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Breast milk storage provides flexibility for working mothers, though its effects on milk fat globule membrane (MFGM) lipids are not fully understood. This study examined breast milk stored under refrigerated (2 and 4 days) and frozen (7, 14, and 21 days) conditions, finding that these storage durations preserved similar structural characteristics during in vitro gastrointestinal digestion. The analysis focused on MFGM lipid composition under various storage conditions using non-targeted lipidomics. Results revealed that freezing for 14 days reduced phosphatidylserine (PS) levels by 64.55%, while 21 days of freezing significantly decreased both PS (74.59%) and sphingomyelin (SM) (43.85%). Examination of MFGM lipid species indicated that refrigeration for 4 days and freezing for 21 days led to notable reductions in key MFGM lipid species. Thus, breast milk should be refrigerated for up to 4 days to minimize nutrient depletion or frozen for no more than 7 days., 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.Supplementary data, (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Groundwater quality is strongly compromised by polluted surface water recharge in rapidly developing urban regions. However, gaps still remain in the understanding of the critical contaminants controlling water quality and the health risks associated with groundwater consumption, particularly considering seasonal and climate changes in rainfall. This work focused on changes in groundwater quality and critical contaminants in domestic wells in the fast-developing Pearl River Delta (PRD) from the wet season to the dry season. The stable isotope δ D and δ 18 O values indicated that groundwater was largely impacted by precipitation and has experienced strong evaporation. The groundwater generally exhibited oxidizing and slightly alkaline properties and was predominantly of the Ca-HCO 3 type. Owing to the dominant water type of Ca-HCO 3 and the high concentrations of Ca, concerns related to hard water arose, particularly during the wet season, which promotes the need for water softening before groundwater use. Although the heavy metal pollution index (HPI) and water quality index (WQI) indicated excellent or good water quality, 34% and 47% of the groundwater samples presented elevated concentrations of arsenic and nitrate, respectively, compared with the WHO recommended levels, and the contamination level was elevated during the dry season. To our knowledge, this study is the first to report the fluoride concentrations in the PRD groundwater, with median values below 0.5 mg L -1 , underscoring the need for dietary fluoride supplementation. Health risk assessment confirmed the presence of both noncarcinogenic risks from arsenic and nitrate and cancer risk from arsenic in local populations resulting from groundwater consumption in the PRD region. This research emphasizes the importance of critical contaminants that constrain groundwater quality from different seasons with large variations in rainfall. Our work highlights the urgent need for the construction of adequate sanitation systems and for the control of agricultural nonpoint source pollution in rapidly urbanizing areas to safeguard both surface water and groundwater resources.

Regioselective functionalization of alkenes to create nitrogen- and oxygen-containing heterocycles remains a significant challenge in organic synthesis. Due to their unique electronic and biological properties, these heterocycles are crucial in pharmaceuticals and materials. Herein, we present an electrochemical amino-oxygenation of alkenes using alkene radical cations and bisnucleophiles, enabling the synthesis of saturated N/O-heterocycles in an undivided cell. This method employs readily available amides and alkenes, eliminating the need for additional oxidants or redox catalysts. The in situ generation of alkene radical cations results in high yields with excellent regio- and chemoselectivity. Our approach offers a direct route to six-, seven-, and eight-membered N/O-heterocycles from simple starting materials, broadening access to complex molecules essential for medicinal chemistry and materials science., (© 2025 Wiley‐VCH GmbH.)

Edible maize is an important food crop, providing energy and nutrients to meet human health and nutritional requirements. However, how environmental pressures and human activity have shaped the edible maize metabolome remains unclear. In this study, we collected 452 diverse edible maize accessions worldwide, comprising waxy, sweet, and field maize. A total of 3,020 non-redundant metabolites, including 802 annotated metabolites, were identified by a two-step optimized approach, which generated the most comprehensive annotated metabolites dataset in plants to date. Although specific metabolite differentiation was detected in Field-Sweet and Field-Waxy differentiations, convergent metabolite differentiation was the dominant differentiation pattern. We identified hub genes in all metabolite classes by mGWAS hotspot analysis. A total of 17 and 15 hub genes were selected as the key differentiation genes for flavonoids and lipids, respectively. Surprisingly, almost all of these genes were under diversifying selection, which indicated diversifying selection was the main genetic mechanism of convergent metabolic differentiation. Furthermore, the genetic and molecular studies reveal the roles and diversifying selection genetic mechanisms of ZmGPAT11 in convergent metabolite differentiation in lipid pathway. Based on our research, we established the first edible maize metabolome database, EMMDB (www.maizemdb.site/home/). We successfully applied EMMDB for precision improvement of nutritional and flavor traits, and an elite inbred line 6644_2 was bred with greatly improved in contents of flavonoids, lysophosphatidylcholines, lysophosphatidylethanolamines, and vitamins. These findings provide insights into the underlying genetic mechanisms of edible maize metabolite differentiation and provide a database for the breeding improvement of edible maize flavor and nutritional traits by metabolome precision design., (Copyright © 2025. Published by Elsevier Inc.)

Colorectal cancer (CRC) is a prevalent malignancy and a significant proportion of patients with CRC develop liver metastasis (CRLM), which is a major contributor to CRC‑related mortality. The present review aimed to comprehensively examine the pathogenetic development and diagnosis of CRLM and the clinical therapeutic approaches for treatment of this disease. The molecular mechanisms underlying CRLM were discussed, including the role of the tumour microenvironment and epithelial‑mesenchymal transition. The present review also highlighted the importance of early detection and the current challenges in predicting the development of CRLM. Various treatment strategies were reviewed, including surgical resection, chemotherapy and immunotherapy, and the potential of novel therapies, such as selective internal radiation therapy and Traditional Chinese Medicine. Despite recent advancements in treatment options, the treatment of CRLM remains a therapeutic challenge due to the complexity of the liver microenvironment and the heterogeneity of CRC. The present review emphasized the need for a multidisciplinary approach and the integration of emerging therapies to improve patient outcomes.

To understand the smoke level and NO x emission characteristics of in-use construction machinery in Beijing, we selected 905 construction machines in Beijing from August 2022 to April 2023 to monitor the emission level of smoke and NO x . The exhaust smoke level and excessive emission situation of different machinery types were identified, and their NO x emission levels were monitored according to the free acceleration method. We investigated the correlation of NO x and smoke emission, and proposed suggestions for controlling pollution discharge from construction machinery in the future. The results show that the exhaust smoke level was 0-2.62 m -1 , followed a log-normal distribution (μ = -1.73, δ = 1.09, R 2 = 0.99), with a 5.64% exceedance rate. Differences were observed among machinery types, with low-power engine forklifts showing higher smoke levels. The NO x emission range was 71-1516 ppm, followed a normal distribution (μ = 565.54, δ = 309.51, R 2 = 0.83). Differences among machinery types were relatively small. Engine rated net power had the most significant impact on NO x emissions. Thus, NO x emissions from construction machinery need further attention. Furthermore, we found a weak negative correlation (p < 0.05) between the emission level of smoke and NO x , that is the synergic emission reduction effect is poor, emphasizing the need for NO x emission limits. In the future, the oversight in Beijing should prioritize phasing out China Ⅰ and China Ⅱ machinery, and monitor emissions from high-power engine China Ⅲ machinery., 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: Limited passage numbers of mesenchymal stem cells (MSCs) present challenges in producing sufficient exosomes for spinal cord injury (SCI) treatment., Objectives: This study investigates whether β-mercaptoethanol (BME) preconditioning of MSCs can increase exosome yield for SCI therapy., Methods: Exosomal content was analyzed using silver staining and SYBR Gold staining. Cell viability was assessed via CCK-8 and EdU assays. IL-1β, IL-6, TNF-α, and MCP-1 levels were measured by enzyme-linked immunosorbent assay (ELISA). Neuronal differentiation influenced by astrocytes was evaluated through neurite outgrowth and migration assays. Neuronal survival and motor function recovery in SCI mice were assessed using TUNEL staining, the Basso Mouse Scale (BMS), muscle strength tests, and motor evoked potential (MEP) measurements., Results: BME treatment significantly increased exosome quantity, including proteins and microRNAs, without drastic changes in exosomal content spectrum. Exosomes from BME-treated MSCs more effectively suppressed IL-1β, IL-6, TNF-α, and MCP-1 secretion by astrocytes, reducing neuronal inflammation. Yap1 activation reduced the exosomes' inhibitory effects on inflammatory cytokines. Mice treated with exosomes from BME-treated MSCs showed better outcomes: lower GFAP and C3 expression, reduced inflammation, increased NF-H levels, higher BMS scores, and greater MEP peaks. Exosome treatment also reduced bladder volume, residual urine, and the time to regain spontaneous urination after uroschesis., Conclusion: BME preconditioning enhances exosome yield from hUC-MSCs, offering improved therapeutic potential for SCI., 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 © 2025 Elsevier Inc. All rights reserved.)

Catalytic purification of sulphur-containing malodorous gases has attracted wide attention because of its advantages of high purification efficiency, low energy consumption and lack of secondary pollution. The selection of efficient catalysts is the key to the problem, while the preparation and optimisation of catalysts depend on the analysis of experimental results and in-depth mechanistic analysis. By analysing the published literature, bibliometric analysis can identify existing research hotspots, the areas of interest and predict development trends, which can help to identify hot catalysts in the catalytic purification of sulphur-containing odours and to investigate their catalytic purification mechanisms. Therefore, this paper uses bibliometric analysis, based on Web Of Science and CNKI databases, CiteSpace and VOS viewer software to collate and analyse the literature on the purification of sulphur-containing odour pollutants, to identify the current research hotspots, to summarise the progress of research on the catalytic purification of different types of sulphur-containing odours, and to analyse their reaction mechanisms and kinetics. On this basis, the research progress of catalytic purification of different kinds of sulfur odour is summarized, and the reaction mechanism and dynamics are summarized., 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. Published by Elsevier B.V.)

Aims and Objectives: To explore the relationships among post-stroke fatigue, hope and discharge readiness in stroke patients, and to determine whether hope mediates the relationship between post-stroke fatigue and discharge readiness., Background: In stroke patients, inadequate discharge readiness has been found to correlate with higher readmission and mortality rates. Although previous qualitative studies have confirmed the impact of fatigue on discharge readiness, few studies explore the impact of post-stroke fatigue and hope on discharge readiness of stroke patients. Consequently, the current research on this relationship and its underlying mechanisms is still quite limited., Design: Cross-sectional study., Methods: Data were collected from 340 stroke patients. The research tools included demographic and disease characteristics, Discharge Readiness Assessment Scale for Stroke, Neurological Fatigue Index for Stroke and Herth Hope Index. The STROBE checklist was used to guide the presentation of this study., Results: Discharge readiness was negatively correlated with post-stroke fatigue and positively correlated with hope. Additionally, post-stroke fatigue was negatively correlated with hope. Post-stroke fatigue had a direct negative effect on discharge readiness, and it can also generate indirect effects through hope. Hope was the partial mediator between post-stroke fatigue and discharge readiness, explaining 55.8% of the total effect., Conclusion: Discharge readiness of this population can be improved by reducing post-stroke fatigue and increasing hope. Therefore, effective management of post-stroke fatigue and hope will help improve discharge readiness., Relevance to Clinical Practice: It is recommended that nursing staff should monitor the occurrence and development of post-stroke fatigue in stroke patients, dynamically evaluate the patient's level of hope, and pay attention to the important role of positive psychological qualities in the outcome of discharge. If medical staff can formulate corresponding intervention measures based on the influence path of discharge readiness, then the discharge readiness of stroke patients can be improved., (© 2024 John Wiley & Sons Ltd.)

Background: Melanin pigmentation in oocytes is a critical feature for both the esthetic and developmental aspects of oocytes, influencing their polarity and overall development. Despite substantial knowledge of melanogenesis in melanocytes and retinal pigment epithelium cells, the molecular mechanisms underlying oocyte melanogenesis remain largely unknown., Results: Here, we compare the oocytes of wild-type, tyr -/- and mitf -/- Xenopus tropicalis and found that mitf -/- oocytes exhibit normal melanin deposition at the animal pole, whereas tyr -/- oocytes show no melanin deposition at this site. Transmission electron microscopy confirmed that melanogenesis in mitf -/- oocytes proceeds normally, similar to wild-type oocytes. Transcriptomic analysis revealed that mitf -/- oocytes still express melanogenesis-related genes, enabling them to complete melanogenesis. Additionally, in Xenopus tropicalis oocytes, the expression of the MiT subfamily factor tfe3 is relatively high, while tfeb, mitf, and tfec levels are extremely low. The expression pattern of tfe3 is similar to that of tyr and other melanogenesis-related genes. Thus, melanogenesis in Xenopus tropicalis oocytes is independent of Mitf and may be regulated by other MiT subfamily factors such as Tfe3, which control the expression of genes like tyr, dct, and tyrp1. Furthermore, transcriptomic data revealed that changes in the expression of genes related to mitochondrial cloud formation represent the most significant molecular changes during oocyte development., Conclusions: Overall, these findings suggest that further elucidation of Tyr-dependent and Mitf-independent mechanisms of melanin deposition at the animal pole will enhance our understanding of melanogenesis and Oogenesis., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

A distinguishing characteristic of Josephson junctions (JJs) is their nonlinear current-voltage response, which fulfills the requirements for superconducting quantum computing. Achieving atomically sharp interfaces between superconductors and weak links in JJs can realize the superconductivity proximity effect, advancing the investigation of intrinsic properties in unconventional superconductors and their potential applications. Here, a contamination-free approach to fabricating planar JJs using molecular beam epitaxy (MBE) is presented. The self-assembled Bi buffer layer forms a ladder-like framework on Si (111) 7 × 7 reconstructions, consisting of a wetting layer of Bi interspersed with Bi crystalline islands. Upon depositing Pb on this Bi buffer layer, Pb atoms dominantly nucleate on the Bi wetting layer, bypassing the Bi islands to form arrayed JJs. The selective area growth of Pb thin films is attributed to the higher nucleation densities for Pb on the Bi wetting layer compared to Bi crystalline islands. In situ scanning tunneling microscopy (STM) measurements reveal the superconducting correlations within the interior of junctions. The study establishes an in-vacuo deposition method for fabricating pristine JJs, facilitating the potential investigation of emergent superconducting phenomena in designed heterostructures., (© 2025 Wiley‐VCH GmbH.)

Rationale: Obstructive sleep apnea (OSA) is associated with cognitive impairment. The effects of continuous positive airway pressure (CPAP) on neuroimaging biomarkers and cognitive performance among middle-aged patients with OSA and normal cognition remain unclear., Objectives: To investigate the effects of CPAP therapy over 12 months on neuroimaging biomarkers and cognitive performance., Methods: In this multicenter, randomized clinical trial, we randomly assigned 148 participants with normal cognition and an apnea-hypopnea index ≥15/hour into two groups: patients receiving CPAP with best supportive care (BSC); and patients receiving BSC alone. The primary endpoint was MoCA score at 6 months after enrollment. The secondary endpoints were intranetwork functional connectivity (FC) of default mode network (DMN) and cortical thickness assessed by functional and structural magnetic resonance imaging, other neuroimaging biomarkers and neurobehavioral tests., Measurements and Main Results: Between 2017 and 2021, 148 patients were recruited from 5 hospitals. Linear mixed models showed that there was no significant difference in MoCA scores at 6 months between the CPAP and BSC groups (difference, -0.04, 95% confidence interval (CI), -0.72 to 0.65, P=0.91). However, there were significant differences in the FC of DMN (difference, -13.73, 95% CI, -23.40 to -4.06, P=0.01) and cortical thickness (difference, -0.06 mm, 95% CI, -0.10 to -0.01mm, P=0.02) between CPAP and BSC groups at 6 months after treatment. No serious adverse events occurred., Conclusions: CPAP improved cortical thickness and FC of DMN, suggesting that patients with OSA may recover from brain atrophic processes following CPAP treatment. However, no improvement in MoCA was found. Clinical trial registration available at www., Clinicaltrials: gov, ID: NCT02886156.

Foul-smelling organic sulfur gases removal of which is crucial for improving environmental quality and protecting human health. Herein, in this study, Pt single-atom (SA) loaded magnesium oxide (MgO) nanosheet catalysts were prepared, which exhibited the dual effects of anchored sulfur and activated oxygen that greatly enhanced the catalytic oxidation efficiency of methyl mercaptan (CH 3 SH), and 90 % complete oxidation of CH 3 SH could be achieved by Pt SA/MgO at 325 °C, with an oxidation efficiency that was 8 times higher than that of MgO nanosheets. A series of characterization results indicate that the valence state of Pt in the Pt SA/MgO catalyst ranges between 0 and +4, demonstrating its inherent electron-donating capability. Theoretical calculations show that the oxygen vacancy formation energy is reduced to 4.0 eV after the introduction of Pt SA, and the adsorption energy of atomic groups SH and CH 3 is reduced to -1.5 and -2.0 eV. And the bond length of the MgO bond in Pt SA/MgO is shortened to 2.083 Å, forming an asymmetric structure with the PtO bond of 2.142 Å, effectively activating the lattice oxygen. Furthermore, A series of activity tests confirmed that the introduction of Pt SA reduced sulfate deposition, while the reaction pathway of CH 3 SH catalytic oxidation was optimised by changing the oxidation mechanism. The investigation offers a significant experimental foundation and novel viewpoints for the enhancement of high-performance catalytic oxidation catalysts targeting sulfur-containing volatile organic compounds (VOCs)., 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 © 2025 Elsevier Inc. All rights reserved.)

Previous observational clinical studies have found a causal relationship between neurotic personality traits and various disorders. However, the relationship between neurotic personality characteristics and pre-eclampsia (PE) is not unclear. Two-sample Mendelian randomization (MR) was employed to examine the influence of neurotic personality traits on the risk of PE. From the Finnish genome-wide database, we identified 32 single-nucleotide polymorphisms linked to neuroticism personality traits, excluding 7 confounding variables related to blood pressure and BMI. The number of tool variables associated with PE was 25. Causality was assessed using inverse variance weighting, weighted median, MR-Egger, and weighted model methods. Sensitivity analyses, such as Cochran's Q statistic, MR-Egger intercept, MR pleiotropy residual sum and outlier, and leave-one-out analysis, were conducted to identify potential heterogeneity and horizontal pleiotropy. The present 2-sample MR study did not reveal any genetic associations between neuroticism and PE. A 2-sample Mendelian randomization analysis of 12 dichotomous neuroticism items indicated that genetic predisposition to worrying elevates the risk of PE. The inverse variance weighted method produced an odds ratio (OR) of 2.23 (95% CI: 1.36-3.65, P < .05), while the weighted median analysis indicated an OR of 2.41 (95% CI: 1.20-4.85, P < .05). However, there were no significant correlations between the MR Egger and weighted modes. This study found no genetic causal link between neuroticism and PE; however, carriers may have a genetically increased risk of PE, offering a more reliable foundation for future prevention efforts., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2025 the Author(s). Published by Wolters Kluwer Health, Inc.)

Importance: We recently observed an inverse and time-dependent association between systemic oxidative stress (OxS), measured by urinary biomarkers of nucleic acid oxidation, and colorectal cancer (CRC) risk. Further investigations into other types of OxS markers are warranted., Objective: To extend the investigation into systemic lipid peroxidation and CRC risk., Design Setting and Participants: Utilizing a nested case-control design, this study's primary analysis was performed in two large prospective cohorts in Shanghai, China, and replicated in an independent cohort in the US., Exposures: Systemic lipid peroxidation was assessed by urinary F 2 -isoprostanes (F 2 -IsoPs) using UPLC-MS/MS assays., Main Outcomes and Measures: During 15.1-year follow-up in the Shanghai cohorts, 1938 incident CRC cases were identified and matched to one control each through incidence-density sampling. In the US cohort, 285 incident CRC cases were included, each matched to two controls. Odds ratios (ORs) for CRC were calculated using multivariable conditional logistic regression models., Results: Elevated levels of urinary 5-F 2t -IsoP (5-iPF 2α -VI), a major isomer of F 2 -IsoPs induced solely by free radicals, were associated with reduced risk of CRC in the Shanghai cohorts. This finding was replicated in the US cohort. Moreover, this inverse association was time-dependent, manifesting only in the later years of cancer development. Multivariable-adjusted ORs (95% CI) for CRC diagnosed within 5 years of enrollment at the 10th and 90th percentiles of 5-F 2t -IsoP levels, relative to the median, were 1.57 (1.26-1.96) and 0.61 (0.42-0.89), respectively, indicating a 2.2-fold difference in risk between the two groups. A stronger association was observed when using the composite index of DNA, RNA and lipid OxS markers, showing a 3.9-fold difference in risk between the two groups. No significant association was found for CRC diagnosed beyond 5 years of enrollment., Conclusions: This study provides new evidence that systemic OxS is inversely and time-dependently associated with CRC risk in humans., Key Points: Question: Is the time-dependent relationship between oxidative stress and tumorigenesis observed at the cellular level in experimental models also present at the systemic level in a population-based setting? Findings: Elevated systemic lipid peroxidation, measured by urinary F 2 -isoprostanes, was associated with a reduced risk of colorectal cancer (CRC) in two large prospective cohort studies in Shanghai, China, which was replicated in an independent cohort in the United States. This association varied over time, showing a stronger effect as cancer advanced. Meaning: This study provides new evidence that systemic oxidative stress is inversely and time-dependently associated with CRC risk in humans.

Objective: The objective of this study was to estimate cancer burden attributable to excess body weight (EBW) and identify its main source., Methods: We obtained relative risks from meta-analyses, cancer and population data from the Global Burden of Disease Study (GBD) 2021, and BMI prevalence data from the NCD Risk Factor Collaboration (NCD-RisC). We calculated the incidence of 11 cancers attributable to high BMI from 1990 to 2021, analyzed trends using joinpoint regression, and assessed cohort effects with the age-period-cohort model. Decomposition analysis was conducted by cancer-specific risk factors and by population size, aging, and epidemiological changes., Results: The incidence of 11 EBW-related cancers has increased from 1990 to 2021. Later-born cohorts and older age groups had higher cancer incidence rates. High BMI was the top contributor to changes in cancer burden (15.96% of all disability-adjusted life years [DALYs]), particularly in high Sociodemographic Index (SDI) regions. Colorectal, esophageal, and liver cancer had the highest burden due to high BMI (1,349,622; 1,284,385; and 944,616 DALYs, respectively). Epidemiological changes in BMI contributed to the rising DALY burden, ranging from 7.88% for postmenopausal breast cancer to 49.20% for liver cancer., Conclusions: The rising prevalence of EBW contributed to the global cancer burden, showing a significant birth cohort effect. High BMI was the top contributing factor to obesity-related cancers, surpassing other epidemiological risk factors., (© 2025 The Obesity Society.)

Background: Soft tissue sarcomas (STS) are a heterogeneous group of tumors with diverse clinical and molecular characteristics, characterized by limited treatment options and poor prognosis. Immune checkpoint inhibitors (ICIs) have emerged as promising therapies for STS, yet comprehensive evaluations of their efficacy, especially in combination with other treatments, are scarce., Methods: We conducted a systematic review and meta-analysis of clinical trials on ICIs in STS treatment, sourced from PubMed, Embase, and the Cochrane Central Register of Controlled Trials up to May 31, 2024. The studies included both monotherapy and combination therapies with ICIs. We assessed the methodological quality using the Cochrane Risk of Bias 2 tool and the Methodological Index for Non-Randomized Studies. Data synthesis involved random-effects meta-analysis to determine pooled proportions and 95% confidence intervals (CIs) for objective response rates (ORR), disease control rates (DCR), and high-grade treatment-related adverse events (TRAEs)., Results: The analysis included 38 studies with 1349 patients covering 24 STS subtypes. The overall ORR was 16% (95% CI 0.12-0.21), DCR was 64% (95% CI 0.57-0.70), and the rate of Grade 3-5 TRAEs was 19% (95% CI 0.13-0.27). Treatments combining ICIs with tyrosine kinase inhibitors (TKIs) showed the highest efficacy (ORR 28%, 95% CI 0.18-0.40), albeit with increased adverse events. ORRs in first-line treatments were substantially higher (28%) compared to second-line treatments or beyond (11%). Subtypes like alveolar soft part sarcoma (ASPS), angiosarcoma (AS), and epithelioid sarcoma (ES) exhibited favorable responses exceeding 30%., Conclusions: This systematic review and meta-analysis indicate that ICIs, particularly when combined with TKIs, provide substantial therapeutic benefits in treating STS, significantly enhancing response rates in specific subtypes such as ASPS and AS. The results underscore the transformative potential of ICIs in STS treatment strategies. However, the variability across subtypes and treatment lines emphasizes the need for further randomized controlled trials to refine and personalize therapeutic approaches, ensuring optimal outcomes for patients with these diverse malignancies., 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 © 2025 Elsevier B.V. All rights reserved.)

Introduction: This study aimed to explore the epidemiological trends of laryngeal cancer (LC) using the 2021 Global Burden of Disease (GBD) data., Methods: We analyzed the global LC incidence, deaths, disability-adjusted life years (DALYs), and risk factors from 1990 to 2021. We evaluated trends using the annual percentage change (EAPC) and examined variations and associations in LC burden across regions, sociodemographic index (SDI) categories, and age groups., Results: In 2021, the global age-standardized incidence rate (ASIR) for LC was 2.293 (95% UI: 2.133-2.466), the age-standardized death rate (ASDR) was 1.35 (1.259-1.449), and the age-standardized DALYs rate was 35.803 (33.294-38.538). The EAPCs for ASIR, ASDR, and age-standardized DALYs were -1.089, -1.659, and -1.816, respectively. The ASIR was positively correlated with the SDI (R = 0.32, P < 0.05). The Caribbean had the highest ASDR (2.69) and second-highest EAPC of ASDR (-0.151). Tobacco accounted for 66.46% of global LC deaths, with a decreasing trend over the last 30 years (R = -1, P < 0.05). Conversely, occupational exposure among females showed an increasing trend (R = 0.61, P < 0.05). The reduction in death rate for the 80-89 years age group was nearly twice as high in the high SDI regions as in the low SDI regions (21.89% vs. 11.92%)., Conclusions: From 1990 to 2021, global LC incidence, deaths, and DALYs decreased, although regional disparities persisted. Death rates remain high in economically disadvantaged regions, especially among the elderly and females with occupational risk. Continued efforts to control tobacco use, develop equitable screening programs, and enhance occupational safety are crucial for addressing global disparities in LC outcomes., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Electroacupuncture (EA) demonstrates neuroprotective in cerebral ischemia-reperfusion (I/R) injury. N6-methyladenosine (m6A) is found to contribute to the pathogenesis of neurological conditions recently. The objective of this study is to investigate the effects of EA on m6A and related mechanism in cerebral I/R injury. After the middle cerebral artery occlusion/reperfusion (MCAO/R) operation was used to establish rat models with cerebral I/R injury, EA was applied to Baihui (GV20) and Dazhui (GV14) once daily for 7 consecutive days. Subsequently, the modified Neurological Severity Score, 2,3,5-triphenyltetrazolium chloride staining, and hematoxylin and eosin staining were performed to assess the neurological damage. To investigate the potential target, the total RNA m6A level and relevant regulators (METTL3, METTL14, WTAP, FTO, and ALKBH5) were examined. In the next step, FTO, Nrf2, NLRP3, IL-18, IL-1β, and TUNEL-positive rates were detected, while the shRNA-FTO was administered to suppress FTO expression. EA improved neurobehavioral disorders, infarct volume, and pathological damage induced by cerebral I/R injury. Mechanically, EA reduced the total RNA m6A level by selectively regulating FTO, but not METTL3, METTL14, WTAP, and ALKBH5. Furthermore, EA could enhance Nrf2 and suppress NLRP3, IL-18, IL-1β, and TUNEL-positive rates, which was reversed by the shRNA-FTO injection. Our findings indicate that EA may alleviate FTO/Nrf2/NLRP3 axis-mediated pyroptosis in cerebral I/R injury, providing a more unified understanding of the neuroprotective effects of EA. Specifically, EA intervention appears to promote the expression of FTO, leading to a reduction of m6A level, which activates Nrf2 and subsequently suppresses NLRP3-mediated pyroptosis., (Copyright © 2025 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The idiopathic pulmonary fibrosis (IPF) is a progressive and lethal interstitial lung disease with high morbidity and mortality. IPF is characterized by excessive extracellular matrix accumulation (ECM) and epithelial-mesenchymal transformation (EMT). To date, few anti-fibrotic therapeutics are available to reverse the progression of pulmonary fibrosis, and it is important to explore new profibrotic molecular regulators mediating EMT and pulmonary fibrosis., Methods: Based on our model of TGF-β1-induced EMT in BEAS-2B cells, we performed the genome-wide CRISPR/Cas9 knockout (GeCKO) screening technique, pathway and functional enrichment analysis, loss-of-function experiment, as well as other experimental techniques to comprehensively investigate profibrotic regulators contributing to EMT and the pathogenesis of pulmonary fibrosis., Results: Utilizing the GeCKO library screening, we identified 76 top molecular regulators. Ten candidate genes were subsequently confirmed by integrating the high-throughput data with findings from pathway and functional enrichment analysis. Among the candidate genes, knockout of COL20A1 and COL27A1 led to decreased mRNA expression of ECM components (Fibronectin and Collagen-I), as well as an increased rate of cell apoptosis. The mRNA expression of Collagen-I, together with the cell viability and migration, were inhibited when knocking out the WNT11 . In addition, a decrease in the protein deposition of ECM components was observed by suppressing the expression of COL20A1 , COL27A1 , and WNT11 ., Conclusion: Our study demonstrates that the COL20A1 , COL27A1 , and WNT11 serve as key profibrotic regulators of EMT. Gaining understanding and insights into these key profibrotic regulators of EMT paves the way for the discovery of new therapeutic targets against the onset and progression of IPF., 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 © 2025 Tan, Wang, Ye, Kasimu, Li, Luo, Yi and Luo.)

The third generation of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) is recommended universally as the standard treatment for non-small cell lung cancer (NSCLC) carrying the EGFR T790M mutation. With the approval of multiple third-generation EGFR-TKIs, questions have arisen regarding the differences in their efficacy and how to select the most appropriate agent for individual patients. The study reports a case of an advanced NSCLC patient with multiple brain metastases. The patient initially received the pemetrexed plus carboplatin (PC) regimen for 5 months and displayed stable disease. Upon disease progression, the patient was treated with aumolertinib as second-line treatment due to the detection of EGFR L858R and T790M mutations, but the symptoms of brain metastases deteriorated. Switching to osimertinib successfully relieved the patient's symptoms and achieved a long progression-free survival (PFS) of nearly 2 years. Leptomeningeal metastasis was then definitively diagnosed, and the patient eventually died approximately 4 months after osimertinib resistance. This case suggests that osimertinib may be a viable option for EGFR -mutant NSCLC patients after aumolertinib failure, especially for those with intracranial metastases., Competing Interests: The authors declare no conflicts of interest., (© 2025 The Author(s). Clinical Case Reports published by John Wiley & Sons Ltd.)

Objective : The study aims to explore the association between intake of dietary flavonoids and global cognition, domain-specific cognition and mild cognitive impairment (MCI) in middle-aged and older adults in China. Design : A cross-sectional study. Methods : This study used baseline data collected during 2021-2023 from the Chinese Square Dance Cohort. Dietary information was collected using a semi-quantitative food frequency questionnaire, and flavonoid intakes were calculated. Cognitive function was evaluated using a battery of neuropsychological tests, and global cognition was assessed using the composite z -score. Participants with MCI were diagnosed by Petersen's criteria. The relationship between flavonoid intake and cognitive score was determined using multiple linear regression and presented as β values with 95%CIs. The association of flavonoid intake with MCI was evaluated using logistic regression models and presented as odds ratios (ORs) with 95%CIs. Results : Among 3990 middle-aged and older participants, the median (P25-P75) age was 63 (59-67) years, and 85.05% were females. After adjusting for various covariates, compared to the lowest quartile (Q1), the highest intakes (Q4) of total flavonoids, anthocyanidins and flavan-3-ols, flavanones, flavones, flavonols, procyanidins, and isoflavones were associated with higher composite z -scores, with β values (95%CIs) of 0.12 (0.06, 0.17), 0.15 (0.10, 0.21), 0.09 (0.04, 0.15), 0.11 (0.06, 0.17), 0.08 (0.02, 0.13), 0.09 (0.03, 0.14), and 0.09 (0.04, 0.15), respectively. In addition, higher dietary intakes of anthocyanidins and isoflavones were associated with lower odds of MCI, where the corresponding ORs (95%CIs) for Q4 were 0.69 (0.51, 0.94) and 0.72 (0.54, 0.97), respectively. Conclusion : Higher flavonoid intakes were related to better cognitive function. These findings suggest a beneficial effect of flavonoid intake on the cognitive aging process.

Plant Toll/interleukin-1 receptor (TIR) domains function as NADases and ribosyl-transferases generating second messengers that trigger hypersensitive responses. TIR-X (TX) proteins contain a TIR domain with or without various C-terminal domains and lack the canonical nucleotide-binding site and leucine-rich repeat domain. In a previous study, we identified an Arabidopsis thaliana activation-tagging line with severe growth defects caused by the overexpression of the AtTX12 gene. Here, we investigated the domains and specific amino acid residues required for the growth inhibition activity of AtTX12 and its homolog AtTX11. C-terminal truncation analysis revealed that the AtTX12C173Δ mutant, lacking 30 C-terminal amino acids, retained partial activity, whereas the C163Δ, lacking 40 amino acids, lost activity entirely indicating that the fifth α-helix within the TIR domain is critical for activity, while the sixth α-helix in the extra domain is dispensable. The substitution mutagenesis revealed that residues essential for enzymatic activities (E79 for NADase, C76 for 2',3'-cAMP/cGMP synthetase), self-association (H25, E43, K142/G144, K150), and undefined roles (I97) were crucial for growth inhibition activity with varying effects. Temperature sensitivity tests revealed that the AtTX12 N36D mutant, which exhibited moderately strong growth inhibition activity at normal temperatures, became inactive under high-temperature conditions in which Enhanced Disease Susceptibility 1 (EDS1) is almost non-functional. In contrast, wild-type AtTX12 retained activity under elevated temperatures, implicating N36 in maintaining temperature-insensitive functionality. Furthermore, a slightly reduced growth inhibition phenotype induced by AtTX12 overexpression in the eds1 mutant was consistently observed under both normal and high temperatures. These results suggest that AtTX12-mediated growth inhibition integrates EDS1-dependent (temperature-sensitive) and EDS1-independent (temperature-insensitive) pathways. Our findings suggest that attenuated AtTX11/12 mutants could be used to optimize the growth-defense trade-off, enhancing plant defense with minimal growth penalties., 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 © 2025 Elsevier Inc. All rights reserved.)

Background: Anti-tuberculosis drug-induced liver injury (ATLI) is a significant adverse drug reaction with genetic susceptibility implications., Aim: This study aimed to integrate findings from systematic reviews and meta-analyses on genetic polymorphisms associated with ATLI risk, enhance evidence synthesis, and identify susceptibility gene polymorphisms linked to ATLI occurrence., Method: The protocol was registered in PROSPERO (CRD42024517311). Systematic searches of PubMed, EMBASE, Web of Science, and Cochrane Library databases were conducted to identify eligible studies from inception to February 21, 2024. Two authors independently reviewed eligibility, extracted data, and assessed quality. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to evaluate associations between genetic polymorphisms and ATLI susceptibility., Results: A total of 25 meta-analyses were included, including 57 single nucleotide polymorphisms (SNPs) in 15 candidate genes. Significant associations were found for the glutathione S-transferase M1 (GSTM1) null genotype (OR = 1.43, 95% CI: 1.18-1.73, P < 0.001) and N-acetyltransferase 2 (NAT2) polymorphisms, including rs1799929 (dominant model, OR = 1.35, 95% CI: 1.12-1.63, P < 0.001), rs1799930 (dominant model, OR = 1.43, 95% CI: 1.23-1.66, P < 0.001), rs1799931 (dominant model, OR = 1.22, 95% CI: 1.02-1.46, P = 0.03), and the slow acetylator (SA) phenotype (OR = 2.91, 95% CI: 2.43-3.49, P < 0.001). No significant association was found between the CYP2E1 RsaI/PstI polymorphism (C1/C1 genotype) and ATLI risk (dominant model, OR = 0.79, 95% CI: 0.61-1.02, P = 0.08)., Conclusion: This umbrella review confirms that the GSTM1 null genotype, NAT2 polymorphisms (rs1799929, rs1799930, rs1799931), and the slow acetylator phenotype are associated with increased ATLI risk. These findings provide a foundation for further research on genotype-guided approaches to mitigating ATLI., Competing Interests: Conflicts of interest: The authors have no conflicts of interest to declare., (© 2025. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Hypoxia, which is a common characteristic of most solid tumors, not only contributes to the immunosuppressive nature of the tumor microenvironment (TME) but also reduces the efficacy of many oxygen-depleting therapies, including photodynamic therapy (PDT). In this study, we developed acidity-responsive biodegradable iridium-coordinated (IPC) nanodrugs consisting of iridium ions, the photosensitizer chlorin e6 (Ce6), and polyvinylpyrrolidone to potentiate the effects of PDT and immunotherapy by modulating the TME. IPC nanodrugs that accumulate at high levels in tumors catalyze excess hydrogen peroxide to produce oxygen while depleting glutathione levels within cancer cells; thus, the released Ce6 is more efficient at producing reactive oxygen species (ROS) in response to laser irradiation. In addition, IPC nanodrugs alleviate tumor hypoxia, induce more immunogenic cell death by amplifying PDT responses, and synergistically inhibit tumor growth by initiating robust antitumor immunity and reversing the immunosuppressive nature of the TME. As a result, IPC nanodrugs exert pronounced combined therapeutic effects in vitro and in vivo, without obvious toxic effects due to acidity-responsive degradation. These iridium-coordinated nanodrugs have the potential to modulate the TME, amplify the effects of PDT, and substantially inhibit tumors, and they are expected to provide novel ideas for combination therapy of hypoxic cancer., 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.)

Cancer stem cells (CSCs) play an important role in the development of triple-negative breast cancer (TNBC), including metastasis, invasion, tumorigenicity, and drug resistance. Moreover, non-CSCs can spontaneously transform into CSCs in special tumor microenvironments, thereby leading to poor prognosis or even failed treatments. Therefore, reversing CSCs into normal tumor cells in a sustained-acting manner is a promising strategy. It has been reported that down-regulation of FBXO44 protein expression inhibits tumor cell stemness. Moreover, CRISPR/Cas9 technology, a well-known precise gene editing tool, was adopted to permanently block FBXO44 within the genome upon its successful implementation. Given this, a core-shell nanoparticle (NP) consisting of amphiphilic polymer core and crosslinked-hyaluronic acid shell (nDOX-PL/pFBXO44 NPs) is developed in this work to concurrently deliver FBXO44-targeted CRISPR/Cas9 plasmids (pFBXO44) and doxorubicin (DOX) for combinational CSC reprogramming and chemotherapy of TNBC, which exhibits tumor cell targeting, endosomal escape, and reduction responsiveness to release DOX and plasmids in the cytoplasma. CRISPR/Cas9-mediated downregulation of FBXO44 expression could convert CSC into normal tumor cells, and effectively inhibit tumor growth without obvious side effects in vivo after combining with chemotherapy. In summary, we developed an intelligent system to co-deliver genetic and hydrophobic drugs, achieving effective cancer stemness reversal and synergistic suppression of contractable TNBC., Competing Interests: Declaration of competing interest The authors declare no competing financial interest., (Copyright © 2024. Published by Elsevier B.V.)

The isolation of nucleophilic boron bases has led to a paradigm shift in boron chemistry. Previous studies of the bis(carbene) borylene complexes revealed that these compounds possess strong donor abilities, and their reaction inertness is due to the large steric hindrance between boron reagents and reactant. In the present study, we have theoretically studied the [(N 5 ) 2 BX] 2- and [(N 5 ) 2 B 2 X 2 ] 2- compounds (X = H, F, Cl, Br). Their electronic structures and properties are discussed by using the NBO, LOL, and ELF methods. We found that both π-conjugation and hyperconjugation effects can effectively stabilize the substituted nucleophilic anionic boron compounds [(N 5 ) 2 BX] 2- and [(N 5 ) 2 B 2 X 2 ] 2- . Substituents, especially X = H, stabilize the boron center through highly delocalized π-bonding, involving the formally "empty" in-plane p orbitals of the boron atom. While the halogen substituents have high electron withdrawal ability, leading to systems being less stable, we suggest the borinium anions [(N 5 ) 2 BH] 2- and [(N 5 ) 2 B 2 H 2 ] 2- as possible synthetic targets of novel environmentally friendly catalysts.

Background: Single-cell technologies enable comprehensive profiling of diverse immune cell-types through the measurement of multiple genes or proteins per individual cell. In order to translate immune signatures assayed from blood or tissue into powerful diagnostics, machine learning approaches are often employed to compute immunological summaries or per-sample featurizations, which can be used as inputs to models for outcomes of interest. Current supervised learning approaches for computing per-sample representations are trained only to accurately predict a single outcome and do not take into account relevant additional clinical features or covariates that are likely to also be measured for each sample., Results: Here, we introduce a novel approach for incorporating measured covariates in optimizing model parameters to ultimately specify per-sample encodings that accurately affect both immune signatures and additional clinical information. Our introduced method CytoCoSet is a set-based encoding method for learning per-sample featurizations, which formulates a loss function with an additional triplet term penalizing samples with similar covariates from having disparate embedding results in per-sample representations., Conclusions: Overall, incorporating clinical covariates enables the learning of encodings for each individual sample that ultimately improve prediction of clinical outcome. This integration of information disparate more robust predictions of clinical phenotypes and holds significant potential for enhancing diagnostic and treatment strategies., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: Not applicable., (© 2025. The Author(s).)

Janus hydrogels have promising applications in tendon healing and anti-peritendinous adhesions. However, their complicated preparation methods, weak mechanical properties, and unstable adhesion interfaces have severely limited their application in suture-free and high-quality tendon healing. In this work, by controlling the interfacial distribution of free -COOH groups and cationic-π structures on both sides of the hydrogels, a series of PZBA-EGCG-ALC Janus hydrogels with varying degrees of asymmetric properties are successfully prepared using a simple and efficient one-step synthesis method. The tensile strength and elongation at the break of the Janus hydrogel are as high as 0.51 ± 0.04 MPa and 922.89 ± 28.59%. In addition, the Janus hydrogel can achieve a high difference in adhesion strength (nearly 20-fold) while maintaining a strong adhesion strength on their bottom sides (up to 524.8 ± 33.1 J m -2 ). In the spatial dimension, its excellent mechanical compliance and one-sided adhesion behavior can provide effective mechanical support and physical barriers for the injured Achilles tendons. More importantly, the Janus hydrogel can also minimize early inflammation generation in the time dimension via its ROS-responsive PZBA-EGCG prodrug macromolecules. This study provided a more effective and convenient suture-free strategy for constructing Janus hydrogels to promote high-quality tendon healing., (© 2025 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

In the context of Industry 4.0, addressing the challenge of dynamic obstacle avoidance for Automated Guided Vehicles (AGVs) in complex industrial environments, this paper proposes an algorithm that integrates an enhanced social force model (SFM) and an improved dynamic window approach (DWA), leveraging SparkLink communication technology to enhance data transmission speed and reliability. The introduction of SparkLink technology significantly improves the environmental perception capabilities of AGVs, optimizing their dynamic obstacle-avoidance performance. Experimental results demonstrate that this method effectively increases the efficiency of AGVs in dynamic obstacle avoidance, offering significant practical value.

We present results over an 11-year Solar cycle of cosmic antiprotons based on 1.1×10^{6} events in the rigidity range from 1.00 to 41.9 GV. The p[over ¯] fluxes exhibit distinct properties. The magnitude of the p[over ¯] flux temporal variation is significantly smaller than those of p, e^{-}, and e^{+}. A hysteresis between the p[over ¯] fluxes and the p fluxes is observed, whereas the p[over ¯] and e^{-} fluxes show a linear correlation. With a model-independent analysis, we found a universal relation between the shape of the rigidity spectrum and the magnitude of flux temporal variation over an 11-year Solar cycle for both positively and negatively charged particles. The simultaneous results on p[over ¯] and p, e^{-}, and e^{+} provide unique information for understanding particle transport in the Solar System as a function of mass, charge, and spectral shape.

We report the properties of precision time structures of cosmic nuclei He, Li, Be, B, C, N, and O fluxes over an 11-year solar cycle from May 2011 to November 2022 in the rigidity range from 1.92 to 60.3 GV. The nuclei fluxes show similar but not identical time variations with amplitudes decreasing with increasing rigidity. In particular, below 3.64 GV the Li, Be, and B fluxes, and below 2.15 GV the C, N, and O fluxes, are significantly less affected by solar modulation than the He flux. We observe that these differences in solar modulation are linearly correlated with the differences in the spectral indices of the cosmic nuclei fluxes. This shows, in a model-independent way, that solar modulation of galactic cosmic nuclei depends on their spectral shape. In addition, solar modulation differences due to nuclei velocity dependence on the mass-to-charge ratio (A/Z) are not observed.

Polysaccharides as modifiers can solve native starch gel problem of weaker gel strength and lower gelation trend. The key structures of foxtail millet bran polysaccharides (FMBPs) in improving millet starch gel properties were investigated. Results showed that FMBPs were high molecular weight (Mw) heteropolysaccharides and the distribution of total sugar, uronic acid and monosaccharides was non-uniform in four FMBPs. Structural analysis revealed triple helix polysaccharides (THPs) existed in independent triple helix (ITH) and aggregates forms. The redshift degree of Congo red-FMBP complexes illustrated that FMBP-S1 contain the most ITHs, followed by FMBP-S2 and FMBP-S4, and the least in FMBP-S3. The porous structure of FMBPs promoted the adsorption of Congo red, bringing about the increase in weight and volume of the complexes and eventual precipitation. Separation of THPs provided a new method to investigate its role in starch gel. The results showed FMBPs with more ITHs showed higher peak viscosity, breakdown and setback. The presence of ITHs could reduce gel point temperature (ΔT = 6.62-29.86 °C) and water holding capacity (from 50 to 66 ms to 231 ms), but improve the viscoelasticity of gel. The study not only improved the quality of starch-based gel but also achieved high-value utilization of foxtail millet bran., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2025. Published by Elsevier B.V.)

The microstructure of 40CrMnMoA during hot forging determines its macroscopic mechanical properties. Dynamic recrystallization (DRX) behavior is commonly used to refine grains and improve the microstructure of materials; therefore, it is important to be able to predict mechanical behavior during hot forging and the microstructure evolution during dynamic recrystallization. In order to accurately determine the DRX model parameters of 40CrMnMoA steel, an inverse optimization method is proposed in this work. The uniaxial isothermal compression experiment of 40CrMnMoA steel was carried out on a Gleeble-1500D thermal simulation tester (Dynamic Systems Inc. (DSI), Poestenkill, NY, USA) under the temperature range of 900~1200 °C and the strain rate range of 0.005 to 5 s -1 . Based on the true stress-strain data obtained by a compression test, the DRX model of 40CrMnMoA was initially established using the traditional averaging method. Subsequently, the DRX model parameters calculated by the conventional averaging method were used as the initial values, the mean-square error between the experimental and calculated values of the DRX volume fraction was set as the objective function, and the DRX model parameters were optimized by the adaptive simulated annealing (ASA) algorithm. By comparing the correlation coefficient R , average absolute relative error ( AARE ), and the root mean square error ( RMSE ) of the predicted DRX percentage with the experimental values before and after optimization, it was found that the optimized model achieved an R -value of 0.992, with AARE and RMSE decreased by 34% and 2%, respectively, which verified the accuracy of the optimized DRX model. Through the program's secondary development, the optimized DRX model of 40CrMnMoA was integrated into finite element software Forge ® 3.2 to simulate the isothermal compression process. The comparison between grain size from the central region of simulation results and actual samples revealed that the relative error is less than 3%. This result demonstrated that the inverse optimization method can accurately identify the DRX model parameters of 40CrMnMoA alloy steel., Competing Interests: The authors declare no conflicts of interest.

Recent advances in developing photonic technologies using various materials offer enhanced biosensing, therapeutic intervention, and non-invasive imaging in healthcare. Here, this article summarizes significant technological advancements in materials, photonic devices, and bio-interfaced systems, which demonstrate successful applications for impacting human healthcare via improved therapies, advanced diagnostics, and on-skin health monitoring. The details of required materials, necessary properties, and device configurations are described for next-generation healthcare systems, followed by an explanation of the working principles of light-based therapeutics and diagnostics. Next, this paper shares the recent examples of integrated photonic systems focusing on translation and immediate applications for clinical studies. In addition, the limitations of existing materials and devices and future directions for smart photonic systems are discussed. Collectively, this review article summarizes the recent focus and trends of technological advancements in developing new nanomaterials, light delivery methods, system designs, mechanical structures, material functionalization, and integrated photonic systems to advance human healthcare and digital healthcare., (© 2025 The Author(s). Advanced Materials published by Wiley‐VCH GmbH.)

Background: Barriers to the diagnosis and treatment of rifampicin-resistant TB (RR-TB) have not been fully elucidated. This study aimed to map the diagnostic and treatment delays among patients with RR-TB in China and investigate related factors., Methods: Between June and July 2023, the diagnostic and treatment pathways of patients with RR-TB were obtained through interviews at eight hospitals across China. Information on the TB service of hospitals was collected via telephone., Results: Ninety-eight patients were included. On average, each patient required 4.6 visits to start RR-TB treatment. The median delay from illness onset to RR-TB treatment was 238.0 days (IQR 85.8-469.2), primarily driven by the delay between TB diagnosis and identifying rifampicin (RIF) resistance (median: 43.5 days, IQR 3.0-160.5). Referral to appropriate hospitals (adjusted hazard ratio [aHR] 2.32; 95% CI 1.37-3.92) or considering drug susceptibility testing (DST) when initiating treatment (aHR 2.56, 95% CI 1.39-4.72) significantly reduced delay between TB diagnosis and identifying RIF resistance, while stigma regarding TB (aHR 0.61, 95% CI 0.38-0.98) was an independent risk factor., Conclusions: Patients with RR-TB experienced substantial delays in identifying RIF resistance. Referring patients to hospitals with molecular DST capabilities and awareness may reduce these delays., Competing Interests: Conflict of interest: none declared., (© 2025 The Authors.)

Suantangzi is a fermented corn food product with Manchu characteristics from Liaoning Province, China. To analyze the microbial diversity and flavor compounds in Suantangzi dough, this study utilized high-throughput sequencing of the 16S rRNA and internal transcribed spacer regions, high-performance liquid chromatography, and gas chromatography time-of-flight mass spectrometry. Spearman correlation analysis and random forest model were conducted to investigate the correlation between the dominant genera and flavor compounds. A total of 267 and 123 bacterial and fungal genera, respectively, were identified. Flavor compound analysis identified 7 and 156 organic acids and other flavor compounds, respectively, and partial least squares discriminant analysis was used to screen 22 differential flavor compounds. Additionally, Paucilactobacillus, Pediococcus, and Tausonia genera were speculated to produce different flavors in Suantangzi dough made in different regions. These findings provide a theoretical foundation for microbial community dynamics and the formation of key flavor compounds in Suantangzi dough., 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.)

High concentrations of nitrite stress aquatic animals, leading to significant fish and shrimp deaths as well as environmental pollution. Reducing nitrite levels in high-density aquaculture is crucial for both aquaculture safety and environmental protection. Nitrite reductase (NiR) can rapidly reduce nitrite in water, offering potential applications in aquaculture and water treatment. In this study, a novel NiR gene (nasD) was isolated from Bacillus velezensis GXMZU-B1, a highly effective nitrite-degrading bacterium, and expressed heterologously in Escherichia coli. The recombinant NASD was purified using Ni-NTA affinity chromatography, and its physicochemical properties and reaction products were analyzed. The enzyme showed optimal activity at 30°C and pH 6.5. Metal ions such as Fe 3+ , Zn 2+ , and Ba 2+ enhanced enzyme activity, whereas Cu 2+ , K + , Mg 2+ , and Mn 2+ reduced it. The best electron donors was NADPH. NASD converts nitrite (NO 2 - ) into ammonium (NH 4 + ), making it environmentally friendly and potentially valuable for aquaculture and water pollution control. Bioinformatics analysis indicated that the enzyme is stable, with a conserved sequence and a Pyr&#95;redox&#95;2 domain. Using NADPH as a coenzyme, AlphaFold3 modeling and molecular docking with nitrite identified 14 potential catalytic sites. These findings highlight the potential of recombinant NASD as a promising candidate for nitrite degradation in aquaculture., 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.)

The accumulation of protoporphyrin IX in the liver caused by isoniazid and rifampicin through the disorder of heme biosynthesis was considered an important mechanism of anti-tuberculosis drug-induced liver injury (ATLI). Alanine synthase 1 (ALAS1) is a rate-limiting enzyme in the process of heme synthesis. This study aimed to investigate the association between ALAS1 gene polymorphism, serum ALAS1 level, and the risk of ATLI. This study was a case-control study including 58 ATLI cases and 192 controls. Four single nucleotide polymorphisms (SNPs) of the ALAS1 gene were selected for genotyping and serum ALAS1 concentrations were detected using ELISA kits. There was no significant difference in the genotype distribution of four SNPs between the ATLI cases and the controls under different genetic models. Patients carrying the GG genotype of SNP rs352163 in controls had higher baseline ALAS1 levels than those in ATLI cases (243.6 vs 290.2 ng/L, P = .034), and patients with baseline ALAS1 < 337.85 ng/L had a higher risk of ATLI than those with ALAS1 ≥ 337.85 ng/L (HR = 2.679, 95% CI: 1.360-5.278, P = .004). Our findings indicated that the serum ALAS1 concentrations in the ATLI cases were lower than those in the controls, and the lower baseline ALAS1 levels can be associated with higher ATLI risk., (© 2024, The American College of Clinical Pharmacology.)

In the selective catalytic reduction of NOx by NH 3 (NH 3 -SCR), conventional Mn-based denitration catalysts often suffered from susceptibility to poisoning by alkali and alkaline earth metals, this paper presented an innovative self-protected Chlorella@Mn denitration catalyst. Remarkably, in the presence of high concentrations (2 wt%) of alkali and alkaline earth metal oxides, the Chlorella@Mn catalyst sustained a NOx conversion exceeding 96 % at 175 °C. At an even higher concentration (4 wt%), NOx conversion above 90 % at 175 °C, surface analysis revealed that POMn sites acted as sacrificial sites, binding to the alkali and alkaline earth metals, the Chlorella@Mn catalyst surface naturally carried a spectrum of acidic species (such as SO 4 2- , PO 3 - , SiO 3 2- ), proficient in capturing alkali/alkaline earth metal effectively, elements such as S, P, and Si formed bonds with K, Na, Ca, and Mg. The synergistic protection of the active sites and the surface elements avoided the deactivation of the catalyst. The detrimental effects of high concentrations of alkali and alkaline earth metals were primarily due to promoting an excessively high valence state of Mn on the catalyst surface and the reduction or loss of NH 3 adsorption and activation at Brønsted acid sites. This research provided valuable insights for advancing the development of low-temperature denitration catalysts with improved resistance to alkali and alkaline earth metal poisoning., 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.)

Cancer immunotherapy holds significant promise for improving cancer treatment efficacy; however, the low response rate remains a considerable challenge. To overcome this limitation, advanced catalytic materials offer potential in augmenting catalytic immunotherapy by modulating the immunosuppressive tumor microenvironment (TME) through precise biochemical reactions. Achieving optimal targeting precision and therapeutic efficacy necessitates a thorough understanding of the properties and underlying mechanisms of tumor-targeted catalytic materials. This review provides a comprehensive and systematic overview of recent advancements in tumor-targeted catalytic materials and their critical role in enhancing catalytic immunotherapy. It highlights the types of catalytic reactions, the construction strategies of catalytic materials, and their fundamental mechanisms for tumor targeting, including passive, bioactive, stimuli-responsive, and biomimetic targeting approaches. Furthermore, this review outlines various tumor-specific targeting strategies, encompassing tumor tissue, tumor cell, exogenous stimuli-responsive, TME-responsive, and cellular TME targeting strategies. Finally, the discussion addresses the challenges and future perspectives for transitioning catalytic materials into clinical applications, offering insights that pave the way for next-generation cancer therapies and provide substantial benefits to patients in clinical settings., (© 2024 Wiley‐VCH GmbH.)

Hainan Island, the largest tropical island in China, is a notable source of pollutants, with a significant proportion of terrigenous contaminants discharged into the ocean. Platinum group elements (PGEs) pose potential risks to both the environment and human health, but research on this topic remains limited. In this study, we analyzed water from Hainan Island offshore area to investigate distribution characteristics of PGEs and its trend into the sea. It is found that the concentration of dissolved PGEs (PGEs D ) is Pd D  > Rh D  > Pt D , and the concentration of suspended particular PGEs (PGEs P ) is Pd P  > Pt P  > Rh P . Concentrations of PGEs are generally lower in the western part of the island compared to the east, due to differences in climate, regional development, and coastal zone types, and the high concentration of PGEs is relatively concentrated in the estuary-offshore of large rivers. Affected by the physical and chemical properties of the water, hydrodynamic conditions and the shape of the estuary, the average concentration of PGEs D increased greatly at first and then decreased slowly from the estuary to the offshore as the average concentration of PGEs P showed a slow decreasing trend. According to the K d , Pd and Rh mainly exist in dissolved state, while Pt mainly exists in suspended state. It is calculated that Hainan Island annually discharges an average of Pd 787.98 kg, Rh 33.14 kg, and Pt 193.48 kg into the sea. This study further expands and deepens the research on the environmental geochemical process of new pollutant PGEs., 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 © 2025 Elsevier B.V. All rights reserved.)

Competing Interests: Competing interests: The authors declare no competing interests. Ethics approval and consent to participate: Research involving human material and data was conducted by the procedures approved by the Institutional Review Board of Ruijin Hospital, affiliated with Shanghai Jiao Tong University School of Medicine (2021/154). Materials and data were collected after obtaining informed consent from all study participants.

Background: Our previous animal study revealed that supplementation with milk fat globule membrane (MFGM) alleviated Alzheimer's disease pathology in mice. We hypothesized that supplementation with whey protein powder rich in MFGM, taurine, and B vitamins would improve cognitive function in subjects with mild cognitive impairment (MCI)., Objectives: We conducted a 12-mo randomized controlled trial to investigate the effects of whey protein powder on cognitive function in older adults with MCI., Methods: Participants were randomly assigned in a 1:1 ratio to either the active intervention group (whey protein powder, 15 g/d) or the control group (placebo, 15 g/d). We performed comprehensive cognitive function tests at baseline, 6 mo, and 12 mo. The primary outcome was global cognitive function determined by the Montreal Cognitive Assessment (MoCA). Secondary outcomes included other cognitive subdomains, and body composition. The data were analyzed using the intention-to-treat (ITT) principle., Results: A total of 107 participants [mean (standard deviation) age 62.94 (4.33) y] were randomly assigned to the active intervention group (n = 53), or control group (n = 54). In the ITT analysis, the mean change in MoCA score at 12 mo was 3.23 [95% confidence interval (CI): 2.17, 4.30] in the active intervention group and 1.42 (95% CI: 0.36, 2.48) in the control group, with the mean difference between groups (group × time interaction) in change of MoCA score was 1.81 (95% CI: 0.32, 3.30). The modified ITT and per-protocol analyses showed similar results. The results also found a significant beneficial effect of the active intervention for several secondary cognitive outcomes such as Digit Symbol Substitution Test score, and the mean difference between groups in the ITT analysis was 2.72 (95% CI: 0.20, 5.23). Few side effects were reported during the study, and there was no statistically significant difference between groups (P = 0.74)., Conclusions: Supplementation with whey protein powder rich in MFGM, taurine, and B vitamins for 12 mo improve cognitive function in older adults with MCI. This trial was registered at the https://www.chictr.org.cn/showproj.html?proj=150871 as ChiCTR2200062705., Competing Interests: Conflict of interest This study was supported by BYHEALTH Co. Ltd. RKH and ZBY are employed by BYHEALTH Co. Ltd. The remaining authors declare no conflicts of interest. Any findings, conclusions, or recommendations expressed in this manuscript are those of the authors and do not reflect the views of BYHEALTH Co. Ltd., (Copyright © 2024 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Hemophilia A (HA) is caused by mutations in coagulation factor VIII (FVIII). Genome editing in conjunction with patient-derived induced pluripotent stem cells (iPSCs) is a promising cell therapy strategy, as it replaces dysfunctional proteins resulting from genetic mutations with normal proteins. However, the low expression level and short half-life of FVIII still remain significant limiting factors in the efficacy of these approaches in HA. Here, we constructed a functionally enhanced FVIII variant, F309S/E1984V-mutated B domain-deleted (BDD)-FVIII (FE-FVIII), with increased activity and stability. We inserted FE-FVIII with a human elongation factor-1 alpha (EF1α) promoter into the AAVS1 locus of HA patient-derived iPSCs via CRISPR/Cas9 (D10A) nickase to ensure expression in any cell type. FE-FVIII was expressed not only in undifferentiated FE-FVIII-inserted (FE-KI) iPSCs but also in endothelial cells (ECs) differentiated from them in vitro. Compared with mice transplanted with wild-type BDD-FVIII-containing ECs, immunocompetent HA mice intravenously transplanted with FE-KI ECs presented a 2.12-fold increase in FVIII activity in the blood and an approximately 20% greater survival rate after hemorrhagic tail injury. For sustained efficacy, FE-KI ECs were subcutaneously transplanted into immunodeficient HA mice, resulting in amelioration of the hemophilia phenotype for more than 3 months. This strategy can improve FVIII function and may provide a universal therapeutic approach for treating HA., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)