were used to construct a nomogram to predict postoperative recurrence in these patients. The C-index of the nomogram for predicting RFS was higher than that of the eighth T-stage system (0.873 for the nomogram and 0.643 for the eighth T stage). The nomogram also achieved good predictive performance for RFS with a well-fitted calibration curve. CONCLUSIONS: We developed and validated a nomogram based on CTR and SMP patterns for predicting postoperative recurrence in pathological stage IA LUAD. This model is simple to operate and has better predictive performance than the eighth T stage system, making it suitable for selecting further adjuvant treatment and follow-up.

Precipitation modulates the net effect of solar radiation on litter decomposition and CO2 emission - a meta-analysis.

Introduction: Solar radiation plays a crucial role in the decomposition of litter and the cycling of nutrients. Previous studies have investigated that the net effect of solar radiation on litter decomposition depends on the balance of its facilitative and inhibitory effects on microbial activity; however, a gap in understanding the mechanism by which precipitation affects the net effect of solar radiation and the mechanism of litter decomposition on a global scale was observed. Methods: In addressing this gap, a comprehensive meta-analysis of 351 data points from 37 published studies was conducted to estimate the sole radiation effect and interactive effect of solar radiation and precipitation on a global scale, as well as how they vary at different precipitation levels. In addition, the importance of influential factors regulating the net effect of solar radiation on litter decomposition was assessed to identify the key drivers of the response of mass loss to solar radiation at different precipitation levels. Results: Our findings indicated that solar radiation largely regulates litter decomposition, and the direction and magnitude are potentially dependent on the precipitation regime. In addition, solar radiation significantly increased mass loss and decreased the nutrient remaining. Furthermore, the effects of solar radiation on mass loss, C remaining, and N remaining were found to be similar among areas with precipitation levels below 200 and above 800 mm and greater than in areas with precipitation levels between 200-400 mm and 400-800 mm. The effect of solar radiation on CO2 emissions varied from 13.97% when precipitation was below 200 mm to -0.707% when precipitation was between 200 and 400 mm. Conclusion: Climatic factors determine the response ratio of mass loss to solar radiation in arid lands, whereas the initial litter characteristics have a great influence on the response of mass loss to solar radiation in ecosystems that are not moisture limited. The effect of precipitation on the photodegradation mechanism of litter was primarily achieved by influencing the decomposition of lignin, and the main effect of solar radiation on litter decomposition will shift from the positive effect of "photopriming" to the negative effect of "microbial inhibition" with the increase of precipitation. Our findings can provide a comprehensive understanding of litter decomposition patterns on a global scale, and our results showed that CO2 emissions from photodegradation will be lessened by precipitation, which is important in predicting CO2 emission and separating sources of CO2 under future increasing precipitation scenarios, particularly in arid lands.

Characterization of the alternative splicing landscape in lung adenocarcinoma reveals novel prognosis signature associated with B cells.

BACKGROUND: Lung cancer is the second most commonly diagnosed cancer and the leading cause of cancer-related death. Malignant pleural effusion (MPE) is a special microenvironment for lung cancer metastasis. Alternative splicing, which is regulated by splicing factors, affects the expression of most genes and influences carcinogenesis and metastasis. METHODS: mRNA-seq data and alternative splicing events in lung adenocarcinoma (LUAD) were obtained from The Cancer Genome Atlas (TCGA). A risk model was generated by Cox regression analyses and LASSO regression. Cell isolation and flow cytometry were used to identify B cells. RESULTS: We systematically analyzed the splicing factors, alternative splicing events, clinical characteristics, and immunologic features of LUAD in the TCGA cohort. A risk signature based on 23 alternative splicing events was established and identified as an independent prognosis factor in LUAD. Among all patients, the risk signature showed a better prognostic value in metastatic patients. By single-sample gene set enrichment analysis, we found that among tumor-infiltrating lymphocytes, B cells were most significantly correlated to the risk score. Furthermore, we investigated the classification and function of B cells in MPE, a metastatic microenvironment of LUAD, and found that regulatory B cells might participate in the regulation of the immune microenvironment of MPE through antigen presentation and promotion of regulatory T cell differentiation. CONCLUSIONS: We evaluated the prognostic value of alternative splicing events in LUAD and metastatic LUAD. We found that regulatory B cells had the function of antigen presentation, inhibited naïve T cells from differentiating into Th1 cells, and promoted Treg differentiation in LUAD patients with MPE.

Determination of the Oxygen Content in the LiF-NaF-KF Melt.

The present paper is dedicated to the quantitative determination of oxygen-containing impurities in the LiF-NaF-KF eutectic using electrochemical (cyclic and square-wave voltammetry) and reduction melting methods. The LiF-NaF-KF melt was analyzed before and after purifying electrolysis. The amount of oxygen-containing impurities removed from the salt during purification was determined. It was found that after electrolysis, the concentration of oxygen-containing impurities decreased by 7 times. The results obtained via electrochemical techniques and reduction melting were well-correlated, which made it possible to evaluate the quality of the LiF-NaF-KF F melt. To verify the analysis conditions, mechanical mixtures of LiF-NaF-KF containing Li2O were analyzed using the reduction melting method. The oxygen concentration in the mixtures varied from 0.672 to 2.554 wt. %. Based on the analysis results, the dependence approximated by the straight line was obtained. These data may be used to draw calibration curves and to further develop the procedure of oxygen analysis of fluoride melts.