Risk of hepatocellular carcinoma occurrence after antiviral therapy for patients with chronic hepatitis C Infection: a systematic review and meta-analysis.

BACKGROUND AND AIMS: The risk of hepatocellular carcinoma (HCC) occurrence following antiviral therapy in patients with chronic hepatitis C (CHC) remains unclear. The current study aims to compare: (1) the HCC occurrence rate following sustained virological response (SVR) versus non-response (NR); (2) the HCC occurrence rate following direct-acting antiviral (DAA) therapy versus interferon (IFN)-based therapy, and (3) the HCC occurrence rate in SVR patients with or without cirrhosis. METHODS: A search was performed for articles published between January 2017 and July 2022. Studies were included if they assessed HCC occurrence rate in CHC patients following anti-HCV therapy. Random effects meta-analysis was used to synthesize the results from individual studies. RESULTS: A total of 23 studies including 29,395 patients (IFN-based = 6, DAA = 17; prospective = 10, retrospective = 13) were included in the review. HCC occurrence was significantly lower in CHC with SVR (1.54 per 100 person-years (py, 95% CI 1.52, 1.57) than those in non-responders (7.80 py, 95% CI 7.61, 7.99). Stratified by HCV treatment regimens, HCC occurrence following SVR was 1.17 per 100 py (95% CI 1.11, 1.22) and 1.60 per 100 py (95% CI 1.58, 1.63) in IFN- and DAA treatment-based studies. HCC occurrence was 0.85 per 100 py (95% CI 0.85, 0.86) in the non-cirrhosis population and rose to 2.47 per 100 py (95% CI 2.42, 2.52) in the cirrhosis population. Further meta-regression analysis showed that treatment types were not associated with a higher HCC occurrence rate, while cirrhosis status was an important factor of HCC occurrence rate. CONCLUSION: HCC occurrence was significantly lower in the SVR population than in the NR population. HCC risk following SVR occurred three times more frequently in patients with cirrhosis than patients without cirrhosis. However, we found no significant difference in HCC occurrence risk following SVR between DAA and IFN therapies. CLINICAL TRIAL NUMBER: CRD42023473033.

Antiplatelet drug ticagrelor suppresses triple negative breast cancer metastasis by targeting PI3K.

Metastatic recurrence is still a major challenge in breast cancer treatment. Patients with triple negative breast cancer (TNBC) develop early recurrence and relapse more frequently. Due to the lack of specific therapeutic targets, new targeted therapies for TNBC are urgently needed. Phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathway is one of the active pathways involved in chemoresistance and survival of TNBC, being considered as a potential target for TNBC treatment. Our present study identified ticagrelor, an anti-platelet drug, as a pan-PI3K inhibitor with potent inhibitory activity against four isoforms of class I PI3K. At doses normally used in clinic, ticagrelor showed weak cytotoxicity against a panel of breast cancer cells, but significantly inhibited the migration, invasion and the actin cytoskeleton organization of human TNBC MDA-MB-231 and SUM-159PT cells. Mechanistically, ticagrelor effectively inhibited PI3K downstream mTOR complex 1 (mTORC1) and mTORC2 signaling by targeting PI3K and decreased the protein expression of epithelial-mesenchymal transition (EMT) markers. In vivo, ticagrelor significantly suppressed tumor cells lung metastasis in 4T1 tumor bearing BALB/c mice model and experimental lung metastasis model which was established by tail vein injection of GFP-labeled MDA-MB-231 cells. The above data demonstrated that ticagrelor can inhibit the migration and invasion of TNBC both in vitro and in vivo by targeting PI3K, suggesting that ticagrelor, a pan-PI3K inhibitor, might represent a promising therapeutic agent for the treatment of metastatic TNBC.

Biodegradable gelatin/pectin films containing cellulose nanofibers and biguanide polymers: Characterization and application in sweet cherry packaging.

To expand the utilization of gelatin and pectin derived from agricultural by-products, the composite films composed of gelatin, citrus pectin, cellulose nanofibers (CNF), and polyhexamethylene biguanide hydrochloride (PHMB) were prepared through the solvent casting method. Fourier infrared spectroscopy analysis verified the successful integration of CNF and PHMB into the gelatin-pectin matrix. The incorporation of CNF as a reinforcing agent substantially enhanced the barrier capabilities of the composite film. Moreover, the addition of PHMB, functioning as an antimicrobial agent, not only granted the film with antibacterial properties but also improved its physical characteristics and biodegradability. A water contact angle experiment revealed the film presented a certain degree of hydrophobicity. The optimal performances were attained with a composition in which CNF and PHMB constituted 8 % and 3 %, respectively, of the total weight of gelatin and pectin. As a packaging film, the composite film demonstrated its effectiveness by reducing the decay index and weight loss rate of sweet cherries during a 12-day storage period. In the soil degradation test, the composite film exhibited notable structural degradation by the 16th day. Consequently, the composite film will be used as an innovative and biodegradable packaging material to provide a sustainable solution for food packaging industries.

Arboviruses antagonize insect Toll antiviral immune signaling to facilitate the coexistence of viruses with their vectors.

Many plant arboviruses are persistently transmitted by piercing-sucking insect vectors. However, it remains largely unknown how conserved insect Toll immune response exerts antiviral activity and how plant viruses antagonize it to facilitate persistent viral transmission. Here, we discover that southern rice black-streaked dwarf virus (SRBSDV), a devastating planthopper-transmitted rice reovirus, activates the upstream Toll receptors expression but suppresses the downstream MyD88-Dorsal-defensin cascade, resulting in the attenuation of insect Toll immune response. Toll pathway-induced the small antibacterial peptide defensin directly interacts with viral major outer capsid protein P10 and thus binds to viral particles, finally blocking effective viral infection in planthopper vector. Furthermore, viral tubular protein P7-1 directly interacts with and promotes RING E3 ubiquitin ligase-mediated ubiquitinated degradation of Toll pathway adaptor protein MyD88 through the 26 proteasome pathway, finally suppressing antiviral defensin production. This virus-mediated attenuation of Toll antiviral immune response to express antiviral defensin ensures persistent virus infection without causing evident fitness costs for the insects. E3 ubiquitin ligase also is directly involved in the assembly of virus-induced tubules constructed by P7-1 to facilitate viral spread in planthopper vector, thereby acting as a pro-viral factor. Together, we uncover a previously unknown mechanism used by plant arboviruses to suppress Toll immune response through the ubiquitinated degradation of the conserved adaptor protein MyD88, thereby facilitating the coexistence of arboviruses with their vectors in nature.

Potential SLA Hp-4.0 haplotype-restricted CTL epitopes identified from the membrane protein of PRRSV induce cell immune responses.

Swine leukocyte antigen (SLA) class I molecule-restricted T-cell epitopes, which induce cytotoxic T lymphocyte (CTL) responses, play a critical role in the clearance of porcine reproductive and respiratory syndrome virus (PRRSV) and the development of efficient protective vaccines. The SLA-1*04:01:01, SLA-2*04:01, and SLA-3*04:01 alleles, assigned the Hp-4.0 haplotype, are highly prevalent and usually present in all pig breeds. However, the SLA Hp-4.0 haplotype-restricted CTL epitopes in the structural membrane (M) protein of PRRSV are still unknown. In this study, we predicted 27 possible 9-mer epitope peptides in M protein with high binding scores for SLA-1*04:01:01 using CTL epitope prediction tools. In total, 45 SLA class I complexes, comprising the predicted peptide, extracellular region of the SLA-I molecules, and ß2-microglobulin, were constructed in vitro to detect the specific binding of these peptides to SLA-1*04:01:01 (27 complexes), SLA-2*04:01 (9 complexes), and SLA-3*04:01 (9 complexes), respectively. Our results showed that the M27 (T91WKFITSRC), M39 (N130HAFVVRRP), and M49 (G158RKAVKQGV) peptides bind specifically to SLA-1*04:01:01, SLA-2*04:01, and SLA-3*04:01, respectively. Subsequently, using peripheral blood mononuclear cells (PBMCs) isolated from the homozygous Hp-4.0 and Hp-26.0 haplotype piglets vaccinated with commercial PRRSV HuN4-F112 strain, we determined the capacities of these 27 potential peptides to stimulate their proliferation with a Cell Counting Kit-8 and their secretion and expression of interferon gamma (IFN-γ) with an ELISpot assay and real-time qPCR, respectively. The immunological activities of M27, M39, and M49 were therefore confirmed when they efficiently induced PBMC proliferation and IFN-γ secretion in PBMCs from piglets with the prevalent SLA Hp-4.0 haplotype. The amino acid sequence alignment revealed that M27, M39, and M49 are highly conserved among 248 genotype II PRRSV strains collected between 1998 and 2019. These findings contribute to the understanding of the mechanisms of cell-mediated immune responses to PRRSV. Our study also provides a novel strategy for identifying and confirming potential SLA haplotype-restricted CTL epitopes that could be used to develop novel peptide-based vaccines against swine diseases.

Enhancer demethylation-regulated gene score identified molecular subtypes, inspiring immunotherapy or CDK4/6 inhibitor therapy in oesophageal squamous cell carcinoma.

BACKGROUND: The 5-year survival rate of oesophageal squamous cell carcinoma (ESCC) is approximately 20%. The prognosis and drug response exhibit substantial heterogeneity in ESCC, impeding progress in survival outcomes. Our goal is to identify a signature for tumour subtype classification, enabling precise clinical treatments. METHODS: Utilising pre-treatment multi-omics data from an ESCC dataset (n = 310), an enhancer methylation-eRNA-target gene regulation network was constructed and validated by in vitro experiments. Four machine learning methods collectively identified core target genes, establishing an Enhancer Demethylation-Regulated Gene Score (EDRGS) model for classification. The molecular function of EDRGS subtyping was explored in scRNA-seq (n = 60) and bulk-seq (n = 310), and the EDRGS's potential to predict treatment response was assessed in datasets of various cancer types. FINDINGS: EDRGS stratified ESCCs into EDRGS-high/low subtypes, with EDRGS-high signifying a less favourable prognosis in ESCC and nine additional cancer types. EDRGS-high exhibited an immune-hot but immune-suppressive phenotype with elevated immune checkpoint expression, increased T cell infiltration, and IFNγ signalling in ESCC, suggesting a better response to immunotherapy. Notably, EDRGS outperformed PD-L1 in predicting anti-PD-1/L1 therapy effectiveness in ESCC (n = 42), kidney renal clear cell carcinoma (KIRC, n = 181), and bladder urothelial carcinoma (BLCA, n = 348) cohorts. EDRGS-low showed a cell cycle-activated phenotype with higher CDK4 and/or CDK6 expression, demonstrating a superior response to the CDK4/6 inhibitor palbociclib, validated in ESCC (n = 26), melanoma (n = 18), prostate cancer (n = 15) cells, and PDX models derived from patients with pancreatic cancer (n = 30). INTERPRETATION: Identification of EDRGS subtypes enlightens ESCC categorisation, offering clinical insights for patient management in immunotherapy (anti-PD-1/L1) and CDK4/6 inhibitor therapy across cancer types. FUNDING: This study was supported by funding from the National Key R&D Program of China (2021YFC2501000, 2020YFA0803300), the National Natural Science Foundation of China (82030089, 82188102), the CAMS Innovation Fund for Medical Sciences (2021-I2M-1-018, 2022-I2M-2-001, 2021-I2M-1-067), the Fundamental Research Funds for the Central Universities (3332021091).

Land use transition and its effect on ecosystem service value with introducing "three wastes" factor in the industrial county, China.

Land use transition and its impact on ecosystem service value (ESV) are the foundation for optimizing the layout of territorial space and ecological civilization construction. With the acceleration of industrialization and urbanization, the area of construction land expands in China. To accurately estimate the ESV in industrial counties, the impact of construction land on the ecological environment should be fully considered. This paper took Gangcheng District, Jinan City, a steel base in the Shandong Province of China as an example, then the value coefficients of "three wastes" factors (waste gas, wastewater, and waste) were introduced, and an improved calculation method of ESV was put forward for industrial counties in combination with remote sensing and land use data. Finally, the land use transition and its ESV effect in typical industrial counties were analyzed using geo-informatic Tupu and grid method. The results showed that the most important land use transitions were from grassland and forestland to cultivated land, from cultivated land and forestland to construction land in 1990-2010, and from cultivated land transformed to forestland in 2010-2021. The types of land use transition were mainly repetitive and continuous. The ESV first decreased and then increased, with a slight overall decline for more than 30 years, showing a spatial distribution characteristic of "low in the south-central and high around." Land use transition had the impact on ESV with the negative contribution rate of 68.28% in 1990-2000 and 73.16% in 2000-2010, mainly caused by the transition from forestland and grassland to cultivated land and construction land, and the positive contribution rate of 81.72% in 2010-2021, mainly caused by the transition from cultivated land to forestland. Compared with the ESV calculation method without introducing the "three wastes" factor and Xie Gaodi's method, the improved method in this paper considered the inevitable impact of construction land on ESV in industrial counties and made the ESV calculated more accurate according to the regional nature. This paper cannot only enrich the theories and technical methods of land use transition and its effects, and provide a case reference for similar industrial counties, but also provide data and decision-making support for the spatial layout and ecological protection in the study area.

Leafhopper salivary carboxylesterase suppresses JA-Ile synthesis to facilitate initial arbovirus transmission in rice phloem.

Plant jasmonoyl-L-isoleucine (JA-Ile) is a major defense signal against insect feeding, but whether or how insect salivary effectors suppress JA-Ile synthesis and thus facilitate viral transmission in the plant phloem remains elusive. Insect carboxylesterases (CarEs) are the third major family of detoxification enzymes. Here, we identify a new leafhopper CarE, CarE10, that is specifically expressed in salivary glands and is secreted into the rice phloem as a saliva component. Leafhopper CarE10 directly binds to rice jasmonate resistant 1 (JAR1) and promotes its degradation by the proteasome system. Moreover, the direct association of CarE10 with JAR1 clearly impairs JAR1 enzyme activity for conversion of JA to JA-Ile in an in vitro JA-Ile synthesis system. A devastating rice reovirus activates and promotes the co-secretion of virions and CarE10 via virus-induced vesicles into the saliva-storing salivary cavities of the leafhopper vector and ultimately into the rice phloem to establish initial infection. Furthermore, a virus-mediated increase in CarE10 secretion or overexpression of CarE10 in transgenic rice plants causes reduced levels of JAR1 and thus suppresses JA-Ile synthesis, promoting host attractiveness to insect vectors and facilitating initial viral transmission. Our findings provide insight into how the insect salivary protein CarE10 suppresses host JA-Ile synthesis to promote initial virus transmission in the rice phloem.

Comparative Assessments of Dental Resin Composites: A Focus on Dense Microhybrid Materials.

The performance of dental resin composites is crucially influenced by the sizes and distributions of inorganic fillers. Despite the investigation of a variety of functional particles, glass fillers and nanoscale silica are still the predominant types in dental materials. However, achieving an overall improvement in the performance of resin composites through the optimization of their formulations remains a challenge. This work introduced a "dense" microhybrid filler system with 85 wt % filler loading, leading to the preparation of self-developed resin composites (SRCs). Comparative evaluations of these five SRCs against four commercial products were performed, including mechanical property, polymerization conversion, and shrinkage, along with water sorption and solubility and wear resistance. The results showed that among all SRC groups, SRC3 demonstrated superior mechanical performance, high polymerization conversion, reduced shrinkage, low water absorption and solubility, and acceptable wear resistance. In contrast to commercial products, this optimal SRC3 material was comparable to Z350 XT in flexural and diametral tensile strength and better in flexural modulus and surface hardness. The use of a "dense" microhybrid filler system in the development of resin composites provides a balance between physicochemical property and wear resistance, which may be a promising strategy for the development of composite products.

Exosomes regulate SIRT3-related autophagy by delivering miR-421 to regulate macrophage polarization and participate in OSA-related NAFLD.

PURPOSE: To analyze the role of and mechanism underlying obstructive sleep apnea (OSA)-derived exosomes in inducing non-alcoholic fatty liver (NAFLD). METHODS: The role of OSA-derived exosomes was analyzed in inducing hepatocyte fat accumulation in mice models both in vivo and in vitro. RESULTS: OSA-derived exosomes caused fat accumulation and macrophage activation in the liver tissue. These exosomes promoted fat accumulation; steatosis was more noticeable in the presence of macrophages. Macrophages could internalize OSA-derived exosomes, which promoted macrophage polarization to the M1 type. Moreover, it inhibited sirtuin-3 (SIRT3)/AMP-activated protein kinase (AMPK) and autophagy and promoted the activation of nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3) inflammasomes. The use of 3-methyladenine (3-MA) to inhibit autophagy blocked NLRP3 inflammasome activation and inhibited the M1 polarization of macrophages. miR-421 targeting inhibited SIRT3 protein expression in the macrophages. miR-421 was significantly increased in OSA-derived exosomes. Additionally, miR-421 levels were increased in OSA + NAFLD mice- and patient-derived exosomes. In the liver tissues of OSA and OSA + NAFLD mice, miR-421 displayed similar co-localization with the macrophages. Intermittent hypoxia-induced hepatocytes deliver miR-421 to the macrophages via exosomes to inhibit SIRT3, thereby participating in macrophage M1 polarization. After OSA and NAFLD modeling in miR-421-/- mice, liver steatosis and M1 polarization were significantly reduced. Additionally, in the case of miR-421 knockout, the inhibitory effects of OSA-derived exosomes on SIRT3 and autophagy were significantly alleviated. Furthermore, their effects on liver steatosis and macrophage M1 polarization were significantly reduced. CONCLUSIONS: OSA promotes the delivery of miR-421 from the hepatocytes to macrophages. Additionally, it promotes M1 polarization by regulating the SIRT3/AMPK-autophagy pathway, thereby causing NAFLD.

A phytoplasma effector destabilizes chloroplastic glutamine synthetase inducing chlorotic leaves that attract leafhopper vectors.

Leaf yellowing is a well-known phenotype that attracts phloem-feeding insects. However, it remains unclear how insect-vectored plant pathogens induce host leaf yellowing to facilitate their own transmission by insect vectors. Here, we report that an effector protein secreted by rice orange leaf phytoplasma (ROLP) inhibits chlorophyll biosynthesis and induces leaf yellowing to attract leafhopper vectors, thereby presumably promoting pathogen transmission. This effector, designated secreted ROLP protein 1 (SRP1), first secreted into rice phloem by ROLP, was subsequently translocated to chloroplasts by interacting with the chloroplastic glutamine synthetase (GS2). The direct interaction between SRP1 and GS2 disrupts the decamer formation of the GS2 holoenzyme, attenuating its enzymatic activity, thereby suppressing the synthesis of chlorophyll precursors glutamate and glutamine. Transgenic expression of SRP1 in rice plants decreased GS2 activity and chlorophyll precursor accumulation, finally inducing leaf yellowing. This process is correlated with the previous evidence that the knockout of GS2 expression in rice plants causes a similar yellow chlorosis phenotype. Consistently, these yellowing leaves attracted higher numbers of leafhopper vectors, caused the vectors to probe more frequently, and presumably facilitate more efficient phytoplasma transmission. Together, these results uncover the mechanism used by phytoplasmas to manipulate the leaf color of infected plants for the purpose of enhancing attractiveness to insect vectors.

Highly bifunctional Rh2P on N,P-codoped carbon for hydrazine oxidation assisted energy-saving hydrogen production.

Highly pure Rh2P nanoparticles on N,P-codoped carbon were synthesized by a simple "mix-and-pyrolyze" method using one kind of low-cost nucleotide as the carbon, nitrogen and phosphorus source, which exhibits excellent bifunctional activity for the hydrogen reduction and hydrazine oxidation reactions, achieving energy-efficient hydrogen production.

A Novel Approach of Electrocatalytic Deamination from Aromatic Amide to Diarylimide on Ni-PTFE Modified Electrode.

A hydrophobic Ni-PTFE modified electrode has been prepared by constant current and cathodic electroplating with a nickel sheet as substrate in a PTFE suspension. Then the Ni-PTFE modified electrode was used for electroreduction from aromatic amide to diarylimide. The electrochemical characterizations such as cyclic voltammogram, EIS, polarization curves, and electrode stability have been carried out by electrochemical workstation. The structure of the electroreduction product diarylimide was characterized by 1HNMR, FT-IR, MS(Mass Spectrum), and EA(Elemental Analyzer). Based on the hydrophobicity of the electrode, an approach suggested that the phenyl ketone radical may be formed by electroreductive deamination at the cathode. With the construction of C-N bond by the radical coupling, the electrocatalytic reduction may be comprised of a one-electron process including an ECC (Electrochemical-Chemical-Chemical) process. The electroreduction of aromatic amide to diarylimide may be controlled by both charge migration and concentration polarization. Electrocatalytic reduction of aromatic amides on Ni-PTFE-modified electrodes is all well conversion ratio.

Construction of Cs2AgBiCl6/COF Heterojunction for Boosted Photocatalytic Thioester Oxidation.

Lead-free halide perovskites as a new kind of potential candidate for photocatalytic organic synthesis have attracted much attention recently. The rational heterojunction construction is regarded as an efficient strategy to delicately regulate their catalytic performances. Herein, a semi-conductive covalent organic framework (COF) nanosheet, C4N, is employed as the functional component to construct Cs2AgBiCl6/C4N (CABC/C4N) heterojunction. It is found that the C4N nanosheets with rich surface functional groups can serve as heterogeneous nucleation sites to manipulate the growth of CABC nanocrystals and afford close contact between each other, therefore facilitate the transfer and spatial separation of photogenerated charge carriers, as verified by in situ X-ray photoelectronic spectroscopy and Kelvin probe force microscopy. Moreover, the oxygen affinity of C4N endows the heterojunctions with outstanding aerobic reactivity, thus improving the photocatalytic performance largely. The optimal CABC/C4N heterojunction delivers a thioanisole conversion efficiency of 100% after 6 h, which is 2.2 and 7.7-fold of that of CABC and C4N. This work provides a new ideal for the design and application of lead-free perovskite heterojunction photocatalysts for organic reactions.

Blood microbial signatures associated with mortality in patients with sepsis: A pilot study.

Sepsis is a life-threatening illness caused by the dysregulated host response to infection. Nevertheless, our current knowledge of the microbial landscape in the blood of septic patients is still limited. Next-generation sequencing (NGS) is a sensitive method to quantitatively characterize microbiomes at various sites of the human body. In this study, we analyzed the blood microbial DNA of 22 adult patients with sepsis and 3 healthy subjects. The presence of non-human DNA was identified in both healthy and septic subjects. Septic patients had a markedly altered microbial DNA profile compared to healthy subjects over α- and ß-diversity. Unexpectedly, the patients could be further divided into two subgroups (C1 and C2) based on ß-diversity analysis. C1 patients showed much higher bacteria, viruses, fungi, and archaea abundance, and a higher level of α-diversity (Chao1, Observed and Shannon index) than both C2 patients and healthy subjects. The most striking difference was seen in the case of Streptomyces violaceusniger, Phenylobacterium sp. HYN0004, Caulobacter flavus, Streptomyces sp. 11-1-2, and Phenylobacterium zucineum, the abundance of which was the highest in the C1 group. Notably, C1 patients had a significantly poorer outcome than C2 patients. Moreover, by analyzing the patterns of microbe-microbe interactions in healthy and septic subjects, we revealed that C1 and C2 patients exhibited distinct co-occurrence and co-exclusion relationships. Together, our study uncovered two distinct microbial signatures in the blood of septic patients. Compositional and ecological analysis of blood microbial DNA may thus be useful in predicting mortality of septic patients.

Innate Immune Evasion of PRRSV nsp11 through Degradation of the HDAC2 by Its Endoribonuclease Activity.

Porcine reproductive and respiratory syndrome virus (PRRSV), a member of the Arteriviridae family, represents a persistent menace to the global pig industry, causing reproductive failure and respiratory disease in pigs. In this study, we delved into the role of histone deacetylases (HDAC2) during PRRSV infection. Our findings revealed that HDAC2 expression is downregulated upon PRRSV infection. Notably, suppressing HDAC2 activity through specific small interfering RNA led to an increase in virus production, whereas overexpressing HDAC2 effectively inhibited PRRSV replication by boosting the expression of IFN-regulated antiviral molecules. Furthermore, we identified the virus's nonstructural protein 11 (nsp11) as a key player in reducing HDAC2 levels. Mutagenic analyses of PRRSV nsp11 revealed that its antagonistic effect on the antiviral activity of HDAC2 is dependent on its endonuclease activity. In summary, our research uncovered a novel immune evasion mechanism employed by PRRSV, providing crucial insights into the pathogenesis of this virus and guiding the development of innovative prevention strategies against PRRSV infection.

Surface modifications of short quartz fibers and their influence on the physicochemical properties and in vitro cell viability of dental composites.

OBJECTIVE: Although glass fibers are more common, quartz fibers (QFs) are also considered as the ideal reinforcing material in dentistry, due to their superior mechanical strength, high purity, and good photoconductive properties. However, the relatively inert surfaces limit their further applications. Therefore, the aim of this study is to modify the fiber surface properties to improve the interfacial interactions with polymeric resins. METHODS: In this study, we systematically introduced four different surface modification strategies onto short quartz fibers (SQFs) for the preparation of dental composites. Particularly, the acid etching was a facile way to create mechanical interlocking structures. In addition, the silanization process, the sol-gel treatment, and the polymer grafting were further proposed to increase the surface roughness and the reactive sites. The effect of surface modifications on the fiber surface morphological changes, mechanical properties, water stability, and in vitro cell viability of dental composites were investigated. RESULTS: Among all surface-modified SQFs, SQFs-POSS (SQFs modified with methacrylate-POSS) exhibited the roughest surface morphology and highest grafting rates compared with other three materials. Furthermore, all these SQFs were applied as reinforcements to make dimethacrylate-based dental resin composites. Of all fillers, SQFs-POSS demonstrated the best reinforcing effect, providing significantly higher improvements of 55.7 %, 114.3 %, and 164.7 % for flexural strength, flexural modulus, and breaking energy, respectively, over those of SQFs-filled composite. The related reinforcing mechanism was further investigated. The SQFs-POSS-filled composite also exhibited the best water stability performance and in vitro cell viability. SIGNIFICANCE: This work provided valuable insights into the optimization of filler-matrix interaction through fiber surface modifications. Specifically, SQFs-POSS markedly outperformed other formulations in terms of the physicochemical performance and in vitro cytotoxicity, which offers possibilities for developing high-performance dental composites for clinical applications in restorative dentistry.

Multimodal analysis of cfDNA methylomes for early detecting esophageal squamous cell carcinoma and precancerous lesions.

Detecting early-stage esophageal squamous cell carcinoma (ESCC) and precancerous lesions is critical for improving survival. Here, we conduct whole-genome bisulfite sequencing (WGBS) on 460 cfDNA samples from patients with non-metastatic ESCC or precancerous lesions and matched healthy controls. We develop an expanded multimodal analysis (EMMA) framework to simultaneously identify cfDNA methylation, copy number variants (CNVs), and fragmentation markers in cfDNA WGBS data. cfDNA methylation markers are the earliest and most sensitive, detectable in 70% of ESCCs and 50% of precancerous lesions, and associated with molecular subtypes and tumor microenvironments. CNVs and fragmentation features show high specificity but are linked to late-stage disease. EMMA significantly improves detection rates, increasing AUCs from 0.90 to 0.99, and detects 87% of ESCCs and 62% of precancerous lesions with >95% specificity in validation cohorts. Our findings demonstrate the potential of multimodal analysis of cfDNA methylome for early detection and monitoring of molecular characteristics in ESCC.

Molecular identification and probiotic potential characterization of lactic acid bacteria isolated from the pigs with superior immune responses.

Lactic acid bacteria (LAB) belong to a significant group of probiotic bacteria that provide hosts with considerable health benefits. Our previous study showed that pigs with abundant LAB had more robust immune responses in a vaccination experiment. In this study, 52 isolate strains were isolated from the pigs with superior immune responses. Out of these, 14 strains with higher antibacterial efficacy were chosen. We then assessed the probiotic features of the 14 LAB strains, including such as autoaggregation, coaggregation, acid resistance, bile salt resistance, and adhesion capability, as well as safety aspects such as antibiotic resistance, hemolytic activity, and the presence or absence of virulence factors. We also compared these properties with those of an opportunistic pathogen EB1 and two commercial probiotics (cLA and cLP). The results showed that most LAB isolates exhibited higher abilities of aggregation, acid and bile salt resistance, adhesion, and antibacterial activity than the two commercial probiotics. Out of the 14 strains, only LS1 and LS9 carried virulence genes and none had hemolytic activity. We selected three LAB strains (LA6, LR6 and LJ1) with superior probiotic properties and LS9 with a virulence gene for testing their safety in vivo. Strains EB1, cLA and cLP were also included as control bacteria. The results demonstrated that mice treated LAB did not exhibit any adverse effects on weight gain, organ index, blood immune cells, and ileum morphology, except for those treated with LS9 and EB1. Moreover, the antimicrobial effect of LR6 and LA6 strains was examined in vivo. The results indicated that these strains could mitigate the inflammatory response, reduce bacterial translocation, and alleviate liver, spleen, and ileum injury caused by Salmonella typhimurium infection. In addition, the LR6 treatment group showed better outcomes than the LA6 treatment group; treatment with LR6 substantially reduced the mortality rate in mice. The study results provide evidence of the probiotic properties of the LAB isolates, in particular LR6, and suggest that oral administration of LR6 could have valuable health-promoting benefits.