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Photocatalyst-activated peroxymonosulfate (PMS) degradation of pollutants is already widely used for wastewater treatment under visible light. Polyethylene terephthalate (PET) is widely used in daily life, but waste plastics have an irreversible negative impact on the environment. In this paper, the ZIF-67/g-C 3 N 4 S-scheme heterojunction catalyst was synthesized as a photocatalyst to achieve a good effect on PET degradation in coordination with PMS. The results indicated that PET could be degraded up to 60.63 ± 2.12 % under the combined effect of catalyst, PMS, and light. In this experiment, the influence of catalyst-to-plastic ratio, PMS concentration, aqueous pH, and inorganic anions on plastic degradation by the photocatalytic synergistic PMS system was discussed, and the excellent performance of this system for degrading PET was highlighted through a comparative test. Electron spin resonance (ESR) and free radical quenching experiments demonstrated that SO 4 •- contributes the largest amount to the PET degradation performance. Furthermore, results from gas chromatography and liquid chromatography-mass spectrometry (LC-MS) indicated that the plastic degradation products include CO, CH 4 , and organic small-molecule liquid fuels. Finally, a possible mechanism for the light/PMS system to degrade PET in water was suggested. This paper provides a feasible solution to treat waste microplastics in water., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Ferroptosis is a type of regulated cell death driven by iron-dependent accumulation of lipid peroxidation, exhibiting unique morphological changes. While actin microfilaments are crucial for various cellular processes, including morphogenesis, motility, endocytosis, and cell death, their role in ferroptosis remains unclear. Here, our study reveals that actin microfilaments undergo remodeling and disassembly during ferroptosis. Interestingly, inhibitors that target actin microfilament remodeling do not affect cell sensitivity to ferroptosis, with the exception of CK-666 and its structural analogue CK-636. Mechanistically, CK-666 attenuates ferroptosis independently of its canonical function in inhibiting the Arp2/3 complex. Further investigation revealed that CK-666 modulates the ferroptotic transcriptome, prevents lipid degradation, and diminishes lipid peroxidation. In addition, CK-666 does not impact the labile iron pool within cells, nor does the inhibition of FSP1 impact its anti-ferroptosis activity. Notably, the results of DPPH assay and liposome leakage assay suggest that CK-666 mitigates ferroptosis by directly eliminating lipid peroxidation. Importantly, CK-666 significantly ameliorated renal ischemia-reperfusion injury and ferroptosis in renal tissue, underscoring its potential therapeutic impact., Competing Interests: Conflict of Interest The authors declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

A simple one-pot green synthesis method was used to prepare urease-inorganic hybrid nanoflowers (UE-HNFs), which had a high surface-to-volume ratio to improve enzyme catalytic efficiency and make urease reusable. A portable colorimetric microliter tube based on urease-inorganic hybrid nanoflowers (UE-HNFs-PCMT), as an urea colorimetric biosensor, was developed for determining urea concentration in milk. The combination of urea colorimetric biosensor and a smartphone is used for capturing the colour change of milk after reaction. There was a good linear relationship between colour intensity of the image (Δ intensity) and urea concentration (43-600 mg L -1 ), with a detection limit of 12.81 mg L -1 . UE-HNFs-PCMT has the advantages of no need for complex equipment, easy operation, reusability, low detection cost, good portability, and environmental friendliness and can achieve urea detection in milk., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Pharmaceuticals and personal care products (PPCPs) have received global attention owing to their potential risks to human health and the ecological environment. However, limited research has explored the occurrence and ecological risks of PPCPs in the Qiantang River (QTR). QTR, the largest water system in Zhejiang Province, China, is significantly influenced by human activities. This study investigated the occurrence, distribution, and ecological risks of 10 types of PPCPs in both surface water and sediment within QTR. The findings revealed that the concentrations of PPCPs detected in surface water ranged from 81.26 to 149.45 ng L -1 during the wet season (April) and from 98.66 to 198.55 ng L -1 during the dry season (September). Moreover, in the sediments, PPCP concentration ranged from 63.24 to 80.66 and 72.54 to 75.06 ng per g dw during both wet and dry seasons, respectively. Among the selected PPCPs, triclosan (TCS) exhibited the highest concentration across, different phases and seasons, followed by benzotriazole in surface water. The analysis of sediment-water equilibrium distribution indicated that the diffusion tendency of PPCPs was closely correlated with their molecular weights. Particularly, TCS exhibited dynamic equilibrium between water and sediment. Principal component analysis and positive matrix factorization model results indicated similar pollution sources for the detected PPCPs. The dominant sources of the detected PPCPs were identified as wastewater of electroplating enterprises, discharge from wastewater treatment plants, and domestic sewage. The ecological risk assessment based on the risk quotient method revealed that TCS with the highest detected concentration posed a high risk in surface water and a low risk in sediment across all sampling sites. However, other detected PPCPs showed either no or low risks. Additionally, PPCPs showed a higher ecological risk during the dry season than during the wet season.

Neonicotinoids (NEOs) are commonly used pesticides in agriculture. Urban parks containing numerous green plants and flowers also require NEOs for pest control. However, information on the distribution patterns and environmental risks of NEOs and their metabolites in urban park soils has yet to be discovered, which seriously limits the comprehensive evaluation of the potential hazards of NEOs. Our study explored the occurrence and distribution patterns of ten NEOs and five major metabolites in park soils from Guangzhou, Shijiazhuang, and Urumqi of China. At least three NEOs were detected in 95 % of soil samples, with the sum of all NEOs (∑ 10 NEOs) ranging from 2.21 to 204 ng/g. Guangzhou has the highest levels of ∑ 10 NEOs (median: 52.1 ng/g), followed by Urumqi (49.3 ng/g) and Shijiazhuang (21.7 ng/g). The top three most common NEOs in all three cities are imidacloprid, acetamiprid, and thiacloprid, which together account for 67 % to 70 % of ∑ 10 NEOs. The levels of the metabolites of NEOs show a significant positive correlation with their corresponding parent NEOs. These NEOs pose detrimental effects to non-targeted invertebrates in the soil. Our findings raise concern about the environmental risks posed by NEO exposure to humans and other organisms in urban parks., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Background: Chronic alcohol drinking increases the risk of alcohol use disorders, causing various neurological disorders. However, the impact of different ethanol levels on a spectrum of behaviors during chronic drinking remains unclear. In this study, we established an intermittent access to ethanol in a two-bottle choice (IA2BC) procedure to explore the dose-dependent effects of ethanol on the behavioral performance of C57BL/6 J mice., Methods: Adult male C57BL/6 J mice were provided voluntary access to different ethanol concentrations (0 %, 5 %, 10 %, and 20 % ethanol) under a 12-week IA2BC paradigm. A battery of behavioral tests was administered to assess alterations in pain threshold, anxiety-like behaviors, locomotor activity, motor coordination, and cognition. Ethanol consumption and preference were monitored during each session. Moreover, the liver, heart, and lung tissues were examined using pathological microscopy., Results: The average (standard deviation) ethanol consumption of mice under the IA2BC paradigm increased dose-dependently to 5.1 (0.2), 8.7 (0.7), and 15.9 (0.8) g/kg/24 h with 5 %, 10 %, and 20 % ethanol, respectively. However, there is no significant difference in ethanol preference among all the ethanol groups. Chronic ethanol drinking caused hyperalgesia, cognitive impairment, and motor incoordination, but caused no changes in body temperature, locomotor activity, or anxiety-like behaviors. Minor histopathological alterations in the liver were detected; however, no major abnormal pathology was observed in the heart or lungs., Conclusion: These findings clarify the link between ethanol dosage and behavioral changes in mice over a 12-week IA2BC paradigm, thereby bridging the knowledge gap regarding the effects of chronic ethanol drinking on neurological disorders., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: We evaluated preliminary feasibility of a digital, culturally-informed approach to recruit and screen participants for the Alzheimer's Disease Neuroimaging Initiative (ADNI4)., Methods: Participants were recruited using digital advertising and completed digital surveys (e.g., demographics, medical exclusion criteria, 12-item Everyday Cognition Scale [ECog-12]), Novoic Storyteller speech-based cognitive test). Completion rates and assessment performance were compared between underrepresented populations (URPs: individuals from ethnoculturally minoritized or low education backgrounds) and non-URPs., Results: Of 3099 participants who provided contact information, 654 enrolled in the cohort, and 595 completed at least one assessment. Two hundred forty-seven participants were from URPs. Of those enrolled, 465 met ADNI4 inclusion criteria and 237 evidenced possible cognitive impairment from ECog-12 or Storyteller performance. URPs had lower ECog and Storyteller completion rates. Scores varied by ethnocultural group and educational level., Discussion: Preliminary results demonstrate digital recruitment and screening assessment of an older diverse cohort, including those with possible cognitive impairment, are feasible. Improving engagement and achieving educational diversity are key challenges., Highlights: A total of 654 participants enrolled in a digital cohort to facilitate ADNI4 recruitment. Culturally-informed digital ads aided enrollment of underrepresented populations. From those enrolled, 42% were from underrepresented ethnocultural and educational groups. Digital screening tools indicate > 50% of participants likely cognitively impaired. Completion rates and assessment performance vary by ethnocultural group and education., (© 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Whether stem-cell-like cancer cells avert ferroptosis to mediate therapy resistance remains unclear. In this study, using a soft fibrin gel culture system, we found that tumor-repopulating cells (TRCs) with stem-cell-like cancer cell characteristics resist chemotherapy and radiotherapy by decreasing ferroptosis sensitivity. Mechanistically, through quantitative mass spectrometry and lipidomic analysis, we determined that mitochondria metabolic kinase PCK2 phosphorylates and activates ACSL4 to drive ferroptosis-associated phospholipid remodeling. TRCs downregulate the PCK2 expression to confer themselves on a structural ferroptosis-resistant state. Notably, in addition to confirming the role of PCK2-pACSL4(T679) in multiple preclinical models, we discovered that higher PCK2 and pACSL4(T679) levels are correlated with better response to chemotherapy and radiotherapy as well as lower distant metastasis in nasopharyngeal carcinoma cohorts., (© 2024. The Author(s).)

Yunnan in southwest China is a geographically and ethnically complex region at the intersection of southern China and Southeast Asia, and a focal point for human migrations. To clarify its maternal genetic history, we generated 152 complete mitogenomes from 17 Yunnan archaeological sites. Our results reveal distinct genetic histories segregated by geographical regions. Maternal lineages of ancient populations from northwestern and northern Yunnan exhibit closer affinities with past and present-day populations from northern East Asia and Tibet, providing important genetic evidence for the migration and interaction of populations along the Tibetan-Yi corridor since the Neolithic. Between 5500 to 1800 years ago, central Yunnan populations maintained their internal genetic relationships, including a 7000-year-old basal lineage of the rare and widely dispersed haplogroup M61. At the Xingyi site, changes in mitochondrial DNA haplogroups occurred between the Late Neolithic and Bronze Age, with haplogroups shifting from those predominant in the Yellow River region to those predominant in coastal southern China. These results highlight the high diversity of Yunnan populations during the Neolithic to Bronze Age., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2024. Published by Elsevier Ltd.)

Introduction: MicroRNAs are short non-coding RNAs that control proteostasis at the systems level and are emerging as potential prognostic and diagnostic biomarkers for Alzheimer's disease (AD)., Methods: We performed small RNA sequencing on plasma samples from 847 Alzheimer's Disease Neuroimaging Initiative (ADNI) participants., Results: We identified microRNA signatures that correlate with AD diagnoses and help predict the conversion from mild cognitive impairment (MCI) to AD., Discussion: Our data demonstrate that plasma microRNA signatures can be used to not only diagnose MCI, but also, critically, predict the conversion from MCI to AD. Moreover, combined with neuropsychological testing, plasma microRNAome evaluation helps predict MCI to AD conversion. These findings are of considerable public interest because they provide a path toward reducing indiscriminate utilization of costly and invasive testing by defining the at-risk segment of the aging population., Highlights: We provide the first analysis of the plasma microRNAome for the ADNI study. The levels of several microRNAs can be used as biomarkers for the prediction of conversion from MCI to AD. Adding the evaluation of plasma microRNA levels to neuropsychological testing in a clinical setting increases the accuracy of MCI to AD conversion prediction., (© 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Introduction: MicroRNAs (miRNAs) play important roles in gene expression regulation and Alzheimer's disease (AD) pathogenesis., Methods: We investigated the association between baseline plasma miRNAs and central AD biomarkers from the Alzheimer's Disease Neuroimaging Initiative (ADNI; N = 803): amyloid, tau, and neurodegeneration (A/T/N). Differentially expressed miRNAs and their targets were identified, followed by pathway enrichment analysis. Machine learning approaches were applied to investigate the role of miRNAs as blood biomarkers., Results: We identified nine, two, and eight miRNAs significantly associated with A/T/N positivity, respectively. We identified 271 genes targeted by amyloid-related miRNAs with estrogen signaling receptor-mediated signaling among the enriched pathways. Additionally, 220 genes targeted by neurodegeneration-related miRNAs showed enrichment in pathways including the insulin growth factor 1 pathway. The classification performance of demographic information for A/T/N positivity was increased up to 9% with the inclusion of miRNAs., Discussion: Plasma miRNAs were associated with central A/T/N biomarkers, highlighting their potential as blood biomarkers., Highlights: We performed association analysis of microRNAs (miRNAs) with amyloid/tau/neurodegeneration (A/T/N) biomarker positivity. We identified dysregulated miRNAs for A/T/N biomarker positivity. We identified Alzheimer's disease biomarker-specific/common pathways related to miRNAs. miRNAs improved the classification for A/T/N positivity by up to 9%. Our study highlights the potential of miRNAs as blood biomarkers., (© 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Intestinal lymphatic transport offers an alternative and effective way to deliver drugs, such as avoiding first-pass metabolism, enhancing oral bioavailability, and facilitating the treatment of targeted lymphoid-related diseases. However, the clinical use of luteolin (LUT) is limited by its poor water solubility and low bioavailability, and enhancing lymphatic transport by nanoemulsion may be an efficient way to enhance its oral bioavailability. The objective of this work is to prepare the luteolin nanoemulsions (LUT NEs), optimized its preparation parameters by using Box-Behnken design optimization (BBD) and evaluated it in vitro and in vivo. An Caco-2 / Raji B cell co-incubation monolayer model was established to simulate the M-cell pathway, and the differences in the transmembrane transport of LUT and NEs were compared. Cycloheximide (CHX) was utilized to establish rat chylomicron (CM) blocking model, and for investigating the influence of pharmacokinetic parameters in rats thereafter. The results showed that LUT NEs have good stability, the particle sizes were about 23.87 ± 0.57 nm. Compared with LUT suspension, The P app of LUT NEs was enhanced for 3.5-folds, the oral bioavailability was increased by about 2.97-folds. In addition, after binding with chylomicron, the oral bioavailability of LUT NEs was decreased for about 30% (AUC 0-∞ (μg/L*h): 5.356 ± 1.144 vs 3.753 ± 0.188). These results demonstrated that NEs could enhance the oral absorption of luteolin via lymphatic transport routes., (© 2024. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.)

Ferroptosis holds significant potential for application in cancer therapy. However, ferroptosis inducers are not cell-specific and can cause phospholipid peroxidation in both tumor and non-tumor cells. This limitation greatly restricts the use of ferroptosis therapy as a safe and effective anticancer strategy. Our previous study demonstrated that macrophages can engulf ferroptotic cells through Toll-like receptor 2 (TLR2). Despite this advancement, the precise mechanism by which phospholipid peroxidation in macrophages affects their phagocytotic capability during treatment of tumors with ferroptotic agents is still unknown. Here, we utilized flow sorting combined with redox phospholipidomics to determine that phospholipid peroxidation in tumor microenvironment (TME) macrophages impaired the macrophages ability to eliminate ferroptotic tumor cells by phagocytosis, ultimately fostering tumor resistance to ferroptosis therapy. Mechanistically, the accumulation of phospholipid peroxidation in the macrophage endoplasmic reticulum (ER) repressed TLR2 trafficking to the plasma membrane and caused its retention in the ER by disrupting the interaction between TLR2 and its chaperone CNPY3. Subsequently, this ER-retained TLR2 recruited E3 ligase MARCH6 and initiated the proteasome-dependent degradation. Using redox phospholipidomics, we identified 1-steaoryl-2-15-HpETE-sn-glycero-3-phosphatidylethanolamine (SAPE-OOH) as the crucial mediator of these effects. Conclusively, our discovery elucidates a novel molecular mechanism underlying macrophage phospholipid peroxidation-induced tumor resistance to ferroptosis therapy and highlights the TLR2-MARCH6 axis as a potential therapeutic target for cancer therapy., (© 2024. The Author(s), under exclusive licence to ADMC Associazione Differenziamento e Morte Cellulare.)

Inflammatory bowel disease (IBD) has high prevalence in Western counties. The high fat content in Western diets is one of the leading causes for this prevalence; however, the underlying mechanisms have not been fully defined. Here, we find that high-fat diet (HFD) induces ferroptosis of intestinal regulatory T (Treg) cells, which might be the key initiating step for the disruption of immunotolerance and the development of colitis. Compared with effector T cells, Treg cells favor lipid metabolism and prefer polyunsaturated fatty acids (PUFAs) for the synthesis of membrane phospholipids. Therefore, consumption of HFD, which has high content of PUFAs such as arachidonic acid, cultivates vulnerable Tregs that are fragile to lipid peroxidation and ferroptosis. Treg-cell-specific deficiency of GPX4, the key enzyme in maintaining cellular redox homeostasis and preventing ferroptosis, dramatically aggravates the pathogenesis of HFD-induced IBD. Taken together, these studies expand our understanding of IBD etiology., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

A previous study showed that the length of the foreskin plays a role in the risk of sexually transmitted infections and chronic prostatitis, which can lead to poor quality of sexual life. Here, the association between foreskin length and sexual dysfunction was evaluated. A total of 5700 participants were recruited from the andrology clinic at The First Affiliated Hospital of University of Science and Technology of China (Hefei, China). Clinical characteristics, including foreskin length, were collected, and sexual function was assessed by the International Index of Erectile Function-5 (IIEF-5) and Premature Ejaculation Diagnostic Tool (PEDT) questionnaires. Men with sexual dysfunction were more likely to have redundant foreskin than men without sexual dysfunction. Among the 2721 erectile dysfunction (ED) patients and 1064 premature ejaculation (PE) patients, 301 (11.1%) ED patients and 135 (12.7%) PE patients had redundant foreskin, respectively. Men in the PE group were more likely to have redundant foreskin than men in the non-PE group (P = 0.004). Logistic regression analyses revealed that the presence of redundant foreskin was associated with increased odds of moderate/severe ED (adjusted odds ratio [aOR] = 1.31, adjusted P = 0.04), moderate PE (aOR = 1.38, adjusted P = 0.02), and probable PE (aOR = 1.37, adjusted P = 0.03) after adjusting for confounding variables. Our study revealed a positive correlation between the presence of redundant foreskin and the risk of sexual dysfunction, especially in PE patients. Assessment of the length of the foreskin during routine clinical diagnosis may provide information for patients with sexual dysfunction., (Copyright © 2024 Copyright: ©The Author(s)(2024).)

Sustained compressive injury (SCI) in the brain is observed in numerous injury and pathological scenarios, including tumors, ischemic stroke, and traumatic brain injury-related tissue swelling. Sustained compressive injury is characterized by tissue loading over time, and currently, there are few in vitro models suitable to study neural cell responses to strain-dependent sustained compressive injury. Here, we present an in vitro model of sustained compressive neural injury via centrifugation. Spheroids were made from neonatal rat cortical cells seeded at 4000 cells/spheroid and cultured for 14 days in vitro. A subset of spheroids was centrifuged at 104, 209, 313 or 419 rads/s for 2 minutes. Modeling the physical deformation of the spheroids via finite element analyses, we found that spheroids centrifuged at the aforementioned angular velocities experienced pressures of 10, 38, 84 and 149 kPa, respectively, and compressive (resp. tensile) strains of 10% (5%), 18% (9%), 27% (14%) and 35% (18%), respectively. Quantification of LIVE-DEAD assay and Hoechst 33342 nuclear staining showed that centrifuged spheroids subjected to pressures above 10 kPa exhibited significantly higher DNA damage than control spheroids at 2, 8, and 24 hours post-injury. Immunohistochemistry of β3-tubulin networks at 2, 8, and 24 hours post-centrifugation injury showed increasing degradation of microtubules over time with increasing strain. Our findings show that cellular injuries occur as a result of specific levels and timings of sustained tissue strains. This experimental SCI model provides a high throughput in vitro platform to examine cellular injury, to gain insights into brain injury that could be targeted with therapeutic strategies., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 González-Cruz et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

With the increasing requirements of agricultural machinery, the study of the contact relationship between the tire-soil interface and the improvement of traction efficiency has gradually become a main concern. In this study, the pattern on the agricultural tire was simplified into single-pitch pattern blocks. The pattern blocks were made of rubber material that was highly resistant to abrasion and bending. The experiment was carried out by pressing the three types of patterned block construction into the soil and the pure sliding under the soil. The simulation used the Coupled Eulerian-Lagrangian Method (CEL) to verify the experimental results. We found that the herringbone pattern block was subjected to the highest stress for the same depth of downward pressure. The horizontal force generated by the pure sliding was also the highest. The results showed that the numerically simulated and experimentally measured data exhibited similar trends and average values. In addition, the increase in the contact area between the tire and the soil reduced the compaction and sinking of the soil. The herringbone pattern structure not only had a large contact area but also produced the most significant shear force on the soil. Thus, it may generate greater traction in actual operations.

Brain injuries resulting from mechanical trauma represent an ongoing global public health issue. Several in vitro and in vivo models for traumatic brain injury (TBI) continue to be developed for delineating the various complex pathophysiological processes involved in its onset and progression. Developing an in vitro TBI model that is based on cortical spheroids is especially of great interest currently because they can replicate key aspects of in vivo brain tissue, including its electrophysiology, physicochemical microenvironment, and extracellular matrix composition. Being able to mechanically deform the spheroids are a key requirement in any effective in vitro TBI model. The spheroids' shape and size, however, make mechanically loading them, especially in a high-throughput, sterile, and reproducible manner, quite challenging. To address this challenge, we present an idea for a spheroid-based, in vitro TBI model in which the spheroids are mechanically loaded by being spun by a centrifuge. (An experimental demonstration of this new idea will be published shortly elsewhere.) An issue that can limit its utility and scope is that imaging techniques used in 2D and 3D in vitro TBI models cannot be readily applied in it to determine spheroid strains. In order to address this issue, we developed a continuum mechanics-based theory to estimate the spheroids' strains when they are being spun at a constant angular velocity. The mechanics theory, while applicable here to a special case of the centrifuge-based TBI model, is also of general value since it can help with the further exploration and development of TBI models., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The interaction between relativistic intense laser pulses and near-critical-density targets has been sought after in order to increase the efficiency of laser-plasma energy coupling, particularly for laser-driven proton acceleration. To achieve the density regime for high-repetition-rate applications, one elusive approach is to use gas targets, provided that stringent target density profile requirements are met. These include reaching the critical plasma density while maintaining micron-scale density gradients. In this Letter, we present a novel scheme for achieving the necessary requirements using optical laser pulses to transversely shape the target and create a colliding shock wave in both planar and cylindrical geometries. Utilizing this approach, we experimentally demonstrated stable proton acceleration and achieved up to 5 MeV in a monoenergetic distribution and particle numbers above 10^{8}  Sr^{-1} MeV^{-1} using a 1.5 J energy on-target laser pulse. The Letter also reports for the first time an extend series of 200 consecutive shots that demonstrates the robustness of the approach and its maturity for applications. These results open the door for future work in controlling gas targets and optimizing the acceleration process for more energetic multipetawatt laser systems.

Background and Aims: H-type hypertension is essential hypertension combined with high homocysteine, and both synergistically increase the risk of cardiovascular and cerebrovascular events. The aim of this study was to investigate the risk factors of H-type hypertension in Tibetan plateau population and correlation with MTHFR C677T gene., Methods and Results: A multi-stage cluster random sampling method was used to select the research subjects in Tibet Autonomous Region from June 2020 to November 2021. Among Tibetans, the incidence of H-type hypertension accounted for 84.31% of hypertensive patients. The logistic regression analysis demonstrated that age, uric acid (UA), triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C) were risk factors for the prevalence of H-type hypertension, the OR (95% CI) was 1.083(1.073-1.094), 1.002(1.001-1.004), 1.240(1.050-1.464) and 2.274(1.432-3.611), respectively. MTHFR C677T TT genotype patients with H-type hypertension OR (95% CI) was 1.629(1.004-2.643). Based on this, a nomogram model was established, and the reliability of the model was proved by area under ROC curve, Brier score and average absolute error. The model's results indicate that for every five years of age, the score increases by 6 points; for a 2mmol/L increase in TG, the score increases by 5.5 points; for a 1mmol/L increase in LDL-C, the score increases by 10 points; and individuals with the TT genotype receive 8 points. The higher the score, the greater the risk of disease., Conclusion: The MTHFR C677T TT genotype is a risk locus for Tibetan patients with H-type hypertension, with age, TG, and LDL-C were identified as risk factors for the disease., (© 2024. The Author(s).)

Inherited non-hemolytic anemia is a group of rare bone marrow disorders characterized by erythroid defects. Although concerted efforts have been made to explore the underlying pathogenetic mechanisms of these diseases, the understanding of the causative mutations are still incomplete. Here we identify in a diseased pedigree that a gain-of-function mutation in toll-like receptor 8 (TLR8) is implicated in inherited non-hemolytic anemia. TLR8 is expressed in erythroid lineage and erythropoiesis is impaired by TLR8 activation whereas enhanced by TLR8 inhibition from erythroid progenitor stage. Mechanistically, TLR8 activation blocks annexin A2 (ANXA2)-mediated plasma membrane localization of STAT5 and disrupts EPO signaling in HuDEP2 cells. TLR8 inhibition improves erythropoiesis in RPS19 +/- HuDEP2 cells and CD34 + cells from healthy donors and inherited non-hemolytic anemic patients. Collectively, we identify a gene implicated in inherited anemia and a previously undescribed role for TLR8 in erythropoiesis, which could potentially be explored for therapeutic benefit in inherited anemia., (© 2024. The Author(s).)

Background: Psychological stress is associated with various diseases including liver dysfunction, yet effective intervention strategies remain lacking due to the unrevealed pathogenesis mechanism., Purpose: This study aims to explore the relevance between BMAL1-controlled circadian rhythms and lipoxygenase 15 (ALOX15)-mediated phospholipids peroxidation in psychological stress-induced liver injury, and to investigate whether hepatocyte phospholipid peroxidation signaling is involved in the hepatoprotective effects of a Chinese patent medicine, Pien Tze Huang (PZH)., Methods: Restraint stress models were established to investigate the underlying molecular mechanisms of psychological stress-induced liver injury and the hepatoprotective effects of PZH. Redox lipidomics based on liquid chromatography-tandem mass spectrometry was applied for lipid profiling., Results: The present study discovered that acute restraint stress could induce liver injury. Notably, lipidomic analysis confirmed that phospholipid peroxidation was accumulated in the livers of stressed mice. Additionally, the essential core circadian clock gene Brain and Muscle Arnt-like Protein-1 (Bmal1) was altered in stressed mice. Circadian disruption in mice, as well as BMAL1-overexpression in human HepaRG cells, also appeared to have a significant increase in phospholipid peroxidation, suggesting that stress-induced liver injury is closely related to circadian rhythm and phospholipid peroxidation. Subsequently, arachidonate 15-lipoxygenase (ALOX15), a critical enzyme that contributed to phospholipid peroxidation, was screened as a potential regulatory target of BMAL1. Mechanistically, BMAL1 promoted ALOX15 expression via direct binding to an E-box-like motif in the promoter. Finally, this study revealed that PZH treatment significantly relieved pathological symptoms of psychological stress-induced liver injury with a potential mechanism of alleviating ALOX15-mediated phospholipid peroxidation., Conclusion: Our findings illustrate the critical role of BMAL1-triggered phospholipid peroxidation in psychological stress-induced liver injury and provide new insight into treating psychological stress-associated liver diseases by TCM intervention., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Background: The association between serum lipids and migraine is controversial. However, randomized controlled trials have suggested that statins may be efficacious for the prevention of migraine. In this study, we aim to investigate the relationship between lipids metabolism and migraine risk., Methods: Single-nucleotide polymorphisms (SNPs), relating to the serum lipid traits and the effect of lipid-lowering drugs that target APOB, CETP, HMGCR, NPC1L1, and PCSK9, were extracted from genome-wide association studies (GWAS) summary data. The GWAS summary data were obtained from the Global Lipids Genetic Consortium (GLGC), the UK Biobank, and the FinnGen study, respectively. Mendelian randomization (MR) analysis was performed to evaluate the association between serum lipid traits and lipid-lowering drugs with migraine risk., Results: Regarding serum lipids, it was found that SNPs related to high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), total cholesterol (TC), or triglycerides (TG) levels were not associated with migraine, migraine with aura (MA) or migraine without aura (MO). In addition, genotypes of HMGCR related to higher LDL-C levels were associated with increased risk of migraine (OR = 1.46, p = 0.035) and MA (OR = 2.03, p = 0.008); However, genotypes of PCSK9 related to higher LDL-C levels were associated with decreased risk of migraine (OR = 0.75, p = 0.001) and MA (OR = 0.69, p = 0.004); And genotypes of APOB related to higher LDL-C levels were associated with decreased risk of MO (OR = 0.62, p = 0.000)., Conclusions: There is a relationship between lipid metabolism characteristics and migraine risk., Significance: Based on the genome-wide association summary data, single-nucleotide polymorphisms (SNPs) related to high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), total cholesterol (TC), or triglycerides (TG) level were not associated with risk of migraine, migraine with aura (MA) or migraine without aura (MO). However, genotypes of HMGCR related to higher LDL-C levels have shown an increased risk on migraine and MA. And genotypes of APOB or PCSK9 related to higher LDL-C levels have shown a decreased risk on MO, or migraine and MA, respectively. These results suggested that there may be a relationship between lipid metabolism characteristics and the risk for migraine development., (© 2024 European Pain Federation ‐ EFIC ®.)

Background: The intricate interactions between chronic psychological stress and susceptibility to breast cancer have been recognized, yet the underlying mechanisms remain unexplored. Danzhi Xiaoyao Powder (DZXY), a traditional Chinese medicine (TCM) formula, has found clinical utility in the treatment of breast cancer. Macrophages, as the predominant immune cell population within the tumor microenvironment (TME), play a pivotal role in orchestrating tumor immunosurveillance. Emerging evidence suggests that lipid oxidation accumulation in TME macrophages, plays a critical role in breast cancer development and progression. However, a comprehensive understanding of the pharmacological mechanisms and active components of DZXY related to its clinical application in the treatment of stress-aggravated breast cancer remains elusive., Purpose: This study sought to explore the plausible regulatory mechanisms and identify the key active components of DZXY contributing to its therapeutic efficacy in the context of breast cancer., Methods: Initially, we conducted an investigation into the relationship between the phagocytic capacity of macrophages damaged by psychological stress and phospholipid peroxidation using flow cytometry and LC-MS/MS-based phospholipomics. Subsequently, we evaluated the therapeutic efficacy of DZXY based on the results of the tumor size, tumor weight, the phospholipid peroxidation pathway and phagocytosis of macrophage. Additionally, the target-mediated characterization strategy based on binding of arachidonate 15-lipoxygenase (ALOX15) to phosphatidylethanolamine-binding protein-1 (PEBP1), including molecular docking analysis, microscale thermophoresis (MST) assay, co-immunoprecipitation analysis and activity verification, has been further implemented to reveal the key bio-active components in DZXY. Finally, we evaluated the therapeutic efficacy of isochlorogenic acid C (ICAC) based on the results of tumor size, tumor weight, the phospholipid peroxidation pathway, and macrophage phagocytosis in vivo., Results: The present study demonstrated that phospholipid peroxides, as determined by LC-MS/MS-based phospholipidomics, triggered in macrophages, which in turn compromised their capacity to eliminate tumor cells through phagocytosis. Furthermore, we elucidate the mechanism behind stress-induced PEBP1 to form a complex with ALOX15, thereby mediating membrane phospholipid peroxidation in macrophages. DZXY, demonstrates potent anti-breast cancer therapeutic effects by disrupting the ALOX15/PEBP1 interaction and inhibiting phospholipid peroxidation, ultimately enhancing macrophages' phagocytic capability towards tumor cells. Notably, ICAC emerged as a promising active component in DZXY, which can inhibit the ALOX15/PEBP1 interaction, thereby mitigating phospholipid peroxidation in macrophages., Conclusion: Collectively, our findings elucidate stress increases the susceptibility of breast cancer by driving lipid peroxidation of macrophages and suggest the ALOX15/PEBP1 complex as a promising intervention target for DZXY., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024. Published by Elsevier GmbH.)

Background: Encephalitozoon hellem (E. hellem) infection is a zoonotic disease, rarely observed in individuals, causing various clinical manifestations including diarrhea, keratoconjunctivitis, cystitis, etc. E. hellem infection after hematopoietic stem-cell transplantation (HSCT) is a rare, serious complication., Case Presentation: Herein, we present a case of E. hellem infection developing during HLA-haploidentical HSCT in a 9-year-old boy who suffered from aplastic anemia. On 15 days after HSCT, the patient developed recurrent and prolonged fever, diarrhea and hematuria. It is challenging to differentiate whether the symptoms mentioned in this case are caused by graft-versus-host disease (GVHD) or a specific infection. Based on the result of metagenomic next-generation sequencing (mNGS) and clinical observation, the patient was diagnosed as E. hellem infection, and received albendazole and decreased the immunosuppressive treatment. Finally, he had recovered., Conclusion: We should pay attention to the uncommon disease caused by the E. hellem infection after HSCT, especially in cases with immune reconstitution unrecovered. Among those rare infection, mNGS can be performed for better understanding the source of infection and targeted therapy, which can benefit the patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Shang, Ren, Liu, Chen, Liu, Li, Wan, An, Yang, Zhu and Guo.)

Palladium contaminants can pose risks to human health and the natural environment. Once Pd 2+ enters the body, it can bind with DNA, proteins, and other macromolecules, disrupting cellular processes and causing serious harm to health. Therefore, it becomes critical to develop simple, highly selective and precise methods for detecting Pd 2+ in vivo. Here, we have successfully developed the first activated second near-infrared region fluorescence (NIR-II FL) and ratio photoacoustic (PA) probe NYR-1 for dual-modal accurate detection of Pd 2+ levels. NYR-1 is capable of rapidly (< 60 s) and sensitively detection of Pd 2+ in solution, providing switched on NIR-II FL 920 and ratio PA 808 /PA 720 dual-mode signal change. More notably, the probe NYR-1 was successfully used for non-invasive imaging of Pd 2+ overload in mouse liver by NIR-II FL/Ratio PA dual-modality imaging technology for the first time. Thus, this work opens up a promising dual-modal detection method for the precise detection of Pd 2+ in organisms and in the environment., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Based on the neuroprotection of butylphthalide and donepezil, a series of indanone/benzofuranone and piperidine hybrids were designed and synthesized for assessment of their neuroprotective activities, aiming to enhance the bioavailability and therapeutic efficacy of natural phthalide analogues. Within this study, it was observed that most indanone derivatives bearing 1-methylpiperidine in the tail segment demonstrated superior neuroprotective effects on the oxygen glucose deprivation/reperfusion (OGD/R)-induced rat primary neuronal cell injury model in vitro compared to benzofuranone compounds. Among the synthesized compounds, 11 ( 4 , 14 , 15 , 22 , 26 , 35 , 36 , 37 , 48 , 49 , and 52 ) displayed robust cell viabilities in the OGD/R model, along with favorable blood-brain barrier permeability as confirmed by the parallel artificial membrane permeability assay. Notably, compound 4 showed significant neuronal cell viabilities within the concentration range of 3.125 to 100 μM, without inducing cytotoxicity. Further results from in vivo middle cerebral artery occlusion/R experiments revealed that 4 effectively ameliorated ischemia-reperfusion injury, reducing the infarct volume to 18.45% at a dose of 40 mg/kg. This outcome suggested a superior neuroprotective effect compared to edaravone at 20 mg/kg, further highlighting the potential therapeutic efficacy of compound 4 in addressing neurological disorders.

Not available.

Since the discovery of tocopherols a century ago, α-tocopherol has been distinguished for its unique biological functions. In this study, we aim to elucidate the unique characteristics of α-tocopherol from a chemical perspective. Utilizing density functional theory (DFT) calculations, we evaluated the thermodynamic and kinetic properties of tocopherols, tocotrienols and their oxidation products. Our findings highlight the superior thermodynamic and kinetic properties of α-tocopherol. Although tocopherol substrates generally exhibit similar reactivities, α-tocopherol is distinguished by a larger gap between the highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) in intermediates, indicating a potential for greater energy release and favoring reaction progression. Moreover, α-tocopherol shows enhanced efficiency in quenching radical intermediates, especially when combined with vitamin C. All these dates provide valuable support for the naming of vitamin E., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Myelodysplastic syndrome (MDS) is a rare clonal hematopoietic disorder in children. The risk stratification system and treatment strategy for adults are unfit for children. The role of hypomethylating agents (HMAs) in higher-risk childhood MDS has not been identified. This study aimed to investigate the outcomes of hematopoietic stem cell transplantation (HSCT) in children with higher-risk MDS at one single center. A retrospective study was conducted in children with higher-risk MDS undergoing HSCT between September 2019 and March 2023 at Blood Diseases Hospital CAMS. The clinical characteristics and transplantation information were reviewed and analyzed. A total of 27 patients were analyzed, including 11 with MDS with excess blasts (MDS-EB), 14 with MDS-EB in transformation (MDS-EBt) or acute myeloid leukemia with myelodysplasia-related changes (AML-MRC), and 2 with therapy-related MDS/AML (t-MDS/AML). Eight patients harbored monosomy 7. Before transplantation, induction therapy was administered to 25 patients, and 19 of them achieved bone marrow blasts <5% before HSCT. The stem cell source was unmanipulated-related bone marrow or peripheral blood stem cells for nineteen patients and unrelated cord blood for eight. All patients received decitabine-containing and Bu/Cy-based myeloablative conditioning; 26 patients achieved initial engraftment. The cumulative incidences of grade II-IV and grade III-IV acute graft-versus-host disease (GvHD) at 100 days were 65.4% and 42.3%, respectively. The incidence of cGvHD was 38.5%. The median follow-up was 26 (range 4-49) months after transplantation. By the end of follow-up, two patients died of complications and two died of disease progression. The probability of 3-year overall survival (OS) was 84.8% (95%CI, 71.1 to 98.5%). In summary, decitabine-containing myeloablative conditioning resulted in excellent outcomes for children with higher-risk MDS undergoing allogeneic HSCT., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Relapsed or Refractory (R/R) Acute Myeloid Leukemia (AML) patients usually have very poor prognoses, and drug-resistance is one of the major limiting factors. In this study, we aimed to explore the functions of Transforming Growth Factor-β1 (TGFB1) in AML drug-resistance. First, TGFB1 levels in serum and bone marrow are higher in R/R patients compared with newly diagnosed patients, this phenomenon could be due to different sources of secreted TGFB1 according to immunohistochemistry of marrow biopsies. Similarly, TGFB1 expression in AML drug-resistant cell lines is higher than that in their parental cell lines, and blocking the TGFB signaling pathway by specific inhibitors decreased resistance to chemotherapeutic agents. On the other hand, exogenous TGFB1 can also promote AML parental cells senescence and chemotherapy resistance. Next, we found SOX4 level is upregulated in drug-resistant cells, and parental cells treated with exogenous TGFB1 induced upregulation of SOX4 levels. Interference of SOX4 expression by siRNA diminished the TGFB1-induced sensitivity to chemotherapeutic agents. Finally, we conduct metabolomic analysis and find Alanine, aspartate and glutamate metabolism pathway, and Glycerophospholipid metabolism pathway are decreased after inhibiting TGFB signaling pathway or interfering SOX4 expression. This study concludes that TGFB1 level in R/R AML patients and drug-resistant strains is significantly increased. Blocking the TGFB signaling pathway can enhance the chemosensitivity of drug-resistant cells by suppressing SOX4 expression and metabolic reprogramming., Competing Interests: Declaration of competing interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023. Published by Elsevier Inc.)

Objective: To investigate the prevalence and influencing factors of isolated diastolic hypertension (IDH) in the Tibetan population in Tibet and to provide some evidence for the prevention and control of hypertension and other related diseases in high-altitude areas., Methods: A multistage stratified whole-group random sampling method was used to enroll participants from Ngari Prefecture, Nagqu City, Shannan City, and Lhasa City, Tibet. A total of 3918 native Tibetans with complete data were enrolled in the survey between June 2020 and August 2023. The participants were aged from 18 to 80. The demographic data, life habits, and chronic disease prevalence of the participants were collected. Fasting venous blood samples were collected to perform the routine blood tests and blood biochemistry tests. The prevalence of IDH in subgroups with different characteristics was analyzed and the influencing factors were analyzed by multivariate logistic regression, accordingly. The predictive value of influencing factors on the prevalence of IDH was analyzed by the receiver operating characteristic (ROC) curve and the findings were compared with those of the previous prediction models for IDH., Results: The prevalence of hypertension in the participants was 33.7% ( n =1321), among which, 395 had IDH, accounting for 29.9% of the hypertensive patients. The results of multivariate regression showed that age, heart rate, body mass index, waist circumference, hemoglobin, and low-density lipoprotein cholesterol were associated with risks of developing IDH ( P <0.05). The area under the ROC curve ( AUC ) was 0.71, which indicated improved accuracy for predicting the risks for IDH in comparison with previous predictive models for IDH. Among the influencing factors, BMI showed the best predictive value for IDH risks., Conclusion: The prevalence of IDH is high among Tibetans in Tibet, suggesting the necessity for rational allocation of health resources in accordance. Compared with the previous IDH prediction models, the model proposed in this study is more suited for the Tibetan population. Targeted interventions should be carried out for the high-risk populations, such as young and middle-aged adults and populations suffering from overweight/obesity, central obesity, high-altitude polycythemia, and dyslipidemia, so as to effectively control the occurrence and development of IDH., Competing Interests: 利益冲突　所有作者均声明不存在利益冲突, (© 2024《四川大学学报（医学版）》编辑部 版权所有Copyright ©2024 Editorial Board of Journal of Sichuan University (Medical Sciences).)

This study aimed to determine the effect of supervised exercise training (SET) on cardiovascular function in patients with intermittent claudication (IC). A systematic search in MEDLINE, Embase, and Cochrane Central Register of Controlled Trials databases was conducted. Primary outcomes were systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), rate pressure product (RPP), cardiac output (CO), peak oxygen consumption (VO 2peak ), and heart rate variability (HRV). Secondary outcomes were maximum walking distance (MWD) and pain-free walking distance (PFWD). Outcomes were reported as weighted mean difference (WMD) between the SET group and the control group and synthesized by using the random-effects model. Seventeen RCTs with a total of 936 patients were included in this review. SET resulted in significant improvements of SBP (WMD =  - 7.40, 95% CI - 10.69 ~  - 4.11, p < 0.001, I 2  = 15.2%), DBP (WMD =  - 1.92, 95% CI - 3.82 ~  - 0.02, p = 0.048, I 2  = 0.0%), HR (WMD =  - 3.38, 95% CI - 6.30 ~  - 0.46, p = 0.023, I 2  = 0.0%), RPP (WMD =  - 1072.82, 95% CI - 1977.05 ~  - 168.59, p = 0.020, I 2  = 42.7%), and VO 2peak with plantar flexion ergometer exercise (WMD = 5.57, 95% CI 1.66 ~ 9.49, p = 0.005, I 2  = 62.4%), whereas CO and HRV remained statistically unaltered. SET also improved MWD (WMD = 139.04, 95% CI 48.64 ~ 229.44, p = 0.003, I 2  = 79.3%) and PFWD (WMD = 40.02, 95% CI 23.85 ~ 56.18, p < 0.001, I 2  = 0.0%). In conclusion, SET is effective in improving cardiovascular function in patients with IC, which was confirmed on outcomes of cardiovascular function associated with exercise ability. The findings hold out that the standard therapy of SET can improve not only walking distance but also cardiovascular function in patients with IC., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Growth differentiation factor 15 (GDF15), a member of the transforming growth factor-beta superfamily, is expressed in several human organs. In particular, it is highly expressed in the placenta, prostate, and liver. The expression of GDF15 increases under cellular stress and pathological conditions. Although numerous transcription factors directly up-regulate the expression of GDF15, the receptors and downstream mediators of GDF15 signal transduction in most tissues have not yet been determined. Glial cell-derived neurotrophic factor family receptor α-like protein was recently identified as a specific receptor that plays a mediating role in anorexia. However, the specific receptors of GDF15 in other tissues and organs remain unclear. As a marker of cell stress, GDF15 appears to exert different effects under different pathological conditions. Cell senescence may be an important pathogenetic process and could be used to assess the progression of various lung diseases, including COVID-19. As a key member of the senescence-associated secretory phenotype protein repertoire, GDF15 seems to be associated with mitochondrial dysfunction, although the specific molecular mechanism linking GDF15 expression with ageing remains to be elucidated. Here, we focus on research progress linking GDF15 expression with the pathogenesis of various chronic lung diseases, including neonatal bronchopulmonary dysplasia, idiopathic pulmonary fibrosis, chronic obstructive pulmonary disease, and pulmonary hypertension, suggesting that GDF15 may be a key biomarker for diagnosis and prognosis. Thus, in this review, we aimed to provide new insights into the molecular biological mechanism and emerging clinical data associated with GDF15 in lung-related diseases, while highlighting promising research and clinical prospects., (© 2023. The Author(s).)

Energy metabolism in the context of erythropoiesis and related diseases remains largely unexplored. Here, we developed a primary cell model by differentiating hematopoietic stem progenitor cells toward the erythroid lineage and suppressing the mitochondrial oxidative phosphorylation (OXPHOS) pathway. OXPHOS suppression led to differentiation failure of erythroid progenitors and defects in ribosome biogenesis. Ran GTPase-activating protein 1 (RanGAP1) was identified as a target of mitochondrial OXPHOS for ribosomal defects during erythropoiesis. Overexpression of RanGAP1 largely alleviated erythroid defects resulting from OXPHOS suppression. Coenzyme Q10, an activator of OXPHOS, largely rescued erythroid defects and increased RanGAP1 expression. Patients with Diamond-Blackfan anemia (DBA) exhibited OXPHOS suppression and a concomitant suppression of ribosome biogenesis. RNA-seq analysis implied that the substantial mutation (approximately 10%) in OXPHOS genes accounts for OXPHOS suppression in these patients. Conclusively, OXPHOS disruption and the associated disruptive mitochondrial energy metabolism are linked to the pathogenesis of DBA., Competing Interests: The authors declare that there are no competing financial interests in this study., (© 2024 The Author(s).)

The exploration of new acceleration mechanisms for compactly delivering high-energy particle beams has gained great attention in recent years. One alternative that has attracted particular interest is the plasma-based wakefield accelerator, which is capable of sustaining accelerating fields that are more than three orders of magnitude larger than those of conventional radio-frequency accelerators. In this device, acceleration is generated by plasma waves that propagate at nearly light speed, driven by intense lasers or charged particle beams. Here, we report on the direct visualization of the entire plasma wake dynamics by probing it with a femtosecond relativistic electron bunch. This includes the excitation of the laser wakefield, the increase of its amplitude, the electron injection, and the transition to the beam-driven plasma wakefield. These experimental observations provide first-hand valuable insights into the complex physics of laser beam-plasma interaction and demonstrate a powerful tool that can largely advance the development of plasma accelerators for real-time operation.

Objective: To explore the relationship between hearing loss and cognitive function in the elderly population through propensity score matching method., Methods: We analyzed the data of 7605 participants aged 60 and above who were included in the 2018 China Health and Retirement Longitudinal Study (CHARLS). The non-substitutable 1∶1 nearest neighbor matching method without caliper value was used for propensity score matching and G-computation was used to estimate the average treatment effect (ATE) of hearing loss on all dimensions of cognitive function., Results: Before matching, there were 3626 (47.68%) women, with 1409 (18.53%) of whom suffering from hearing loss and 3031 (39.86%) of whom suffering from cognitive impairment. After matching, 1409 subjects were included in the hearing loss group and 1409, in the normal hearing group, with both groups sharing similar distribution of basic demographic characteristics. The results for the average treatment effect of the population indicated that the cognitive function scores of the hearing loss group were lower than those of the normal hearing group, with the overall cognitive function being 0.593 points lower (95% confidence intervel [ CI ]: －0.916-－0.257, P <0.001), orientation being 0.183 points lower (95% CI : －0.302-－0.055, P =0.004), immediate memory being 0.150 points lower (95% CI : －0.218-－0.085, P <0.001), and language skills being 0.178 points lower (95% CI : －0.303-－0.058, P =0.006). The prevalence of cognitive impairment of the hearing loss group was 4.2% higher than that of the normal hearing group (95% CI : 0.007-0.077, P =0.020)., Conclusion: Hearing loss adversely affects the orientation, memory, and language skills of the elderly population and forms a potential risk factor for cognitive impairment in the elderly population., Competing Interests: 利益冲突　所有作者均声明不存在利益冲突, (© 2024《四川大学学报（医学版）》编辑部 版权所有Copyright ©2024 Editorial Board of Journal of Sichuan University (Medical Sciences).)

Objective: To analyze the prevalence of hyperuricemia (HUA) among the Tibetan population in Nagqu City, Tibet and to uncover the relevant influencing factors., Methods: From July 2020 to August 2021, 763 Tibetan natives from Bangor County (specifically Xinji Township and Jiaqiong Township) and Seni District (specificially Sexiong Township), Nagqu City were investigated by multi-stage cluster random sampling method and the prevalence of HUA was studied by retrospective analysis. Chi-square test and multiple logistic regression were used to analyze the influencing factors of HUA prevalence., Results: The overall prevalence of HUA among the Tibetan population in the three townships of Nagqu City was 19.66% (150/763). In particular, the prevalence in men was 35.00%, while that in women was 8.58%, showing significant difference ( P <0.05). According to the results of univariate analysis, there were significant differences in the distribution of sex, abnormal liver function, abnormal hemoglobin, hyperlipidemia, high level of low-density lipoprotein, hypertriglyceridemia, hypercholesterolemia, abnormal creatinine, hyperhomocysteinemia, obesity, and hypertension between HUA and non-HUA patients ( P <0.05). Multiple logistic regression showed that female sex (odds ratio [ OR ]=0.195, 95% confidence interval [ CI ]: 0.120-0.315) was a protective factor for HUA, while abnormal liver function ( OR =2.812, 95% CI : 1.685-4.692), abnormal creatinine ( OR =7.374, 95% CI : 1.446-37.620), high level of low-density lipoprotein ( OR =2.357, 95% CI : 1.011-5.492), and hyperlipidemia ( OR =3.056, 95% CI : 1.886-4.951) were independent risk factors., Conclusion: The prevalence of HUA is relatively high in Nagqu city and the prevalence of HUA is much higher in men than that in women. Male sex, abnormal liver function, abnormal creatinine, elevated low-density lipoprotein, and hyperlipidemia may be the risk factors for HUA in the local Tibetan population., Competing Interests: 利益冲突　所有作者均声明不存在利益冲突, (© 2024《四川大学学报（医学版）》编辑部 版权所有Copyright ©2024 Editorial Board of Journal of Sichuan University (Medical Sciences).)

A novel alkaloid with a hexa-tetra-hexa-cyclic skeleton, Bi-4-methoxycarbonyl-2-quinolone ( 1 ), was discovered during the investigation of Brucea javanica . Additionally, six known alkaloids ( 2 - 7 ) were also found. The chemical structures of these compounds were identified using HRESIMS and 1D and 2D NMR spectroscopic analysis. Additionally, the absolute configuration of the new compound 1 was determined through X-ray single crystal diffraction. Compound 1 exhibited significant anti-inflammatory activity in RAW264.7 cells and demonstrated promising anti-cancer effects in Lewis cells.

Objective: To evaluate the clinical value of positive copy number variations (CNVs) results by non-invasive prenatal testing (NIPT) without fetal ultrasonography-identified structural anomalies, especially with several known CNVs results., Methods: A total of 135,981 results of NIPT performed between April 1, 2017, and March 31, 2020, enrolled in the free NIPT service program implemented by the local government were retrospectively analyzed. Of these, 87 cases with positive NIPT screens for CNVs and no fetal ultrasonography-identified anomalies were recalled and provided genetic counseling. After obtaining full informed consent, these cases were provided invasive prenatal diagnosis by karyotyping and chromosomal microarray analysis (CMA)/copy number variation sequencing (CNV-seq) with follow-up. One case was lost, while 86 cases were successfully followed up., Results: A total of 44 (50.6%) cases underwent invasive prenatal diagnosis, of which six cases were detected with abnormal karyotype. CMA/CNV-Seq revealed 11 fetuses with positive results for CNVs, among whom eight were consistent with NIPT results, two were partially consistent, one was inconsistent, and positive predictive value (PPV) was 22.7% (10/44). For known CNVs, PPVs were 20% (15q11.2-q13 microdeletion) and 33.3% (5p end deletions). Among 11 pregnant women with positive prenatal diagnosis, seven were confirmed to have pathogenic CNVs in their fetuses; four had CNVs of unknown clinical significance., Conclusions: Even in pregnancies without ultrasonography-identified anomalies, a positive NIPT screen for CNVs must be interpreted with caution and validated by additional diagnostic study., (© 2024 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.)

Genetic risk factors have been shown to contribute to the development of sexual dysfunction. However, the role of methylenetetrahydrofolate reductase ( MTHFR ) gene variants in the risk of erectile dysfunction (ED) remains unclear. In this study, we recruited 1254 participants who underwent ED assessed by the International Index of Erectile Function-5. The MTHFR c.677C>T variant was also measured by fluorescence polymerase chain reaction (PCR). No significant difference in the genotypic frequency of the MTHFR C677T polymorphism (CC, CT, and TT) was observed between men from the ED and non-ED groups. In addition, on binary logistic regression analysis, both crude and adjusted models showed that the risk of ED was not significantly associated with the C677T polymorphism. Interestingly, a significantly higher frequency of the 677TT polymorphism was found in severe and moderate ED (P = 0.02). The positive correlation between the MTHFR 677TT polymorphism and severe ED was confirmed by logistic regression analysis, even after adjusting for potential confounders (odds ratio [OR] = 2.46, 95% confidence interval [CI] 1.15-5.50, P = 0.02). These findings suggest a positive correlation between the MTHFR 677TT polymorphism and the risk of severe ED. Identification of MTHFR gene polymorphisms may provide complementary information for ED patients during routine clinical diagnosis., (Copyright © 2023 Copyright: © The Author(s)(2023).)

Background: Unrelated umbilical cord blood transplantation (UCBT) for bone marrow failure (BMF) disorders using conditioning regimens without Anti-Thymocyte Globulin (ATG) has been used as an alternative transplantation for emerging patients without matched-sibling donors. Experience with this transplant modality in children is limited, especially as a secondary treatment for transplant failure patients., Procedure: We retrospectively reviewed 17 consecutive bone marrow failure patients who underwent unrelated umbilical cord blood transplantation in our center and received conditioning regimens of Total Body Irradiation (TBI) or Busulfan (BU) + Fludarabine (FLU) + Cyclophosphamide (CY)., Results: Among the 17 BMF patients, 15 patients were treated with first cord blood transplantation and another 2 with secondary cord blood transplantation because of graft failure after first haploidentical stem cell transplantation at days +38 and +82. All patients engrafted with a median donor cell chimerism of 50 % at days +7 (range, 16 %-99.95 %) and finally rose to 100 % at days +30. Median time to neutrophil engraftment was 19 days (range, 12-30) and time to platelet engraftment was 32 days (range, 18-61). Pre-engraftment syndrome (PES) was found in 16 patients (94.11 %, 16/17). Cumulative incidence of grades II to IV acute GVHD was 58.8 % (95 % CI: 32.7-84.9 %), and 17.6 % (95 % CI: 2.6-37.9 %) of patients developed chronic GVHD. The 3-year overall survival (OS) and failure-free survival (FFS) rates were 92.86 ± 6.88 %., Conclusion: UCBT is an effective alternative treatment for bone marrow failure pediatric patients. TBI/BU + FLU + CY regimen ensure a high engraftment rate for unrelated umbilical cord blood transplantation, which overcomes the difficulty of graft failure. Secondary salvage use of cord blood transplantation may still be useful for patients who have failed after other transplantation., Competing Interests: Conflict of interest The authors declare no competing interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)

It is important to detect the presence of biogenic amines (BAs) as indicators of food freshness. The purpose of this study was to develop a novel ultrasonic-microwave synergistic supramolecular solvent liquid-liquid microextraction based on solidification of floating organic droplet (UMS-SUPRAS-SFO-LLME) combined with high-performance liquid chromatography for the determination of BAs. The physical properties and microstructure of SUPRAS based on 1-dodecanol and tetrahydrofuran were studied, and the extraction conditions such as the SUPRAS volume, the UMS process, and the centrifugal conditions were optimized. The results for the extraction kinetics and thermodynamics showed that UMS-SUPRAS-SFO-LLME is a spontaneous, endothermic diffusion process. The linear ranges of this method are 0.1-2.0 × 10 5 ng·mL -1 (R 2  > 0.994), the limits of detection are 4.0 × 10 -3 -6.0 × 10 -2 ng·mL -1 , and the recoveries were 96.28-103.15%. Compared with existing analysis methods, UMS-SUPRAS-SFO-LLME is a sensitive, green and economical sample pretreatment method for analyzing the enrichment of BAs in beer and fish., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Prenatal stress has been extensively documented as a contributing factor to adverse cardiac development and function in fetuses and infants. The release of glucocorticoids (GCs), identified as a significant stressor, may be a potential factor inducing cardiac hypertrophy. However, the underlying mechanism remains largely unknown. Herein, we discovered that corticosterone (CORT) overload induced cardiac hypertrophy in embryonic chicks and fetal mice in vivo , as well as enlarged cardiomyocytes in vitro . The impaired mitochondria dynamics were observed in CORT-exposed cardiomyocytes, accompanied by dysfunction in oxidative phosphorylation and ATP production. This phenomenon was found to be linked to decreased mitochondrial fusion protein mitofusin 2 (MFN2). Subsequently, we found that CORT facilitated the ubiquitin-proteasome-system-dependent degradation of MFN2 with an enhanced binding of appoptosin to MFN2, serving as the underlying cause. Collectively, our findings provide a comprehensive understanding of the mechanisms by which exposure to stress hormones induces cardiac hypertrophy in fetuses., Competing Interests: The authors declare no competing interests., (© 2023 The Authors.)

Background: Utilizing the traditional Cox regression model to identify the factors affecting the risk of mortality due to microinvasive cutaneous squamous cell carcinoma (micSCC) may produce skewed results. Since cause-specific mortality can guide clinical decision-making, this study employed the Fine-Gray model based on the Surveillance, Epidemiology, and End Results (SEER) database to identify significant predictive variables for the risk of micSCC-related mortality., Methods: This study used the information of patients with micSCC who were listed in the SEER database during 2000-2015. Cox regression and Fine-Gray models were utilized for the multivariable analysis, and Gray's test and the cumulative incidence function were used for the univariable analyses., Results: There were 100 patients who died from other reasons and 38 who died from micSCC among the 1259 qualified patients with micSCC. Most were female, white, married, had localized metastasis, etc. According to the univariable Gray's test (P < 0.05), the cumulative incidence rate for events of interest was strongly associated with age, sex, marital status, American Joint Committee on Cancer staging, radiation status, summary stage, chemotherapy status, surgery status, and tumor size. Multivariable Cox regression analysis and multivariable competing-risks analysis indicated that age, tumor size, and income were independent risk variables for the prognosis of patients with micSCC. In both age and tumor size variables, the competing-risks model showed a slight decrease in the hazard ratio and a slight narrowing of the 95% confidence interval compared with the Cox regression model. However, this pattern is not evident in the income variable., Conclusions: This study established a Fine-Gray model for identifying the independent risk factors that influence the risk of mortality among patients with micSCC. This study uncovers that, in the context of competing risks, age, tumor size, and income serve as independent risk factors influencing the risk of mortality due to micSCC among patients. Our findings have the potential to provide more accurate risk assessments for patient outcomes and contribute to the development of individualized treatment plans., (© 2023. The Author(s).)

Lysine methyltransferase 2A-rearranged acute myeloid leukemia ( KMT2A -r AML) is a special entity in the 2022 World Health Organization classification of myeloid neoplasms, characterized by high relapse rate and adverse outcomes. Current risk stratification was established on the treatment response and translocation partner of KMT2A . To study the transcriptomic feature and refine the current stratification of pediatric KMT2A -r AML, we analyzed clinical and RNA sequencing data of 351 patients. By implementing least absolute shrinkage and selection operator algorithm, we identified 7 genes ( KIAA1522 , SKAP2 , EGFL7 , GAB2 , HEBP1 , FAM174B , and STARD8 ) of which the expression levels were strongly associated with outcomes. We then developed a transcriptome-based score, dividing patients into 2 groups with distinct gene expression patterns and prognosis, which was further validated in an independent cohort and outperformed the LSC17 score. We also found cell cycle, oxidative phosphorylation, and metabolism pathways were upregulated in patients with inferior outcomes. By integrating clinical characteristics, we proposed a simple-to-use prognostic scoring system with excellent discriminability, which allowed us to distinguish allogeneic hematopoietic stem cell transplantation candidates more precisely. In conclusion, pediatric KMT2A -r AML is heterogenous on transcriptomic level and the newly proposed scoring system combining clinical characteristics and transcriptomic features can be instructive in clinical routines., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the European Hematology Association.)

Background: Individuals diagnosed with Fanconi anemia (FA), an uncommon disorder characterized by chromosomal instability affecting the FA signaling pathway, exhibit heightened vulnerability to the onset of myelodysplastic syndromes (MDS) or acute myeloid leukemia (AML)., Methods: Herein, we employed diverse bioinformatics and statistical analyses to investigate the potential associations between the expression/mutation patterns of FA pathway genes and MDS/AML., Results: The study included 4295 samples, comprising 3235 AML and 1024 MDS from our and nine other online cohorts. We investigated the distinct proportion of race, age, French-American-British, and gender factors. Compared to the FA wild-type group, we observed a decrease in the expression of FNACD2, FANCI, and RAD51C in the FA mutation group. The FA mutation group exhibited a more favorable clinical overall survival prognosis. We developed a random forest classifier and a decision tree based on FA gene expression for cytogenetic risk assessment. Furthermore, we created an FA-related Nomogram to predict survival rates in AML patients., Conclusions: This investigation facilitates a deeper understanding of the functional links between FA and MDS/AML., (© 2023. The Author(s).)

Background: Development of validated biomarkers to detect early Alzheimer disease (AD) neuropathology is needed for therapeutic AD trials. Abnormal concentrations of "core" AD biomarkers, cerebrospinal fluid (CSF) amyloid beta1-42, total tau, and phosphorylated tau correlate well with neuroimaging biomarkers and autopsy findings. Nevertheless, given the limitations of established CSF and neuroimaging biomarkers, accelerated development of blood-based AD biomarkers is underway., Content: Here we describe the clinical significance of CSF and plasma AD biomarkers to detect disease pathology throughout the Alzheimer continuum and correlate with imaging biomarkers. Use of the AT(N) classification by CSF and imaging biomarkers provides a more objective biologically based diagnosis of AD than clinical diagnosis alone. Significant progress in measuring CSF AD biomarkers using extensively validated highly automated assay systems has facilitated their transition from research use only to approved in vitro diagnostics tests for clinical use. We summarize development of plasma AD biomarkers as screening tools for enrollment and monitoring participants in therapeutic trials and ultimately in clinical care. Finally, we discuss the challenges for AD biomarkers use in clinical trials and precision medicine, emphasizing the possible ethnocultural differences in the levels of AD biomarkers., Summary: CSF AD biomarker measurements using fully automated analytical platforms is possible. Building on this experience, validated blood-based biomarker tests are being implemented on highly automated immunoassay and mass spectrometry platforms. The progress made developing analytically and clinically validated plasma AD biomarkers within the AT(N) classification scheme can accelerate use of AD biomarkers in therapeutic trials and routine clinical practice., (© Association for Diagnostics & Laboratory Medicine 2023. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The antibiotic pollution emerged in different environments has raised a great concern. Adsorption is an effective method to solve the problem. However, conventional adsorbents are not always efficient for antibiotic removal with interferences. Therefore, in this study, molecularly imprinted polymer (EMIP) with selective adsorption ability was prepared to remove a typical antibiotic-erythromycin (ERY) at environmentally relevant concentration. The specific surface area of EMIP was 265.62 m 2 /g with large pore volume, small pore size and hydrophobic surface. The adsorption capacity of EMIP was increased from 211.08 to 4015.51 μg/g when the concentration of ERY was increased from 5.00 to 100.00 μg/L. The isothermal adsorption process was fitted well with the Langmuir model. The adsorption kinetic could be well described by the pseudo-second-order model. With co-existing of interferences, the imprinting factor for ERY was 2.57, which demonstrated EMIP had good adsorption selectivity. After five consecutive adsorption-desorption experiments, the adsorption capacity of EMIP was still over 80%. The results of molecular dynamic simulation showed the adsorption energy between ERY and EMIP was high, which was favorable for ERY adsorption removal. Hopefully, the results of this study could provide new insights for trace antibiotic removal by molecular imprinting polymers in different aqueous environments., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Electroacupuncture (EA) can effectively reduce surgical stress reactions and promote postoperative recovery, but the mechanisms remain unclear. The present study aims to examine the effects of EA on the hyperactivity of the hypothalamic‒pituitary‒adrenal (HPA) axis and investigate its potential mechanisms. Male C57BL/6 mice were subjected to partial hepatectomy (HT). The results showed that HT increased the concentrations of corticotrophin-releasing hormone (CRH), corticosterone (CORT), and adrenocorticotropic hormone (ACTH) in the peripheral blood and upregulated the expression of CRH and glucocorticoid receptors (GR) proteins in the hypothalamus. EA treatment significantly inhibited the hyperactivity of the HPA axis by decreasing the concentration of CRH, CORT, and ACTH in peripheral blood and downregulating the expression of CRH and GR in the hypothalamus. Moreover, EA treatment reversed the HT-induced downregulation of oxytocin (OXT) and oxytocin receptor (OXTR) in the hypothalamus. Furthermore, intracerebroventricular injection of the OXTR antagonist atosiban blocked the effects of EA. Thus, our findings implied that EA mitigated surgical stress-induced HPA axis dysfunction by activating the OXT/OXTR signaling pathway., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)