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Abstract Immune-based checkpoint therapy has made significant progress in cancer treatment, but its therapeutic effect is limited. A replication-defective adenovirus (Ad) vaccine encoding tumor antigen carbonic anhydrase IX (CAIX) combined with Ad-encoding immune checkpoint PD-L1 was developed to treat renal carcinoma. Three tumor models, subcutaneous, lung metastasis and orthotopic tumor were established, and Ad vaccines were used to immunize them and evaluate the vaccine’s therapeutic effect. Compared to the single Ad vaccine group, the subcutaneous tumor growth was significantly reduced in Ad-CAIX/Ad-PD-L1 combination group. Co-immunization of Ad-CAIX/Ad-PD-L1 enhanced the induction and maturation of CD11c+ or CD8+CD11c+ DCs in the spleen and tumor and promoted the strong tumor-specific CD8+ T cell immune responses. In vivo CD8 T cell deletion assay showed that the anti-tumor effect of the Ad-CAIX/Ad-PD-L1 vaccine was mainly dependent on functional CD8+ T cell immune responses. Furthermore, the Ad-CAIX/Ad-PD-L1 vaccine effectively inhibited tumor growth and lung metastasis in metastatic or orthotopic models. These results indicate that the combination strategy of the immune checkpoint vaccine shows promising potential as an approach for malignant tumor therapy.

Abstract Soil nitrogen (N) is a vital source of nutrients for maintaining soil fertility and crop production. However, the effect of biochar application rate on the mechanism of organic N transformation and the contribution of enzyme mineralization is still unclear. Therefore, we conducted two 5‐year field experiments in contrasting soils (Phaeozem and Luvisol) with biochar application rate at 0 t hm−2 (CK, 0), 22.5 t hm−2 (D1, 1%), 67.5 t hm−2 (D2, 3%), and 112.5 t hm−2 (D3, 5%) to investigate the potential effects of biochar application rate on soil organic nitrogen (N) turnover and its linkage to enzymatic mineralization in contrasting soil. The results showed that soil organic carbon (SOC) and microbial biomass nitrogen (MBN) contents, microbial biomass carbon to nitrogen ratio (MBC:MBN) and protease activity are significantly influenced by biochar application rate whereas not by soil type. Ammonium nitrogen (NH4+‐N) and nitrate nitrogen (NO3−‐N) contents, and dehydrogenase activity are significantly changed by soil type whereas not by biochar application rate. Based on the redundancy analysis, we found that organic N fractions are associated with MBN, SOC, and protease in Phaeozem, but related to protease activity in Luvisol. Our findings indicate that organic N turnover is not only related to the bioavailability of N but also requires carbon substrates in Phaeozem, whereas the transformation of organic N in Luvisol is dominated by enzymatic mineralization as the relatively low level of bioavailable N.

Abstract Imaging biomolecules in real space is crucial for gaining a comprehensive understanding of the properties and functions of biological systems at the most fundamental level. Among the various imaging techniques available for biomolecules and their assembled nanostructures, scanning probe microscopy (SPM) provides a powerful and nondestructive imaging option. SPM is unique in visualizing intrinsically disordered biomolecules at the nanometer scale (e.g., glycans). This review highlights recent achievements in studying biomolecules using SPM technique, focusing on DNA bases, amino acids, proteins, and glycans. The atomic‐level analysis of biomolecules made possible by SPM allows for a more accurate definition of the local structure–property relationship. High‐resolution SPM imaging of single biomolecules offers a new way to study basic processes of life at the molecular level.

The Idaea proximaria complex is reviewed and four new species are described from China: Idaea rectangularis Cheng & Han, sp. nov. from Guangxi and Fujian provinces, Idaea rectispina Cheng & Han, sp. nov. from Hunan province, Idaea setosa Xue & Han, sp. nov. from Hainan province, and Idaea linearis Xue & Han, sp. nov. from Hubei and Shaanxi provinces. Illustrations of adults and genitalia of the new species and known species are presented, and the variations in the form of the aedeagus of Idaea proximaria are discussed.

Many efforts have been made to understand excitotoxicity and develop neuroprotectants for the therapy of ischemic stroke. The narrow treatment time window is still to be solved. Given that the ischemic core expanded over days, treatment with an extended time window is anticipated. Bestrophin 1 (BEST1) belongs to a bestrophin family of calcium-activated chloride channels. We revealed an increase in neuronal BEST1 expression and function within the peri-infarct from 8 to 48 h after ischemic stroke in mice. Interfering the protein expression or inhibiting the channel function of BEST1 by genetic manipulation displayed neuroprotective effects and improved motor functional deficits. Using electrophysiological recordings, we demonstrated that extrasynaptic glutamate release through BEST1 channel resulted in delayed excitotoxicity. Finally, we confirmed the therapeutic efficacy of pharmacological inhibition of BEST1 during 6–72 h post-ischemia in rodents. This delayed treatment prevented the expansion of infarct volume and the exacerbation of neurological functions. Our study identifies the glutamate-releasing BEST1 channel as a potential therapeutic target against ischemic stroke with a wide time window.

Abstract Background Polyhydroxybutyrate (PHB) is currently the most common polymer produced by natural bacteria and alternative to conventional petrochemical-based plastics due to its similar material properties and biodegradability. Massilia sp. UMI-21, a newly found bacterium, could produce PHB from starch, maltotriose, or maltose, etc. and could serve as a candidate for seaweed-degrading bioplastic producers. However, the genes involved in PHB metabolism in Massilia sp. UMI-21 are still unclear. Results In the present study, we assembled and annotated the genome of Massilia sp. UMI-21, identified genes related to the metabolism of PHB, and successfully constructed recombinant Escherichia coli harboring PHB-related genes (phaA2, phaB1 and phaC1) of Massilia sp. UMI-21, which showed up to 139.41% more product. Also, the vgb gene (encoding Vitreoscilla hemoglobin) was introduced into the genetically engineered E. coli and gained up to 117.42% more cell dry weight, 213.30% more PHB-like production and 44.09% more product content. Fermentation products extracted from recombinant E. coli harboring pETDuet1-phaA2phaB1-phaC1 and pETDuet1-phaA2phaB1-phaC1-vgb were identified as PHB by Fourier Transform Infrared and Proton nuclear magnetic resonance spectroscopy analysis. Furthermore, the decomposition temperature at 10% weight loss of PHB extracted from Massilia sp. UMI-21, recombinant E. coli DH5α-pETDuet1-phaA2phaB1-phaC1 and DH5α-pETDuet1-phaA2phaB1-phaC1-vgb was 276.5, 278.7 and 286.3 °C, respectively, showing good thermal stability. Conclusions Herein, we presented the whole genome information of PHB-producing Massilia sp. UMI-21 and constructed novel recombinant strains using key genes in PHB synthesis of strain UMI-21 and the vgb gene. This genetically engineered E. coli strain can serve as an effective novel candidate in E. coli cell factory for PHB production by the rapid cell growth and high PHB production.

AIM: To compare the macular ganglion cell-inner plexiform layer (GCIPL) thickness, retinal nerve fiber layer (RNFL) thickness, optic nerve head (ONH) parameters, and retinal vessel density (VD) measured by spectral-domain optical coherence tomography (SD-OCT) and analyze the correlations between them in the early, moderate, severe primary angle-closure glaucoma (PACG) and normal eyes. METHODS: Totally 70 PACG eyes and 20 normal eyes were recruited for this retrospective analysis. PACG eyes were further separated into early, moderate, or severe PACG eyes using the Enhanced Glaucoma Staging System (GSS2). The GCIPL thickness, RNFL thickness, ONH parameters, and retinal VD were measured by SD-OCT, differences among the groups and correlations within the same group were calculated. RESULTS: The inferior and superotemporal sectors of the GCIPL thickness, rim area of ONH, average and inferior sector of the retinal VD were significantly reduced (all P

Local geometric information and discontinuity features are key aspects of the analysis of the evolution and failure mechanisms of unstable rock blocks in rock tunnels. This study demonstrates the integration of terrestrial laser scanning (TLS) with distinct element method for rock mass characterization and stability analysis in tunnels. TLS records detailed geometric information of the surrounding rock mass by scanning and collecting the positions of millions of rock surface points without contact. By conducting a fuzzy K-means method, a discontinuity automatic identification algorithm was developed, and a method for obtaining the geometric parameters of discontinuities was proposed. This method permits the user to visually identify each discontinuity and acquire its spatial distribution features (e.g. occurrences, spacings, trace lengths) in great detail. Compared with hand mapping in conventional geotechnical surveys, the geometric information of discontinuities obtained by this approach is more accurate and the identification is more efficient. Then, a discrete fracture network with the same statistical characteristics as the actual discontinuities was generated with the distinct element method, and a representative numerical model of the jointed surrounding rock mass was established. By means of numerical simulation, potential unstable rock blocks were assessed, and failure mechanisms were analyzed. This method was applied to detection and assessment of unstable rock blocks in the spillway and sand flushing tunnel of the Hongshiyan hydropower project after a collapse. The results show that the noncontact detection of blocks was more labor-saving with lower safety risks compared with manual surveys, and the stability assessment was more reliable since the numerical model built by this method was more consistent with the distribution characteristics of actual joints. This study can provide a reference for geological survey and unstable rock block hazard mitigation in tunnels subjected to complex geology and active rockfalls.

Rockfall intrusion detection is crucial for the safety management of railway operations, and video detection methods help reduce deployment costs and improve detection efficiency. Mainstream neural network-based video detection methods have rapidly evolved in recent years but struggle to adapt to complex scenarios such as existing railway slope constructions due to weak generalization ability, low accuracy, and limited information acquisition. Therefore, this paper introduces a dynamic neural network detection model and establishes a dataset for rockfall intrusions in existing railway slope scenarios. The model initially relies on the YOLOv5 neural network, adopting an activation function suitable for the target scenario and addressing overfitting to achieve precise target recognition. Based on the neural network, the model dynamically detects rolling rockfalls by integrating a background subtraction algorithm based on the Gaussian Mixture Model and captures target dimensions using monocular vision technology, thus broadening the dimensions of detection information. Trials conducted on a railway in Shandong, China, demonstrate that the model accurately identifies moving rockfalls along the railway slopes and acquires the dimensions of moving rockfalls, successfully filtering out low-risk targets in the scene.

Debris flow, driven by natural events like heavy rainfall and snowmelt, involves sediment, rocks, and water, posing destructive threats to life and infrastructure. The accurate prediction of its activity range is crucial for prevention and mitigation efforts. Cellular automata circumvent is the cumbersome process of solving partial differential equations, thereby efficiently simulating complex dynamic systems. Given the anisotropic characteristics of square cells in the simulation of dynamic systems, this paper proposes a novel approach, utilizing a hexagonal cellular automaton for the numerical simulation of debris flows, where the direction judgment efficiency increased by 25%. Employing cubic interpolation, the model thereby determines the central elevation of each hexagonal cell. By modifying the flow direction function and stopping conditions, it achieves more accurate predictions of the debris flow run-out extent. This method was applied to the 2010 Yohutagawa debris flow event and the flume test. To evaluate the simulation’s accuracy, the Ω value and Fβ score were used. The Ω value is a comprehensive evaluation factor that takes into account missed or misjudgment areas. On this basis, the Fβ score emphasizes that the missed identification of debris flow areas will bring greater harm. Research indicates that the Ω value showed improvements of 6.47% and 3.96%, respectively, while the Fβ score improved by 3.10% and 4.61%.

Rhinogobio ventralis is a rare fish found in the Yangtze River in China and has significant ecological and economic value. In this study, a bacterial strain (RV-JZ01) was isolated from the livers of diseased R. ventralis. This isolate was identified as Aeromonas veronii based on its morphology, biochemical features and 16S rDNA phylogenetic analysis. The artificial infection of healthy R. ventralis (16 ± 2 cm) with RV-JZ01 resulted in the manifestation of clinical symptoms, in accordance with those of naturally infected fish. The 50% lethal dose (LD50) of RV-JZ01 for R. ventralis was 6.3 × 106 CFU/mL. Histopathological examination revealed various pathological changes in the diseased fish, including intestinal villus swelling and rupture, hepatocyte vacuolization, renal tubular cell nuclear enlargement and pyknosis, and myocardial fiber fracture and atrophy. RV-JZ01 infection significantly reduced the gut flora diversity of R. ventralis, with the relative abundances of Firmicutes and Fusobacteria increasing, and those of the Proteobacteria and Bacteroidetes decreasing. The abundance of Lactobacillus and Streptococcus dramatically increased, and the abundance of Clostridium and Escherichia reduced in the intestinal microbiota of R. ventralis infected with RV-JZ01. Antibiotic sensitivity testing revealed that RV-JZ01 was highly susceptible to 12 antimicrobials, including erythromycin, cefalexin, norfloxacin, furazolidone, sulfonamides, enrofloxacin, doxycycline, piperacillin, florfenicol, gentamicin, and lincomycin. These results contribute to the understanding of pathological alterations in R. ventralis following A. veronii infection, offering valuable data to support the implementation of disease treatment.

The Qaidam Block, located at the northern Qinghai–Tibet Plateau, is a pivotal area in unraveling the closure time of the Kunlun Ocean basin which might have recorded the transformation process between the Proto-Tethys and Paleo-Tethys Ocean basins. However, the late Triassic position of the Qaidam Block remains enigmatic, largely due to the scarcity of paleomagnetic data essential for quantitatively determining its paleolatitude. The widespread presence of the Elashan formation, particularly along the southern periphery of the Qaidam block, presents good material for conducting paleomagnetic work. Nevertheless, the primary magnetic carriers preserved within the Elashan formation might be influenced by multiple tectonic thermal events, particularly those associated with collisions between southern blocks and the Qaidam Block. Here we present rock magnetism and magnetic fabrics studies to identify the content and composition of magnetic minerals within the Elashan formation. The rock magnetic and petrologic results show that the magnetic carriers in the samples from the Elashan formation are dominated by magnetite with a small amount of goethite, pyrrhotite, and hematite. The results of Anisotropy in Magnetic Susceptibility indicate that the south of the Longwalangku section might not be obviously influenced by the tectonic events. Our results also provided guidance for future paleomagnetic research, emphasizing the importance of conducting further sampling away from adjacent faults, particularly in the southern Longwalangku area.

The high prevalence of constipation after fracture surgery brings intolerable discomfort to patients on the one hand, and affects post-surgery nutrient absorption on the other hand, resulting in poor prognosis. Given the acknowledged probiotic properties of Lactobacillus rhamnosus, 100 fracture patients with post-surgery constipation were centrally enrolled and administered orally with L. rhamnosus JYLR-127 to assess the efficacy of probiotic-adjuvant therapy in alleviating post-fracture constipation symptoms. The results showed that L. rhamnosus JYLR-127 improved fecal properties, promoted gastrointestinal recovery, and relieved constipation symptoms, which were mainly achieved by elevating Firmicutes (p < 0.01) and descending Bacteroidetes (p < 0.001), hence remodeling the disrupted intestinal microecology. In addition, blood routine presented a decrease in C-reactive protein levels (p < 0.05) and an increase in platelet counts (p < 0.05) after probiotic supplementation, prompting the feasibility of L. rhamnosus JYLR-127 in anti-inflammation, anti-infection and hemorrhagic tendency prevention after fracture surgery. Our study to apply probiotics in ameliorating constipation after fracture surgery is expected to bless the bothered patients, and provide broader application scenarios for L. rhamnosus preparations.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces direct cytopathic effects, complicating the establishment of low-cytotoxicity cell culture models for studying its replication. We initially developed a DNA vector-based replicon system utilizing the CMV promoter to generate a recombinant viral genome bearing reporter genes. However, this system frequently resulted in drug resistance and cytotoxicity, impeding model establishment. Herein, we present a novel cell culture model with SARS-CoV-2 replication induced by Cre/LoxP-mediated DNA recombination. An engineered SARS-CoV-2 transcription unit was subcloned into a bacterial artificial chromosome (BAC) vector. To enhance biosafety, the viral spike protein gene was deleted, and the nucleocapsid gene was replaced with a reporter gene. An exogenous sequence was inserted within NSP1 as a modulatory cassette that is removable after Cre/LoxP-mediated DNA recombination and subsequent RNA splicing. Using the PiggyBac transposon strategy, the transcription unit was integrated into host cell chromatin, yielding a stable cell line capable of inducing recombinant SARS-CoV-2 RNA replication. The model exhibited sensitivity to the potential antivirals forsythoside A and verteporfin. An innovative inducible SARS-CoV-2 replicon cell model was introduced to further explore the replication and pathogenesis of the virus and facilitate screening and assessment of anti-SARS-CoV-2 therapeutics.

Rice blast, caused by the fungus Magnaporthe oryzae, and brown planthopper (BPH) infestation are two of the most destructive problems of rice production in China. The development of multi-resistant varieties is widely recognized as the most efficient and environmentally friendly approach to controlling crop diseases and pests. Functional molecular markers (FMMs) have been developed from functional variants in the genic region associated with trait variation, greatly enhancing the efficiency of identifying and pyramiding valuable genes in crop breeding. In this study, two FMMs and a multiplex PCR amplification system were developed for two major broad-spectrum BPH resistance genes, Bph6 and Bph9. With the assistance of FMMs in the multi-resistant rice restorer-line development pipeline, two lines (Huahui7713 and Huahui3006) with blast and BPH resistance were developed by pyramiding three resistance genes Pigm, Bph6 and Bph9. Two new hybrid rice varieties, Weiliangyou7713 and Xuanliangyou3006, derived from Huahui7713 and Huahui3006, have been developed and commercialized in China. Weiliangyou7713 and Xuanliangyou3006 exhibit enhanced resistance to both blast and BPH, while maintaining optimal yield and grain quality. The adoption of Weiliangyou7713 continues to expand, now being cultivated on a large scale, which is promising for its future role in reducing the dependence on chemical fungicides and pesticides in rice production. This suggests that the implementation of Huahui7713 and Huahui3006 in targeted breeding programs could be highly beneficial for developing rice varieties with strong resistance to blast and BPH.

The breeding of laying hens and broilers in China has increased tremendously. Wet organic fertilizer prepared from hen manure using high-temperature container fermentation preserves high levels of nutrients and a diverse microbial community. We applied low doses of organic fertilizer to peanuts in the black soil area of China’s northeastern region. Based on the calculation of nitrogen content, treatments were set as follows: chemical fertilizer (PCF), organic fertilizer (POF, 4500 kg·ha−1), and replacement of 50% chemical fertilizer with organic fertilizer (PR, 2250 kg·ha−1). Compared to the plots with chemical fertilizers, the use of organic fertilizer and replacing 50% of the chemical fertilizers with organic fertilizer significantly increased peanut yields. Both the organic fertilizer and replacing 50% of the chemical fertilizers with organic fertilizer did not significantly affect the activities of the most tested soil enzymes related to carbon transformation and the absolute abundance of microorganisms. However, they did significantly enhance soil dehydrogenase and α-glucosidase. The community abundance ratio of fungi/bacteria trended downward, leading to soil with a high-fertility bacterial composition. The replacement of 50% chemical fertilizer with organic fertilizer significantly enhanced the species richness and diversity of the bacterial and fungal communities. Organic fertilizer treatment significantly increased the relative abundance of Gemmatimonas and Sphingomonas. The relative abundance of Mycobacterium in the treatment where 50% of the chemical fertilizers were replaced with organic fertilizer was significantly lower than that in the organic fertilizer treatment. PCoA results showed that the low-dose organic fertilizer treatment, replacing 50% of the chemical fertilizers with organic fertilizer, had a significant impact on the composition of soil bacterial communities.

The preparation of electrocatalysts with high performance for the ethanol oxidation reaction is vital for the large-scale commercialization of direct ethanol fuel cells. Here, we successfully synthesized a high-performance electrocatalyst of a AuPd alloy with a decreased alloying degree via pulsed laser irradiation in liquids. As indicated by the experimental results, the photochemical effect-induced surficial deposition of Pd atoms, combined with the photothermal effect-induced interdiffusion of Au and Pd atoms, resulted in the formation of AuPd alloys with a decreased alloying degree. Structural characterization reveals that L-AuPd exhibits a lower degree of alloying compared to C-AuPd prepared via the conventional co-reduction method. This distinct structure endows L-AuPd with outstanding catalytic activity and stability in EOR, achieving mass and specific activities as high as 16.01 A mgPd−1 and 20.69 mA cm−2, 9.1 and 5.2 times than that of the commercial Pd/C respectively. Furthermore, L-AuPd retains 90.1% of its initial mass activity after 300 cycles. This work offers guidance for laser-assisted fabrication of efficient Pd-based catalysts in EOR.

In the original publication [...]

The emergence of multi-drug-resistant (MDR) pathogens has considerably challenged the development of new drugs. Probiotics that inhibit MDR pathogens offer advantages over chemical antibiotics and drugs due to their increased safety and fewer side effects. This study reported that Weissella cibaria P-8 isolated from pickles showed excellent antibacterial activity against intestinal pathogens, particularly the antibacterial activity against MDR Escherichia coli B2 was the highest. This study showed that the survival rates of W. cibaria P-8 at pH 2.0 and 0.3% bile salt concentration were 72% and 71.56%, respectively, and it still had antibacterial activity under pepsin, trypsin, protease K, and catalase hydrolysis. Moreover, W. cibaria P-8 inhibits the expression of inflammatory factors interleukin-1β, tumor necrosis factor-α, and interleukin-6, upregulates the interleukin-10 level, and increases total antioxidant capacity and superoxide dismutase enzyme activity in serum. W. cibaria P-8 also efficiently repairs intestinal damage caused by E. coli infection. The gut microbiota analysis demonstrated that W. cibaria P-8 colonizes the intestine and increases the abundance of some beneficial intestinal microorganisms, particularly Prevotella. In conclusion, W. cibaria P-8 alleviated MDR E. coli-induced intestinal inflammation by regulating inflammatory cytokine and enzyme activity and rebalancing the gut microbiota, which could provide the foundation for subsequent clinical analyses and probiotic product development.

Nanocellulose materials have been widely used in biomedicine, food packaging, aerospace, composite material, and other fields. In this work, cellulose obtained from Camellia shells through alkali boiling and subbleaching was micro-dissolved and regenerated using the DMAc (N,N-Dimethylacetamide)/LiCl system, and TOCNs (TEMPO-oxidized cellulose nanofibers) with different degrees of oxidation. The membrane was prepared by filtration of polytetrafluoroethylene (pore size 0.1 μm), and the oxidized nanocellulose film was obtained after drying, Then, the crystallinity, mechanical properties and oxygen barrier properties of the TOCN film were investigated. Furthermore, based on TS (tea saponin) from Camellia oleifera seed cake and TOCNs, TS-TOCN film was prepared by the heterogeneous reaction. The TS-TOCN film not only shows excellent oxygen barrier properties (the oxygen permeability is 2.88 cc·m−2·d−1) but also has good antibacterial effects on both Gram-negative and Gram-positive bacteria. The antibacterial property is comparable to ZnO-TOCN with the same antibacterial content prepared by the in-situ deposition method. Antioxidant activity tests in vitro showed that TS-TOCN had a significant scavenging effect on DPPH (2,2-Diphenyl-1-picrylhydrazyl) radicals. This design strategy makes it possible for inexpensive and abundant Camellia oleifera remainders to be widely used in the field of biobased materials.

Tight sandstone and shale oil and gas are the key targets of unconventional oil and gas exploration in the lake-delta sedimentary systems of China. Understanding the coevolutionary diagenesis of sandstone and shale reservoirs is crucial for the prediction of reservoir quality, ahead of drilling, in such systems. Thin-section description, scanning electron microscopy (SEM), X-ray diffraction (XRD), fluid inclusion analysis, porosity and permeability tests, high-pressure mercury intrusion (HPMI) measurements and nuclear magnetic resonance tests (NMR) were used to reveal the coevolutionary diagenetic mechanisms of a sandstone and shale reservoir in the Lianggaoshan Formation of the Eastern Sichuan Basin, China. The thermally mature, organic-matter-rich, dark shale of layer3 is the most important source rock within the Lianggaoshan Formation. It started to generate abundant organic acids at the early stage of mesodiagenesis and produced abundant hydrocarbons in the early Cretaceous. Porewater with high concentrations of Ca2+ and CO32− entered the sandstone reservoir from dark shale as the shale was compacted during burial. Potassium feldspar dissolution at the boundary of the sandstone was more pervasive than at the center of the sandstone. The K+ released by potassium feldspar dissolution migrated from the sandstone into mudstone. Grain-rimming chlorite coats occurred mainly in the center of the sandstone. Some silica exported from the shale was imported by the sandstone boundary and precipitated close to the shale/sandstone boundary. Some intergranular dissolution pores and intercrystal pores were formed in the shale due to dissolution during the early stages of mesodiagenesis. Chlorite coats, which precipitated during eodiagenesis, were beneficial to the protection of primary pore space in the sandstone. Calcite cement, which preferentially precipitated at the boundary of sandstone, was not conducive to reservoir development. Dissolution mainly occurred at the early stage of mesodiagenesis due to organic acids derived from the dark shale. Calcite cement could also protect some primary pores from compaction and release pore space following dissolution. The porosity of sandstone and shale was mainly controlled by the thickness of sandstone and dark shale.

Pulpitis is a common and frequent disease in dental clinics. Although vital pulp therapy and root canal treatment can stop the progression of inflammation, they do not allow for genuine structural regeneration and functional reconstruction of the pulp–dentin complex. In recent years, with the development of tissue engineering and regenerative medicine, research on stem cell-based regenerative endodontic therapy (RET) has achieved satisfactory preliminary results, significantly enhancing its clinical translational prospects. As one of the crucial paracrine effectors, the roles and functions of exosomes in pulp–dentin complex regeneration have gained considerable attention. Due to their advantages of cost-effectiveness, extensive sources, favorable biocompatibility, and high safety, exosomes are considered promising therapeutic tools to promote dental pulp regeneration. Accordingly, in this article, we first focus on the biological properties of exosomes, including their biogenesis, uptake, isolation, and characterization. Then, from the perspectives of cell proliferation, migration, odontogenesis, angiogenesis, and neurogenesis, we aim to reveal the roles and mechanisms of exosomes involved in regenerative endodontics. Lastly, immense efforts are made to illustrate the clinical strategies and influencing factors of exosomes applied in dental pulp regeneration, such as types of parental cells, culture conditions of parent cells, exosome concentrations, and scaffold materials, in an attempt to lay a solid foundation for exploring and facilitating the therapeutic strategy of exosome-based regenerative endodontic procedures.

Adaptation aftereffects—in which prolonged prior experience (adaptation) can bias the subsequent judgment of ambiguous stimuli—are a ubiquitous phenomenon. Numerous studies have found behaviorally stable adaptation aftereffects in a variety of areas. However, it is unclear which brain regions are responsible for this function, particularly in the case of high-level emotional adaptation aftereffects. To address this question, the present study used fMRI technology to investigate the neural mechanism of emotional adaptation aftereffects. Consistent with previous studies, we observed typical emotional adaptation effects in behavior. Specifically, for the same morphed facial images, participants perceived increased sadness after adapting to a happy facial image and increased happiness after adapting to a sad facial image. More crucially, by contrasting neural responses to ambiguous morphed facial images (i.e., facial images of intermediate morph levels) following adaptation to happy and sad expressions, we demonstrated a neural mechanism of emotional aftereffects supported by the left amygdala/insula, right angular gyrus, and right inferior frontal gyrus. These results suggest that the aftereffects of emotional adaptation are supported not only by brain regions subserving emotional processing but also by those subserving cognitive control.

Herein, prepared Ti40–Ni40–Nb20 (at. %) alloy was utilized as a filler metal to join Al2O3 ceramic. The effect of brazing temperature and holding time on the interfacial microstructure evolution and shear strength of joints were analyzed systematically. The results demonstrated that AlNi2Ti, Ni6Nb7 and layered Ni2Ti4O formed adjacent to Al2O3 ceramic. The microstructure of Al2O3 joint brazed at 1200 °C for 10 min was Al2O3/AlNi2Ti + Ni6Nb7 + Ni2Ti4O/Ti2Ni/TiNi + Nb solid solution (Nbss) eutectic + (Ti,Nb)2Ni/Ti2Ni/Ni2Ti4O + Ni6Nb7 + AlNi2Ti/Al2O3. As brazing temperature or holding time raised, the Ni2Ti4O layer nearby Al2O3 ceramic, AlNi2Ti and Ni6Nb7 developed tremendously whereas TiNi + Nbss eutectic structure gradually increased and tended to coarsen. Eventually, the TiNi + Nbss eutectic structure and (Ti,Nb)2Ni in brazing seam were replaced gradually by bulk Ni6Nb7 because of the depleted Ti element. The shear strength of joints was first increased and then decreased with the increasing of the temperature/holding time. The Al2O3/Al2O3 joints brazed at 1200 °C for 10 min received the maximum shear strength of 93.2 MPa, and the joints fractured primarily at the brazing seam/Al2O3 interface.

Abstract Background Radiation-induced xerostomia and oral mucositis are serious complications of radiation therapy for head and neck cancers. Current treatment options have limited efficacy. Mesenchymal stem cell (MSC) therapy has shown promising results in supporting the restoration of glandular secretion function and the regeneration of damaged tissues. This study aim to (1) assess the quality of evidence for MSCs treatment in rodent models of radiation-induced oral complications and (2) determine whether MSCs can improve the therapeutic effect of radiation-induced oral mucositis. Methods Intervention studies using MSCs in rodent models were comprehensively retrieved in the Pubmed, Medline, Embase, Web of Science, and Cochrane library databases on June 1, 2022. The quality of all in vivo experiments was assessed using SYRCLE, and this article is written following the PRISMA guidelines. Results A total of 12 studies were included in this systematic review. The study found that in animal models of radiation-induced xerostomia, MSCs could increase salivary protein secretion, improve SFR, shorten the salivary lag time, anti-apoptosis, etc. In animal models of radiation-induced oral mucositis, MSCs improve the micromorphology and macromorphology of RIOM. Moreover, the effect of MSCs on the modification of ulcer duration and latency may be related to the time of MSCs transplantation but further studies are needed. Conclusion The results of our systematic review suggest that MSCs appeared to be effective in the treatment of radiation-induced xerostomia and oral mucositis. Graphical Abstract

Abstract Background The aim was to develop a personalized survival prediction deep learning model for cervical adenocarcinoma patients and process personalized survival prediction. Methods A total of 2501 cervical adenocarcinoma patients from the surveillance, epidemiology and end results database and 220 patients from Qilu hospital were enrolled in this study. We created our deep learning (DL) model to manipulate the data and evaluated its performance against four other competitive models. We tried to demonstrate a new grouping system oriented by survival outcomes and process personalized survival prediction by using our DL model. Results The DL model reached 0.878 c-index and 0.09 Brier score in the test set, which was better than the other four models. In the external test set, our model achieved a 0.80 c-index and 0.13 Brier score. Thus, we developed prognosis-oriented risk grouping for patients according to risk scores computed by our DL model. Notable differences among groupings were observed. In addition, a personalized survival prediction system based on our risk-scoring grouping was developed. Conclusions We developed a deep neural network model for cervical adenocarcinoma patients. The performance of this model proved to be superior to other models. The results of external validation supported the possibility that the model can be used in clinical work. Finally, our survival grouping and personalized prediction system provided more accurate prognostic information for patients than traditional FIGO stages.

Abstract Background Nicotine dependence is a significant public health issue, and understanding the factors associated with nicotine dependence in this population is crucial for developing effective interventions. This study examined the association between family functioning and nicotine dependence levels of smoking fathers based on the McMaster model of family functioning (MMFF), providing evidence for future interventions. Methods In this study, we selected fathers of first- to fifth-grade students from 10 pilot elementary schools in Qingdao whose families smoked. We used the Fagerstrom test to assess nicotine dependence and the Family Assessment Device to evaluate family functioning. We performed univariate analysis to compare differences among those with different levels of nicotine dependence, and we used an ordinal logistic regression analysis to investigate the influences related to nicotine dependence. Results This study included 874 smokers, with 78.5% having mild nicotine dependence, 11.7% having moderate dependence, and 9.84% having severe dependence. Univariate analysis showed that smokers with severe dependence had lower education levels, higher prevalence of chronic diseases, more frequent alcohol consumption, and poorer family functioning compared to those with mild to moderate dependence. Ordinal logistic regression analysis showed that poorer general functioning scores (OR = 1.087, 95% CI: 1.008–1.173, P = 0.030), poorer behavioral control (OR = 1.124, 95% CI: 1.026–1.232, P = 0.012), more quit attempts, frequent alcohol consumption, and longer smoking duration may be associated with a higher likelihood of developing severe nicotine dependence. The older age of starting smoking and higher education level may be associated with a lower likelihood of developing severe nicotine dependence. However, it is important to note that the cross-sectional nature of this study precludes the determination of causal relationships. Conclusions This study finds that heavy nicotine dependence in smoking fathers is associated with risky behaviors and demographics such as longer smoking duration and frequent alcohol consumption. Targeted smoking cessation interventions are crucial for this group, taking these specific factors into consideration. Family functioning, particularly general functioning and behavioral control, may also be linked to nicotine dependence, indicating the need for further research in this area.

Abstract Background Neuropsychiatric involvement is one of the major concerns in systemic lupus erythematosus (SLE). The therapeutic effect of intrathecal treatment of methotrexate and dexamethasone has been investigated in some exploratory studies, but its influence on the long-term prognosis of neuropsychiatric SLE (NPSLE) remains unknown. Methods This was a propensity score-matched retrospective study. Outcomes at discharge and time free from NPSLE relapse or death were evaluated by multivariate logistic regression, survival analysis, and Cox regression as appropriate. Results Among 386 hospitalized patients with NPSLE, the median [IQR] age was 30.0 [23.0–40.0] years, and 342 patients (88.4%) were female. Of those, 194 patients received intrathecal treatment. Patients in the intrathecal treatment group had higher Systemic Lupus Erythematosus Disease Activity Index 2000 scores (median 17 vs. 14 points, IQR 12–22 vs. 10–19 points, P

High density polyethylene(HDPE) material is excellent, often made into bellows, and is an important part of the urban drainage system. The blasting seismic dynamic load is one of the key problems affecting the safety of buried pipeline structures. As a commonly used artificial source excitation method, blasting is often used to study the seismic structural response test. Combined with the characteristics of the buried typical stratum of pipelines in urban areas, full-scale blasting tests of embedded HDPE bellows are conducted. The characteristics of vibration acceleration and strain in the empty pipe under blasting vibration are monitored and analyzed. LS-DYNA is used to establish the model based on the field test conditions and verify the rationality of the model. Then, the models of different water levels are added and the dynamic response characteristics of the pipeline are calculated and analyzed. Finally, according to the max allowable stress criterion, the safety of the pipeline is evaluated.

Development of biocompatible and biodegradable 3D scaffold for biomedical application has been challenging. Herein, the application of a novel nanocomposite 3D scaffold based on poly vinyl alcohol and sodium alginate embedded with Ca2+ doped titanium dioxide nanoparticle (PVA + SA/Ca@TiO2) as bioactive material was investigated. The 3D scaffold was prepared using a solvent casting method and characterized using FTIR, SEM, XRD and TGA to study their physiochemical properties. The spectroscopy techniques were used to confirm the formation of the required poly vinyl alcohol and sodium alginate with Ca doped TiO2 nanoparticles fillers interaction by the identification of bands. The TiOH bonds and the bonds related to the interconnected network between the inorganic and the organic components from hybrids. The PVA + SA/Ca@TiO2 nanocomposite 3D scaffold was demonstrated good bioactivity to promote nucleation and growth of hydroxyapatite (HAp) in the simulated body fluid. The PVA + SA/Ca@TiO2 nanocomposite 3D scaffold supported the growth and proliferation of 3 T3 mouse fibroblast cells with strong proliferation and cell attachment. The biocompatibility and nontoxic character of the 3D scaffold was probed using fibroblast cell with over 90 % of cell viability. It offers a potential for cell attachment and captured for biomedical application.

Introduction The strategy for initiating antithrombotic therapy to prevent bioprosthetic valve thrombosis (BPVT) after transcatheter aortic valve replacement (TAVR) remains uncertain. There is still lacking evidence on the efficacy and safety of early 6 months usage of single-antiplatelet therapy (SAPT) or oral anticoagulant (OAC) after TAVR in patients without anticoagulant indications.Methods and analysis This is a multicentre, randomised controlled, open-label trial, and 650 patients undergoing TAVR from 13 top TAVR centres in China will be recruited. Each eligible participant will be randomly assigned to two groups (1:1 ratio) as (1) SAPT (aspirin 75–100 mg for 6 months) group or (2) OAC group (warfarin, therapeutic international normalised ratio at 1.8–2.5 for 6 months), both followed by sequential aspirin 75–100 mg for 6 months. Participants in both groups will be invited for three follow-up visits of 1, 6 and 12 months after discharge. We will use both the net clinical benefit endpoint (composite of all-cause mortality, myocardial infarction, stroke/transient ischaemic attacks, peripheral artery thrombosis, intracardiac thrombosis and major bleeding and disabling or life-threatening bleeding) and the BPVT endpoint evaluated by four-dimensional CT as our primary endpoints. P value of

Sucrosic dolomite, an important hydrocarbon reservoir, has long been the focus of carbonate sedimentological and reservoir geological studies. This study investigated a kind of heterogeneous sucrosic dolomite in the Lower Permian Qixia Formation of NW Sichuan Basin, which has recently been the location of giant natural gas discoveries. The heterogeneous sucrosic dolomite is characterized by coexistence of porous euhedral dolomite and tight anhedral dolomite, and it is mainly distributed in the platform-marginal shoal facies with a quasi-layered structure. Further geochemical analysis, including C, O, and Sr isotopes as well as rare earth elements, reveals that the euhedral dolomite and anhedral dolomite have similar geochemical properties to the matrix limestone representing coeval seawater, and they were mainly generated from dolomitization by the closed marine-related fluid (left-leaning REE and δPr

Tripterygium hypoglaucum (Levl.) Hutch (THH) has long been used as a remedy for rheumatoid arthritis (RA) in China. However, it is unclear whether the anti-RA mechanism of THH is associated with inflammasome or gut-joint axis. In this study, we aimed to explore the critical role of NOD-like receptor thermal protein domain associated protein 3 (NLRP3) and bile acid (BA) in the anti-RA mechanism. Complete Freund’s adjuvant (CFA)-injected mice were treated with THH extract (250 mg/kg/d) for 35 days, and joint swelling and disease scores were measured. After THH treatment, the joint swelling and RA disease score in CFA-treated mice significantly subsided. The increased ratios of lymphocytes, monocytes, and white blood cells were attenuated by THH treatment. Notably, THH treatment blocked the inflammation in both joints and colons by suppressing the NLRP3-mediated inflammasome, as indicated by NLRP3, interleukin 1beta (IL-1β), and Caspase-1. Meanwhile, THH significantly remodeled the bile acid (BA) profiles in RA mice. Spearman’s analysis shed light on the close link between BAs, NLRP3 inflammasome, and RA indicators. However, THH treatment failed to improve inflammasome activation, snoptivis, and joint swelling in RA mice with gut microbiota depletion. In summary, we revealed the pivotal role of BA-mediated gut-joint axis and inflammasome in THH’s RA amelioration. In the future, more work should be done to explain the in-depth mechanism between altered BAs and inflammasome.

Protein acetylation modifications play a central and pivotal role in a myriad of biological processes, spanning cellular metabolism, proliferation, differentiation, apoptosis, and beyond, by effectively reshaping protein structure and function. The metabolic state of cells is intricately connected to epigenetic modifications, which in turn influence chromatin status and gene expression patterns. Notably, pathological alterations in protein acetylation modifications are frequently observed in diseases such as metabolic syndrome, cardiovascular disorders, and cancer. Such abnormalities can result in altered protein properties and loss of function, which are closely associated with developing and progressing related diseases. In recent years, the advancement of precision medicine has highlighted the potential value of protein acetylation in disease diagnosis, treatment, and prevention. This review includes provocative and thought-provoking papers outlining recent breakthroughs in acetylation modifications as they relate to cardiovascular disease, mitochondrial metabolic regulation, liver health, neurological health, obesity, diabetes, and cancer. Additionally, it covers the molecular mechanisms and research challenges in understanding the role of acetylation in disease regulation. By summarizing novel targets and prognostic markers for the treatment of related diseases, we aim to contribute to the field. Furthermore, we discuss current hot topics in acetylation research related to health regulation, including N4-acetylcytidine and liquid-liquid phase separation. The primary objective of this review is to provide insights into the functional diversity and underlying mechanisms by which acetylation regulates proteins in disease contexts.

Abstract The South Qiangtang block of the Qinghai‐Tibet Plateau represents an area critical to understanding the late Paleozoic and early Mesozoic history of the Tethyan realm, but its drift history remains poorly constrained. Here we report a new quantitative paleogeographic constraint for the South Qiangtang block from a paleomagnetic study of Late Triassic volcanic rocks of the Xiaoqiebao Formation. A characteristic remanent magnetization isolated from 25 sites passes both fold‐ and reversal tests, and likely represents a primary magnetization. On the basis of these data, we estimate that the South Qiangtang block occupied a paleolatitude of 30.1 ± 4.6°N at ca. 222 Ma. When combined with existing paleomagnetic constraints, these new results indicate that the South Qiangtang block (and other “Cimmerian” blocks) moved rapidly northward (in true latitude) between the middle Permian and Late Triassic. Our new data further suggest that the southern branch of the Paleo‐Tethys (Longmuco‐Shuanghu Ocean) likely closed by the mid‐Late Triassic.

Abstract The entire global operation of the newly launched BDS global navigation satellite system (BDS‐3) was completed in July 2020. After that, a series of performance tests were conducted, such as positioning, navigation, and signal experiments. However, the precipitable water vapor (PWV) retrieval performance evaluation of BDS‐3 has not yet been carried out, so in this paper, we thoroughly verified its accuracy with AIRS v7, ERA5, and radiosonde data to know the current performance of BDS‐3 PWV. From the tests applied with different satellite systems, we found that BDS‐3 has a comparable PWV retrieval performance as global positioning system (GPS), and a better outcome was achieved using the combined data from GPS and BDS‐3. Furthermore, BDS‐3 PWV accuracy calibrated by AIRS v7 showed a strong correlation with the spatial distribution. In addition, the PWV content decreased with the climbing of the latitude and elevation, and the relative root mean square error (ReRMSE) indicated better in the low‐latitude areas. Finally, the effect of different surface types on PWV performance was analyzed, showing the BDS‐3 PWV accuracy in the land type was the highest, the sea one was the lowest, and the coast type was in the middle. These findings will provide a good reference for the community to understand the PWV performance of BDS‐3 at the present stage.

IntroductionVarious immunosuppressive regimens have been developed for the treatment of lupus nephritis (LN). This study aimed to compare the efficacy and safety of immunosuppressive regimens in adults with LN.MethodsWe systematically searched the PubMed, Embase, and Cochrane Central Register of Controlled Trials databases, including conference proceedings, trial registries, and reference lists, from inception until July 10, 2022. The effects of treatment were compared and ranked using the surface under the cumulative ranking curve (SUCRA). The primary endpoint was total remission. The secondary endpoints were complete remission, systemic lupus erythematosus disease activity index (SLEDAI), relapse, all-cause mortality, end-stage renal disease (ESRD), infection, herpes zoster, ovarian failure, myelosuppression, and cancer.ResultsSixty-two trials reported in 172 studies involving 6,936 patients were included in the network meta-analysis. The combination of tacrolimus (TAC), mycophenolate mofetil (MMF), and glucocorticoid (GC) provided the best result for the total remission rate (SUCRA, 86.63%) and SLEDAI (SUCRA, 91.00%), while the combination of voclosporin (VCS) , MMF and GC gave the best improvement in the complete remission rate (SUCRA, 90.71%). The combination of cyclophosphamide (CYC), MMF and GC was associated with the lowest risk of relapse (SUCRA, 85.57%) and cancer (SUCRA, 85.14%), while the combination of obinutuzumab (OTB), MMF and GC was associated with the lowest risk of all-cause mortality (SUCRA, 84.07%). Rituximab (RTX) plus MMF plus GC was associated with the lowest risk of ESRD (SUCRA, 83.11%), while the risk of infection was lowest in patients treated with azathioprine (AZA) plus CYC plus GC (SUCRA, 68.59%). TAC plus GC was associated with the lowest risk of herpes zoster (SUCRA, 87.67%) and ovarian failure (SUCRA, 73.60%). Cyclosporine (CsA) plus GC was associated with the lowest risk of myelosuppression (SUCRA, 79.50%), while AZA plus GC was associated with the highest risk of myelosuppression (SUCRA, 16.25%).DiscussionThis study showed that a combination of TAC, MMF and GC was the best regimen for improving the total remission rate. The optimal regimen for specific outcomes should be highlighted for high-risk patients.

Introduction: The severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) has posed a significant challenge to individuals’ health. Increasing evidence shows that patients with metabolic unhealthy obesity (MUO) and COVID-19 have severer complications and higher mortality rate. However, the molecular mechanisms underlying the association between MUO and COVID-19 are poorly understood.Methods: We sought to reveal the relationship between MUO and COVID-19 using bioinformatics and systems biology analysis approaches. Here, two datasets (GSE196822 and GSE152991) were employed to extract differentially expressed genes (DEGs) to identify common hub genes, shared pathways, transcriptional regulatory networks, gene-disease relationship and candidate drugs.Results: Based on the identified 65 common DEGs, the complement-related pathways and neutrophil degranulation-related functions are found to be mainly affected. The hub genes, which included SPI1, CD163, C1QB, SIGLEC1, C1QA, ITGAM, CD14, FCGR1A, VSIG4 and C1QC, were identified. From the interaction network analysis, 65 transcription factors (TFs) were found to be the regulatory signals. Some infections, inflammation and liver diseases were found to be most coordinated with the hub genes. Importantly, Paricalcitol, 3,3′,4,4′,5-Pentachlorobiphenyl, PD 98059, Medroxyprogesterone acetate, Dexamethasone and Tretinoin HL60 UP have shown possibility as therapeutic agents against COVID-19 and MUO.Conclusion: This study provides new clues and references to treat both COVID-19 and MUO.

BackgroundLife satisfaction (LS) serves as a crucial indicator of social wellbeing and plays a significant role in formulating strategies aimed at enhancing health outcomes among the hearing-disabled population. This study aimed to examine the effect of anxiety, depression, and structural social capital on life satisfaction among people with hearing disabilities in Shanghai, China.MethodsA cross-sectional study was conducted in Shanghai, China. As of March 2022, 337 people with hearing disabilities were recruited from the Shanghai Disabled Persons' Federation. An online survey was conducted using a four-part questionnaire to collect data including demographic characteristics, the Hospital Anxiety and Depression Scale (HADS), the Social Capital Scale (SCS), and a single-item question to measure life satisfaction. One-sample t-tests, Pearson's correlation analysis, and hierarchical multiple regression analysis were performed.ResultsAnxiety (β = – 0.153) and depression (β = – 0.242) were significant factors influencing life satisfaction among people with hearing disabilities. Structural social capital also played an influential role in life satisfaction, and people with hearing disabilities who lack social networks (β = 0.125) and social support (β = 0.121) reported significantly lower levels of life satisfaction. However, no significant relationship was found in this study between LS and other components of structural social capital, such as social participation.ConclusionThis study shows that paying attention to mental health is critical for people with hearing disabilities to achieve social wellbeing and promote LS improvement. At the same time, the government and society also need to focus on the structural social capital, provide various social service programs, enhance social support, and expand social networks, improving LS for people with hearing disabilities.

Summary: Background: Pre-procedural computed tomography (CT) imaging assessment of the aortic valvular complex (AVC) is essential for the success of transcatheter aortic valve replacement (TAVR). However, pre-TAVR assessment is a time-intensive process, and the visual assessment of anatomical structures at the AVC shows interobserver variability. This study aimed to develop and validate a deep learning-based algorithm for pre-TAVR CT assessment and anatomical risk factor detection. Methods: This retrospective, multicentre study used AVC CT scans to develop a deep learning-based, fully automated algorithm, which was then internally and externally validated. After loading CT scans into the algorithm, it automatically assessed the essential anatomical structure data required for TAVR planning. CT scans of 1252 TAVR candidates continuously enrolled from Fuwai Hospital were used to establish training and internal validation datasets, while CT scans of 100 patients with aortic valve disease across 19 Chinese hospitals served as an external validation dataset. The validation focused on segmentation performance, localisation and measurement accuracy of key anatomical structures, detection ability of specific anatomical risk factors, and improvement in assessment efficiency. Findings: Relative to senior observers, our algorithm achieved significant consistent performance with remarkable accuracy, efficiency and ease in segmentation, localisation, and the assessment of the aortic annulus perimeter-derived diameter, and other basic planes, coronary ostia height, calcification volume, and aortic angle. The intraclass correlation coefficient values for the algorithm in the internal and external validation datasets were up to 0.998 (95% confidence interval 0.998–0.998), respectively. Furthermore, the algorithm demonstrated high alignment in detecting specific anatomical risk factors, with accuracy, sensitivity, and specificity up to 0.989 (95% CI 0.973–0.996), 0.979 (95% CI 0.936–0.995), 0.986 (95% CI 0.945–0.998), respectively. Interpretation: Our algorithm efficiently performs pre-TAVR assessments by using AVC CT imaging with accuracy comparable to senior observers, potentially improving TAVR planning in clinical practice. Funding: National Key R&D Program of China (2020YFC2008100), CAMS Innovation Fund for Medical Sciences (2022-I2M-C&T-B-044).

B-cell lymphoma-2 (BCL-2) superfamily molecules play crucial roles in mitochondrial apoptosis induced by Chinese giant salamander iridovirus (GSIV). As an anti-apoptotic molecule in the BCL-2 family, the molecular mechanism of Bcl-w during GSIV infection remains unknown. In this study, we characterized for the first time an amphibian Bcl-w from Chinese giant salamander Andrias davidianus (AdBcl-w), and its function and regulatory mechanism during GSIV infection were investigated. AdBcl-w possesses the conserved structural features of Bcl-w and shares 35–54% sequence identities with other Bcl-w. mRNA expression of AdBcl-w was most abundant in liver and muscle. The AdBcl-w mRNA expression was regulated during GSIV infection. Western blotting assays revealed that the level of Bcl-w protein was downregulated markedly as the infection progresses. Confocal microscopy showed that overexpressed AdBcl-w was translocated to the mitochondria after infection with GSIV. Flow cytometry analysis demonstrated that compared with control, the apoptotic progress in cells transfected with AdBcl-w was reduced while that in cells transfected with AdBcl-w siRNA was enhanced. The number of virus major capsid protein gene copies was lower and protein synthesis was reduced in AdBcl-w overexpressing cells. In addition, AdBcl-w could bind directly to the pro-apoptotic molecule AdBak, while this interaction was weakened with GSIV infection. Moreover, p53 level was reduced and the mRNA expression levels of crucial regulatory molecules in the p53 pathway were regulated in AdBcl-w overexpressing cells during GSIV infection. These results suggested that AdBcl-w inhibit GSIV replication by regulating the virus induced mitochondrial apoptosis.

Gut microbiota disturbance, autophagy dysregulation, and accumulation of hepatic bile acids (BAs) are essential features of liver injury. Therefore, regulating autophagy and BA metabolism are potential strategies for treating liver diseases. Vine tea has been seen beyond a pleasant tea in food science. Our previous study found that vine tea extract (VTE) intervention alleviated acute liver injury (ALI) by restoring gut microbiota dysbiosis. In this study, we aim to investigate the effect of VTE on carbon tetrachloride (CCl4)-induced hepatic autophagy and BA metabolism disorder in mice. The results showed that VTE effectively suppressed CCl4-induced liver fibrosis and hepatic autophagy. LC-MS/MS assay suggested that VTE affected fecal BA production by reducing the fecal BA levels and improving cholestasis in ALI mice. Besides, VTE inhibited BA synthesis, promoted BA transport in the liver, and enhanced BA reabsorption in the ileum through the farnesoid X receptor (FXR)-related signaling pathway. The hepatic expressions of Fxr and Abca1 were elevated by VTE. Finally, the depletion of gut microbiota in ALI mice had a negative impact on abnormal autophagy and BA metabolism. It was also noted that the administration of VTE did not provide any additional improvement in this regard. Overall, VTE ameliorated ALI by reversing hepatic autophagy and abnormal BA metabolism, and the beneficial effects of VTE on liver injury depended on the existence of gut microbiota.

BackgroundMixed vaginitis is the infection of the vagina by at least two different pathogens at the same time, both of which contribute to an abnormal vaginal environment leading to signs and symptoms. Baicao Fuyanqing suppository (BCFYQ) is a Miao ethnomedicine, used to treat various vaginitis. The aim of this study was to investigate the efficacy and possible mechanism of BCFYQ in the treatment of mixed vaginitis based on 16S rRNA high-throughput sequencing and metabonomics.MethodsEscherichia coli and Candida albicans were used to establish mixed vaginitis model in SD rats. Three groups of low, medium and high doses (0.18/0.36/0.64 g.kg-1) were established, and administered vaginally once a day for 6 consecutive days. After the last administration, vaginal pH and IL-1β, IL-2, IL-13 and IgA levels were measured, and the vaginal tissue was examined pathologically. In addition, the vaginal flora was characterised by 16S rRNA, and endogenous metabolites in the vaginal tissue were detected by UHPLC-Q-Exactive MS.ResultsCompared with the model group, BCFYQ can reduce the vaginal pH of rats, make it close to the normal group and improve the damaged vaginal epithelial tissue. The results of ELISA showed that BCFYQ decreased the levels of IL-1 β and IL-2 and increased the levels of IL-13 and IgA (P

Biomaterials with exceptional biocompatibility and bioactivity are now pushing the boundaries of bone tissue engineering. In this study, natural Arabic gum biopolymer incorporating titanium dioxide nanoparticles (NAG + TiO2NP) nanocomposite film was fabricated. The FTIR and XRD analysis show the presence of functional groups assigned to NAG biopolymers and highly crystalline anatase TiO2NP. Well dispersed TiO2NP can be seen from SEM micrograph suggesting good interaction between TiO2NP filler and NAG biopolymer matrix to enhance the mechanical characteristics of nanocomposite film. The NAG + TiO2NP nanocomposite film exhibited strong bioactivity to form bone-like apatite and promoted the proliferation of MG-63 cells attributed to their excellent biocompatibility and non-toxicity. The NAG + TiO2NP nanocomposite film also displays high antibacterial activity with (36.33 ± 1.53) mm and (27.00 ± 2.00) mm inhibition zone were recorded against Staphylococcus aureus and Escherichia coli. The findings indicate that the NAG + TiO2NP nanocomposite film, with its improved mechanical properties, high swelling capacity, biodegradability, and non-toxicity, shows promise as a viable option for bone tissue regeneration materials.

Fusion-associated small transmembrane (FAST) proteins can promote cell fusion, alter membrane permeability and trigger apoptosis to promote virus proliferation in orthoreoviruses. However, it is unknown whether FAST proteins perform these functions in aquareoviruses (AqRVs). Non-structural protein 17 (NS17) carried by grass carp reovirus Honghu strain (GCRV-HH196) belongs to the FAST protein family, and we preliminarily explored its relevance to virus infection. NS17 has similar domains to FAST protein NS16 of GCRV-873, comprising a transmembrane domain, a polybasic cluster, a hydrophobic patch and a polyproline motif. It was observed in the cytoplasm and the cell membrane. Overexpression of NS17 enhanced the efficiency of cell-cell fusion induced by GCRV-HH196 and promoted virus replication. Overexpression of NS17 also led to DNA fragmentation and reactive oxygen species (ROS) accumulation, and it triggered apoptosis. The findings illuminate the functions of NS17 in GCRV infection, and provide a reference for the development of novel antiviral strategies.

Hexavalent chromium [Cr(VI)] is a well-known environmental carcinogen. Recent studies revealed that chronic exposure of human bronchial epithelial cells (BEAS-2B, B2B) to Cr(VI) activated several signaling pathways and induced cell malignant transformation and tumor growth. However, new mechanisms of Cr(VI) in inducing carcinogenesis remains to be elucidated. This study showed that miR-199a expression levels were significantly lower in Cr(VI)-transformed Cr-T cells. By using the mouse model, the expression levels of miR-199a were significantly decreased in blood samples and lung tissues of mice intranasally exposed to Cr(VI) for 12 weeks compared to the solvent exposure control. Overexpression of miR-199a inhibited tube formation and angiogenesis. C-X-C motif chemokine ligand 8 (CXCL8, IL8) levels were significantly higher in blood samples of Cr (VI)-exposed workers compared to normal workers, and forced expression of miR-199a in the cells suppressed IL8 levels. miR-199a suppression induced expression of hypoxia-inducible factor 1α (HIF-1α) and nuclear factor kappa B (NF-κB) p65 to increase IL8 expression. With animal experiment, the results showed that miR-199a overexpression inhibited tumor growth and angiogenesis through inhibiting IL8, HIF-1α and NF-κB p65 expression in vivo. These results show that miR-199a/IL8 pathway is important in Cr(VI)-induced carcinogenesis and angiogenesis.

Honeybees play a crucial role as pollinators for crops and are regarded as sensitive bioindicators of environmental health. The widespread use of pesticides poses a severe threat to honeybee survival. However, there is limited information available on the specific risks associated with fipronil exposure in honeybees, particularly concerning the impact on RNA methylation throughout their lifespan. This study aimed to evaluate the effects of sublethal concentrations of fipronil on RNA m6A and m5C methylations, along with the associated genes in honeybee larvae and newly emerged adults. LC-MS/MS analysis revealed a notable hypomethylation of m5C in larvae, while hypermethylation of m6A was observed in the adult brain. Significant changes in the expression of genes such as AmWTAP, AmYTHDF, AmALKBH4, AmALKBH6, AmALKBH8, AmNSUN5, AmNOP2, AmTET1, and AmYBX1 were observed in the adult brain, whereas alterations in the expression of AmNSUN2, AmMETTL14, AmALKBH1, AmALKBH4, AmALKBH6 AmALYREF, AmTET1, and AmYBX1 were observed in the larvae. Notably, the expression of AmALKBH1 was not detected in any fipronil-treated larvae, suggesting its potential as an early risk indicator for honeybee larvae in future assessments. This pioneering study provides insights into the effects of fipronil on RNA methylations in honeybees and explores the possibility of employing RNA methylation as a tool for assessing pesticide risks in this important pollinator species. These findings offer new perspectives on honeybee protection and the development of toxicity evaluation systems for pesticides.

Background: Deep brain stimulation (DBS) is a well-established treatment for the tremor symptoms of Parkinson’s disease (PD) or essential tremor. Various structures can be considered targets to be stimulated in tremor treatment.Case description: We described a case of a patient with tremor-dominant Parkinson's disease (td-PD) and a family history of essential tremor, who underwent one-trajectory subthalamic nucleus (STN) and ventral intermediate nucleus (Vim) DBS surgery via a parietal approach under general anesthesia. Microelectrode recordings were performed to localize the STN and Vim. Two years postoperatively, there was an improvement of 61.64% in total motor symptoms and of 80.77% in tremor symptoms in the off-medication and on-stimulation states compared with that in the preoperative off-medication state. The levodopa equivalent daily dosage was reduced from 450 mg to 300 mg. Conclusion: For patients with td-PD with refractory tremors, one-trajectory STN and Vim DBS surgery could improve symptoms and might provide a wider programming window for postoperative management.

Abstract Background Obesogenic environment is important in driving obesity epidemic. Children spend large amount of their time in schools. School neighborhood environment, as well as its interaction with socioeconomic status (SES) needs to be explored to provide evidence for children obesity prevention policies. Methods Objective anthropometric measurement, a household structured questionnaire, and school geospatial analyses were carried out on 3670 children (aged 9–12 years) of 26 schools in northeast China. Interaction between SES inter-categorical intersectionality group and school neighborhood environment was tested for the effect on children’s body mass index z scores (z-BMI) and waist–hip ratio z scores (z-WHR), following formulation of SES inter-categorical intersectionality group based on household wealth, parental education, and parental occupation. Results SES groups formed by household wealth, parental education and parental occupation was associated with z-BMI and z-WHR for girls. Those from moderate wealth & self-employed (M&S) families had the highest adjusted z-BMI and z-WHR among all SES groups. School neighborhood environment factors interacted with SES groups in association with WHR for girls. Number of school neighborhood supermarkets and residential sites were negatively associated with z-WHR for girls from M&S families (β= -0.45 (95%CI: -0.76, -0.15) for supermarkets; β= -0.01 (95%CI: -0.03, 0.00) for residential sites). Number of school neighborhood convenience stores and public transport stops were positively associated with z-WHR for girls from M&S families (β = 0.02 (95%CI: 0.00, 0.03) for convenience stores; β = 0.23 (95%CI: 0.15, 0.31) for public transport stops). While non-significant association was found for number of vegetable stores. Conclusion Girls from moderate wealth & self-employed families may be the group susceptible to school neighborhood environment. Local policies targeted at improving the school neighborhood environment may be one avenue for reducing socioeconomic disparities in obesity especially for girls.

Abstract Previous studies have documented substantial advancing trends in the onset date of vegetation green-up (VGD) during the 1980s and 1990s over the Northern Hemisphere, while later studies based on data from the spaceborne advanced very high-resolution radiometer (AVHRR) have reported this trend stalled during the warming hiatus from the late 1990s to early 2010s. However, there is uncertainty in this finding of a hiatus in VGD advance due to the identification of quality issues associated with the data from AVHRR. Using the high-quality data from the Moderate Resolution Imaging Spectroradiometer, we show VGD significantly advanced despite the warming hiatus due to the high sensitivity of VGD to temperature and the magnitude of VGD advance over 2000–2021 (2.5–2.6 days decade–1, P