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Abstract Background Postoperative radiotherapy (PORT) is crucial for patients with thoracic locally advanced esophageal squamous cell carcinoma (LA-ESCC, pT3-4aN0-3M0) following esophagectomy. However, the appropriate radiation volume has not been well established. This study aimed to determine the optimal PORT volume for LA-ESCC patients. Methods LA-ESCC patients post-esophagectomy were randomly assigned to either the large-field irradiation (LFI, primary lesion and lymph node tumor bed plus elective nodal irradiation) group or the small-field irradiation (SFI, primary lesion and lymph node tumor bed alone) group. Stratification was based on T stage and the number of lymph node metastases. The primary endpoint was disease-free survival (DFS), while the secondary endpoints included overall survival (OS), adverse events, and patterns of initial failure. Results A total of 401 patients were randomly assigned to the intention-to-treat analysis(LFI group, n = 210; SFI group, n = 191). The median DFS of patients in the LFI group was 47.9 months and 48.1 months in the SFI group (HR = 0.87, 95%CI, 0.65 to 1.16; p = 0.32). The estimated one-year and three-year OS rates were 89.2% and 63.2% for patients in the LFI group, compared to 86.6% and 60.7% for the SFI group, respectively. The difference of OS between the two groups was not significant (HR = 0.86, 95%CI, 0.63 to 1.16; p = 0.35). Fewer patients in the LFI group experienced locoregional recurrence compared to the SFI group (12.9% vs 20.4%, p = 0.013). Additionally, locoregional recurrence-free survival of the LFI group was significantly longer than that of SFI group (HR = 0.54, 95%CI, 0.34–0.87; p = 0.01). The most common toxicity was grade 2 esophagitis, observed in 22.9% of the LFI group and 16.8% of the SFI group. Grade 3 adverse events occurred in 6.7% of the LFI group and 2.6% of the SFI group. No grade 4 or 5 toxicities were observed. Adverse events did not significantly differ between the two groups. Conclusions Postoperative radiotherapy, with the specified radiation volume shows encouraging survival outcomes that are comparable to those of neoadjuvant chemoradiotherapy in patients with thoracic LA-ESCC. Both postoperative irradiation fields were found to be feasible and safe.

Abstract Touch displays are ubiquitous in modern technologies. However, current protective methods for emerging flexible displays against static, scratches, bending, and smudge rely on multilayer materials that impede progress towards flexible, lightweight, and multifunctional designs. Developing a single coating layer integrating all these functions remains challenging yet highly anticipated. Herein, we introduce an organic–inorganic covalent–ionic hybrid network that leverages the reorganizing interaction between siloxanes (i.e., trifluoropropyl–funtionalized polyhedral oligomeric silsesquioxane and cyclotrisiloxane) and fluoride ions. This nanoscale organic–inorganic covalent–ionic hybridized crosslinked network, combined with a low surface energy trifluoropropyl group, offers a monolithic layer coating with excellent optical, antistatic, anti–smudge properties, flexibility, scratch resistance, and recyclability. Compared with existing protective materials, this all–in–one coating demonstrates comprehensive multifunctionality and closed–loop recyclability, making it ideal for future flexible displays and contributing to ecological sustainability in consumer electronics.

Abstract Background Advance care planning (ACP) is pivotal in mitigating end-of-life suffering and ensuring healthcare congruence with the values of older adults and dignity in death. Despite its paramount importance, the current readiness for ACP among community-dwelling older adults and the intricate influencing factors have yet to be explored. Objective To review the literature focusing on ACP readiness among community-dwelling older adults and the influencing factors. Methods A scoping review conducted using the Arksey and O’Malley (2005) framework. Electronic databases (PubMed, CINAHL, Cochrane, Web of Science, PsycINFO), as well as grey literature databases (OpenGrey and GreyLit.org) were searched to identify studies published in English between January 2012 and March 2023. Results 19 studies were selected, comprising 3 qualitative, 13 quantitative, 2 mixed-methods, and 1 review article. The study evaluated the readiness of older adults for ACP by examining their knowledge and attitudes. It categorizes influencing factors into intrinsic and extrinsic levels. This review revealed that the knowledge about ACP among older adults across all settings was limited. However, they had positive attitudes toward it. In addition, intrinsic factors including sociodemographic characteristics, psychological factors, and family relationships, along with extrinsic factors including health care professionals’ attitudes and experience, as well as policies and laws, influenced the ACP readiness among older adults. Conclusions This study established the groundwork for future ACP intervention trials, providing a theoretical framework to guide their design and implementation. operationalization.

Abstract Aiming at the problem that the overlapping of multipath signals seriously affects the radar's performance of the elevation angle estimation for low‐altitude targets, the authors combine the unitary ESPRIT (UESPRIT) and the multi‐input and multi‐output (MIMO) radar system and propose an algorithm based on UESPRIT to estimate the direction of arrival for low‐altitude targets. Firstly, the virtual matrix after generalised matched filtering of MIMO radar multipath received signals is vectorised. Secondly, for the coherence of direct and reflected wave signals, which cannot be directly processed by the UESPRIT algorithm, the signal preprocessing is performed by spatial smoothing of the sampled data matrices. Finally, the low‐altitude target estimation is carried out by using the UESPRIT algorithm. The Cramer–Rao bound (CRB) for arbitrary unbiased estimation of angle estimation is derived. The relationship between the estimation performance of the algorithm and the signal‐to‐noise ratio, the number of snapshots and the number of elements is analysed by simulation and compared with CRB. The simulation results show that the algorithm can still effectively estimate the elevation angle of low‐altitude targets under the mutual weakening of direct and multipath reflection signals, and has better performance for low‐altitude targets than generalised MUSIC.

Abstract Walking pace is a simple and functional form of exercise and a strong predictor of health, but little is known about its causal association with rheumatoid arthritis. This study aimed to investigate the causal effect of WP on the developing RA using Mendelian randomization analysis. The genetic variation associated with WP was selected as an instrumental variable from the latest genome-wide association studies. Summary-level data for the outcomes were obtained from the corresponding GWAS. The inverse-variance weighted method was used as the primary MR analysis. The results were further tested using a multivariable MR approach based on Bayesian model averaging. Confounders (BMI, SMK, HBP, TD) with close associations with RA were included in the analysis. An observational study with individual data from UK Biobank was performed to reinforce our findings. The MR results indicated the significant inverse associations of WP with the risk of RA (odds ratio (OR), 0.31; 95% confidence interval (CI), 0.15, 0.62; p = 1.05 × 10 −3). After adjusting for the risk factors, the associations for WP and RA did not change substantially. Observational study results demonstrated the same effect of WP on reducing the risk of RA. The Mendelian randomization analysis and observational study provide evidence suggesting that walking pace is a protective factor for rheumatoid arthritis. Given its simple measurement, walking pace may be a pragmatic target for interventions.

Abstract The sedimentary environment in the eastern Ordos area of China is complex and contains a large number of transitional facies environments. Yet, there are many characteristics such as large vertical lithology changes, complex lateral sedimentary environment changes, small monolith thickness and large organic matter content changes, which lead to large uncertainty in the prediction of favorable areas for transitional shale gas. As the intricate reservoirs continue to unfold, the conventional linear prediction methods find themselves facing an arduous path to meet the demands of development. The ever-evolving complexity of these reservoirs has outpaced the capabilities of these traditional approaches. It becomes apparent that a more comprehensive and adaptable approach is necessary to navigate the intricacies of these reservoirs and unlock their hidden potential. Therefore, we put forward a method of introducing knowledge graph into transitional shale gas reservoir prediction in the eastern Ordos region by using big data technology. Because artificial intelligence big data relies heavily on data tags, it is particularly important for the construction of tags. Firstly, a top-down knowledge graph in the field of reservoir prediction is constructed to determine the key parameters used in prediction, namely porosity, total organic carbon and brittleness index. Secondly, the decision tree knowledge graph optimization label is constructed in a bottom-up way. The key parameter of this prediction is the knowledge graph obtained according to the professional knowledge of reservoir prediction, so as to optimize the school label of U-net and reduce the workload of artificial judgment. The results of the combination of the two methods are applied to 11 wells in Daji area of Ordos, and the experimental results are consistent with the actual situation of the reservoir. Based on the foundation of theoretical knowledge, this method enhances the efficiency and accuracy of interpretation and evaluation. It provides fundamental and technical support for the selection of favorable areas in shale gas exploration and the evaluation of exploration and development prospects, particularly in transitional shale gas areas, which is innovative and advanced in the field.

Abstract Background SHR-1707 is a novel humanized anti-Aβ IgG1 monoclonal antibody that binds to Aβ fibrils and monomers to block the formation of Aβ plaques or to promote the microglial phagocytosis of Aβ. Preclinical studies showed that SHR-1707 reduced brain Aβ deposition in 5xFAD transgenic mice. Herein, we conducted two phase 1 studies to evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of a single intravenous dose of SHR-1707 in healthy adult subjects. Methods Two randomized, double-blind, single-ascending-dose, phase 1 studies were conducted in China (Study CHN) and Australia (Study AUS). Study CHN consisted of 2 parts. In Part 1, eligible healthy young adults (18–45 years) were sequentially randomized 8:2 to receive SHR-1707 (five cohorts: 2, 6, 20, 40, and 60 mg/kg) or placebo in each cohort; in Part 2, elderly subjects (55–80 years) were randomized 8:4 to receive SHR-1707 (20 mg/kg) or placebo. A similar design was used in Study AUS, but with only healthy young adults enrolled across three dosing cohorts (2, 20, and 60 mg/kg). Results Sixty-two (part 1/2, n = 50/12; age range, 18–42/55–63 years) and 30 subjects (age range, 18–42 years) received SHR-1707 or placebo in Study CHN and Study AUS, respectively. In Study CHN, all treatment-related adverse events (TRAEs) were mild, with the most common being transient laboratory abnormalities. In Study AUS, TRAEs were mostly mild (1 moderate event each with SHR-1707/placebo); the most common TRAEs with SHR-1707 were dysgeusia and fatigue (8.3% each). In both studies, the exposure of SHR-1707 increased in a slightly greater than dose-proportional manner over the dose range of 2–60 mg/kg in young adults; there was a dose-dependent increase in plasma Aβ42 concentration following SHR-1707 administration compared with the placebo group. The safety and PK and PD profiles of SHR-1707 in the elderly subjects were consistent with the younger counterpart at the same dose level. No ethnic difference in safety, PK and PD of SHR-1707 was observed. Conclusions A single intravenous dose of SHR-1707 at 2–60 mg/kg was safe and well tolerated in healthy young adult and elderly subjects. The PK and PD profiles are supportive for further clinical development. Trial registration NCT04973189 (retrospectively registered on Jul.21, 2021) and NCT04745104 (registered on Feb.6, 2021) on clinicaltrials.gov.

Abstract This study investigates global extreme precipitation events (EPEs) during warm seasons, with a particular focus on EPEs preceded by extreme heat stress (EPE-Hs) and a comparative analysis with those not (EPE-NHs). Using reanalysis product and Earth System Model data, the spatiotemporal characteristics and temperature sensitivities of EPEs are analyzed. Results show that EPE-Hs, while less frequent, have longer duration and greater magnitude compared to EPE-NHs, particularly in high latitude regions. In the future, a significant increase is projected in the characteristics of EPE-Hs, in contrast to the stable duration and magnitude of EPE-NHs. EPE-Hs demonstrate substantially higher temperature sensitivity than EPE-NHs, especially in low latitudes. The precipitation-temperature scaling relationships diverge markedly between EPE-Hs and EPE-NHs, with notable regional variations. These insights are pivotal for crafting region-specific early warning and adaptation strategies to mitigate the risks associated with extreme precipitation under the backdrop of global warming.

Abstract Background This study aims to delineate the long-term outcomes and recurrence patterns of locally advanced thoracic esophageal squamous cell carcinoma (TESCC) patients managed with or without postoperative radiotherapy (PORT). Methods A retrospective cohort from two academic centers, encompassing patients who initially underwent esophagectomy and were pathologically staged T3-4, was analyzed. Survival outcomes were constructed using Kaplan–Meier method, with survival significance was evaluated using the log-rank test. Propensity score matching (PSM) was utilized to balance potential selection bias. Results Among the 506 patients, 251 underwent surgery alone and 255 received radiotherapy following radical surgery. With a median follow-up of 49.1 months, PORT significantly improved 5-year overall survival (53.8% vs. 25.3%; p

Abstract Epigenetic readers frequently affect gene regulation, correlate with disease prognosis, and hold significant potential as therapeutic targets for cancer. Zinc finger MYND-type containing 11 (ZMYND11) is notably recognized for reading the epigenetic marker H3.3K36me3; however, its broader functions and mechanisms of action in cancer remain underexplored. Here, we report that ZMYND11 downregulation is prevalent across various cancers and profoundly correlates with poorer outcomes in prostate cancer patients. Depletion of ZMYND11 promotes tumor cell growth, migration, and invasion in vitro, as well as tumor formation and metastasis in vivo. Mechanistically, we discover that ZMYND11 exhibits tumor suppressive roles by recognizing arginine-194-methylated HNRNPA1 dependent on its MYND domain, thereby retaining HNRNPA1 in the nucleus and preventing the formation of stress granules in the cytoplasm. Furthermore, ZMYND11 counteracts the HNRNPA1-driven increase in the PKM2/PKM1 ratio, thus mitigating the aggressive tumor phenotype promoted by PKM2. Remarkably, ZMYND11 recognition of HNRNPA1 can be disrupted by pharmaceutical inhibition of the arginine methyltransferase PRMT5. Tumors with low ZMYND11 expression show sensitivity to PRMT5 inhibitors. Taken together, our findings uncover a previously unexplored noncanonical role of ZMYND11 as a nonhistone methylation reader and underscore the critical importance of arginine methylation in the ZMYND11-HNRNPA1 interaction for restraining tumor progression, thereby proposing novel therapeutic targets and potential biomarkers for cancer treatment.

Abstract Background Whole exome sequencing (WES) has been recommended to investigate the genetic cause of fetal structural anomalies. In this retrospective study, we aimed to evaluate the diagnostic yield of WES in our cohort of families with pregnancy loss or termination of pregnancy due to structural anomalies. Methods As aneuploidy, triploidy and copy number variations (CNVs) could be detected by exome-based CNV analysis, only WES is performed in this study. And the results of 375 cases assessed by WES were analyzed. Results The overall detection rate was 32.3% (121/375), including aneuploidy and triploidy (7.5%, 28/375), CNVs (5.1%, 19/375) and single-nucleotide variants (SNVs) /insertions or deletions (Indels) (19.7%, 74/375). Among these, the diagnostic yield for likely pathogenic (LP) or pathogenic (P) CNVs is 4.8% (18/375), and the diagnostic yield for LP or P SNVs/Indels is 15.2% (57/375). And an additional 4.8% (18/375) of cases had CNVs or SNVs/Indels classified as variants of uncertain significance (VUS) with potential clinical significance. Conclusions Our findings expand the known mutation spectrum of genetic variants related to fetal abnormalities, increase our understanding of prenatal phenotypes, and enable more accurate counseling of recurrence risk for future pregnancies.

To explore the effects of different preservation treatments on the storage quality of green walnut, this study took green walnut as test material and adopted 4 different preservation. Methods: Soaked in cold water at 0 ℃ for 5 min, 150 mg/L ClO2 for 20 min, 100 mg/L gibberellin for 20 min and mixed with gibberellin (100 mg/L)+imidamine (active component content 450 g/L) for 20 min. The browning index, moisture content, color difference, respiratory intensity, hardness, chlorophyll content, malondialdehyde (MDA) content, polyphenol oxidase (PPO) and peroxidase (POD) activity, total phenol and total flavonoids content of walnut with green peel as control were studied during storage under 0±0.3 ℃.The results showed that during the storage, compared with the control group, the treatment group significantly (P

Abstract Background Accurate breed identification is essential for the conservation and sustainable use of indigenous farm animal genetic resources. In this study, we evaluated the phylogenetic relationships and genomic breed compositions of 13 sheep breeds using SNP and InDel data from whole genome sequencing. The breeds included 11 Chinese indigenous and 2 foreign commercial breeds. We compared different strategies for breed identification with respect to different marker types, i.e. SNPs, InDels, and a combination of SNPs and InDels (named SIs), different breed-informative marker detection methods, and different machine learning classification methods. Results Using WGS-based SNPs and InDels, we revealed the phylogenetic relationships between 11 Chinese indigenous and two foreign sheep breeds and quantified their purities through estimated genomic breed compositions. We found that the optimal strategy for identifying these breeds was the combination of DFI_union for breed-informative marker detection, which integrated the methods of Delta, Pairwise Wright's FST, and Informativeness for Assignment (namely DFI) by merging the breed-informative markers derived from the three methods, and KSR for breed assignment, which integrated the methods of K-Nearest Neighbor, Support Vector Machine, and Random Forest (namely KSR) by intersecting their results. Using SI markers improved the identification accuracy compared to using SNPs or InDels alone. We achieved accuracies over 97.5% when using at least the 1000 most breed-informative (MBI) SI markers and even 100% when using 5000 SI markers. Conclusions Our results provide not only an important foundation for conservation of these Chinese local sheep breeds, but also general approaches for breed identification of indigenous farm animal breeds.

Abstract Tight sandstone reservoirs are a primary focus of research on the geological exploration of petroleum. However, many reservoir classification criteria are of limited applicability due to the inherent strong heterogeneity and complex micropore structure of tight sandstone reservoirs. This investigation focused on the Chang 8 tight reservoir situated in the Jiyuan region of the Ordos Basin. High-pressure mercury intrusion experiments, casting thin sections, and scanning electron microscopy experiments were conducted. Image recognition technology was used to extract the pore shape parameters of each sample. Based on the above, through grey relational analysis (GRA), analytic hierarchy process (AHP), entropy weight method (EWM) and comprehensive weight method, the relationship index Q1 between initial productivity and high pressure mercury injection parameters and the relationship index Q2 between initial productivity and pore shape parameters are obtained by fitting. Then a dual-coupled comprehensive quantitative classification prediction model for tight sandstone reservoirs was developed based on pore structure and shape parameters. A quantitative classification study was conducted on the target reservoir, analyzing the correlation between reservoir quality and pore structure and shape parameters, leading to the proposal of favourable exploration areas. The research results showed that when Q1 ≥ 0.5 and Q2 ≥ 0.5, the reservoir was classified as type I. When Q1 > 0.7 and Q2 > 0.57, it was classified as type I1, indicating a high-yield reservoir. When 0.32

Background: Flavonoids are one of the most important metabolites with vast structural diversity and a plethora of potential pharmacological applications, which have drawn considerable attention in the laboratory. Nevertheless, it remains uncertain how many candidates were progressed to clinical application. Aim of Review: We carried out a critical review of natural and semi-synthetic flavonoid drugs and candidates undergoing different clinical phases worldwide by applying an adequate search method and conducted a brief cheminformatic and bioinformatic analysis. It was expected that the obtained results might narrow the screening scope and reduce the cost of drug research and development. Key scientific Concepts of Review: To our knowledge, this is the most systematic summarization of flavonoid-based drugs and clinical candidates to date. It was found that a total of 19 flavonoid-based drugs have been approved for the market, and of these, natural flavonoids accounted for 52.6%. Besides, a total of 36 flavonoid-based clinical candidates are undergoing or suspended in different phases, and of these, natural flavonoids account for 44.4%. Thus, natural flavonoids remain the best option for finding novel agents/active templates, and when investigated in conjunction with synthetic chemicals and biologicals, they offer the potential to discover novel structures that can lead to effective agents against a variety of human diseases. Additionally, flavonoid-based marketed drugs have been successful in cardiovascular treatment, and the related drugs account for more than 30% of marketed drugs. However, the use of flavonoids as antineoplastic and immunomodulating agents is not likely for approximately 50% of the candidates suspended in the clinical stage. Interestingly, the marketed drugs covered a broader range of chemical spaces based on size, polarity, and three-dimensional structure compared to the clinical candidates. In addition, flavonoid glycosides with poor oral bioavailability account for 36.8% of the marketed drugs, and thus, they could be thoroughly investigated.

Abnormal hyperphosphorylation of tau protein is a principal pathological hallmark in the onset of neurodegenerative disorders, such as Alzheimer's disease (AD), which can be induced by an excess of reactive oxygen species (ROS). As an antioxidant, hydrogen gas (H2) has the potential to mitigate AD by scavenging highly harmful ROS such as •OH. However, conventional administration methods of H2 face significant challenges in controlling H2 release on demand and fail to achieve effective accumulation at lesion sites. Herein, we report artificial nanoreactors that mimic natural photosynthesis to realize near-infrared (NIR) light-driven photocatalytic H2 evolution in situ. The nanoreactors are constructed by biocompatible crosslinked vesicles (CVs) encapsulating ascorbic acid and two photosensitizers, chlorophyll a (Chla) and indoline dye (Ind). In addition, platinum nanoparticles (Pt NPs) serve as photocatalysts and upconversion nanoparticles (UCNP) act as light-harvesting antennas in the nanoreacting system, and both attach to the surface of CVs. Under NIR irradiation, the nanoreactors release H2 in situ to scavenge local excess ROS and attenuate tau hyperphosphorylation in the AD mice model. Such NIR-triggered nanoreactors provide a proof-of-concept design for the great potential of hydrogen therapy against AD.

Fluid intelligence is an individual's innate ability to cope with complex situations and is gradually reduced across adults aging. The realization of fluid intelligence requires the simultaneous activity of multiple brain regions and depends on the structural connection of distributed brain regions. Uncovering the structural features of brain connections associated with fluid intelligence decline will provide reference for the development of intervention and treatment programs for cognitive decline. Using structural magnetic resonance imaging data of 454 healthy participants (18–87 years) from the Cam-CAN dataset, we constructed structural similarity network for each participant and calculated the node degree. Spearman correlation analysis showed that age was positively correlated with degree centrality in the cingulate cortex, left insula and subcortical regions, while negatively correlated with that in the orbito-frontal cortex, right middle temporal and precentral regions. Partial least squares (PLS) regression showed that the first PLS components explained 32 % (second PLS component: 20 %, pperm < 0.001) of the variance in fluid intelligence. Additionally, the degree centralities of anterior insula, supplementary motor area, prefrontal, orbito-frontal and anterior cingulate cortices, which are critical nodes of the multiple-demand network (MDN), were linked to fluid intelligence. Increased degree centrality in anterior cingulate cortex and left insula partially mediated age-related decline in fluid intelligence. Collectively, these findings suggest that the structural stability of MDN might contribute to the maintenance of fluid intelligence.

The intricate task of precisely segmenting retinal vessels from images, which is critical for diagnosing various eye diseases, presents significant challenges for models due to factors such as scale variation, complex anatomical patterns, low contrast, and limitations in training data. Building on these challenges, we offer novel contributions spanning model architecture, loss function design, robustness, and real-time efficacy. To comprehensively address these challenges, a new U-Net-like, lightweight Transformer network for retinal vessel segmentation is presented. By integrating MobileViT+ and a novel local representation in the encoder, our design emphasizes lightweight processing while capturing intricate image structures, enhancing vessel edge precision. A novel joint loss is designed, leveraging the characteristics of weighted cross-entropy and Dice loss to effectively guide the model through the task's challenges, such as foreground-background imbalance and intricate vascular structures. Exhaustive experiments were performed on three prominent retinal image databases. The results underscore the robustness and generalizability of the proposed LiViT-Net, which outperforms other methods in complex scenarios, especially in intricate environments with fine vessels or vessel edges. Importantly, optimized for efficiency, LiViT-Net excels on devices with constrained computational power, as evidenced by its fast performance. To demonstrate the model proposed in this study, a freely accessible and interactive website was established (https://hz-t3.matpool.com:28765?token=aQjYR4hqMI), revealing real-time performance with no login requirements.

Abstract Background Postoperative respiratory adverse events are the most common perioperative complications in pediatric anesthesia, particularly prevalent in children undergoing tonsillectomy and adenoidectomy, with an incidence rate as high as 50%. The choice of anesthetic induction regimen directly influences the incidence of respiratory adverse events during the induction period. However, this effect seems to have minimal impact on postoperative outcomes. The occurrence rate of postoperative respiratory adverse events is likely more closely associated with the anesthetic maintenance phase, yet this relationship remains uncertain at present. Methods The objective of this study was to assess the impact of different anesthetic maintenance regimens on postoperative respiratory adverse events in pediatric patients undergoing tonsillectomy and adenoidectomy. The AmPRAEC study is a multicenter, randomized, double-blind controlled trial. A total of 717 pediatric patients were recruited from 12 medical centers and randomly assigned to three groups: group A (intravenous maintenance group, receiving propofol infusion); group B (intravenous-inhalational combination group, maintained with 1% sevoflurane combined with propofol); and group C (inhalational maintenance group, maintained with 2–3% sevoflurane inhalation). The primary outcome measure was the incidence rate of postoperative respiratory adverse events. Discussion This clinical trial aims to elucidate the impact of various anesthetic maintenance regimens on postoperative respiratory adverse events in pediatric patients. The outcomes of this study are anticipated to facilitate anesthesiologists in devising more comprehensive perioperative management strategies, enhancing comfort, and improving the clinical outcomes for this patient population. Trial registration Chinese Clinical Trial Registry ( http://www.chictr.org.cn ) ChiCTR2300074803. Registered on August 16, 2023.

Abstract Background Epidermal growth factor receptor (EGFR) fusions are rare but potentially actionable oncogenic drivers across multiple solid tumors. However, the distribution and molecular characteristics of EGFR fusions in Chinese patients with solid malignancies have not been explored. Methods Panel-based next-generation sequencing (NGS) data of 35,023 patients with various types of solid tumors was collected and analyzed from the Simcere Diagnostics (Nanjing, China) database. A 9563-patient cohort was derived from The Cancer Genome Atlas (TCGA) to explore the relationship between EGFR fusion status and overall survival (OS). Results In this study, prevalence of functional EGFR fusions was 0.303% (106/35,023) in total across solid tumors, which occur more commonly in gastroesophageal junction cancer (1/61, 1.613%), followed by medulloblastoma (1/66, 1.515%) and glioma (33/2409, 1.370%). Analysis showed a prevalence for fusion partners in different tumor types. The top 3 co-mutant genes with EGFR fusion were TP53 (mutation frequency, MF: 65%), BRCA2 (MF: 43%), and ALK (MF: 41%). Furthermore, patients in the EGFR fusion group had a significantly shorter OS than those in the non-EGFR fusion group (p

Abstract Alzheimer’s disease (AD) is the most common cause of dementia characterized by amyloid-β (Aβ) deposition, tau hyperphosphorylation, and neuroinflammation. Naringenin (NRG), a natural flavonoid widely present in citrus fruits, has been reported can penetrate the blood-brain barrier and exert anti-inflammatory effects in the central nervous system. Here, we investigate the protective effects of long-term NRG treatment on AD. The novel object recognition test and Morris water maze test reveal that NRG treatment can improve the learning and memory ability of APP/PS1 mice. Besides, we find that NRG can significantly reduce Aβ deposition, microglial and astrocytic activation, and pro-inflammatory cytokine levels in APP/PS1 mice. Results further show that NRG effectively decreases pro-inflammatory cytokines in LPS/Aβ-stimulated BV2 cells. Lastly, the molecular mechanistic study reveals that NRG attenuates neuroinflammatory responses via inhibition of the MAPK signaling pathway in vivo and in vitro. Overall, NRG may emerge as a promising compound for the prevention and treatment of AD.

Degradable rotator cuff patches, followed over five years, have been observed to exhibit high re-tear rates exceeding 50%, which is attributed to the inability of degradable polymers alone to restore the post-rotator cuff tear (RCT) inflammatory niche. Herein, poly(ester-ferulic acid-urethane)urea (PEFUU) was developed, featuring prolonged anti-inflammatory functionality, achieved by the integration of ferulic acid (FA) into the polyurethane repeating units. PEFUU stably releases FA in vitro, reversing the inflammatory niche produced by M1 macrophages and restoring the directed differentiation of stem cells. Utilizing PEFUU, hierarchical composite nanofiber patch (HCNP) was fabricated, simulating the natural microstructure of the tendon-to-bone interface with an aligned-random alignment. The incorporation of enzymatic hydrolysate derived from decellularized Wharton jelly tissue into the random layer could further enhance cartilage regeneration at the tendon-to-bone interface. Via rat RCT repairing model, HCNP possessing prolonged anti-inflammatory properties uniquely facilitated physiological healing at the tendon-to-bone interface's microstructure. The alignment of fibers was restored, and histologically, the characteristic tripartite distribution of collagen I – collagen II - collagen I was achieved. This study offers a universal approach to the functionalization of degradable polymers and provides a foundational reference for their future applications in promoting the in vivo regeneration of musculoskeletal tissues.

Abstract Photothermal therapy (PTT) is a promising cancer treatment method due to its ability to induce tumor-specific T cell responses and enhance therapeutic outcomes. However, incomplete PTT can leave residual tumors that often lead to new metastases and decreased patient survival in clinical scenarios. This is primarily due to the release of ATP, a damage-associated molecular pattern that quickly transforms into the immunosuppressive metabolite adenosine by CD39, prevalent in the tumor microenvironment, thus promoting tumor immune evasion. This study presents a photothermal nanomedicine fabricated by electrostatic adsorption among the Fe-doped polydiaminopyridine (Fe-PDAP), indocyanine green (ICG), and CD39 inhibitor sodium polyoxotungstate (POM-1). The constructed Fe-PDAP@ICG@POM-1 (FIP) can induce tumor PTT and immunogenic cell death when exposed to a near-infrared laser. Significantly, it can inhibit the ATP-adenosine pathway by dual-directional immunometabolic regulation, resulting in increased ATP levels and decreased adenosine synthesis, which ultimately reverses the immunosuppressive microenvironment and increases the susceptibility of immune checkpoint blockade (aPD-1) therapy. With the aid of aPD-1, the dual-directional immunometabolic regulation strategy mediated by FIP can effectively suppress/eradicate primary and distant tumors and evoke long-term solid immunological memory. This study presents an immunometabolic control strategy to offer a salvage option for treating residual tumors following incomplete PTT.

This is an article in the field of mineral processing engineering. Fatty acid collectors are widely used in the flotation of oxidized ores, and the molecular structure is an important factor affecting the flotation performance. To reveal the effect of the structural change of fatty acid collector on its reaction activity from the microscopic point of view, the relationship between electronic structure and properties of fatty acid collectors was studied by the density functional theory. The research results show that the oxygen atom in oleic acid molecule and oleate ion has strong reaction activity, which is the bonding atom of oleic acid interaction with oxidized minerals. The two oxygen atoms of oleate ion have similar chemical activity, and the density of states at Fermi level is higher than that of oleic acid molecule, which makes the activity of oleate ion much stronger than that of oleic acid molecule. The length of the carbon chain and the unsaturation of the alkyl have almost no effect on the density of states of the oxygen atoms in fatty acids, their effect on the properties of fatty acids is not through the action of carboxyl groups. The interaction energy between fatty acids and common metal cations is consistent with the decrease of their solubility product constants, and there is a good corresponding relationship between them. The research has certain theoretical significance and reference value for understanding the relationship between the structure and performance of fatty acid collectors and developing new fatty acid collectors.

Abstract To analyze the current status of "pseudo" unplanned endotracheal extubation in ICU patients in China's tertiary hospitals and to provide a reference for improving the quality of medical care. Through the National Nursing Quality Data Platform, unplanned endotracheal extubation data reported by ICUs in China's tertiary hospitals from 2019 to 2022 were analyzed. The situation of reported hospitals, causes, and the current status of "pseudo" unplanned endotracheal extubation in ICU patients was analyzed. The indicator of unplanned endotracheal extubation in ICUs of China’s tertiary hospitals is mainly from first-class tertiary hospitals (74.9%), most of which are self-extractions by patients (74.6%). The proportion of "pseudo" unplanned endotracheal extubation is 45.1%. "Pseudo" unplanned endotracheal extubation is common in the ICUs of China's tertiary hospitals. As such, management blind spots deserve attention from managers and clinical staff.

Abstract The triglyceride glucose body mass index (TyG-BMI) is a potential indicator for insulin resistance, but its association with mortality in diabetic patients is unclear. This study investigates the relationship between TyG-BMI and all-cause and cardiovascular mortality in diabetics. The study included 3109 diabetic patients from the National Health and Nutrition Examination Survey (2001–2018). Mortality data were obtained from National Death Index records until 31 December 2019. Multivariate Cox models analyzed the association between TyG-BMI and mortality. Non-linear correlations were assessed using restricted cubic splines, and a two-piecewise Cox model evaluated the relationship on both sides of the inflection point. Over a median 7.25-year follow-up, 795 total and 238 cardiovascular deaths occurred. A U-shaped link was found between initial TyG-BMI and mortality in diabetic patients. Low TyG-BMI ( 279.67 for all-cause, > 270.19 for CVD) increased these risks (all-cause: HR 1.26, 95% CI 1.10–1.44; CVD: HR 1.33, 95% CI 1.06–1.68). In the NHANES study population, a U-shaped association was observed between the baseline TyG-BMI index and all-cause mortality or CVD in diabetic patients.

PurposeAtrial tachycardia is an uncommon supraventricular tachycardia in children. It is often drug-resistant and likely to occur concomitantly with tachycardia-induced cardiomyopathy, making radiofrequency catheter ablation the preferred treatment. The aim of this study was to assess the feasibility, safety, and effectiveness of radiofrequency catheter ablation for the treatment of different types of atrial tachycardia in children, particularly in those with drug-resistant and tachycardia-induced cardiomyopathy.MethodsA total of 28 children with atrial tachycardia (including focal atrial tachycardia and atrial flutter) who underwent atrial radiofrequency ablation at the Children's Hospital Affiliated to Chongqing Medical University from May 2018 to December 2023 were included. The baseline characteristics, preoperative medication, surgical information, and postoperative follow-up data of these children were analyzed statistically.ResultsThe mean age patients at ablation was 10.24 ± 3.40 years. A total of 78.6% of the patients (22/28) who received preoperative pharmacological treatment had intermittent or persistent atrial tachycardia. Of the 28 children who underwent radiofrequency ablation, 24 (85.7%) were diagnosed with focal atrial tachycardia, three (10.7%) with atrial flutter, and one (3.6%) with both. No postoperative complications occurred in any patient. The immediate ablation success rate in the 25 patients with focal atrial tachycardia was 96.0% (24/25). After 26.89 ± 18.17 months of follow-up, only three patients had recurrence. The ablation difficulty of focal atrial tachycardia originating in the appendage was higher than that originating in the non-atrial appendage (44.4% vs. 6.3%, p = 0.01). The success rate of ablation for atrial flutter was 100%, except in one child with underlying cardiomyopathy who experienced recurrence. Final success was achieved in 25 of the 28 patients (89.2%) at the end of the follow-up period. In addition, eight children (28.6%) in this study were diagnosed with tachycardia-induced cardiomyopathy, with significantly increased ejection fraction and shortening rate after radiofrequency ablation (p 0.05).ConclusionRadiofrequency catheter ablation is safe and effective for the treatment of atrial tachycardia in children in the short- and long-term.It can be used as the first treatment option for children with medically refractory atrial tachycardia and tachycardia-induced cardiomyopathy.

ABSTRACT Background The increasing incidence of endometrial cancer (EC) has highlighted the need for improved early detection methods. This study aimed to develop and validate a novel DNA methylation classifier, EMPap, for EC detection using cervical scrapings. Methods EMPap incorporated the methylation status of BHLHE22 and CDO1, along with age and body mass index (BMI), into a logistic regression model to calculate the endometrial cancer methylation (EM) score for identifying EC in cervical scrapings. We enrolled 1297 patients with highly suspected EC, including 196 confirmed EC cases, and assessed the EMPap performance in detecting EC. Results EMPap demonstrated robust diagnostic accuracy, with an area under the curve of 0.93, sensitivity of 90.3%, and specificity of 89.3%. It effectively detected EC across various disease stages, grades, and histological subtypes, and consistently performed well across patient demographics and symptoms. EMPap correctly identified 87.5% of the type II ECs and 53.8% of premalignant lesions. Notably, compared with transvaginal ultrasonography (TVS) in patients with postmenopausal bleeding, EMPap exhibited superior sensitivity (100% vs. 82.0%) and specificity (85.2% vs. 38.5%). In asymptomatic postmenopausal women, EMPap maintained high sensitivity (89.5%) and negative predictive value (NPV) (98.3%). Conclusions This study demonstrated the potential of EMPap as an effective tool for EC detection. Despite the limited sample size, EMPap showed promise for identifying type II EC and detecting over 50% of premalignant lesions. As a DNA methylation classifier, EMPap can reduce unnecessary uterine interventions and improve diagnosis and outcomes.

Hepatic myelopathy (HM) is a rare complication of end-stage chronic liver disease, primarily presenting as symmetrical lower limb weakness that progresses to spastic paralysis without sensory or sphincter dysfunction. We report a case of decompensated cirrhosis associated with hepatitis B virus and HM. The patient showed significant recovery after liver transplantation (LT) and comprehensive rehabilitation training. We summarize the patient’s clinical characteristics post-diagnosis and the assessment outcomes following integrated treatment.

Diquat (DQ) is a widely utilized nonselective herbicide that is primarily used to control a wide range of weeds and crop residues. It also has significant environmental implications. DQ exposure can cause severe damage to the central nervous system (CNS), a critical symptom of acute poisoning that endangers patients. Despite its severity, the underlying mechanisms of DQ-induced toxic encephalopathy remain unclear, hindering the development of precise treatments. Our research demonstrated that acute DQ exposure in mice significantly increases oxidative stress and triggers neuroinflammation in the hippocampus. Furthermore, in vitro findings indicate that the detrimental effects of DQ are mediated by its disruption of autophagic processes, leading to exacerbated neural damage. DQ initially promotes autophagy in BV2 microglia for self-protection against oxidative stress and inflammation. However, this process is subsequently blocked, intensifying neural damage. Crucially, our results show that the activation of autophagy can reverse these adverse effects. This study not only sheds light on the intricate mechanisms of DQ neurotoxicity but also provides potential therapeutic targets for mitigating DQ-induced toxic encephalopathy.

Tissue kallikrein (TK) has emerged as a potential neuroprotective agent in ischemic stroke (IS), yet the optimal timing and mechanisms of TK therapy remain unclear. Here, we established a causal link between lower baseline TK levels and an increased risk of stroke through a retrospective, multicenter cohort study involving 2115 initially non-stroke subjects monitored for 5 years. Sequentially, we observed a notable increase in bradykinin receptor 2 (B2R) levels during the ischemic phase of the IS model, while levels of TK and bradykinin receptor 1 (B1R) remained stable. Intriguingly, both B1R and B2R exhibited a significant elevation 24 h after reperfusion. Further investigations in preclinical models demonstrated that TK supplementation activates the PI3K/AKT signaling pathway via enhanced B2R expression during the ischemic phase, leading to nuclear translocation of Hif-1α. This activation enhances the expression of VEGF and eNOS, thereby fortifying the neurovascular unit. Moreover, it suppresses the activation of the kallikrein-kinin system induced by reperfusion injury, effectively reducing inflammation, ROS production, apoptosis, and endothelial barrier dysfunction. Thus, our findings highlight the significance of TK supplementation during the ischemic phase in attenuating reperfusion-induced injury in IS, providing a mechanistic rationale for determining the optimal timing for TK supplementation therapy.

ABSTRACT Background The pathophysiological mechanisms underlying migraine without aura (MwoA) in females remain incompletely elucidated. Currently, the association between headache laterality and iron deposition (ID), and functional connectivity (FC) in female MwoA patients has not been fully studied. Methods We prospectively recruited 63 female patients with MwoA and 31 matched healthy controls (HC) from the hospital. ID and FC among the four groups were analyzed using two‐sample t‐tests (with cluster‐wise family‐wise error [FWE] correction). Pearson correlation analysis was used to evaluate the relationships between clinical variables and both ID and FC values. Significance level: p

Objective To assess the efficacy and safety of intracavitary electrocardiography (IC-ECG)-guided peripherally inserted central catheter (PICC) placements in pediatric patients, emphasizing improvements over traditional placement methods. Methods A literature search was conducted in April 2024 across PubMed, Cochrane Library, and EMBASE. Studies focusing on pediatric patients and reporting the efficacy and safety of IC-ECG-guided PICC placement via the upper extremity were included. This study was registered with the PROSPERO database (CRD42024549037) in accordance with PRISMA guidelines. Results Eleven studies were included, comprising five randomized controlled trials (RCTs) and six quasi-experimental studies. The pooled analysis showed that IC-ECG had an applicability and feasibility of 97% and 98%, respectively. The first puncture success rate was 91%, and the overall success rate was 98%. Sensitivity and specificity were 97% and 80%, respectively. IC-ECG significantly reduced overall complications compared to traditional methods (RR: 0.31, 95% CI [0.20–0.46], p < 0.00001), particularly in phlebitis (RR: 0.25, 95% CI [0.11–0.57], p = 0.001) and arrhythmias (RR: 0.09, 95% CI [0.01–0.70], p = 0.021). Similar results were observed in neonates. Only one case of catheter-related bloodstream infection (CRBSI) was reported, and no arrhythmia events were noted. Conclusion IC-ECG-guided PICC placement is a highly effective and safe method for pediatric patients, including neonates, offering significant advantages over traditional techniques. Further high-quality studies are needed to standardize procedural techniques and explore cost-effectiveness.

The dense structure of solid tumor tissues and the selective permeability of cell membranes impede the effective penetration of chemotherapeutic agent-loaded liposomes into tumors and their subsequent uptake by cells. Dermaseptin-PP, a cationic antimicrobial peptide, has demonstrated the ability to enhance the penetration and accumulation of drugs within solid tumors due to its unique membrane-breaking action. Based on this, we designed glutathione (GSH)-sensitive paclitaxel liposomes modified with Dermaseptin-PP. Dermaseptin-PP was modified through disulfide bonding, which could be broken at the tumor site due to high GSH levels. This cleavage resulted in the release of Dermaseptin-PP, thereby enhancing the permeability of the paclitaxel liposomes within the tumor. We found that the paclitaxel liposomes modified with Dermaseptin-PP were extensively distributed to the tumor site, and the Dermaseptin-PP modification significantly enhanced liposome penetration within the tumor. Our study significantly increased the anti-tumor efficacy of paclitaxel liposomes. Our study confirms that paclitaxel liposomes modified with Dermaseptin-PP is an effective anti-tumor therapy that enhances deep penetration into tumors. Additionally, this broadens the applications of cationic antimicrobial peptides.

ABSTRACT The combination of aztreonam with ceftazidime/avibactam is considered a potential therapeutic approach for the treatment of infections caused by metallo-β-lactamase (MBL)-producing isolates. In this study, in vitro antibacterial activity of aztreonam with avibactam against 204 carbapenemase-producing Enterobacterales was determined by broth disk elution (BDE) method of two detection volumes (5- and 2-mL broth), with broth microdilution (BMD) method as a reference. For the BDE-5mL test, the categorical agreement (CA) of ATM+CZA-lo tube (aztreonam/ceftazidime/avibactam: 6/6/4 mg/L) was 99.5%, with 0.5% major error (ME) and 0% very major error (VME); the CA of 2ATM+CZA-lo tube (12/6/4 mg/L) was 100%, with no ME and VME. For the BDE-2mL test, the CA of ATM+2CZA-hi tube (15/10/4 mg/L) was 98.5%, with 0% ME and 37.5% VME; the CA of 2ATM+2CZA-hi tube (30/10/4 mg/L) was 97.1%, with 0% ME and 75% VME. The BDE-5 mL test is an economical and practical method for clinical microbiology laboratories to determine the antibacterial susceptibility of aztreonam with avibactam against Enterobacterales, especially the 2ATM+CZA-lo tube with a final concentration of 12/6/4 mg/L of aztreonam/ceftazidime/avibactam.IMPORTANCEInfections caused by metallo-β-lactamase (MBL)-producing Enterobacterales are increasingly reported worldwide, and it is a significant challenge for clinical infection treatment. MBLs are adept at hydrolyzing almost all traditional β-lactam antibiotics except aztreonam, and the enzyme activity cannot be inhibited by traditional or novel β-lactamase inhibitors. The good thing is that the combination of aztreonam with ceftazidime/avibactam has been proven to be one of the potential therapeutic approaches for treating infections related with MBL-producing isolates. Broth microdilution (BMD) method is recommended as a reference method for its accuracy, but it is too complex to perform in most routine laboratories. Finding a more convenient, practical, and accurate susceptibility testing method for aztreonam/avibactam in clinical microbiology laboratories is very necessary. Here, we evaluated the performance of broth disk elution (BDE) method for aztreonam in combination with ceftazidime/avibactam against Enterobacterales isolates, with BMD as a reference.

Arachnoid cysts (ACs) are frequently encountered as incidental findings in the brain, with most cases being asymptomatic and not requiring intervention. However, severe brain malformations caused by ACs are rare. In this study, we describe the case of an 8-day-old female infant with a left mandibular mass that was diagnosed as an insular operculum, which has become disconnected and herniated into the parapharyngeal space through an incompletely ossified greater wing of the sphenoid, caused by a fetal Galassi Type III AC. The newborn also exhibited left hearing impairment, which did not improve at the 6-month follow-up after the cyst peritoneal shunt. This report highlights that ACs that manifest during the early fetal period may protrude from the cranial cavity through an unossified skull, potentially affecting the development of brain tissues.

The advanced prostate biopsy robot system has broad application prospects in clinical practice, but due to the deformation and distortion between MR-TRUS (magnetic resonance transrectal ultrasound) images, it poses challenges in biopsy accuracy and safety. The study utilized an advanced prostate biopsy robot system based on MR-TRUS image flexible registration technology and conducted experiments on animal models. Retrospective analysis of the puncture accuracy of 12 animal experiments undergoing prostate puncture using MR-TRUS flexible registration technology from May 2022 to October 2023, and observation of intraoperative and 7-day postoperative complications. The study obtained MR-TRUS images and utilized image processing algorithms for registration to reduce image deformation and distortion. Then, precise positioning and operation are carried out through the robot system to execute the prostate biopsy program. The experimental results indicate that the advanced prostate biopsy robot system based on MR-TRUS image flexible registration technology has demonstrated good feasibility and safety in animal experiments. Image registration technology has successfully reduced image distortion and deformation, improving biopsy accuracy. The precise positioning and operation of robot systems play a crucial role in the biopsy process, reducing the occurrence of complications.

Patients with EGFR-mutated non-small cell lung cancer (NSCLC) respond poorly to immune checkpoint inhibitors (ICIs). It has been reported that the number of CD8+ T cells is reduced in EGFR-mutated NSCLC. However, the extent of heterogeneity and effector function of distinct populations of CD8+ T cells has not been investigated intensively. In addition, studies investigating whether a combination of radiotherapy and ICIs can improve the efficacy of ICIs in EGFR-mutated lung cancer are lacking. Single-cell RNA sequencing (scRNA-seq) was used to investigate the heterogeneity of CD8+ T cell populations in EGFR-mutated NSCLC. The STING pathway was explored after hypofractionated radiation of EGFR-mutated and wild-type cells. Mice bearing LLC-19del and LLC-EGFR tumors were treated with radiotherapy plus anti-PD-L1. The scRNA-seq data showed the percentage of progenitor exhausted CD8+ T cells was lower in EGFR-mutated NSCLC. In addition, CD8+ T cells in EGFR-mutated NSCLC were enriched in oxidative phosphorylation. In EGFR-mutated and wild-type cells, 8 Gy × 3 increased the expression of chemokines that recruit T cells and activate the cGAS-STING pathway. In the LLC-19del and LLC-EGFR mouse model, the combination of radiation and anti-PD-L1 significantly inhibited the growth of abscopal tumors. The enhanced abscopal effect was associated with systemic CD8+ T cell infiltration. This study provided an intensive understanding of the heterogeneity and effector functions of CD8+ T cells in EGFR-mutated NSCLC. We showed that the combination of hypofractionated radiation and anti-PD-L1 significantly enhanced the abscopal responses in both EGFR-mutated and wild-type lung cancer by activating CD8+T cells in mice.

Abstract Genetic and epigenetic alterations occur in many physiological and pathological processes. The existing knowledge regarding the association of PIWI‐interacting RNAs (piRNAs) and their genetic variants on risk and progression of prostate cancer (PCa) is limited. In this study, three genome‐wide association study datasets are combined, including 85,707 PCa cases and 166,247 controls, to uncover genetic variants in piRNAs. Functional investigations involved manipulating piRNA expression in cellular and mouse models to study its oncogenetic role in PCa. A specific genetic variant, rs17201241 is identified, associated with increased expression of PROPER (piRNA overexpressed in prostate cancer) in tumors and are located within the gene, conferring an increased risk and malignant progression of PCa. Mechanistically, PROPER coupled with YTHDF2 to recognize N6‐methyladenosine (m6A) and facilitated RNA‐binding protein interactions between EIF2S3 at 5′‐untranslated region (UTR) and YTHDF2/YBX3 at 3′‐UTR to promote DUSP1 circularization. This m6A‐dependent mRNA‐looping pattern enhanced DUSP1 degradation and inhibited DUSP1 translation, ultimately reducing DUSP1 expression and promoting PCa metastasis via the p38 mitogen‐activated protein kinase (MAPK) signaling pathway. Inhibition of PROPER expression using antagoPROPER effectively suppressed xenograft growth, suggesting its potential as a therapeutic target. Thus, targeting piRNA PROPER‐mediated genetic and epigenetic fine control is a promising strategy for the concurrent prevention and treatment of PCa.

BackgroundResting-state functional magnetic resonance imaging (rs-fMRI) reveals diverse neural activity patterns in cervical spondylosis (CS) patients. However, the reported results are inconsistent. Therefore, our objective was to conduct a meta-analysis to synthesize the findings from existing rs-fMRI studies and identify consistent patterns of neural brain activity alterations in patients with CS.Materials and methodsA systematic search was conducted across PubMed, Web of Knowledge, Embase, Google Scholar, and CNKI for rs-fMRI studies that compared CS patients with healthy controls (HCs), up to January 28, 2024. Significant cluster coordinates were extracted for comprehensive analysis.ResultsWe included 16 studies involving 554 CS patients and 488 HCs. CS patients demonstrated decreased brain function in the right superior temporal gyrus and left postcentral gyrus, and increased function in the left superior frontal gyrus. Jackknife sensitivity analysis validated the robustness of these findings, and Egger’s test confirmed the absence of significant publication bias (p > 0.05). Meta-regression showed no significant impact of age or disease duration differences on the results.ConclusionThis meta-analysis confirms consistent alterations in specific brain regions in CS patients, highlighting the potential of rs-fMRI to refine diagnostic and therapeutic strategies.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42024496263.

The cell wall serves as the primary barrier against the entry of heavy metal ions into cells. However, excessive accumulation of heavy metals within plants can lead to alterations in the spatial structure and physical properties of the cell wall, thereby affecting the capacity of plants to capture heavy metals. Proline (Pro) is involved in the synthesis of the cell wall, modulating the stability and integrity of its structure. Extensins, core proteins that maintain the cell wall structure, are proline/hydroxyproline-rich glycoproteins that contain the characteristic sequence Ser-[Pro]3–5. They act as intermediates in the regulation of biological processes such as cell wall synthesis, assembly, and signal transduction, typically forming a network structure of cell wall proteins through cross-linking with pectin. This network is essential for the self-assembly expansion of the plant cell wall and plays an indispensable role in cell wall stress signal transduction through its interaction with intracellular signalling molecules. However, the mechanisms by which Pro affects the synthesis of cell wall structural proteins, cell wall assembly, and the sensing of cell wall stress under heavy metal stress remain unclear. This review, from the perspectives of biochemistry and molecular biology, comprehensively elaborates on the impact of Pro and Pro-rich proteins on the structure and function of the cell wall. These findings emphasize the mechanism by which Pro enhances the ability of the cell wall to capture heavy metals, providing new research ideas for the use of genetic engineering to manipulate cell wall synthesis and repair, thereby reducing the phytotoxicity of heavy metals.

Silicosis is the most common type of pneumoconiosis, having a high incidence in workers chronically exposed to crystalline silica (CS). No specific medication exists for this condition. GHK, a tripeptide naturally occurring in human blood and urine, has antioxidant effects. We aimed to investigate the therapeutic effect of GHK-Cu on silicosis and its potential underlying molecular mechanism. An experimental silicosis mouse model was established to observe the effects of GHK-Cu on lung inflammation and fibrosis. Moreover, the effects of GHK-Cu on the alveolar macrophages (AM) were examined using the RAW264.7 cell line. Its molecular target, peroxiredoxin 6 (PRDX6), has been identified, and GHK-Cu can bind to PRDX6, thus attenuating lung inflammation and fibrosis in silicosis mice without significant systemic toxicity. These effects were partly related to the inhibition of the CS-induced oxidative stress in AM induced by GHK-Cu. Thus, our results suggest that GHK-Cu acts as a potential drug by attenuating alveolar macrophage oxidative stress. This, in turn, attenuates the progression of pulmonary inflammation and fibrosis, which provides a reference for the treatment of silicosis.

Abstract Sarcopenia has been associated with higher toxicity induced by anti-cancer treatments and shorter survival in patients with squamous cell lung carcinoma (SqCLC). Over the past few decades, immune checkpoint inhibitors (ICIs) significantly improves the prognosis. However, few clinical studies explored the effectiveness of immunotherapy in the elderly population. Here, we performed a retrospective analysis to determine the prognostic role of sarcopenia in older patients with SqCLC receiving ICIs. We retrospectively assessed SqCLC patients who were treated with PD-1 inhibitors and all patients were at least 70 years old. Pre-treatment sarcopenic status was determined by analyzing L3 skeletal muscle index (SMI) with chest CT. Progression-free survival (PFS), disease-specific survival (DSS) and overall survival (OS) were estimated using the Kaplan–Meier method, and the differences in survival were compared using the log-rank test. Among 130 male SqCLC patients, 93 had sarcopenia. Patients with sarcopenia were older and had a lower body mass index (BMI). Over an average follow-up of 20.8 months, 92 patients died. For all 130 patients, the mean OS was 13.3 months. Patients with sarcopenia had a significantly shorter OS and PFS than those without sarcopenia (OS, 12.4 ± 5.2 months vs. 15.5 ± 10.5 months, P = 0.028; PFS, 6.4 ± 2.9 months vs. 7.7 ± 4.2 months; P = 0.035). Multivariable analysis showed that sarcopenia was an independent prognostic factor for shorter OS and PFS. CT-determined sarcopenia is an independent prognostic factor for older patients with SqCLC receiving ICIs.

Abstract Background Appendicular lean mass (ALM) is a good predictive biomarker for sarcopenia. And previous studies have reported the association between ALM and stroke or Alzheimer’s disease (AD), however, the causal relationship is still unclear, The purpose of this study was to evaluate whether genetically predicted ALM is causally associated with the risk of stroke and AD by performing Mendelian randomization (MR) analyses. Methods A two-sample MR study was designed. Genetic variants associated with the ALM were obtained from a large genome-wide association study (GWAS) and utilized as instrumental variables (IVs). Summary-level data for stroke and AD were generated from the corresponding GWASs. We used random-effect inverse-variance weighted (IVW) as the main method for estimating causal effects, complemented by several sensitivity analyses, including the weighted median, MR-Egger, and MR-pleiotropy residual sum and outlier (MR-PRESSO) methods. Multivariable analysis was further conducted to adjust for confounding factors, including body mass index (BMI), type 2 diabetes mellitus (T2DM), low density lipoprotein-C (LDL-C), and atrial fibrillation (AF). Results The present MR study indicated significant inverse associations of genetically predicted ALM with any ischemic stroke ([AIS], odds ratio [OR], 0.93; 95% confidence interval [CI], 0.89–0.97; P = 0.002) and AD (OR, 090; 95% CI 0.85–0.96; P = 0.001). Regarding the subtypes of AIS, genetically predicted ALM was related to the risk of large artery stroke ([LAS], OR, 0.86; 95% CI 0.77–0.95; P = 0.005) and small vessel stroke ([SVS], OR, 0.80; 95% CI 0.73–0.89; P

Abstract Background Orthostatic intolerance, which includes vasovagal syncope and postural orthostatic tachycardia syndrome, is common in children and adolescents. Elevated plasma homocysteine levels might participate in the pathogenesis of orthostatic intolerance. This study was designed to analyze the plasma metabolomic profile in orthostatic intolerance children with high levels of plasma homocysteine. Methods Plasma samples from 34 orthostatic intolerance children with a plasma homocysteine concentration > 9 µmol/L and 10 healthy children were subjected to ultra-high-pressure liquid chromatography and quadrupole-time-of-flight mass spectrometry analysis. Results A total of 875 metabolites were identified, 105 of which were significantly differential metabolites. Choline, 1-stearoyl-2-linoleoyl-sn-glycero-3-phosphocholine, 1-(1Z-octadecenyl)-2-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-sn-glycero-3-phosphocholine, histidine, isocitric acid, and DL-glutamic acid and its downstream metabolites were upregulated, whereas 1-palmitoyl-sn-glycero-3-phosphocholine, 1-stearoyl-sn-glycerol 3-phosphocholine, sphingomyelin (d18:1/18:0), betaine aldehyde, hydroxyproline, and gamma-aminobutyric acid were downregulated in the orthostatic intolerance group compared with the control group. All these metabolites were related to choline and glutamate. Heatmap analysis demonstrated a common metabolic pattern of higher choline, 1-stearoyl-2-linoleoyl-sn-glycero-3-phosphocholine, and DL-glutamic acid, and lower sphingomyelin (d18:1/18:0), 1-stearoyl-sn-glycerol 3-phosphocholine, and 1-palmitoyl-sn-glycero-3-phosphocholine in patients with certain notable metabolic changes (the special group) than in the other patients (the common group). The maximum upright heart rate, the change in heart rate from the supine to the upright position, and the rate of change in heart rate from the supine to the upright position of vasovagal syncope patients were significantly higher in the special group than in the common group (P

Abstract Background This multicenter observational study aimed to determine whether dyslipidemia or obesity contributes more significantly to unfavorable clinical outcomes in patients experiencing a first-ever ischemic stroke (IS). Methods The study employed a machine learning predictive model to investigate associations among body mass index (BMI), body fat percentage (BFP), high-density lipoprotein (HDL), triglycerides (TG), and total cholesterol (TC) with adverse outcomes in IS patients. Extensive real-world clinical data was utilized, and risk factors significantly linked to adverse outcomes were identified through multivariate analysis, propensity score matching (PSM), and regression discontinuity design (RDD) techniques. Furthermore, these findings were validated via a nationwide multicenter prospective cohort study. Results In the derived cohort, a total of 45,162 patients diagnosed with IS were assessed, with 522 experiencing adverse outcomes. A multifactorial analysis incorporating PSM and RDD methods identified TG (adjusted odds ratio (OR) = 1.110; 95% confidence interval (CI): 1.041–1.183; P

Neoadjuvant therapy followed by surgery is a common clinical strategy for operable non-small cell lung cancer (NSCLC), and the mainstream neoadjuvant therapies include chemoimmunotherapy, targeted therapy, and chemotherapy. However, there is a lack of studies to report the difference in benefits between these treatment modalities in the same institution. Therefore, this study aimed to depict the short-term efficacy of radiology and pathology achieved by different therapies and their impact on long-term survival as well as the underlying clinical significance. A total of 243 NSCLC patients who underwent different neoadjuvant therapies were eligible for inclusion. Demographic, radiological, and pathological features of patients were recorded. The event-free survival (EFS) outcome was analyzed using Kaplan-Meier analysis. The objective response rates (ORR) of primary tumor in the chemoimmunotherapy, targeted therapy, and chemotherapy cohorts were 48.95 %, 57.58 %, and 34.09 % respectively, major pathological response (MPR) rates were 58.74 %, 15.15 %, and 20.83 % (P

In view of the strong uncertainty and intermittency of distributed power sources in microgrids and the shortcomings of the traditional dung beetle optimizer (DBO) algorithm with slow convergence, poor robustness and ease of falling into a local optimum, an optimal scheduling model for microgrids based on the improved dung beetle optimization algorithm is proposed. First, a multiobjective optimal scheduling model of the microgrid is constructed and a typical daily output scenario generation method for wind power generation and photovoltaic power generation is constructed based on the Gaussian kernel density estimation, Frank-copula and K-means clustering algorithms. Second, to address the shortcomings of the DBO algorithm, the spiral position update strategy, adaptive weight factor, levy flight strategy and t-distribution variation strategy are introduced on the basis of the DBO algorithm, which effectively solves the problem of premature convergence of particles owing to falling into a local optimum. Finally, five benchmark test functions were selected for simulation experiments. Finally, the simulation results show that the computational performance of the IDBO algorithm is significantly better than the other five intelligent algorithms. The algorithm proposed in this paper also achieves more satisfactory results in microgrid optimal scheduling based on the scenario generation method.