Passive Transfer of Vaccine-Elicited Antibodies Protects against SIV in Rhesus Macaques.

Several HIV-1 and SIV vaccine candidates have shown partial protection against viral challenges in rhesus macaques. However, the protective efficacy of vaccine-elicited polyclonal antibodies has not previously been demonstrated in adoptive transfer studies in nonhuman primates. In this study, we show that passive transfer of purified antibodies from vaccinated macaques can protect naive animals against SIVmac251 challenges. We vaccinated 30 rhesus macaques with Ad26-SIV Env/Gag/Pol and SIV Env gp140 protein vaccines and assessed the induction of antibody responses and a putative protective signature. This signature included multiple antibody functions and correlated with upregulation of interferon pathways in vaccinated animals. Adoptive transfer of purified immunoglobulin G (IgG) from the vaccinated animals with the most robust protective signatures provided partial protection against SIVmac251 challenges in naive recipient rhesus macaques. These data demonstrate the protective efficacy of purified vaccine-elicited antiviral antibodies in this model, even in the absence of virus neutralization.

Characterization of humoral and cellular immunologic responses to an mRNA-based human cytomegalovirus vaccine from a phase 1 trial of healthy adults.

mRNA-1647 is an investigational mRNA-based vaccine against cytomegalovirus (CMV) that contains sequences encoding the CMV proteins glycoprotein B and pentamer. Humoral and cellular immune responses were evaluated in blood samples collected from healthy CMV-seropositive and CMV-seronegative adults who participated in a phase 1 trial of a three-dose series of mRNA-1647 (NCT03382405). Neutralizing antibody (nAb) titers against fibroblast and epithelial cell infection in sera from CMV-seronegative mRNA-1647 recipients were higher than those in sera from control CMV-seropositive samples and remained elevated up to 12 months after dose 3. nAb responses elicited by mRNA-1647 were comparable across 14 human CMV (HCMV) strains. Frequencies of antigen-specific memory B cells increased in CMV-seropositive and CMV-seronegative participants after each mRNA-1647 dose and remained elevated for up to 6 months after dose 3. mRNA-1647 elicited robust increases in frequencies and polyfunctionality of CD4+ T helper type 1 and effector CD8+ T cells in samples from CMV-seronegative and CMV-seropositive participants after stimulation with HCMV-specific peptides. The administration of three doses of mRNA-1647 to healthy adults elicited high nAb titers with wide-breadth, long-lasting memory B cells, and strong polyfunctional T-cell responses. These findings support further clinical development of the mRNA-1647 vaccine against CMV.IMPORTANCECytomegalovirus (CMV), a common virus that can infect people of all ages, may lead to serious health problems in unborn babies and those with a weakened immune system. Currently, there is no approved vaccine available to prevent CMV infection; however, the investigational messenger RNA (mRNA)-based CMV vaccine, mRNA-1647, is undergoing evaluation in clinical trials. The current analysis examined samples from a phase 1 trial of mRNA-1647 in healthy adults to better understand how the immune system reacts to vaccination. Three doses of mRNA-1647 produced a long-lasting immune response, thus supporting further investigation of the vaccine in the prevention of CMV infection.CLINICAL TRIALSRegistered at ClinicalTrials.gov (NCT03382405).

Ionic Hyperbranched Poly(amido-amine)-Incorporated Nanofiltration Membranes for High-Efficiency Dye Desalination.

High-efficiency dye desalination is crucial in the textile industry, considering its importance for human health, safe aquatic ecological systems, and resource recovery. In order to solve the problem of effective separation of univalent salt and ionic dye under the condition of high salt, ionic hyperbranched poly(amido-amine) (HBPs) were synthesized based on a simple and scalable one-step polycondensation method and then incorporated into the polyamide (PA) selective layers to construct charged nanochannels through interfacial polymerization (IP) on the surface of a polyvinyl chloride ultrafiltration (PVC-UF) hollow fiber membrane. Both the internal nanopores of HBPs (internal nanochannels) and the interfacial voids between HBPs and the PA matrix (external nanochannels) can be regarded as a fast water molecule transport pathway, while the terminal ionic groups of ionic HBPs endow the nanochannels with charge characteristics for improving ionic dye/salt selectivities. The permeate fluxes and dye/salt selectivities of HBP-TAC/PIP (57.3 L m-2 h-1 and rhodamine B (RB)/NaCl selectivity of 224.0) and HBP-PS/PIP (63.7 L m-2 h-1 and lemon yellow (LY)/NaCl selectivity of 664.0) membranes under 0.4 MPa operation pressure are much higher than PIP-only and HBP-NH2/PIP membranes. At the same time, this project also studied the membrane desalination process in a simulated high-salinity dye/salt mixture system to provide a theoretical basis and technical support for the actual dye desalination process.

Gene signature discovery and systematic validation across diverse clinical cohorts for TB prognosis and response to treatment.

While blood gene signatures have shown promise in tuberculosis (TB) diagnosis and treatment monitoring, most signatures derived from a single cohort may be insufficient to capture TB heterogeneity in populations and individuals. Here we report a new generalized approach combining a network-based meta-analysis with machine-learning modeling to leverage the power of heterogeneity among studies. The transcriptome datasets from 57 studies (37 TB and 20 viral infections) across demographics and TB disease states were used for gene signature discovery and model training and validation. The network-based meta-analysis identified a common 45-gene signature specific to active TB disease across studies. Two optimized random forest regression models, using the full or partial 45-gene signature, were then established to model the continuum from Mycobacterium tuberculosis infection to disease and treatment response. In model validation, using pooled multi-cohort datasets to mimic the real-world setting, the model provides robust predictive performance for incipient to active TB risk over a 2.5-year period with an AUROC of 0.85, 74.2% sensitivity, and 78.3% specificity, which approximates the minimum criteria (>75% sensitivity and >75% specificity) within the WHO target product profile for prediction of progression to TB. Moreover, the model strongly discriminates active TB from viral infection (AUROC 0.93, 95% CI 0.91-0.94). For treatment monitoring, the TB scores generated by the model statistically correlate with treatment responses over time and were predictive, even before treatment initiation, of standard treatment clinical outcomes. We demonstrate an end-to-end gene signature model development scheme that considers heterogeneity for TB risk estimation and treatment monitoring.

Antibody and TLR7 agonist delay viral rebound in SHIV-infected monkeys.

The latent viral reservoir is the critical barrier for the development of a cure for HIV-1 infection. Previous studies have shown direct antiviral activity of potent HIV-1 Env-specific broadly neutralizing antibodies (bNAbs) administered when antiretroviral therapy (ART) was discontinued, but it remains unclear whether bNAbs can target the viral reservoir during ART. Here we show that administration of the V3 glycan-dependent bNAb PGT121 together with the Toll-like receptor 7 (TLR7) agonist vesatolimod (GS-9620) during ART delayed viral rebound following discontinuation of ART in simian-human immunodeficiency virus (SHIV)-SF162P3-infected rhesus monkeys in which ART was initiated during early acute infection. Moreover, in the subset of monkeys that were treated with both PGT121 and GS-9620 and that did not show viral rebound after discontinuation of ART, adoptive transfer studies and CD8-depletion studies also did not reveal virus. These data demonstrate the potential of bNAb administration together with innate immune stimulation as a possible strategy for targeting the viral reservoir.

Publisher Correction: Antibody and TLR7 agonist delay viral rebound in SHIV-infected monkeys.

In Fig. 4b of this Article, the x-axis labels 'PGT121' and 'GS-9620' were inadvertently swapped in both graphs. In Fig. 5a, b, 'TLR7' should have been 'GS-9620'. These figures have been corrected online.

Real-World Emission Characteristics of Full-Volatility Organics Originating from Nonroad Agricultural Machinery during Agricultural Activities.

Nonroad agricultural machinery (NRAM) emissions constitute a significant source of air pollution in China. Full-volatility organics originating from 19 machines under 6 agricultural activities were measured synchronously. The diesel-based emission factors (EFs) for full-volatility organics were 4.71 ± 2.78 g/kg fuel (average ± standard deviation), including 91.58 ± 8.42% volatile organic compounds (VOCs), 7.94 ± 8.16% intermediate-volatility organic compounds (IVOCs), 0.28 ± 0.20% semivolatile organic compounds (SVOCs), and 0.20 ± 0.16% low-volatility organic compounds (LVOCs). Full-volatility organic EFs were significantly reduced by stricter emission standards and were the highest under pesticide spraying activity. Our results also demonstrated that combustion efficiency was a potential factor influencing full-volatility organic emissions. Gas-particle partitioning in full-volatility organics could be affected by multiple factors. Furthermore, the estimated secondary organic aerosol formation potential based on measured full-volatility organics was 143.79 ± 216.80 mg/kg fuel and could be primarily attributed to higher-volatility-interval IVOCs (bin12-bin16 contributed 52.81 ± 11.58%). Finally, the estimated emissions of full-volatility organics from NRAM in China (2021) were 94.23 Gg. This study provides first-hand data on full-volatility organic EFs originating from NRAM to facilitate the improvement of emission inventories and atmospheric chemistry models.

Real-world emission characteristics of carbonyl compounds from agricultural machines based on a portable emission measurement system.

Emissions of carbonyl compounds from agricultural machines cannot be ignored. Carbonyl compounds can cause the formation of ozone (O3) and secondary organic aerosols, which can cause photochemical smog to form. In this study, 20 agricultural machines were tested using portable emission measurement system (PEMS) under real-world tillage processes. The exhaust gases were sampled using 2,4-dinitrophenylhydrazine cartridges, and 15 carbonyl compounds were analyzed by high-performance liquid chromatography. Carbonyl compound emission factors for agricultural machines were 51.14-3315.62 mg/(kg-fuel), and were 2.58 ± 2.05, 0.86 ± 1.07 and 0.29 ± 0.20 g/(kg-fuel) for China 0, China II and China III emission standards, respectively. Carbonyl compound emission factor for sowing seeds of China 0 agricultural machines was 3.32 ± 1.73 g/(kg-fuel). Formaldehyde, acetaldehyde and acrolein were the dominant carbonyl compounds emitted. Differences in emission standards and tillage processes impact ozone formation potential (OFP). The mean OFP was 20.15 ± 16.15 g O3/(kg-fuel) for the China 0 emission standard. The OFP values decreased by 66.9% from China 0 to China II, and 67.4% from China II to China III. The mean OFP for sowing seeds of China 0 agricultural machines was 25.92 ± 13.84 g O3/(kg-fuel). Between 1.75 and 24.22 times more ozone was found to be formed during sowing seeds than during other processes for China 0 and China II agricultural machines. Total carbonyl compound emissions from agricultural machines in China was 19.23 Gg in 2019. The results improve our understanding of carbonyl compound emissions from agricultural machines in China.

Restoration of RPGR expression in vivo using CRISPR/Cas9 gene editing.

Mutations in the gene for Retinitis Pigmentosa GTPase Regulator (RPGR) cause the X-linked form of inherited retinal degeneration, and the majority are frameshift mutations in a highly repetitive, purine-rich region of RPGR known as the OFR15 exon. Truncation of the reading frame in this terminal exon ablates the functionally important C-terminal domain. We hypothesized that targeted excision in ORF15 by CRISPR/Cas9 and the ensuing repair by non-homologous end joining could restore RPGR reading frame in a portion of mutant photoreceptors thereby correcting gene function in vivo. We tested this hypothesis in the rd9 mouse, a naturally occurring mutant line that carries a frameshift mutation in RPGRORF15, through a combination of germline and somatic gene therapy approaches. In germline gene-edited rd9 mice, probing with RPGR domain-specific antibodies demonstrated expression of full length RPGRORF15 protein. Hallmark features of RPGR mutation-associated early disease phenotypes, such as mislocalization of cone opsins, were no longer present. Subretinal injections of the same guide RNA (sgRNA) carried in AAV sgRNA and SpCas9 expression vectors restored reading frame of RPGRORF15 in a subpopulation of cells with broad distribution throughout the retina, confirming successful correction of the mutation. These data suggest that a simplified form of genome editing mediated by CRISPR, as described here, could be further developed to repair RPGRORF15 mutations in vivo.

Prediction of VRC01 neutralization sensitivity by HIV-1 gp160 sequence features.

The broadly neutralizing antibody (bnAb) VRC01 is being evaluated for its efficacy to prevent HIV-1 infection in the Antibody Mediated Prevention (AMP) trials. A secondary objective of AMP utilizes sieve analysis to investigate how VRC01 prevention efficacy (PE) varies with HIV-1 envelope (Env) amino acid (AA) sequence features. An exhaustive analysis that tests how PE depends on every AA feature with sufficient variation would have low statistical power. To design an adequately powered primary sieve analysis for AMP, we modeled VRC01 neutralization as a function of Env AA sequence features of 611 HIV-1 gp160 pseudoviruses from the CATNAP database, with objectives: (1) to develop models that best predict the neutralization readouts; and (2) to rank AA features by their predictive importance with classification and regression methods. The dataset was split in half, and machine learning algorithms were applied to each half, each analyzed separately using cross-validation and hold-out validation. We selected Super Learner, a nonparametric ensemble-based cross-validated learning method, for advancement to the primary sieve analysis. This method predicted the dichotomous resistance outcome of whether the IC50 neutralization titer of VRC01 for a given Env pseudovirus is right-censored (indicating resistance) with an average validated AUC of 0.868 across the two hold-out datasets. Quantitative log IC50 was predicted with an average validated R2 of 0.355. Features predicting neutralization sensitivity or resistance included 26 surface-accessible residues in the VRC01 and CD4 binding footprints, the length of gp120, the length of Env, the number of cysteines in gp120, the number of cysteines in Env, and 4 potential N-linked glycosylation sites; the top features will be advanced to the primary sieve analysis. This modeling framework may also inform the study of VRC01 in the treatment of HIV-infected persons.

Exploiting glycan topography for computational design of Env glycoprotein antigenicity.

Mounting evidence suggests that glycans, rather than merely serving as a "shield", contribute critically to antigenicity of the HIV envelope (Env) glycoprotein, representing critical antigenic determinants for many broadly neutralizing antibodies (bNAbs). While many studies have focused on defining the role of individual glycans or groups of proximal glycans in bNAb binding, little is known about the effects of changes in the overall glycan landscape in modulating antibody access and Env antigenicity. Here we developed a systems glycobiology approach to reverse engineer the complexity of HIV glycan heterogeneity to guide antigenicity-based de novo glycoprotein design. bNAb binding was assessed against a panel of 94 recombinant gp120 monomers exhibiting defined glycan site occupancies. Using a Bayesian machine learning algorithm, bNAb-specific glycan footprints were identified and used to design antigens that selectively alter bNAb antigenicity as a proof-of concept. Our approach provides a new design strategy to predictively modulate antigenicity via the alteration of glycan topography, thereby focusing the humoral immune response on sites of viral vulnerability for HIV.

The Mycobacterium tuberculosis regulatory network and hypoxia.

We have taken the first steps towards a complete reconstruction of the Mycobacterium tuberculosis regulatory network based on ChIP-Seq and combined this reconstruction with system-wide profiling of messenger RNAs, proteins, metabolites and lipids during hypoxia and re-aeration. Adaptations to hypoxia are thought to have a prominent role in M. tuberculosis pathogenesis. Using ChIP-Seq combined with expression data from the induction of the same factors, we have reconstructed a draft regulatory network based on 50 transcription factors. This network model revealed a direct interconnection between the hypoxic response, lipid catabolism, lipid anabolism and the production of cell wall lipids. As a validation of this model, in response to oxygen availability we observe substantial alterations in lipid content and changes in gene expression and metabolites in corresponding metabolic pathways. The regulatory network reveals transcription factors underlying these changes, allows us to computationally predict expression changes, and indicates that Rv0081 is a regulatory hub.

Database of emission factors of volatile organic compound (VOC) species in motor vehicle exhaust in China.

The synergistic strategy for fine particulate matter (PM2.5) and O3 pollution prevention and control has emerged as a pivotal approach in combating air pollution. Volatile organic compounds (VOCs) serve as crucial precursors to both O3 and secondary organic aerosols (SOAs), with motor vehicles representing one of their significant sources. In this study, a standard for establishing a database of VOC species emission factors for motor vehicles was developed, and a database containing 134 VOC species was constructed through field tests and literature surveys. The VOC emissions of light-duty gasoline passenger vehicles (LDGPVs) comprised primarily alkanes and aromatics. The VOC emissions of light-duty diesel trucks (LDDTs) comprised mostly alkanes. Regarding low-speed trucks, 3-wheel vehicles, medium-duty diesel trucks (MDDTs) and heavy-duty diesel trucks (HDDTs), their VOC emissions comprised mainly oxygenated volatile organic compounds (OVOCs). The update of emission standards resulted in a reduction in VOC species emission factors while altering the composition of VOCs. Attention should be directed toward isopentane, benzene and dichloromethane emitted by LDGPVs, dodecane, undecane, ethene and propene emitted by LDDTs, and acetaldehyde emitted by HDDTs. VOC species originating from LDGPVs were more dispersed than those originating from LDDTs and HDDTs. In addition, variations in VOC species were observed among motor vehicles with different fuel types. Toluene, ethene, benzene, m,p-xylene, isopentane, hexanal, ethyne and 1,2,4-trimethylbenzene were the predominant VOC species emitted by gasoline vehicles. Diesel vehicles emitted mainly dodecane, formaldehyde, propene, undecane, acetaldehyde, ethene, decane and benzene. The results could enhance our comprehension of the emission characteristics of VOC species originating from motor vehicles and provide data support and a scientific foundation for achieving synergistic PM2.5 and O3 pollution prevention and control.

Prospective randomized, double-blind, placebo controlled trial to evaluate infection prevention in adult patients after tension-free inguinal hernia repair.

OBJECTIVE: Infection is one of possible complications after prosthetic material hernia repair surgery. Antibiotic prophylaxis is applied routinely in China, but its effect is still controversial. The present study aims to offer direct clinical evidence on prevention of infection after tension-free inguinal hernia repair. METHODS: A total of 1,200 cases with primary inguinal hernia treated in 6 hospitals in Shaanxi Province were enrolled in this study. They were randomly divided into three groups (n = 400 per group): placebo control group, Cefazolin group and Levofloxacin group after tensionfree inguinal hernia repair using polypropylene mesh. Hernia type, age, gender, weight and complications were recorded. The surgical-site infection was diagnosed according to APIC, CDC criteria (http://www.apic. org). Infections were evaluated every other day in the first week, and then at 14 days, 21 days and 30 days following surgery. RESULTS: Two cases from the placebo group, 3 from the Cefazolin group and 3 from the Levofloxacin group failed to follow-up. Six patients (2 non-following the protocol, 2 severe depression, and 2 laparoscopic surgery) from the placebo group, 14 (8 nonreceiving trial medication, 5 laparoscopic surgery, and 1 failure to tolerance) from the Cefazolin group, and 12 (2 combination of antibiotic usage, 5 laparoscopic surgery and 5 failure to tolerance) from the Levofloxacin group were excluded. The data of the 1,160 cases were statistically analyzed in the incidence rates of surgical-site infection and complications after inguinal hernia repair. Surgical-site infection including wound infection, cellulitis or mesh-related infection was found in 20 cases (5.1%) of the control group, 15 (3.92%) of the Cefazolin group and 17 (4.42%) of the Levofloxacin group, and the difference among the three groups was not statistically significant (χ2 = 0.438, p = 0.803). There was also no significant difference in post-surgery complications including seroma (p = 0.6366), urinary retention (p = 0.8136), fat liquefaction (p = 0.8061), pulmonary infection (p = 0.1911), and urinary tract infection (p = 0.8144) among the three groups. CONCLUSIONS: Prophylactic use of Cefazolin or Levofloxacin did not significantly decrease the risk of wound infection in these patients undergoing inguinal hernia repair. The present results do not support the administration of antibiotic prophylaxis for tension-free inguinal hernia repair. *The authors contributed equally to this work.

Transient receptor potential ankyrin 1 (TRPA1) modulators: Recent update and future perspective.

The transient receptor potential ankyrin 1 (TRPA1) channel is a non-selective cation channel that senses irritant chemicals. Its activation is closely associated with pain, inflammation, and pruritus. TRPA1 antagonists are promising treatments for these diseases, and there has been a recent upsurge in their application to new areas such as cancer, asthma, and Alzheimer's disease. However, due to the generally disappointing performance of TRPA1 antagonists in clinical studies, scientists must pursue the development of antagonists with higher selectivity, metabolic stability, and solubility. Moreover, TRPA1 agonists provide a deeper understanding of activation mechanisms and aid in antagonist screening. Therefore, we summarize the TRPA1 antagonists and agonists developed in recent years, with a particular focus on structure-activity relationships (SARs) and pharmacological activity. In this perspective, we endeavor to keep abreast of cutting-edge ideas and provide inspiration for the development of more effective TRPA1-modulating drugs.

The Application of the Generalized Additive Model to Represent Macrobenthos near Xiaoqing Estuary, Laizhou Bay.

Macrobenthos is widely used as an indicator of ecological health in marine monitoring and assessment. The present study aimed to characterize the interrelationships between the distribution of the macrobenthos community and environmental factors near Xiaoqing Estuary, Laizhou Bay. Responses of species richness to environmental factors were studied using the generalized additive model (GAM) and the Margalef diversity index (dM) as indicators of species diversity instead of individual indicator species. Six factors were selected in the optimal model by stepwise regression: sediment factors (organic matter, phosphate, nitrate nitrogen, and ammonium nitrogen) and water factors (salinity, and ammonium nitrogen). The response curves generated by the GAM showed a unimodal relationship among taxa diversity, salinity in water, and sediment organic matter. dM was positively correlated with ammonium nitrogen in water and was negatively correlated with phosphate in the sediment. The model optimized by forward stepwise optimization explained 92.6% of the Margalef diversity index with a small residual (2.67). The model showed good performance, with the measured dM strongly correlated with the predicted dM (Pearson R2 = 0.845, p < 0.05). The current study examined the combined influence of multiple eco-factors on macrobenthos, and the Margalef diversity index of macrobenthos was predicted by the GAM model in a salinity-stressed estuary.

Does genotypic diversity of Hydrocotyle vulgaris affect CO2 and CH4 fluxes?

Biodiversity plays important roles in ecosystem functions and genetic diversity is a key component of biodiversity. While effects of genetic diversity on ecosystem functions have been extensively documented, no study has tested how genetic diversity of plants influences greenhouse gas fluxes from plant-soil systems. We assembled experimental populations consisting of 1, 4 or 8 genotypes of the clonal plant Hydrocotyle vulgaris in microcosms, and measured fluxes of CO2 and CH4 from the microcosms. The fluxes of CO2 and CO2 equivalent from the microcosms with the 1-genotype populations of H. vulgaris were significantly lower than those with the 4- and 8-genotype populations, and such an effect increased significantly with increasing the growth period. The cumulative CO2 flux was significantly negatively related to the growth of the H. vulgaris populations. However, genotypic diversity did not significantly affect the flux of CH4. We conclude that genotypic diversity of plant populations can influence CO2 flux from plant-soil systems. The findings highlight the importance of genetic diversity in regulating greenhouse gas fluxes.

Comprehensive transcriptome analysis of the periodontopathogenic bacterium Porphyromonas gingivalis W83.

High-density tiling microarray and RNA sequencing technologies were used to analyze the transcriptome of the periodontopathogenic bacterium Porphyromonas gingivalis. The compiled P. gingivalis transcriptome profiles were based on total RNA samples isolated from three different laboratory culturing conditions, and the strand-specific transcription profiles generated covered the entire genome, including both protein coding and noncoding regions. The transcription profiles revealed various operon structures, 5'- and 3'-end untranslated regions (UTRs), differential expression patterns, and many novel, not-yet-annotated transcripts within intergenic and antisense regions. Further transcriptome analysis identified the majority of the genes as being expressed within operons and most 5' and 3' ends to be protruding UTRs, of which several 3' UTRs were extended to overlap genes carried on the opposite/antisense strand. Extensive antisense RNAs were detected opposite most insertion sequence (IS) elements. Pairwise comparative analyses were also performed among transcriptome profiles of the three culture conditions, and differentially expressed genes and metabolic pathways were identified. With the growing realization that noncoding RNAs play important biological functions, the discovery of novel RNAs and the comprehensive transcriptome profiles compiled in this study may provide a foundation to further understand the gene regulation and virulence mechanisms in P. gingivalis. The transcriptome profiles can be viewed at and downloaded from the Microbial Transcriptome Database website, http://bioinformatics.forsyth.org/mtd.

Roles of clonal parental effects in regulating interspecific competition between two floating plants.

Parental effects can influence offspring fitness, which may further impact interspecific competition. However, few studies have tested the role of clonal parental effects in regulating interspecific interactions and examined the underlying mechanisms. We conducted two consecutive experiments with two clonal plants (Pistia stratiotes and Eichhornia crassipes). In the first experiment, the mother ramet of P. stratiotes and E. crassipes were grown in two nutrient levels and treated with a DNA demethylation reagent (5-azacytidine) or not. In the second experiment, the offspring ramets from each of the four treatments in the first experiment were grown alone (no competition) or with a heterospecific neighbor (with interspecific competition). We found no parental nutrient effect on the competitive ability of E. crassipes, but a significant parental nutrient effect of both E. crassipes and P. stratiotes on the competitive ability of P. stratiotes. Furthermore, the parental nutrient effect of P. stratiotes on the competitive ability of P. stratiotes varied depending on the DNA methylation status of both P. stratiotes and E. crassipes. These clonal parental effects were related to resource provisioning and/or DNA methylation. We conclude that clonal parental nutrient effects can regulate interspecific competition between P. stratiotes and E. crassipes by altering the competitive ability of P. stratiotes. Both resource provisioning and epigenetic mechanisms can be involved in these clonal parental effects. By regulating interspecific competition, clonal parental effects may further influence species coexistence, community structure, and ecosystem functioning.

The efficacy of combined therapy of qingfeiPaidu capsule and lianhuaqingwen capsule nursing interventions for hospitalized patients with COVID-19: A retrospective study of medical records.

Coronavirus disease-19 (COVID-19) caused a global pandemic burden, affecting hundreds of thousands of individuals, having life-threatening outcomes. Traditional Chinese Medicine plays a crucial role in the treatment of patients with COVID-19. The purpose of this study was to investigate the efficacy of combined therapy of qingfeiPaidu (QFPD) capsule and lianhuaqingwen (LHQW) capsule nursing interventions in the treatment of patients with COVID-19. A total of 318 patients with COVID-19 were enrolled and randomly received QFPD (n = 106), LHQW (n = 106), and QFPD-LHQW (n = 106). The clinical characteristics of COVID-19, the total lung severity scores, and blood laboratory indices were recorded in each patient in each group before treatment and at the end of treatment. The outcomes demonstrated that QFPD-LHQW group shortened the length of hospitalization, decreased C-reactive protein, creatine kinase, creatine kinase-myocardial band, lactate dehydrogenase, and blood urea nitrogen levels, and improved clinical symptoms, pulmonary inflammation, and prognosis. At the end of treatment, inflammation, immune function, circulating white blood cells, total lymphocyte count, and glutamic-oxaloacetic transaminase levels improved dramatically in 3 groups compared with baseline. All patients met the discharge criteria after 30-day treatment in 3 groups. Combined therapy of QFPD and LHQW demonstrated significant anti-inflammatory effects compared with those of only QFPD or LHQW in patients with mild and moderate COVID-19. The combined therapies may alleviate clinical symptoms of COVID-19 patients by improving inflammation and immune function.