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A prolific multi-product sesterterpene synthase CbTPS1 is characterized from the medicinal Brassicaceae plant Capsella bursa-pastoris. Twenty different sesterterpenes including 16 undescribed compounds, possessing 10 different mono-/di-/tri-/tetra-/penta-carbocyclic skeletons, including the unique 15-membered macrocyclic and 24(15→14)-abeo-capbuane scaffolds, are isolated and structurally elucidated from engineered Escherichia coli strains expressing CbTPS1. Site-directed mutagenesis assisted by molecular dynamics simulations resulted in the variant L354M with up to 13.2-fold increased sesterterpene production. These structurally diverse products suggest a comprehensive cyclization mechanism for plant sesterterpenes and provide compelling evidence for the initial cyclization of geranylfarnesyl diphosphate via a crucial 15-membered monocyclic carbocation. The activities of these sesterterpenes against liver fibrosis is inferred from the inhibition of the transforming growth factor-β/Smad signaling pathway and collagen synthesis. These findings greatly expand the chemical space and biological functions of sesterterpenes and provide new insights into the catalytic mechanism of terpene synthases., (© 2025 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Background: Vonoprazan and amoxicillin (VA) dual therapy as a mainstream Helicobacter pylori regimen has gained momentum worldwide, but the optimum dosages remain unclear. We aimed to compare the efficacy and safety of VA dual therapy with 2 g amoxicillin or 3 g amoxicillin, and to assess the short-term effects of therapy on the gut microbiota and antibiotic resistome., Methods: We conducted an open-label, non-inferiority randomised controlled trial at 12 centres in China. Individuals infected with H pylori, aged 18-70 years, and without previous eradication therapy were recruited. Participants were randomly assigned at a 1:1 ratio (block size of six) to receive vonoprazan (20 mg twice a day) with either low-dose amoxicillin (1 g twice a day; LVA therapy) or high-dose amoxicillin (1 g three times a day; HVA therapy) for 14 days. Gastric biopsies were collected before treatment for detection of antibiotic resistance. Stool samples were collected at baseline, week 2, and week 8-10 for shotgun metagenomic sequencing. The primary outcome was the eradication rate of H pylori, assessed by 13 C urea breath test, in both intention-to-treat and per-protocol analyses. Secondary outcomes were adverse events, adherence, antibiotic resistance, and alterations to the gut microbiota and antibiotic resistome. The margin used to establish non-inferiority was -0·10. The trial was registered with ClinicalTrials.gov, NCT05649709., Findings: Between Feb 13, 2023, and Jan 25, 2024, 504 patients (204 [40%] male and 300 [60%] female; mean age 43 years [SD 13]) were randomly assigned to LVA therapy or HVA therapy (n=252 in each group). No infections were resistant to amoxicillin. The H pylori eradication rate was 85·3% (215 of 252; 95% CI 80·4 to 89·2) in the LVA group and 86·5% (218 of 252; 81·7 to 90·2) in the HVA group in the intention-to-treat analysis (p=0·70) and 88·8% (213 of 240; 84·1 to 92·2) and 92·4% (218 of 236; 88·3 to 95·1), respectively, in the per-protocol analysis (p=0·18). The efficacy of LVA was non-inferior to HVA in the intention-to-treat analysis (risk difference -1·2%, 95% CI -7·3 to 4·9, p=0·0022) and the per-protocol analysis (-3·6%, -9·0 to 1·7, p=0·0085). 31 (12%) patients in the LVA group and 43 (17%) patients in the HVA group reported adverse events. Adherence to therapy was 97% in the LVA group and 96% in the HVA group. The diversity of gut microbiota decreased after treatment but was restored to baseline at week 8-10 in both groups. The abundance of beta-lactam-related resistance genes was increased at week 2 after treatment, and was restored to pretreatment level at week 8-10 for the LVA group but not the HVA group., Interpretation: LVA dual therapy was effective and non-inferior to HVA dual therapy as first-line treatment of H pylori infection and showed a non-lasting effect on the abundance of beta-lactam-related resistance genes. High amoxicillin dosage (eg, 3 g per day) is not required to achieve high cure rates with vonoprazan dual therapy., Funding: National Natural Science Foundation of China, Project for Academic and Technical Leaders of Major Disciplines in Jiangxi Province, and Key Research and Development Program of Jiangxi Province., Competing Interests: Declaration of interests DYG is a consultant with Janssen Research & Development regarding potential gastrointestinal effects of drugs under development and has collaborated on research projects with American Molecular regarding molecular diagnostics for H pylori. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Submerged macrophytes in constructed wetlands (CWs) can effectively improve wastewater quality. However, the effectiveness of different submerged macrophytes in removing antibiotic-resistant genes (ARGs) from wastewater remains unexplored. Additionally, wastewater loading in wetlands can fluctuate due to climate change, potentially affecting ARG removal efficiency. In this study, we systematically constructed microscale wetlands using three submerged plants: Vallisneria natans (VN), Sagittaria pygmaea (SP), and Myriophyllum spicatum (MS). Their effectiveness in ARGs removal was analyzed at hydraulic retention times (HRTs) of 0, 3, 6, and 9 days under high (HWL) and low (LWL) wastewater loading. The results indicated that under LWL conditions, all ecosystems exhibited a higher reduction rate of ARG diversity and relative abundance (RS) compared to HWL conditions. The efficiency of all ecosystems in reducing ARG diversity and abundance followed the order: MS > VN > SP. The sul resistance gene exhibited the highest RS and was degraded most rapidly in all samples. Additionally, sulfadimidine concentrations significantly decreased under LWL conditions, which was significantly correlated with sul reduction. Chemical oxygen demand, total phosphorus, total nitrogen, ammonium nitrogen, and nitrate nitrogen were identified as key factors influencing bacterial and ARG profiles. The increase in rhizobial bacteria and decrease in aerobic denitrifying bacteria likely contributed significantly to ARGs removal. This study offers new insights into ARG removal by submerged macrophytes in CWs, emphasizing the role of wastewater loading and the potential of MS in enhancing ARG degradation. These findings enhance CW design and management to mitigate ARG contamination in wastewater., 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.)

Background: The association of the p53 rs1042522 and rs17878362 polymorphisms with cervical cancer risk has been reported in several published original studies and meta-analyses. However, the conclusions of these studies were contradictory. Consequently, we conducted an updated meta-analysis to further validate these debates., Objective: To evaluate the association between the p53 rs1042522 and rs17878362 polymorphisms and cervical cancer risk., Materials and Methods: PubMed, Medline, Ovid, Embase, CNKI, and China Wanfang databases were searched. Association was assessed using odds ratio (OR) with 95% confidence interval (CI). Moreover, the false-positive reporting probability (FPRP), Bayesian false-finding probability (BFDP), and Venice criteria were used to assess the credibility of statistically significant association., Results: A significantly decreased cervical cancer risk was revealed for the p53 rs1042522 polymorphism (Pro/Pro +Arg/Pro vs. Arg/Arg: OR = 0.79, 95% CI = 0.71-0.87; Pro/Pro vs. Arg/Arg: OR = 0.80, 95% CI = 0.70-0.91; Arg/Pro vs. Arg/Arg: OR = 0.78, 95% CI = 0.71-0.86; Pro vs. Arg: OR = 0.87, 95% CI = 0.81-0.93) in overall analysis and several subgroup analyses, such as in Caucasians, Asians, Indians, and so on. However, no significant association was found between the p53 rs17878362 polymorphism and cervical cancer risk. Despite these statistically significant results, reliability analysis using FPRP, BFDP, and Venice criteria deemed all associations "unreliable"., Conclusions: After considering the reliability of the results, this study indicates that the p53 rs1042522 polymorphism is not associated with the cervical cancer risk., 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 Zhang, Bai, Zhang and He.)

Polynuclear Au(I) cluster photocatalysts, known for their high activity and stability, hold substantial potential in organic synthetic chemistry. This study synthesized two Au(I) supramolecular cluster catalysts with different nuclearities: a tetranuclear cluster, C1 ([(dppmAu 2 ) 2 L 1 ] • PF 6 - ), and a hexadecanuclear cluster, C2 [(dppmAu 2 ) 6 (Au 4 )(L 1 ) 4 ] • 4PF 6 - , through a multicomponent stepwise self-assembly approach. Both cluster structures feature aurophilicity interaction motifs that endow them with exceptional photocatalytic performance, exhibiting optical band gaps of 2.27 eV and 2.41 eV, respectively. Upon photoexcitation, these clusters efficiently generate reactive oxygen species, significantly enhancing their photocatalytic efficacy for the oxidative hydroxylation of phenylboronic acids and oxidative coupling of benzylamines under mild conditions. Catalytic efficiencies exceeding 90 % were achieved. Turnover frequencies for C2 and C1 were measured at 52.045 h -1 and 6.030 h -1 , respectively, representing the highest efficiencies reported for photocatalysts to date. Compared to C1, C2 exhibited superior photocatalytic activity, attributed to its higher photoelectric sensitivity and greater exposure of active metal sites. Using a combination of experimental data and density functional theory calculations, the plausible mechanisms were proposed for two photocatalytic reactions. This study demonstrates that the use of multicomponent cooperative self-assembly strategy to synthesize high-nuclearity Au(I) clusters offers innovative pathways for the development of efficient, green, light-driven organic synthesis., (© 2024 Wiley-VCH GmbH.)

This study aimed to manage Helicobacter pylori (H. pylori) infection through a family-centered approach. It conducted a two-year follow-up on infected individuals' family members in Yichun, Jiangxi, China, to gain comprehensive insights into the transmission dynamics, treatment adherence, and associated risk factors of H. pylori within households. A retrospective analysis was performed on the data obtained from households in Yichun City that participated in the nationwide multicenter H. pylori prevalence study in 2021, along with the corresponding subsequent follow-up data. The collected information encompassed fundamental demographic details of the families, their lifestyle patterns, and the status of H. pylori infection. Among 514 households, 222 comprised two individuals, whereas 68 constituted larger families with five or more members. All member was infected in 9.34% of households. Larger family sizes (≥ 5 individuals) and higher generational counts were closely associated with H. pylori infection (e.g., family size > 6: OR 4.46, 95%CI 1.29 to 15.46). Adult age, marital status, and household members' infections were identified as primary risk factors (e.g., married individuals: OR 2.03, 95%CI 1.56 to 2.65). Students and previously uninfected individuals exhibited lower infection risks (e.g., tested as negative: OR 0.48, 95%CI 0.31 to 0.73). Maternal, paternal, or sibling infections were linked to increased risks of child infections (e.g., mother infected: OR 2.58 95%CI 1.37 to 4.87). Successful eradication in ≥ 2 individuals reduced the infection risk for other members (OR 0.25, 95%CI (0.07 to 0.89). H. pylori displayed noticeable clustering infection characteristics within families. This study lends support to family-based management strategies, but given suboptimal adherence to household management, there is a need to enhance education on the hazards of H. pylori before implementing screening programs., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: Vaccinium dunalianum ("Que Zui Tea") has been traditionally consumed as a tea substitute in Yunnan, China, for its health benefits, i.e., improving vascular health. 6'-O-caffeoylarbutin (CA) is its major bioactive compound (∼20 %). However, the potential of CA against ischemic stroke remains unknown., Purpose: This study explores the protective properties of CA in ischemic stroke, providing empirical support for the folk use of the plant and further drug development., Methods: An oxygen-glucose deprivation/reoxygenation (OGD/R)-induced BV2 cells were utilized to identify potential bioactive compounds. Moreover, the pathway and targets were predicted and further verified in OGD/R-induced microglia, nerve cells and in mice of middle cerebral artery occlusion., Results: CA effectively reduced nitric oxide (NO) release and transcript-level expression of inflammatory factors in OGD/R-stimulated BV2 cells. NF-κB1, IL-6, AKT1, CASP3, and MMP9 were identified as key CA targets for ischemic stroke treatment. In silico predictions suggested that phosphatidylinositol 3-kinase (PI3K)/protein kinase B (PI3K/AKT), mitogen-activated protein kinase (MAPK), and tumor necrosis factor (TNF) were the relevant pathways. These predictions were supported in vitro by an observed decrease in NO, reactive oxygen species, lactate dehydrogenase, and inflammatory cytokines (IL-6, IL-1β, and TNF-α) levels following CA treatment. Western blotting confirmed the regulation of p-IκBα, P65, AKT, and apoptosis-related proteins (further confirmed by PI3K inhibitor LY294002 treatment). These findings were further supported in vivo, with CA ameliorating neurological functions and deficits in ischemic mice. This amelioration correlated with increased cerebral blood flow, and alleviated neuron wrinkling, necrosis, and cell shrinkage. CA also increased brain superoxide dismutase, catalase, and glutathione peroxidase levels., Conclusion: CA exerts neuroprotective effects in ischemic stroke by inhibiting inflammation and oxidative stress through the PI3K/AKT/NF-κB pathway, suggesting its therapeutic potential for cerebral ischemia and supporting the traditional use of V. dunalianum., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2025 Elsevier GmbH. All rights reserved.)

Ultraviolet absorbents （UVAs） are common additives in personal care and industrial products. Due to their pseudo-persistence, bioaccumulation, and toxicity, environmental pollution and the risks associated with UVAs have raised widespread concern. However, current understanding of the pollution characteristics and ecological risks of UVAs in urban aquatic environments is still limited. To investigate the occurrence, composition, and spatial distribution characteristics of UVAs in the aquatic environment, eight UVAs in 40 paired water and suspended particulate matter （SPM） samples in the Guangzhou reach of the Pearl River were analyzed, and their potential aquatic ecological risks were further assessed using risk quotients. The results showed that UVAs were widely detected in the aqueous and SPM phases of the Guangzhou reach of the Pearl River, with total concentrations （∑ 8 UVA, range and mean ± standard deviation，ng·L -1 ) of 6.52-85.8 （2.80 ± 6.34） and 5.69-461 （6.57 ± 34.1）, respectively. The concentrations of individual UVAs in the aqueous phase accounted for 16% to 99% of the sum concentrations in the aqueous and SPM phases. Specifically, two UVAs （2-ethylhexyl 4-（dimethylamino）benzoate （ODPABA） and 2-（2-hydroxy-5-methylphenyl）benzotriazole （UV-P）） were almost exclusively （97% and 99% on average, respectively） distributed in the aqueous phase, one UVA （2-（2H-benzotriazol-2-yl）-4-（1,1,3,3-tetramethylbutyl）phenol （UV-329）） was mostly （84% on average） distributed in the SPM, and the remaining UVAs were similarly distributed to the aqueous and SPM phases, with concentrations in the aqueous phase accounting for 42%-74% of the sum concentrations in both phases. Concentrations of UVAs in the downstream were generally higher than those in the upstream. Compared with that in other regions, the pollution of UVAs in the waterbodies from the Guangzhou reach of the Pearl River was at a moderate to high level. UVAs were detected at higher concentrations in waterbodies near recreational sites, industrial areas, and wastewater treatment plants. The personal care additive 2-cyano-3,3-diphenyl acrylic acid-2-ethylhexyl ester （OCR） was the most dominant component in the aqueous and SPM phases, with detection frequencies of 98% and 100%, respectively, and its concentrations accounting for 50% and 60% of the sum concentrations in both phases, respectively. The risk quotients of individual UVAs in the aqueous phase from the Guangzhou reach of the Pearl River ranged from <0.1 to 1.08, indicating low to moderate risk. Three UVAs, i.e., ODPABA, OCR, and 2-（2H-benzotriazol-2-yl）-4,6-di-tert-pentylphenol （UV-328）, were the potential chemicals at risk. Moreover, it is urgent to pay attention to their long-term risk to aquatic organisms.

Fruits from the Schisandraceae family are renowned for their exceptional medicinal and nutritional properties. These fruits exhibit distinctive shapes and are rich in nutrients, offering edible, ornamental, aesthetic, and therapeutic qualities. Traditional uses of Schisandraceae fruits include the treatment of conditions such as rheumatism, chronic diarrhea, chronic cough, and neurological disorders. Emerging scientific and clinical evidence suggests these fruits have significant potential for various applications in the life sciences. This comprehensive review seeks to achieve two main goals: first, to provide a thorough overview of the chemophenetic relationships among the isolated compounds in Schisandraceae fruits and their underlying significance; second, to describe the development of an important database containing the molecular formulas and molecular weights of all the compounds identified within the Schisandraceae family. This database can facilitate targeted and rapid chemical detection studies using UPLC/MS n techniques. The information and findings discussedin this paper were obtained through a thorough search of digital databases, including SciFinder, Google Scholar, PubMed, Elsevier, and the China Knowledge Resource Integrated (CNKI) databases, covering the period from 1988 to 2024. Approximately 326 phytochemicals were reviewed and identified, with lignans representing the predominant chemotaxonomic markers (∼73 %) in the fruits of Schisandraceae species. Other reported compound classes include terpenoids, fatty acids, and phenolic compounds. Furthermore, the reviewed literature highlights the main pharmacological properties of these Schisandraceae compounds, which include antiviral, cytotoxic, anti-inflammatory, neuroprotective, antiproliferative, hepatoprotective, and antioxidant activities. This comprehensive information will inspire phytochemists to explore the rich chemical diversity of Schisandraceae fruits, potentially leading to the discovery of new medicines and advancing human health., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2024. Published by Elsevier B.V.)

Objective: Immune-mediated necrotizing myopathy (IMNM) is pathologically characterized by diffuse myofibre necrosis and regeneration, myophagocytosis and a sparse inflammatory infiltrate. Monocyte chemoattractant protein-1 (MCP-1) is a key chemokine that regulates monocyte/macrophage infiltration into injured tissues. IL-6 signalling in the induction of MCP-1 expression has not been investigated in IMNM., Methods: MCP-1 expression in muscle specimens was assessed using immunohistochemistry and Reverse transcription quantitative polymerase chain reaction (RT-qPCR). Levels of multiple serological cytokines were evaluated using the electrochemiluminescence-based immunoassays. Flow cytometry, RT-qPCR, enzyme-linked immunosorbent assay, western blot, dual-luciferase reporter assays and chromatin immunoprecipitation qPCR were performed to explore the effects of IL-6 signalling on MCP-1 production in human myoblasts., Results: MCP-1 was scattered and was positively expressed within myofibres and a few inflammatory cells in the muscles of patients with IMNM. Sarcoplasmic MCP-1 expression significantly correlated with myonecrosis, myoregeneration and inflammatory infiltration. Serum MCP-1, IL-6 and the soluble form of the IL-6 receptor (sIL-6R) were elevated in patients with IMNM compared with controls. Serological MCP-1 levels were significantly associated with serum IL-6 expression and clinical disease severity in IMNM patients. The IL-6/sIL-6R complex induced MCP-1 expression via the signal transducer and activator of transcription 3 (STAT3) pathway in human myoblasts. Mechanistically, phospho-STAT3 was enriched in the MCP-1 promoter region and promoted the transcription., Conclusion: IL-6 trans-signalling may contribute to the immunopathogenesis of IMNM by augmenting inflammation through regulation of MCP-1 expression in IMNM., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: The interaction between the metastatic microenvironment and tumor cells plays an important role in metastatic tumor formation. Platelets play pivotal roles in hematogenous cancer metastasis through tumor cell-platelet interaction in blood vessels. Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy distinguished by its notable tendency to metastasize to the liver. However, the role of platelet in the liver metastatic niche of PDAC remains elusive. This study aimed to elucidate the role of platelets and their interactions with tumor cells in the liver metastatic niche of PDAC., Methods: An mCherry niche-labeling system was established to identify cells in the liver metastatic niche of PDAC. Platelet depletion in a liver metastasis mouse model was used to observe the function of platelets in PDAC liver metastasis. Gain-of-function and loss-of-function of erythropoietin-producing hepatocellular receptor B1 (Ephb1), tumor cell-platelet adhesion, recombinant protein, and tryptophan hydroxylase 1 (Tph1)-knockout mice were used to study the crosstalk between platelets and tumor cells in the liver metastatic niche., Results: The mCherry metastatic niche-labeling system revealed the presence of activated platelets in the liver metastatic niche of PDAC patients. Platelet depletion decreased liver metastatic tumor growth in mice. Mechanistically, tumor cell-expressed EPHB1 and platelet-expressed Ephrin B1 (EFNB1) mediated contact-dependent activation of platelets via reverse signaling-mediated AKT signaling activation, and in turn, activated platelet-released 5-HT, further enhancing tumor growth., Conclusion: We revealed the crosstalk between platelets and tumor cells in the liver metastatic niche of PDAC. Reciprocal tumor-platelet interaction mediated by the EPHB1-EFNB1 reverse signaling promoted metastatic PDAC outgrowth via 5-HT in the liver. Interfering the tumor-platelet interaction by targeting the EPHB1-EFNB1 axis may represent a promising therapeutic intervention for PDAC liver metastasis., (© 2024 The Author(s). Cancer Communications published by John Wiley & Sons Australia, Ltd. on behalf of Sun Yat‐sen University Cancer Center.)

Background: Bronchiectasis is a disease with a global impact, but most published data come from high-income countries. We aimed to describe the clinical characteristics of patients with bronchiectasis in China., Methods: The Chinese Bronchiectasis Registry (BE-China) is a prospective, observational cohort enrolling patients from 111 hospitals in China. Data on demographics, comorbidities, and aetiological testing results were collected from adult patients with bronchiectasis at baseline and annual follow-up. Patients who met the inclusion criteria (age ≥18 years; received chest high-resolution CT in the past year showing bronchiectasis affecting one or more lung lobes; and clinical history consistent with bronchiectasis, including chronic cough, daily sputum production, and history of exacerbations) were included. Patients with known cystic fibrosis were excluded. To investigate variations according to different economic regions, two groups were compared based on whether per capita disposable income of residents was greater than US$5553. Clinical characteristics were compared with the European (EMBARC) registry and other national registries., Findings: Between Jan 10, 2020, and March 31, 2024, 10 324 patients from 97 centres were included in the study. Among 9501 participants with available data, the most common cause of bronchiectasis was post-infective disease (4101 [43·2%] patients), followed by idiopathic (2809 [29·6%] patients). 6676 (70·0%) of 9541 patients with available data had at least one exacerbation in the year before enrolment and 5427 (57·2%) of 9489 patients with available data were hospitalised at least once due to exacerbations. Treatments commonly used in high-income countries, such as inhaled antibiotics and macrolides, were infrequently used in China. Implementation of airway clearance in China was scarce, with only 1177 (12·2%) of 9647 patients having used at least one method of airway clearance. Compared with upper-middle-income regions, patients from lower-middle-income regions were younger (61·0 years [SD 14·0] vs 63·9 years [14·2]) with a higher proportion of pulmonary comorbidities (521 [17·8%] of 2922 patients vs 639 [8·6%] of 7402 with chronic obstructive pulmonary disease and 194 [6·6%] of 2922 patients vs 364 [4·9%] of 7402 patients with asthma), a higher tuberculosis burden (442 [16·0%] of 2768 patients vs 715 [10·6%] of 6733 patients), more severe radiological involvement (1160 [42·4%] of 2736 patients vs 2415 [35·4%] of 6816 patients with cystic bronchiectasis), more exacerbations (median 1·4 [IQR 0-2] in both groups; mean 1·4 [SD 1·6] vs 1·2 [1·4] in the previous year) and hospitalisations (1662 [60·6%] of 2743 patients vs 3765 [55·8%] of 6746 patients hospitalised at least once in the previous year), and poorer quality of life (median 57·4 [IQR 53·5-63·1] vs 58·7 [54·8-64·8] assessed by the Bronchiectasis Health Questionnaire)., Interpretation: The clinical characteristics of patients with bronchiectasis in China show differences compared with cohorts in Europe and India. Bronchiectasis is more severe with a higher burden of exacerbations in lower-income regions. The management of patients with bronchiectasis in China urgently needs standardisation and improvement., Funding: National Natural Science Foundation of China, Innovation Program of the Shanghai Municipal Education Commission, Program of the Shanghai Municipal Science and Technology Commission, and Program of the Shanghai Shenkang Development Center., Translation: For the Chinese translation of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests JDC declares grants or contracts from Astrazeneca, Genentech, Gilead Sciences, GlaxoSmithKline, Insmed, Grifols, Novartis, and Boehringer Ingelheim; and consulting fees from Astrazeneca, Chiesi, GlaxoSmithKline, Insmed, Grifols, Novartis, Boehringer Ingelheim, Pfizer, Janssen, Antabio, and Zambon. All other authors declare no competing interests., (Copyright © 2025 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Low-dose computed tomography screening reduces lung cancer-specific mortality in high-risk individuals. Lung cancer risk factors overlap with comorbid diseases, highlighting the significance of frailty and comorbidities for lung cancer screening (LCS). Here, we describe the prevalence of frailty and comorbidity in those invited for LCS and evaluate their associations with response to telephone risk assessment invitation and subsequent uptake of LCS., Methods: Analysis was based on the intervention arm of the Yorkshire Lung Screening Trial, where ever-smoked individuals aged 55-80 were invited to telephone risk assessment followed by community-based LCS if at higher risk. The electronic frailty index (eFI) was used to compute individual frailty scores (categorised as fit, mild, moderate and severe) and derive comorbidity data., Results: Of 27,761 individuals invited, 24.1% ( n  = 6702), 8.5% ( n  = 2353) and 1.7% ( n  = 459) had mild, moderate and severe frailty, respectively. Over half responded to the invitation to telephone risk assessment ( n  = 14,523, 52.5%) with frailty associated with a higher response rate compared to fit individuals: adjusted odds ratio (OR adj ) 1.34, 95% confidence interval (CI) 1.26-1.42 for mild frailty; OR adj 1.28, 95%CI 1.16-1.40 for moderate frailty; and OR adj 1.32, 95%CI 1.08-1.61 for severe frailty. Similar patterns were seen with comorbidity counts. After assessment, moderate (OR adj 0.75, 95%CI 0.59-0.96) and severe (OR adj 0.67, 95%CI 0.43-1.04) frailty were associated with reduced screening uptake., Conclusion: The presence of frailty was associated with increased response to LCS invitation. Given the strong association between frailty and reduced life expectancy, these results suggest that people with potentially more life years to be gained from LCS may be less inclined to take part. Further research is needed to explore the interactions between frailty and LCS decision-making to inform future invitation strategies., Competing Interests: Declaration of conflicting interestsP.A.J. Crosbie reports stock options from Everest Detection, and lecture honoraria from Bayer, outside the submitted work. R.J. Beeken reports fellowship and grant funding from Yorkshire Cancer Research and grant funding from Roy Castle Lung Cancer Foundation, outside the submitted work. A. Clegg has received consultancy fees from the Geras Centre for Aging Research, received meeting/travel support from the Australian and New Zealand Society of Geriatric Medicine, and is a chair of the global Ageing Research Trialists collaborative.

The APETALA2/ethylene-responsive factor (AP2/ERF) superfamily represents a class of transcription factors involved in plant growth, development, and stress responses. Carthamus tinctorius L ., also known as safflower, is an important plant whose flowers contain carthamin, an expensive aromatic pigment with various medicinal and flavoring properties. This study aimed to elucidate the roles of these transcription factors in plant growth, metabolic regulation, and environmental adaptation in safflower, providing foundational information and theoretical support for genetic improvement and stress resilience research in this crop. In this study, we identified and characterized the AP2/ERF family genes in safflower through a comprehensive genomic analysis. A total of 127 AP2/ERF genes were identified and clustered into seven groups and 14 subgroups based on phylogenetic analysis. Multiple sequence alignment revealed that the basic region and two helical structures were highly conserved in most AP2/ERF proteins. Cis -acting elements in the promoters of the AP2/ERF genes were analyzed, and a degree of safflower specificity was observed among different safflower species. Tissue-specific expression analysis showed that 23, 21, 15, and 9 genes were most abundantly expressed in the roots, leaves, flowers, and buds, respectively, while only eight genes were highly expressed in all tissues examined. These results indicate that the AP2/ERF family genes in safflower are diverse and complex, with distinct expression patterns for different genes in different safflower species. The findings provide important fundamental data for in-depth studies of the growth, development, and stress response mechanisms in safflower., Competing Interests: The authors declare no conflicts of interest., (© 2025 The Author(s). Plant Direct published by American Society of Plant Biologists and the Society for Experimental Biology and John Wiley & Sons Ltd.)

In this study, rice husk biochar was engineered with abundant iron ion sites to enhance the enrichment of antioxidant peptides from rice protein hydrolysates through metal-chelating interactions. The π-π interactions and metal ion chelation were identified as the primary mechanisms for the enrichment process. Through peptide sequencing, four peptides were identified: LKFL (P1: Leu-Lys-Phe-Leu), QLLF (P2: Gln-Leu-Leu-Phe), WLAYG (P3: Trp-Leu-Ala-Tyr-Gly), and HFCGG (P4: His-Phe-Cys-Gly-Gly). The vitro analysis and molecular docking revealed that peptides P1-P4 possessed remarkable scavenging ability against radicals and Fe 2+ chelating ability. Notably, peptide P4 showed radical scavenging activity comparable to glutathione (GSH) against 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azinobis-3-ethylbenzthiazoline-6-sulphonate (ABTS) radicals. Cellular experiments further confirmed that peptide P4 effectively protected HepG2 cells from oxidative stress-induced damage. The modified rice husk biochar proved to be an effective means for enriching rice antioxidant peptides from protein hydrolysates., 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.)

Background and Objective: Living guidelines contain continually updated, and potentially changing, clinical recommendations. The implications of living guidelines for consumers (eg, patients, carers, and people with lived experience) - particularly how living guidelines should be developed and disseminated - are yet to be established. The objective of this study was to explore consumers' views about how best to support the use and usefulness of living guidelines to consumers., Methods: This study used a qualitative (online survey) design. We invited consumers who were familiar with guidelines (living or conventional) to participate in the study. The survey was distributed globally. Recruitment was conducted via the Australian and international networks of the Australian Living Evidence Collaboration. We invited consumers who were familiar with guidelines (living or conventional) to participate in the study. The survey was distributed globally. Recruitment was conducted via the Australian and international networks of the Australian Living Evidence Collaboration. The 5-10 minute survey collected demographic data then, after introducing the living guidelines concept, asked questions about what living guidelines mean for consumers, how we might make them easy for consumers to find and use, and potential challenges to their use. We analyzed the data using inductive thematic analysis., Results: Forty-five people (71% women) from 12 countries completed the survey. Participants were enthusiastic about the concept of living guidelines and what they might mean for consumers' ability to make informed health-care decisions and receive best care. They also identified potential challenges related to living guideline dissemination, such as low public awareness of guidelines and confusion about updated recommendations. Participants described practical strategies to support consumers' awareness and use of, and access to, living guidelines. These included: meaningful involvement of consumers in the development and dissemination of living guidelines; raising awareness by promoting the guidelines widely through trusted health information sources and on social media; and using user-centered formatting and design principles (eg, considering accessibility needs, and publishing lay summaries with plain and culturally-appropriate language)., Conclusion: Consumers suggested a comprehensive range of dissemination strategies to support the use and usefulness of living guidelines to consumers, which largely reflect best practice in conventional guideline dissemination. Promoting and explaining the living nature of guideline recommendations might support their use by consumers. There should also be a close link between the living guidelines and any versions or additional content created for both consumers and clinicians., Competing Interests: Declaration of competing interest There are no competing interests for any author., (Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.)

Nowadays, the development of plant extracts as corrosion inhibitors to protect metals from corrosion is a popular research direction. However, given the vast diversity of plant species in nature, it is imperative to explore effective methods to improve screening efficiency in order to quickly identify the corrosion inhibition potential of plants. In this work, a new strategy for developing plant-extracted eco-friendly corrosion inhibitors based on the family and genus of plants is proposed. Three plants of different genera in the Asteraceae family, including Artemisia argyi extract (AAE), Chrysanthemum indicum extract (CIE), and Centipeda minima extract (CME), were selected and successfully prepared as novel corrosion inhibitors for Q235 steel in a sulfuric acid solution. The corrosion inhibition behavior and corresponding mechanism were systematically investigated by using some electrochemical tests (open circuit potential, potentiodynamic polarization, and electrochemical impedance spectroscopy) and surface characterizations (Fourier transform infrared spectroscopy, scanning electron microscopy, and X-ray photoelectron spectroscopy). The experimental results illustrated that the main components of the three extracts were similar and that when combined with KI as mixed-type corrosion inhibitors, they could dramatically slow down the metal corrosion rate. The maximum value of the corrosion inhibition efficiency reached 96.29%, 96.50%, and 97.52%, respectively, at 200 mg/L and could increase to 98.64%, 97.65%, and 99.06%, respectively, with a prolonged immersion time. A synergistic effect exists between the three plant extracts and KI, leading to the firm adsorption of the three plant extract molecules onto a Q235 steel surface, thereby forming a robust protective film. This work demonstrated that plants of different genera in the Asteraceae family possessed similar corrosion inhibition capabilities, providing a novel way to select potential corrosion inhibitors from numerous plants based on family and genus classification.

Introduction: Despite the high prevalence of cognitive impairment or dementia post-coronary artery bypass grafting (CABG), the incidence of cognitive impairment or dementia post-CABG in contemporary practice is currently unclear. Therefore, this paper aims to investigate the incidence and associated risk factors of cognitive impairment or dementia in patients' post-CABG., Methods: A systematic search across three databases (PubMed, SCOPUS, and Embase) was conducted for studies published in or after 2013 that reported cognitive impairment or dementia post-CABG. Subgroup analyses and meta-regression by risk factors were performed to determine their influence on the results., Results: This analysis included 23 studies with a total of 2,620 patients. The incidence of cognitive impairment or dementia less than 1 month, 2 to 6 months, and more than 12 months post-CABG was 35.96% (95% confidence interval [CI]: 28.22-44.51, I2 = 87%), 21.33% (95% CI: 13.44-32.15, I2 = 88%), and 39.13% (95% CI: 21.72-58.84, I2 = 84%), respectively. Meta-regression revealed that studies with more than 80% of the cohort diagnosed with hypertension were significantly associated with incidence of cognitive impairment or dementia less than 1 month post-CABG., Conclusion: This meta-analysis demonstrates a high incidence of cognitive impairment or dementia in patients' post-CABG in contemporary practice, particularly less than 1 month post-CABG and more than 12 months post-CABG. We found that hypertension was a significant risk factor in the short-term (less than 1 month) follow-up period for cognitive impairment or dementia post-CABG. Future research should be done to assess strategies to reduce cognitive impairment post-CABG., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Rare earth elements (REEs) are emerging contaminants rendering potential risks in soils to environmental quality and human health. The causation between their geochemical signatures and contamination levels with parent rocks and soil properties are critical for REEs risk assessments, which are urgently needed globally. Thus, this study aimed to elucidate cause-and-effect among hydrofluoric-acid-digested total and ethylenediaminetetraacetic acid extracted bioavailable soil REEs and their contamination degree evaluated by pollution indices in 268 soil layer (horizon) samples from 50 soil profiles derived from felsic, intermediate, mafic, ultramafic, and sedimentary rocks in Taiwan. The total REEs was 133 ± 61.9 mg/kg and all individual REEs were classified as minimal contamination by the enrichment factor. The highest total soil REEs was from granite, followed by sandstone and shale, mafic rocks, andesite, and ultramafic rocks. All soils were ranked as significantly pollution risk by the pollution loading index. Furthermore, REEs were accumulated in all subsoils due to the co-translocation with soil colloids during the intensive leaching, corresponding with their higher geoaccumulation index value than those in surface soils. The contamination degree and bioavailable REEs significantly increased with the increasing total REEs. However, the stronger sequestration of clay and free Fe oxides for heavy REEs (HREEs) over light REEs (LREEs) mitigated their bioavailability, especially in the highly weathered soils like Ultisols and Oxisols. This study highlighted the dominance of soil properties in REEs fractionation, where the preferential fixation of soil colloids for HREEs throughout soil profiles reduced their uptake risk for biome even under the rising contamination potential., Competing Interests: Declarations. Ethical approval: The authors have not submitted my manuscript to a preprint server before submitting it to Environmental Science and Pollution Research, and the publication has been approved by all co-authors. Consent to participate: The authors declare that they consent to participate in the work. Consent for publication: The authors declare that they consent to publish this paper. Competing interests: The authors declare no competing interests., (© 2025. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: Since its introduction in 2011, FDG-PET/MRI has been advocated as a useful adjunct in colorectal cancer care. However, gaps and limitations in current research remain. This systematic review aims to review the current literature to quantify the utility of FDG-PET/MRI in colorectal cancer care., Methods: An up-to-date review was performed on the available literature between 2000 and 2023 on PubMed, EMBASE, Medline, databases. All studies reporting on the use of FDG-PET/MRI in colorectal cancer care were analyzed. The main outcome measures were accuracy in initial staging, restaging, and detection of metastatic disease in both rectal as well as colon cancers. The secondary outcome was comparing the performance of FDG-PET/MRI versus Standard of Care Imaging (SCI). Finally, the clinical significance of FDG-PET/MRI was measured in the change in management resulting from imaging findings., Results: A total of 22 observational studies were included, accounting for 988 patients. When individually compared to current Standard of Care Imaging (SCI)-MRI pelvis for rectal cancer and thoraco-abdominal contrast CT, PET/MRI proved superior in terms of distant metastatic disease detection. This led to as much as 21.0% change in management. However, the technological limitations of PET/MRI were once again highlighted, suggesting SCI should retain its place as first-line imaging., Conclusion: FDG-PET/MRI appears to be a promising adjunct in staging and restaging of colorectal cancer in carefully selected patients., Competing Interests: Declarations. Conflict of interest: The authors declare no conflict of interest. Consent for publication: Not Applicable., (© 2024. Crown.)

Developing economical and efficient electrocatalysts is critical for hydrogen energy industrialization through water electrolysis. Herein, a novel dual-site synergistic NiFe/Y 2 O 3 hybrid with abundant interfacial Ni/Fe─O─Y bonds is designed by density functional theory (DFT) simulations. In situ Raman spectra combined with DFT calculations reveal that the interfacial Ni/Fe─O─Y units greatly promote H 2 O dissociation and optimize the adsorption of both H* and oxygen species, achieving excellent activity and durability for hydrogen evolution reaction. As expected, NiFe/Y 2 O 3 exhibits a low overpotential of 27 mV at 10 mA cm -2 and robust stability of over 200 h at 1000 mA cm -2 , and also outstanding water splitting performance with a low cell voltage of 1.64 V at 100 mA cm -2 , showing significant potential for real-world applications., (© 2024 Wiley‐VCH GmbH.)

The field of conservation genomics is becoming increasingly interested in whether, and how, structural variant (SV) genotype information can be leveraged in the management of threatened species. The functional consequences of SVs are more complex than for single nucleotide polymorphisms (SNPs), as SVs typically impact a larger proportion of the genome due to their size and thus may be more likely to contribute to load. While the impacts of SV-specific genetic load may be less consequential for large populations, the interplay between weakened selection and stochastic processes means that smaller populations, such as those of the threatened Aotearoa hihi/New Zealand stitchbird (Notiomystis cincta), may harbour a high SV load. Hihi were once confined to a single remnant population, but have been reestablished into six sanctuaries and reserves, often via secondary bottlenecks, resulting in low genetic diversity, low adaptive potential, and inbreeding depression. In this study, we use whole genome resequencing of 30 individuals from the Tiritiri Matangi population to identify the nature and distribution of both SNPs and SVs within this small avian population. We find that SNP and SV individual mutation load is only moderately correlated, likely because SVs arise in regions of high recombination and that are less evolutionarily conserved. Finally, we leverage a long-term monitoring dataset of pedigree and fitness data to assess the impact of SNP and SV mutation loads on individual fitness, and find that SNP and SV realised load had similar negative correlations with lifetime fitness. However, of the masked load metrics, only SVs had a positive significant correlation with lifetime fitness, indicating that masking of deleterious alleles may be more important for SVs than for SNPs. The results of this study indicate that only examining SNPs neglects important aspects of intra-specific variation and that studying SVs has direct implications for linking genetic diversity and genomic health to inform management decisions., (© 2024 John Wiley & Sons Ltd.)

Introduction: Traditional risk factors do not fully explain the increased risk of cardiovascular disease (CVD) in patients with rheumatoid arthritis (RA). The Haptoglobin (Hp) 2-2 genotype confers a lower anti-oxidant and higher inflammatory effect on the vasculature compared to the non- Hp 2-2 genotype. This study investigates the association of the Hp genotype with CVD in patients with RA., Methods: Data from 69 RA patients with CVD and 207 sex- and ethnicity-matched RA patients without CVD, collected from 1 January 2000 to 31 December 2020, were retrieved from the Tan Tock Seng Hospital RA Registry. CVD was examined against demographics, clinical and laboratory variables in univariate models. Associations between the Hp genotypes and CVD were analyzed using conditional logistic regression., Results: We studied 276 patients (65.2% female, 82.6% Chinese, median age 60.9 years). Most participants were in low disease activity or remission (79.3%). The Hp 2-2 genotype was present in 49.6% (137/276). In the group with CVD, the prevalence of the Hp 2-2 genotype was 50.9% (29/57) in the Chinese, 100% (5/5) in the Indians, and 28.6% (2/7) in the Malays. In the non-CVD group, the respective prevalence was 46.8% (80/171), 66.7% (10/15), and 52.4% (11/21). In univariate analysis, the matched odds ratio (OR) of the Hp 2-2 genotype for CVD in RA was 1.34 [95% confidence interval (CI): 1.22-1.47; p  < 0.001]. The Hp 2-2 genotype was significantly associated with CVD (adjusted matched OR: 1.13; 95% CI: 1.01-1.27; p  = 0.033) in the multivariate logistic regression model after adjusting the confounding factors, including age, smoking, diabetes, hypertension, hyperlipidemia, anti-CCP autoantibodies, and disease activity., Conclusion: The Hp 2-2 genotype is associated with an increased risk of CVD in patients with RA in this multi-ethnic cohort., 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 Xu, Khin, Tam, Goh, Koh, Dalan and Leong.)

The catalytic α-deuteration of sulfides was developed under mild conditions by using alkali metal amides [KN(SiMe 3 ) 2 and CsN(SiMe 3 ) 2 ] as the catalyst. This approach successfully achieves a selective and efficient H/D exchange reaction of sulfides with D 2 without using transition metal catalysts. A series of deuterium-labeled thioanisoles and alkyl methyl sulfides were obtained in good to high levels of deuterium incorporation.

The expansion of human settlements over the past few centuries is responsible for an unprecedented number of invasive species introductions globally. An important component of biological invasion management is understanding how introduction history and postintroduction processes have jointly shaped present-day distributions and patterns of population structure, diversity and adaptation. One example of a successful invader is the European starling (Sturnus vulgaris), which was intentionally introduced to numerous countries in the 19th century, including Aotearoa New Zealand, where it has become firmly established. We used reduced representation sequencing to characterise the genetic population structure of the European starling in New Zealand, comparing it to that present in sampling locations in the native range and invasive Australian range. The population structure and genetic diversity patterns we found suggested restricted gene flow from the majority of New Zealand to the northmost sampling location (Auckland). We also profiled genetic bottlenecks and shared outlier genomic regions, which supported historical accounts of translocations between both Australian subpopulations and New Zealand, and provided evidence of which documented translocation events were more likely to have been successful. Using these results as well as historic demographic patterns, we demonstrate how genomic analysis complements even well-documented invasion histories to better understand invasion processes, with direct implications for understanding contemporary gene flow and informing invasion management., (© 2024 John Wiley & Sons Ltd.)

Five new secoiridoids, gentianopsins A-E (1-5), along with two known analogues (6 and 7) were isolated from the whole plants of the medicinal herb Gentianopsis barbata. Their structures were elucidated by a comparison of extensive spectroscopic analysis (1D and 2D NMR, and HRMS) and quantum chemical calculations. Gentianopsins A (1) and B (2) represented two unusual skeletons of trihomo-secoiridoids. Anti-inflammatory activity of these isolates was evaluated via suppressing the secretion of cytokines TNF-α and IL-6 in LPS-induced macrophages RAW264.7. Significant inhibitory activity was observed for compounds 3 and 7 on IL-6 secretion with IC 50 values of 10.22 and 13.30 μM, respectively., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

Swine acute diarrhoea syndrome coronavirus (SADS-CoV) causes vomiting, severe diarrhoea and death in newborn piglets. The spike (S) protein plays a crucial role in promoting virus invasion and inducing neutralizing antibody production. In this study, the extracellular region of the S protein was used as an immunogen to immunize BALB/c mice. After immunization, B cells were collected, fused with SP2/0 myeloma cells, cultured and subcloned, and a cell line capable of secreting neutralizing antibodies was obtained and named as 5D6. Additionally, it was determined that the 5D6 mAb could be used as the primary antibody for western blotting and indirect immunofluorescence assay (IFA) to detect SADS-CoV. Further studies indicated that the 5D6 mAb binds to the 136 STSHAAD 142 motif, which located in the N-terminal domain (NTD) of the spike protein. This result suggested that the NTD of the S protein can induce the production of neutralizing antibodies. Amino acid sequence alignment revealed that the epitope of the 5D6 mAb was conserved among SADS-CoV strains. This study helps elucidate the S protein function of SADS-CoV, and the 5D6 mAb may be used to develop diagnostic and treatment tools for detecting SADS-CoV infection., (© 2024. The Author(s).)

Objective: Expand genetic screening for atypical Type I sialidosis (ST-1) could address its underdiagnosed in both progressive myoclonic ataxia (PMA) and ataxia patients. To evaluate the potential founder effect of mutation in the population., Methods: We enrolled 231 patients with PMA or ataxia from the First Affiliated Hospital of Fujian Medical University. Through Whole Exome Sequencing and Sanger sequencing, we identified the causative gene in patients. Haplotype analysis was employed to explore a potential founder effect of the NEU1 c.544A>G mutation., Results: A total of 31 patients from 23 unrelated families were genetically diagnosed with ST-1. A significant 80.6% of these patients were homozygous for the c.544A>G mutation. We discovered six different NEU1 variants, including two novel mutations: c.951&#95;968del and c.517T>G. The mean age of onset was 18.0 ± 7.1 years. The clinical spectrum of ST-1 featured ataxia and myoclonus as the most common initial symptoms. Over 40% suffered from controlled generalized tonic-clonic seizures. Mobility and independence varied greatly across the cohort. Cherry-red spots were rare, occurring in just 9.5% (2/21) of patients. Brain MRIs were typically unremarkable, except for two patients with unusual findings. EEGs showed diffuse paroxysmal activity in 17 patients. The c.544A>G mutation in NEU1 is a founder variant in Fujian, with a unique haplotype prevalent in East Asians., Interpretation: ST-1 should be suspected in patients with PMA or ataxia in Southeast China, even without macular cherry-red spots and seizures, and the premier test could be a variant screening of the founder variant NEU1 c.544A>G., (© 2024 The Author(s). Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Background: Antihistamines alleviate the side effects of antitumor drugs and exert antitumor effects. This study aimed to investigate the potential impact of short-term concomitant use of antihistamines with immune checkpoint inhibitor (ICI) therapy on the efficacy and immune-related adverse events (irAEs) of immunotherapy for patients with advanced lung cancer., Methods: We retrospectively analyzed the medical records of 211 patients diagnosed with advanced primary lung cancer and treated with immunotherapy at Tianjin Medical University Cancer Institute and Hospital between January 1, 2018, and January 1, 2022. Among these patients, 109 who received H1 antihistamine during the infusion of anti-programmed cell death-1 (PD-1) and anti-programmed cell death ligand 1 (PD-L1) antibodies were assigned to the experimental group; meanwhile, the remaining 102 patients who did not receive H1 antihistamines were assigned to the control group. Balancing was achieved through inverse probability of treatment weight (IPTW) estimation. The data were analyzed using Kaplan-Meier curves and Cox regression analyses., Results: The median progression-free survival (mPFS) was 12.7 months in the experimental group and 4.3 months in the control group, while the median overall survival (mOS) was 32.8 months in the experimental group and 18.1 months in the control group. In the experimental group, patients treated with only H1 antihistamines had longer mPFS and mOS compared with those who received H1 plus H2 antihistamines. Similarly, in the control group, patients who did not receive antihistamines had a longer mPFS and mOS than those who only received H2 antihistamines. After conducting multivariate analyses, we found that H1 and H2 antihistamines were respectively identified as good and poor independent prognostic factors for both progression-free survival (PFS) and overall survival (OS). The rates of irAEs in the experimental and control groups were 52.4% and 69.2%, respectively, and grade ≥3 irAEs occurred in 4.5% and 25.9% of patients, respectively., Conclusions: Concomitant use of H1 antihistamines can improve immunotherapy efficacy and reduce irAEs. Meanwhile, concomitant use of H2 antihistamines is associated with reduced PFS and OS time., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-24-795/coif). The authors have no conflicts of interest to declare., (2024 AME Publishing Company. All rights reserved.)

Ethnopharmacological Relevance: The traditional medicinal formulation, Qifu-yin (QFY), has been widely prescribed for Alzheimer's disease (AD) treatment in China, yet the comprehensive mechanisms through which QFY mitigates AD pathology remain to be fully delineated., Aim of the Study: This study aimed to explore the therapeutic implications of QFY on the synaptic injury and oxidative stress in the hippocampus of APPswe/PS1dE9 (APP/PS1) mice, with a concerted effort to elucidate the molecular mechanisms related to synaptic preservation and memory improvement., Materials and Methods: The components of QFY were identified by ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). The neuroprotective effects of QFY was evaluated using six-month-old male APP/PS1 mice. Subsequent to a 15 days of QFY regimen, spatial memory was assessed utilizing the Morris water maze (MWM) test. Amyloid-beta (Aβ) aggregation was detected via immunostaining, while the quantification of Aβ 1-40 and Aβ 1-42 was achieved through enzyme-linked immunosorbent assay (ELISA). Transmission electron microscopy (TEM) was used to investigate the synaptic structure and mitochondrial morphology. Golgi staining was applied to examine dendritic spine density. Reactive oxygen species (ROS), 3-nitrotyrosine (3-NT) and 4-hydroxy-nonenal (4-HNE) assays were employed to assess oxidative stress. The expression profiles of Aβ metabolism-associated enzymes and the Keap1/Nrf2/ARE signaling pathway were determined by Western blot., Results: A total of 20 principal compounds in QFY were identified. QFY mitigated memory deficits of APP/PS1 mice, including reducing escape latency and search distance and increasing the time and distance spent in the target quadrant. In addition, QFY increased platform crossings of APP/PS1 mice in the probe trial of MWM tests. TEM analysis showed that QFY increased synapse number in the CA1 region of APP/PS1 mice. Further studies indicated that QFY elevated the expression levels of Post synaptic density protein 95 (PSD95) and synaptophysin, and mitigated the loss of dendritic spine density in the hippocampus of APP/PS1 mice. QFY has been shown to ameliorated the structural abnormalities of mitochondria, including mitochondrial dissolution and degradation, up-regulate ATP synthesis and membrane potential in the hippocampus of APP/PS1 mice. Moreover, QFY activated the Keap1/Nrf2/ARE signaling pathway in the hippocampus of APP/PS1 mice, which might contribute to the neuroprotective effects of QFY., Conclusion: QFY activates the Keap1/Nrf2/ARE signaling, and protects against synaptic and mitochondrial dysfunction in APP/PS1 mice, proposing a potential alternative therapeutic strategy for AD management., 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.)

Primary familial brain calcification (PFBC) is a genetic neurological disease, yet no effective treatment is currently available. Here, we identified five novel intronic variants in SLC20A2 gene from six PFBC families. Three of these variants increased aberrant SLC20A2 pre-mRNA splicing by altering the binding affinity of splicing machineries to newly characterized cryptic exons, ultimately causing premature termination of SLC20A2 translation. Inhibiting the cryptic-exon incorporation with splice-switching ASOs increased the expression levels of functional SLC20A2 in cells carrying SLC20A2 mutations. Moreover, by knocking in a humanized SLC20A2 intron 2 sequence carrying a PFBC-associated intronic variant, the SLC20A2-KI mice exhibited increased inorganic phosphate (Pi) levels in cerebrospinal fluid (CSF) and progressive brain calcification. Intracerebroventricular administration of ASOs to these SLC20A2-KI mice reduced CSF Pi levels and suppressed brain calcification. Together, our findings expand the genetic etiology of PFBC and demonstrate ASO-mediated splice modulation as a potential therapy for PFBC patients with SLC20A2 haploinsufficiency., Competing Interests: Declaration of interests W.-J.C., Z.-Q.X., X.C., M.Z., Y.-H.Z., and L.C. have filed patents (CN2023113708968) to protect the application of CRACE therapy for the treatment of brain calcification., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: To investigate the clinical characteristics and prognosis of single center adult chronic myeloid leukemia in chronic phase (CML-CP)., Methods: Clinical data of 41 adult CML-CP patients in Department of Hematology, Shanghai Fengxian District Central Hospital from January 2015 to May 2021 were retrospectively analyzed. The clinical characteristics and prognosis of patients between <60 years group and ≥60 years group were compared., Results: The 41 patients included 27 (65.9%) males and 14 (34.1%) females. The median age of the patients was 56(19-84) years, with 22 cases (53.7%) <60 years and 19 cases (46.3%) ≥60 years. Univariate analysis indicated that the proportions of patients with comorbidities, intermediate/high-risk Sokal score, myelofibrosis, and lactate dehydrogenase ≥1 000 U/L were significantly increased in ≥60 years group compared with <60 years group at initial diagnosis (all P <0.05). There were no statistical differences in the distribution of sex, ELST score, white blood cell count, platelet count, peripheral blood basophil percentage, peripheral blood eosinophil percentage and bone marrow primitive cell percentage between the two groups ( P >0.05). The proportion of patients taking reduced-dose imatinib in ≥60 years group significantly increased ( P <0.001). Patients <60 years had a higher proportion of molecular biological remission after treatment of tyrosine kinase inhibitors (TKIs) than patients ≥60 years ( P <0.001). The incidence of non-hematologic adverse reactions to TKI therapy significantly increased in patients ≥60 years ( P <0.001). Multivariate analysis showed that no adverse factors affecting the efficacy and prognosis of TKI., Conclusion: Compared with adult CML-CP patients <60 years, patients ≥60 years gain fewer benefits from TKI treatment and increased adverse reactions.

Recombination, the process of DNA exchange between homologous chromosomes during meiosis, plays a major role in genomic diversity and evolutionary change. Variation in recombination rate is widespread despite recombination often being essential for progression of meiosis. One such variation is heterochiasmy, where recombination rates differ between sexes. Heterochiasmy has been observed across broad taxonomic groups, yet it remains an evolutionary enigma. We used Lep-MAP3, a pedigree-based software that is efficient in handling large datasets, to generate linkage maps for the hihi or stitchbird (Notiomystis cincta), utilising information from >36 K SNPs and 36 families. We constructed 29 linkage maps, including for the previously unscaffolded Z chromosome. The hihi is an endangered passerine endemic to Aotearoa New Zealand that is sexually dimorphic and exhibits high levels of sexual conflict, including sperm competition. Patterns in recombination in the hihi are consistent with those in other birds, including higher recombination rates in micro-chromosomes. Heterochiasmy in the hihi is male-biased, in line with predictions of the Haldane-Huxley rule, with the male linkage map being 15% longer. Micro-chromosomes exhibit heterochiasmy to a greater extent, contrary to that reported in other birds. At the intra-chromosomal level, heterochiasmy is higher nearer to chromosome ends and in gene-rich regions. Regions of extreme heterochiasmy are enriched for genes implicated in cell structure. This study adds an important contribution in assessing evolutionary theories of heterochiasmy and provides a framework for future studies investigating fine-scale heterochiasmy., (© 2024. The Author(s).)

Objectives: In 2017, the World Health Organization (WHO) medical eligibility criteria (MEC) for contraception category for intramuscular depot medroxyprogesterone acetate (DMPA-IM) was changed from MEC category 1 to 2 for women at high risk of HIV acquisition. We assessed the impact of communicating this category change among women in the Evidence for Contraceptive options and HIV Outcomes (ECHO) trial., Study Design: ECHO was conducted in eSwatini, Kenya, South Africa and Zambia. Women were randomized (1:1:1) to DMPA-IM, levonorgestrel (LNG) implant or copper intrauterine device (Cu IUD). We compared the hazards of DMPA-IM discontinuation and assessed sexual behavior and DMPA-IM satisfaction before and after MEC category change., Results: In DMPA-IM users there was a decrease in the hazards of discontinuation after the MEC change (hazard ratio 0.37; 95% CI = 0.26-0.52, p  < 0.001). No evidence of an effect of the MEC change was observed in sexual behaviour outcomes. There was some evidence of an increase in disatisfaction with DMPA-IM immediately after the MEC change, with the odds of women reporting a higher score (more dissatisfied) increasing by 1.38 compared with before the MEC change (95% CI = 1.11-1.72)., Conclusions: While counseling on possible theoretical risks associated with contraceptive methods in the MEC is an important medical ethical standard, in this study it did not adversely impact continuation or sexual behavior, while there was some evidence on increase in dissatisfaction. There is however a need to monitor how changes in MEC categories are implemented., Implications: Although we found no evidence in this analysis of an effect of the MEC change on any of the sexual behavioral outcomes among women after the change in category, it is still an important medical ethical standard to counsel on possible theoretical risks associated with contraceptive methods. Given the challenges of translating research findings to guidelines and further to counseling messages, evaluation of clinical guidelines implementation is necessary to understand the effects of implementation and to monitor both intended impacts and unintended consequences., Competing Interests: 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., (© 2024 The Author(s).)

Background: The combination of acute ST-segment elevation myocardial infarction (STEMI) and gastric ulcers poses a challenge to primary percutaneous coronary intervention (PPCI), particularly for young patients. The role of drug-coated balloons (DCBs) in the treatment of de novo coronary artery lesions in large vessels remains unclear, especially for patients with STEMI. Our strategy is to implement drug balloon angioplasty following the intracoronary administration of low-dose prourokinase and adequate pre-expansion., Case Summary: A 54-year-old male patient presented to the emergency department due to chest pain on June 24, 2019. Within the first 3 minutes of the initial assessment in the emergency room, the electrocardiogram (ECG) showed significant changes. There was atrial fibrillation with ST-segment elevation. Subsequently, atrial fibrillation terminated spontaneously and reverted to sinus rhythm. Soon after, the patient experienced syncope. The ECG revealed torsades de pointes ventricular tachycardia. A few seconds later, it returned to sinus rhythm. High-sensitivity tropon in I was normal. The diagnosis was acute STEMI. Emergency coronary angiography revealed subtotal occlusion with thrombus formation in the proximal segment of the left anterior descending artery. Considering the patient's age and history of peptic ulcer disease, after the intracoronary injection of prourokinase, percutaneous transluminal coronary angioplasty and cutting balloon angioplasty were conducted for thorough preconditioning, and paclitaxel drug-eluting balloon angioplasty was performed without any stents, achieving favorable outcomes., Conclusion: A PPCI without stents may be a viable treatment strategy for select patients with STEMI, and further research is warranted., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflict of interest., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Previous studies have demonstrated that TRIB3 plays a carcinogenic role in tumor progression. However, the exploration of TRIB3 at the pan-cancer level has not been reported., Aims: This study aimed to conduct a comprehensive pan-cancer analysis of TRIB3., Objective: We explored the expression pattern and functional mechanism of TRIB3 on the basis of multiple databases., Method: We first explored the expression level of TRIB3 in the TCGA database. Then, the receiver operation characteristic curve (ROC), Kaplan-Meier plotter, and Cox regression were used to estimate the diagnostic and prognostic value of TRIB3, respectively. We also explored the relationship between TRIB3 and the infiltration of tumor immune cells, as well as the expression of immune checkpoint molecules. Gene enrichment and protein interaction network analysis were carried out to identify possible carcinogenic molecular mechanisms and functional pathways. Finally, we compared the non-promoter region methylation of TRIB3 in normal and tumor tissues and explored potential systems with unique functions in TRIB3-mediated tumorigenesis., Result: The expression level of TRIB3 was elevated in multiple tumor types, and the high expression of TRIB3 was associated with poor prognosis. TRIB3 had a higher frequency of genetic changes in several tumors and showed varying trends in TRIB3 methylation levels. Additionally, high expression of TRIB3 was also associated with infiltration of cancer-related fibroblasts and different types of immune cells and was positively correlated with the expression of immune checkpoint molecules. Furthermore, gene enrichment analysis suggested that TRIB3 may play a role in the malignant progression of cancer by participating in protein post-translational modifications and activating transcription initiation factors., Conclusion: Our pan-cancer analysis provided the potential carcinogenic role of TRIB3 in tumors and verified a promising target for clinical immune treatment., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Transient neonatal diabetes mellitus (TNDM) is a rare form of diabetes mellitus that usually presents within the first 6 mo of life. Patients often enter remission within several months, although relapse can occur later in life. Mutations in the ABCC8 gene, which encodes the sulfonylurea receptor 1 of the ATP-sensitive potassium channel in pancreatic beta cells, are associated with TNDM and permanent neonatal diabetes. This study describes a novel de novo c.3880C>T heterozygous ABCC8 variant that causes TNDM and can be treated with sulf-onylurea therapy., Case Summary: We retrospectively analyzed 2 Chinese patients with TNDM who were diagnosed, treated, or referred for follow-up between September 2017 and September 2023. The patients were tested for mutations using targeted next-generation sequencing. Patients with neonatal diabetes mellitus caused by a c.3880C>T heterozygous missense variant in the ABCC8 gene have not been reported before. Both children had an onset of post-infectious diabetic ketoacidosis, which is worth noting. At a follow-up visit after discontinuing insulin injection, oral glyburide was found to be effective with no adverse reactions., Conclusion: Early genetic testing of neonatal diabetes mellitus aids in accurate diagnosis and treatment and helps avoid daily insulin injections that may cause pain., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Asperphenol A ( 1 ), a new isoprenyl-phenol-type meroterpenoid, was isolated from the mangrove endophytic fungus Aspergillus sp. GXNU-Y65 together with five known compounds ( 2 - 6) . All structures were assigned using extensive NMR spectroscopic data and electronic circular dichroism (ECD) calculations. Compounds 1-6 were evaluated for their cytotoxic activity against A549 and T24 human cancer cell lines. Among them, compounds 1 and 5 exhibited moderate inhibitory activities against T24 cancer cell lines with the IC 50 values of 26.71 and 43.50 μM, respectively.

Background: This study aimed to compare the lipemia removal efficiency of highspeed centrifugation, lipid scavengers, and dilution for biochemical analytes., Methods: We collected 30 cases of lipemic plasma in an emergency laboratory and divided them into 4 aliquots. Lipemia was removed by highspeed centrifugation, lipid scavenger, dilution, and ultracentrifugation, then analytes were measured by an AU5800 analyzer. Taking ultracentrifugation as reference, the efficiencies of the other three methods were evaluated based on the deviation., Results: When highspeed centrifugation was used for lipemia removal, DBIL (18.62%), and Magnesium (6.09%) could not satisfy the criterion. When lipid scavengers were applied to remove lipemia, CRP (-86.70%), TP (-8.29%), CKMB (-44.85%), DBIL (37.96%), Glu (4.20%) and phosphate (14.32%) were not suggested as lipid scavengers. For dilution, nearly half of the analytes could satisfy the criterion, including AMY (2.41%), CRP (5.54%), ALT (2.85%), GGTL (-1.73%), ALP (-0.04%), Glu (-0.84%), LDH (0.06%), CK (0.68%), BUN (3.80%), CREA (-1.54%), UA (5.42%), and magnesium (0.43%)., Conclusions: Neither of the methods for lipid removal could satisfy all emergency department tests for lipid removal. This finding suggests that removing lipemia in the clinical laboratory should be based on the characteristics and the method of testing.

Purpose: To report the use of anterior segment optical coherence tomography (AS-OCT) for superficial keratectomy (SK) in anterior corneal opacity., Methods: The characteristics of 43 eyes (39 patients) with various lesions responsible for anterior corneal opacity were included in this retrospective non-comparative study. AS-OCT was performed on all eyes before surgery. The thickness of corneal opacity and the underlying healthy stroma were measured. SK was performed on each individual., Results: Four types of anterior corneal opacity were evaluated, including corneal degeneration (26/43), Reis-Bücklers corneal dystrophy (8/43), alkali burn (1/43) and corneal tumors (8/43). Based on AS-OCT images, all eyes showed abnormal hyper-reflective signals in the superficial cornea to less than one-third of the normal corneal thickness in the deepest corneal opacity. All 43 eyes underwent an SK procedure. In addition, 1 eye with alkali burns and 7 eyes with corneal tumors were combined with amniotic membrane transplantation. All eyes restored transparency without significant complications., Conclusion: AS-OCT is a valuable method for objective preoperative and noninvasive assessments of anterior corneal opacities and is useful for guiding SK., 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 © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Nitric oxide (NO) / β-Lapachone (Lap) combined therapy by causing oxidative stress is an effective tumor therapy strategy. Herein, a dual-responsive lipid nanoparticles (LNPs) LSNO for NO / Lap co-delivery were constructed from the zinc-coordinated lipid (DSNO(Zn)) and the hydrophobic drug Lap in the presence of helper lipids (DOPE and DSPE-PEG 2000 ). The zinc-coordinated structure in LSNO might elevate the Zn 2+ content in tumor cells, contributing to antioxidant imbalance. The fluorescent assays proved the light-triggered NO release and fluorescent self-reporting abilities of LSNO. In addition, the LNPs had good drug release behavior under high concentration of GSH, indicating the NO / drug co-delivery capacity. In vitro antitumor assays showed that the NO / Lap combination treatment group could induce more significant tumor cell growth inhibition and cell apoptosis than individual NO or Lap treatment. The following mechanism studies revealed that NO / Lap combination treatment led to distinct oxidative stress by producing reactive oxygen species (ROS) and peroxynitrite anion (ONOO - ). On the other hand, the intracellular redox balance could be further disrupted by Lap-induced NADPH consumption and Zn 2+ / NO-induced reductase activities downregulation, thus promoting the degree of cell damage. Besides, it was also found that NO and Lap could directly damage nuclear DNA and induce mitochondrial dysfunction, thereby leading to caspase-3 activation and tumor cell death. These results proved that LSNO could serve as a promising multifunctional tumor therapy platform., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: High mammographic density increases breast cancer risk and reduces mammographic sensitivity. We reviewed evidence on accuracy of supplemental MRI for women with dense breasts at average or increased risk., Methods: PubMed and Embase were searched 1995-2022. Articles were included if women received breast MRI following 2D or tomosynthesis mammography. Risk of bias was assessed using QUADAS-2. Analysis used independent studies from the articles. Fixed-effect meta-analytic summaries were estimated for predefined groups (PROSPERO: 230277)., Results: Eighteen primary research articles (24 studies) were identified in women aged 19-87 years. Breast density was heterogeneously or extremely dense (BI-RADS C/D) in 15/18 articles and extremely dense (BI-RADS D) in 3/18 articles. Twelve of 18 articles reported on increased-risk populations. Following 21 440 negative mammographic examinations, 288/320 cancers were detected by MRI. Substantial variation was observed between studies in MRI cancer detection rate, partly associated with prevalent vs incident MRI exams (prevalent: 16.6/1000 exams, 12 studies; incident: 6.8/1000 exams, 7 studies). MRI had high sensitivity for mammographically occult cancer (20 studies with at least 1-year follow-up). In 5/18 articles with sufficient data to estimate relative MRI detection rate, approximately 2 in 3 cancers were detected by MRI (66.3%, 95% CI, 56.3%-75.5%) but not mammography. Positive predictive value was higher for more recent studies. Risk of bias was low in most studies., Conclusion: Supplemental breast MRI following negative mammography in women with dense breasts has breast cancer detection rates of ~16.6/1000 at prevalent and ~6.8/1000 at incident MRI exams, considering both high and average risk settings., (© Society of Breast Imaging 2024. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Fever is one of the most common clinical conditions and is characterized by pyrogenic infection, malignancy, inflammation, and tissue damage, among others. Ellagic acid (EA) can inhibit the expression of related proteins on the pathway by blocking the nuclear factor kappa-B(NF-κB) signaling pathway, inhibit the levels of pro-inflammatory factors interleukin-1β(IL-1β), interleukin-6(IL-6), and tumor necrosis factor-α(TNF-α), increase the level of anti-inflammatory factor IL-10, and effectively alleviate inflammatory symptoms. In addition, EA can also reduce the levels of malondialdehyde(MDA) and nitric oxide(NO) in the body, increase the activities of superoxide dismutase (SOD), glutathione (GSH), and catalase(CAT), scavenge oxidative free radicals, inhibit lipid oxidation, and achieve antipyretic and anti-inflammatory effects. The purpose of this study was to establish the relationship between EA and various inflammatory markers, such as TNF-α, IL-6, IL-1β, prostaglandin E2(PGE 2 ), and cyclic adenosine monophosphate(cAMP), and clarify the mechanism of the cyclooxidase-2(COX-2)/NF-κB signaling pathway. Combined with the metabolomics analysis, our study revealed the effects of EA on multiple endogenous biomarkers, reflecting the characteristics of a multi-component, multi-target, and multi-pathway mechanism. Compared to lipopolysaccharide (LPS)- treated animals, subsequent administration of EA significantly lowered the LPS-induced rectal temperature increase ( p < 0.05 or p < 0.01), significantly increased serum SOD and GSH levels ( p < 0.05 or p < 0.01), and significantly decreased serum MDA, IL-1β, IL-6, and TNF-α levels ( p < 0.05 or p < 0.01). In addition, compared to LPS-treated animals, subsequent administration of EA significantly decreased cerebrospinal fluid cAMP and PGE 2 levels ( p < 0.05 or p < 0.01), significantly decreased cAMP, significantly increased 5-HT levels ( p < 0.05 or p < 0.01), and significantly down-regulated p-NF-κB p65 and COX-2 protein levels in the hypothalamus. Subsequent gas chromatography mass spectrometry(GC-MS) metabolite analysis indicated that 12 differential metabolites were detected in serum isolated 4 h after LPS treatment, and 10 differential metabolites were detected in serum collected 7 h after LPS treatment. Next, Pearson correlation analysis was used to systematically characterize the relationship between the identified metabolites and TNF-α, IL-6, MDA, SOD, PGE 2 , and cAMP. The levels of propionic acid, pyridine, and L-valine were up-regulated by EA, which inhibited the expression of MDA, IL-1β, and TNF-α and increased the activity of GSH. The levels of inositol, urea, and 2-monopalmitin were down-regulated by EA, which inhibited the expression of MDA, IL-1β, and TNF-α, increased the activity of SOD and GSH, reduced the inflammatory response, and alleviated the oxidative stress state. Combined with the results of the metabolic pathway analysis, we suggest that the pathways of the galactose metabolism, synthesis and degradation of ketone bodies, as well as ascorbic acid and aldehyde acid metabolism are closely related to the antipyretic and anti-inflammatory effects of EA. Our study established the relationship between EA and various inflammatory markers, such as TNF-α, IL-6, IL-1β, PGE 2 , and cAMP, and clarified the mechanism of the COX-2/NF-κB signaling pathway. Combined with the metabolomics analysis, our study revealed the effects of EA on multiple endogenous biomarkers, reflecting the characteristics of a multi-component, multi-target, and multi-pathway mechanism., Competing Interests: The authors declare no competing interests.

Ovarian cancer (OV) is a highly aggressive malignancy with poor prognosis due to recurrence and drug resistance. Therefore, it is imperative to investigate the key molecular mechanisms underlying OV progression in order to develop promising diagnostic and therapeutic interventions. Although the importance of hematological and neurological expressed 1 (HN1) protein in hemopoietic cell and neurological development has been well-established, its function in cancer, particularly in OV, remains uncertain. In this study, we compared the expression of HN1 in ovarian cancers and para-tumor tissues and predicted potential related signaling pathways through enrichment analysis. In order to confirm the role of HN1 in vitro and vivo, we carried out a variety of experiments including bioinformation analysis, colony formation, flow cytometry analysis, and subcutaneous tumor models. The results demonstrated that HN1 was upregulated in OV and was negatively associated with clinical prognosis. Moreover, we observed that HN1 enhances cell proliferation, migration, and drug resistance, while suppressing apoptosis in OV cells. Notably, we discovered that HN1 functions as a novel regulator of mTOR pathways. Our findings suggest that HN1-mediated mTOR regulation facilitates OV advancement and targeting HN1 could provide a promising therapeutic approach for clinical OV treatment., (© 2024. The Author(s), under exclusive licence to Society for Reproductive Investigation.)

Nicotinic acetylcholine receptors (nAChRs) regulate pain pathways with various outcomes depending on receptor subtypes, neuron types, and locations. But it remains unknown whether α4β2 nAChRs abundantly expressed in the substantia nigra pars reticulata (SNr) have potential to mitigate hyperalgesia in pain states. We observed that injection of nAChR antagonists into the SNr reduced pain thresholds in naïve mice, whereas injection of nAChR agonists into the SNr relieved hyperalgesia in mice, subjected to capsaicin injection into the lower hind leg, spinal nerve injury, chronic constriction injury, or chronic nicotine exposure. The analgesic effects of nAChR agonists were mimicked by optogenetic stimulation of cholinergic inputs from the pedunculopontine nucleus (PPN) to the SNr, but attenuated upon downregulation of α4 nAChRs on SNr GABAergic neurons and injection of dihydro-β-erythroidine into the SNr. Chronic nicotine-induced hyperalgesia depended on α4 nAChRs in SNr GABAergic neurons and was associated with the reduction of ACh release in the SNr. Either activation of α4 nAChRs in the SNr or optogenetic stimulation of the PPN-SNr cholinergic projection mitigated chronic nicotine-induced hyperalgesia. Interestingly, mechanical stimulation-induced ACh release was significantly attenuated in mice subjected to either capsaicin injection into the lower hind leg or SNI. These results suggest that α4 nAChRs on GABAergic neurons mediate a cholinergic analgesic circuit in the SNr, and these receptors may be effective therapeutic targets to relieve hyperalgesia in acute and chronic pain, and chronic nicotine exposure., (© 2024. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Background: Cry1Ab has emerged as a bio-insecticide to control Spodoptera litura (Lepidoptera: Noctuidae). However, the sublethal effects of Cry1Ab on the physiological changes and molecular level of S. litura have not been well documented. Our aims in this study were to assess the sublethal effect of Cry1Ab on S. litura, including midgut and Malpighian tubules as targets., Results: After sublethal Cry1Ab exposure, distinct histological alterations were mainly observed in the midgut. Furthermore, the results of comparative RNA sequencing and tandem mass tag-based proteomics showed that, in the midgut, most differential expression genes (DEGs) were up-regulated and significantly enriched in the serine protease activity pathway, and up-regulated differential expression proteins (DEPs) were mainly associated with the oxidative phosphorylation pathway, whereas the down-regulated involved in the ribosome pathways. In the Malpighian tubules, DEGs and DEPs were significantly enriched in the ribosome pathway. We proposed that ribosome may act as a universal target in energy metabolism with other pathways via the results of protein-protein interaction analysis. Further, by verification of the mRNA expression of some Cry protein receptor and detoxification genes after Cry1Ab treatment, it was suggested that the ribosomal proteins (RPs) possibly participate in influencing the Bt-resistance of S. litura larvae under sublethal Cry1Ab exposure., Conclusion: Under sublethal Cry1Ab exposure, the midgut of S. litura was damaged, and the proteotranscriptomic analysis elucidated that Cry1Ab disrupted the energy homeostasis of larvae. Furthermore, we emphasized the potential role of ribosomes in sublethal Cry1Ab exposure. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive malignancies, with a notoriously dismal prognosis. As a competitive inhibitor of DNA synthesis, gemcitabine is the cornerstone drug for treating PDAC at all stages. The therapeutic effect of gemcitabine, however, is often hindered by drug resistance, and the underlying mechanisms remain largely unknown. It is unclear whether their response to chemotherapeutics is regulated by endocrine regulators, despite the association between PDAC risk and endocrine deregulation. Here, we show that prolactin receptor (PRLR) synergizes with gemcitabine in both in vitro and in vivo treatment of PDAC. Interestingly, PRLR promotes the expression of miR-4763-3p and miR-3663-5p, two novel miRNAs whose functions are unknown. Furthermore, the analysis of transcriptome sequencing data of tumors from lactating mouse models enriches the PPP pathway, a multifunctional metabolic pathway. In addition to providing energy, the PPP pathway mainly provides a variety of raw materials for anabolism. We demonstrate that two key enzymes of the pentose phosphate pathway (PPP), G6PD and TKT, are directly targeted by miR-4763-3p and miR-3663-5p. Notably, miR-4763-3p and miR-3663-5p diminish the nucleotide synthesis of the PPP pathway, thereby increasing gemcitabine sensitivity. As a result, PRLR harnesses these two miRNAs to suppress PPP and nucleotide synthesis, subsequently elevating the gemcitabine sensitivity of PDAC cells. Also, PDAC tissues and tumors from LSL-KrasG12D/+, LSL-Trp53R172H/+, and PDX1-cre (KPC) mice exhibit downregulation of PRLR. Bisulfite sequencing of PDAC tissues revealed that PRLR downregulation is due to epigenetic methylation. In this study, we show for the first time that the endocrine receptor PRLR improves the effects of gemcitabine by boosting two new miRNAs that block the PPP pathway and nucleotide synthesis by inhibiting two essential enzymes concurrently. The PRLR-miRNAs-PPP axis may serve as a possible therapeutic target to supplement chemotherapy advantages in PDAC., (© 2024 Federation of American Societies for Experimental Biology.)

In the malignant progression of tumors, there is deposition and cross-linking of collagen, as well as an increase in hyaluronic acid content, which can lead to an increase in extracellular matrix stiffness. Recent research evidence have shown that the extracellular matrix plays an important role in angiogenesis, cell proliferation, migration, immunosuppression, apoptosis, metabolism, and resistance to chemotherapeutic by the alterations toward both secretion and degradation. The clinical importance of tumor-associated macrophage is increasingly recognized, and macrophage polarization plays a central role in a series of tumor immune processes through internal signal cascade, thus regulating tumor progression. Immunotherapy has gradually become a reliable potential treatment strategy for conventional chemotherapy resistance and advanced cancer patients, but the presence of immune exclusion has become a major obstacle to treatment effectiveness, and the reasons for their resistance to these approaches remain uncertain. Currently, there is a lack of exact mechanism on the regulation of extracellular matrix stiffness and tumor-associated macrophage polarization on immune exclusion. An in-depth understanding of the relationship between extracellular matrix stiffness, tumor-associated macrophage polarization, and immune exclusion will help reveal new therapeutic targets and guide the development of clinical treatment methods for advanced cancer patients. This review summarized the different pathways and potential molecular mechanisms of extracellular matrix stiffness and tumor-associated macrophage polarization involved in immune exclusion and provided available strategies to address immune exclusion., (© 2024. The Author(s).)

Background: Up to 50% of those attending for low-dose computed tomography screening for lung cancer continue to smoke and co-delivery of smoking cessation services alongside screening may maximise clinical benefit. Here we present data from an opt-out co-located smoking cessation service delivered alongside the Yorkshire Lung Screening Trial (YLST)., Methods: Eligible YLST participants were offered an immediate consultation with a smoking cessation practitioner (SCP) at their screening visit with ongoing smoking cessation support over subsequent weeks., Results: Of 2150 eligible participants, 1905 (89%) accepted the offer of an SCP consultation during their initial visit, with 1609 (75%) receiving ongoing smoking cessation support over subsequent weeks. Uptake of ongoing support was not associated with age, ethnicity, deprivation or educational level in multivariable analyses, although men were less likely to engage (adjusted OR (OR adj ) 0.71, 95% CI 0.56-0.89). Uptake was higher in those with higher nicotine dependency, motivation to stop smoking and self-efficacy for quitting. Overall, 323 participants self-reported quitting at 4 weeks (15.0% of the eligible population); 266 were validated by exhaled carbon monoxide (12.4%). Multivariable analyses of eligible smokers suggested 4-week quitting was more likely in men (OR adj 1.43, 95% CI 1.11-1.84), those with higher motivation to quit and previous quit attempts, while those with a stronger smoking habit in terms of cigarettes per day were less likely to quit., Conclusions: There was high uptake for co-located opt-out smoking cessation support across a wide range of participant demographics. Protected funding for integrated smoking cessation services should be considered to maximise programme equity and benefit., Competing Interests: Conflict of interest: R.L. Murray reports lecture honoraria and travel reimbursement from AstraZeneca, grant funding from Cancer Research UK, Horizon 2020 and UK Prevention Partnership, is a member of the Board of Trustees of and has received consultancy fees from Action on Smoking and Health, and is a member of the Royal College of Physicians, outside the submitted work. P.A.J. Crosbie reports consulting fees and stock options from Everest Detection, lecture honoraria from AstraZeneca, designing a questionnaire for Novartis, and designing a study for North West eHealth, outside the submitted work. D. Baldwin reports lecture honoraria from MSD, AstraZeneca, Roche and BMS, outside the submitted work. J. Britton reports provision of a legal report commissioned by lawyers acting for vape retailers in Canada against a proposed prohibition of vape flavours by the New Brunswick government. The remaining authors have no conflicts of interest relevant to this article to disclose., (Copyright ©The authors 2024.)