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Abstract Background Most guidelines propose inducing labor within 24 h following term (37 or more weeks of gestation) prelabor rupture of membranes (PROM). However, the exact timing for initiating induction within the 24 h period remains unknown. This study aims to comparatively assess the efficacy and safety of the use of vaginal dinoprostone within 6 h versus within 6–24 h for singleton pregnancies with PROM and an unfavorable cervix (Bishop score

Epidermal wax is strategically situated at the interface between plants and air; therefore, it plays a key role in plants’ interactions with their surroundings. It is also unstable and susceptible to light intensity. Hosta plants are shade-loving herbs with admirable flowers and leaves. Hosta ‘Halcyon’ and Hosta ensata F. Maek. are two species of Hosta with a glaucous and a glossy appearance, respectively. Light intensity can affect the composition of epicuticular wax on the leaf surface, which influences the leaf color phenotype and ornamental value. In this paper, the crystal micromorphology, content, and components of epicuticular wax on the leaves of two species of Hosta under different light conditions (10%-, 30%-, 50%-, 70%-, and 100%-intensity sunlight, relative light intensity (RLI)) have been studied using pot experiments. The results indicate that the epicuticular wax crystals of H. ‘Halcyon’ and H. ensata are tubular and platelet-like, respectively. The wax crystals of H. ‘Halcyon’ melted and formed a thick crust under 100% RLI, and those of H. ensata melted and formed a thick crust under 70% and 100% RLI conditions. The primary ingredients of the epicuticular wax of the two species of Hosta contained primary alcohols, alkanes, fatty acids, and esters; β-diketones were only detected in H. ‘Halcyon’. The quantity of epicuticular wax of H. ‘Halcyon’ reduced at first and then increased with an RLI increase, achieving its lowest value at 50% RLI, but that of H. ensata declined little by little. The amounts of C28 primary alcohols, C31 alkanes, and C18 fatty acids were significantly higher than those of other carbon atoms in the two genotypes of Hosta. The C31β-diketones content decreased with the increase in light intensity, which caused the white frost phenotype to gradually weaken in H. ‘Halcyon’.

Plant communities may be co-invaded by invasive plants, sometimes even by congeneric invasive plants (CIPs). Despite the growing understanding of co-invasion in the environment, little is known about how CIP interactions and mechanisms regulate co-invasion. Darwin’s naturalisation conundrum predicts that the coexistence of closely related species is difficult due to their structural and behavioural similarities. Nevertheless, communities containing closely related species are more susceptible to being invaded because close relatives may favour similar environments; therefore, this hypothesis should be followed in the co-invasion of CIPs. To explore whether the phylogenetic relatedness and origins of invasive species to CIPs can promote or hinder co-invasion, we conducted a controlled interaction and soil-legacy greenhouse experiment to quantify the growth response of invasive plants and their congeners. We consistently found that CIPs of identical origin were more likely to co-invade compared to CIPs of distinct origins. CIPs of distinct origins exhibited an antagonistic effect on co-invasion by allelopathy. Invasive plant-conditioned soil was more conducive to the growth of CIPs of identical origin than CIPs of distinct origins. Our results revealed the different effects of invader–invader phylogenetic relatedness on co-invader success and impact, suggesting the operation of different mechanisms across co-invasion.

Pelophylax plancyi (Lataste, 1880), Pelophylax chosenicus (Okada, 1931) and Pelophylax hubeiensis (Fei & Ye, 1982) were described chronologically from East Asia. The three species have similar morphological and molecular characteristics, but the taxonomic relationships amongst them have long been ambiguous. To deal with this taxonomic issue, we examined newly-obtained topotypic specimens of P. plancyi, P. chosenicus and P. hubeiensis for morphological comparison. Furthermore, we investigated the phylogeny of pond frogs in Eurasia by Bayesian Inference and Maximum Likelihood analyses of a fragment consisting of mitochondrial DNA gene 16s and provided a molecular phylogeny of the genus Pelophylax. There were no morphological and molecular differences between P. plancyi and P. chosenicus, but both morphological and molecular differences between P. hubeiensis and P. plancyi. Hence, we conclude that P. chosenicus is a junior synonym of P. plancyi and P. hubeiensis is a separate species from P. plancyi.

BackgroundTreatment of metastatic cervical cancer is a tricky issue. Currently, the National Comprehensive Cancer Network (NCCN) guideline recommends chemotherapy combined with bevacizumab for recurrent or metastatic cervical cancer. Still, the recurrence rate is high and the survival rate is low after standard treatment. We urgently need to achieve a multimodal therapy approach for recurrent or metastatic cervical cancer.Case descriptionWe report the case of a patient with stage IB2 cervical squamous carcinoma who developed multiple metastases within a short term after receiving first-line standard treatment, and she underwent interstitial brachytherapy after systemic therapy with an encouraging outcome. The patient developed suspected inguinal lymph node metastases after 9 months at the end of first-line therapy and multiple metastases in the inguinal lymph nodes, anterior abdominal wall, and right lung after 17 months. As the patient had residual inguinal lymph nodes after systemic therapy, she received 3D-printed template-guided interstitial brachytherapy to the inguinal lymph nodes and maintenance therapy. By Sep 2023, she had achieved a good treatment outcome with a progression-free survival (PFS) of 36 months.ConclusionBased on our patient response, when multiple metastases develop in the short term in early-stage cervical squamous carcinoma after first-line therapy, we may consider implementing local therapy combined with systemic therapy.

BackgroundTreatment for platinum-resistant ovarian cancer is challenging. Currently, platinum-resistant ovarian cancer is typically treated with non-platinum single-agent chemotherapy ± bevacizumab, but the prognosis is often extremely poor. In the treatment of platinum-resistant ovarian cancer patients, reports of triple therapy with interstitial implantation radiotherapy combined with immunotherapy and granulocyte-macrophage colony-stimulating factor (GM-CSF) (PRaG for short) are relatively rare.Case descriptionHere, we report a patient with oligometastatic platinum-resistant ovarian cancer. The patient achieved partial response (PR) of the lesion and sustained benefit for more than six months after receiving interstitial implantation radiotherapy combined with immunotherapy along with GM-CSF.ConclusionThis triple therapy may provide additional options for these patients.

ABSTRACT The polymorphism at amino acid 17 of quinolone resistance-determining region of GyrA has been stated with a potential role in fluoroquinolone susceptibility in different mycobacterial species. However, no study has provided dependable evidence so far. Here, we verified that gene-edited Mycobacterium abscessus mutants bearing Ser/Gly at this position were more susceptible to fluoroquinolones than their parent strain and the revertant that supports mycobacteria containing Ser/Gly at this position were more susceptible to fluoroquinolones than those containing Ala. IMPORTANCE Fluoroquinolones (FQs) play a key role in the treatment regimens against tuberculosis and non-tuberculous mycobacterial infections. However, there are significant differences in the sensitivities of different mycobacteria to FQs. In this study, we proved that this is associated with the polymorphism at amino acid 17 of quinolone resistance-determining region of Gyrase A by gene editing. This is the first study using CRISPR-associated recombination for gene editing in Mycobacterium abscessus to underscore the contribution of the amino acid substitutions in GyrA to FQ susceptibilities in mycobacteria.

The invasive vine Sicyos angulatus L. destroys the natural ecosystem of invaded areas. Understanding the differences in growth and development between S. angulatus and other plants is necessary to explore the invasion mechanisms of S. angulatus and implement appropriate prevention and control measures. Thus, this study compared the growth, photosynthesis, and root characteristics of invasive liana S. angulatus and other three vine plants, Ipomoea nil (L.) Roth, Ipomoea purpurea (L.), and Thladiantha dubia Bunge, at different growth stages: seedling, flowering, and fruiting. The results showed that the total biomass of S. angulatus in the fruiting stage was 3–6 times that of the other three plants, and the root biomass ratio and root–shoot ratio decreased throughout the growth stage. Throughout the growth stage, the total leaf area of S. angulatus was significantly higher than that of the other three plant types, and the specific leaf area of S. angulatus at the seedling and flowering stages was 2.5–3 and 1.4–3 times that of the other three plants, respectively. The photosynthetic rate, stomatal conductance, and transpiration rate of S. angulatus at the fruiting stage were significantly higher than those of the other three plants, and its water use efficiency was higher than that of the other three plants at the three growth stages, indicating its strong photosynthetic capacity. The root activity and root pressure of S. angulatus were also significantly higher than those of the other three plants at the seedling and flowering stages. These results show that S. angulatus flexibly allocates resources to its aboveground parts during the growth stage to ensure that the plant obtains the space necessary for its growth and development and that with the help of higher root pressure and root activity, S. angulatus can maintain higher photosynthesis and water use efficiency with fewer resources. Therefore, the prevention and control of S. angulatus requires a combination of aboveground and underground measures. Spraying conventional weedicide/herbicide and manually removing aboveground plants may lead to its resurgence.

The Cenozoic climatic evolution of the Tibetan Plateau (TP), together with its driving mechanism, have been a subject of interest for decades. This study presents detailed sedimentology, mineralogical (XRD), carbon, and oxygen isotope analyses of lacustrine deposits from the Eocene to the Miocene in the western Qaidam Basin, the northern TP. The petrological observation and XRD data of 109 samples reveal that the sediments are composed of mixed siliciclastic, carbonate, and evaporate minerals. And the carbonate isotopic results show negative δ13C (−7.49‰ to −3.41‰) and negative to slightly positive δ18 values (−14.65‰ to 0.2‰). Both isotopes display a positive correlation with the contents of carbonates and evaporates, which suggests that evaporation is the major controlling factor of carbon and oxygen isotope. Therefore, the isotopes can be used as reliable indicators of the intensity of evaporation for paleoclimatic reconstruction. The reconstruction results reveal three distinct arid stages: top of the lower Xiaganchaigou Formation to the upper Xiaganchaigou Formation (ca.40-32 Ma), bottom of the Xiayoushashan Formation (ca.22-20 Ma), top of the Shangyoushashan Formation (ca.13-8.2 Ma). We suggest that the aridity during ∼40-32 Ma may have been related to the regression of the Paratethys Sea and uplift of the TP, while the aridity during 22-20 Ma may have been caused by the uplift and denudation of the mountains around the basin. The aridity after ∼13 Ma could be attributed to both global cooling and tectonic events in the northern TP. Furthermore, by comparing the climate records of the Qaidam Basin with those of other basins in Central Asia, a regional correlation can be established between different basins during the first and third drought stages. This study reveals that during the Eocene to Miocene, the climate change between different regions in the Qaidam Basin was synchronized and had a good connection with the surrounding basins, which responded to global climate change and regional tectonic activities.

Abstract Formalin fixation of biological specimens damages nucleic acids and limits their use in genomic analyses. Previously, we showed that RNA isolation with an organocatalyst (2-amino-5-methylphenyl phosphonic acid, used to speed up reversal of formalin-induced adducts) and extended heated incubation (ORGΔ) improved RNA-sequencing data from formalin-fixed paraffin-embedded (FFPE) tissue samples. The primary goal of this study was to evaluate whether ORGΔ treatment improves DNA-sequencing data from clinical FFPE samples. We isolated RNA and DNA ± ORGΔ from paired FFPE and frozen human renal and ovarian carcinoma specimens collected as part of the National Cancer Institute Biospecimen Pre-analytical Variables program. Tumor types were microscopically confirmed from adjacent tissue sections. Following extraction, DNA was fragmented and sequenced and differences were compared between frozen and FFPE sample pairs. Treatment with ORGΔ improved concurrent SNP calls in FFPE DNA compared to non-ORGΔ FFPE samples and enhanced confidence in SNP calls for all FFPE DNA samples, beyond that of matched frozen samples. In general, the concordant SNPs identified in paired frozen and FFPE DNA samples agreed for both genotype and homozygosity vs. heterozygosity of calls regardless of ORGΔ treatment. The increased confidence in ORGΔ FFPE DNA variant calls relative to the matched frozen DNA suggests a novel application of this method. With further optimization, this method may improve quality of DNA-sequencing data in FFPE as well as frozen tissue samples.

The Shenhu area of the South China Sea is one of the leading areas for natural gas hydrate investigation and exploitation in China. In this study, total organic carbon (TOC) content, total nitrogen (TN) content, and gas chromatographic-mass spectrometric (GC–MS) analysis of the soluble organic matter of sediments from sites W01B, W02B, and W03B were completed to understand the characteristics of organic matter in the sedimentary system with gas hydrates and provide theoretical support for further exploration in this area. Source indicators such as δ13Corg, TAR, and C21-/C21+ revealed that sites W01B and W02B have similar provenance characteristics in vertical profiles, with an increase of terrestrial source in the hydrate occurrence layers, while site W03B shows a gradual increase in marine source contribution as depth decreases. The asymmetric erosion and lateral deposition of the channel-levee depositional system are considered the controlling factors for the discrepancies in provenance indexes among the three sites. Analysis of the different source indicators revealed that the different kinds of soluble organic matter were subjected to varying degrees of biodegradation, and the distribution characteristics of n-alkanes were preferentially altered. Furthermore, it is found that biodegradations at sites W01B and W02B were more pronounced, particularly in hydrate occurrence layers. All of the microbial degradation indexes increase simultaneously and are consistent with the vertical distribution of hydrates, showing a similar triangular distribution trend. The increase in squalane, a characteristic compound representing methanogens, indicates that microbial degradation and methanogenesis are synchronized in the hydrate occurrence horizon, providing sufficient microbial gases for gas hydrates formation.

The high therapeutic resistance of tumor is the primary cause behind tumor recurrence and incurability. In recent years, scientists have devoted themselves to find a variety of treatments to solve this problem. Herein, we propose a multi-hit strategy that is based on the biodegradable hollow mesoporous Prussian blue (HMPB)-based nanosystem for tumor-specific therapy that encapsulated the critical heat shock protein 90 (HSP90) inhibitor 17-dimethylamino-ethylamino-17-demethoxydeldanamycin (17-DMAG). The nanosystem was further modified using thermotropic phase transition material star-PEG-PCL (sPP) and hyaluronic acid (HA), which offers near infrared light (NIR) responsive release characteristic, as well as enhanced tumor cell endocytosis. Upon cell internalization of 17-DMAG-HMPB@sPP@HA and under 808 nm laser irradiation, photothermal-conversion effect of HMPB directly kills cells using hyperthermia, which further causes phase transition of sPP to trigger release of 17-DMAG, inhibits HSP90 activity and blocks multiple signaling pathways, including cell cycle, Akt and HIF pathways. Additionally, the down-regulation of GPX4 protein expression by 17-DMAG and the release of ferric and ferrous ions from gradual degradation of HMPB in the endogenous mild acidic microenvironment in tumors promoted the occurrence of ferroptosis. Importantly, the antitumor effect of 17-DMAG and ferroptosis damage were amplified using photothermal effect of HMPB by accelerating release of ferric and ferrous ions, and reducing HSP90 expression in cells, which induced powerful antitumor effect in vitro and in vivo. This multi-hit therapeutic nanosystem helps provide a novel perspective for solving the predicament of cancer treatment, as well as a promising strategy for design of a novel cancer treatment nanoplatform.

IntroductionInfections caused by non-tuberculosis mycobacteria are significantly worsening across the globe. M. fortuitum complex is a rapidly growing pathogenic species that is of clinical relevance to both humans and animals. This pathogen has the potential to create adverse effects on human healthcare.MethodsThe MF GZ001 clinical strain was collected from the sputum of a 45-year-old male patient with a pulmonary infection. The morphological studies, comparative genomic analysis, and drug resistance profiles along with variants detection were performed in this study. In addition, comparative analysis of virulence genes led us to understand the pathogenicity of this organism.ResultsBacterial growth kinetics and morphology confirmed that MF GZ001 is a rapidly growing species with a rough morphotype. The MF GZ001 contains 6413573 bp genome size with 66.18 % high G+C content. MF GZ001 possesses a larger genome than other related mycobacteria and included 6156 protein-coding genes. Molecular phylogenetic tree, collinearity, and comparative genomic analysis suggested that MF GZ001 is a novel member of the M. fortuitum complex. We carried out the drug resistance profile analysis and found single nucleotide polymorphism (SNP) mutations in key drug resistance genes such as rpoB, katG, AAC(2')-Ib, gyrA, gyrB, embB, pncA, blaF, thyA, embC, embR, and iniA. In addition, the MF GZ001strain contains mutations in iniA, iniC, pncA, and ribD which conferred resistance to isoniazid, ethambutol, pyrazinamide, and para-aminosalicylic acid respectively, which are not frequently observed in rapidly growing mycobacteria. A wide variety of predicted putative potential virulence genes were found in MF GZ001, most of which are shared with well-recognized mycobacterial species with high pathogenic profiles such as M. tuberculosis and M. abscessus.DiscussionOur identified novel features of a pathogenic member of the M. fortuitum complex will provide the foundation for further investigation of mycobacterial pathogenicity and effective treatment.

BackgroundChemoresistance generally develops in patients with advanced epithelial ovarian cancer, and the prognosis is still very poor, with an expected survival time of less than one year. For this population of individuals, there is currently no standard protocol for clinical benefit.Case presentationWe report a case of an elderly woman diagnosed with stage IIIC high-grade serous ovarian cancer (HGSOC). During a follow-up time of 6 years, the patient initially received multiple sequential courses of chemotherapy with platinum-based regimens and with no maintenance therapy. Similar to most patients with advanced HGSOC, she developed platinum resistance and experienced poor treatment results with a short progression-free survival (PFS). Ultimately, we gave the patient traditional non-platinum-based chemotherapy with bevacizumab and high-dose-rate interstitial brachytherapy followed by olaparib as a maintenance therapy. Up to now, the patient did response well to the treatment, and the PFS had exceeded 12 months.ConclusionHigh-dose-rate interstitial brachytherapy combination with PARP inhibitors may be an option for isolated chemoresistant recurrent epithelial ovarian cancer.

Sinomicrurus peinani is a new species of the genus Sinomicrurus (Serpentes: Elapidae) from China and Vietnam in 2020. In this study, we successfully sequenced mitochondrial genome of an individual S. peinani. The complete mitochondrial genome of S. peinani is a circular molecule with the entire length of 19,477 bp. The base composition is T (28.1%), G (11.9%), and GC (38.5%), which contains two ribosomal RNA (rRNA) genes, 22 transfer RNA (tRNA) genes, 13 protein-coding genes, one origin of replication gene (D-loop), and two non-coding control regions, an origin of light-strand replication, and a 2346 bp non-coding region between tRNA-N and tRNA-Y. A maximum-likelihood (ML) tree of S. peinani and 13 other related species was constructed. The DNA data presented here will be useful to study the evolutionary relationships and genetic diversity of S. peinani.

Abstract Pyroptosis has been implicated in the pathophysiology of myocardial infarction (MI) in rodents, but its contribution to reperfusion injury in MI patients is unclear. Here, we evaluated pyroptosis in MI patients in vitro and in vivo models of myocardial ischemia/reperfusion (I/R) injury. We also investigated the molecular mechanisms that regulate pyroptosis and myocardial I/R injury in these in vitro and in vivo models. The study showed that MI patients exhibited elevated serum concentrations of the pyroptosis-related pro-inflammatory cytokines IL-1β and IL-18. Increased levels of IL-1β and IL-18 as well as the pyroptosis-related inflammatory caspases (caspase-1 and 11) were detected in cultured cardiomyocytes after anoxia/reoxygenation (A/R) and in cardiac tissues after I/R. Circ-NNT and USP46 were upregulated while miR-33a-5p was downregulated in MI patients, as well as in cultured cardiomyocytes after A/R and cardiac tissues after I/R. Circ-NNT or USP46 knockdown or miR-33a-5p overexpression inhibited the expression of pro-caspase-1, cleaved caspase-1, pro-caspase-11, cleaved caspase-11, IL-1β, and IL-18 in A/R cardiomyocytes and attenuated myocardial infarction in I/R mice. The results from luciferase reporter assays and gene overexpression/knockdown studies indicated that miR-33a-5p directly targets USP46, and circ-NNT regulates USP46 by acting as a miR-33a-5p sponge. Direct association between circ-NNT and miR-33a-5p in cardiomyocytes was confirmed by pull-down assays. In summary, pyroptosis is activated during myocardial I/R and contributes to reperfusion injury. Circ-NNT promotes pyroptosis and myocardial I/R injury by acting as a miR-33a-5p sponge to regulate USP46. This circ-NNT→miR-33a-5p→USP46 signaling axis may serve as a potential target for the development of cardio-protective agents to improve the clinical outcome of reperfusion therapy.

The tectonic evolution of the Altyn Tagh Fault (ATF) remains controversial during the Tertiary. Qaidam Basin is the largest and highest plateau inland basin inside the Tibet Plateau. Sediments in the basin provide sedimentary records of the evolution history of its surrounding orogens, such as the ATF, located on the northwest margin of the Qaidam Basin. Comprehensive analyses of sandstone petrography, heavy mineral assemblages, and mineral geochemistry were adopted to effectively indicate the tectonic evolution history of ATF. The result indicates that the sediments in a wide range of the northwestern Qaidam Basin (e.g., the Xichagou section, the Yueyashan section) were derived from the Altyn Mountains. The increasing immaturity of sediments, increased denudation, and sedimentation processes from the early-middle Miocene to the Pliocene can be explained by the active tectonic setting of the ATF. During the early Miocene (ca. 22 Ma), there was an abrupt change in the heavy mineral composition of sediments in the northwestern Qaidam Basin. This change may be attributed to the large-scale slip motion along the ATF. Therefore, ~22 Ma is the key transforming period of the ATF system. On the foundation of the above, we suggest a two-stage evolution model of the ATF during the Tertiary: (1) From the late Eocene to the Oligocene, the tectonic setting of the ATF was relatively calm; (2) During the early Miocene period, the ATF underwent large-scale tectonic activation. It is likely to be a strike-slip tectonic activity, accompanied by an uplift of the Altyn Mountains. The active tectonic setting of the ATF was sustained after the Miocene.

Abstract Aims Heart failure with preserved ejection fraction (HFpEF) develops in response to hypertensive left ventricular (LV) hypertrophy and is associated with increased cardiovascular events. Although the progression to systolic heart failure is a known consequence of LV hypertrophy and HFpEF, few data are available on the LV geometry change and frequency of deterioration to systolic dysfunction in this population. Methods and results We evaluated the baseline and follow‐up characteristics in 680 patients with LV hypertrophy and HFpEF in this prospective cohort study. The primary endpoint was 5 year all‐cause mortality. The changes of LV geometry and heart failure transition were analysed. Systolic dysfunction [left ventricular ejection fraction (LVEF)

Abstract Background We performed a prospective multicentre diagnostic study to evaluate the combined interferon-γ (IFN-γ) and interleukin-2 (IL-2) release assay for detect active pulmonary tuberculosis (TB) in China. Methods Adult patients presenting symptoms suggestive of pulmonary TB were consecutively enrolled in three TB-specialized hospitals. Sputum specimens and blood sample and were collected from each participant at enrolment. The levels of Mycobacterium tuberculosis (MTB)-specific antigen-stimulated IFN-γ and IL-2 were determined using enzyme-linked immunosorbent assay (ELISA). Results Between July 2017 and December 2018, a total of 3245 patients with symptoms suggestive of pulmonary TB were included in final analysis. Of 3245 patients, 2536 were diagnosed as active TB, consisting of 1092 definite TB and 1444 clinically diagnosed TB. The overall sensitivity and specificity of IFN-γ were 83.8% and 81.5%, respectively. In addition, compared with IFN-γ, the specificity of IL-2 increased to 94.3%, while the sensitivity decreased to 72.6%. In addition, the highest sensitivity was achieved with parallel combination of IFN-γ/IL-2, with a sensitivity of 87.9%, and its overall specificity was 79.8%. The sensitivity of series combination test was 68.5%. Notably, the sensitivity of series combination test in definite TB (72.1%) was significantly higher than that in clinically diagnosed TB (65.8%). Conclusion In conclusion, we develop a new immunological method that can differentiate between active TB and other pulmonary diseases. Our data demonstrates that the various IFN-γ/IL-2 combinations provides promising alternatives for diagnosing active TB cases in different settings. Additionally, the diagnostic accuracy of series combination correlates with severity of disease in our cohort.

Nb-Si based ultrahigh-temperature alloys with the composition of Nb-22Ti-15Si-5Cr-3Al (atomic percentage, at. %) were prepared by hot press sintering (HPS) at 1250, 1350, 1400, 1450 and 1500 °C. The effects of HPS temperatures on the microstructure, room temperature fracture toughness, hardness and isothermal oxidation behavior of the alloys were investigated. The results showed that the microstructures of the alloys prepared by HPS at different temperatures were composed of Nbss, βTiss and γ(Nb,X)5Si3 phases. When the HPS temperature was 1450 °C, the microstructure was fine and nearly equiaxed. When the HPS temperature was lower than 1450 °C, the supersaturated Nbss with insufficient diffusion reaction still existed. When the HPS temperature exceeded 1450 °C, the microstructure coarsened obviously. Both the room temperature fracture toughness and Vickers hardness of the alloys prepared by HPS at 1450 °C were the highest. The alloy prepared by HPS at 1450 °C exhibited the lowest mass gain upon oxidation at 1250 °C for 20 h. The oxide film was mainly composed of Nb2O5, TiNb2O7, TiO2 and a small amount of amorphous silicate. The formation mechanism of oxide film is concluded as follows: TiO2 forms by the preferential reaction of βTiss and O in the alloy; after that, a stable oxide film composed of TiO2 and Nb2O5 forms; then, TiNb2O7 is formed by the reaction of TiO2 and Nb2O5.

Scholars have used the method of splicing various experimental data to evaluate the full-range pore structure of tight reservoirs, but its applicability has not been discussed. When the fractal theory is used to characterize the heterogeneity of tight reservoirs, there is a lack of research on the controlling factors of segmented fractal pore size (the inflection points in the fractal curve) and the relationship between the fractal dimensions of different dimensions. In this paper, mercury intrusion porosimetry (MIP), N2 adsorption (N2-GA), and large-field splicing scanning electron microscopy (MAPs) were conducted to study the pore structure and full-range pore size distribution (PSD) of tight sandstone, and fractal theory was used to evaluate the heterogeneity of the reservoir. Combining the PSD of MIP and N2-GA, two parameters “cosine similarity” and “data similarity” were introduced to characterize the overlapping pore size range of the two experimental methods; then, the PSD of MAPs was used to verify the rationality of the data splicing. The results show that the characterization of the full-range pore structure should not only be based on simple data splicing but should focus on the data similarity of the overlapping pore size range. The study on the segmented fractal pore size of MIP shows that the segmented fractal pore size increases gradually with an increase in the main skeleton mineral content, the decrease in the clay mineral content, and the increase in the pore radius and porosity. For the same sample, the segmented fractal pore size is fixed and does not change with the calculation model of fractal dimension. Comparing the two-dimensional (2D) fractal dimension with the three-dimensional (3D) fractal dimension, calculating the 3D fractal dimension by +1 directly with the 2D fractal dimension is more applicable for the large pores, but it is not applicable for the small pores due to the influence of the extensive development of linear pores.

Hydrate-bearing sediments provide excellent materials for studying the primary sources and diagenetic alterations of organic matter. In this study, the elemental and isotopic signatures of total organic carbon (TOC), total inorganic carbon (TIC), total nitrogen (TN), and total sulfur (TS) are systematically investigated in three hydrate-bearing sediment cores (∼240 m) retrieved from the Shenhu area, South China Sea. All sediment layers from three sites are with low TOC content (average 0.35%) with marine and terrestrial mixed sources (-23.6‰ < δ13Corg < -21.4‰). However, the generally low δ15N (2.49–5.31‰) and C/N ratios (4.35–8.2) and their variation with depth cannot be explained by the terrestrial sources (Pearl River) and marine sources, binary end-member mixing processes. Contribution from lateral allochthonous organic matter from the mountainous river is considered after excluding other possible factors and ingeniously elucidating the organic matter origins. Furthermore, specific layers in W01B and W02B exhibit elevated S/C ratios (up to 2.39), positive bias of δ34S-TS (up to +29.7‰), and negative excursion of δ13C-TIC (up to -8.29‰), which are the characteristics of sustained occurrence of sulfate-driven anaerobic oxidation of methane. The occurrence of coupled carbon–sulfur anomaly may be accompanied by deep hydrocarbon leakage and the formation of hydrate with high saturation.

Drug-resistant tuberculosis (DR-TB) poses a new threat to global health; to improve the treatment outcome, therapeutic vaccines are considered the best chemotherapy adjuvants. Unfortunately, there is no therapeutic vaccine approved against DR-TB. Our study assessed the therapeutic efficacy of a recombinant drug-resistant BCG (RdrBCG) vaccine in DR-TB. We constructed the RdrBCG overexpressing Ag85B and Rv2628 by selecting drug-resistant BCG strains and transformed them with plasmid pEBCG or pIBCG to create RdrBCG-E and RdrBCG-I respectively. Following successful stability testing, we tested the vaccine’s safety in severe combined immune deficient (SCID) mice that lack both T and B lymphocytes plus immunoglobulins. Finally, we evaluated the RdrBCG’s therapeutic efficacy in BALB/c mice infected with rifampin-resistant M. tuberculosis and treated with a second-line anti-TB regimen. We obtained M. bovis strains which were resistant to several second-line drugs and M. tuberculosis resistant to rifampin. Notably, the exogenously inserted genes were lost in RdrBCG-E but remained stable in the RdrBCG-I both in vitro and in vivo. When administered adjunct to a second-line anti-TB regimen in a murine model of DR-TB, the RdrBCG-I lowered lung M. tuberculosis burden by 1 log10. Furthermore, vaccination with RdrBCG-I adjunct to chemotherapy minimized lung tissue pathology in mice. Most importantly, the RdrBCG-I showed almost the same virulence as its parent BCG Tice strain in SCID mice. Our findings suggested that the RdrBCG-I was stable, safe and effective as a therapeutic vaccine. Hence, the “recombinant” plus “drug-resistant” BCG strategy could be a useful concept for developing therapeutic vaccines against DR-TB.

Amyloid aggregation and fungal infection, especially amyloid beta (Aβ) peptide and Candida albicans are considered as two of the crucial pathogenic agents in Alzheimer's disease (AD). In this work, we propose an innovative treatment strategy for AD, targeting at not only Aβ aggregation but also Candida albicans infection. Here, a high-performance nanomaterial, namely gCDs-E, have been prepared by self-assembled of glycosylated carbon dots (gCDs) and epigallocatechin-3-gallate (EGCG). Surprisingly, gCDs-E can not only suppress the fibrillation of Aβ and disaggregate Aβ fibrils, but also effectively inhibit the activity of Candida albicans. More importantly, the prepared gCDs-E can effectively cut down the cytotoxicity of amyloid aggregations, and the cell viability reached to 99.2%. In addition, the capability of the gCDs-E for blood brain barrier (BBB) penetration was also observed using a normal mice model. Above all, the gCDs-E greatly cleaned Aβ deposition and improved memory impairment in APP/PS1 transgenic AD model mice, confirming its potential as therapeutic agent for AD treatment.

The formation of the Qaidam Basin plays an important role in unraveling the growth history of the Tibetan plateau. An extraordinary thick Cenozoic sedimentary succession of the Qaidam Basin is a great contributor to the study of the basin’s evolution history. To date, there has been disagreement on the southwestern boundary of the Paleogene Qaidam Basin. In this study, the method of heavy mineral analysis was adopted to reconstruct the southwestern boundary of the Qaidam Basin. The stable heavy minerals which represent the maturity of detrital sediments can roughly reflect the distance between the source and the deposit area. Therefore, the isogram of the stable heavy mineral index (ZTR = 20) was compiled to infer the location of the source area of the southwestern Qaidam Basin. The isogram shows that the boundary of the southwestern Qaidam Basin stretched southwesterly to the present-day Qiman Tagh Eastern Kunlun Mountains during the Paleogene. Additionally, the isolines present a remarkable northward migration since the late Eocene, which indicates the boundary of the Cenozoic Qaidam Basin that withdrew northward since the late Eocene. The specific location of the southern source area of the Qaidam Basin can be deduced at the Adatan fault, the middle of the present-day Eastern Kunlun Mountains. This result also supports the idea that the Qaidam Basin was an independent basin during the early Cenozoic era, and the Eastern Kunlun Mountains have already been exhumed during that time, serving as a prominent source of clastic sediments in the southwestern Qaidam Basin.

Rock-Eval pyrolysis and the biomarker composition of organic matter were systematically studied in hydrate-bearing sediments from the Shenhu area, South China Sea. The n-alkane distribution patterns revealed that the organic matter in the sediments appeared to originate from mixed sources of marine autochthonous input, terrestrial higher plants, and ancient reworked organic matter. The low total organic carbon contents (average < 0.5%) and the low hydrogen index (HI, 2+ hydrate-bound gases. The biomarker of methanogens, squalane, was recognized in the sediments of this study, possibly suggesting the generation of secondary microbial gases which are coupled with the biodegradation of the deep allochthonous hydrocarbons.

Objective This study aimed to analyze the effects of maternal weight on adverse pregnancy outcomes. Methods Data were retrospectively collected from a hospital in Wuhan, China. A total of 1593 pregnant women with singletons were included. Adverse outcomes during pregnancy, such as small for gestational age (SGA), large for gestational age (LGA), and hypertensive disorders in pregnancy (HDP) were analyzed. Results The risks of low birth weight, SGA, and preterm birth were significantly higher in the inadequate gestational weight gain (GWG) group compared with the adequate GWG group. GWG over the guidelines was related to a higher risk of macrosomia, LGA, cesarean section, and HDP than GWG within the guidelines. The risks of low birth weight (OR = 5.082), SGA (OR = 3.959), preterm birth (OR = 3.422), and gestational diabetes mellitus (OR = 1.784) were significantly higher in women with a normal pre-pregnancy body mass index (BMI) and inadequate GWG compared with women with a normal pre-pregnancy BMI and adequate GWG. The risks of macrosomia (OR = 3.654) and HDP (OR = 1.992) were increased in women with normal pre-pregnancy BMI and excessive GWG. Conclusion Women with an abnormal BMI and inappropriate GWG have an increased risk of adverse maternal and infant outcomes. Weight management during the perinatal period is required.

Molecularly imprinted mesoporous materials (MIMs) were synthesized to improve the adsorption performance of Cytochrome c (Cyt c) by using an imidazolium-based amphiphilic ionic liquid 1-octadecyl-3-methylimidazolium chloride (C18MIMCl) as surfactant in aqueous solution via the epitope imprinting approach. The surface-exposed C-terminus nonapeptide of Cyt c (residues 96–104, AYLKKATNE) was utilized as the imprinted template. The nitrogen adsorption-desorption, thermo-gravimetric analysis, and transmission electron microscopy verified the successful preparation of MIMs with ordered mesoporous structure. The adsorption isotherm studies showed that the obtained MIMs exhibited superior adsorption capacity toward Cyt c of 86.47 mg·g−1 because of the high specific surface areas of 824 m2·g−1, and the appropriate pore size promoted the mass transfer of Cyt c, causing a rapid adsorption equilibrium within 20 min. Furthermore, these MIMs still remained excellent selectivity and recognition ability according to the selective as well as the competitive adsorption studies, suggesting that the molecularly imprinted mesoporous materials is expected to be used in the field of highly efficient separation and enrichment of proteins.

Novel types of polymeric membranes containing molecular recognition sites for selective recognition of lysozyme (Lyz) have been prepared using a surface-initiated atom transfer radical polymerization approach. The surface compositions of the regenerated cellulose (RC) membranes before and after polymerization were characterized by X-ray photoelectron spectroscopy analysis, which demonstrated that the molecular imprinting layer was successfully fabricated onto the surface of RC membranes. The selective recognition of Lyz molecularly imprinted membranes (Lyz–MIMs) for Lyz was evaluated by protein adsorption penetration tests. It was found that Lyz–MIMs have excellent adsorption capacity and specific recognition for Lyz adsorption from aqueous solutions. In the presence of competitive substances, a separation factor of 23.08 was achieved. The molecularly imprinted RC composite membrane is promising for separation and purification of specific protein compositions in biosamples. In addition, it may have good prospect for enriching target protein, which requires further study.

HERG K(+) channel, the genetic counterpart of rapid delayed rectifier K(+) current in cardiac cells, is responsible for many cases of inherited and drug-induced long QT syndromes. HERG has unusual biophysical properties distinct from those of other K(+) channels. While the conventional pulse protocols in patch-clamp studies have helped us elucidate these properties, their limitations in assessing HERG function have also been progressively noticed. We employed AP-clamp techniques using physiological action potential waveforms recorded from various regions of canine heart to study HERG function in HEK293 cells and identified several novel aspects of HERG function. We showed that under AP-clamp IHERG increased gradually with membrane repolarization, peaked at potentials around 20-30 mV more negative than revealed by pulse protocols and at action potential duration (APD) to 60%-70% full repolarization, and fell rapidly at the terminal phase of repolarization. We found that the rising phase of IHERG was conferred by removal of inactivation and the decaying phase resulted from a fall in driving force, which were all determined by the rate of membrane repolarization. We identified regional heterogeneity and transmural gradient of IHERG when quantified with the area covered by IHERG trace. In addition, we observed regional and transmural differences of IHERG in response to dofetilide blockade. Finally, we characterized the influence of HERG function by selective inhibition of other ion currents. Based on our results, we conclude that the distinct biophysical properties of HERG reported by AP-clamp confer its unique function in cardiac repolarization thereby in antiarrhythmia and arrhythmogenesis.

Developing durable and sustainable flame retardant (FR) polyamide 6 (PA6) fabric is of great interest. Herein, an eco-friendly Maillard reaction product (MRP) was developed by carbonyl-amino condensation between glucose and thiourea. Then, the functional PA6 fabric was developed through an exhaustion process. We further explored the anti-dripping ability, flame retardancy and washing durability, FR mechanism and physical properties of MRP-modified PA6 fabric. The modified PA6 fabric possessed a high LOI of 31.6% and a low damaged length of 11.3 cm without dripping action. The smoke emission was also reduced by 38.2% after MRP modification, although the Caramel skeleton exerted a scaffold effect with PA6. The MRP macromolecule inhibited PA6 flammability through gas-phase FR mechanism. In addition, the MRP macromolecule could firmly adsorb on PA6 fabric, corresponding to superior washing durability, and the V-0 rate was also reached after 40 washings. The modified PA6 fabric also had a yellowish-brown color and improved tensile strength.

The fabrication of long-lasting flame retardant wool textiles through an eco-friendly scheme is still an urgent task. In the present study, an eco-friendly and innovative hybrid silica sol with core-shell structure was prepared by using phytic acid (PA) as catalyst and dopant for tetraethoxysilane. PA/silica organic-inorganic hybrid sol (PA/silica sol) was then employed to produce durable flame retardant wool fabric using a combined nanoparticle adsorption and pad-dry-cure procedure. The treated wool had enhanced thermal stability and greatly suppressed smoke production capacity. It could still be self-extinguishing after 30 washing cycles. The present approach brought no great negative influence on the handle and mechanical performance of wool fabric. The PA/silica sol network was found to participate in the degradation of the treated wool in the solid phase. The formation of highly inflated char during burning also revealed the flame retarding activity of the PA/silica sol on wool by a condensed charring action. Keywords: Sol-gel, Nanotechnology, Silica, Phytic acid, Wool, Flame retardancy