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River ecological protection and rational utilization of water resources provide an important support for the sustainable development for human beings and nature. In view of the lack of ecological compensation research on river ecological water demand and socio-economic water demand, a mechanism and methodology for ecological compensation based on the synergistic control of river ecological water demand and river water rights allocation is proposed. The variable monthly flow method and the improved dynamic calculation method are applied to obtain the river basic and suitable ecological water demands as the river protection threshold. A two-layer decision model for water rights allocation is established, which realizes the cascading allocation of initial water rights from city to counties to sectors, and the socio-economic water usage threshold for each level is obtained based on the model. Developing compensation discrimination guidelines under the dual-threshold synergistic control and using the unilateral water resources value by sub-sector as the compensation standard, realize the quantification and sharing of compensation funds. The Nanyang section of the Bai River basin in China is used as an example. The ecological compensation value for wet year (2011), normal year (2012), and dry years (2014-2013) are 0, 15.09 × 108 and 12.04 × 108 (average value for dry years) RMB. The adoption of suitable ecological water demand thresholds in 2012 increases the ecological protection requirements thus leading to an internal compensation situation between Nanyang County and Xinye County. From 2014 to 2016, river runoff continued to be low, and excessive water intake from upstream lead to a chain of compensation situations in the midstream and downstream. It is essential to establish a basin and regionally nested ecological compensation mechanism. The research results are conducive to improving the eco-compensation theory and provide scientific references for water resources management and high-quality development in the basin.

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A novel water-soluble polysaccharide, named PF90-1, with a molecular weight of 1.8 kDa, was isolated and purified from the fibrous root of Pseudostellaria heterophylla. PF90-1 is composed of Gal, Glc and Man in a molar ratio of 73.61: 19.11: 7.28. Methylation analysis revealed that PF90-1 comprises of T-Galp, 1,4-Galp, 1,3,4-Galp, 1,2,3,4-Galp, T-Glcp and 1,3-Manp in a molar ratio of 37.89: 9.37: 17.01: 12.01: 15.88: 7.83. Bioactivity experiments showed that PF90-1 significantly improved lipopolysaccharide (LPS)-induced inflammatory damage in RAW264.7 cells by inhibiting nitric oxide (NO) production and reducing the levels of pro-inflammatory factors (IL-1ß and TNF-α). In addition, PF90-1 exhibited strong antioxidant effects, protecting PC12 cells from H2O2-induced oxidative damage. This findings suggest that PF90-1 holds potential therapeutic value for the treatment of inflammatory and oxidative injuries.

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The identification of key areas for ecological restoration in national land space is crucial for anchoring the bottom line of urban ecological security. As the core of ecological restoration in many resource-based cities, the zoning construction of abandoned mining sites has practical significance. We classified the abandoned mining sites in Handan City based on ecological functions and spatial importance, aiming to provide theoretical support for the orderly development of urban ecological restoration work. In terms of research framework, we proposed to overlay the importance of ecological protection at the functional level and the ecological security pattern at the spatial level, in order to obtain more accurate identification results of key ecological restoration areas at the urban scale. During the study process, we selected four indicators that fitting the regional characteristics of water conservation, soil conservation, biodiversity conservation, and soil erosion sensitivity for ecological protection importance evaluation, and selected the MSPA-Conefor-SPCA-MCR-circuit theory to construct the ecological security pattern. The results showed that 73 out of the remaining 204 abandoned mining sites belonged to the key ecological restoration areas, with a total area of 1500.9 hm2 in Handan City, which were mainly concentrated in the regions of Gushan, Fenghuangshan, and Fushan mountains. These regions had serious ecological and enviornmental problems, but with enormous potential value. Actively seeking site transformation on the basis of simple greening to extend the value chain and industrial chain of mining ecological restoration may become a more important goal in these regions.

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Coronary heart disease, hypertension, myocarditis, and valvular disease cause myocardial fibrosis, leading to heart enlargement, heart failure, heart rate failure, arrhythmia, and premature ventricular beat, even defibrillation can increase the risk of sudden death. Although cardiac fibrosis is common and widespread, there are still no effective drugs to provide adequate clinical intervention for cardiac fibrosis. In this review article, we classify the compounds for treating cardiac fibrosis into natural products, synthetic compounds, and patent drugs according to their sources. Additionally, the structures, activities and signaling pathways of these compounds are discussed. This review provides insight and could provide a reference for the design of new anti-cardiac fibrosis compounds and the new use of older drugs.

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Patient 1, a 12-day-old female infant, presented with fever, cough, dyspnea, and elevated infection markers, requiring respiratory support. Metagenomic next-generation sequencing (mNGS) of blood and bronchoalveolar lavage fluid revealed Legionella pneumophila (LP), leading to diagnoses of LP pneumonia and LP sepsis. The patient was treated with erythromycin for 15 days and azithromycin for 5 days, resulting in recovery and discharge. Patient 2, an 11-day-old female infant, presented with dyspnea, fever, elevated infection markers, and multiple organ dysfunction, requiring mechanical ventilation. mNGS of blood and cerebrospinal fluid indicated LP, leading to diagnoses of LP pneumonia, LP sepsis, and LP intracranial infection. The patient was treated with erythromycin for 19 days and was discharged after recovery. Neonatal LP pneumonia lacks specific clinical symptoms, and azithromycin is the preferred antimicrobial agent. The use of mNGS can provide early and definitive diagnosis for severe neonatal pneumonia of unknown origin.

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Background and Aims: Metabolic dysfunction-associated steatotic liver disease (MASLD) and its more advanced form, metabolic dysfunction-associated steatohepatitis, have emerged as the most prevalent liver diseases worldwide. Currently, lifestyle modification is the foremost guideline-recommended management strategy for MASLD. However, it remains unclear which detrimental signals persist in MASLD even after disease remission. Thus, we aimed to examine the persistent changes in liver transcriptomic profiles following this reversal. Methods: Male C57BL/6J mice were divided into three groups: Western diet (WD) feeding, chow diet (CD) feeding, or diet reversal from WD to CD. After 16 weeks of feeding, RNA sequencing was performed on the mice's livers to identify persistent alterations characteristic of MASLD. Additionally, RNA sequencing databases containing high-fat diet-fed P53-knockout mice and human MASLD samples were utilized. Results: WD-induced MASLD triggered persistent activation of the DNA damage response (DDR) and its primary transcription factor, P53, long after the resolution of the hepatic phenotype through dietary reversal. Elevated levels of P53 might promote apoptosis, thereby exacerbating metabolic dysfunction-associated steatohepatitis, as they strongly correlated with hepatocyte ballooning, an indicator of apoptosis activation. Moreover, P53 knockout in mice led to downregulated expression of apoptosis signaling in the liver. Mechanistically, P53 may regulate apoptosis by transcriptionally activating the expression of apoptosis-enhancing nuclease (AEN). Consistently, P53, AEN, and the apoptosis process all exhibited persistently elevated expression and showed a strong inter-correlation in the liver following dietary reversal. Conclusions: The liver demonstrated upregulation of DDR signaling and the P53-AEN-apoptosis axis both during and after exposure to WD. Our findings provide new insights into the mechanisms of MASLD relapse, highlighting DDR signaling as a promising target to prevent MASLD recurrence.

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Understanding the differences in ubiquitination-modified proteins between Duroc pigs and Tibetan fragrant pigs is crucial for comprehending the growth and development of their skeletal muscles. In this study, skeletal muscle samples from 30-day-old Duroc pigs and Tibetan fragrant pigs were collected. Using ubiquitination 4D-Label free quantitative proteomics, we analyzed and identified ubiquitination-modified peptides, screening out 109 differentially expressed ubiquitination-modified peptides. Further enrichment analysis was conducted on the proteins associated with these differential peptides. GO analysis results indicated that the differential genes were primarily enriched in processes such as regulation of protein transport, motor activity, myosin complex, and actin cytoskeleton. KEGG pathway analysis revealed significant enrichment in pathways such as Glycolysis/Gluconeogenesis and Hippo signaling pathway. The differentially expressed key ubiquitinated proteins, including MYL1, MYH3, TNNC2, TNNI1, MYLPF, MYH1, MYH7, TNNT2, TTN, and TNNC1, were further identified. Our analysis demonstrates that these genes play significant roles in skeletal muscle protein synthesis and degradation, providing new insights into the molecular mechanisms of muscle development in Duroc pigs and Tibetan fragrant pigs, and offering theoretical support for breeding improvements in the swine industry.

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Background: Drought constitutes a major abiotic stress factor adversely affecting plant growth and productivity. Plant-microbe symbiotic associations have evolved regulatory mechanisms to adapt to environmental stress conditions. However, the interactive effects of different fungi on host growth and stress tolerance under drought conditions remain unclear. Objective: This study explored the effects of varying polyethylene glycol (PEG-6000) concentrations (0%, 15%, 25%, and 35%) on the growth and physiological responses of two ectomycorrhizal fungi (Suillus granulatus (Sg) and Pisolithus tinctorius (Pt)) and two dark septate endophytes (Pleotrichocladium opacum (Po) and Pseudopyrenochaeta sp. (Ps)) isolated from the root system of Pinus tabuliformis. Specifically, the study aimed to evaluate six inoculation treatments, including no inoculation (CK), single inoculations with Sg, Pt, Po, Ps, and a mixed inoculation (Sg: Pt : Po: Ps = 1:1:1:1), on the growth and physiological characteristics of P. tabuliformis seedlings under different water regimes: well-watered at 70% ± 5%, light drought at 50% ± 5%, and severe drought at 30% ± 5% of the maximum field water holding capacity. Results: All four fungi exhibited the capacity to cope with drought stress by enhancing antioxidant activities and regulating osmotic balance. Upon successful root colonization, they increased plant height, shoot biomass, root biomass, total biomass, and mycorrhizal growth response in P. tabuliformis seedlings. Under drought stress conditions, fungal inoculation improved seedling drought resistance by increasing superoxide dismutase and catalase activities, free proline and soluble protein contents, and promoting nitrogen and phosphorus uptake. Notably, mixed inoculation treatments significantly enhanced antioxidant capacity, osmotic adjustment, and nutrient acquisition abilities, leading to superior growth promotion effects under drought stress compared to single inoculation treatments. Conclusion: All four fungi tolerated PEG-induced drought stress, with increased antioxidant enzyme activities and osmotic adjustment substances and they promoted the growth and enhanced drought resistance of P. tabuliformis seedlings.

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Difenoconazole (DIF) is frequently used for the management of fungal infections in fruit and vegetables and excessive residues in the aquatic environment can have adverse effects on fish such as growth inhibition. A treatment based on the dietary additive quercetin (QUE) is a promising approach to positively regulate the state of fish growth. This study focused on whether and how QUE alleviated DIF-induced growth inhibition in fish. In this study, carp were exposed to DIF (0.3906 mg/L) for consecutive 30 d, which showed growth inhibition. Disruption of the intestinal barrier led to elevated levels of intestinal lipopolysaccharide (LPS) and an inflammatory response. Through the intestinal-brain axis, LPS entered the brain where it disrupted the blood-brain barrier, triggered neuroinflammation, caused brain cell apoptosis, and damaged nerves in addition to other things. The dietary supplementation of QUE (400 mg/kg) reduced the levels of LPS in the intestinal and brain, while reducing inflammation and increasing the expression of appetite factors, thereby reducing growth inhibition in carp. This work provided evidence for QUE from the intestinal-brain axis perspective as a potential candidate for alleviating growth inhibition in fish.

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BACKGROUND: Extending the dosing interval of a primary series of mRNA COVID-19 vaccination has been employed to reduce myocarditis risk in adolescents, but previous evaluation of impact on vaccine effectiveness (VE) is limited to risk after second dose. METHODS: We quantified the impact of the dosing interval based on case notifications and vaccination uptake in Hong Kong from January to April 2022, based on calendar-time proportional hazards models and matching approaches. RESULTS: We estimated that the hazard ratio (HR) and odds ratio (OR) of infections after the second dose for extended (28 days or more) versus regular (21-27 days) dosing intervals ranged from 0.86 to 0.99 from calendar-time proportional hazards models, and from 0.85 to 0.87 from matching approaches, respectively. Adolescents in the extended dosing groups (including those who did not receive a second dose in the study period) had a higher hazard of infection than those with a regular dosing interval during the intra-dose period (HR 1.66; 95% CI 1.07, 2.59; p = 0.02) after the first dose. CONCLUSIONS: Implementing an extended dosing interval should consider multiple factors including the degree of myocarditis risk, the degree of protection afforded by each dose, and the extra protection achievable using an extended dosing interval.

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BACKGROUND: The prevalence of Pneumocystis jirovecii (PJ) pneumonia among rheumatic patients is rising. PJ colonization serves as a reservoir for transmission and precedes the development of PJ pneumonia. We aim to clarify the association of PJ colonization in patients of rheumatoid arthritis (RA) treated with biologics or Janus kinase inhibitors (JAKi). METHODS: A prospective cohort study was performed from March 2021 to July 2022 in the rheumatology outpatient department of National Cheng Kung University Hospital. We obtained oral-wash samples from asymptomatic RA patients treated with biologic disease-modifying antirheumatic drugs (bDMARDs) and JAKi. A real-time quantitative polymerase chain reaction assay focusing on the mitochondrial large subunit ribosomal ribonucleic acid gene of PJ was applied to detect colonization. RESULTS: One hundred and ten RA patients were enrolled. Adjusted odds ratios (ORs) of PJ colonization were 6.40 (95% CI 1.34-30.57, p-value =0.02) in patients receiving bDMARDs or JAKi. Specifically, in patients treated with bDMARDs the adjusted OR was 8.08 (95% CI 1.57-41.51, p-value=0.012), and a trend toward developing PJ colonization was further identified in patients receiving JAKi (adjusted OR: 4.79, 95% CI 0.89-25.91, p=0.069). Among patients treated with bDMARDs or JAKi, medication duration >3 years and age >60 y/o are risk factors for PJ colonization. CONCLUSION: RA patients on bDMARDs or JAK inhibitors have an approximately 6-fold higher risk of developing P. jirovecii colonization. Patients treated with bDMARDs had an 8-fold higher risk of P. jirovecii colonization. Risk factors of PJ colonization are medication duration >3 years and age > 60 y/o.

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BACKGROUND: Previous studies reported that lead (Pb) exposure induced adverse health effects at high exposure concentrations, however, there have been limited data on sensitivity comparisons among different health outcomes at low blood Pb levels. OBJECTIVES: To compare sensitivity between blood parameters and a genotoxic biomarker among workers exposed to low blood Pb levels (< 20 µg/dl), and to estimate a benchmark dose (BMD). METHODS: Pb-exposed workers were recruited from a lead-acid storage battery plant. Their blood lead levels (BLLs) were measured. Blood parameters and micronuclei (MN) frequencies were determined. Multivariate linear or Poisson regression was used to analyze relationships between blood parameters or MN frequencies with BLLs. Two BMD software were used to calculate BMD and its 95 % lower confidence limit (BMDL) for BLLs. RESULTS: The median BLL for 611 workers was 10.44 µg/dl with the 25th and 75th percentile being 7.37 and 14.62 µg/dl among all participants. There were significantly negative correlations between blood parameters and BLLs. However, MN frequencies correlated positively with BLLs (all P<0.05). Results from the two BMD software revealed that the dichotomous model was superior to the continuous model, and the BMDL for BLL derived from red blood cell (RBC) was 15.11 µg/dl, from hemoglobin (HGB) was 8.50 µg/dl, from mean corpuscular hemoglobin (MCH) was 7.87 µg/dl, from mean corpuscular hemoglobin concentration (MCHC) was 3.98 µg/dl, from mean corpuscular volume (MCV) was 11.44 µg/dl, and from hematocrit (HCT) was 6.65 µg/dl. The conservative BMDL obtained from the MN data was 7.52 µg/dl. CONCLUSION: Our study shows that low dose Pb exposure caused decrease of blood parameters and increase of MN frequencies. The genotoxic biomarker was more sensitive than most blood parameters. BMDLs for BLL derived from MN frequencies and the red blood cell indicators should be considered as new occupational exposure limits. Our results suggest that MN assay can be considered as a part of occupational health examination items.

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Inflammatory arthritis leads to peripheral nerve sensitization, but the therapeutic effect is often unsatisfactory. Our preliminary studies have found that in mice with inflammatory arthritis, the use of ionotropic glutamate receptor antagonists can produce a good analgesic effect without altering foot swelling, suggesting that pain relief may be related to the improvement of neuropathic pain. However, the underlying mechanisms remain unclear. To further investigate the effects of neuropathic pain medications on inflammatory arthritis and the impact of the ionotropic glutamate receptor NR2B subunit (NR2B) on inflammatory arthritis, this study employed gabapentin (GBP) treatment on the inflammatory arthritis mouse model (the adjuvant induced arthritis, AIA), and we found a significant reduction in pain. Further studies revealed that in AIA, the expression levels of NR2B, TRPV1, pain-related molecules (substance P, PGE2), inflammatory cytokines (IL-1, IL-6, TNF-α, and GM-CSF) and Ca2+ were elevated in the foot and dorsal root ganglia (DRG). GBP treatment was able to influence the downregulation of the expression levels of NR2B, TRPV1, pain-related molecules, inflammatory cytokines and Ca2+. Mechanistic studies have shown that GBP treatment affects the downregulation of NR2B, and the downregulation of NR2B expression leads to the downregulation of TRPV1, pain-related molecules and inflammatory cytokines, thereby alleviating pain. These results suggest that in peripheral sensitization caused by AIA, GBP can play a role in improving pain, and NR2B may be a key target of peripheral nerve sensitization induced by inflammatory arthritis. GBP provides a theoretical basis for the clinical treatment of inflammatory arthritis.

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Single crystals of a new titanium oxysulfide, LiLa3Ti2S3O6, were grown from a KI molten salt. Single-crystal X-ray diffraction analysis revealed that LiLa3Ti2S3O6 crystallizes in the space group Pnma with lattice parameters of a = 11.7319(4) Å, b = 3.94787(14) Å, and c = 20.6885(6) Å. In this structure, the one-dimensional chains of corner-sharing TiO5S octahedra are further corner-linked via equatorial and apical oxygen atoms to form unique corrugated two-dimensional perovskite-type layers in the ab plane with one octahedral thickness. These layers were intervened along the c-axis by the LaS rock-salt layers corrugated concomitantly with the perovskite-type layers, and LiO2S2 tetrahedral chains were located between these two types of two-dimensional layers. LiLa3Ti2S3O6 can be viewed as a modified K2NiF4-type structure with TiO5S octahedral layers stacked in a zigzag manner along the c axis. The oxysulfide has a direct-type band gap of 1.85 eV, based on UV-vis-NIR diffuse reflectance measurements. First-principles calculations showed that the conduction band minimum mainly consists of Ti 3d orbitals, and the valence band maximum consists of S 3p, O 2p, and Li 2s orbitals. The electronic structures near the Fermi level are similar to those of the structurally related photocatalytic oxysulfides Y2Ti2S2O5 and La5Ti2CuS5O7.

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One challenge for gas sensors is humidity interference, as dynamic humidity conditions can cause unpredictable fluctuations in the response signal to analytes, increasing quantitative detection errors. Here, we introduce a concept: Select humidity sensors from a pool to compensate for the humidity signal for each gas sensor. In contrast to traditional methods that extremely suppress the humidity response, the sensor pool allows for more accurate gas quantification across a broader range of application scenarios by supplying customized, high-dimensional humidity response data as extrinsic compensation. As a proof-of-concept, mitigation of humidity interference in colorimetric gas quantification was achieved in three steps. First, across a ten-dimensional variable space, an algorithm-driven high-throughput experimental robot discovered multiple local optimum regions where colorimetric humidity sensing formulations exhibited high evaluations on sensitivity, reversibility, response time, and color change extent for 10-90% relative humidity (RH) in room temperature (25 °C). Second, from the local optimum regions, 91 sensing formulations with diverse variables were selected to construct a parent colorimetric humidity sensor array as the sensor pool for humidity signal compensation. Third, the quasi-optimal sensor subarrays were identified as customized humidity signal compensation solutions for different gas sensing scenarios across an approximately full dynamic range of humidity (10-90% RH) using an ingenious combination optimization strategy, and two accurate quantitative detections were attained: one with a mean absolute percentage error (MAPE) reduction from 4.4 to 0.75% and the other from 5.48 to 1.37%. Moreover, the parent sensor array's excellent humidity selectivity was validated against 10 gases. This work demonstrates the feasibility and superiority of robot-assisted construction of a customizable parent colorimetric sensor array to mitigate humidity interference in gas quantification.

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OBJECTIVE: Limited research has focused on the role of dihydrouridine synthases (DUS) family members in human tumors. Our previous findings indicated an impact of dihydrouridine synthase 4 like (DUS4L) on cell proliferation and apoptosis in lung adenocarcinoma (LUAD) A549 cell, yet its broader functions and regulatory mechanisms in LUAD remain elusive. METHODS: Using a LUAD tissue microarray and immunohistochemical (IHC) staining, we validated variations in DUS4L protein expression levels among LUAD patients and assessed its clinical significance. Additional experiments using short hairpin RNA (shRNA) against DUS4L (sh-DUS4L-2), LUAD cell lines, cell function assays (including wound healing, transwell migration and invasion, colony formation, and apoptosis assays), and mouse tumor xenografts were performed to examine the biological roles of DUS4L in LUAD progression. RNA sequencing, proteomic analyses, mass spectrometry, and co-immunoprecipitation experiments were conducted to identify and validate DUS4L-regulated downstream target genes and signaling pathways. RESULTS: We identified a consistent upregulation of DUS4L in LUAD tissues. In vitro and in vivo experiments underscored the inhibitory effect of DUS4L downregulation on LUAD progression, including migration, invasion, and proliferation. Mechanistically, DUS4L was found to interact with the signaling molecule GRB2, promoting LUAD progression and metastasis by inducing epithelial-mesenchymal transition (EMT) via the PI3K/AKT and ERK/MAPK pathways. CONCLUSION: Our results establish the functional role of DUS4L in driving the progression and metastasis of LUAD, implicating its potential as a candidate therapeutic target for LUAD.

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Detect the expression of Farnesoid X Receptor(FXR), Multiple Drug Resistance Associated Protein-1(MRP-1) and Solute Carrier Family 7, Member 5 (SLC7A5) in hepatocellular carcinoma(HCC) of rat model, so as to provide new therapeutic targets for gene therapy of HCC. Sixty male Wistar rats were randomly divided into three groups. The rats in experimental group were given 0.2% diethylnitrosamine (DEN) by gavage with a dose of 10 mg/kg, 3 times a week, and it stopped at 12 weeks. The control group rats were given physiological saline by gavage, while the sham operation group did not receive anything by gavage. At 10 weeks, one rat in the experimental group was euthanized, and the changes of livers were recorded. The procedure was repeated at 12 weeks. After 12 weeks, HCC only occurred in the experimental group. After confirming the formation of the tumor through pathological examination, liver tissues and tumor tissues were taken from the three groups. FXR, MRP-1 and SLC7A5 expression in liver tissues and tumor tissues was detected. After 7 weeks the rats in experimental group ate less, and their weight was significantly reduced. Three months later, HCC was detected in 15 rats in the experimental group. The ratio of FXR/GAPDH mRNA, MRP-1/GAPDH mRNA, SLC7A5/GAPDH mRNA were significantly different among the three groups. Under the light microscope the FXR protein, MRP-1 protein, and SLC7A5 protein react with their respective antibodies, and they showed granular expression. Every pathological section included different numbers of positive cells in each group. FXR expression in HCC of rats was significantly lower than that in normal liver tissues, but MRP-1 and SLC7A5 expression in HCC were significantly higher than that in normal liver tissues, suggesting that drugs targeting FXR, MRP-1 and SLC7A5 may be new strategies for the treatment of HCC.

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In this study, eight lindenane-type sesquiterpene dimers, including five previously undescribed sesquiterpene dimers (1-5), were isolated from the roots of Chloranthus fortunei, and their structures were elucidated using 1D/2D NMR, HRESIMS, and ECD calculations. Compound 1 presents the second example of a type of novel 8,9-seco lindenane-type sesquiterpene dimer, considered a product of 8/9-diketone oxidation. Compounds 2 and 3 represent the third and fourth examples, respectively, of this kind of C-11 methine dimer. Furthermore, compound 4 was considered as an artifact generated from the radical reaction of a known compound chlojaponilide F (6), which was explained by the density functional theory quantum calculation. All isolates were evaluated for their protective activity against the LPS-induced pulmonary epithelial cell line with compound 7 exhibiting the most potent bioactivity. Further in vitro biological evaluation demonstrated that 7 reduced the production of reactive oxygen species and interleukin-1ß, further regulated by the expression of the NLRP3. These results show that compound 7 exhibits therapeutic potential for lung inflammatory diseases.

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BACKGROUND: The emergence of SARS-CoV-2 in late 2019 sparked the global COVID-19 pandemic, leading to varied vaccine policies worldwide. The evolving patterns of respiratory pathogens, aside from SARS-CoV-2, during the pandemic have had a significant impact on the development of vaccine strategies. METHODS: This study explores the landscape of respiratory pathogens, encompassing SARS-CoV-2, respiratory syncytial virus (RSV), and influenza viruses, through a retrospective analysis of data obtained from the BioFire Respiratory Panel 2.1 (RP 2.1) at China Medical University Hospital (Taichung, Taiwan) spanning from January 2020 to November 2023. RESULTS: Among the 7950 respiratory samples studied, pediatric cases exhibited higher positivity (64.9%, 2488/3835) and mixed detection rates (43.8%, 1090/2488) than adults. Annual mixed detection rates increased (27.9-48%). Prevalence analysis revealed diverse patterns across age groups, with higher rates in pediatrics. Notably, human rhinovirus/enterovirus predominated (48.1%). Mixed detection illustrated viral co-detections, notably with parainfluenza viruses and adenovirus. Government policies and pandemic dynamics influenced infection patterns, with RSV resurgence after May 2022. Age-specific RSV detection demonstrated a shift, influencing vaccine considerations. Amid global vaccine initiatives, RSV's increasing trend in adults warrants attention. CONCLUSIONS: This comprehensive analysis emphasizes the importance of multiplex PCR testing in shaping targeted vaccination strategies during evolving respiratory pathogen landscapes.

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Mammalian cochlea spiral ganglion neurons (SGNs) are crucial for sound transmission, they can be damaged by chemotherapy drug cisplatin and lead to irreversible sensorineural hearing loss (SNHL), while such damage can also render cochlear implants ineffective. However, the mechanisms underlying cisplatin-induced SGNs damage and subsequent SNHL are still under debate and there is no currently effective clinical treatment. Here, this study demonstrates that ferroptosis is triggered in SGNs following exposure to cisplatin. Inhibiting ferroptosis protects against cisplatin-induced SGNs damage and hearing loss, while inducing ferroptosis intensifies these effects. Furthermore, cisplatin prompts nuclear receptor coactivator 4 (NCOA4)-mediated ferritinophagy in SGNs, while knocking down NCOA4 mitigates cisplatin-induced ferroptosis and hearing loss. Notably, the upstream regulator of NCOA4 is identified and transcription factor forkhead box O1 (FOXO1) is shown to directly suppress NCOA4 expression in SGNs. The knocking down of FOXO1 amplifies NCOA4-mediated ferritinophagy, increases ferroptosis and lipid peroxidation, while disrupting the interaction between FOXO1 and NCOA4 in NCOA4 knock out mice prevents the cisplatin-induced SGN ferroptosis and hearing loss. Collectively, this study highlights the critical role of the FOXO1-NCOA4 axis in regulating ferritinophagy and ferroptosis in cisplatin-induced SGNs damage, offering promising therapeutic targets for SNHL mitigation.