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Chong-Rui Xu,1* Huan Lin,1,2* Jian Su,1 Xu-Chao Zhang,1 Yi-Sheng Huang,3 Xue-Ning Yang,1 Qing Zhou,1 Jin-Ji Yang,1 Wen-Zhao Zhong,1 Yi-Long Wu11Guangdong Lung Cancer Institute, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, People’s Republic of China; 2The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, People’s Republic of China; 3Affiliated Zhongshan Hospital of Guangdong Medical University, Zhongshan, Guangdong, People’s Republic of China*These authors contributed equally to this work Purpose: Besides the smoking and occupational exposures, heritable factors have been proven to be a risk factor for lung cancer by several population-based studies, which would misestimate the risk of lung cancer.Patients and methods: To quantify the magnitude of the high risk of lung cancer with family history, we performed a case-based study with 1373 enrolled individuals, which may be more accurate than a population-based study.Results: Risk of lung cancer was higher in people with lung cancer family history than in the control group (OR 2.50, p

The study of terrestrial phosphorus inflow （hereafter referred to as phosphorus inflow） fluxes is essential for controlling non-point source （NPS） pollution. The SWAT model was successfully used to simulate phosphorus inflow fluxes in the Dongting Lake area, while a hybrid model （LSTM and SWAT） was developed and validated for predicting the reduction in phosphorus inflow fluxes among rivers based on three typical reduction scenarios： agricultural control, livestock and poultry reduction, and soil and water conservation measures. The results showed that the inflow flux of TP was 3.9×10 4 t·a -1 , with a TP load of 14.4 kg·（hm 2 ·a） -1 . The flux exhibited notable seasonal variation, peaking during the flood season and decreasing during the non-flood season, which was strongly correlated with runoff, soil erosion, and cropping density. The Sankou area, with an annual average phosphorus inflow flux of 1.87×10 4 t, provided the highest risk and required specific regulation for its phosphorus levels, with the river system area and agricultural land emerging as the principal factors contributing to this risk. The LSTM model, using multi-feature input, effectively simulated phosphorus input fluxes at the sub-basin scale, achieving NSE > 0.6. Additionally, the hybrid model demonstrated better performance at the river system scale, with NSE > 0.8, RPE < 10%, and reduced data feature requirements. The study identified soil inflow reduction as a relatively effective approach for reducing phosphorus flux in the Sankou area, highlighting soil as the primary carrier of phosphorus and emphasizing its significance in non-point source pollution control, in addition to the fact that attention should be paid to the problem of livestock and poultry pollution. These findings offer valuable scientific insights and data support for understanding the spatial and temporal patterns of phosphorus input fluxes and devising phosphorus reduction strategies in the Dongting Lake area.

Coronary microembolization (CME) is defined as atherosclerotic plaque erosion, spontaneous rupture, or rupture of the plaque while undergoing interventional therapy resulting in the formation of tiny emboli that obstruct the coronary microcirculatory system. For percutaneous coronary intervention, CME is a major complication, with a periprocedural incidence of up to 25%. Recent studies have demonstrated that regulatory cell death (RCD) exerts a profound influence on CME through its modulation of inflammatory responses, oxidative stress, cell death, and angiogenesis. RCD, including apoptosis, autophagy, and pyroptosis, is a unique class of genetically highly regulated death patterns pervasive in instances of coronary microembolization. The aim of this review is to summarize the currently known molecular mechanisms underlying CME. Further investigations of the RCD mechanisms may unravel new avenues for the prevention and treatment of CME., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Introduction: An increasing number of early-stage lung adenocarcinomas (LUAD) are detected as lung nodules. The radiological features related to LUAD progression warrant further investigation. Exploration is required to bridge the gap between radiomics-based features and molecular characteristics of lung nodules., Methods: Consensus clustering was applied to the radiomic features of 1212 patients to establish stable clustering. Clusters were illustrated using clinicopathological and next-generation sequencing. A classifier was constructed to further investigate the molecular characteristics in patients with paired computed tomography and RNA sequencing data., Results: Patients were clustered into four clusters. Cluster 1 was associated with a low consolidation-to-tumor ratio, preinvasion, grade I disease, and good prognosis. Clusters 2 and 3 reported increasing malignancy with a higher consolidation-to-tumor ratio, higher pathologic grade, and poor prognosis. Cluster 2 possessed more spread through air spaces and cluster 3 reported a higher proportion of pleural invasion. Cluster 4 had similar clinicopathological features as cluster 1 except but a proportion of grade II disease. RNA sequencing indicated that cluster 1 represented nodules with indolent growth and good differentiation, whereas cluster 4 reported progression in cell development but still had low proliferative activity. Nodules with high proliferation were classified into clusters 2 and 3. In addition, the radiomics classifier distinguished cluster 2 as nodules harboring an activated immune environment, whereas cluster 3 represented nodules with a suppressive immune environment. Furthermore, signatures associated with the prognosis of early-stage LUAD were validated in external datasets., Conclusions: Radiomics features can manifest molecular events driving the progression of LUAD. Our study provides molecular insight into radiomics features and assists in the diagnosis and treatment of early-stage LUAD., Competing Interests: Disclosure Dr. Zhong declares honoraria from AstraZeneca, Bristol-Myers Squibb, Merck Sharp & Dohme, Roche, and Innovent, outside the submitted work. Dr. Wu declares advisory services for AstraZeneca, Boehringer Ingelheim, Novartis, and Takeda; speaker fees from AstraZeneca, Beigene, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, Merck Sharp & Dohme, Pfizer, Roche, Sanofi; and grants from AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Hengrui, and Roche outside the submitted work. The remaining authors declare no conflict of interest., (Copyright © 2024 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Objectives: In recent years, with the advancement of sublobar resection, A safe, painless method for locating peripheral pulmonary nodules is required. Previously, an alternative method of arterial watershed localization was been introduced to remedy the shortcomings of preoperative CT-guided localization or other methods for locating pulmonary nodules, but its technical limitations were discovered during clinical application. Therefore, we innovated a technique to localize non-subpleural nodules using basin analysis of the target vein and validated its feasibility and safety., Methods: Retrospective analysis of surgical cases of pulmonary nodules smaller than 2 cm in our center. Comparison of vein watershed locational method (V-WALM) and CT-guided percutaneous puncture localization wedge dissection based on locating success rate, mean operation duration, mean intraoperative bleeding and median postoperative stay, mean postoperative drainage and mean drainage tube indwelling time., Results: V-WALM and CT-guided localization were used for localized resection of pulmonary nodules in 50 patients each. The localization success rates were 94.0% for V-WALM and 90.0% for CT-guided localization, respectively, with no statistical difference. There was also no statistical difference in patient population distribution between the two groups. The operation time was 95.5 ± 26.4 min for V-WALM and 94.3 ± 37.5 min for CT-guided with no statistical difference, and there was no statistical difference in intraoperative bleeding, postoperative drainage and drainage tube indwelling time. And the lymph node simpling rate of V-WALM was 48.0% much higher than 24% in the localization group., Conclusions: This study demonstrates that the V-WALM is a safe and feasible intraoperative localization method for peripheral lung nodules. It provides a high-precision, fast and minimally invasive approch of intraoperative localization., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery.)

Background: To clearly reveal the correlations between tumor characteristics, age at diagnosis, and epidermal growth factor receptor (EGFR) mutation rates in patients with pulmonary ground-glass opacities (GGOs)., Methods: We retrospectively reviewed 1473 patients with GGOs between January 2015 and May 2020 from two cancer centers. The tumor characteristics and EGFR mutation rates were compared between different age groups. Multivariate logistic regression was fitted to analyze the relationship between age, tumor characteristics, and EGFR mutation rates., Results: The older patients had more large tumors, mixed GGOs with a consolidation-to-tumor ratio (CTR) of >0.5, and invasive adenocarcinoma (IAC) and pathologic stage IA2-IB. Overall, the rate of EGFR mutations in GGOs was 57.3% and the main subtypes were L858R and 19del mutations. The distribution of EGFR subtypes varied in different age and GGO diameter groups. Age (p = 0.036), GGO types (p = 0.005), tumor diameter (p = 0.039), and pathological types (p < 0.001) were significant predictors for EGFR mutation status. Importantly, significant differences in EGFR mutation rates between age groups were mainly observed in the GGO ≤2 cm diameter (p < 0.001), pure GGOs (p = 0.001), and IAC (p = 0.039) cohorts. Overall, those diagnosed at >50 years of age had a 47.0% increased likelihood of harboring EGFR mutations. Compared with the older group, the increased chance of harboring EGFR mutations for patients with larger tumors, mixed GGOs, and IAC was greater in the younger group., Conclusions: The EGFR mutation rates were varied among different tumor characteristics and age at diagnosis. These findings provide new insights into the treatment of GGOs., Competing Interests: Discloure: Wen-Fang Tang, Zhen-Bin Qiu, Xiang-Peng Chu, Yu-Mei Zeng, Yi-Bin Hu, Xuan Tang, Ye-Feng Yu, Wen-Hao Li, Wen-Zhao Zhong, Wei-Zhao Huang, and Yi Liang have declared no conflicts of interest that may be relevant to the contents of this study., (© 2024. The Author(s).)

Helicobacter pylori is increasingly resistant to antibiotics, significantly lowering eradication rates and posing a major public health challenge. This study investigated the distribution of antibiotic-resistant phenotypes and genotypes of H. pylori in Hainan Province. It determined the minimum inhibitory concentrations (MICs) of six antibiotics using the E-test method and detected resistance genes via Sanger sequencing. Furthermore, we compared resistance detection based on phenotypic analysis and whole genome sequencing (WGS) across 19 clinical isolates of H. pylori . A total of 140 H. pylori strains were isolated. The resistance rates to levofloxacin (LEV), clarithromycin (CLA), and metronidazole (MTZ) were 37.9%, 40.0%, and 93.6%, respectively. Notably, only 3.3% of the strains were susceptible to all six antibiotics. Multidrug-resistant strains accounted for 25.0% of the total, with no resistance detected to amoxicillin (AMX), tetracycline (TET), or furazolidone (FR) during the study period. Genotypic resistance to CLA and LEV showed near-perfect concordance with phenotypic resistance, with Kappa values of 0.910 and 0.938, respectively. Although all isolates were phenotypically sensitive to TET, 16 exhibited a mutation in the 16S rRNA gene (A926G). All strains harboring the R16H/C mutation and truncated rdxA were resistant to metronidazole, demonstrating a specificity of 100%. Therefore, FR, AMX, and TET are recommended as suitable empirical treatment options for H. pylori infections in this region. Genotypic analysis provides a reliable method for predicting resistance to CLA and LEV. WGS proves to be a valuable tool for identifying novel resistance loci in H. pylori and contributes to the phylogenetic classification of strains., 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 Lv, Li, Zhang, Chen, Chen, Wang, Yang, Gao, Zeng, Xiong, Huang, Huang, Zhang, Chen and Bai.)

Cancer stands as a predominant cause of mortality across the globe. Traditional cancer treatments, including surgery, radiotherapy, and chemotherapy, are effective yet face challenges like normal tissue damage, complications, and drug resistance. Biomaterials, with their advantages of high efficacy, targeting, and spatiotemporal controllability, have been widely used in cancer treatment. However, the biocompatibility limitations of traditional synthetic materials have restricted their clinical translation and application. Natural cell-inspired biomaterials inherently possess the targeting abilities of cells, biocompatibility, and immune evasion capabilities. Therefore, cell-inspired biomaterials can be used alone or in combination with other drugs or treatment strategies for cancer therapy. In this review, we first introduce the timeline of key milestones in cell-inspired biomaterials for cancer therapy. Then, we describe the abnormalities in cancer including biophysics, cellular biology, and molecular biology aspects. Afterwards, we summarize the design strategies of cell-inspired antitumor biomaterials. Subsequently, we elaborate on the application of antitumor biomaterials inspired by various cell types. Finally, we explore the current challenges and prospects of cell-inspired antitumor materials. This review aims to provide new opportunities and references for the development of antitumor cell-inspired biomaterials., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Wenzhi Song reports financial support was provided by International Cooperation Project of the Jilin Department of Science and Technology. If there are other authors, they 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 Published by Elsevier Ltd.)

Temperature-responsive metamaterials have remarkable shape-morphing ability during thermal energy conversion. However, integrating the thermal shape programmability, wide-working temperature range, fast temperature response, and actuation into metamaterials remains challenging. Here, we introduce using thermostat metal strips to assemble metamaterials with desirable and balanced temperature-responsive properties, and we systematically investigate the thermal deformation performance. Achieving 70 to 80% of the designed strain requires only 5 seconds of heating. A thermal strain of around 30% is achieved for the assembled metamaterials, surpassing other bimetallic metamaterials by a magnitude of 100 to 200. The actuation capacity of thermostat metal strips exceeds 26 times their weight. Further, by leveraging the highly programmable thermal deformation, the tuneable bandgap range is 3847 to 40,000 hertz. These fully integrated mechanical performances in the multiphysics have great application potential, for example, as soft actuators and soft robots in intelligent structure systems, vibration isolation and noise reduction in hypersonic vehicles, and unique thermal deformation in precision instruments.

This study investigates the enhancement of diesel degradation in contaminated soil through the synergistic effects of functional microbiomes and phytoremediation, emphasizing increased enzyme activity. The approach integrates a hydrogen-producing microbiome (HMb) with phytoremediation techniques. Observations revealed changes in soil conditions, including increases in moisture levels from 12.5% to 20% and a shift in pH from 6.9 to an alkaline range of 8.0-8.5 due to the treatment. Organic matter content also improved, supporting microbial activity. These modifications were closely monitored to evaluate their impact on microbial growth and enzyme activity. The findings showed that total petroleum hydrocarbons (TPH) in diesel-contaminated soil decreased by 78.1% using the combined HMb and phytoremediation method. This decrease was markedly higher than the 30.4% achieved through water drenching and the 30.9% with HMb alone. Central to this success were Clostridium sp. and Sporolactobacillus sp., which played essential roles in hydrocarbon degradation. Improved soil conditions supported an increase in microbial populations, with bacterial counts peaking at 6.0 x 10 11 by day 4, enhancing degradation. Additionally, Bermuda grass survival rates increased to 35% by day 35. In the HMb and planting combination, amylase activity peaked at 100% by day 10, significantly aiding degradation, although it later decreased to 1% by day 35. This research presents a robust strategy for diesel-contaminated soil remediation, highlighting significant advancements in microbial growth and degradation efficiency., 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: Patients with ALK-rearranged non-small cell lung cancer (ALK+ NSCLC) with symptomatic brain (BM) and leptomeningeal (LM) metastases are underrepresented in clinical trials due to poor performance status. Additionally, the need for improved and validated assessment criteria for evaluating central nervous system (CNS) response remains critical. Lorlatinib has demonstrated systemic activity in patients with ALK+ NSCLC. This ongoing phase II study aims to evaluate the efficacy and safety of lorlatinib in ALK+ NSCLC patients with progressive CNS metastases., Patients and Methods: This study is a multicenter, open-label, single-arm, prospective trial. Fifty eligible subjects will be divided into 2 cohorts: BM (progressive or new brain parenchymal; n = 30) and LM (positive cerebrospinal fluid cytology and/or MRI ± brain parenchymal metastasis; n = 20). Key inclusion criteria include ALK status confirmed using FDA-approved tests, at least 1 CNS lesion, with or without CNS-related symptoms, and an ECOG performance status of 0-2 for the BM cohort and 0-3 for the LM cohort. Primary endpoint is intracranial objective response rate based on the modified version of response evaluation criteria in solid tumors v1.1 for BM and modified RANO-LM criteria for LM. Key secondary endpoints include intracranial progression-free survival, overall progression-free survival, objective response rate, overall survival, safety and quality of life. Biomarker analysis of paired pretreatment tumor, blood and optional cerebrospinal fluid will be performed as preplanned exploratory analyses., Conclusions: The PEARL study (CTONG2303) will evaluate efficacy of lorlatinib in CNS metastases in ALK+ NSCLC using refined CNS response evaluation criteria, with biomarker analyses providing insights into response and resistance mechanisms., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Numerous systematic reviews and meta-analyses have been published that evaluate the association between periodontal disease and systemic diseases, many of which address similar topics. Moreover, their quality requires assessment. Therefore, we performed a cross-sectional analysis to examine the evidence on the relationship between periodontal disease and systemic diseases., Methods: The PubMed, Embase, Web of Science, and the Cochrane Library databases were systematically searched to identify relevant systematic reviews and meta-analyses. Only studies that considered periodontal disease as the exposure factor and various systemic diseases as the outcome were included. The basic characteristics and pertinent data from the selected studies were extracted. The modified version of A Measurement Tool to Assess Systematic Reviews 2 (AMSTAR 2) was employed for quality assessment, while R software was used for statistical analysis., Results: Among the 212 relevant systematic reviews and meta-analyses, 57 were finally included in our analysis. These studies involved 75 diseases and 81 disease-related outcomes, with cancer (19/81) being the most frequently addressed topic. Of the 81 outcomes, 67 demonstrated a significant association. Notably, the highest risk estimate was found for head and neck cancer [odds ratio (OR) = 3.17, 95% confidence interval (CI) 1.78 - 5.64], while the lowest was observed for premature rupture of the amniotic sac [relative risk (RR) = 1.10, 95% CI 1.08 - 1.12]. The methodological quality ratings indicated that approximately 71.93% of included studies were classified as "Critically low", with another 17.54% rated as "Low", and only about 10.53% categorized as "Moderate"., Conclusions: Periodontal disease significantly elevates the risks associated with 15 cancer-related, 8 cardiovascular-related, 8 metabolic-related, and 5 neurological-related outcomes. However, the overall methodological quality of existing systematic reviews and meta-analyses is generally suboptimal and requires enhancement to generate higher-quality evidence in the future., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare that they have no competing interests., (© 2024. The Author(s).)

Ferroptosis is a newly discovered type of cell death that exerts a crucial role in hepatic fibrosis. Formononetin (FMN), a natural isoflavone compound mainly isolated from Spatholobus suberectus Dunn, shows multiple biological activities, including antioxidant, anti-inflammatory, and hepatoprotection. This research aims to explore the regulatory mechanism of FMN in liver fibrosis and the relationship between NADPH oxidase 4 (NOX4) and ferroptosis. The effects of FMN on HSC ferroptosis were evaluated in rat model of CCl 4 -induced hepatic fibrosis. In vitro, N-acetyl-L-cysteine (NAC) and deferoxamine (DFO) were used to block ferroptosis and then explored the anti-fibrotic effect of FMN. The target protein of FMN was identified by bio-orthogonal click chemistry reaction as well as drug affinity responsive target stability (DARTS), cellular thermal shift (CETSA), surface plasmon resonance (SPR) assays, and isothermal titration calorimetry (ITC) analysis. Here, we found that FMN exerted anti-fibrotic effects via inducing ferroptosis in activated HSCs. NAC and DFO prevented FMN-induced ferroptotic cell death and collagen reduction. Furthermore, FMN bound directly to NOX4 through possible active amino acid residues sites, and increased NOX4-based NADPH oxidase activity to enhance levels of NADP + /NADPH, thus promoting ferroptosis of activated HSCs and relieving liver fibrosis. These results demonstrate that the direct target and mechanism by which FMN improves liver fibrosis, suggesting that FMN may be a natural candidate for further development of liver fibrosis therapy., (© 2024 John Wiley & Sons Ltd.)

Metabolic syndrome (MetS) is a significant public health problem and presents an escalating clinical challenge globally. To combat this problem effectively, urgent measures including identify some modifiable environmental factors are necessary. Outdoor artificial light at night (LAN) exposure garnered much attention due to its impact on circadian rhythms and metabolic process. However, epidemiological evidence on the association between outdoor LAN exposure and MetS remains limited. To determine the relationship between outdoor LAN exposure and MetS, 15,477 adults participated the 33 Communities Chinese Health Study (33CCHS) in 2009 were evaluated. Annual levels of outdoor LAN exposure at participants' residential addresses were assessed using satellite data from the Defense Meteorological Satellite Program (DMSP) Operational Linescan System (OLS). Generalized linear mixed effect models were utilized to assess the association of LAN exposure with MetS and its components, including elevated waist circumference (WC), triglycerides (TG), blood pressure (BP), fasting blood glucose (FBG), and reduced high-density lipoprotein cholesterol (HDL-C). Effect modification by various social demographic and behavior factors was also examined. Overall, 4701 (30.37 %) participants were defined as MetS. The LAN exposure ranged from 6.03 to 175.00 nW/cm 2 /sr. The adjusted odds ratio (OR) of MetS each quartile increment of LAN exposure were 1.43 (95 % CI: 1.21-1.69), 1.44 (95 % CI: 1.19-1.74) and 1.52 (95 % CI: 1.11-2.08), respectively from Q2-Q4. Similar adverse associations were also found for the components of MetS, especially for elevated BP, TG and FBG. Interaction analyses indicated that the above associations were stronger in participants without habitual exercise compared with those with habitual exercise (e.g. OR were 1.52 [95 % CI: 1.28-1.82] vs. 1.27 [95 % CI, 1.04-1.55], P -interaction  = 0.042 for MetS). These findings suggest that long-term exposure to LAN can have a significant deleterious effect on MetS, potentially making LAN an important modifiable environmental factor to target in future preventive strategies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The understanding of cellular energy metabolism activation by engineered scaffolds remains limited, posing challenges for therapeutic applications in tissue regeneration. This study presents biosynthesized poly(3-hydroxybutyrate-co-4-hydroxybutyrate) [P(3HB-co-4HB)] and its major degradation product, 3-hydroxybutyrate (3HB), as endogenous bioenergetic fuels that augment cellular anabolism, thereby facilitating the progression of human bone marrow-derived mesenchymal stem cells (hBMSCs) towards osteoblastogenesis. Our research demonstrated that 3HB markedly boosts in vitro ATP production, elevating mitochondrial membrane potential and capillary-like tube formation. Additionally, it raises citrate levels in the tricarboxylic acid (TCA) cycle, facilitating the synthesis of citrate-containing apatite during hBMSCs osteogenesis. Furthermore, 3HB administration significantly increased bone mass in rats with osteoporosis induced by ovariectomy. The findings also showed that P(3HB-co-4HB) scaffold substantially enhances long-term vascularized bone regeneration in rat cranial defect models. These findings reveal a previously unknown role of 3HB in promoting osteogenesis of hBMSCs and highlight the metabolic activation of P(3HB-co-4HB) scaffold for bone regeneration., Competing Interests: Declaration of interests The authors declare no conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Hypoxia can aggravate tumor occurrence, development, invasion, and metastasis, and greatly inhibit the photodynamic therapy (PDT) effect. Herein, carbon nitride (CNs)-based DNA and photosensitizer co-delivery systems (BPSCNs) with oxygen-producing functions are developed to address this problem. Selenide glucose (Seglu) is used as the dopant to prepare red/NIR-active CNs (SegluCNs). The tumor-targeting unit Bio-PEG 2000 is utilized to construct BPSCNs nanoparticles through esterification reactions. Furthermore, DNA hydrophobization is realized via mixing P53 gene with a positively charged mitochondrial-targeted near-infrared (NIR) emitting photosensitizer (MTTPY), which is encapsulated in non-cationic BPSCNs for synergistic delivery. Ester bonds in BPSCNs@MTTPY-P53 complexes can be disrupted by lipase in the liver to facilitate P53 release, upregulated P53 expression, and promoted HIF-1α degradation in mitochondria. In addition, the oxygen produced by the complexes improved the hypoxic microenvironment of hepatocellular carcinoma (HCC), synergistically downregulated HIF-1α expression in mitochondria, promoted mitochondrial-derived ferroptosis and enhanced the PDT effect of the MTTPY unit. Both in vivo and in vitro experiments indicated that the transfected P53-DNA, produced O 2 and ROS by these complexes synergistically led to mitochondrial-derived ferroptosis in hepatoma cells through the HIF-1α/SLC7A11 pathway, and completely avoiding PDT resistance caused by hypoxia, exerting a significant therapeutic role in HCC treatment., (© 2024 Wiley‐VCH GmbH.)

Vascular remodeling represents a pathological basis for myocardial pathologies, including myocardial hypertrophy and myocardial infarction, which can ultimately lead to heart failure. The molecular mechanism of angiotensin II (Ang II)-induced vascular remodeling following myocardial infarction reperfusion is complex and not yet fully understood. In this study, we examined the effect of Ang II infusion on cardiac vascular remodeling in mice. Single-cell sequencing showed Ang II induced cytoskeletal pathway enrichment and that FOS like-1 (FOSL1) affected mouse cardiac endothelial dysfunction by pseudotime analysis. Myosin heavy chain 9 (MYH9) was predominantly expressed in primary cardiac endothelial cells. The Ang II type I receptor blocker telmisartan and the protein kinase C inhibitor staurosporine suppressed Ang II-induced upregulation of MYH9 and FOSL1 phosphorylation in human umbilical vein endothelial cells. Silencing MYH9 abolished Ang II-mediated inhibition of angiogenesis in human umbilical vein endothelial cells, and attenuated AngII-induced vascular hyperpermeability. We found that FOSL1 directly bound to the MYH9 promoter and thus activated transcription of MYH9 by the dual luciferase reporter and chromatin immunoprecipitation assays, leading to vascular dysfunction. In vivo, 6 weeks after injecting adeno-associated virus-ENT carrying the TEK tyrosine kinase (tie) promoter-driven short hairpin RNA for silencing FOSL1 (AAV-tie-shFOSL1), cardiac function represented by the ejection fraction and fractional shortening was improved, myocardial fibrosis was decreased, protein levels of phosphorylated FOSL1, MYH9, and collagen type I alpha were reduced, and cardiac vascular density was recovered in mice with endothelial Fosl1-specific knockdown in Ang II-infused mice. In ischemia-reperfusion mice, AAV-shFosl1 mice had a reduced infarct size and preserved cardiac function compared with control AAV mice. Our findings suggest a critical role of the FOSL1/MYH9 axis in hindering Ang II-induced vascular remodeling, and we identified FOSL1 as a potential therapeutic target in endothelial cell injuries induced by myocardial ischemia-reperfusion., Competing Interests: Competing interests: The authors declare no competing interests. Institutional review board statement: All of the experimental processes were complied with the US National Institutes of Health Guidelines for Care and Use of Laboratory Animals, and were approved by the Committee of Nantong University (approval No. IACUC20220314-1004.)., (© 2024. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Objectives: To observe the effect of electroacupuncture (EA) on sleep quality and electroencephalogram (EEG) signal in the patients with chronic insomnia and to explore its mechanism., Methods: Sixty patients with chronic insomnia were randomized into an EA group (30 cases, 3 cases dropped out) and a health learning group (30 cases, 3 cases dropped out). In the health learning group, the sleep health education was provided. In the EA group, besides the health education as the health learning group, EA was delivered at Baihui (GV20), Yintang (GV24 + ), bilateral Shenmen (HT7), bilateral Sanyinjiao (SP6), with continuous wave, 2 Hz in frequency, once every other day, and 3 interventions a week. EA was given for 4 weeks successi-vely, composed of 12 treatments. The score of Pittsburgh sleep quality index (PSQI), Hamilton anxiety scale (HAMA), and patient health questionnaire-9 (PHQ-9) before and after treatment were compared between the two groups. The EEG signals were collected and the relative power and entropy of EEG before and after treatment were compared between the two groups., Results: After treatment, the scores of PSQI, HAMA and PHQ-9, the relevant power of β wave in F8 and T3 channels, and that of α wave in T4 channel, and the entropy in T3 channel under the eyes-open (EO) resting state, as well as the relevant power and the entropy of γ wave in F8 channel under the eyes-closed (EC) resting state in the EA group were lower ( P <0.05) than those before the treatment. All of the above results were lower than those of the health learning group at the same time points ( P <0.05). Under the EO resting state, the relevant power of the θ and δ waves of T3 channel and θ wave of T4, O2 and Pz channels of patients in the EA group after the treatment were increased ( P <0.05) than those before the treatment, and higher ( P <0.05) than those of the health learning group at the same time points., Conclusions: Acupuncture is effective on chronic insomnia, which may be related to the regulation EEG signals.

Background: Streptococcus pyogenes is a common gram-positive bacterium, belonging to group A Streptococcus (GAS), and is responsible for causing a range of clinical conditions. Brain abscess caused by GAS is uncommon in pediatric infectious diseases, and GAS brain abscess without acute infectious symptoms has been rarely reported., Case Presentation: We present a case of one GAS brain abscess in a previously healthy child with unusual clinical manifestations of decreased muscle strength in the left limbs. The right frontal lobe mass lesion was resected using a microscope-based neuronavigation system. A sole defectively beta-hemolytic Streptococcus pyogenes was isolated from the lesion. The patient's peripheral blood whole-exome and the pathogen's whole-genome sequencing were performed respectively, revealing a heterozygous mutation in the interferon regulatory factor-8 (IRF8) gene in the patient and lack of hyaluronic acid capsules in Streptococcus pyogenes (genotype emm22). The patient eventually recovered after prompt surgical drainage of the abscess and appropriate antibiotic treatment., Conclusions: It is important to pay attention to Streptococcus pyogenes brain abscesses with mild clinical manifestations. Upon reviewing all the cases of pediatric GAS brain abscess reported in the published literature, we discovered that early diagnosis and treatment are crucial factors that impact the prognosis of GAS brain abscess., Competing Interests: Declarations Ethics approval and consent to participate Study approval and ethical clearance were obtained from the Children’s Hospital, Zhejiang University School of Medicine. Written informed consent was obtained from the guardian of the child and all the participants for participation before data collection. All methods were performed following the ethical standards as laid down in the Declaration of Helsinki and its later amendments or comparable ethical standards. Consent for publication Written informed consent was obtained from the guardian of the child and all the participants for publication of medical images were taken from the patient. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Introduction: EGFR tyrosine kinase inhibitor (TKI) is the standard adjuvant treatment for patients with stages IB to IIIA EGFR -mutated NSCLC. Nevertheless, adapting this approach to include a molecular residual disease (MRD)-guided de-escalation strategy warrants further investigation., Methods: From January 2019 to December 2022, 71 patients with stages I to III NSCLC and EGFR (exon 19 deletion or L858R) mutations were enrolled in this observational study. A total of 375 blood samples were analyzed using the MRD&#95;Navigator assay. Among them, 27 patients suspended EGFR TKI treatment based on undetectable MRD and were thus included in the adaptive, de-escalation group., Results: Overall, the sensitivity of longitudinal MRD was 86.2%. Only four patients (11.8%) recurred with longitudinal undetectable MRD, indicating a negative predictive value of 88.2%. Of the patients who had detectable MRD after surgery, nine subsequently received EGFR TKI treatment, with only one (11.1%) achieving persistent circulating tumor DNA clearance post-EGFR TKI. Furthermore, 22 patients with stages IB to III disease who had previously suspended their TKI treatment based on undetectable MRD were included in the adaptive group, with an average duration of TKI 3.9 (range: 0-35.0) months. The 2-year disease-free survival rate of these 22 patients was 80.2%, and the median was not reached. Five patients (n = 5 of 22, 22.7%) had disease recurrence during the period of drug cessation but were stable under EGFR TKI treatment until the latest follow-up. Two patients remained in complete remission., Conclusions: Our initial findings underscore the potential of an adaptive, de-escalation approach to adjuvant EGFR TKIs based on circulating tumor DNA-MRD monitoring., Competing Interests: Dr. Zhou declares receiving speaker fees from 10.13039/100004325AstraZeneca and 10.13039/100004337Roche. Dr. Zhong declares receiving speaker fees from AstraZeneca and Roche. Dr. Wu declares receiving speaker fees from AstraZeneca, Eli Lilly, Pfizer, Roche, and Sanofi. The remaining authors declare no conflict of interest., (© 2024 The Authors.)

Taenia multiceps is a neglected parasite having veterinary and public health importance. The predilection sites of the parasite larva (Coenurus cerebralis) are brain (cerebral coenurosis) and subcutaneous (non-cerebral coenurosis). There is a dearth of data regarding molecular characterization of T. multiceps and even fewer population structure-based studies on T. multiceps. The current study was conducted to provide epidemiological information regarding the global population structure of the parasite. The NCBI GenBank database was accessed to download the sequences of cox1 gene, which were further subjected to PopArt software to construct median-joining networks. The DnaSp software was used to compute neutrality and diversity indices. Host and region-wise indices of neutrality and diversity were also computed. There were 166 gene sequences found in the NCBI database. Followed by removal of short gene sequences, 143 were considered to perform bioinformatic analyses. A total of 30 haplotypes with 46 mutations and 23 parsimony informative sites were found. High diversity (Hd = 0.889, π = 0.01186) and negative but statistically insignificant neutrality indices (Tajima's D = -1.57659, Fu's Fs = -10.552) were found. Region-wise results revealed highest haplotype diversities in isolates from KSA (Hd = 1.00) followed by Greece and Italy (Hd = 0.962), and China (Hd = 0.931). Host-wise data analysis showed an overall negative Tajima's D value and there exists highest haplotype diversity in cattle (Hd = 1.00) followed by dogs (Hd = 0.833), sheep (Hd = 0.795) and goats (Hd = 0.788). The findings of the study indicate that the population diversity of T. multiceps will increase worldwide as shown by high diversity and negative neutrality indices. The findings of the study significantly add-in to the existing bank of knowledge about population structure of T. multiceps. We recommend conducting more studies employing different genetic markers to better comprehend the epidemiology of the parasite., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

In the work, the 1/2 order subharmonic wave of two coupling cavitation bubbles is investigated numerically via Fourier spectrum analysis. By analyzing the dynamics of bubble, we find that the mutual interaction between bubbles can affect the appearance of 1/2 order subharmonic. The results of parameter dependence show that the intensity of 1/2 order subharmonic would be promoted or inhibited with the increase of mutual interaction. The higher the driving amplitude or the smaller the distance between bubbles, the stronger the mutual interaction is, and also the greater the promotion or suppression of the 1/2 order subharmonic is. Moreover, while the 1/2 order subharmonic occurs, the energy of bubble would alternate between two different peaks, and the temperature inside bubble has a similar fluctuation while the bubble collapses. This qualitative analysis suggests that the bubble's dynamics for multi-bubble case is complex. Understanding the generation of subharmonic of bubble's dynamics is of great significance for helpful applying of cavitation bubble., 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 The Author(s). Published by Elsevier B.V. All rights reserved.)

Purpose: Hepatocellular carcinoma (HCC) represents a significant global health problem, requiring precise prognostic tools for optimal treatment stratification. This study aimed to develop a new risk prediction score, called AD score, based on the serum markers alpha-fetoprotein (AFP) and des-γ-carboxy prothrombin (DCP), to offer an objective and accurate preoperative assessment of HCC in patients undergoing transarterial chemoembolization (TACE)., Patients and Methods: This was a retrospective study that included 295 HCC patients who were subjected to TACE (training set, n=147; testing set, n=148). Serum AFP and DCP levels were log-transformed to construct the AD score. Multivariate Cox regression analysis on cirrhosis subgroups validated the objectivity of the model. Performance comparison of established models (Child Pugh, BCLC, ALBI, Up-to-seven, Six-and-twelve, Four and seven, HAP score, mHAP-II, FAIL-T score), was assessed through time-dependent receiver operating characteristic (ROC) curves and risk stratification., Results: The AD score, incorporating lgAFP and lgDCP, demonstrated superior predictive accuracy than the existing models. Time-dependent ROC curve revealed the consistent superiority of the AD score over a 5-year period. The risk stratification into low, intermediate, and high group based on the AD score showed a significant survival difference in both training and testing set., Conclusion: For HCC patients undergoing TACE, the AD score serves as an objective and straightforward prognostic tool, enhancing predictive accuracy and showcasing its clinical utility. It demonstrates potential significance as a crucial addition to preoperative risk assessment for TACE., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Lu et al.)

Astrocytes play significant roles in regulating the central stress response. Chronic stress impairs the structure and function of astrocytes in many brain regions such as media prefrontal cortex (mPFC) in multiple neuropsychiatric conditions, but the astrocytic dynamics on the timescale of behavior remains unclear. Here, we recorded mPFC astrocytic activity in freely behaving mice and found that astrocytes are activated immediately by different aversive stimuli. Astrocyte specific GCaMP6s calcium indicator were virally expressed in mPFC astrocytes and fiber photometry experiments revealed that astrocytes are activated by tail-restraint (TRT), foot shock (FS), open arm exploration, stressor of height, predator odor and social defeat (SD) stress. ΔF/F analyses demonstrated that an unpredictable stimulus such as elevated platform stress (EPS) at the initial encounter induced the most intense and rapid changes in astrocytic calcium activity, while a predictable 2,5-dihydro-2,4,5-trimethylthiazoline (TMT) stimulus resulted in the weakest response with a longer peak latency. In TRT, FS or SD test, a somatic stimulus led to higher average calcium activity level and faster average peak latency in repeated trails. Similar to TMT stimulus, astrocytic calcium activity in elevated plus maze (EPM) test exhibited a smaller average change in amplitude and the longest peak latency during open arm exploration. Moreover, astrocytic calcium activity exhibited different changes across behavioral states in SD tests. Our findings show that mPFC astrocytes exhibit distinct patterns of calcium activity in response to various negative stimuli, indicating that the dynamic activity of astrocytes may reflect the stress-related behavioral state under different stimulus conditions., 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., (© 2024 The Authors. Published by Elsevier Inc.)

Background: This study aimed to compare the survival outcomes of transarterial chemoembolization (TACE) between patients with early recurrent hepatocellular carcinoma (rHCC) after hepatic resection, stratified by cytokeratin (CK) 19 expression., Methods: A retrospective analysis was conducted on 63 patients with early rHCC after hepatic resection who underwent TACE between January 2017 and December 2021. Patients were divided into two groups based on CK19 expression: CK19-negative (n=31) and CK19-positive (n=32). Overall survival (OS) and progression-free survival (PFS) were compared between the two groups using the Kaplan-Meier method and log-rank test. Cox regression analysis was performed to identify independent risk factors for OS and PFS., Results: The CK19-negative group demonstrated a significantly longer median OS compared to the CK19-positive group (635 days vs. 432 days, p=0.013). Similarly, the CK19-negative group had a longer median PFS than the CK19-positive group (291 days vs. 117 days, p=0.014). Multivariate Cox analysis identified Child-Pugh A grade, CK19-negative expression, and increased TACE sessions as protective factors for OS. No severe TACE-related adverse events were observed., Conclusion: In patients with early rHCC after hepatic resection, those with CK19-positive expression had poorer survival outcomes following TACE compared to CK19-negative patients. These findings suggest the need for additional therapies to improve survival in CK19-positive individuals., (© 2024. The Author(s).)

Titanium (Ti) and its alloys are known to exhibit room-temperature fracture toughness below 130 MPa m 1/2 , only about one half of the best austenitic stainless steels. It is purported that this is not the best possible fracture resistance of Ti, but a result of oxygen impurities that sensitively retard the activities of plasticity carriers in this hexagonal close-packed metal. By a reduction of oxygen content from the 0.14 wt% in commercial purity Ti to 0.02 wt%, the mode-Ι fracture toughness of the low-oxygen Ti is measured to be as high as K J Ic ≈ 255 MPa m 1/2 , corresponding to J-integral-based crack-initiation toughness of up to J Ic ≈ 537 kJ m -2 . This extraordinary toughness, reported here for the first time for pure Ti, places Ti among the toughest known materials. The intrinsic high fracture resistance is attributed to the profuse plastic deformation in a significantly enlarged plastic zone, rendered by the pronounced deformation twinning ahead of the crack tip along with ample twin-stimulated 〈c+a〉 dislocation activities, in the absence of impeding oxygen. Controlling the content of a property-controlling impurity thus holds the promise to be a readily applicable strategy to reach for unprecedented damage tolerance in some other structural alloys., (© 2024 Wiley‐VCH GmbH.)

Powerful distributed computing can be achieved by communicating cells that individually perform simple operations. Here, we report design software to divide a large genetic circuit across cells as well as the genetic parts to implement the subcircuits in their genomes. These tools were demonstrated using a 2-bit version of the MD5 hashing algorithm, which is an early predecessor to the cryptographic functions underlying cryptocurrency. One iteration requires 110 logic gates, which were partitioned across 66 Escherichia coli strains, requiring the introduction of a total of 1.1 Mb of recombinant DNA into their genomes. The strains were individually experimentally verified to integrate their assigned input signals, process this information correctly and propagate the result to the cell in the next layer. This work demonstrates the potential to obtain programable control of multicellular biological processes., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

The community structure of natural mature forests is determined by long-term forest succession, characterized by rational structure, rich biodiversity, and high ecological function. Understanding the spatial structure and formation mechanisms of mature forests is a fundamental prerequisite for forest management. We analyzed four structure parameters, including diameter structure, angular scale, size ratio, and mixture degree, as well as the Hegyi competition index, of secondary Quercus mongolica (Mongolian oak) mature forests in the mountainous area of eastern Liaoning Province. The results showed that Q. mongolica predominated the tree layer. In the sapling layer, Q. mongolica , Tilia amurensis , and Acer pictum were the dominant species. In the seedling layer, Acer pseudosieboldianum , T. amurensis , and A. amurensis dominated, with very few Q. mongolica seedlings. The overall diameter distribution of the stand showed an inverse "J" shape, while the diameter distribution of Q. mongolica , the dominant tree species, followed a normal distribution. The horizontal spatial structure of the stand was generally randomly distributed, with an average angle scale of 0.505, size ratio of 0.219, and mixture degree of 0.670 for Q. mongolica . From the perspective of spatial structure binary distribution, Q. mongolica individuals which had a random distribution exhibited greater growth advantages and higher levels of mixing, in comparison to other distribution types. Randomly distributed dominant and subdominant individuals made up nearly half individuals in the stand, and showed a high degree of mixing with surrounding trees. The stand-level individual tree competition index decreased with increasing diameter classes. When the diameter at breast height exceeded 20 cm, the competition index tended to stabilize (ΔCI<2). The competitive radius of individual Q. mongolica trees was 8 m, with intraspecific competition as the main pressure. Other species experienced competition pressure primarily from interspecific sources. Our results suggested that competition played an important role in shaping the spatial structure of secondary Q. mongolica mature forests.

Background: Currently, there are no optimal biomarkers available for distinguishing patients who will respond to immune checkpoint inhibitors (ICIs) therapies. Consequently, the exploration of novel biomarkers that can predict responsiveness to ICIs is crucial in the field of immunotherapy., Methods: We estimated the proportions of 22 immune cell components in 10 cancer types (6,128 tumors) using the CIBERSORT algorithm, and further classified patients based on their tumor immune cell proportions in a pan-cancer setting using k-means clustering. Differentially expressed immune genes between the patient subgroups were identified, and potential predictive biomarkers for ICIs were explored. Finally, the predictive value of the identified biomarkers was verified in patients with urothelial carcinoma (UC) and esophageal squamous cell carcinoma (ESCC) who received ICIs., Results: Our study identified two subgroups of patients with distinct immune infiltrating phenotypes and differing clinical outcomes. The patient subgroup with improved outcomes displayed tumors enriched with genes related to immune response regulation and pathway activation. Furthermore, CCL5 and CSF2 were identified as immune-related hub-genes and were found to be prognostic in a pan-cancer setting. Importantly, UC and ESCC patients with high expression of CCL5 and low expression of CSF2 responded better to ICIs., Conclusion: We demonstrated CCL5 and CSF2 as potential novel biomarkers for predicting the response to ICIs in patients with UC and ESCC. The predictive value of these biomarkers in other cancer types warrants further evaluation in future studies., (© 2024. The Author(s).)

The regulation of small- and medium-sized floods （RSMF） has become the main mode of regulation in the flood season of the Three Gorges Reservoir （TGR）. To study the response of phytoplankton in the tributary bays of the TGR to the RSMF, a typical eutrophic tributary of the TGR, Xiangxi River, was investigated for the spatiotemporal distribution characteristics of phytoplankton and nutrients in the main and tributary streams from 2020 to 2021. The response characteristics of phytoplankton in the tributary bays to the RSMF were analyzed. The results indicated that during the RSMF, the chlorophyll a （Chl-a） in the water body of the Xiangxi River decreased with the increase in the water level in front of the dam, whereas during the reservoir impounding at the end of flood season, the concentration of Chl-a increased again. During the RSMF, the Chlorophyta and Diatoma were the main communities of planktonic algae in the Xiangxi River. The phytoplankton community changed with the RSMF. When the water level fluctuation increased, diatoms were the main species, whereas when the water level fluctuation was small, blue and green algae were the main species. The concentration of Chl-a was more sensitive to changes in TN concentration. When the flow velocity was &gt;0.25 m·s -1 or the suspended sediment content was &gt;10 mg·L -1 , the concentration of Chl-a in the water was inhibited. After 2010, the typical outbreak time of algal blooms in the Xiangxi River Reservoir Bay shifted to the flood season, with only two non-flood season algal blooms. Further attention needs to be paid to the response of algal blooms in the reservoir to small- and medium-sized flood control during the flood season.

Leptomeningeal metastases (LMs) remain a devastating complication of non-small cell lung cancer (NSCLC), particularly following osimertinib resistance. We conducted single-cell RNA sequencing on cerebrospinal fluid (CSF) from EGFR-mutant NSCLC with central nervous system metastases. We found that macrophages of LMs displayed functional and phenotypic heterogeneity and enhanced immunosuppressive properties. A population of lipid-associated macrophages, namely RNASE1&#95;M, were linked to osimertinib resistance and LM development, which was regulated by Midkine (MDK) from malignant epithelial cells. MDK exhibited significant elevation in both CSF and plasma among patients with LMs, with higher MDK levels correlating to poorer outcomes in an independent cohort. Moreover, MDK could promote macrophage M2 polarization with lipid metabolism and phagocytic function. Furthermore, malignant epithelial cells in CSF, particularly after resistance to osimertinib, potentially achieved immune evasion through CD47-SIRPA interactions with RNASE1&#95;M. In conclusion, we revealed a specific subtype of macrophages linked to osimertinib resistance and LM development, providing a potential target to overcome LMs., Competing Interests: Declaration of interests Y.-L.W. has received honoraria from AstraZeneca, Eli Lilly, Roche, Pierre Fabre, Pfizer, and Sanofi and has consulting or advisory roles with AstraZeneca, Roche, Merck, Boehringer Ingelheim, and Roche outside the submitted work., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Harmful algal blooms (HABs), caused by the rapid proliferation or aggregation of microorganisms, are catastrophic for the environment. The Prymnesium parvum is a haptophyte algal species that is found worldwide and is responsible for extensive blooms and death of larval amphibians and bivalves, causing serious negative impacts on the ecological environment. For the prevention and management of environmental pollution, it is crucial to explore and develop early detection strategies for HABs on-site using simple methods. The major challenge related to early detection is the accurate and sensitive detection of algae present in low abundance., Results: Herein, recombinase polymerase amplification (RPA) was combined with clustered regularly interspaced short palindromic repeats and Cas12a protein (CRISPR-LbaCas12a) systems, and the lateral flow dipstick (LFD) was used for the first time for early detection of P. parvum. The internal transcribed spacer (ITS) of P. parvum was selected as the target sequence, and the concentration of single-strand DNA reporters, buffer liquid system, reaction time, and amount of gold particles were optimized. The RPA-CRISPR-LbaCas12a-LFD approach demonstrated highly specificity during experimental testing, with no cross-reaction against different microalgae used as controls. In addition, the lowest detection limit was 10,000 times better than the lowest detection limit of the standalone RPA approach. The feasibility and robustness of this approach were further verified by using the different environmental samples. It also observed that P. parvum are widely distributed in Chinese Sea, but the cell density of P. parvum is relatively low (<0.1 cells/mL)., Significance: The developed approach has an excellent specificity and offers 10,000 times better sensitivity than the standalone RPA approach. These advantages make this approach suitable for early warning detection and prevention of HAB events in environmental water. Also, the outcomes of this study could promote a shift from traditional laboratory-based detection to on-site monitoring, facilitating early warning against HABs., 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.)

Background: There is currently a shortage of accurate, efficient, and precise predictive instruments for rectal neuroendocrine neoplasms (NENs)., Aim: To develop a predictive model for individuals with rectal NENs (R-NENs) using data from a large cohort., Methods: Data from patients with primary R-NENs were retrospectively collected from 17 large-scale referral medical centers in China. Random forest and Cox proportional hazard models were used to identify the risk factors for overall survival and progression-free survival, and two nomograms were constructed., Results: A total of 1408 patients with R-NENs were included. Tumor grade, T stage, tumor size, age, and a prognostic nutritional index were important risk factors for prognosis. The GATIS score was calculated based on these five indicators. For overall survival prediction, the respective C-indexes in the training set were 0.915 (95% confidence interval: 0.866-0.964) for overall survival prediction and 0.908 (95% confidence interval: 0.872-0.944) for progression-free survival prediction. According to decision curve analysis, net benefit of the GATIS score was higher than that of a single factor. The time-dependent area under the receiver operating characteristic curve showed that the predictive power of the GATIS score was higher than that of the TNM stage and pathological grade at all time periods., Conclusion: The GATIS score had a good predictive effect on the prognosis of patients with R-NENs, with efficacy superior to that of the World Health Organization grade and TNM stage., 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.)

To investigate the efficacy of chiropractic rehabilitation therapy in Crowe IV developmental dysplasia of the hip (DDH) patients after total hip arthroplasty. Seventy-two patients with Crowe IV type DDH hospitalized in the Department of Orthopedics I of Ya'an Hospital of Traditional Chinese Medicine from January 2021 to June 2023 were selected for the study, and they were divided into 36 cases in the chiropractic rehabilitation therapy group (the treatment group) and 36 cases in the traditional rehabilitation therapy group (the control group) according to the method of randomized grouping. All patients were evaluated at preoperative, 1, 3, and 6 months postoperatively for follow-up, and the muscle strength of the affected limb, the patient's walking gait, the shortened length of the affected limb, the visual analog scale score (VAS score), the Oswestry Dysfunction Index Score (ODI score), the Harris Hip Score, and the degree of pelvic tilt were recorded to evaluate the results of the study. A total of 4 subjects withdrew from the study, 2 in the treatment group, and 2 in the control group. The muscle strength of the affected limb, walking gait, shortened length of the affected limb, VAS score, ODI score, Harris score, and pelvic tilt in the treatment and control groups improved significantly compared with the preoperative period. Comparisons between the 2 groups revealed that at the final follow-up visit, the limp gait of the patients in the treatment group was significantly reduced, the shortened length of the affected limb was significantly reduced, the VAS score was significantly reduced, and the ODI score was significantly reduced, in the treatment group relative to that of the control group, Harris Hip Score was significantly improved, and the degree of pelvic tilt was significantly reduced, but the improvement in muscle strength of the affected limb was not statistically significant. In future clinical practice, we recommend that chiropractic rehabilitation be used as a routine adjunctive treatment after TKA in patients with Crowe IV DDH to optimize outcomes and improve patients' quality of life., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Human respiratory syncytial virus (HRSV) is the most prevalent pathogen contributing to acute respiratory tract infections (ARTI) in infants and young children and can lead to significant financial and medical costs. Here, we developed a simultaneous, dual-gene and ultrasensitive detection system for typing HRSV within 60 minutes that needs only minimum laboratory support. Briefly, multiplex integrating reverse transcription-recombinase polymerase amplification (RT-RPA) was performed with viral RNA extracted from nasopharyngeal swabs as a template for the amplification of the specific regions of subtypes A (HRSV A ) and B (HRSV B ) of HRSV. Next, the Pyrococcus furiosus Argonaute ( PfAgo ) protein utilizes small 5'-phosphorylated DNA guides to cleave target sequences and produce fluorophore signals (FAM and ROX). Compared with the traditional gold standard (RT-qPCR) and direct immunofluorescence assay (DFA), this method has the additional advantages of easy operation, efficiency and sensitivity, with a limit of detection (LOD) of 1 copy/μL. In terms of clinical sample validation, the diagnostic accuracy of the method for determining the HRSV A and HRSV B infection was greater than 95%. This technique provides a reliable point-of-care (POC) testing for the diagnosis of HRSV-induced ARTI in children and for outbreak management, especially in resource-limited settings., 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 Liao, Feng, Zhang, Yang, Zhan, Zeng, Huang, Lian, Ke, Cai, Zhang, Fang, Cai, Chen, Lin, Lin, Chen, Liu, Huang, Lin and Lin.)

Phosphorus concentration on the surface of seawater varies greatly with different environments, especially in coastal. The molecular mechanism by which cyanobacteria adapt to fluctuating phosphorus bioavailability is still unclear. In this study, transcriptomes and gene knockouts were used to investigate the adaptive molecular mechanism of a model coastal cyanobacterium Synechococcus sp. PCC 7002 during periods of phosphorus starvation and phosphorus recovery (adding sufficient phosphorus after phosphorus starvation). The findings indicated that phosphorus deficiency affected the photosynthesis, ribosome synthesis, and bacterial motility pathways, which recommenced after phosphorus was resupplied. Even more, most of the metabolic pathways of cyanobacteria were enhanced after phosphorus recovery compared to the control which was kept in continuous phosphorus replete conditions. Based on transcriptome, 54 genes potentially related to phosphorus-deficiency adaptation were selected and knocked out individually or in combination. It was found that five mutants showed weak growth phenotype under phosphorus deficiency, indicating the importance of the genes ( A0076 , A0549-50 , A1094 , A1320 , A1895 ) in the adaptation of phosphorus deficiency. Three mutants were found to grow better than the wild type under phosphorus deficiency, suggesting that the products of these genes ( A0079 , A0340 , A2284-86 ) might influence the adaptation to phosphorus deficiency. Bioinformatics analysis revealed that cyanobacteria exposed to highly fluctuating phosphorus concentrations have more sophisticated phosphorus acquisition strategies. These results elucidated that Synechococcus sp. PCC 7002 have variable phosphorus response mechanisms to adapt to fluctuating phosphorus concentration, providing a novel perspective of how cyanobacteria may respond to the complex and dynamic environments., Supplementary Information: The online version contains supplementary material available at 10.1007/s42995-024-00244-y., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest., (© The Author(s) 2024.)

The clinical efficacy of neoadjuvant immunotherapy plus chemotherapy remains elusive in localized epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC). Here, we report interim results of a Simon's two-stage design, phase 2 trial using neoadjuvant sintilimab with carboplatin and nab-paclitaxel in resectable EGFR-mutant NSCLC. All 18 patients undergo radical surgery, with one patient experiencing surgery delay. Fourteen patients exhibit confirmed radiological response, with 44% achieving major pathological response (MPR) and no pathological complete response (pCR). Similar genomic alterations are observed before and after treatment without influencing the efficacy of subsequent EGFR-tyrosine kinase inhibitors (TKIs) in vitro. Infiltration and T cell receptor (TCR) clonal expansion of CCR8 + regulatory T (Treg) hi /CXCL13 + exhausted T (Tex) lo cells define a subtype of EGFR-mutant NSCLC highly resistant to immunotherapy, with the phenotype potentially serving as a promising signature to predict immunotherapy efficacy. Informed circulating tumor DNA (ctDNA) detection in EGFR-mutant NSCLC could help identify patients nonresponsive to neoadjuvant immunochemotherapy. These findings provide supportive data for the utilization of neoadjuvant immunochemotherapy and insight into immune resistance in EGFR-mutant NSCLC., Competing Interests: Declaration of interests W.-Z.Z.. received speech honoraria from AstraZeneca, Roche, Eli Lilly, and Pfizer outside the submitted work. Z.-M.Z. is a founder of Analytical BioSciences. Y.-L.W. received research funding from Roche and speech honoraria from AstraZeneca, Roche, Eli Lilly, Pfizer, and Sanofi, and he was a research consultant for AstraZeneca. Q.Z. reports honoraria from AstraZeneca, Boehringer Ingelheim, BMS, Eli Lilly, MSD, Pfizer, Roche, and Sanofi outside the submitted work., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Hypoxia can lead to liver fibrosis and severely limits the efficacy of photodynamic therapy (PDT). Herein, carbon nitride (CN)-based hybrid nanoparticles (NPs) VPSGCNs@TSI for light-driven water splitting were utilized to solve this problem. CNs were doped with selenide glucose (Se-glu) to enhance their red/NIR region absorption. Then, vitamin A-poly(ethylene glycol) (VA-PEG) fragments and aggregation-induced emission (AIE) photosensitizers TSI were introduced into Se-glu-doped CN NPs (VPSGCNs) to construct VPSGCNs@TSI NPs. The introduction of VA-PEG fragments enhanced the targeting of the NPs to activated hepatic stellate cells (HSCs) and reduced their toxicity to ordinary liver cells. VPSGCN units could trigger water splitting to generate O 2 under 660 nm laser irradiation, improve the hypoxic environment of the fibrosis site, downregulate HIF-1α expression, and activate HSC ferroptosis via the HIF-1α/SLC7A11 pathway. In addition, generated O 2 could also increase the reactive oxygen species (ROS) production of TSI units in a hypoxic environment, thereby completely reversing hypoxia-triggered PDT resistance to enhance the PDT effect. The combination of water-splitting materials and photodynamic materials showed a 1 + 1 > 2 effect in increasing oxygen levels in liver fibrosis, promoting ferroptosis of activated HSCs and reversing PDT resistance caused by hypoxia.

Importance: Uninterrupted targeted therapy until disease progression or intolerable toxic effects is currently the routine therapy for advanced non-small cell lung cancer (NSCLC) involving driver gene variations. However, drug resistance is inevitable., Objective: To assess the clinical feasibility of adaptive de-escalation tyrosine kinase inhibitor (TKI) treatment guided by circulating tumor DNA (ctDNA) for achieving complete remission after local consolidative therapy (LCT) in patients with advanced NSCLC., Design, Setting, and Participants: This prospective nonrandomized controlled trial was conducted at a single center from June 3, 2020, to July 19, 2022, and included 60 patients with advanced NSCLC with driver variations without radiologically detectable disease after TKI and LCT. The median (range) follow-up time was 19.2 (3.8-29.7) months. Data analysis was conducted from December 15, 2022, to May 10, 2023., Intervention: Cessation of TKI treatment and follow-up every 3 months. Treatment was restarted in patients with progressive disease (defined by the Response Evaluation Criteria in Solid Tumors 1.1 criteria), detectable ctDNA, or elevated carcinoembryonic antigen (CEA) levels, whichever manifested first, and treatment ceased if all indicators were negative during follow-up surveillance., Main Outcomes and Measures: Progression-free survival (PFS). Secondary end points were objective response rate, time to next treatment, and overall survival., Results: Among the total study sample of 60 participants (median [range] age, 55 [21-75] years; 33 [55%] were female), the median PFS was 18.4 (95% CI, 12.6-24.2) months and the median (range) total treatment break duration was 9.1 (1.5-28.1) months. Fourteen patients (group A) remained in TKI cessation with a median (range) treatment break duration of 20.3 (6.8-28.1) months; 31 patients (group B) received retreatment owing to detectable ctDNA and/or CEA and had a median PFS of 20.2 (95% CI, 12.9-27.4) months with a median (range) total treatment break duration of 8.8 (1.5-20.6) months; and 15 patients (group C) who underwent retreatment with TKIs due to progressive disease had a median PFS of 5.5 (95% CI, 1.5-7.2) months. For all participants, the TKI retreatment response rate was 96%, the median time to next treatment was 29.3 (95% CI, 25.3-35.2) months, and the data for overall survival were immature., Conclusions and Relevance: The findings of this nonrandomized controlled trial suggest that this adaptive de-escalation TKI strategy for patients with NSCLC is feasible in those with no lesions after LCT and a negative ctDNA test result. This might provide a de-escalation treatment strategy guided by ctDNA for the subset of patients with advanced NSCLC., Trial Registration: ClinicalTrials.gov Identifier: NCT03046316.

Purpose: The aim of this work was to determine whether locally advanced rectal cancer (LARC) with negative mesorectal fascia (MRF) predicted by magnetic resonance imaging (MRI) can be excluded from preoperative radiation therapy treatment., Methods and Materials: This multicenter, open-label, non-inferiority, randomized clinical trial enrolled patients with LARC within 6 to 12 cm from the anal verge and with negative MRI-predicted MRF. Participants were randomized to the intervention group (primary surgery, in which the patients with positive pathologic [CRM] circumferential margins were subjected to chemoradiotherapy [CRT] and those with negative CRM underwent adjuvant chemotherapy according to pathologic staging) or the control group (preoperative CRT, in which all patients underwent subsequent surgery and adjuvant chemotherapy). The primary endpoint was 3-year disease-free survival (DFS)., Results: A total of 275 patients were randomly assigned to the intervention (n = 140) and control (n = 135) groups, in which 33.57% and 28.15% patients were at clinical T4 stage and 85.92% and 80.45% patients were at "bad" or "ugly" risk in the intervention and control groups, respectively. There were 2 patients (1.52%) and 1 patient (0.77%) with positive CRM in the intervention and control groups, respectively (P > .05). The non-adherence rates for the intervention and control groups were 3.6% and 23.7%, respectively. After a median follow-up of 34.6 months (IQR, 18.2-45.7), 43 patients had positive events (28 patients and 15 patients in the intervention and control groups, respectively). There were 6 patients (4.4%) with local recurrence in the intervention group and none in the control group, which led to the termination of the trial. The 3-year DFS rate was 81.82% in the intervention group (95% CI, 78.18%-85.46%) and 85.37% in the control group (95% CI, 81.75%-88.99%), with a difference of -3.55% (95% CI, -3.71% to -3.39%; hazard ratio, 1.76; 95% CI, 0.94-3.30). In the per-protocol data set, the difference between 3-year DFS rates was -5.44% (95% CI, -5.63% to -5.25%; hazard ratio, 2.02; 95% CI, 1.01-4.06)., Conclusions: Based on the outcomes of this trial, in patients with LARC and MRI-negative MRF, primary surgery could negatively influence their DFS rates. Therefore, primary surgery was an inferior strategy compared with preoperative CRT followed by surgery and cannot be recommended for patients with LARC., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: To explore the potential of artificial intelligence (AI) to assist prescription determination for orthokeratology (OK) lenses., Methods: Artificial intelligence algorithm development followed by a real-world trial. A total of 11,502 OK lenses fitting records collected from seven clinical environments covering major brands. Records were randomly divided in a three-way data split. Cross-validation was used to identify the most accurate algorithm, followed by an evaluation using an independent test data set. An online AI-assisted system was implemented and assessed in a real-world trial involving four junior and three senior clinicians., Results: The primary outcome measure was the algorithm's accuracy (ACC). The ACC of the best performance of algorithms to predict the targeted reduction amplitude, lens diameter, and alignment curve of the prescription was 0.80, 0.82, and 0.83, respectively. With the assistance of the AI system, the number of trials required to determine the final prescription significantly decreased for six of the seven participating clinicians (all P <0.01). This reduction was more significant among junior clinicians compared with consultants (0.76±0.60 vs. 0.32±0.60, P <0.001). Junior clinicians achieved clinical outcomes comparable to their seniors, as 93.96% (140/149) and 94.44% (119/126), respectively, of the eyes fitted achieved unaided visual acuity no worse than 0.8 ( P =0.864)., Conclusions: AI can improve prescription efficiency and reduce discrepancies in clinical outcomes among clinicians with differing levels of experience. Embedment of AI in practice should ultimately help lessen the medical burden and improve service quality for myopia boom emerging worldwide., (Copyright © 2024 Contact Lens Association of Ophthalmologists.)

Objective: To explore clinical effect of single small incision with honeycomb titanium plate in treating acute acromioclavicular dislocation., Methods: The clinical data of 40 patients with acute acromioclavicular dislocation admitted from December 2019 to December 2021 were retrospectively analyzed and divided into two groups according to different surgical methods. Among them, 20 patients were fixed with single small incision with honeycomb titanium plate (titanium plate group), including 11 males and 9 females, aged from 23 to 65 years old with an average of (47.40±12.58) years old;12 patients on the left side, 8 patients on the right side;11 patients with type Ⅲ, 3 patients with type Ⅳ, and 6 patients with type Ⅴ according to Rockwood classification. Twenty patients were fixed with clavicular hook plate (clavicular hook group), including 8 males and 12 females, aged from 24 to 65 years old with an average of (48.40±12.08) years old;12 patients on the left side, 8 patients on the right side;10 patients with type Ⅲ, 2 patients with type Ⅳ, and 8 patients with type Ⅴ according to Rockwood classification. Operative time, incision length, intraoperative blood loss, hospital stay, visual analogue scale (VAS) and Constant-Murley score of shoulder joint function were compared between two groups. Anteroposterior radiographs of the affected shoulder joint were recorded before, immediately and 6 months after surgery, and the coracoclavicular distance was measured and compared., Results: Both groups of patients were successfully completed operation without serious complications. All patients were followed up for 6 to 15 months with an average of (11.9±4.8) months. There were no incisional infection, internal plant fracture or failure, bone tunnel fracture and other complications occurred. The incision length of titanium plate group (35.90±3.14) mm was significantly shorter than that of clavicular hook group (49.30±3.79) mm ( P <0.05). There were no significant difference in operative time, intraoperative blood loss and hospital stay between two groups ( P >0.05). At 1 and 3 months after operation, VAS of titanium plate group was lower than that of clavicular hook group ( P <0.05). Connstant-Murley scores in titanium plate group at 1, 3 and 6 months after operation were (86.80±1.36), (91.60±2.32) and (94.90±2.22), respectively;and in clavicular hook group were (78.45±5.47), (85.55±2.01) and (90.25±1.92), which were higher than that of clavicular hook group ( P <0.05). There was no significant difference in coracoclavicular distance between two groups immediately and 6 months after operation( P >0.05)., Conclusion: For the treatment of acute acromioclavicular joint dislocation, single small incision combined with honeycomb titanium plate have advantages of shorter incision, fast recovery of shoulder joint function without the second operation, and has good satisfaction of patient.

Ganoderma is a large and diverse genus containing fungi that cause white rot to infect a number of plant families. This study describes G.phyllanthicola and G.suae as new species from Southwest China, based on morphological and molecular evidence. Ganodermaphyllanthicola is characterized by dark brown to purplish black pileus surface with dense concentric furrows, pale yellow margin, irregular pileipellis cells, small pores (5-7 per mm) and ellipsoid to sub-globose basidiospores (8.5-10.0 × 6.0-7.5 µm). Ganodermasuae is characterized by reddish brown to oxblood red pileus surface and lead gray to greyish-white pore surface, heterogeneous context, wavy margin and almond-shaped to narrow ellipsoid basidiospores (8.0-10.5 × 5.0-7.0 μm). The phylogeny of Ganoderma is reconstructed with multi-gene sequences: the internal transcribed spacer region (ITS), the large subunit (nrLSU), translation elongation factor 1-α gene (TEF-1α) and the second subunit of RNA polymerase II (RPB2). The results show that G.suae and G.phyllanthicola formed two distinct line-ages within Ganoderma . Descriptions, illustrations and phylogenetic analyses results of the two new species are presented., Competing Interests: The authors have declared that no competing interests exist., (Jun He, Xiao-Jun Li, Wan-Zhong Tan, Xiao-Qu Wu, Dan Wu, Zong-Long Luo, Qi Wu Zhou, E-Xian Li, Shu-Hong Li.)

Objective: To compare the effectiveness and safety of nab-paclitaxel, cisplatin, and capecitabine (nab-TPC) with gemcitabine and cisplatin as an alternative first line treatment option for recurrent or metastatic nasopharyngeal carcinoma., Design: Phase 3, open label, multicentre, randomised trial., Setting: Four hospitals located in China between September 2019 and August 2022., Participants: Adults (≥18 years) with recurrent or metastatic nasopharyngeal carcinoma., Interventions: Patients were randomised in a 1:1 ratio to treatment with either nab-paclitaxel (200 g/m 2 on day 1), cisplatin (60 mg/m 2 on day 1), and capecitabine (1000 mg/m 2 twice on days 1-14) or gemcitabine (1 g/m 2 on days 1 and 8) and cisplatin (80 mg/m 2 on day 1)., Main Outcome Measures: Progression-free survival was evaluated by the independent review committee as the primary endpoint in the intention-to-treat population., Results: The median follow-up was 15.8 months in the prespecified interim analysis (31 October 2022). As assessed by the independent review committee, the median progression-free survival was 11.3 (95% confidence interval 9.7 to 12.9) months in the nab-TPC cohort compared with 7.7 (6.5 to 9.0) months in the gemcitabine and cisplatin cohort. The hazard ratio was 0.43 (95% confidence interval 0.25 to 0.73; P=0.002). The objective response rate in the nab-TPC cohort was 83% (34/41) versus 63% (25/40) in the gemcitabine and cisplatin cohort (P=0.05), and the duration of response was 10.8 months in the nab-TPC cohort compared with 6.9 months in the gemcitabine and cisplatin cohort (P=0.009). Treatment related grade 3 or 4 adverse events, including leukopenia (4/41 (10%) v 13/40 (33%); P=0.02), neutropenia (6/41 (15%) v 16/40 (40%); P=0.01), and anaemia (1/41 (2%) v 8/40 (20%); P=0.01), were higher in the gemcitabine and cisplatin cohort than in the nab-TPC cohort. No deaths related to treatment occurred in either treatment group. Survival and long term toxicity are still being evaluated with longer follow-up., Conclusion: The nab-TPC regimen showed a superior antitumoural efficacy and favourable safety profile compared with gemcitabine and cisplatin for recurrent or metastatic nasopharyngeal carcinoma. Nab-TPC should be considered the standard first line treatment for recurrent or metastatic nasopharyngeal carcinoma. Longer follow-up is needed to confirm the benefits for overall survival., Trial Registration: Chinese Clinical Trial Registry ChiCTR1900027112., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/disclosure-of-interest/ and declare: support from the Guangdong Basic and Applied Basic Research Foundation, National Natural Science Foundation of China, CPSF, and Postdoctoral Fellowship Program of CPSF for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

As a kind of tonic Chinese medicine with dual use in medicine and food, there is a large market demanding for Codonopsis pilosula . Taking one-year-old C. pilosula seedlings as materials, we conducted a field experiment to examine the effect of compound fertilizer (750 kg·hm -2 ), organic fertilizer (15 t·hm -2 ) and Streptomyces pactum Act12 agent (9 t·hm -2 Act12+10 t·hm -2 organic fertilizer) treatments on root morphology, secondary metabolite content and expression level of lobetyolin metabolic pathway gene of C. pilosula , to clarify the effects of three fertilizers on the root morphology and medicinal quality. Compared to the control (10 t·hm -2 organic fertilizer, conventional fertilization), three fertilization treatments could promote root growth and formation. All fertilization treatments promoted the accumulation of C. pilosula polysaccharides and secondary metabolites. Act12 agent significantly increased the content of lobetyolin, atractylenolideIII, and 5-hydroxymethylfurfural. The qRT-PCR analysis indicated that three fertilization treatments increased the expression level of lobetyolin metabolic pathway genes, with Act12 agent treatment showing the most significant effect. Pearson correlation analysis demonstrated that the expression level of CpHCT and CpFAD genes was significantly positively correlated with atractylenolide III content. In conclusion, three fertilization treatments could effectively improve the yield and quality of C. pilosula . Among the three treatments, Act12 agent performed better than that of compound fertilizer and organic fertilizer, which was an effective measure to increase the yield and quality of C. pilosula.

Few studies have been conducted that use biomarkers as early warning signals for noise-associated health hazards. To explore potentially effective biomarkers for noise-exposed populations, we recruited 218 noise-exposed male workers in China. We calculated cumulative noise exposure (CNE) through noise intensity and noise-exposed duration. When the model was fully adjusted, ln-transformed relative mitochondrial DNA copy number (mtDNAcn) decreased by 0.014 (95% confidence interval (CI): -0.026, -0.003) units with each 1 dB(A)∙year increase in CNE levels. CNE was further included in the model as a grouping variable, and the results showed a negative dose-effect relationship between relative mtDNAcn and CNE ( P-trend  = 0.045). However, we did not find a correlation between CNE and micronucleus (MN) frequencies. Our findings suggest that CNE in workers was associated with a decrease in relative mtDNAcn which may provide a potential biomarker for noise and for certain health risk but not with MN frequencies.

Background: The spleen plays a critical role in the immune response against malaria parasite infection, where splenic fibroblasts (SFs) are abundantly present and contribute to immune function by secreting type I collagen (collagen I). The protein family is characterized by Plasmodium vivax tryptophan-rich antigens (PvTRAgs), comprising 40 members. PvTRAg23 has been reported to bind to human SFs (HSFs) and affect collagen I levels. Given the role of type I collagen in splenic immune function, it is important to investigate the functions of the other members within the PvTRAg protein family., Methods: Protein structural prediction was conducted utilizing bioinformatics analysis tools and software. A total of 23 PvTRAgs were successfully expressed and purified using an Escherichia coli prokaryotic expression system, and the purified proteins were used for co-culture with HSFs. The collagen I levels and collagen-related signaling pathway protein levels were detected by immunoblotting, and the relative expression levels of inflammatory factors were determined by quantitative real-time PCR., Results: In silico analysis showed that P. vivax has 40 genes encoding the TRAg family. The C-terminal region of all PvTRAgs is characterized by the presence of a domain rich in tryptophan residues. A total of 23 recombinant PvTRAgs were successfully expressed and purified. Only five PvTRAgs (PvTRAg5, PvTRAg16, PvTRAg23, PvTRAg30, and PvTRAg32) mediated the activation of the NF-κBp65 signaling pathway, which resulted in the production of inflammatory molecules and ultimately a significant reduction in collagen I levels in HSFs., Conclusions: Our research contributes to the expansion of knowledge regarding the functional role of PvTRAgs, while it also enhances our understanding of the immune evasion mechanisms utilized by parasites., (© 2024. The Author(s).)