Solidification/stabilization and optimization of municipal solid waste incineration fly ash with aluminosilicate solid wastes.

Alkali-activation is an effective municipal solid waste incineration fly ash (MSWIFA) solidification/stabilization (S/S) technology. However, the characteristics of calcium-rich silica-poor aluminum phase in MSWIFA easily cause the structural instability and contamination of alkali activated MSWIFA S/S bodies. Therefore, the aluminosilicate solid wastes are used in this work to optimize the immobilization and structural properties. Results showed that incorporation of aluminosilicate solid wastes significantly improved the compressive strength and heavy metals pollution toxicity of MSWIFA S/S bodies. Compared to alkali activated MSWIFA, the compressive strength of S/S bodies with addition of coal fly ash, silica fume and granulated blast furnace slag improved by 31.0%, 47.6% and 50.8% when the curing time was 28 days, respectively. Leachability of Pb, Zn and Cd in these alkali activated MSWIFA S/S bodies was far below the threshold value specified in Standard GB16889. Aluminosilicate solid wastes provided abundant Si/Al structural units, and some new phases such as ettringite(AFt, 3CaO⋅Al2O3⋅3CaSO4⋅32H2O), calcium sulfoaluminate hydrate (3CaO⋅Al2O3⋅CaSO4⋅12H2O) and Friedel's salt (CaO⋅Al2O3⋅CaCl2⋅10H2O) can be detected in S/S matrix with aluminosilicate solid wastes, along comes increased the amount of the amorphous phases. Lower Ca/Si molar ratio tended to form the network structure gel similar to tobermorite with higher polymerization degree. Meanwhile, the silica tetrahedron of the gels changed from the oligomerization state like island to the hyperomerization state like chain, layer network or three-dimensional structure, and average molecular chain length increased. These findings provide theoretical basis for structural properties optimization and resource utilization of MSWIFA S/S matrices.

Preparation of ionic porous polymers for extraction of four phenolic endocrine disrupting chemicals from fish and water samples.

In this paper, series of ionic polymers were synthesized by crosslinking alkyl quaternary ammonium salts with 1,4-bis(chloromethyl)benzene. Among them, hyper-crosslinked polymer fabricated with dodecyl dimethyl benzyl ammonium chloride (HCP-DD) as monomer delivered superior adsorption performance for endocrine disrupting chemicals (EDCs). The adsorption mechanism mainly includes π-π stacking, hydrophobic and electrostatic interaction. With HCP-DD as solid phase extraction sorbent, a high performance liquid chromatography-diode array detection method was developed for the detection of four phenolic EDCs in water and fish samples. The detection limits of the method were 0.005-0.02 ng mL-1 for water samples and 3-30 ng g-1 for fish samples. The recoveries of EDCs in water samples and fish samples were 80-119% and 81.3-117% (relative standard deviations <4.4%), respectively. The study not only provides a route for preparation ionic porous polymers, but also highlights the applications of ionic polymers as efficient adsorbent to enrich organic pollutants.

Consolidation chemotherapy after definitive concurrent chemoradiotherapy in patients with inoperable esophageal squamous cell carcinoma: a multicenter non-inferiority phase III randomized clinical trial.

BACKGROUND: Definitive concurrent chemoradiotherapy (dCCRT) is the gold standard for the treatment of locally advanced esophageal squamous cell carcinoma (ESCC). However, the potential benefits of consolidation chemotherapy after dCCRT in patients with esophageal cancer remain debatable. Prospective randomized controlled trials comparing the outcomes of dCCRT with or without consolidation chemotherapy in patients with ESCC are lacking. In this study, we aim to generate evidence regarding consolidation chemotherapy efficacy in patients with locally advanced, inoperable ESCC. METHODS: This is a multicenter, prospective, open-label, phase-III randomized controlled trial comparing non-inferiority of dCCRT alone to consolidation chemotherapy following dCCRT. In total, 600 patients will be enrolled and randomly assigned in a 1:1 ratio to receive either consolidation chemotherapy after dCCRT (Arm A) or dCCRT alone (Arm B). Overall survival will be the primary endpoint, whereas progression-free survival, locoregional progression-free survival, distant metastasis-free survival, and treatment-related toxicity will be the secondary endpoints. DISCUSSION: This study aid in further understanding the effects of consolidation chemotherapy after dCCRT in patients with locally advanced, inoperable ESCC. TRIAL REGISTRATION: ChiCTR1800017646.

CF2-II Alternative Splicing Isoform Regulates the Expression of Xenobiotic Tolerance-Related Cytochrome P450 CYP6CY22 in Aphis gossypii Glover.

The expression of P450 genes is regulated by trans-regulatory factors or cis-regulatory elements and influences how endogenous or xenobiotic substances are metabolized in an organism's tissues. In this study, we showed that overexpression of the cytochrome P450 gene, CYP6CY22, led to resistance to cyantraniliprole in Aphis gossypii. The expression of CYP6CY22 increased in the midgut and remaining carcass of the CyR strain, and after repressing the expression of CYP6CY22, the mortality of cotton aphids increased 2.08-fold after exposure to cyantraniliprole. Drosophila ectopically expressing CYP6CY22 exhibited tolerance to cyantraniliprole and cross-tolerance to xanthotoxin, quercetin, 2-tridecanone, tannic acid, and nicotine. Moreover, transcription factor CF2-II (XM_027994540.2) is transcribed only as the splicing variant isoform CF2-II-AS, which was found to be 504 nucleotides shorter than CF2-II in A. gossypii. RNAi and yeast one-hybrid (Y1H) results indicated that CF2-II-AS positively regulates CYP6CY22 and binds to cis-acting element p (-851/-842) of CYP6CY22 to regulate its overexpression. The above results indicated that CYP6CY22 was regulated by the splicing isoform CF2-II-AS, which will help us further understand the mechanism of transcriptional adaption of cross-tolerance between synthetic insecticides and plant secondary metabolites mediated by P450s.

Mosaic sarbecovirus vaccination elicits cross-reactive responses in pre-immunized animals.

Immunization with mosaic-8b [60-mer nanoparticles presenting 8 SARS-like betacoronavirus (sarbecovirus) receptor-binding domains (RBDs)] elicits more broadly cross-reactive antibodies than homotypic SARS-CoV-2 RBD-only nanoparticles and protects against sarbecoviruses. To investigate original antigenic sin (OAS) effects on mosaic-8b efficacy, we evaluated effects of prior COVID-19 vaccinations in non-human primates and mice on sarbecovirus response breadths elicited by mosaic-8b, admix-8b (8 homotypics), and homotypic SARS-CoV-2, finding greatest cross-reactivity for mosaic-8b. As demonstrated by molecular fate-mapping in which antibodies derived from specific cohorts of B cells are differentially detected, B cells primed by WA1 spike mRNA-LNP dominated antibody responses after RBD-nanoparticle boosting. While mosaic-8b- and homotypic-nanoparticles boosted cross-reactive antibodies, de novo antibodies were predominantly induced with mosaic-8b boosting, and these were specific for variant RBDs with increased identity to RBDs on mosaic-8b. These results inform OAS mechanisms and support using mosaic-8b to protect COVID-19 vaccinated/infected humans against as-yet-unknown SARS-CoV-2 variants and animal sarbecoviruses with human spillover potential.

18F-FP-DTBZ PET/CT detectable associations between monoaminergic depletion in the putamen with rigidity and the pallidus with tremor in Parkinson's disease.

INTRODUCTION: The motor subtypes of Parkinson's disease (PD) are widely accepted and implemented. However, the motor subtypes have been thought to represent different stages of PD recently because some patients experience tremor-dominant (TD) conversion to the non-tremor-dominant subtype, such as postural instability-gait difficulty (PIGD). In this study, we explore the monoaminergic denervation features of the striatal and extra-striatal areas in patients with different subtypes of PD with 18F-9-fluoropropyl-(+)-dihydrotetrabenazine (18F-FP-DTBZ) PET/CT. METHODS: Sixty-five patients diagnosed with PD were included and classified as TD (n = 25) and PIGD (n = 40). We evaluated the difference of monoaminergic features of each subregion of brain between motor subtypes of PD, as well as associations between these features and Parkinsonian motor symptoms. RESULTS: The striatal standardized uptake value ratios (SUVR) showed that dopaminergic disruption of patients with PIGD was more symmetrical in the posterior ventral putamen (p < 0.001) and more severe in the ipsilateral posterior dorsal putamen (p < 0.001 corrected) compared with that of patients with TD. The severity of PIGD scores was associated with striatal dopaminergic depletion, while tremor was associated with monoaminergic changes in extra-striatal areas, including pallidus, thalamus, and raphe nuclie. CONCLUSION: These results indicate that patients with different motor subtypes may have different underlying mechanisms of PD pathogenesis. Therefore, accurate diagnosis of PD subtypes can aid prognosis evaluation and treatment decision-making.

Chemical Evolution and Biological Evaluation of Natural Products for Efficient Therapy of Acute Lung Injury.

Acute lung injury (ALI) is one of the most common complications in COVID-19 and also a syndrome of acute respiratory failure with high mortality rates, but lacks effective therapeutic drugs. Natural products provide inspiration and have proven to be the most valuable source for bioactive molecule discovery. In this study, the chemical evolution of the natural product Tanshinone IIA (Tan-IIA) to achieve a piperidine-fused scaffold through a synthetic route of pre-activation, multi-component reaction, and post-modification is presented. Through biological evaluation, it is pinpointed that compound 8b is a standout candidate with remarkable anti-inflammation and anti-oxidative stress properties, coupled with low toxicity. The mechanistic study unveils a multifaceted biological profile of 8b and shows that 8b is highly efficient in vivo for the treatment of ALI. Therefore, this work not only provides an effective strategy for the treatment of ALI, but also offers a distinctive natural product-inspired drug discovery.

Solidification of municipal solid waste incineration fly ash with alkali-activated technology.

Alkali-activation is effective municipal solid waste incineration fly ash (MSWIFA) solidification/stabilization (S/S) technology. Percolation and migration of heavy metals in MSWIFA S/S matrix is a complicated and slow process. Here, several alkali-activated MSWIFA samples are selected to comparatively investigate the long-term leaching behavior and environmental availability of Pb, Zn and Cd when exposed in different erosion environment. Acid environment posed the more serious destroy to MSWIFA S/S matrices. RAC demonstrated that potential risk level of heavy metals is higher in acid rain environment, and Cd, Zn showed the prominent risk. When soaked in acid rain solution, the surface of alkali-activated MSWIFA S/S matrices was cracked seriously and a large number of hardened slurry peeled off. However, more stable structural properties and lower heavy metal leachability can be found in alkali-activated MSWIFA/aluminosilicate. The immobilization efficiency of Pb, Zn and Cd were all above 99.0%. Microstructure and morphology results indicated that there is new phase Friedel's salts generated and much more amorphous substance such as C-(A)-S-H gel with incorporation of aluminosilicate, which all contributed much to the formation of compact and stable microstructure, then significantly facilitated the encapsulation of heavy metal. These findings will provide theoretical basis and new insight for resource utilization and security landfill of MSWIFA.

Intermediate conformations of CD4-bound HIV-1 Env heterotrimers.

HIV-1 envelope (Env) exhibits distinct conformational changes in response to host receptor (CD4) engagement. Env, a trimer of gp120 and gp41 heterodimers, has been structurally characterized in a closed, prefusion conformation with closely associated gp120s and coreceptor binding sites on gp120 V3 hidden by V1V2 loops1-4 and in fully saturated CD4-bound open Env conformations with changes including outwardly rotated gp120s and displaced V1V2 loops3-9. To investigate changes resulting from substoichiometric CD4 binding, we solved single-particle cryo-electron microscopy (cryo-EM) structures of soluble, native-like heterotrimeric Envs bound to one or two CD4 molecules. Most of the Env trimers bound to one CD4 adopted the closed, prefusion Env state, with a minority exhibiting a heterogeneous partially open Env conformation. When bound to two CD4s, the CD4-bound gp120s exhibited an open Env conformation including a four-stranded gp120 bridging sheet and displaced gp120 V1V2 loops that expose the coreceptor sites on V3. The third gp120 adopted an intermediate, occluded-open state10 that showed gp120 outward rotation but maintained the prefusion three-stranded gp120 bridging sheet with only partial V1V2 displacement and V3 exposure. We conclude that most of the engagements with one CD4 molecule were insufficient to stimulate CD4-induced conformational changes, whereas binding two CD4 molecules led to Env opening in CD4-bound protomers only. The substoichiometric CD4-bound soluble Env heterotrimer structures resembled counterparts derived from a cryo-electron tomography study of complexes between virion-bound Envs and membrane-anchored CD4 (ref. 11), validating their physiological relevance. Together, these results illuminate intermediate conformations of HIV-1 Env and illustrate its structural plasticity.

Pd-Catalyzed Regiodivergent Hydrocarboxylation of Olefins with Oxalic Acid: A Remarkable Effect of the Counteranion on Regioselectivity.

A regioselective Pd-catalyzed hydrocarboxylation of vinyl arenes with oxalic acid is described. A wide variety of either linear or branched carboxylic acids can be readily obtained with high regioselectivities under mild reaction conditions. The reaction process is operationally simple and requires no handling of toxic CO. Besides the ligand, the counteranion of the Pd catalyst system plays an important role in the regioselectivity.

Temporal-frequency-phase feature classification using 3D-convolutional neural networks for motor imagery and movement.

Recently, convolutional neural networks (CNNs) have been widely applied in brain-computer interface (BCI) based on electroencephalogram (EEG) signals. Due to the subject-specific nature of EEG signal patterns and the multi-dimensionality of EEG features, it is necessary to employ appropriate feature representation methods to enhance the decoding accuracy of EEG. In this study, we proposed a method for representing EEG temporal, frequency, and phase features, aiming to preserve the multi-domain information of EEG signals. Specifically, we generated EEG temporal segments using a sliding window strategy. Then, temporal, frequency, and phase features were extracted from different temporal segments and stacked into 3D feature maps, namely temporal-frequency-phase features (TFPF). Furthermore, we designed a compact 3D-CNN model to extract these multi-domain features efficiently. Considering the inter-individual variability in EEG data, we conducted individual testing for each subject. The proposed model achieved an average accuracy of 89.86, 78.85, and 63.55% for 2-class, 3-class, and 4-class motor imagery (MI) classification tasks, respectively, on the PhysioNet dataset. On the GigaDB dataset, the average accuracy for 2-class MI classification was 91.91%. For the comparison between MI and real movement (ME) tasks, the average accuracy for the 2-class were 87.66 and 80.13% on the PhysioNet and GigaDB datasets, respectively. Overall, the method presented in this paper have obtained good results in MI/ME tasks and have a good application prospect in the development of BCI systems based on MI/ME.

UDP-glucuronosyltransferase is involved in susceptibility of Chironomus kiiensis Tokunaga, 1936 (Diptera: Chironomidae) to insecticides.

UDP-glucuronosyltransferases (UGTs) could transform various exogenous and endogenous compounds, which help detoxification of pesticides in insects. To investigate the role of UGTs in the detoxification metabolism of insecticides in Chironomus kiiensis, CkUGT302M1, CkUGT302N1, CkUGT308N1 and CkUGT36J1 genes were identified with 1449-1599 bp encoding 482-532 amino acids. Four UGT genes shared 40.86∼53.36% identity with other homologous insect species, and expressed in all developmental stages, notably in the larval and adult stages. Expression of CkUGTs was higher in the gastric caecum, midgut and head. Moreover, CkUGTs expression and activity were significantly increased in C. kiiensis larvae in exposure to sublethal concentrations of carbaryl, deltamethrin and phoxim, respectively. To further explore the functions of UGT genes, the CkUGT308N1 was effectively silenced in 4th instar C. kiiensis larvae by RNA interference, which resulted in the mortality of dsCkUGT308N1 treated larvae increased by 71.43%, 111.11% and 62.50% under sublethal doses of carbaryl, deltamethrin and phoxim at the 24-h time point, respectively. The study revealed that the CkUGT308N1 gene in C. kiiensis could contribute to the metabolism of pesticides and provide a scientific basis for evaluating the water pollution of pesticides.

Engineering RNA export for measurement and manipulation of living cells.

A system for programmable export of RNA molecules from living cells would enable both non-destructive monitoring of cell dynamics and engineering of cells capable of delivering executable RNA programs to other cells. We developed genetically encoded cellular RNA exporters, inspired by viruses, that efficiently package and secrete cargo RNA molecules from mammalian cells within protective nanoparticles. Exporting and sequencing RNA barcodes enabled non-destructive monitoring of cell population dynamics with clonal resolution. Further, by incorporating fusogens into the nanoparticles, we demonstrated the delivery, expression, and functional activity of exported mRNA in recipient cells. We term these systems COURIER (controlled output and uptake of RNA for interrogation, expression, and regulation). COURIER enables measurement of cell dynamics and establishes a foundation for hybrid cell and gene therapies based on cell-to-cell delivery of RNA.

Soliton solution, breather solution and rational wave solution for a generalized nonlinear Schrödinger equation with Darboux transformation.

In this paper, the exact solutions of generalized nonlinear Schrödinger (GNLS) equation are obtained by using Darboux transformation(DT). We derive some expressions of the 1-solitons, 2-solitons and n-soliton solutions of the GNLS equation via constructing special Lax pairs. And we choose different seed solutions and solve the GNLS equation to obtain the soliton solutions, breather solutions and rational wave solutions. Based on these obtained solutions, we consider the elastic interactions and dynamics between two solitons.

Network pharmacology and bioinformatics to identify molecular mechanisms and therapeutic targets of Ruyi Jinhuang Powder in the treatment of monkeypox.

Monkeypox outbreaks across the globe has aroused widespread concern. Ruyi Jinhuang Powder (RJP), a common formula in Chinese medicine, is used to treat pox-like illnesses. This study aimed to identify the molecular mechanisms and therapeutic targets of RJP for the treatment of monkeypox using network pharmacology and bioinformatics techniques. The bioactive substances and potential targets of each component of RJP were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). The differentially expressed genes (DEGs) of the monkeypox virus (MPXV) were identified from the GSE24125 by GEO2R. Key signaling pathways, bioactive components, and potential targets were obtained by bioinformatics analysis, including gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG), disease ontology (DO), and protein-protein interactions (PPI) analyses. Finally, molecular docking was used to predict the interaction between active compounds and core targets. A total of 158 active ingredients and 17 drug-disease-shared targets of RJP were screened. Bioinformatics indicated that wogonin and quercetin might be potential drug candidates. Potential therapeutic targets were identified. Immune-related mechanisms that exerted antiviral effects included signaling pathways like TNF, age-rage, and c-type lectin receptor pathways. Our results illustrated the good therapeutic effect of RJP on monkeypox in terms of biological activity, potential targets, and molecular mechanism. This also offered a promising strategy to reveal the scientific basis and therapeutic mechanism of herbal formulas used to treat the disease.

Preparation of Trichoderma asperellum Microcapsules and Biocontrol of Cucumber Powdery Mildew.

Microencapsulation is an important technique for protecting the viability and activity of microorganisms under adverse environmental conditions. To improve biological control, controlled-release microcapsules of Trichoderma asperellum were prepared and embedded in combinations of the biodegradable wall materials sodium alginate (SA). The microcapsules were evaluated for their ability to control cucumber powdery mildew in the greenhouse. The results showed that the highest encapsulation efficiency of 95% was obtained by applying 1% SA and 4% calcium chloride. The microcapsules provided good, controlled release and UV resistance, and could be stored for a long time. The greenhouse experiment revealed that the T. asperellum microcapsules had a maximal biocontrol efficiency of 76% against cucumber powdery mildew. In summary, embedding T. asperellum in microcapsules is a promising technique to improve the survivability of T. asperellum conidia. The T. asperellum microcapsules exerted significant biocontrol efficiency against cucumber powdery mildew. IMPORTANCE Trichoderma asperellum is widely found in plant roots and soil and has been used for the biocontrol of various plant pathogens; however, the control efficiency of T. asperellum is usually unstable in field trials. To improve the control efficiency of T. asperellum, in the present study, T. asperellum microcapsules were prepared using sodium alginate as wall material to reduce the effects of temperature, UV irradiation, and other environmental factors on its activity, and to significantly improve its biocontrol efficiency on cucumber powdery mildew. Microcapsules can prolong the shelf life of microbial pesticides. This study provides a new way to prepare a biocontrol agent against cucumber powdery mildew with high efficiency.

Structural characterization of HIV-1 Env heterotrimers bound to one or two CD4 receptors reveals intermediate Env conformations.

HIV-1 envelope (Env) exhibits distinct conformational changes in response to host receptor (CD4) engagement. Env, a trimer of gp120/gp41 heterodimers, has been structurally characterized in a closed, prefusion conformation with closely associated gp120s and coreceptor binding sites on gp120 V3 hidden by V1V2 loops, and in fully-saturated CD4-bound open Env conformations with changes including outwardly rotated gp120s and displaced V1V2 loops. To investigate changes resulting from sub-stoichiometric CD4 binding, we solved 3.4Å and 3.9Å single-particle cryo-EM structures of soluble, native-like Envs bound to one or two CD4 molecules. Env trimer bound to one CD4 adopted the closed, prefusion Env state. When bound to two CD4s, the CD4-bound gp120s exhibited an open Env conformation including a four-stranded gp120 bridging sheet and displaced gp120 V1V2 loops that expose the coreceptor sites on V3. The third gp120 adopted an intermediate, occluded-open state that included gp120 outward rotation but maintained the prefusion, three-stranded gp120 bridging sheet and showed only partial V1V2 displacement and V3 exposure. We conclude that engagement of one CD4 molecule was insufficient to stimulate CD4-induced conformational changes, while binding two CD4 molecules led to Env opening in CD4-bound protomers only. Together, these results illuminate HIV-1 Env intermediate conformations and illustrate the structural plasticity of HIV-1 Env.

Neutralizing monoclonal antibodies elicited by mosaic RBD nanoparticles bind conserved sarbecovirus epitopes.

Increased immune evasion by SARS-CoV-2 variants of concern highlights the need for new therapeutic neutralizing antibodies. Immunization with nanoparticles co-displaying spike receptor-binding domains (RBDs) from eight sarbecoviruses (mosaic-8 RBD-nanoparticles) efficiently elicits cross-reactive polyclonal antibodies against conserved sarbecovirus RBD epitopes. Here, we identified monoclonal antibodies (mAbs) capable of cross-reactive binding and neutralization of animal sarbecoviruses and SARS-CoV-2 variants by screening single mouse B cells secreting IgGs that bind two or more sarbecovirus RBDs. Single-particle cryo-EM structures of antibody-spike complexes, including a Fab-Omicron complex, mapped neutralizing mAbs to conserved class 1/4 RBD epitopes. Structural analyses revealed neutralization mechanisms, potentials for intra-spike trimer cross-linking by IgGs, and induced changes in trimer upon Fab binding. In addition, we identified a mAb-resembling Bebtelovimab, an EUA-approved human class 3 anti-RBD mAb. These results support using mosaic RBD-nanoparticle vaccination to generate and identify therapeutic pan-sarbecovirus and pan-variant mAbs.