Efficacy and immunogenicity of AS04-HPV-16/18 vaccine in females with existing cervical HR-HPV infection at first vaccination: A pooled analysis of four large clinical trials worldwide.

Females with existing high-risk HPV (HR-HPV) infections remain at risk of subsequent multiple or recurrent infections, on which benefit from HPV vaccines was under-reported. We pooled individual-level data from four large-scale, RCTs of AS04-HPV-16/18 vaccine to evaluate efficacy and immunogenicity in females DNA-positive to any HR-HPV types at first vaccination. Females receiving the AS04-HPV-16/18 vaccine in the original RCTs constituted the vaccine group in the present study, while those unvaccinated served as the control group. Vaccine efficacy (VE) against new infections and associated cervical intraepithelial neoplasia (CIN) 2+ in females DNA-negative to the considered HR-HPV type but positive to any other HR-HPV types, VE against reinfections in females DNA-positive to the considered HR-HPV type but cleared naturally during later follow-up, and levels of anti-HPV-16/18 IgG were assessed. Our final analyses included 5137 females (vaccine group = 2532, control group = 2605). The median follow-up time was 47.88 months (IQR: 45.72-50.04). For the prevention of precancerous lesions related to the non-infected HR-HPV types at baseline, VE against HPV-16/18 related CIN 2+ was 82.70% (95% CI: 63.70-93.00%). For the prevention of reinfections related to the infected HR-HPV types following natural clearance, VE against HPV-16/18 12MPI was non-significant (p > .05), albeit robust immunity persisted for at least 48 months. Females with existing HR-HPV infections at first vaccination still benefit from vaccination in preventing precancers related to the non-infected types at baseline. VE against reinfections related to the infected types following natural clearance remains to be further investigated.

Operando Spectroscopy Observation of Mo Clusters-Ti3 C2 TX Catalyst/Support Interface's Dynamic Evolution in Hydrogen Evolution Reaction.

The interaction between catalyst and support plays an important role in electrocatalytic hydrogen evolution (HER), which may explain the improvement in performance by phase transition or structural remodeling. However, the intrinsic behavior of these catalysts (dynamic evolution of the interface under bias, structural/morphological transformation, stability) has not been clearly monitored, while the operando technology does well in capturing the dynamic changes in the reaction process in real time to determine the actual active site. In this paper, nitrogen-doped molybdenum atom-clusters on Ti3 C2 TX (MoACs /N-Ti3 C2 TX ) is used as a model catalyst to reveal the dynamic evolution of MoAcs on Ti3 C2 TX during the HER process. Operando X-ray absorption structure (XAS) theoretical calculation and in situ Raman spectroscopy showed that the Mo cluster structure evolves to a 6-coordinated monatomic Mo structure under working conditions, exposing more active sites and thus improving the catalytic performance. It shows excellent HER performance comparable to that of commercial Pt/C, including an overpotential of 60 mV at 10 mA cm-2 , a small Tafel slope (56 mV dec-1 ), and high activity and durability. This study provides a unique perspective for investigating the evolution of species, interfacial migration mechanisms, and sources of activity-enhancing compounds in the process of electroreduction.

Mitigating cadmium accumulation in dicotyledonous vegetables by iron fertilizer through inhibiting Fe transporter IRT1-mediated Cd uptake.

The solubility of cadmium (Cd) in soil and its transfer to plants are influenced by soil pH. While increasing soil pH reduces Cd solubility and accumulation in rice plants grown in acidic soils, its effect on Cd accumulation in vegetables remains inconclusive. Here, we investigated the impact of soil pH on Cd accumulation in dicotyledonous vegetables and elucidated the underlying molecular mechanisms. Soils collected from various locations were supplemented with varying quantities of lime to achieve soil pH values of around 5.0, 6.0, 7.0, and 8.0. Raising soil pH from around 5.0 to 8.0 markedly decreased extractable Cd. However, increasing soil pH tended to promote shoot Cd accumulation in dicotyledonous vegetable species including lettuce, pakchoi, and Chinese cabbage, and the model dicotyledonous plant Arabidopsis thaliana. Conversely, soil pH increase resulted in a monotonic decrease in rice Cd accumulation. In our hydroponic experiments, we discovered that iron (Fe) deficiency substantially increased Cd uptake and accumulation in dicotyledonous plants but not in rice. Increasing soil pH reduced soil Fe availability and induced the Fe transporter gene IRT1 expression in dicotyledonous vegetables roots, which led to an increase in IRT1-mediated Cd uptake and subsequently increased Cd accumulation as soil pH increases. A comprehensive model incorporating extractable Cd and root IRT1 expression better explained Cd accumulation in vegetable shoots. The application of 50 mg/kg of Fe fertilizer in neutral or alkaline soils resulted in a significant reduction in Cd accumulation by 34-58% in dicotyledonous vegetables. These findings reveal that increasing soil pH has two opposite effects, decreasing soil Cd availability while promoting Cd uptake through IRT1 upregulation, reconciling the inconsistency in its effect on Cd accumulation in dicotyledonous plants. Our findings provide important insights for understanding the factors affecting Cd uptake in plants and offer a practical solution to mitigate Cd contamination in vegetables.

Deciphering the Potential of Multidimensional Carbon Materials for Surface-Enhanced Raman Spectroscopy through Density Functional Theory.

Surface-enhanced Raman spectroscopy (SERS) is a potent analytical tool, particularly for molecular identification and structural analysis. Conventional metallic SERS substrates, however, suffer from low reproducibility and compatibility with biological molecules. Recently, metal-free SERS substrates based on chemical enhancement have emerged as a promising alternative with carbon-based materials offering excellent reproducibility and compatibility. Nevertheless, our understanding of carbon materials in SERS remains limited, which hinders their rational design. Here we systematically explore multidimensional carbon materials, including zero-dimensional fullerenes (C60), one-dimensional carbon nanotubes, two-dimensional graphene, and their B-, N-, and O-doped derivatives, for SERS applications. Using density functional theory, we elucidate the nonresonant polarizability-enhanced and resonant charge-transfer-based chemical enhancement mechanisms of these materials by evaluating their static/dynamic polarizability and electron excitation properties. This work provides a critical reference for the future design of carbon-based SERS substrates, opening a new avenue in this field.

Cost-effectiveness of the screen-and-treat strategies using HPV test linked to thermal ablation for cervical cancer prevention in China: a modeling study.

BACKGROUND: Self-sampling HPV test and thermal ablation are effective tools to increase screening coverage and treatment compliance for accelerating cervical cancer elimination. We assessed the cost-effectiveness of their combined strategies to inform accessible, affordable, and acceptable cervical cancer prevention strategies. METHODS: We developed a hybrid model to evaluate costs, health outcomes, and incremental cost-effectiveness ratios (ICER) of six screen-and-treat strategies combining HPV testing (self-sampling or physician-sampling), triage modalities (HPV genotyping, colposcopy or none) and thermal ablation, from a societal perspective. A designated initial cohort of 100,000 females born in 2015 was considered. Strategies with an ICER less than the Chinese gross domestic product (GDP) per capita ($10,350) were considered highly cost-effective. RESULTS: Compared with current strategies in China (physician-HPV with genotype or cytology triage), all screen-and-treat strategies are cost-effective and self-HPV without triage is optimal with the most incremental quality-adjusted life-years (QALYs) gained (220 to 440) in rural and urban China. Each screen-and-treat strategy based on self-collected samples is cost-saving compared with current strategies (-$818,430 to -$3540) whereas more costs are incurred using physician-collected samples compared with current physician-HPV with genotype triage (+$20,840 to +$182,840). For screen-and-treat strategies without triage, more costs (+$9404 to +$380,217) would be invested in the screening and treatment of precancerous lesions rather than the cancer treatment compared with the current screening strategies. Notably, however, more than 81.6% of HPV-positive women would be overtreated. If triaged with HPV 7 types or HPV16/18 genotypes, 79.1% or 67.2% (respectively) of HPV-positive women would be overtreated with fewer cancer cases avoided (19 cases or 69 cases). CONCLUSIONS: Screen-and-treat strategy using self-sampling HPV test linked to thermal ablation could be the most cost-effective for cervical cancer prevention in China. Additional triage with quality-assured performance could reduce overtreatment and remains highly cost-effective compared with current strategies.

Rapid identification of high and low cadmium (Cd) accumulating rice cultivars using machine learning models with molecular markers and soil Cd levels as input data.

Excessive accumulation of cadmium (Cd) in rice grains threatens food safety and human health. Growing low Cd accumulating rice cultivars is an effective approach to produce low-Cd rice. However, field screening of low-Cd rice cultivars is laborious, time-consuming, and subjected to the influence of environment × genotype interactions. In the present study, we investigated whether machine learning-based methods incorporating genotype and soil Cd concentration can identify high and low-Cd accumulating rice cultivars. One hundred and sixty-seven locally adapted high-yielding rice cultivars were grown in three fields with different soil Cd levels and genotyped using four molecular markers related to grain Cd accumulation. We identified sixteen cultivars as stable low-Cd accumulators with grain Cd concentrations below the 0.2 mg kg-1 food safety limit in all three paddy fields. In addition, we developed eight machine learning-based models to predict low- and high-Cd accumulating rice cultivars with genotypes and soil Cd levels as input data. The optimized model classifies low- or high-Cd cultivars (i.e., the grain Cd concentration below or above 0.2 mg kg-1) with an overall accuracy of 76%. These results indicate that machine learning-based classification models constructed with molecular markers and soil Cd levels can quickly and accurately identify the high- and low-Cd accumulating rice cultivars.

The ferroxidases LPR1 and LPR2 control iron translocation in the xylem of Arabidopsis plants.

Iron (Fe) deficiency is common in agricultural crops and affects millions of people worldwide. Translocation of Fe in the xylem is a key step for Fe distribution in plants. The mechanism controlling this process remains largely unknown. Here, we report that two Arabidopsis ferroxidases, LPR1 and LPR2, play a crucial and redundant role in controlling Fe translocation in the xylem. LPR1 and LPR2 are mainly localized in the cell walls of xylem vessels and the surrounding cells in roots, leaves, and stems. Knockout of both LPR1 and LPR2 increased the proportion of Fe(II) in the xylem sap, and caused Fe deposition along the vascular bundles especially in the petioles and main veins of leaves, which was alleviated by blocking blue light. The lpr1 lpr2 double mutant displayed constitutive expression of Fe deficiency response genes and overaccumulation of Fe in the roots and mature leaves under Fe-sufficient supply, but Fe deficiency chlorosis in the new leaves and inflorescences under low Fe supply. Moreover, the lpr1 lpr2 double mutant showed lower Fe concentrations in the xylem and phloem saps, and impaired 57Fe translocation along the xylem. In vitro assays showed that Fe(III)-citrate, the main form of Fe in xylem sap, is easily photoreduced to Fe(II)-citrate, which is unstable and prone to adsorption by cell walls. Taken together, these results indicate that LPR1 and LPR2 are required to oxidize Fe(II) and maintain Fe(III)-citrate stability and mobility during xylem translocation against photoreduction. Our study not only uncovers an essential physiological role of LPR1 and LPR2 but also reveals a new mechanism by which plants maintain Fe mobility during long-distance translocation in the xylem.

Efficiently unsterile polyhydroxyalkanoate production from lignocellulose by using alkali-halophilic Halomonas alkalicola M2.

The alkali-halophilic Halomonas alkalicola M2 was isolated and developed for an open unsterile polyhydroxyalkanoate (PHA) fermentation from lignocellulose at pH 10.0 and NaCl 70 g/L. The alkaline pretreatment liquid (APL) was converted into PHA by the strain, which was significantly affected by the cultural conditions, including pH, NaCl concentration, nitrogen source, and APL concentration. The extracted PHA was composed of three monomers and similar in physicochemical properties to conventional short chain-length PHA. A record yield of 2.1 and 5.9 g of PHA was accumulated from 100 g dry bamboo powder (BP) by using APL and APL combined with hydrolysate during a 48-h open unsterile fermentation process, respectively. In summary, the alkali-halophilic H. alkalicola M2 achieved the open unsterile fermentation for lignocellulose efficient bioconversion into PHA under high alkalinity and salinity conditions and would be an ideal producer in the field.

Prenatal inflammation exposure-programmed hypertension exhibits multi-generational inheritance via disrupting DNA methylome.

The multi-generation heredity trait of hypertension in human has been reported, but the molecular mechanisms underlying multi-generational inheritance of hypertension remain obscure. Recent evidence shows that prenatal inflammatory exposure (PIE) results in increased incidence of cardiovascular diseases, including hypertension. In this study we investigated whether and how PIE contributed to multi-generational inheritance of hypertension in rats. PIE was induced in pregnant rats by intraperitoneal injection of LPS or Poly (I:C) either once on gestational day 10.5 (transient stimulation, T) or three times on gestational day 8.5, 10.5, and 12.5 (persistent stimulation, P). Male offspring was chosen to study the paternal inheritance. We showed that PIE, irrespectively induced by LPS or Poly (I:C) stimulation during pregnancy, resulted in multi-generational inheritance of significantly increased blood pressure in rat descendants, and that prenatal LPS exposure led to vascular remodeling and vasoconstrictor dysfunction in both thoracic aorta and superior mesenteric artery of adult F2 offspring. Furthermore, we revealed that PIE resulted in global alteration of DNA methylome in thoracic aorta of F2 offspring. Specifically, PIE led to the DNA hypomethylation of G beta gamma (Gßγ) signaling genes in both the F1 sperm and the F2 thoracic aorta, and activation of PI3K/Akt signaling was implicated in the pathologic changes and dysregulated vascular tone of aortic tissue in F2 LPS-P offspring. Our data demonstrate that PIE reprogrammed DNA methylome of cells from the germline/mature gametes contributes to the development of hypertension in F2 PIE offspring. This study broadens the current knowledge regarding the multi-generation effect of the cumulative early life environmental factors on the development of hypertension.

Fabrication of a Flexible Gold Nanorod Polymer Metafilm via a Phase Transfer Method as a SERS Substrate for Detecting Food Contaminants.

Surface enhanced Raman scattering (SERS) has been widely used in detection of food safety due to the nondestructive examination property. Here, we reported a flexible SERS film based on a polymer-immobilized gold nanorod polymer metafilm. Polystyrene-polyisoprene-polystyrene (SIS), a transparent and flexible, along with having excellent elasticity, polymer, was chosen as the main support of gold nanorods. A simple phase transfer progress was adopted to mix the gold nanorods with the polymer, which can further be used in most water-insoluble polymers. The SERS film performed satisfactorily while being tested in a series of standard Raman probes, like crystal violet (CV) and malachite green (MG). Moreover, the excellent reproducibility and elastic properties make the film a promising substrate in practical detection. Hence, the MG detection on the fish surface and trace thiram detection on orange pericarp were inspected with detection results of 1 × 10-10 and 1 × 10-6 M, which were below the demand of the National standard of China, exactly matching the realistic application requirements.

Rapid fabrication of flexible and transparent gold nanorods/poly (methyl methacrylate) membrane substrate for SERS nanosensor application.

Flexible substrates have been proposed for daily-life applications in SERS detection due to the prominent sample collection properties such as they can be wrapped around non-planar object surface. Combining the noble metals with polymers, flexible SERS substrates could be fabricated with advantages of light weight, transparency and high SERS sensitivity. Herein, we prepare a gold nanorods (AuNRs)/poly(methyl methacrylate) (PMMA) film as flexible SERS substrate by self-assembling a uniformly AuNRs array layer on PMMA template. This AuNRs/PMMA film performs excellently on thiram trace detection with the lowest detection concentration of 0.5 ppb. The fabricated substrates were applied for practical detection with cucumber by directly covering the AuNRs/PMMA flexible film on the target surface. Furthermore, the high SERS sensitivity as well as great reproducibility present a wide range of prospections for the further application of non-plane surface.

Interfacial synthesis of a three-dimensional hierarchical MoS2-NS@Ag-NP nanocomposite as a SERS nanosensor for ultrasensitive thiram detection.

Interfacial self-assembly of ordered nanostructures at oil-water interfaces towards the fabrication of nanofilms has attracted the interest of plenty of scientists, since its discovery in 2004. Herein, further developments have been achieved, and we report a new strategy for the synthesis of a three-dimensional (3D) hierarchical nanostructure, through an interfacial synthesis driven microemulsion process. Thus, the synthesis route has been simplified, with the rigorous experimental conditions of traditional compositing technology. Combined with a two-step seed-mediated growth method for preparing uniform Ag-NPs, a plasmonic 3D MoS2-NS@Ag-NP nanostructure was successfully developed as a Surface-Enhanced Raman Scattering (SERS) active substrate, with plenty of surface hot spots, leading to an enhancement factor (EF) of 1.2 × 108 derived from both electromagnetic mechanism (EM) and chemical mechanism (CM) effects. The 3D MoS2-NS@Ag-NP nanostructure can be applied to detect trace thiram in apple juice and local lake water, with a detection limit as low as 10 ppb (42 nM), which is much lower than the maximal residue limit (MRL) of 7 ppm in fruit prescribed by the U.S. Environmental Protection Agency (EPA). Furthermore, quantitative analysis was achieved in the range of 10 ppb-1 ppm with good homogeneity and selectivity.

Progressive deconstruction of Arundo donax Linn. to fermentable sugars by acid catalyzed ionic liquid pretreatment.

Acid enhanced ionic liquid (IL) 1-n-butyl-3-methylimidazolium chloride ([C4 mim]Cl) pretreatment has shown great potential for boosting the yield of sugars from biomass cost-effectively and environmental-friendly. Pretreatment with shorter processing time will promote the commercial viability. In this work, pretreatment of reduced Amberlyst catalysis time of 34 min was demonstrated to be the most effective among time-varying pretreatments, evidenced by partial removal of hemicellulose and cellulose crystal transformation of Arundo donax Linn. A higher fermentable sugar concentration of 10.42 g/L (2% substrate) was obtained after 72 h of saccharification than the others. Total processing time to reach 92% glucose yield was cut down to approximately 26 h. Progressive deconstruction of crop cell wall was occurred with increased catalysis time by gradual releasing of H3O(+) of Amberlyst. However, vast lignin re-deposited polymers on fibers could hinder further enzymatic hydrolysis. These discoveries provide new insights into a more economic pretreatment for bioethanol production.

[Imported falciparum malaria: one case report and literature review].

This paper reports the hematology screening and parasite morphological features of one case of imported falciparum malaria, and reviews the relevant literature.

[Study of alkaline lignin from Arundo donax linn based on FT Raman spectroscopy].

Arundo donax linn, as a perennial energy crop, has promising application prospect. In the present study, Fourier transform Raman (FT Raman) spectroscopy was applied to determine the structural information of materials, milled wood lignin (MWL), and alkaline lignins (AL, under different treated time) from A. donax stem nondestructively. The results indicated that, extractable compounds in A. donax had negative contribution to the Raman spectra without rising new Raman peaks. FT Raman spectrum of MWL indicated that MWL from A. donax was HGS type lignins. Compared with the spectra of MWL from wood materials, the peak at 1173 cm(-1) was much higher in intensity for the MWL from A. donax stem, which may be assigned to hydroxycinnamic acid by analyzing the standard. With respect to FT Raman spectra of ALs, the relatively highest intensity of 1173 cm(-1) was found in alkaline lignin (AL2), which was treated for 40 min by alkaline. Moreover, the peak of coniferaldehyde/sinapaldehyde (1630 cm(-1)) was lowest in intensity while the band attributed to coniferyl alcohol/sinapyl alcohol (1660 cm(-1)) was almost disappeared in AL2. It could be inferred that AL2 demonstrated a highest content of phenolic acid, which may improve its potential application, such as for antioxidant activity. Furthermore, the results obtained by FT Raman spectra were verified by two dimensional heteronuclear singlequantum coherence nuclear magnetic resonance analyses. Above all, FT Raman spectroscopy provided alternative safe, rapid, accurate, and nondestructive technology for lignin structure determination.

Chemical composition, properties, and antimicrobial activity of the water-soluble pigments from Castanea mollissima shells.

Agricultural residues Castanea mollissima shells represent a promising resource for natural pigments for the food industry. This study provides a comprehensive and systematic evaluation of water-soluble pigments (CSP) from C. mollissima shells, which were obtained by 50% ethanol with microwave-assisted extraction. Spectroscopic techniques (UV, FT-IR, (13)C NMR), elemental analysis, and chromatographic techniques (HPAEC, GPC) revealed that the main components in the CSP were flavonoids procyanidin B3 (condensed tannin), quercetin-3-O-glycoside, and steroidal sapogenins. As a consequence, CSP was water-soluble and presented significant DPPH scavenge capacity (EC50 value was 0.057 mg/mL). Specially, CSP gave excellent antibacterial activity, and even better than 5% aqueous phenol in some case. Moreover, CSP was practically nontoxic and exhibited good stability with temperature, natural light, and metal ions. These outstanding properties will enlarge the application of CSP for natural food additives production.

Structural elucidation of the lignins from stems and foliage of Arundo donax Linn.

As one of the potential energy crops, Arundo donax Linn. is a renewable source for the production of biofuels and bioproducts. In the present study, milled wood lignin (MWL) and alkaline lignin (AL) from stems and foliage of A. donax were isolated and characterized by FT-IR spectroscopy, UV spectroscopy, GPC, ³¹P NMR, 2D HSQC NMR, and DFRC. The results indicated that both stem and foliage lignins were HGS type lignins. The semiquantitative HSQC spectra analysis demonstrated a predominance of ß-O-4' aryl ether linkages (71-82%), followed by ß-ß', ß-5', ß-1', and α,ß-diaryl ethers linkages in the lignins. Compared to stem lignins, foliage lignins had less ß-O-4' alkyl-aryl ethers, lower weight-average molecular weight, less phenolic OH, more H units, and lower S/G ratio. Moreover, tricin was found to incorporate into the foliage lignins (higher content of condensed G units) in significant amounts and might be alkaline-stable.

Synergistic benefits of ionic liquid and alkaline pretreatments of poplar wood. Part 2: characterization of lignin and hemicelluloses.

The effect of proposed integrated pretreatment on enzymatic hydrolysis of poplar wood has been reported in Part 1. Part 2 of this work investigated the detailed structural features of the isolated lignin and hemicellulosic fractions, which were obtained in high yields. The chemical structures of these polymer fractions obtained were compared with the corresponding alkaline lignin and hemicelluloses extracted from the raw material without ionic liquid (IL) pretreatment. The yields of alkaline lignin and hemicelluloses obviously increased after the IL pretreatment. No apparent degradation occurred for both lignin and hemicellulosic fractions during this integrated pretreatment process. The lignin fraction (RCEL), which obtained after the enzymatic hydrolysis, exhibited high percentages of ß-O-4' aryl ether linkages and S/G ratio. It is believed that the high molecular weight and high purity hemicellulosic and lignin fractions obtained can serve as raw materials for the production of value-added products.

Three dimensional design of large-scale TiO(2) nanorods scaffold decorated by silver nanoparticles as SERS sensor for ultrasensitive malachite green detection.

We have designed a large-scale three-dimensional (3D) hybrid nanostructure as surface-enhanced Raman scattering (SERS) sensor by decorating silver nanoparticles on TiO2 nanorods scaffold (Ag/TiO2). Taking p-mercaptobenzoic acid (PMBA) as the probe molecule, the SERS signals collected by point-to-point and time mapping modes show that the relative standard deviation (RSD) in the intensity of the main Raman vibration modes (1079, 1586 cm(-1)) is less than 10%, demonstrating good spatial uniformity and time stability. This hybrid substrate also exhibits excellent SERS enhancement effect due to the formation of high-density hot spots among the AgNPs, which was proved by finite-difference time-domain (FDTD) simulations. The application of the new nanostructures as SERS sensors was demonstrated with the detection of malachite green (MG). The quantification of MG can be accomplished with the detection limit of 1 × 10(-12) M based on the Raman intensity. The results show that the Ag/TiO2 nanostructure can be a promising candidate for SERS sensor.

In situ identification of the adsorption of 4,4'-thiobisbenzenethiol on silver nanoparticles surface: a combined investigation of surface-enhanced Raman scattering and density functional theory study.

We investigated the configuration characteristic and adsorption behavior of 4,4'-thiobisbenzenethiol (TBBT) on the surface of silver nanoparticles (NPs). Under different conditions and preparation processes, several possible surface species were produced including single-end adsorption on a silicon wafer, double-end adsorption and bridge-like adsorption. Although consisting of the same molecule and nano material, different adsorption systems exhibited different spectral characteristics in the surface-enhanced Raman spectroscopy (SERS). A density functional theory (DFT) study further verified the corresponding adsorption states. The combined SERS-DFT study provided a framework towards investigating and designing adsorption systems at a molecular level, indicating the potential use in applications such as nano-sensors.