Distribution and Main Controlling Factors of Gas and Water in Tight Sandstone Gas Fields: A Case Study of Sudong 41-33 Block in Sulige Gas Field, Ordos Basin, China.

Studying the gas-water distribution characteristics is essential in guiding the efficient development of gas fields. The relationship between gas and water in the Sudong 41-33 Block is complicated and has not been adequately researched. In recent years, gas wells have suffered from increased water/gas ratios and significant liquid loadings, which greatly affect the development of the block. A comprehensive analysis of formation water, log interpretation, and production data was conducted to determine the gas-water distribution characteristics and main controlling factors in the Sudong 41-33 Block. The findings indicate the following. (1) The formation water in the study area consists mainly of CaCl2 brine with high total dissolved solids (TDS) (with an average value of 36.06 g/L). The hydrochemical characteristics indicate that the formation water is typical sedimentary buried water under well-sealing conditions, which is markedly different from shallow river water and seawater. (2) The formation water can be categorized into three types: edge-bottom water under the gas layer (Type I), stagnant water in tight sandstone (Type II), and isolated lenticular water (Type III). The water layer distribution in the plane is mainly concentrated in the northwest region, whereas it is dispersed in other regions. On the vertical, the water layer mainly appears in P2x8-1, P2x8-2, and P1s2 Members. (3) The physical properties of the reservoir, hydrocarbon generation intensity (HGI), source rock-reservoir relationship, and mini-structure are the main factors affecting the gas-water distribution in the study area. Based on the clarification of the characteristics of gas and water distribution and its main controlling factors, it is of great importance to accurately identify the water layer, avoid the direct development of the water layer, adopt the proper production pressure differential, and carry out drainage gas production measures in time to ensure the effective development of the gas field.

Clinicopathological characteristics and prognostic factors in invasive micropapillary carcinoma of the breast.

Introduction: Invasive micropapillary carcinoma (IMPC) treatment only relies on the standard treatment of nonspecific invasive breast cancer (NSIBC), and it remains controversial whether the survival of patients improves. Therefore, this study aimed to analyze the clinicopathological features of IMPC and to investigate the factors affecting its prognosis. Material and methods: This retrospective cohort study included 104 IMPC patients who met the study's inclusion criteria out of a total of 4,532 patients with invasive breast cancer between January 2015 and December 2019. A contemporaneous cohort of 230 patients with non-specific invasive breast cancer (NSIBC) who underwent surgery was identified and matched using propensity scores. Results: The survival rate for patients with IMPC ranged from 1.12% to 7.03%. Statistically significant differences were observed in the proportion of endocrine treatment, lymphatic invasion, estrogen receptor (ER)-positive rate, molecular subtypes, molecular typing, and 5-year loco-regional recurrence-free survival (LRRFS) between the two cohorts (p < 0.05). The univariate analysis showed that T stage, N stage, lymphatic invasion, vascular invasion, ER-positive rate, and progesterone receptor (PR)-negative rate were all prognosis risk factors (p < 0.05) for IMPC. Furthermore, the multivariate analysis indicated that lymphatic invasion and N stage were independent prognostic factors (p < 0.05). Conclusions: The incidence of micropapillary IMPC, among other pathological subtypes, is steadily increasing. ER-positive and PR-positive rates, as well as luminal subtypes, are frequent, with a concurrent increase in the 5-year locoregional recurrence rate. It would be interesting to compare the effect following these therapeutic modifications in larger cohorts in future studies.

Interactions of oleanane pentacyclic triterpenoids with human organic anion transporting polypeptide 1B1 and 1B3.

Oleanane pentacyclic triterpenoids have been widely used in clinical practice. However, studies on their interactions with hepatic transporters remain limited. In this study, we systematically investigated the inhibitory effects of 14 oleanane pentacyclic triterpenoids on organic anion transporting polypeptide 1B1 and 1B3 (OATP1B1 and OATP1B3), two liver-specific uptake transporters. Through fluorescence-based cellular uptake assays, we identified three potent OATP1B1 inhibitors (saikosaponin B1, saikosaponin A and 18ß-glycyrrhetinic acid) and five potent OATP1B3 inhibitors (echinocystic acid, 3-oxo-16α-hydroxy-olean-12-en-28ß-oic acid, chikusetsu saponin IVa, saikosaponin B1 and 18ß-glycyrrhetinic acid). Structural analysis revealed that free oleanane triterpenoids inhibited OATP1B1/1B3 more potently than triterpene glycosides. Despite their similar structures, 18ß-glycyrrhetinic acid exhibited much stronger inhibition on OATP1B1/1B3 than 18α-glycyrrhetinic acid, while both were substrates of OATP1B3. Interestingly, OATP1B3 overexpression significantly increased reactive oxygen species (ROS) levels in HepG2 cells after treatment with 18ß-glycyrrhetinic acid. To conclude, this study highlights the potential interactions of oleanane pentacyclic triterpenoids with OATP1B1/1B3, and provides novel insights into the anti-cancer activity of 18ß-glycyrrhetinic acid.

Peptide Transporter 1-Mediated Dipeptide Transport Promotes Hepatocellular Carcinoma Metastasis by Activating MAP4K4/G3BP2 Signaling Axis.

Cancer metastasis is the leading cause of mortality in patients with hepatocellular carcinoma (HCC). To meet the rapid malignant growth and transformation, tumor cells dramatically increase the consumption of nutrients, such as amino acids. Peptide transporter 1 (PEPT1), a key transporter for small peptides, has been found to be an effective and energy-saving intracellular source of amino acids that are required for the growth of tumor cells. Here, the role of PEPT1 in HCC metastasis and its underlying mechanisms is explored. PEPT1 is upregulated in HCC cells and tissues, and high PEPT1 expression is associated with poor prognosis in patients with HCC. PEPT1 overexpression dramatically promoted HCC cell migration, invasion, and lung metastasis, whereas its knockdown abolished these effects both in vitro and in vivo. Mechanistic analysis revealed that high PEPT1 expression increased cellular dipeptides in HCC cells that are responsible for activating the MAP4K4/G3BP2 signaling pathway, ultimately facilitating the phosphorylation of G3BP2 at Thr227 and enhancing HCC metastasis. Taken together, these findings suggest that PEPT1 acts as an oncogene in promoting HCC metastasis through dipeptide-induced MAP4K4/G3BP2 signaling and that the PEPT1/MAP4K4/G3BP2 axis can serve as a promising therapeutic target for metastatic HCC.

Metabolic risks remain a serious threat to cardiovascular disease: findings from the Global Burden of Disease Study 2019.

Metabolic factors are major and controllable risk factors for cardiovascular diseases (CVD), and few studies have described this burden. We aim to assess it from 1990 to 2019 and predict the trends through 2034. Global Burden of Disease (GBD) provides data on sex, age, and socio-demographic index (SDI) levels. Numbers, age-standardized death rates (ASDR) and estimated annual percentage change (EAPC) were used. Future trends were estimated by NORDPRED model. The deaths cases of metabolic-related CVD increased from 8.61 million (95% UI: 7.91-9.29) to 13.71 million (95% UI: 12.24-14.94) globally. The ASDR continued to decline globally (EAPC = -1.36). The burden was heavier in male and middle-aged people and elderly people. CVD-related ASDR caused by high systolic blood pressure (SBP) had a downward trend globally (EAPC = -1.45), while trends of high body mass index (BMI) (EAPC = 1.29, 1.97, 0.92) and fasting plasma glucose (FPG) (EAPC = 0.95, 1.08, 0.46) were increasing in the middle, low-middle, and low SDI regions, respectively. Compared to 2015-2019, cumulative deaths will increase by 27.85% from 2030 to 2034, while ASDR will decrease 10.47%. The metabolic-related CVD burden remained high globally and deaths will continue to rise in the future. Men, middle-aged and elderly people were focus of concern. High SBP was globally well-managed over the past 30 years, but the CVD burden due to high BMI and FPG remained high. Exceptional initiatives are needed to regarding interventions targeting high BMI and FPG in middle and lower SDI regions.

Rutin Attenuates Gentamycin-induced Hair Cell Injury in the Zebrafish Lateral Line via Suppressing STAT1.

Aminoglycoside antibiotics, including gentamicin (GM), induce delayed ototoxic effects such as hearing loss after prolonged use, which results from the death of hair cells. However, the mechanisms underlying the ototoxicity of aminoglycosides warrant further investigation, and there are currently no effective drugs in the clinical setting. Herein, the therapeutic effect of the flavonoid compound rutin against the ototoxic effects of GM in zebrafish hair cells was investigated. Animals incubated with rutin (100-400 µmol/L) were protected against the pernicious effects of GM (200 µmol/L). We found that rutin improves hearing behavior in zebrafish, and rutin was effective in reducing the number of Tunel-positive cells in the neuromasts of the zebrafish lateral line and promoting cell proliferation after exposure to GM. Subsequently, rutin exerted a protective effect against GM-induced cell death in HEI-OC1 cells and could limit the production of cytosolic reactive oxygen species (ROS) and diminish the percentage of apoptotic cells. Additionally, the results of the proteomic analysis revealed that rutin could effectively inhibit the expression of necroptosis and apoptosis related genes. Meanwhile, molecular docking analysis revealed a high linking activity between the molecular docking of rutin and STAT1 proteins. The protection of zebrafish hair cells or HEI-OC1 cells from GM-induced ototoxicity by rutin was attenuated by the introduction of STAT1 activator. Finally, we demonstrated that rutin significantly improves the bacteriostatic effect of GM by in vitro experiments, emphasising its clinical application value. In summary, these results collectively unravel a novel therapeutic role for rutin as an otoprotective drug against the adverse effects of GM.

SF3B3-regulated mTOR alternative splicing promotes colorectal cancer progression and metastasis.

BACKGROUND: Aberrant alternative splicing (AS) is a pervasive event during colorectal cancer (CRC) development. SF3B3 is a splicing factor component of U2 small nuclear ribonucleoproteins which are crucial for early stages of spliceosome assembly. The role of SF3B3 in CRC remains unknown. METHODS: SF3B3 expression in human CRCs was analyzed using publicly available CRC datasets, immunohistochemistry, qRT-PCR, and western blot. RNA-seq, RNA immunoprecipitation, and lipidomics were performed in SF3B3 knockdown or overexpressing CRC cell lines. CRC cell xenografts, patient-derived xenografts, patient-derived organoids, and orthotopic metastasis mouse models were utilized to determine the in vivo role of SF3B3 in CRC progression and metastasis. RESULTS: SF3B3 was upregulated in CRC samples and associated with poor survival. Inhibition of SF3B3 by RNA silencing suppressed the proliferation and metastasis of CRC cells in vitro and in vivo, characterized by mitochondria injury, increased reactive oxygen species (ROS), and apoptosis. Mechanistically, silencing of SF3B3 increased mTOR exon-skipped splicing, leading to the suppression of lipogenesis via mTOR-SREBF1-FASN signaling. The combination of SF3B3 shRNAs and mTOR inhibitors showed synergistic antitumor activity in patient-derived CRC organoids and xenografts. Importantly, we identified SF3B3 as a critical regulator of mTOR splicing and autophagy in multiple cancers. CONCLUSIONS: Our findings revealed that SF3B3 promoted CRC progression and metastasis by regulating mTOR alternative splicing and SREBF1-FASN-mediated lipogenesis, providing strong evidence to support SF3B3 as a druggable target for CRC therapy.

Effect of platelet-rich plasma combined with negative pressure wound therapy in treating patients with chronic wounds: A meta-analysis.

A meta-analysis was conducted to comprehensively explore the effects of platelet-rich plasma (PRP) combined with negative pressure wound therapy (NPWT) in treating patients with chronic wounds. Computer searches were conducted, from database infection to November 2023, in EMBASE, Google Scholar, Cochrane Library, PubMed, Wanfang and China National Knowledge Infrastructure databases for randomized controlled trials (RCTs) on the use of PRP combined with NPWT technology for treating chronic wounds. Two researchers independently screened the literature, extracted data and conducted quality assessments according to the inclusion and exclusion criteria. Stata 17.0 software was employed for data analysis. Overall, 18 RCTs involving 1294 patients with chronic wounds were included. The analysis revealed that, compared with NPWT alone, the use of PRP combined with NPWT technology significantly improved the healing rate (odds ratios [OR] = 1.92, 95% confidence intervals [CIs]: 1.43-2.58, p < 0.001) and total effective rate (OR = 1.31, 95% CI: 1.23-1.39, p < 0.001), and also significantly shortened the healing time of the wound (standardized mean difference = -2.01, 95% CI: -2.58 to -1.45, p < 0.001). This study indicates that the treatment of chronic wounds with PRP combined with NPWT technology can significantly enhance clinical repair effectiveness and accelerate wound healing, with a high healing rate, and is worth further promotion and practice.

Advances in the mechanism of inflammasomes activation in herpes virus infection.

Herpesviruses, prevalent DNA viruses with a double-stranded structure, establish enduring infections and play a part in various diseases. Despite their deployment of multiple tactics to evade the immune system, both localized and systemic inflammatory responses are triggered by the innate immune system's recognition of them. Recent progress has offered more profound understandings of the mechanisms behind the activation of the innate immune system by herpesviruses, specifically through inflammatory signaling. This process encompasses the initiation of an intracellular nucleoprotein complex, the inflammasome associated with inflammation.Following activation, proinflammatory cytokines such as IL-1ß and IL-18 are released by the inflammasome, concurrently instigating a programmed pathway for cell death. Despite the structural resemblances between herpesviruses, the distinctive methods of inflammatory activation and the ensuing outcomes in diseases linked to the virus exhibit variations.The objective of this review is to emphasize both the similarities and differences in the mechanisms of inflammatory activation among herpesviruses, elucidating their significance in diseases resulting from these viral infections.Additionally, it identifies areas requiring further research to comprehensively grasp the impact of this crucial innate immune signaling pathway on the pathogenesis of these prevalent viruses.

Combined exposure of emamectin benzoate and microplastics induces tight junction disorder, immune disorder and inflammation in carp midgut via lysosome/ROS/ferroptosis pathway.

Pesticides and plastics bring convenience to agriculture and life, but also bring residual pollution in the environment. Emamectin benzoate (EMB) is the most popular pesticide at present. The harm of microplastics (MPs) to water and aquatic organisms is gradually increasing, and the possibility that it appears synchronously with various pesticides increases. However, the damage of EMB and MPs to the carp midgut and its mechanism have not been clarified. Therefore, based on the EMB or/and MPs exposure models, this study explored the mechanism of midgut injury through transcriptomics, immunofluorescence, western blot methods, and so on. Studies in vivo and in vitro showed that EMB or MPs exposure caused cilia shortening, lysosome damage, and ROS overproduction, which led to Fe2+ content increase, GSH/GSSG system disorder, lipid peroxidation, and ferroptosis. This process further led to the down-regulation of Cx43, Occludin, Claudin, and ZO-1, which further caused barrier damage, immune-related genes (immunoglobulin, IFN-γ) decrease and inflammation-related genes (TNF-α, IL-1ß) increase. Combined exposure was more significant than that of single exposure, and the addition of EN6 and NAC proved that lysosome/ROS/ferroptosis regulated these midgut damages. In conclusion, EMB or/and MPs exposure induce tight junction disorder, immune disorder and inflammation in carp midgut through the lysosome/ROS/ferroptosis pathway.

Evaluation of aconitine cardiotoxicity with a heart-on-a-particle prepared by a microfluidic device.

A heart-on-a-particle model based on multicompartmental microgel is proposed to simulate the heart microenvironment and study the cardiotoxicity of drugs. The relevant microgel was fabricated by a biocompatible microfluidic-based approach, where heart function-related HL-1 and HUVEC cells were arranged in separate compartments. Finally, the mechanism of aconitine-induced heart toxicity was elucidated using mass spectrometry and molecular biotechnology.

Transcriptome and metabolome analysis reveals PRV XJ delgE/gI/TK protects intracranially infected mice from death by regulating the inflammation.

Pseudorabies virus can cause inflammation in the central nervous system and neurological symptoms. To further investigate the protective mechanism of PRV XJ delgE/gI/TK in the central nervous system, an intracranial PRV-infection mice model was developed. The results demonstrated that immunization with PRV XJ delgE/gI/TK successfully prevented death caused by PRV-intracranial infection. Subsequently, the brains were collected for transcriptome and metabolome analysis. GO and KEGG enrichment analysis indicated that the differentially expressed genes were primarily enriched in pathways such as TNF, NOD-like receptor, JAK-STAT, MAPK, IL-17 and apoptosis signaling. Metabolomics analysis revealed that the differential metabolites were mainly associated with pathways such as fatty acid degradation, arachidonic acid metabolism, linoleic acid metabolism and unsaturated fatty acid biosynthesis. The combined analysis of metabolites and differentially expressed genes revealed a strong correlation between the differential metabolites and TNF, PI3K, and MAPK signaling pathways. Anti-inflammatory metabolites have been shown to inhibit the inflammatory response and prevent mouse death caused by PRV infection. Notably, when glutathione was injected intracranially and dihydroartemisinin was injected intraperitoneally, complete protection against PRV-induced death in mice was observed. Moreover, PRV activates the PI3K/AKT signaling pathway. In conclusion, our study demonstrates that PRV XJ delgE/gI/TK can protects intracranially infected mice from death by regulating various metabolites with anti-inflammatory functions post-immunization.

Multi-interfacial bridging engineering of flexible MXene film for efficient electromagnetic shielding and energy conversion.

Accompanied by the progressive development of electronic equipment, excellent electromagnetic interference (EMI) shielding materials display a satisfying prospect in protecting electronic devices against electromagnetic pollution/radiation, while integrating energy conversion. Heretofore, it remains a conundrum to availably construct thin films with multi-interfacial bridging engineering as multifunctional shielding devices. To effectively achieve electromagnetic wave attenuation and integrate energy conversion, a co-mixed vacuum-assisted filtration strategy is designed to synthesize Au@MXene/cellulose nanocrystal/dodecylbenzenesulfonic acid-doped polyaniline (AMCP) films. Profited from the interfacial engineering, the total EMI shielding effectiveness (SE) can be increased by 27 % with the highest value of 67.9 dB. MXene with localized surface plasmon resonance characteristics gives the composite films good energy conversion performance, that is, the composite film can be rapidly heated up to 100 °C under the irradiation of an infrared lamp, and its surface temperature remains stable after continuous irradiation. Additionally, the infrared emissivity is as low as 0.173 within the 8-14 µm, which is necessary to adapt various application scenarios. Therefore, it is reliable that the AMCP films constructed by multicomponent offer a facile strategy for MXene-based EMI shielding devices with integration characteristics.

Sex differences in the relationships between macronutrients and all-cause mortality in individuals with metabolically unhealthy overweight/obesity.

This study investigates sex differences in the effects of macronutrient quantity, quality, and timing on mortality in metabolically unhealthy overweight/obesity (MUO) populations. The study included 18,345 participants, including 9204 men and 9141 women. The Cox proportional risk model and isocaloric substitution effects were used to examine the association of macronutrient intake and subtype with all-cause mortality in the MUO populations. After adjusting for the potential covariates, The risk of all-cause mortality was elevated in men in the highest 25% percentile of poor-quality carbohydrates compared with men in the lowest quartile (odds ratio [OR]: 2.04; 95% confidence interval [CI], 1.40-2.98). Compared with women in the lowest quartile, the risk of all-cause mortality for women in the highest 25% percentile for high-quality carbohydrates (OR: 0.74; 95% CI, 0.55-0.99) and unsaturated fatty acids (OR: 0.54; 95% CI, 0.32-0.93) were decreased. In women, replacing low-quality carbohydrates with high-quality carbohydrates on an isocaloric basis reduces the risk of all-cause mortality by approximately 9%. We find that different macronutrient consumption subtypes are associated with all-cause mortality in MUO populations, with differential effects between men and women, and that the risk of all-cause mortality is influenced by macronutrient quality and meal timing.

Selection of a Surgical Approach for Middle Ear Cholesteatoma Based on the Fusion Images of Non-Echo Planar Diffusion-Weighted MRI and CT.

PURPOSE: This study aimed to explore the ability of fusion images of non-echo planar diffusion-weighted magnetic resonance imaging (non-EPI-DWI MRI) and computed tomography (CT) to accurately locate cholesteatoma and plan the surgical approach. METHODS: In the first part, 41 patients were included. Their CT images and non-EPI DWMRI images were fused. The scope of cholesteatoma in the fusion image was compared with that in the surgical video to evaluate the capability to locate cholesteatoma. A total of 229 patients were included in the second part, and they were divided into 2 groups. We chose the surgical approach for the CT group and the fusion group, and compared the accuracy of surgical approaches in the CT group and the fusion group using the surgical records. RESULTS: The location of cholesteatoma shown in the fusion images was almost identical to that observed during the operation (kappa = .862). The overall specificity and sensitivity of the fusion images in locating cholesteatoma were 94.12% and 93.06%, respectively. The accuracy of surgical approach selection based on the fusion images (99.02%) was higher than that of surgical approach selection based on the CT images (85.83%). CONCLUSION: It is recommended that the fusion images be used to locate the range of the cholesteatoma before operation.

Isolation and pathogenicity comparison of two novel natural recombinant porcine reproductive and respiratory syndrome viruses with different recombination patterns in Southwest China.

Porcine reproductive and respiratory syndrome virus (PRRSV) causes significant economic losses in the swine industry. Frequent mutations and recombinations account for PRRSV immune evasion and the emergence of novel strains. In this study, we isolated and characterized two novel PRRSV-2 strains from Southwest China exhibiting distinct recombination patterns. They were designated SCABTC-202305 and SCABTC-202309. Phylogenetic results indicated that SCABTC-202305 was classified as lineage 8, and SCABTC-202309 was classified as lineage 1.8. Amino acid mutation analysis identified unique amino acid substitutions and deletions in ORF5 and Nsp2 genes. The results of the recombination analysis revealed that SCABTC-202305 is a recombinant with JXA1 as the major parental strain and NADC30 as the minor parental strain. At the same time, SCABTC-202309 is identified as a recombinant with NADC30 as the major parental strain and JXA1 as the minor parental strain. In this study, we infected piglets with SCABTC-202305, SCABTC-202309, or mock inoculum (control) to study the pathogenicity of these isolates. Although both isolated strains were pathogenic, SCABTC-202305-infected piglets exhibited more severe clinical signs and higher mortality, viral load, and antibody response than SCABTC-202309-infected piglets. SCABTC-202305 also caused more extensive lung lesions based on histopathology. Our findings suggest that the divergent pathogenicity observed between the two novel PRRSV isolates may be attributed to variations in the genetic information encoded by specific genomic regions. Elucidating the genetic determinants governing PRRSV virulence and transmissibility will inform efforts to control this devastating swine pathogen.IMPORTANCEPorcine reproductive and respiratory syndrome virus (PRRSV) is one of the most critical pathogens impacting the global swine industry. Frequent mutations and recombinations have made the control of PRRSV increasingly difficult. Following the NADC30-like PRRSV pandemic, recombination events involving PRRSV strains have further increased. We isolated two novel field PRRSV recombinant strains, SCABTC-202305 and SCABTC-202309, exhibiting different recombination patterns and compared their pathogenicity in animal experiments. The isolates caused higher viral loads, persistent fever, marked weight loss, moderate respiratory clinical signs, and severe histopathologic lung lesions in piglets. Elucidating correlations between recombinant regions and pathogenicity in these isolates can inform epidemiologic tracking of emerging strains and investigations into viral adaptive mechanisms underlying PRRSV immunity evasion. Our findings underscore the importance of continued genomic surveillance to curb this economically damaging pathogen.

Di (2-ethylhexyl) phthalate and polystyrene microplastics co-exposure caused oxidative stress to activate NF-κB/NLRP3 pathway aggravated pyroptosis and inflammation in mouse kidney.

Polystyrene microplastic (PS-MPs) contamination has become a worldwide hotspot of concern, and its entry into organisms can cause oxidative stress resulting in multi-organ damage. The plasticizer di (2-ethylhexyl) phthalate (DEHP) is a common endocrine disruptor, these two environmental toxins often occur together, but their combined toxicity to the kidney and its mechanism of toxicity are unknown. Therefore, in this study, we established PS-MPS and/or DEHP-exposed mouse models. The results showed that alone exposure to both PS-MPs and DEHP caused inflammatory cell infiltration, cell membrane rupture, and content spillage in kidney tissues. There were also down-regulation of antioxidant enzyme levels, increased ROS content, activated of the NF-κB pathway, stimulated the levels of heat shock proteins (HSPs), pyroptosis, and inflammatory associated factors. Notably, the co-exposure group showed greater toxicity to kidney tissues, the cellular assay further validated these results. The introduction of the antioxidant n-acetylcysteine (NAC) and the NLRP3 inhibitor (MCC950) could mitigate the changes in the above measures. In summary, co-exposure of PS-MPs and DEHP induced oxidative stress that activated the NF-κB/NLRP3 pathway and aggravated kidney pyroptosis and inflammation, as well as that HSPs are also involved in this pathologic injury process. This study not only enriched the nephrotoxicity of plasticizers and microplastics, but also provided new insights into the toxicity mechanisms of multicomponent co-pollution in environmental.

Host range expansion of Acinetobacter phage vB_Ab4_Hep4 driven by a spontaneous tail tubular mutation.

Bacteriophages (phages) represent promising alternative treatments against multidrug-resistant Acinetobacter baumannii (MDRAB) infections. The application of phages as antibacterial agents is limited by their generally narrow host ranges, so changing or expanding the host ranges of phages is beneficial for phage therapy. Multiple studies have identified that phage tail fiber protein mediates the recognition and binding to the host as receptor binding protein in phage infection. However, the tail tubular-dependent host specificity of phages has not been studied well. In this study, we isolated and characterized a novel lytic phage, vB_Ab4_Hep4, specifically infecting MDRAB strains. Meanwhile, we identified a spontaneous mutant of the phage, vB_Ab4_Hep4-M, which revealed an expanded host range compared to the wild-type phage. A single mutation of G to C was detected in the gene encoding the phage tail tubular protein B and thus resulted in an aspartate to histidine change. We further demonstrated that the host range expansion of the phage mutant is driven by the spontaneous mutation of guanine to cytosine using expressed tail tubular protein B. Moreover, we established that the bacterial capsule is the receptor for phage Abp4 and Abp4-M by identifying mutant genes in phage-resistant strains. In conclusion, our study provided a detailed description of phage vB_Ab4_Hep4 and revealed the tail tubular-dependent host specificity in A. baumannii phages, which may provide new insights into extending the host ranges of phages by gene-modifying tail tubular proteins.

Targeting DEP domain containing 1 in anaplastic thyroid carcinoma: Implications for stemness regulation and malignant phenotype suppression.

Background: Anaplastic thyroid carcinoma (ATC), a rare but highly aggressive endocrine malignancy, is characterized by a significant presence of cancer stem-like cells (CSCs). These CSCs, known for their self-renewal and differentiation capacities, contribute to various aggressive tumor properties, including recurrence, metastasis, heterogeneity, multidrug resistance, and radiation resistance. Despite their critical role, the regulatory mechanisms of CSCs in ATC remain poorly elucidated, posing challenges in effectively targeting these cells for treatment. Methods: To delve into this, we employed the single sample gene set enrichment analysis (ssGSEA) algorithm to evaluate the stemness of samples in combined datasets. Samples were then classified into high and low stemness subgroups based on their average stemness scores. Differential gene expression between these subgroups was analyzed. We further explored the association of candidate genes with patient prognosis. Additionally, we conducted gene set enrichment analysis (GSEA) and a series of cell biology experiments to validate the role of DEP domain-containing protein 1 (DEPDC1) in fostering CSC-like traits and regulating the malignant phenotypes of ATC. Results: Our investigation demonstrated that DEPDC1 was significantly upregulated in CSCs and is abundantly expressed in ATC tissues. In vitro assays revealed that knockdown of DEPDC1 markedly inhibited tumor sphere formation and attenuated the proliferation, invasion, and migration of ATC cells. This silencing also resulted in reduced expression of stemness markers associated with CSCs. Furthermore, our GSEA findings linked high DEPDC1 expression to cell cycle progression and the maintenance of tumor cell stemness, with DEPDC1 knockdown disrupting these signaling pathways. Collectively, our results position DEPDC1 as a pivotal regulator of CSC-like characteristics in ATC, where aberrant DEPDC1 expression amplifies stemness properties and fuels the cancer's aggressive behavior. Consequently, DEPDC1 emerges as a promising therapeutic target for ATC management. In summary, this study underscores the pivotal role of DEPDC1 in modulating CSC-like features in ATC, offering new avenues for targeted therapy in this challenging malignancy.

A Comparative Study of Two Radiomics-Based Blood Flow Modes with Thyroid Imaging Reporting and Data System in Predicting Malignancy of Thyroid Nodules and Reducing Unnecessary Fine-Needle Aspiration Rate.

RATIONALE AND OBJECTIVES: We aimed to compare superb microvascular imaging (SMI)-based radiomics methods, and contrast-enhanced ultrasound (CEUS)-based radiomics methods to the American College of Radiology Thyroid Imaging Reporting and Data System (ACR TI-RADS) for classifying thyroid nodules (TNs) and reducing unnecessary fine-needle aspiration biopsy (FNAB) rate. MATERIALS AND METHODS: This retrospective study enrolled a dataset of 472 pathologically confirmed TNs. Radiomics characteristics were extracted from B-mode ultrasound (BMUS), SMI, and CEUS images, respectively. After eliminating redundant features, four radiomics scores (Rad-scores) were constructed. Using multivariable logistic regression analysis, four radiomics prediction models incorporating Rad-score and corresponding US features were constructed and validated in terms of discrimination, calibration, decision curve analysis, and unnecessary FNAB rate. RESULTS: The diagnostic performance of the BMUS + SMI radiomics method was better than ACR TI-RADS (area under the curve [AUC]: 0.875 vs. 0.689 for the training cohort, 0.879 vs. 0.728 for the validation cohort) (P < 0.05), and comparable with BMUS + CEUS radiomics method (AUC: 0.875 vs. 0.878 for the training cohort, 0.879 vs. 0.865 for the validation cohort) (P > 0.05). Decision curve analysis showed that the BMUS+SMI radiomics method could achieve higher net benefits than the BMUS radiomics method and ACR TI-RADS when the threshold probability was between 0.13 and 0.88 in the entire cohort. When applying the BMUS+SMI radiomics method, the unnecessary FNAB rate reduced from 43.4% to 13.9% in the training cohort and from 45.6% to 18.0% in the validation cohorts in comparison to ACR TI-RADS. CONCLUSION: The dual-modal SMI-based radiomics method is convenient and economical and can be an alternative to the dual-modal CEUS-based radiomics method in helping radiologists select the optimal clinical strategy for TN management.