P3N-PIPO but not P3 is the avirulence determinant in melon carrying the Wmr resistance against watermelon mosaic virus, although they contain a common genetic determinant.

Viruses employ a series of diverse translational strategies to expand their coding capacity, which produces viral proteins with common domains and entangles virus-host interactions. P3N-PIPO, which is a transcriptional slippage product from the P3 cistron, is a potyviral protein dedicated to intercellular movement. Here, we show that P3N-PIPO from watermelon mosaic virus (WMV) triggers cell death when transiently expressed in Cucumis melo accession PI 414723 carrying the Wmr resistance gene. Surprisingly, expression of the P3N domain, shared by both P3N-PIPO and P3, can alone induce cell death, whereas expression of P3 fails to activate cell death in PI 414723. Confocal microscopy analysis revealed that P3N-PIPO targets plasmodesmata (PD) and P3N associates with PD, while P3 localizes in endoplasmic reticulum in melon cells. We also found that mutations in residues L35, L38, P41, and I43 of the P3N domain individually disrupt the cell death induced by P3N-PIPO, but do not affect the PD localization of P3N-PIPO. Furthermore, WMV mutants with L35A or I43A can systemically infect PI 414723 plants. These key residues guide us to discover some WMV isolates potentially breaking the Wmr resistance. Through searching the NCBI database, we discovered some WMV isolates with variations in these key sites, and one naturally occurring I43V variation enables WMV to systemically infect PI 414723 plants. Taken together, these results demonstrate that P3N-PIPO, but not P3, is the avirulence determinant recognized by Wmr, although the shared N terminal P3N domain can alone trigger cell death.IMPORTANCEThis work reveals a novel viral avirulence (Avr) gene recognized by a resistance (R) gene. This novel viral Avr gene is special because it is a transcriptional slippage product from another virus gene, which means that their encoding proteins share the common N-terminal domain but have distinct C-terminal domains. Amazingly, we found that it is the common N-terminal domain that determines the Avr-R recognition, but only one of the viral proteins can be recognized by the R protein to induce cell death. Next, we found that these two viral proteins target different subcellular compartments. In addition, we discovered some virus isolates with variations in the common N-terminal domain and one naturally occurring variation that enables the virus to overcome the resistance. These results show how viral proteins with common domains interact with a host resistance protein and provide new evidence for the arms race between plants and viruses.

Unravelling the molecular landscape of endometrial cancer subtypes: insights from multi-omics analysis.

BACKGROUND: Endometrial cancer (EC) as one of the most common gynecologic malignancies is increasing in incidence during the past 10 years. Genome-Wide Association Studies (GWAS) extended to metabolic and protein phenotypes inspired us to employ multi-omics methods to analyze the causal relationships of plasma metabolites and proteins with EC to advance our understanding of EC biology and pave the way for more targeted approaches to its diagnosis and treatment by comparing the molecular profiles of different EC subtypes. METHODS: Two-sample Mendelian randomization (MR) was performed to investigate the effects of plasma metabolites and proteins on risks of different subtypes of EC (endometrioid and non-endometrioid). Pathway analysis, transcriptomic analysis, and network analysis were further employed to illustrate gene-protein-metabolites interactions underlying the pathogenesis of distinct EC histological types. RESULTS: We identified 66 causal relationships between plasma metabolites and endometrioid EC, and 132 causal relationships between plasma proteins and endometrioid EC. Additionally, 40 causal relationships between plasma metabolites and non-endometrioid EC, and 125 causal relationships between plasma proteins and non-endometrioid EC were observed. Substantial differences were observed between endometrioid and non-endometrioid histological types of EC at both the metabolite and protein levels. We identified 7 overlapping proteins (RGMA, NRXN2, EVA1C, SLC14A1, SLC6A14, SCUBE1, FGF8) in endometrioid subtype and 6 overlapping proteins (IL32, GRB7, L1CAM, CCL25, GGT2, PSG5) in non-endometrioid subtype and network analysis of above proteins and metabolites to identify coregulated nodes. CONCLUSIONS: Our findings observed substantial differences between endometrioid and non-endometrioid EC at the metabolite and protein levels, providing novel insights into gene-protein-metabolites interactions that could influence future EC treatments.

Sorting Out the Latest Advances in Separators and Pilot-Scale Microbial Electrochemical Systems for Wastewater Treatment: Concomitant Development, Practical Application, and Future Perspective.

To date, dozens of pilot-scale microbial fuel cell (MFC) devices have been successfully developed worldwide for treating various types of wastewater. The availability and configurations of separators are determining factors for the economic feasibility, efficiency, sustainability, and operability of these devices. Thus, the concomitant advances between the separators and pilot-scale MFC configurations deserve further clarification. The analysis of separator configurations has shown that their evolution proceeds as follows: from ion-selective to ion-non-selective, from nonpermeable to permeable, and from abiotic to biotic. Meanwhile, their cost is decreasing and their availability is increasing. Notably, the novel MFCs configured with biotic separators are superior to those configured with abiotic separators in terms of wastewater treatment efficiency and capital cost. Herein, a highly comprehensive review of pilot-scale MFCs (>100 L) has been conducted, and we conclude that the intensive stack of the liquid cathode configuration is more advantageous when wastewater treatment is the highest priority. The use of permeable biotic separators ensures hydrodynamic continuity within the MFCs and simplifies reactor configuration and operation. In addition, a systemic comparison is conducted between pilot-scale MFC devices and conventional decentralized wastewater treatment processes. MFCs showed comparable cost, higher efficiency, long-term stability, and significant superiority in carbon emission reduction. The development of separators has greatly contributed to the availability and usability of MFCs, which will play an important role in various wastewater treatment scenarios in the future.

A ghost epigastric pain.

A 16-year-old woman complained of intermittent epigastric pain for one year. The gastroscopy, colonoscopy and laboratory findings were normal. Physical examination was unremarkable other than upper abdominal tenderness. The symptom was not relieved in past medical treatment. The abdominal computed tomography (CT) scan revealed appendix wall swelling and suspected appendicitis. Endoscopic retrograde appendicitis therapy (ERAT) with eyeMax (Micro-tech, China) was proposed to perform after informed consent obtained. A colonoscopy with a transparent cap (Olympus, Japan) attached to the tip was inserted into the cecum, and advanced the level of appendicular orifice. Subsequently, the Gerlach's valve was pushed aside using the transparent cap. Finally, the eyeMax was placed in the appendicular orifice, slowly moved forward in appendicular lumen. The eyeMax showed a lot of appendicular stones, and irrigated repeatedly. The stones were expulsed smoothly. The patient was discharged two days later without recurrent epigastric pain on follow-up and to date.

Successful removal of a duodenal lesion in difficult location using "a sandwich method".

A 69-year-old woman was diagnosed with a duodenal adenoma near major duodenal papilla during cancer screening examination (Figure 1A). Therefore, endoscopic mucosal resection (EMR) was proposed to remove the duodenal lesion. Unfortunately, satisfactory visualization of the duodenal lesion was not obtained during gastroscopic operation. Unexpectedly, duodenoscopy provided optimal visualization of the duodenal lesion. Consequently, the "sandwich method" using duodenoscopy-gastroscopy-duodenoscopy was successfully performed to remove the challenging duodenal lesion. Firstly, the duodenoscopy was used to create a submucosal bleb through injecting saline containing 0.3 % indigo carmine. Subsequently, the gastroscopy with a transparent capwas used to remove the duodenal lesion with en bloc resection. Then, the duodenoscopy was reused to close the mucosal defect. Finally, pathologic examination showed a tubule-villous adenoma. The patient was recovered uneventfully, and discharged 2 days later.

Hydrogen gas inhalation ameliorates LPS-induced BPD by inhibiting inflammation via regulating the TLR4-NFκB-IL6/NLRP3 signaling pathway in the placenta.

INTRODUCTION: Hydrogen (H2) is regarded as a novel therapeutic agent against several diseases owing to its inherent biosafety. Bronchopulmonary dysplasia (BPD) has been widely considered among adverse pregnancy outcomes, without effective treatment. Placenta plays a role in defense, synthesis, and immunity, which provides a new perspective for the treatment of BPD. This study aimed to investigate if H2 reduced the placental inflammation to protect the neonatal rat against BPD damage and potential mechanisms. METHODS: We induced neonatal BPD model by injecting lipopolysaccharide (LPS, 1 µg) into the amniotic fluid at embryonic day 16.5 as LPS group. LPS + H2 group inhaled 42% H2 gas (4 h/day) until the samples were collected. We primarily analyzed the neonatal outcomes and then compared inflammatory levels from the control group (CON), LPS group and LPS + H2 group. HE staining was performed to evaluate inflammatory levels. RNA sequencing revealed dominant differentially expressed genes. Bioinformatics analysis (GO and KEGG) of RNA-seq was applied to mine the signaling pathways involved in protective effect of H2 on the development of LPS-induced BPD. We further used qRT-PCR, Western blot and ELISA methods to verify differential expression of mRNA and proteins. Moreover, we verified the correlation between the upstream signaling pathways and the downstream targets in LPS-induced BPD model. RESULTS: Upon administration of H2, the inflammatory infiltration degree of the LPS-induced placenta was reduced, and infiltration significantly narrowed. Hydrogen normalized LPS-induced perturbed lung development and reduced the death ratio of the fetus and neonate. RNA-seq results revealed the importance of inflammatory response biological processes and Toll-like receptor signaling pathway in protective effect of hydrogen on BPD. The over-activated upstream signals [Toll-like receptor 4 (TLR4), nuclear factor kappa-B p65 (NF-κB p65), Caspase1 (Casp1) and NLR family pyrin domain containing 3 (NLRP3) inflammasome] in LPS placenta were attenuated by H2 inhalation. The downstream targets, inflammatory cytokines/chemokines [interleukin (IL)-6, IL-18, IL-1ß, C-C motif chemokine ligand 2 (CCL2) and C-X-C motif chemokine ligand 1 (CXCL1)], were decreased both in mRNA and protein levels by H2 inhalation in LPS-induced placentas to rescue them from BPD. Correlation analysis displayed a positive association of TLR4-mediated signaling pathway both proinflammatory cytokines and chemokines in placenta. CONCLUSION: H2 inhalation ameliorates LPS-induced BPD by inhibiting excessive inflammatory cytokines and chemokines via the TLR4-NFκB-IL6/NLRP3 signaling pathway in placenta and may be a potential therapeutic strategy for BPD.

ChineseEEG: A Chinese Linguistic Corpora EEG Dataset for Semantic Alignment and Neural Decoding.

An Electroencephalography (EEG) dataset utilizing rich text stimuli can advance the understanding of how the brain encodes semantic information and contribute to semantic decoding in brain-computer interface (BCI). Addressing the scarcity of EEG datasets featuring Chinese linguistic stimuli, we present the ChineseEEG dataset, a high-density EEG dataset complemented by simultaneous eye-tracking recordings. This dataset was compiled while 10 participants silently read approximately 13 hours of Chinese text from two well-known novels. This dataset provides long-duration EEG recordings, along with pre-processed EEG sensor-level data and semantic embeddings of reading materials extracted by a pre-trained natural language processing (NLP) model. As a pilot EEG dataset derived from natural Chinese linguistic stimuli, ChineseEEG can significantly support research across neuroscience, NLP, and linguistics. It establishes a benchmark dataset for Chinese semantic decoding, aids in the development of BCIs, and facilitates the exploration of alignment between large language models and human cognitive processes. It can also aid research into the brain's mechanisms of language processing within the context of the Chinese natural language.

Shikonin and chitosan-silver nanoparticles synergize against triple-negative breast cancer through RIPK3-triggered necroptotic immunogenic cell death.

Necroptotic immunogenic cell death (ICD) can activate the human immune system to treat the metastasis and recurrence of triple-negative breast cancer (TNBC). However, developing the necroptotic inducer and precisely delivering it to the tumor site is the key issue. Herein, we reported that the combination of shikonin (SHK) and chitosan silver nanoparticles (Chi-Ag NPs) effectively induced ICD by triggering necroptosis in 4T1 cells. Moreover, to address the lack of selectivity of drugs for in vivo application, we developed an MUC1 aptamer-targeted nanocomplex (MUC1@Chi-Ag@CPB@SHK, abbreviated as MUC1@ACS) for co-delivering SHK and Chi-Ag NPs. The accumulation of MUC1@ACS NPs at the tumor site showed a 6.02-fold increase compared to the free drug. Subsequently, upon reaching the tumor site, the acid-responsive release of SHK and Chi-Ag NPs from MUC1@ACS NPs cooperatively induced necroptosis in tumor cells by upregulating the expression of RIPK3, p-RIPK3, and tetrameric MLKL, thereby effectively triggering ICD. The sequential maturation of dendritic cells (DCs) subsequently enhanced the infiltration of CD8+ and CD4+ T cells in tumors, while inhibiting regulatory T cells (Treg cells), resulting in the effective treatment of primary and distal tumor growth and the inhibition of TNBC metastasis. This work highlights the importance of nanoparticles in mediating drug interactions during necroptotic ICD.

Carbon Corrosion Induced by Surface Defects Accelerates Degradation of Platinum/Graphene Catalysts in Oxygen Reduction Reaction.

Graphene supported electrocatalysts have demonstrated remarkable catalytic performance for oxygen reduction reaction (ORR). However, their durability and cycling performance are greatly limited by Oswald ripening of platinum (Pt) and graphene support corrosion. Moreover, comprehensive studies on the mechanisms of catalysts degradation under 0.6-1.6 V versus RHE (Reversible Hydrogen Electrode) is still lacking. Herein, degradation mechanisms triggered by different defects on graphene supports are investigated by two cycling protocols. In the start-up/shutdown cycling (1.0-1.6 V vs. RHE), carbon oxidation reaction (COR) leads to shedding or swarm-like aggregation of Pt nanoparticles (NPs). Theoretical simulation results show that the expansion of vacancy defects promotes reaction kinetics of the decisive step in COR, reducing its reaction overpotential. While under the load cycling (0.6-1.0 V vs. RHE), oxygen containing defects lead to an elevated content of Pt in its oxidation state which intensifies Oswald ripening of Pt. The presence of vacancy defects can enhance the transfer of electrons from graphene to the Pt surface, reducing the d-band center of Pt and making it more difficult for the oxidation state of platinum to form in the cycling. This work will provide comprehensive understanding on Pt/Graphene catalysts degradation mechanisms.

Epigenetic Insights Into Necrotizing Enterocolitis: Unraveling Methylation-Regulated Biomarkers.

Necrotizing enterocolitis (NEC) is a multifactorial gastrointestinal disease with high morbidity and mortality among premature infants. This study aimed to identify novel methylation-regulated biomarkers in NEC intestinal tissue through multiomics analysis. We analyzed DNA methylation and transcriptome datasets from ileum and colon tissues of patients with NEC. We identify methylation-related differential genes (MrDEGs) based on the rule that the degree of methylation in the promoter region is inversely proportional to RNA transcription. These MrDEGs included ADAP1, GUCA2A, BCL2L14, FUT3, MISP, USH1C, ITGA3, UNC93A and IL22RA1. Single-cell data revealed that MrDEGs were mainly located in the intestinal epithelial part of intestinal tissue. These MrDEGs were verified through Target gene bisulfite sequencing and RT-qPCR. We successfully identified and verified the ADAP1, GUCA2A, IL22RA1 and MISP, primarily expressed in intestinal epithelial villus cells through single-cell data. Through single-gene gene set enrichment analysis, we found that these genes participate mainly in the pathological process of T-cell differentiation and the suppression of intestinal inflammation in NEC. This study enhances our understanding of the pathogenesis of NEC and may promote the development of new precision medicine methods for NEC prediction and diagnosis.

Global proteomic analyses of lysine acetylation, malonylation, succinylation, and crotonylation in human sperm reveal their involvement in male fertility.

Protein lysine modifications (PLMs) are hotspots of post-translational modifications and are involved in many diseases; however, their role in human sperm remains obscure. This study examined the presence and functional roles of a classical PLM (lysine acetylation, Kac) and three novel PLMs (lysine malonylation, Kmal; lysine succinylation, Ksucc; lysine crotonylation, Kcr) in human sperm. Immunoblotting and immunofluorescence assays revealed modified proteins (15-150 kDa) in the tails of human sperm. An immunoaffinity approach coupled with liquid chromatography/tandem mass spectrometry revealed 1423 Kac sites in 680 proteins, 196 Kmal sites in 118 proteins, 788 Ksucc sites in 251 proteins, and 1836 Kcr sites in 645 proteins. These modified proteins participate in a variety of biological processes and metabolic pathways. Crosstalk analysis demonstrated that proteins involved in the sperm energy pathways of glycolysis, oxidative phosphorylation, the citrate cycle, fatty acid oxidation, and ketone body metabolism were modified by at least one of these modifications. In addition, these modifications were found in 62 male fertility-related proteins that weave a protein-protein interaction network associated with asthenoteratozoospermia, asthenozoospermia, globozoospermia, spermatogenic failure, hypogonadotropic hypogonadism, and polycystic kidney disease. Our findings shed light on the functional role of PLMs in male reproduction. SIGNIFICANCE: Protein lysine modifications (PLMs) are hotspots of posttranslational modifications and are involved in many diseases. This study revealed the presence of a classical PLM (lysine acetylation) and three novel PLMs (lysine malonylation, lysine succinylation, and lysine crotonylation) in human sperm tails. The modified proteins participate in a variety of biological processes and metabolic pathways. In addition, these modifications were found in 62 male infertility-associated proteins and could serve as potential diagnostic markers and therapeutic targets for male infertility.

Enhancing nitrogen removal in constructed wetlands: The role of influent substrate concentrations in integrated vertical-flow systems.

Recent advancements in constructed wetlands (CWs) have highlighted the imperative of enhancing nitrogen (N) removal efficiency. However, the variability in influent substrate concentrations presents a challenge in optimizing N removal strategies due to its impact on removal efficiency and mechanisms. Here we show the interplay between influent substrate concentration and N removal processes within integrated vertical-flow constructed wetlands (IVFCWs), using wastewaters enriched with NO3--N and NH4+-N at varying carbon to nitrogen (C/N) ratios (1, 3, and 6). In the NO3--N enriched systems, a positive correlation was observed between the C/N ratio and total nitrogen (TN) removal efficiency, which markedly increased from 13.46 ± 2.23% to 87.00 ± 2.37% as the C/N ratio escalated from 1 to 6. Conversely, in NH4+-N enriched systems, TN removal efficiencies in the A-6 setup (33.69 ± 4.83%) were marginally 1.25 to 1.29 times higher than those in A-3 and A-1 systems, attributed to constraints in dissolved oxygen (DO) levels and alkalinity. Microbial community analysis and metabolic pathway assessment revealed that anaerobic denitrification, microbial N assimilation, and dissimilatory nitrate reduction to ammonium (DNRA) predominated in NO3--N systems with higher C/N ratios (C/N ≥ 3). In contrast, aerobic denitrification and microbial N assimilation were the primary pathways in NH4+-N systems and low C/N NO3--N systems. A mass balance approach indicated denitrification and microbial N assimilation contributed 4.12-47.12% and 8.51-38.96% in NO3--N systems, respectively, and 0.55-17.35% and 7.83-33.55% in NH4+-N systems to TN removal. To enhance N removal, strategies for NO3--N dominated systems should address carbon source limitations and electron competition between denitrification and DNRA processes, while NH4+-N dominated systems require optimization of carbon utilization pathways, and ensuring adequate DO and alkalinity supply.

ß-sitosterol Alleviates High Fatty Acid-Induced Lipid Accumulation in Calf Hepatocytes by Regulating Cholesterol Metabolism.

A significant reduction in plasma concentration of cholesterol during early lactation is a common occurrence in high-yielding dairy cows. An insufficient synthesis of cholesterol in the liver has been linked to lipid accumulation caused by high concentrations of fatty acids during negative energy balance (NEB). As ruminant diets do not provide quantitative amounts of cholesterol for absorption, phytosterols such as ß-sitosterol may serve to mitigate the shortfall in cholesterol within the liver during NEB. To gain mechanistic insights, primary hepatocytes were isolated from healthy female 1-day old calves for in vitro studies with or without 1.2mM fatty acids (FA) to induce metabolic stress. Furthermore, hepatocytes were treated with 50µM ß-sitosterol with or without FA. Data were analyzed by one-way ANOVA with subsequent Bonferroni correction. Results revealed that calf hepatocytes treated with FA had greater content of non-esterified fatty acids (NEFA) and triacylglycerol (TAG), and greater mRNA and protein abundance of the lipid synthesis-related SREBF1 and FASN. In contrast, mRNA and protein of CPT1A (fatty acid oxidation) and the cholesterol metabolism-related targets SREBF2, HMGCR, ACAT2, APOA1, ABCA1 and ABCG5 was lower. Content of the antioxidant-related glutathione (GSH) and activities of superoxide dismutase (SOD) also was lower. Compared with FA challenge alone, 50µM ß-sitosterol led to greater mRNA and protein abundance of SREBF2, HMGCR, ACAT2 and ABCG5, and greater content of GSH and activity of SOD. In contrast, compared with the FA group, the mRNA and protein abundance of SREBF1 and ACC1 and the content of TAG and NEFA in the ß-sitosterol + FA group were lower. Overall, ß-sitosterol can promote cholesterol metabolism and reduce oxidative stress while reducing lipid accumulation in hepatocytes challenged with high concentrations of fatty acids.

Ecological filter walls for efficient pollutant removal from urban surface water.

Urban surface water pollution poses significant threats to aquatic ecosystems and human health. Conventional nitrogen removal technologies used in urban surface water exhibit drawbacks such as high consumption of carbon sources, high sludge production, and focus on dissolved oxygen (DO) concentration while neglecting the impact of DO gradients. Here, we show an ecological filter walls (EFW) that removes pollutants from urban surface water. We utilized a polymer-based three-dimensional matrix to enhance water permeability, and emergent plants were integrated into the EFW to facilitate biofilm formation. We observed that varying aeration intensities within the EFW's aerobic zone resulted in distinct DO gradients, with an optimal DO control at 3.19 ± 0.2 mg L-1 achieving superior nitrogen removal efficiencies. Specifically, the removal efficiencies of total organic carbon, total nitrogen, ammonia, and nitrate were 79.4%, 81.3%, 99.6%, and 79.1%, respectively. Microbial community analysis under a 3 mg L-1 DO condition revealed a shift in microbial composition and abundance, with genera such as Dechloromonas, Acinetobacter, unclassified_f__Comamonadaceae, SM1A02 and Pseudomonas playing pivotal roles in carbon and nitrogen elimination. Notably, the EFW facilitated shortcut nitrification-denitrification processes, predominantly contributing to nitrogen removal. Considering low manufacturing cost, flexible application, small artificial trace, and good pollutant removal ability, EFW has promising potential as an innovative approach to urban surface water treatment.

Simultaneous Enhancement of Strength and Sulfide Stress Cracking Resistance of Hot-Rolled Pressure Vessel Steel Q345 via a Quenching and Tempering Treatment.

Sulfide stress cracking (SSC) failure is a main concern for the pressure vessel steel Q345 used in harsh sour oil and gas environments containing hydrogen sulfide (H2S). Methods used to improve the strength of steel usually decrease their SSC resistance. In this work, a quenching and tempering (Q&T) processing method is proposed to provide higher strength combined with better SSC resistance for hot-rolled Q345 pressure vessel steel. Compared to the initial hot-rolled plates having a yield strength (YS) of ~372 MPa, the Q&T counterparts had a YS of ~463 MPa, achieving a remarkable improvement in the strength level. Meanwhile, there was a resulting SSC failure in the initial hot-rolled plates, which was not present in the Q&T counterparts. The SSC failure was not only determined by the strength. The carbon-rich zone, residual stress, and sensitive hardness in the banded structure largely determined the susceptibility to SSC failure. The mechanism of the property amelioration might be ascribed to microstructural modification by the Q&T processing. This work provides an approach to develop improved strength grades of SSC-resistant pressure vessel steels.

Impact of LDLR polymorphisms on lipid levels and atorvastatin's efficacy in a northern Chinese adult Han cohort with dyslipidemia.

BACKGROUND: Dyslipidemia, a significant risk factor for atherosclerotic cardiovascular disease (ASCVD), is influenced by genetic variations, particularly those in the low-density lipoprotein receptor (LDLR) gene. This study aimed to elucidate the effects of LDLR polymorphisms on baseline serum lipid levels and the therapeutic efficacy of atorvastatin in an adult Han population in northern China with dyslipidemia. METHODS: In this study, 255 Han Chinese adults receiving atorvastatin therapy were examined and followed up. The 3' untranslated region (UTR) of the LDLR gene was sequenced to identify polymorphisms. The associations between gene polymorphisms and serum lipid levels, as well as changes in lipid levels after intervention, were evaluated using the Wilcoxon rank sum test, with a P < 0.05 indicating statistical significance. Assessment of linkage disequilibrium patterns and haplotype structures was conducted utilizing Haploview. RESULTS: Eleven distinct polymorphisms at LDLR 3' UTR were identified. Seven polymorphisms (rs1433099, rs14158, rs2738466, rs5742911, rs17249057, rs55971831, and rs568219285) were correlated with the baseline serum lipid levels (P < 0.05). In particular, four polymorphisms (rs14158, rs2738466, rs5742911, and rs17249057) were in strong linkage disequilibrium (r2 = 1), and patients with the AGGC haplotype had higher TC and LDL-C levels at baseline. Three polymorphisms (rs1433099, rs2738467, and rs7254521) were correlated with the therapeutic efficacy of atorvastatin (P < 0.05). Furthermore, carriers of the rs2738467 T allele demonstrated a significantly greater reduction in low-density lipoprotein cholesterol (LDL-C) levels post-atorvastatin treatment (P = 0.03), indicating a potentially crucial genetic influence on therapeutic outcomes. Two polymorphisms (rs751672818 and rs566918949) were neither correlated with the baseline serum lipid levels nor atorvastatin's efficacy. CONCLUSIONS: This research outlined the complex genetic architecture surrounding LDLR 3' UTR polymorphisms and their role in lipid metabolism and the response to atorvastatin treatment in adult Han Chinese patients with dyslipidemia, highlighting the importance of genetic profiling in enhancing tailored therapeutic strategies. Furthermore, this investigation advocates for the integration of genetic testing into the management of dyslipidemia, paving the way for customized therapeutic approaches that could significantly improve patient care. TRIAL REGISTRATION: This multicenter study was approved by the Ethics Committee of Xiangya Hospital Central South University (ethics number K22144). It was a general ethic. In addition, this study was approved by The First Hospital of Hebei Medical University (ethics number 20220418).

Potassium peroxoborate: A sustained-released reactive oxygen carrier with enhanced PAHs contaminated soil remediation performance.

Seeking for a safe, efficient, inexpensive, and eco-friendly oxidizer is always a big challenge for in-situ chemical oxidation (ISCO) technology. This study adopted the potassium peroxoborate (PPB), a novel peroxide, for soil remediation for the first time. PPB based chemical oxidation system (PPB-CO) could efficiently degrade polycyclic aromatic hydrocarbons (PAHs) without other reagents added, reaching 72.1 %, 64.2 %, and 50.0 % removal rates for naphthalene, phenanthrene, and pyrene after 24 h reaction, respectively. The superior total PAHs removal efficiency (60.6 %) was 3.6-4.7 times higher than that of other commercial peroxides (2Na2CO3•3H2O, CaO2, and H2O2). Mechanism analysis revealed that varieties of reactive oxygen species (ROS) can be generated by PPB through Fenton-like or non-Fenton routines, including H2O2, perborates species, O2•-, •OH, and 1O2. The sustainable generation of H2O2 reduced the disproportionation effect of H2O2 by 86 %, significantly improving the utilization rate. Moreover, sandbox experiments and actual contaminated soil remediation experiments verified the feasibility of PPB-CO in a real polluted site. This work provides a novel strategy for effectively soil remediation, highlighting the selection and application of new oxidants.

Effect of IL-17 on pulmonary artery smooth muscle cells and connective tissue disease-associated pulmonary arterial hypertension.

OBJECTIVE: To explore the role of interleukin (IL)-17 in connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH) and to investigate its possible mechanism on pulmonary artery smooth muscle cells (PASMCs). METHODS: Enzyme-linked immunosorbent assay (ELISA) were used to compare levels of serum IL-17 in patients with CTD-PAH and healthy controls (HCs). After treatment for 3 months, the serum IL-17 levels were tested in CTD-PAH. ELISA and immunohistochemistry were used to compare levels of serum IL-17 and numbers of pulmonary artery IL-17+ cells, respectively, in a rat model of monocrotaline-induced PAH and untreated rats. Proliferation, migration, and inflammatory factors expression of PASMCs were assessed after stimulation with different concentrations of IL-17 for various time periods. Proteins in the mitogen-activated protein kinase (MAPK) pathway were examined by western blot. RESULTS: Levels of IL-17 were upregulated in patients with CTD-PAH compared to HCs. After 3 months of treatment, serum IL-17 levels were downregulated with pulmonary artery pressure amelioration. Moreover, serum IL-17 levels and numbers of IL-17+ cells infiltrating lung arterioles were increased in PAH model rats. IL-17 could dose- and time-dependently promote proliferation and migration of PASMCs as well as time-dependently induce IL-6 and intercellular cell adhesion molecule-1 (ICAM-1) expression. The levels of MKK6 increased after IL-17 treatment. Inhibition of MAPK decreased proliferation of PASMCs. CONCLUSION: Levels of IL-17 may increase in CTD-PAH, and IL-17 promotes proliferation, migration, and secretion of IL-6 and ICAM in PASMCs, respectively, which likely involves the p-38 MAPK pathway.

Tc-99m-MIBI SPECT/CT imaging to diagnose secondary hyperparathyroidism after parathyroid forearm transplantation.

This article report a 40-year-old male patient who underwent total thyroidectomy and forearm auto-transplantation in another hospital for secondary hyperparathyroidism. After 4 years of follow-up, the level of parathyroid hormone continued to increase, and ultrasound showed nodules in the neck and right forearm, which were considered to be of parathyroid origin. Technetium 99m sestamibi single photon emission computed tomography and computed tomography (Tc-99m-MIBI SPECT/CT) imaging showed increased radioactive uptake in the submuscular soft tissue nodule of the right medial forearm, maximum standardized uptake value (SUVmax) is 0.98, which was identified as transplanted functioning parathyroid tissue. No parathyroid imaging activity was found in the neck. The patient then underwent partial removal of ectopic parathyroid tissue from the right forearm. Pathological examination confirmed parathyroid tissue, and removal was followed by a rapid decline in serum parathyroid hormone levels.