Nanoscale Sequential Reactor Design Achieves Effective Removal of Disinfection Byproduct Precursors in Catalytic Ozonation.

Transforming dissolved organic matter (DOM) is a crucial approach to alleviating the formation of disinfection byproducts (DBPs) in water treatment. Although catalytic ozonation effectively transforms DOM, increases in DBP formation potential are often observed due to the accumulation of aldehydes, ketones, and nitro compound intermediates during DOM transformation. In this study, we propose a novel strategy for the sequential oxidation of DOM, effectively reducing the levels of accumulation of these intermediates. This is achieved through the development of a catalyst with a tailored surface and nanoconfined active sites for catalytic ozonation. The catalyst features a unique confinement structure, wherein Mn-N4 moieties are uniformly anchored on the catalyst surface and within nanopores (5-20 Å). This design enables the degradation of the large molecular weight fraction of DOM on the catalyst surface, while the transformed smaller molecular weight fraction enters the nanopores and undergoes rapid degradation due to the confinement effect. The generation of *Oad as the dominant reactive species is essential for effectively reducing these ozone refractory intermediates. This resulted in over 70% removal of carbonaceous and nitrogenous DBP precursors as well as brominated DBP precursors. This study highlights the importance of the nanoscale sequential reactor design and provides new insights into eliminating DBP precursors by the catalytic ozonation process.

A novel flavobacterial phage abundant during green tide, representing a new viral family, Zblingviridae.

Flavobacteriia are the dominant and active bacteria during algal blooms and play an important role in polysaccharide degradation. However, little is known about phages infecting Flavobacteriia, especially during green tide. In this study, a novel virus, vB_TgeS_JQ, infecting Flavobacteriia was isolated from the surface water of the Golden Beach of Qingdao, China. Transmission electron microscopy demonstrated that vB_TgeS_JQ had the morphology of siphovirus. The experiments showed that it was stable from -20°C to 45°C and pH 5 to pH 8, with latent and burst periods both lasting for 20 min. Genomic analysis showed that the phage vB_TgeS_JQ contained a 40,712-bp dsDNA genome with a GC content of 30.70%, encoding 74 open-reading frames. Four putative auxiliary metabolic genes were identified, encoding electron transfer-flavoprotein dehydrogenase, calcineurin-like phosphoesterase, phosphoribosyl-ATP pyrophosphohydrolase, and TOPRIM nucleotidyl hydrolase. The abundance of phage vB_TgeS_JQ was higher during Ulva prolifera (U. prolifera) blooms compared with other marine environments. The phylogenetic and comparative genomic analyses revealed that vB_TgeS_JQ exhibited significant differences from all other phage isolates in the databases and therefore was classified as an undiscovered viral family, named Zblingviridae. In summary, this study expands the knowledge about the genomic, phylogenetic diversity and distribution of flavobacterial phages (flavophages), especially their roles during U. prolifera blooms. IMPORTANCE: The phage vB_TgeS_JQ was the first flavobacterial phage isolated during green tide, representing a new family in Caudoviricetes and named Zblingviridae. The abundance of phage vB_TgeS_JQ was higher during the Ulva prolifera blooms. This study provides insights into the genomic, phylogenetic diversity, and distribution of flavophages, especially their roles during U. prolifera blooms.

A review of robot-assisted ultrasound examination: Systems and technology.

BACKGROUND: At present, the number and overall level of ultrasound (US) doctors cannot meet the medical needs, and the medical ultrasound robots will largely solve the shortage of medical resources. METHODS: According to the degree of automation, the handheld, semi-automatic and automatic ultrasound examination robot systems are summarised. Ultrasound scanning path planning and robot control are the keys to ensure that the robot systems can obtain high-quality images. Therefore, the ultrasound scanning path planning and control methods are summarised. The research progress and future trends are discussed. RESULTS: A variety of ultrasound robot systems have been applied to various medical works. With the continuous improvement of automation, the systems provide high-quality ultrasound images and image guidance for clinicians. CONCLUSION: Although the development of medical ultrasound robot still faces challenges, with the continuous progress of robot technology and communication technology, medical ultrasound robot will have great development potential and broad application space.

Study on the failure mechanism of high-temperature granite under two cooling modes.

In the geothermal development of hot dry rock (HDR), both the drilling of the wellbore and the heat exchange of the heat reservoir involve the effects of different cold and hot conditions on the high-temperature rock mass. The testing machine for rock mechanics was used to conduct a uniaxial compression test and carry out micro testing on the treated samples; furthermore, with the help of scanning electron microscopy the fracture mechanism of granite subjected to different temperatures and cooling methods was studied. The results show: (1) With the gradual increase in temperature, the compressive strength of granite under the two cooling methods gradually decreases. (2) The failure modes of the samples under the two cooling methods are mainly shear failure of the "Y" type. The degree of damage of the sample under water cooling is significantly greater than that under natural cooling. Electron micrographs could confirm these results. (3) It can be obtained by testing the mineral composition and element changes of granite at different temperatures. When the temperature reaches 600℃, its change is more pronounced. The results of this study can provide a theoretical reference for the failure of the wellbore and the degree of fracture of the thermal reservoir rock mass during geothermal development.

Recurrent metastatic patterns and prognosis after radical surgery in patients with alpha-fetoprotein-producing gastric cancer: a retrospective cohort study.

Alpha-fetoprotein-producing gastric cancer (AFPGC) is a rare and aggressive subtype of gastric cancer associated with poor prognosis. This study aimed to investigate the recurrent metastatic patterns and prognostic factors in AFPGC patients undergoing radical surgical resection. Data from 241 AFPGC patients diagnosed between January 2017 and January 2020 who underwent surgical resection were analyzed across multiple centers. Recurrence patterns, metastatic sites, and survival outcomes were evaluated. Univariate and multivariate analyses were performed to identify risk factors for recurrent metastasis, overall survival (OS), and disease-free survival (DFS). There is an annual increase in the proportion of AFPGC cases, rising from 3.45% in 2017 to 7.88% in 2023. Higher serum AFP level was associated with increased likelihood of lymph node metastasis (P=0.006), deeper invasion depth (P=0.000) and greater tumor diameter (P=0.036). Independent predictors of recurrent metastasis included T4 infiltration, lymph node metastasis, tumor diameter >5 cm, poorly differentiated-undifferentiated pathology, preoperative AFP>1000 ng/mL, and postoperative increasing trend in AFP levels. The 5-year OS and DFS rates were 36.5% and 34.2%, respectively, with poorer survival linked to higher preoperative AFP levels and postoperative increasing trend in AFP level. Independent risk factors for poor OS and DFS included T4 infiltration, lymph node metastasis, poorly differentiated-undifferentiated pathology, preoperative AFP>1000 ng/mL, and postoperative increasing trend in AFP. Serum AFP level can serve as a potential predictive and prognostic biomarker. Identifying independent risk factors informs risk stratification and personalized treatment for AFPGC patients.

Frank-Kasper phases in charge transfer complexes enable tunable photoelectronic properties.

Understanding how particles pack in space and the mechanisms underlying symmetry selection across soft matter is challenging. The Frank-Kasper (F-K) phase of complex spherical packing is amongst the most fascinating phases; however, it has not been observed in discotic liquid crystals until now. Herein, we report the first observation of F-K phases of charge transfer complexes (CTCs) obtained from triphenylene derivatives as donors and 2,4,7-trinitro-9-fluorenone as the acceptor. The CTCs were characterized using experimental and theoretical calculations, indicating that the F-K A15 cubic lattice possesses a unit cell containing 8 sphere-like supramolecules, each of which was self-assembled from 3 CTC complexes. The lattice constant was only 3.2 nm, which is by far the smallest for the A15 phase. Interestingly, the supramolecular assembly can be regarded as the molecular column splitting into isolated spherical fragments, impeding charge transfer and turning it into one insulator. This provides a simple and effective method for preparing asymmetric complex compounds for the design of unconventional self-assembled nanostructures.

Modeling Ion Transport across Thin-Film Composite Membranes During Saltwater Electrolysis.

Affordable thin-film composite (TFC) membranes are a potential alternative to more expensive ion exchange membranes in saltwater electrolyzers used for hydrogen gas production. We used a solution-friction transport model to study how the induced potential gradient controls ion transport across the polyamide (PA) active layer and support layers of TFC membranes during electrolysis. The set of parameters was simplified by assigning the same size-related partition and friction coefficients for all salt ions through the membrane active layer. The model was fit to experimental ion transport data from saltwater electrolysis with 600 mM electrolytes at a current density of 10 mA cm-2. When the electrolyte concentration and current density were increased, the transport of major charge carriers was successfully predicted by the model. Ion transport calculated using the model only minimally changed when the negative active layer charge density was varied from 0 to 600 mM, indicating active layer charge was not largely responsible for controlling ion crossover during electrolysis. Based on model simulations, a sharp pH gradient was predicted to occur within the supporting layer of the membrane. These results can help guide membrane design and operation conditions in water electrolyzers using TFC membranes.

Using Surface Immunogenic Protein as a Carrier Protein to Elicit Protective Antibody to Multiple Serotypes for Candidate Group B Streptococcal Glycan Conjugate Vaccines.

Group B Streptococcus (GBS) is a life-threatening opportunistic pathogen, particularly in pregnant women, infants, and the elderly. Currently, maternal vaccination is considered the most viable long-term option for preventing GBS mother-to-infant infection, and two polysaccharide conjugate vaccines utilizing CRM197 as a carrier protein have undergone clinical phase II trials. Surface immunogenic protein (Sip), present in all identified serotypes of GBS strains so far, is a protective surface protein of GBS. In this study, the type Ia capsular polysaccharide (CPS) of GBS was utilized as a model to develop candidate antigens for a polysaccharide conjugate vaccine by coupling it with the Sip of GBS and the traditional carrier protein CRM197. Serum analysis from immunized New Zealand rabbits and CD1 mice revealed that there was no significant difference in antibody titers between the Ia-Sip group and Ia-CRM197 group; however, both were significantly higher than those observed in the Ia polysaccharide group. Opsonophagocytosis and passive immune protection results using rabbit serum indicated no significant difference between the Ia-Sip and Ia-CRM197 groups, both outperforming the Ia polysaccharide group. Furthermore, serum from the Ia-Sip group had a cross-protective effect on multiple types of GBS strains. The challenge test results in CD1 mice demonstrated that the Ia-Sip group provided complete protection against lethal doses of bacteria and also showed cross-protection against type III strain. Our study demonstrates for the first time that Ia-Sip is immunogenic and provides serotype-independent protection in glycan conjugate vaccines, which also indicates Sip may serve as an excellent carrier protein for GBS glycan conjugate vaccines and provide cross-protection against multiple GBS strains.

A prostate seed implantation robot system based on human-computer interactions: Augmented reality and voice control.

The technology of robot-assisted prostate seed implantation has developed rapidly. However, during the process, there are some problems to be solved, such as non-intuitive visualization effects and complicated robot control. To improve the intelligence and visualization of the operation process, a voice control technology of prostate seed implantation robot in augmented reality environment was proposed. Initially, the MRI image of the prostate was denoised and segmented. The three-dimensional model of prostate and its surrounding tissues was reconstructed by surface rendering technology. Combined with holographic application program, the augmented reality system of prostate seed implantation was built. An improved singular value decomposition three-dimensional registration algorithm based on iterative closest point was proposed, and the results of three-dimensional registration experiments verified that the algorithm could effectively improve the three-dimensional registration accuracy. A fusion algorithm based on spectral subtraction and BP neural network was proposed. The experimental results showed that the average delay of the fusion algorithm was 1.314 s, and the overall response time of the integrated system was 1.5 s. The fusion algorithm could effectively improve the reliability of the voice control system, and the integrated system could meet the responsiveness requirements of prostate seed implantation.

HPLC with chiral stationary phase for separation and kinetics study of aspartic acid epimerization in Peroxiredoxin 2 active site peptide.

Amino acid epimerization, a process of converting L-amino acids to D-amino acids, will lead to modification in the protein structure and, subsequently, its biological function. This modification causes no change in protein m/z and may be overlooked during protein analysis. Aspartic Acid Epimerization (AAE) is faster than other amino acids and could be accelerated by free radicals and peroxides. In this work, a novel and site-specific HPLC method using a chiral stationary phase for determining the AAE in the active site model peptide (AP) of Peroxiredoxin 2 has been developed and validated. The developed method showed good linearity (1 - 200 µg/mL) and recoveries of the limit of quantification (LOQ), low, medium, and high concentrations were between 85% and 115%. The Kinetics of AAE in AP were studied using the developed method, and the results showed that when ascorbic acid and Cu2+ coexisted, the AP epimerized rapidly. The AAE extent increased with time and was positively correlated with hydrogen peroxide generation.

Carbon dioxide radical anion mediated dehalogenation kinetics and mechanisms of halogenated alkanes.

Carbon dioxide radical anion (CO2•-) recently becomes appreciated in halogenated contaminants elimination; nevertheless, its application has been restricted by insufficient mechanistic understanding. Herein, we provided a quantitative insight into the kinetics and mechanisms of CO2•- mediated dehalogenation of halogenated alkanes. A CO2•- dominated UV254/H2O2/HCOO- system has been successfully established and demonstrated for effective elimination of 7 kinds of halogenated alkanes (71.3 % to 100 % of removal). Using a laser flash photolysis technology, the second-order rate constants of CO2•- ( [Formula: see text] ) reacting with CCl4, CHCl3 and CH2Cl2 were firstly reported, to be 2.5 × 108, 6.2 × 107 and 5.8 × 106 M-1s-1, respectively. [Formula: see text] presented a significant negative correlation with the lowest unoccupied molecular orbital energy (ELUMO) of chlorinated alkanes, proving that the enhanced dehalogenation of CO2•- was attributed by direct electron transfer mechanism. A fitting model was developed accordingly for [Formula: see text] prediction. This study also demonstrated that the CO2•- mediated ARP effectively removed halogenated alkanes regardless of pH condition (6.0∼9.0) and bicarbonate concentrations. These findings are significant in advancing the scientific understanding of CO2•- mediated ARP. This reductive process a promising control strategy for halogenated contaminants, such as polyfluoroalkyl substances (PFAS) and halogenated pharmaceuticals.

Static and Dynamic Filler-Associated Tear Trough Deformities: Manifestations and Treatment Algorithm.

BACKGROUND: Fillers are popular substances for the correction of tear trough deformity. Despite well-documented complications increasing gradually, standardized treatment algorithm for deformity secondary to improper injection is still limited. METHODS: Between April 2020 and April 2023, a total of 22 patients with filler-associated tear trough deformity with static bulges or dynamic swells after injection of tear trough were enrolled. For patients who received hyaluronic acid (HA) and unknown fillers, hyaluronidase dissolution was performed. For patients who received non-HA fillers and unknown fillers that failed to dissolve, a magnetic resonance imaging (MRI) examination was conducted. Surgical approaches were selected based on the filler distribution and the condition of the lower eyelid. Ligament releasement and fat transposition were accomplished when fillers were excised. Aesthetic outcomes were evaluated by double-blind examiners using the Global Aesthetic Improvement Scale after patients were followed up. RESULTS: In total, the study included 3 patients with simple static deformities, 1 patient with simple dynamic, and 18 patients with both. Fourteen patients underwent transconjunctival surgery and 8 patients underwent transcutaneous surgery, among which 18 patients underwent hyaluronidase dissolution and 8 patients underwent MRI prior to surgery. A total of 4 patients with self-limited complications recovered after conservative treatment. 90.9% of patients expressed satisfaction or high satisfaction with the treatment results. CONCLUSION: Filler-associated tear trough deformities could be classified into static and dynamic deformities, which could appear separately or simultaneously. Treatment of deformities should be based on characteristics of fillers, in which MRI could serve as a promising tool. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

Numerical Simulation and Deformation Prediction of Deep Pit Based on PSO-BP Neural Network Inversion of Soil Parameters.

The finite element numerical simulation results of deep pit deformation are greatly influenced by soil layer parameters, which are crucial in determining the accuracy of deformation prediction results. This study employs the orthogonal experimental design to determine the combinations of various soil layer parameters in deep pits. Displacement values at specific measurement points were calculated using PLAXIS 3D under these varying parameter combinations to generate training samples. The nonlinear mapping ability of the Back Propagation (BP) neural network and Particle Swarm Optimization (PSO) were used for sample global optimization. Combining these with actual onsite measurements, we inversely calculate soil layer parameter values to update the input parameters for PLAXIS 3D. This allows us to conduct dynamic deformation prediction studies throughout the entire excavation process of deep pits. The results indicate that the use of the PSO-BP neural network for inverting soil layer parameters effectively enhances the convergence speed of the BP neural network model and avoids the issue of easily falling into local optimal solutions. The use of PLAXIS 3D to simulate the excavation process of the pit accurately reflects the dynamic changes in the displacement of the retaining structure, and the numerical simulation results show good agreement with the measured values. By updating the model parameters in real-time and calculating the pile displacement under different working conditions, the absolute errors between the measured and simulated values of pile top vertical displacement and pile body maximum horizontal displacement can be effectively reduced. This suggests that inverting soil layer parameters using measured values from working conditions is a feasible method for dynamically predicting the excavation process of the pit. The research results have some reference value for the selection of soil layer parameters in similar areas.

Direct Observation of Enhanced Iodine Binding within a Series of Functionalized Metal-Organic Frameworks with Exceptional Irradiation Stability.

Optimization of active sites and stability under irradiation are important targets for sorbent materials that might be used for iodine (I2) storage. Herein, we report the direct observation of I2 binding in a series of Cu(II)-based isostructural metal-organic frameworks, MFM-170, MFM-172, MFM-174, NJU-Bai20, and NJU-Bai21, incorporating various functional groups (-H, -CH3, - NH2, -C≡C-, and -CONH-, respectively). MFM-170 shows a reversible uptake of 3.37 g g-1 and a high packing density of 4.41 g cm-3 for physiosorbed I2. The incorporation of -NH2 and -C≡C- moieties in MFM-174 and NJU-Bai20, respectively, enhances the binding of I2, affording uptakes of up to 3.91 g g-1. In addition, an exceptional I2 packing density of 4.83 g cm-3 is achieved in MFM-174, comparable to that of solid iodine (4.93 g cm-3). In situ crystallographic studies show the formation of a range of supramolecular and chemical interactions [I···N, I···H2N] and [I···C≡C, I-C═C-I] between -NH2, -C≡C- sites, respectively, and adsorbed I2 molecules. These observations have been confirmed via a combination of solid-state nuclear magnetic resonance, X-ray photoelectron, and Raman spectroscopies. Importantly, γ-irradiation confirmed the ultraresistance of MFM-170, MFM-174, and NJU-Bai20 suggesting their potential as efficient sorbents for cleanup of radioactive waste.

Across two phylogeographic breaks: Quaternary evolutionary history of a mountain aspen (Populus rotundifolia) in the Hengduan Mountains.

Biogeographical barriers to gene flow are central to plant phylogeography. In East Asia, plant distribution is greatly influenced by two phylogeographic breaks, the Mekong-Salween Divide and Tanaka-Kaiyong Line, however, few studies have investigated how these barriers affect the genetic diversity of species that are distributed across both. Here we used 14 microsatellite loci and four chloroplast DNA fragments to examine genetic diversity and distribution patterns of 49 populations of Populus rotundifolia, a species that spans both the Mekong-Salween Divide and the Tanaka-Kaiyong Line in southwestern China. Demographic and migration hypotheses were tested using coalescent-based approaches. Limited historical gene flow was observed between the western and eastern groups of P. rotundifolia, but substantial flow occurred across both the Mekong-Salween Divide and Tanaka-Kaiyong Line, manifesting in clear admixture and high genetic diversity in the central group. Wind-borne pollen and seeds may have facilitated the dispersal of P. rotundifolia following prevalent northwest winds in the spring. We also found that the Hengduan Mountains, where multiple genetic barriers were detected, acted on the whole as a barrier between the western and eastern groups of P. rotundifolia. Ecological niche modeling suggested that P. rotundifolia has undergone range expansion since the last glacial maximum, and demographic reconstruction indicated an earlier population expansion around 600 Ka. The phylogeographic pattern of P. rotundifolia reflects the interplay of biological traits, wind patterns, barriers, niche differentiation, and Quaternary climate history. This study emphasizes the need for multiple lines of evidence in understanding the Quaternary evolution of plants in topographically complex areas.

ACBP4-WRKY70-RAP2.12 module positively regulates submergence-induced hypoxia response in Arabidopsis thaliana.

ACYL-CoA-BINDING PROTEINs (ACBPs) play crucial regulatory roles during plant response to hypoxia, but their molecular mechanisms remain poorly understood. Our study reveals that ACBP4 serves as a positive regulator of the plant hypoxia response by interacting with WRKY70, influencing its nucleocytoplasmic shuttling in Arabidopsis thaliana. Furthermore, we demonstrate the direct binding of WRKY70 to the ACBP4 promoter, resulting in its upregulation and suggesting a positive feedback loop. Additionally, we pinpointed a phosphorylation site at Ser638 of ACBP4, which enhances submergence tolerance, potentially by facilitating WRKY70's nuclear shuttling. Surprisingly, a natural variation in this phosphorylation site of ACBP4 allowed A. thaliana to adapt to humid conditions during its historical demographic expansion. We further observed that both phosphorylated ACBP4 and oleoyl-CoA can impede the interaction between ACBP4 and WRKY70, thus promoting WRKY70's nuclear translocation. Finally, we found that the overexpression of orthologous BnaC5.ACBP4 and BnaA7.WRKY70 in Brassica napus increases submergence tolerance, indicating their functional similarity across genera. In summary, our research not only sheds light on the functional significance of the ACBP4 gene in hypoxia response, but also underscores its potential utility in breeding flooding-tolerant oilseed rape varieties.

Constricted posterior fourchette deformities: Definition, classification and surgical treatment.

BACKGROUND: Labiaplasty is one of the top cosmetic procedures patients are seeking in the past two years. However, treatment of disease in posterior fourchette caused by various etiological factors was less investigated and neglected. METHODS: Three types of posterior fourchette deformity were proposed: (1) Redundant posterior fourchette, (2) Relaxed posterior fourchette, and (3) Constricted posterior fourchette. Local flap transfer technique was applied. Y-V-plasty and 5-Z-Flap-plasty were used to treat web type and tight type of the constricted posterior fourchette, respectively. Follow-ups were arranged on the Internet or at the outpatient clinic. Visual analogue scale (VAS) was utilized to evaluate sexual discomfort in the satisfaction questionnaires during follow-up. RESULTS: A total of 48 patients with constricted posterior fourchette deformity from May 2022 to May 2023 were reviewed in the study. Y-V-plasty could decrease VAS in patients with web-type deformity by 4.13 ± 1.46 (p＜0.001). 5-Z-Flap-plasty could decrease VAS in patients with tight-type deformity by 3.76 ± 1.53 (p＜0.05). Satisfaction rates of the web type and tight type were 93.1% (27/29) and 86.7% (13/15) respectively. Complications include two cases of hematoma, one case of persistent pain and two cases of dehiscence. CONCLUSION: Constricted posterior fourchette seriously affects the quality of life. Y-V-plasty and 5-Z-Flap-plasty can be utilized to treat the two subtypes of constricted posterior fourchette, which can effectively reduce the pain score of patients with high satisfaction and few long-term complications.

Simultaneous Vertical Mastopexy During Aquafilling Removal: An Effective Way to Reshape the Breast with Ptosis.

BACKGROUND: Aquafilling was used to be a popular breast filler and was banned due to increasing reports of complications. Debridement surgery is the only available approach to treat complications caused by gel fillers, but it often leads to breast deformity and skin laxity. This study aims to present a new surgical strategy to reshape the breast immediately after Aquafilling removal. METHODS: Twelve patients who underwent Aquafilling removal at our institution were included, with five patients receiving the combined vertical mastopexy in group I and seven patients receiving Aquafilling removal alone in group II. Surgical data, complications and satisfaction were compared between the two groups. Satisfaction was assessed by using the BREAST-Q at least 6 months after surgery. RESULTS: The age range of the 12 patients was 41-56 years. Although the duration of surgery in group I was longer than that in group II (p = 0.011), the drainage duration and postoperative hospitalization between the two groups were comparable. All patients recovered well. Scarring was the only complication in group I, but there was no difference compared to group II (p = 0.711). Group II had a significantly higher incidence of postoperative depression deformity than group I (p = 0.008). Regarding satisfaction, patients in group I had significantly higher scores in satisfaction with breasts, psychosocial well-being and sexual well-being than those in group II. CONCLUSION: Combining Aquafilling removal with vertical mastopexy is an effective method of reshaping the shape of the ptotic breasts, offering superior esthetic outcomes without delaying postoperative recovery or increasing the risk of complications. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Identification of hub genes and potential therapeutic mechanisms related to HPV positive head and neck squamous carcinoma based on full transcriptomic detection and ceRNA network construction.

Infection with human papillomavirus (HPV) is a major risk factor for head and neck squamous cell carcinoma (HNSCC). The objective of this study is to investigate the gene expression profiles and signaling pathways that are specific to HPV-positive HNSCC (HPV+ HNSCC). Moreover, a competing endogenous RNA (ceRNA) network analysis was utilized to identify the core gene of HPV+ HNSCC and potential targeted therapeutic drugs. Transcriptome sequencing analysis identified 3,253 coding RNAs and 3,903 non-coding RNAs (ncRNAs) that exhibited preferentially expressed in HPV+ HNSCC. Four key signaling pathways were selected through pathway enrichment analysis. By combining ceRNA network and protein-protein interaction (PPI) network topology analysis, RNA Polymerase II Associated Protein 2 (RPAP2), which also exhibited high expression in HPV+ HNSCC based on the TCGA database, was identified as the hub gene. Gene set enrichment analysis (GSEA) results revealed RPAP2's involvement in various signaling pathways, encompassing basal transcription factors, ubiquitin-mediated proteolysis, adherens junction, other glycan degradation, ATP-binding cassette (ABC) transporters, and oglycan biosynthesis. Five potential small molecule targeted drugs (enzastaurin, brequinar, talinolol, phenylbutazone, and afuresertib) were identified using the cMAP database, with enzastaurin showing the highest affinity for RPAP2. Cellular functional experiments confirmed the inhibitory effect of enzastaurin on cell viability of HPV+ HNSCC and RPAP2 expression levels. Additionally, enzastaurin treatment suppressed the expression levels of the top-ranked long non-coding RNA (lncRNA), circular RNA (circRNA), and microRNA (miRNA) in the ceRNA network. This study based on the ceRNA network provides valuable insights into the molecular mechanisms and potential therapeutic strategies for HPV+ HNSCC, and provide theoretical basis for the exploration of HPV+ HNSCC biomarkers and the development of targeted drugs.

LRRK2 regulates ferroptosis through the system Xc-GSH-GPX4 pathway in the neuroinflammatory mechanism of Parkinson's disease.

Parkinson's disease (PD) is the most prevalent neurodegenerative disorder. Neuroinflammation mediated by activated microglia and apoptosis of dopaminergic (DA) neurons in the midbrain are its primary pathological manifestations. Leucine-rich repeat protein kinase 2 (LRRK2) kinase has been observed to increase expression during neuroinflammation, however, the effect of LRRK2 on microglia activation remains poorly understood. In this study, we have established lipopolysaccharide (LPS) treated BV2 cells and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) models for both in vivo and in vitro investigation. Our data in vivo reveal that LRRK2 can promote microglia activation by regulating ferroptosis and activating nuclear factor-κB. Inhibition of LRRK2 expression effectively suppressed the LPS-induced pro-inflammatory cytokines and facilitated the secretion of neuroprotective factors. Importantly, by co-overexpressing LRRK2 and glutathione peroxidase 4 (GPX4), we identified the system Xc-GSH-GPX4 pathway as a crucial component in LRRK2-mediated microglial ferroptosis and inflammatory responses. Using a microglial culture supernatant (MCS) transfer model, we found that inhibiting LRRK2 or downregulating ferroptosis in BV2 cells prevented SH-SY5Y cell apoptosis. Additionally, we observed abundant expression of LRRK2 and P-P65 in the midbrain, which was elevated in the MPTP-induced PD model, along with microglia activation. LRRK2 and P-P65 expression inhibition with PF-06447475 attenuated microglia activation in the nigrostriatal dense part of MPTP-treated mice. Based on our findings, it is evident that LRRK2 plays a critical role in promoting the neuroinflammatory response during the pathogenesis of PD by regulating the system Xc-GSH-GPX4 pathway. Taken together, our data highlights the potential research and therapeutic value of targeting LRRK2 to regulate neuroinflammatory response in PD through ferroptosis.