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Meng Xiang,1,* Chengzhi Chen,2,* Yuting Chen,1,* Yuhan Zhang,1 Lei Shi,1 Yan Chen,1 Jie Li,2 Bowen Li,1 Bin Zeng,2 H Rosie Xing,1 Jianyu Wang,2 Zhen Zou2 1State Key Laboratory of Ultrasound in Medicine and Engineering, College of Biomedical Engineering, Chongqing Medical University, Chongqing, 400016, People’s Republic of China; 2Molecular Biology Laboratory of Respiratory Disease, Key Laboratory of Clinical Laboratory Diagnostics (Ministry of Education), College of Laboratory Medicine, Chongqing Medical University, Chongqing, 400016, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhen Zou; Jianyu Wang, Email zouzhen@cqmu.edu.cn; 102758@cqmu.edu.cnIntroduction: Inhalation exposure to silica nanoparticles (SiNPs) is frequently inevitable in modern times. Although the impact of SiNPs on the ecological niche of the lungs has been extensively explored, the role and mechanism of SiNPs in the microenvironment of lung tumors remain elusive.Methods: In this investigation, Lewis lung carcinoma (LLC) was implanted into the left lung in situ after 28 days of intratracheal SiNPs injection into the lungs of mice. This study evaluates the effects of SiNPs on the tumor immune microenvironment both in vitro and in vivo. Our findings indicate that SiNPs can suppress lung cancer by modulating the immune microenvironment of tumors.Results: SiNPs treatment promotes macrophage M1 polarization by activating both NF-κB pathway and glycolytic mechanisms. This phenomenon may be associated with lung inflammation and fluctuation in the pre-metastatic and metastatic microenvironments induced by SiNPs exposure in mice. Additionally, we have shown for the first time that SiNPs have an inhibitory effect on lung carcinogenesis and its progression.Conclusion: This study uniquely demonstrates that SiNPs suppress lung cancer by promoting M1 polarization of macrophages in the immune microenvironment of lung tumors. Our findings are critical in exploring the interaction between SiNPs and lung cancer. Keywords: silicon nanoparticles, lung cancer, macrophage polarization, NF-κB, glycolysis

Fengtao Zhang,1,&ast; Sheng Zhong,2,&ast; Qiming Wei,3 Haiming Zhang,4 Honglei Hu,5 Bicheng Zeng,6 Xiang Zheng7 1Vascular Interventional Surgery, Huazhong University of Science and Technology Union Shenzhen Hospital(Shenzhen Nanshan People’s Hospital), Shenzhen, Guangdong, 518000, People’s Republic of China; 2Department of Tumor and Vascellum Intervention, DongGuan Tungwah Hospital, DongGuan, Guangdong, 523000, People’s Republic of China; 3Department of Interventional Therapy, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510000, People’s Republic of China; 4Department of Radiology, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, Guangdong, 510080, People’s Republic of China; 5Department of Radiology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, 510260, People’s Republic of China; 6Hepatobiliary Surgery, The Sixth Affiliated Hospital of Jinan University, Dongguan, Guangdong, 523000, People’s Republic of China; 7Department of Interventional Therapy, Zhuhai People’s Hospital(Zhuhai Clinical Medical College of Jinan University), Zhuhai, Guangdong, 519000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiang Zheng, Department of Interventional Therapy,Zhuhai People’s Hospital(Zhuhai Clinical Medical College of Jinan University), No. 79 Kangning Road, Zhuhai, 519000, People’s Republic of China, Email zhengxiangzxzx@sina.comAim: To investigate the efficacy and safety of HAIC combined with programmed cell death protein-1 (PD1) inhibitors in MVI-positive advanced hepatocellular carcinoma(HCC).Methods: From September 2017 to May 2019, we retrospectively collected the clinical data from three medical centers in China pertaining to patients diagnosed with BCLC C stage HCC with MVI and receiving treatment with a combination of HAIC and PD-1 inhibitors treatment or HAIC alone, and we compared the efficacy of HAIC combined with PD-1 inhibitors and HAIC monotherapy. Propensity score matching(PSM) was utilized to adjust for baseline differences between groups. Survival outcomes and tumor response rate were used to assess survival benefits, while the incidence of adverse events was used to evaluate safety.Results: After screening for eligibility, 489 patients diagnosed with HCC and concomitant MVI were enrolled. Of these, 173 patients received treatment combining HAIC with PD-1 inhibitors, while 316 patients underwent HAIC monotherapy. After PSM adjustment, the combination therapy group demonstrate superior survival outcomes. Median overall survival(OS) and progression free survival(PFS) were 31.8 months and 10.8 months, respectively, significantly higher than those in the monotherapy group (OS: 10.0 months; PFS: 6.1 months; both P< 0.0001). Moreover, ORR and DCR remained significantly elevated in the combination therapy group (ORR: 44.3% vs 20.4%, P< 0.0001; DCR: 89.8% vs 82.0%, P=0.041). Safety profiles indicated no significant differences in adverse event rates between the two treatment groups, encompassing both overall and grade-specific assessments.Conclusion: Compared to HAIC alone, the combination of HAIC with PD-1 inhibitors represents a more promising and effective approach for patients with HCC complicated by macrovascular invasion.Keywords: hepatocellular carcinoma, programmed cell death protein 1, hepatic artery infusion chemotherapy, macrovascular invasion, propensity score matching

The immune system is often conceptualized as the body's internal police force. Its innate components (macrophag-es, dendritic cells, neutrophils, eosinophils, basophils, mast cells, and the complement system), in conjunction with the acquired immunity (T cells, B cells), are responsible for the surveillance of the body, discrimination between "self" and "non-self," recognition of pathogens and toxins, and appropriate defense if needed. In addition to the classic lymphoid tissues, such as the thymus, spleen, and lymph nodes, immune system cells are found throughout the body, including the cochlea. Several publications have reported the existence of resident immune cells in the human and rodent cochlea, but their role in cochlear biology remains unclear. Our research group has concentrated on characterizing two coch-lear cell types representing the innate immune system: the microglia and the mast cells. Microglia develop from yolk-derived mesodermal precursors and reside exclusively in the central nervous system. Recently, research has identified mi-croglia in the cochlea based on the expression of the Ibal surface molecule. To gain further insight into the nature of these cells, we employed immunofluorescence, confocal microscopy, and Western blot techniques to characterize them using another marker for microglia (TMEM119). Our findings indicate that in the murine cochlea, Iba1+ TMEM119+ double-positive cells are absent before and after the onset of hearing and after acoustic trauma in adult mice. In contrast, the second cell type, mast cells, were present in the developing and adult rodent cochleae, as evidenced by the expression of several markers, including heparin, mast cell tryptase, mast cell chymase, and IgE receptor. Their numbers were sparse, but inhibiting their degranulation reduced cisplatin-induced damage to auditory hair cells. Furthermore, adding the supernatant from degranulated mast cells resulted in the loss of inner and outer hair cells. Moreover, we identified all four receptors for the major mast cell mediator, histamine, in the murine cochlea. Furthermore, our systematic review demonstrated the association between allergies, sudden sen-sorineural hearing loss, Meniere disease, and acute low-tone hearing loss. We conclude that mast cells, but not microglia, are resident cells in the rodent cochlea and that their activation can contribute to cochlear pathologies. [ABSTRACT FROM AUTHOR]

Herein, composites based on Ni-doped ZnO nanorods and Ti3C2 MXene structure (Ni-ZnO NR/Ti3C2) were produced via a simple hydrothermal method for photocatalytic applications. Special attention was paid to their structural and optical properties. The composite exhibited a photocatalytic effectiveness of 88.2% in degrading methyl orange (MO) within a duration of 75 minutes when exposed to a xenon lamp. The enhancement of the catalytic activity was due to the one-dimensional ZnO nanostructure, the Ni doping, and the Schottky heterojunction is formed by the interface within ZnO and Ti3C2. Therefore, this work provides an effective strategy to fabricate metal oxide/MXene photocatalysts. [ABSTRACT FROM AUTHOR]

Dissolution is a ubiquitous process in nature and industry. However, due to technical difficulties, the detailed dissolution process at the nanoscale has seldom been captured experimentally. In this study, we investigated the dissolution dynamics in the confinement of toluene surface nanodroplets on polystyrene (PS) thin films in oversaturated toluene/water mixture solutions. This was achieved by adjusting the immersion durations from several minutes to 9 h. Dissolution takes place upon the deposition of nanodroplets on the PS surfaces, leading to the formation of surface nanostructures. Interestingly, we found that the induced nanostructures underwent complex morphological changes, from complex nanocraters with central bulges and/or multiple rims to simple nanocraters. We speculate that diffusiophoresis plays a key role in the formation of the complex nanocraters, as it facilitates the transportation of dissolved PS molecules inside the nanodroplets. We believe this finding not only enhances our understanding of dissolution dynamics at the nanoscale but also holds promise for applications in dissolution-based nanopatterning.

To overcome C797S mutation, the latest and most common resistance mechanism in the clinical treatment of third-generation EGFR inhibitor, a novel series of substituted 6-(2-aminopyrimidine)-indole derivatives were designed and synthesized. Through the structure-activity relationship (SAR) study, compound 11eg was identified as a novel and potent EGFR L858R/T790M/C797S inhibitor (IC 50  = 0.053 μM) but had a weak effect on EGFR WT (IC 50  = 1.05 μM). 11eg significantly inhibited the proliferation of the non-small cell lung cancer (NSCLC) cells harboring EGFR L858R/T790M/C797S with an IC 50 of 0.052 μM. 11eg also showed potent inhibitory activity against other NSCLC cell lines harboring main EGFR mutants. Furthermore, 11eg exhibited much superior activity in arresting cell cycle and inducing apoptosis of NSCLC cells with mutant EGFR C797S . It blocked cellular EGFR signaling. Importantly, 11eg markedly suppressed the tumor growth in in vivo xenograft mouse model with good safety. Additionally, 11eg displayed good microsomal stability. These results demonstrated the potential of 11eg with novel scaffold as a promising lead compound targeting EGFR C797S to guide in-depth structural optimization., 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 Masson SAS. All rights reserved.)

Introduction: The evidence regarding the effectiveness of Lanzhou Lamb Rotavirus Vaccine (LLR) and RotaTeq (RV5) against gastroenteritis (RVGE) caused by emerging genotypes in Chinese children remains limited., Methods: We conducted a test-negative case-control study using gastroenteritis surveillance data from four cities (2020-2023) in Guangdong Province, China. Children aged 2 months to 5 years hospitalized with acute gastroenteritis were enrolled. Cases were rotavirus-positive; controls were rotavirus-negative. Vaccine effectiveness (VE) was estimated using multivariable logistic regressions., Results: Among 2650 children, 218 (8.2%) were rotavirus-positive, predominantly G8P[8]. Also, 1543 (58.23%) children were unvaccinated, while 632 (23.85%) and 475 (17.92%) received at least one dose of RV5 and LLR, respectively. Adjusted RV5 VE against any RVGE severity was 51.7% [95% confidence interval (CI) - 58.1-85.3%]) for one dose, 37.6% (95% CI - 58.5-75.4%) for two doses, and 64.1% (95% CI 38.0-79.2%) for three doses. For LLR, VE against any RVGE severity was 38.7% (95% CI 5.7-60.2%) for one dose, 74.6% (95% CI 35.3-90.0%) for two doses, and 58.8% (95% CI - 217.6-94.6%) for three doses. Against severe RVGE, RV5 VE was 67.2% (95% CI - 144.7-95.6%) for one dose, 74.0% (95% CI - 92.1-96.5%) for two doses, and 86.6% (95% CI 56.8-95.9%) for three doses. For LLR, VE against severe RVGE was 57.7% (95% CI 20.3-77.6%) for one dose, 73.4% (95% CI 11.9-92.0%) for two doses, and - 27.8% (95% CI - 949.7-84.4%) for three doses., Conclusions: Both RV5 and LLR provided protection against RVGE, including the emerging G8P[8] genotype. Three doses of RV5 offered strong protection, while two doses of LLR also appeared to be an effective strategy against rotavirus infection., (© 2024. The Author(s).)

Background: Sarcandra glabra (S. glabra), a traditional Chinese medicine (TCM), has demonstrated significant anticancer activity; however, the underlying mechanisms have not yet been fully elucidated., Purpose: This study aimed to investigate the effects of S. glabra on lung cancer and to explore its underlying mechanisms., Methods: The chemical profile of S. glabra was analyzed via ultrahigh-performance liquid chromatography coupled with mass spectrometry (UPLC-MS). The effects of S. glabra on the viability, proliferation, apoptosis, migration, and invasion of lung cancer cells were assessed via CCK8, colony formation, flow cytometry, scratch, and Transwell assays. In vivo anticancer activity was evaluated in an LLC mouse model. Proteomic analysis was performed to identify key molecules and pathways in S. glabra-treated LLC cells. The expression of ferroptotic proteins and associated cellular events were examined via western blotting, ROS production, iron accumulation, and lipid peroxidation assays. Immune modulation in tumor-bearing mice was evaluated by detecting immune cells and cytokines in the peripheral blood and tumor tissue., Results: Our analysis quantified 1997 chemical markers in S. glabra aqueous extracts. S. glabra inhibited the viability and proliferation of lung cancer cells and induced cell cycle arrest and apoptosis. Scratch and Transwell assays demonstrated that S. glabra suppressed the migration and invasion of lung cancer cells. Oral administration of S. glabra significantly inhibited tumor growth in LLC tumor-bearing mice. Proteomic analysis revealed that S. glabra upregulated the expression of the HMOX1 protein and activated the ferroptosis pathway. Consistent with these findings, we found that S. glabra triggered ferroptosis in lung cancer cells, as evidenced by the upregulation of HMOX1, downregulation of GPX4 and ferritin light chain proteins, iron accumulation, increased ROS production, and lipid peroxidation. Furthermore, S. glabra demonstrated immunostimulatory properties in LLC tumor-bearing mice, leading to increased populations of immune cells (NK cells) and elevated cytokine levels (IL-2)., Conclusion: This study is the first to demonstrate that S. glabra induces ferroptosis in lung cancer cells by regulating HMOX1, GPX4, and FTL. These findings provide a robust scientific basis for the clinical application of S. glabra in lung cancer treatment., 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 GmbH. All rights reserved.)

Breast cancer, as a malignant tumor disease, has maintained high incidence and mortality rates over the years. Ultrasonography is one of the primary methods for diagnosing early-stage breast cancer. However, correctly interpreting breast ultrasound images requires massive time from physicians with specialized knowledge and extensive experience. Recently, deep learning-based method have made significant advancements in breast tumor segmentation and classification due to their powerful fitting capabilities. However, most existing methods focus on performing one of these tasks separately, and often failing to effectively leverage information from specific tumor-related areas that hold considerable diagnostic value. In this study, we propose a multi-task network with local-global feature interaction and multiple tumoral region guidance for breast ultrasound-based tumor segmentation and classification. Specifically, we construct a dual-stream encoder, paralleling CNN and Transformer, to facilitate hierarchical interaction and fusion of local and global features. This architecture enables each stream to capitalize on the strengths of the other while preserving its unique characteristics. Moreover, we design a multi-tumoral region guidance module to explicitly learn long-range non-local dependencies within intra-tumoral and peri-tumoral regions from spatial domain, thus providing interpretable cues beneficial for classification. Experimental results on two breast ultrasound datasets show that our network outperforms state-of-the-art methods in tumor segmentation and classification tasks. Compared with the second-best competitive method, our network improves the diagnosis accuracy from 73.64% to 80.21% on a large external validation dataset, which demonstrates its superior generalization capability.

Sludge pretreatment plays a crucial role in solubilizing particulate matters to release organic matter for subsequent anaerobic fermentation (AF). This study innovatively combines radio frequency (RF) heating and alkaline treatment, and finds that the combined pretreatment achieved a sludge disintegration rate of 35.11 %, which is 15.19 % and 8.48 % higher than single RF or alkaline pretreatment. The dissociated ions from the alkali are conducive to RF action on sludge. Furthermore, the combined pretreatment significantly benefits the subsequent AF experiments, resulting in a 9-fold increase in volatile fatty acids production. Considering cost-effectiveness, the optimal operating condition is a 10-minute RF treatment at pH 10 with a total cost of 4.35 × 10 -3 dollars per kg soluble chemical oxygen demand (SCOD) increased. These findings provide a foundational basis for the development of a novel technology for sludge pretreatment., 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.)

Natural mollusks perform complex mechanical actions through reversible large-strain deformation and stiffness switching, which are challenging to achieve simultaneously in synthetic materials. Herein, it is shown that a set of polyacrylates designed according to a chain friction and lubrication balanced strategy shows ultra-stretchability (λ up to 324), high resilience (near 100% recovery at strain ≥ 100), and wide-span stiffness switching (up to 2073 times). The typical emulsion polymerization method and casting technique are adopted to fabricate the polyacrylate films. Quaternary ammonium surfactants are used as the emulsifier and reserved in the polymer matrix to enhance the chain segment lubrication with their long alkyl group but improve the whole chain friction through the formation of nano-eutectics. These polyacrylates undergo multimodal mechanical responses, including temperature- or time-programmed deformation and load-bearing like artificial muscles. This molecular design principle and synthetic method provide a robust platform for the fabrication of ultra-tough polymers for soft robots with multiple customized functions., (© 2024 Wiley‐VCH GmbH.)

It is a grand challenge to deep understanding of and precise control over functional sites for the rational design of highly efficient catalysts for methanol electrooxidation. Here, an L1 2 -Pt 2 RhFe intermetallic catalyst with integrated functional components is demonstrated, which exhibits exceptional CO tolerance. The Pt 2 RhFe/C achieves a superior mass activity of 6.43 A mg Pt -1 , which is 2.23-fold and 3.53-fold higher than those of PtRu/C and Pt/C. Impressively, the Pt 2 RhFe/C exhibits a significant enhancement in durability owing to its high CO-tolerance and stability. Density functional theory calculations reveal that high performance of Pt 2 RhFe intermetallic catalyst arises from the synergistic effect: the strong OH binding energy (OHBE) at Fe sites induce stably adsorbed OH species and thus facilitate the dehydrogenation step of methanol via rapid hydrogen transfer, while moderate OHBE at Rh sites promote the formation of the transition state (Pt-CO···OH-Rh) with a low activation barrier for CO removal. This work provides new insights into the role of OH binding strength in the removal of CO species, which is beneficial for the rational design of highly efficient catalysts., (© 2024 Wiley‐VCH GmbH.)

Bioavailable heavy metal and their efficient phytoremediation in mining areas have major implications for environmental and human health. In this study, we investigated 12 dominant plants in a typical Mn ore area of Zunyi, Guizhou Province, China, to determine the heavy metal contents, morphologies, and environmental factors affecting Mn, Cd, Pb, Cu, Zn, and Cr in the plant parts and rhizosphere soil. The bioavailabilities and degrees of metals were evaluated using the ratios of the secondary to primary phase distributions and potential ecological risk indices. Principal component analysis, cluster analysis, positive matrix factorisation modelling, and redundancy analysis were used to trace the origins and correlations among the metals. The results indicate that the bioavailabilities were the highest for Mn and Cd in the study area, and all of the target heavy metals had bioavailabilities above the moderate ecological harm level. Statistical modelling indicates that there are four main pollution sources: mining, smelting, processing operations, and atmospheric deposition. The dominant plants had high heavy metal enrichments, bioconcentration factors, and translocation factors for Mn, Cu, Cr, Cd, and Zn. The redundancy analysis indicates that soil total N, total P, and pH affect metal absorption and distributions in Compositae and non-Compositae plants in low-N, low-P, and slightly alkaline mining environments. This study provides a feasible basis for the screening of heavy metal enrichment plants and the improvement of remediation technology in manganese ore area under the extreme environment of poor nutrition., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Resistance to osimertinib represents a significant challenge for the successful treatment of non-small cell lung cancer (NSCLC) harboring activating mutations in EGFR. N6-methyladenosine (m6A) on mRNAs is critical for various biological processes, yet whether m6A regulates osimertinib resistance of NSCLC remains unknown. In this study, we demonstrated that developing osimertinib-resistant phenotypes depends on m6A reduction resulting from downexpression of m6A methyltransferase METTL14 in EGFR-mutant NSCLCs. Both in vitro and in vivo assays showed that specific knockdown of METTL14 was sufficient to confer osimertinib resistance and that elevated expression of METTL14 rescued the efficacy of osimertinib in the resistant NSCLC cells. Mechanistically, METTL14 promoted m6A methylation of pro-apoptotic Bim mRNA and increased Bim mRNA stability and expression, resulting in activating the Bim-dependent pro-apoptotic signaling and thereby promoting osimertinib-induced cell apoptosis. Analysis of clinical samples revealed that decreased expression of METTL14 was observed in osimertinib-resistant NSCLC tissues and significantly associated with a poor prognosis. In conclusion, our study reveals a novel regulatory mechanism by which METTL14-mediated m6A methylation of Bim mRNA inhibited osimertinib resistance of NSCLC cells. It offers more evidences for the involvement of m6A modification in regulation of osimertinib resistance and provides potential therapeutic targets for novel approaches to overcome the tolerance of osimertinib and other EGFR tyrosine kinase inhibitors. Implications: This study offers more evidences for the involvement of METTL14-mediated N6-methyladenosine modification in regulation of osimertinib resistance and provides potential therapeutic targets for novel approaches to overcome the tolerance of osimertinib and other EGFR tyrosine kinase inhibitors., (©2024 American Association for Cancer Research.)

The combined effects of the novel antifouling biocide tralopyril (TP) nitrile and ocean acidification (OA) on marine organisms are still not well understood, despite the increasing attention given to the toxic effects of emerging pollutants and OA on marine organisms in recent years. In this study, Crassostrea gigas (C. gigas) was exposed to TP, OA, and a combination of TP and OA for 21 days with a 14-day depuration. This study investigated the inter-tissue variability in energy metabolism responses and the impacts on gonadal development in C. gigas under both single and combined exposures to TP and OA. The results indicate that TP exposure and OA resulted in up-regulation of energy metabolism genes in the C. gigas, with tissues exhibiting enhanced aerobic metabolism. Furthermore, OA influences the sex determination of C. gigas, promoting the development of female individuals. Moreover, following depuration, C. gigas is able to restore normal energy metabolism and sexual development through the accumulation of suitable energy reserves. This study provides a valuable reference for the environmental and ecological risk assessment of TP, addressing the research gap in understanding the combined toxicity of TP and OA on aquatic organisms., 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: As the human body ages, adverse body composition status such as sarcopenia and obesity become obvious phenotypes which can cause numerous health problems. We aimed to comprehensively investigate the association of sex hormones and body mass components in adult men of various age groups., Methods: We analysed national representative population data from the US National Health and Nutrition Examination Survey. Generalized linear model regression analyses were used to evaluate the association between sex hormones (total testosterone [TT], bio-available testosterone [BT], sex hormone-binding globulin [SHBG], estradiol [E 2 ] and testosterone to estradiol ratio [T/E ratio]) and body mass components (weight, body mass index (BMI), total lean mass, appendicular lean mass, bone mineral content, total fat and trunk fat). The collection and testing time of blood samples were not fixed and there was no strict fasting, but in subsequent analysis we used statistical methods to minimize the impact of random testing., Results: After screening for inclusion and exclusion, 3759 male participants aged 20-85 years old were included in this study. Higher levels of TT, SHBG, BT and T/E ratios were significantly associated with higher total lean mass, appendicular lean mass and bone mineral content, while lower weight, BMI, total fat and trunk fat. For E 2 levels in men, we found an opposite trend, with higher E 2 levels significantly associated with lower total lean mass and appendicular lean mass, and higher weight, BMI, total fat and trunk fat. Notably, in subgroup analysis, the results showed that there were significant interaction effects of age and smoking history in the association between sex hormones and body mass components., Conclusion: Higher TT levels, BT levels, SHBG levels and T/E ratios are associated with lower body weight and improved body composition in young adult men (characterized by higher lean body mass, higher bone density and lower fat mass). The relationship is especially pronounced among relatively young, nonsmoking men., (© 2024 John Wiley & Sons Ltd.)

The nucleus accumbens (NAc) regulates reward-motivated behavior, but the temporal dynamics of NAc neurons that enable "free-willed" animals to obtain rewards remain elusive. Here, we recorded Ca 2+ activity from individual NAc neurons when mice performed self-paced lever-presses for sucrose. NAc neurons exhibited three temporally-sequenced clusters, defined by times at which they exhibited increased Ca 2+ activity: approximately 0, -2.5 or -5 sec relative to the lever-pressing. Dopamine D1 receptor (D1)-expressing neurons and D2-neurons formed the majority of the -5-sec versus -2.5-sec clusters, respectively, while both neuronal subtypes were represented in the 0-sec cluster. We found that pre-press activity patterns of D1- or D2-neurons could predict subsequent lever-presses. Inhibiting D1-neurons at -5 sec or D2-neurons at -2.5 sec, but not at other timepoints, reduced sucrose-motivated lever-pressing. We propose that the time-specific activity of D1- and D2-neurons mediate key temporal features of the NAc through which reward motivation initiates reward-seeking behavior., (© 2024. The Author(s).)

All-inorganic perovskite CsPbBr3 nanocrystals (NCs) display high photoluminescence quantum yield and narrow emission, which show great potential application in optoelectronic devices. However, the poor environment stability of NCs will hinder their practical application. Herein, a series of ionic liquids with different anions (BF4-, Br-, and NO3-) were used as a sole capping ligand to synthesize NCs. Among the three samples, 1-hexadecyl-3-methylimidazolium tetrafluoroborate ([C16MIM]BF4) capped NCs have the highest stability in light, thermal, and water, possibly attributing to the in situ passivation of bromine vacancy via pseudohalogen BF4- and tight binding of ionic liquid ligands and lead atoms. In addition, green-emission [C16MIM]BF4 NCs were used to assemble a white light-emitting diode device, and it possessed a wide National Television System Committee color gamut of 124.5% and a stable emission peak at high driving currents of 380 mA. This work paves the way for resurfacing perovskite NCs with ultrahigh stability, thereby driving the perovskite NC display industry closer to real-world application., (© 2024 Author(s). Published under an exclusive license by AIP Publishing.)

Objectives: Development of a prediction model using machine learning (ML) method for tumor progression in oral squamous cell carcinoma (OSCC) patients would provide risk estimation for individual patient outcomes., Patients and Methods: This predictive modeling study was conducted of 1163 patients with OSCC from Hospital of Stomatology, SYSU and SYSU Cancer Center from March 2009 to October 2021. Clinical, pathological, and hematological features of the patients were collected. Six ML algorithms were explored, and model performance was assessed by accuracy, sensitivity, specificity, f1 score, and AUC. SHAP values were used to identify the variables with the greatest contribution to the model., Results: Among the 1163 patients (mean [SD] age, 55.36 [12.91] years), 563 are from development cohort and 600 are from validation cohort. The Logistic Regression algorithm outperformed all other models, with a sensitivity of 94.7% (68.2%), a specificity of 55.3% (63.7%), and the AUC of 0.76 ± 0.09 (0.723) in the development (validation) cohort. The most predictive feature was neutrophil count., Conclusion: This study demonstrated ML models can improve clinical prediction of oral squamous cell carcinoma progression through basic information of patients. These tools could be used to provide individual risk estimation and may help direct intervention., (© 2024 Wiley Periodicals LLC.)

Zeolites, the most technically important crystalline microporous materials, are indispensable cornerstones of chemical engineering because of their remarkable catalytic properties and adsorption capabilities. Numerous studies have demonstrated that the hierarchical engineering of zeolites can maximize accessible active sites and improve mass transport, which significantly decreases the internal diffusion limits to achieve the desired performance. However, the construction of hierarchical zeolites with ordered alignments and size-controlled substructures in a convenient way is highly challenging. Herein, we develop a facile procedure using two common structure-directing agents, tetrapropylammonium hydroxide (TPAOH) and tetraethylammonium hydroxide (TEAOH), to synthesize hierarchically aligned ZSM-5 (Hie-ZSM-5) crystals with a -axis alignment substructures of controllable size. The control of the substructure size (α) in the range of 10-60 nm and the corresponding similarity ( r = α/β, where β is the size of Hie-ZSM-5) ranging from 0.004 to 0.033 can be tuned by varying the Si/Al ratios (40-120). A systematic investigation of the overall crystallization process, using time-dependent XRD, SEM, TEM, and solid-state magic-angle spinning NMR ( 13 C, 27 Al, 29 Si) methods, enable us to construct a solid mechanism for the generation of Hie-ZSM-5. Most importantly, directional transport in the unique structures of Hie-ZSM-5 efficiently enhances mass diffusion, as well as catalytic activity and stability. These findings improve our understanding of the zeolite crystallization process and inspire novel methods for the rational design of hierarchical zeolites.

Tungsten is a crucial strategic metal that plays a significant role in various fields, such as the defense industry, fine chemicals, and the preparation of new materials. During the practice of numerous tungsten smelting processes, a large amount of acidic wastewater containing low concentrations of WO 3 is generated. The adsorption method, known for its simplicity, effectiveness, and ease of operation, represents the most promising approach for tungsten recovery and is vital for the sustainable development of the tungsten industry. In this study, D318 macroporous resin was used as an adsorbent to investigate its effectiveness in adsorbing WO 3 from acidic solutions. Static adsorption experiments revealed that the adsorption capacity of D318 resin for WO 3 was 683 mg·g -1 . Kinetic analysis indicated that the controlling step for the adsorption of WO 3 from acidic solutions by D318 resin was intraparticle diffusion. Thermodynamic analysis demonstrated that the adsorption process was endothermic and could occur spontaneously. By fitting the isothermal adsorption equation, it was found that the Langmuir model was more suitable for describing the adsorption process of WO 3 on D318 resin in acidic solutions. The results of dynamic adsorption experiments showed that under optimized conditions, the dynamic adsorption capacity for WO 3 was 529 mg·g -1 ; when using NaOH as the desorbent for cyclic desorption, the desorption rate for WO 3 was 98.21%. XPS and SEM-EDS testing and analysis confirmed that D318 macroporous resin exhibited excellent adsorption performance for tungsten in acidic solutions.

Effective antibacterial therapy while accelerating the repair of bone defects is crucial for the treatment of osteomyelitis. Inspired by the protective mechanism of Andrias davidianus, we constructed an antibacterial hydrogel scaffold with excellent rigidity and long-term slow-release activity. While retaining the toughness of the skin secretion of Andrias davidianus (SSAD), the rigidity of the hydrogel material is increased by incorporating hydroxyapatite to meet the demands of bone-defect-filling materials. It also exerted antibacterial effects via the slow-release of vancomycin from local osteomyelitis lesions. Notably, the hydrogel can also carry a high stable recombinant miR-214-3p inhibitor (MSA-anti214). By the delivery of nano vector polyvinylamine, the long-term slow-release of MSA-anti214 is achieved to promote bone repair, making this composite hydrogel a potential SSAD-based osteomyelitis alleviator (SOA). In vitro and vivo results verified that the SOA effectively eliminated Staphylococcus aureus and repaired bone defects, ultimately mitigating the progression of osteomyelitis. This composite hydrogel extends the economic application prospects of A. davidianus and has provided new insights for the treatment of osteomyelitis. The study also explored new insights for the bone filling materials of bone defection and other skeletal system diseases., (© 2024. The Author(s).)

Document-level relation triplet extraction is crucial in biomedical text mining, aiding in drug discovery and the construction of biomedical knowledge graphs. Current language models face challenges in generalizing to unseen datasets and relation types in biomedical relation triplet extraction, which limits their effectiveness in these crucial tasks. To address this challenge, our study optimizes models from two critical dimensions: data-task relevance and granularity of relations, aiming to enhance their generalization capabilities significantly. We introduce a novel progressive learning strategy to obtain the PLRTE model. This strategy not only enhances the model's capability to comprehend diverse relation types in the biomedical domain but also implements a structured four-level progressive learning process through semantic relation augmentation, compositional instruction, and dual-axis level learning. Our experiments on the DDI and BC5CDR document-level biomedical relation triplet datasets demonstrate a significant performance improvement of 5% to 20% over the current state-of-the-art baselines. Furthermore, our model exhibits exceptional generalization capabilities on the unseen Chemprot and GDA datasets, further validating the effectiveness of optimizing data-task association and relation granularity for enhancing model generalizability., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The brain is the central hub of the entire nervous system. Its development is a lifelong process guided by a genetic blueprint. Understanding how genes influence brain development is critical for deciphering the formation of human cognitive functions and the underlying mechanisms of neurological disorders. Recent advances in multi-omics techniques have now made it possible to explore these aspects comprehensively. However, integrating and analyzing extensive multi-omics data presents significant challenges. Here, we introduced MAPbrain (http://bigdata.ibp.ac.cn/mapBRAIN/), a multi-omics atlas of the primate brain. This repository integrates and normalizes both our own lab's published data and publicly available multi-omics data, encompassing 21 million brain cells from 38 key brain regions and 436 sub-regions across embryonic and adult stages, with 164 time points in humans and non-human primates. MAPbrain offers a unique, robust, and interactive platform that includes transcriptomics, epigenomics, and spatial transcriptomics data, facilitating a comprehensive exploration of brain development. The platform enables the exploration of cell type- and time point-specific markers, gene expression comparison between brain regions and species, joint analyses across transcriptome and epigenome, and navigation of cell types across species, brain regions, and development stages. Additionally, MAPbrain provides an online integration module for users to navigate and analyze their own data within the platform., (© The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research.)

As a significant variant of the Michael reaction, the 1,6-addition reaction has undergone considerable development over the past decade. This effective strategy enables the synthesis of a variety of novel and potentially bioactive functional molecules. In this review, we summarize the recent progress in NHC-catalyzed 1,6-addition reactions, highlighting their efficiency in the rapid synthesis of complex functional molecules. We also provide our perspectives on the future development of this dynamic and highly active research area., (© 2024 The Chemical Society of Japan and Wiley-VCH GmbH.)

Alternative splicing (AS), a crucial mechanism in post-transcriptional regulation, has been implicated in diverse cancer processes. Several splicing variants of solute carrier (SLC) transporters reportedly play pivotal roles in tumorigenesis and tumor development. However, an in-depth analysis of AS landscapes of SLCs in colon adenocarcinoma (COAD) is lacking. Herein, we analyzed data from The Cancer Genome Atlas and identified 1215 AS events across 243 SLC genes, including 109 differentially expressed AS (DEAS) events involving 62 SLC genes in COAD. Differentially spliced SLCs were enriched in biological processes, including transmembrane transporter activity, transporter activity, ferroptosis, and choline metabolism. In patients with COAD, tumor tissues exhibited higher expression of longer mitochondrial carrier SLC25A16 isoforms than adjacent normal tissues, consistent with bioinformatics analysis. Protein-coding sequences and transmembrane helices of survival-related DEAS were predicted, revealing that shifts in splicing sites altered the number and structure of their transmembrane proteins. We developed a prognostic risk model based on the screened 6-SLC-AS (SLC7A6&#95;RI&#95;37208 (SLC7A6-RI), SLC11A2&#95;AP&#95;21724, SLC2A8&#95;ES&#95;87631, SLC35B1&#95;AA&#95;42317, SLC39A11&#95;AD&#95;43204, and SLC7A8&#95;AP&#95;26712). Knockdown of the intronic region of SLC7A6-RI isoform enhanced colon cancer cell proliferation. In vivo, knockdown of the intronic region of SLC7A6-RI isoform enhanced tumor growth in colon cancer. Mechanistically, si-SLC7A6-RI isoform exerted oncogenic effects by activating the PI3K-Akt-mTOR signaling pathway and promoting cell proliferation, evidenced by increased expression of key regulators Phosphorylated Mammalian Target of Rapamycin (p-mTOR) and a cell proliferation marker Proliferating Cell Nuclear Antigen (PCNA) using western blotting. Our study elucidated SLC-AS in COAD, highlighting its potential as a prognostic and therapeutic target and emphasizing the suppressive influence of SLC7A6-RI in colon cancer progression., (© 2024 The Author(s). Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Background: Recent studies have shown that the high salt diet (HSD) is linked to increased dermal pro-inflammatory status and reduced extracellular matrix (ECM) expression in inflamed skin of mice. Decreased ECM content is a known aging phenotype of the skin, and alterations in ECM composition and organization significantly contribute to skin aging. This study aimed to determine whether a high salt diet accelerates skin aging and to identify the time point at which this effect becomes apparent., Methods: Wistar rats were randomly divided into normal diet and high salt diet groups and fed continuously for 8 weeks. Skin samples were collected at weeks 7 and week 8. Skin pathological sections were evaluated and levels of cell cycle inhibitors, senescence-associated secretory phenotype (SASP), oxidative stress and vascular regulatory factors (VRFs) were examined. Correlation analyses were performed to reveal the effect of a high salt diet as an extrinsic factor on skin aging and to analyse the correlation between a high salt diet and intrinsic aging and blood flow status., Results: At week 8, HSD rats exhibited thickened epidermis, thinned dermis, and atrophied hair follicles. The expression of cell cycle inhibitors and oxidative stress levels were significantly elevated in the skin of HSD rats at both week 7 and week 8. At week 7, some SASPs, including TGF-β and PAI-1, were elevated, but others (IL-1, IL-6, IL-8, NO) were not significantly changed. By week 8, inflammatory molecules (IL-1, IL-6, TGF-β), chemokines (IL-8), proteases (PAI-1), and non-protein molecules (NO) were significantly increased. Notably, despite elevated PAI-1 levels suggesting possible blood hypercoagulation, the ET-1/NO ratio was reduced in the HSD group at week 8., Conclusion: The data suggest that a high salt diet causes skin aging by week 8. The effect of a high salt diet on skin aging is related to the level of oxidative stress and the expression of cell cycle inhibitors. Additionally, a potential protective mechanism may be at play, as evidenced by the reduced ET-1/NO ratio, which could help counteract the hypercoagulable state and support nutrient delivery to aging skin., 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 Peng, Liu, Zeng, Bai, Xu, Chen, Chen and Xia.)

Background and Objectives: Image-based 2D/3D registration is a crucial technology for fluoroscopy-guided surgical interventions. However, traditional registration methods relying on a single X-ray image into surgical navigation systems. This study proposes a novel 2D/3D registration approach utilizing biplanar X-ray images combined with computed tomography (CT) to significantly reduce registration and navigation errors. The method is successfully implemented in a surgical navigation system, enhancing its precision and reliability., Methods: First, we simultaneously register the frontal and lateral X-ray images with the CT image, enabling mutual complementation and more precise localization. Additionally, we introduce a novel similarity measure for image comparison, providing a more robust cost function for the optimization algorithm. Furthermore, a multi-resolution strategy is employed to enhance registration efficiency. Lastly, we propose a more accurate coordinate transformation method, based on projection and 3D reconstruction, to improve the precision of surgical navigation systems., Results: We conducted registration and navigation experiments using pelvic, spinal, and femur phantoms. The navigation results demonstrated that the feature registration errors (FREs) in the three experiments were 0.505±0.063 mm, 0.515±0.055 mm, and 0.577±0.056 mm, respectively. Compared to the point-to-point (PTP) registration method based on anatomical landmarks, our method reduced registration errors by 31.3%, 23.9%, and 26.3%, respectively., Conclusion: The results demonstrate that our method significantly reduces registration and navigation errors, highlighting its potential for application across various anatomical sites. Our code is available at: https://github.com/SJTUdemon/2D-3D-Registration., 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.)

Tin (Sn)-based materials are expected to realize efficient CO 2 electroreduction into formate. Herein, we constructed a heterojunction by depositing Cu on Cu-doped SnS 2 nanosheets. During the electrochemical reaction, this heterojunction evolves to a highly active phase of Cu 2 O@Cu 6 Sn 5 while maintaining its two-dimensional morphology. Specifically, a partial current density of 35 mA cm -2 with an impressive faradaic efficiency of 93 % for formate production was achieved over the evolved heterojunction. In situ and ex situ experiments elucidated the formation mechanism of the Cu₂O@Cu₆Sn₅ heterojunction. Cu₆Sn₅ nanosheets were formed via a stepwise desulfurization process, while Cu₂O was generated through its reaction with hydroxyl radicals. This evolved heterojunction with a high electrochemically active surface area synergistically stabilized the *OCHO intermediate, thereby significantly enhancing the selectivity and activity. Our findings provide insight into the structural evolution process and guide the development of selective electrocatalysts for CO 2 reduction., (© 2024 Wiley-VCH GmbH.)

Researchers often combine both positively and negatively worded items when constructing Likert scales. This combination, however, may introduce method effects due to the variances in item wording. Although previous studies have tried to quantify these effects by using factor analysis on scales with different content, the impact of varied item wording on participants' choices among specific options remains unexplored. To address this gap, we utilized four versions of the Undergraduate Learning Burnout (ULB) scale, each characterized by a unique valence of item wording. After collecting responses from 1,131 college students, we employed unidimensional, multidimensional, and bi-factor Graded Response Models for analysis. The results suggested that the ULB scale supports a unidimensional structure for the learning burnout trait. However, the inclusion of different valences of wording within items introduced additional method factors, explaining a considerable degree of variance. Notably, positively worded items demonstrated greater discriminative power and more effectively counteracted the biased outcomes associated with negatively worded items, especially between the "Strongly Disagree" and "Disagree" options. While there were no substantial differences in the overall learning burnout traits among respondents of different scale versions, slight variations were noted in their distributions. The integration of both positive and negative wordings reduced the reliability of the learning burnout trait measurement. Consequently, it is recommended to use exclusively positively worded items and avoid a mix in item wording during scale construction. If a combination is essential, the bi-factor IRT model might help segregate the method effects resulting from the wording valence., 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 Zeng, Jeon and Wen.)

Liposomes have demonstrated great potential for drug delivery and diabetes treatment. However, hydrolysis by enzymes and emulsification by endogenous bile salts make liposomes unstable in the gastrointestinal tract. In this study, sodium tauroursodeoxycholate (TUDCNa)-based multifunctional bilosomes were designed to address the deficiencies of conventional liposomes. In the designed bilosomes, cholesterol was replaced by TUDCNa, which served as both a membrane stabilizer and an antidiabetic drug. Oleanolic acid (OA) was encapsulated in both conventional liposomes (OA-Ch-Lip) and bilosomes (OA-Tu-Bil) to compare their properties. Firstly, OA-Tu-Bil exhibited similar encapsulation efficiency and drug loading compared to OA-Ch-Lip, but with a smaller particle size. Secondly, OA-Tu-Bil showed better stability than OA-Ch-Lip. Thirdly, bilosomes exhibited prolonged intestinal retention time and improved permeability and oral bioavailability. Fourthly, in type 2 diabetes mellitus (T2DM) mice model, TUDCNa synergized with OA to exhibit the strongest therapeutic effect. In conclusion, TUDCNa have demonstrated the ability to substitute cholesterol in conventional liposomes, it provided a new approach for oral delivery of hypoglycemic drugs, and offered an innovative strategy for combination therapy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Rationale and Objectives: Fluid-attenuated inversion recovery vessel hyperintensities (FVHs) reflect the haemodynamic state and may aid in predicting the prognosis of border zone (BZ) infarct patients. This study was to explore the relationship between FVHs and functional outcomes for different BZ infarct subtypes following medical therapy administration., Materials and Methods: Consecutive patients with ischemic stroke were retrospectively enrolled and classified into internal BZ (IBZ) infarct, cortical BZ (CBZ) infarct and mixed-type infarct patients. FVHs were quantified using the FVH-Alberta Stroke Program Early CT Score (ASPECTS) system, and the scores were used to divide the patients into low-FVH (0-3) and high-FVH (4-7) groups. The FVH location and the cerebrovascular stenotic degree were recorded. Logistic regression was performed to identify risk factors for poor outcomes (modified Rankin scale score ≥3)., Results: A total of 207 BZ infarct patients (IBZ, n = 130; CBZ, n = 52; mixed-type, n = 25) were included. The FVH score was positively correlated with cerebrovascular stenosis (r = 0.332, P < 0.001) in all patients. A high FVH score was associated with poor outcomes in all (OR 2.568, 95% CI (1.147 to 5.753), P = 0.022) and in CBZ infarct patients (OR 9.258, 95% CI 1.113 to 77.035), P = 0.040). FVH-diffusion-weighted imaging (DWI) mismatch was not significantly associated with outcomes in the entire patient group or in any subgroup., Conclusions: A high FVH score is associated with poor long-term outcomes in patients with CBZ infarcts but not in those with IBZ or mixed-type infarcts., 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 Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

This study aimed to explore active ingredients in Polygonum cuspidatum with potential effects on odontogenic keratocysts (OKCs) using network pharmacological approach and bioinformatic gene analysis. The active ingredients and targets of P. cuspidatum were selected from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) database, and the ingredient-target network was constructed using Cytoscape software. Differentially expressed genes (DEGs) of OKC were selected and Gene Ontology (GO) enrichment analysis were performed through bioinformatic analysis using Gene Expression Omnibus (GEO) dataset GSE38494. The STRING database platform was used to draw protein-protein interaction network diagram, then the hub gene analysis was performed by Cytoscape software. AutoDock Vina software was used to perform molecular docking verification of the effects of the active ingredients on potential core targets. Finally, we use OKC nude animal model to testify the potential effects of P. cuspidatum. Ten active ingredients of P. cuspidatum were obtained. A total of 205 drug targets and 38 potential core targets of P. cuspidatum were confirmed in OKCs. The hub genes included PPARG, SPP1, COL3A1, MMP2, HMOX1, CCL2, CXCL10, VCAM1, RUNX2 and IRF1. Molecular docking showed that the key active ingredients including luteolin and quercetin which exhibited good docking activity with key target proteins (VCAM1, HMOX1 and MMP2). GO enrichment revealed that the pathways of P. cuspidatum acting on OKCs included the response to toxic substance, response to nutrient levels and response to xenobiotic stimulus. P. cuspidatum treatment in OKC could significantly down-regulate COL3A1 and MMP2 expressions in vivo and vitro. Our study indicated that P. cuspidatum is a potential therapeutic candidate for OKCs., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Toward visible light photocatalysis, covalent organic frameworks (COFs) have recently garnered growing attention. The effect of different orientations of imine of imine-linked COFs on photocatalysis should be elucidated. Here, two COFs are developed with 2,5-diphenylthieno[3,2- b ]thiophene (DPTT) and 1,3,6,8-tetraphenylpyrene (Py) linked by imine, affording DPTT-Py-COF and Py-DPTT-COF, respectively. Distinctly, DPTT-Py-COF and Py-DPTT-COF have high crystallinity and porosity, paving the way to highly efficient photocatalysis. Theoretical calculations demonstrate that both DPTT-Py-COF and Py-DPTT-COF are of similar bandgaps but of varied energy positions due to the different orientations of imine. Besides, characterizations disclose that DPTT-Py-COF delivers more enhanced charge separation and transfer than Py-DPTT-COF. Probed by the oxidation of amine to imine, DPTT-Py-COF exhibits a blue light photocatalytic performance superior to that of Py-DPTT-COF. DPTT-Py-COF, a highly recyclable photocatalyst, enables the oxidation of various amines to imines with oxygen. This work highlights that tuning the microenvironment of COFs unravels tenable performances in photocatalysis.

We report the development of a space-compatible packaging system for an integrated monolithic ultra-stable optical reference toward China's next-generation geodesy mission with low orbit satellite-to-satellite tracking. Building on our previous work, we optimized the mounting structure and thermal insulation mechanism using the finite element method. The comprehensive simulation results demonstrated the robustness of the entire packaging system with enough margins to withstand severe launch loads and maintain an ultra-high geometric cavity length stability. A long-term prediction of the vacuum maintenance around the cavity during in-orbit operation was conducted. An engineering prototype, within which an integrated monolithic optical reference has been mounted, was built based on our optimized design, and it has successfully passed typical aerospace environmental tests, including sinusoidal vibration (∼10 g, 10-100 Hz), random vibration (∼0.045 g2/Hz, 10-2000 Hz), and thermal cycling (0-45, 3 °C/min, lasting for 90 h). The experimental thermal time constant of the prototype exceeded 9.5 × 104 s, enabling a temperature stability of 1.1 × 10-6 K/Hz1/2 at 10 mHz on the optical cavity, with external active temperature control. The design is also suitable and useful for laboratory and terrestrial applications., (© 2024 Author(s). All article content, except where otherwise noted, is licensed under a Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).)

Diabetic ulcers are one of the common complications in diabetic patients. Delayed wound healing is associated with persistent pro-inflammatory M1 polarization, reduced angiogenesis and increased reactive oxygen species (ROS) in the microenvironment. Wound healing consists of multiple phases and therefore requires treatment tailored to each phase. In this study, a biphasic drug-releasing microneedle (MN) was fabricated to achieve early ROS scavenging and late accelerated angiogenesis to promote wound healing. Vascular endothelial growth factor (VEGF) was first encapsulated in methacryloylated sulfonated chitosan (SCSMA) microspheres (V@MP), and then V@MP was loaded into hyaluronic acid (HA) microneedles along with cerium dioxide nanoparticles (CONPs). Rapid dissolution of HA rapidly releases the CONPs to clear ROS, whereas the V@MP stays in the wound. SCSMA slow degradation prolongs the release of VEGF, thereby promoting angiogenesis. In vitro and in vivo studies have shown that this biphasic drug-releasing smart microneedle improves cell proliferation and migration, effectively scavenges ROS, promotes angiogenesis and tissue regeneration, and synergistically promotes M2 macrophage polarization. It provides a new delivery mode for nano-enzymes and growth factors that could be multifunctional and synergistic in the treatment of diabetic ulcers. STATEMENT OF SIGNIFICANCE: In our study, we present a microneedle (V@MP/C@MN) that can release drugs biphasically, which showed good repair ability in diabetic ulcer model. Large amounts of CONPs were rapidly released to alleviate oxidative stress during the inflammation of the wound, and V@MP stayed in the wound for a long period of time to release VEGF and promote angiogenesis in the late stage of wound healing. The results indicated that V@MP/C@MN could promote cell proliferation and migration, effectively scavenge ROS, promote angiogenesis and tissue regeneration, and synergistically promote M2 macrophage polarization, which could play a multifunctional and synergistic role in the treatment of diabetic ulcers., 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 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Pelvic fracture is a severe trauma with life-threatening implications. Surgical reduction is essential for restoring the anatomical structure and functional integrity of the pelvis, requiring accurate preoperative planning. However, the complexity of pelvic fractures and limited data availability necessitate labor-intensive manual corrections in a clinical setting. We describe in this paper a novel bidirectional framework for automatic pelvic fracture surgical planning based on fracture simulation and structure restoration. Our fracture simulation method accounts for patient-specific pelvic structures, bone density information, and the randomness of fractures, enabling the generation of various types of fracture cases from healthy pelvises. Based on these features and on adversarial learning, we develop a novel structure restoration network to predict the deformation mapping in CT images before and after a fracture for the precise structural reconstruction of any fracture. Furthermore, a self-supervised strategy based on pelvic anatomical symmetry priors is developed to optimize the details of the restored pelvic structure. Finally, the restored pelvis is used as a template to generate a surgical reduction plan in which the fragments are repositioned in an efficient jigsaw puzzle registration manner. Extensive experiments on simulated and clinical datasets, including scans with metal artifacts, show that our method achieves good accuracy and robustness: a mean SSIM of 90.7% for restorations, with translational errors of 2.88 mm and rotational errors of 3.18°for reductions in real datasets. Our method takes 52.9 s to complete the surgical planning in the phantom study, representing a significant acceleration compared to standard clinical workflows. Our method may facilitate effective surgical planning for pelvic fractures tailored to individual patients in clinical settings., 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: Previous studies link overweight/obesity to reduced fertility, highlighting weight intervention as vital for better pregnancy outcomes. However, clarity on the role and efficacy of weight loss in enhancing pregnancy is inconsistent., Objective: This study aimed to assess the impact of individualized weight intervention on pregnancy among Chinese overweight/obese infertile women and explore body composition indexes influencing pregnancy outcomes., Methods: This retrospective study involved 363 overweight/obese infertile women admitted to the First Affiliated Hospital of Guangxi Medical University, Guangxi, China, from June 2017 to November 2020. Among them, 249 received personalized weight intervention (intervention group), while 114 did not (control group). Pregnancy outcomes were compared between the two groups, and changes in body composition before and after intervention were measured. Multivariate logistic regression was employed to analyze factors influencing pregnancy outcomes., Results: The intervention group exhibited significantly higher clinical pregnancy rates, natural pregnancy rates, assisted reproductive pregnancy rates, and induced ovulation (IO) pregnancy rates compared to the control group (all P < .05). Following weight intervention, there were significant decreases in body weight, body mass index (BMI), visceral fat area, and body fat (all P < .01). Logistic regression analysis identified polycystic ovary syndrome as the reason for infertility (OR=3.446, P = .016), ∆body weight %≥10% (OR=2.931, P = .014), and ∆visceral fat area% (OR=1.025, P = .047) as positive factors for a successful pregnancy. Conversely, age≥35 years old (OR=0.337, P = .001), BMI≥25 kg/m2 after intervention (OR=0.279, P < .001), and visceral fat area≥100 cm2 after intervention (OR=0.287, P = .007) were identified as negative factors., Conclusions: Individualized weight management enhances pregnancy outcomes in overweight/obese infertile women. Achieving a reduction in body weight by 10% or more, combined with effective control of visceral fat, proves important in improving pregnancy outcomes. Excess visceral fat emerges as an adverse factor impacting successful pregnancy.

A type of colorectal cancer (CRC)，Colitis-associated colorectal cancer (CAC)， is closely associated with chronic inflammation and gut microbiota dysbiosis. Berberine (BBR) has a long history in the treatment of intestinal diseases, which has been reported to inhibit colitis and CRC. However, the mechanism of its action is still unclear. Here, this study aimed to explore the potential protective effects of BBR on azoxymethane (AOM)/dextransulfate sodium (DSS)-induced colitis and tumor mice, and to elucidate its potential molecular mechanisms by microbiota, genes and metabolic alterations. The results showed that BBR inhibited the gut inflammation and improved the function of mucosal barrier to ameliorate AOM/DSS-induced colitis. And BBR treatment significantly reduced intestinal tumor development and ki-67 expression of intestinal tissue along with promoted apoptosis. Through microbiota analysis based on the 16 S rRNA gene, we found that BBR treatment improved intestinal microbiota imbalance in AOM/DSS-induced colitis and tumor mice, which were characterized by an increase of beneficial bacteria, for instance Akkermanisa, Lactobacillus, Bacteroides uniformis and Bacteroides acidifaciens. In addition, transcriptome analysis showed that BBR regulated colonic epithelial signaling pathway in CAC mice particularly by tryptophan metabolism and Wnt signaling pathway. Notably, BBR treatment resulted in the enrichment of amino acids metabolism and microbiota-derived SCFA metabolites. In summary, our research findings suggest that the gut microbiota-amino acid metabolism-Wnt signaling pathway axis plays critical role in maintaining intestinal homeostasis, which may provide new insights into the inhibitory effects of BBR on colitis and colon cancer., Competing Interests: Declaration of Competing Interest The authors declare that there are no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

In the realm of glioma treatment, our groundbreaking research has uncovered the pivotal role of Integrin Beta 2 (ITGB2) in non-apoptotic cell death and its profound implications for immunotherapy efficacy. Gliomas, known for their aggressive and infiltrative nature, demand innovative therapeutic strategies for improved patient outcomes. Our study bridges a critical gap by examining the interplay between non-apoptotic cell death and immunotherapy response in gliomas. Through comprehensive analysis of ten diverse glioma datasets, we developed a unique death enrichment score and identified ITGB2 as a significant risk marker. This study demonstrates that ITGB2 can predict immune activity, mutation characteristics, and drug response in glioma patients. We reveal that ITGB2 not only mediates glioma proliferation and migration but also crucially influences immunotherapy responses by modulating the interaction between gliomas and macrophages by single-cell sequencing analysis (iTalk and ICELLNET). Employing a variety of molecular and cellular methodologies, including in vitro models, our findings highlight ITGB2 as a potent marker in glioma biology, particularly impacting macrophage migration and polarization. We present compelling evidence of ITGB2's dual role in regulating tumor cell behavior and shaping the immune landscape, thereby influencing therapeutic outcomes. The study underlines the potential of ITGB2-targeted strategies in enhancing the efficacy of immunotherapy and opens new avenues for personalized treatment approaches in glioma management. In conclusion, this research marks a significant stride in understanding glioma pathology and therapy, positioning ITGB2 as a key biomarker and a promising target in the quest for effective glioma treatments., (© 2024 Wiley Periodicals LLC.)

Vascular endothelial growth factor (VEGF) signaling is crucial for choroidal neovascularization (CNV), a major pathological feature of neovascular age-related macular degeneration (nAMD). Gene transcription of VEGF is mainly regulated by hypoxia-inducible factor 1-alpha (HIF-1α). The chromobox (CBX) family polycomb protein (Pc) subgroup includes CBX2, CBX4, CBX6, CBX7, and CBX8. CBX4 enhances hypoxia-induced VEGF expression and angiogenesis in hepatocellular carcinoma (HCC) cells by increasing HIF-1α's transcriptional activity. The objective of the study was to examine the functions of members of the CBX family Pc subgroup in choroidal vascular endothelial cells (CVECs) during CNV. CBX4 and CBX7 expression was up-regulated in hypoxic human choroidal vascular endothelial cells (HCVECs). In HCVECs, CBX7 facilitated HIF-1α transcription and expression, while CBX4 did not. In HCVECs, CBX7 stimulated HIF-1α's nuclear translocation and transcriptional activity, which in turn stimulated VEGF transcription and expression. The CBX7/HIF-1α/VEGF pathway promoted the migration, proliferation, and tube formation of HCVECs. The CBX7/HIF-1α/VEGF pathway was up-regulated in CVECs and in the mouse model with laser-induced CNV. Mouse CNV was lessened by the blockade of CBX7 through the down-regulation of HIF-1α/VEGF. In conclusion, CBX7 enhanced pro-angiogenic behaviors of hypoxic CVECs by up-regulating the HIF-1α/VEGF pathway, which contributing to the formation of mouse laser-induced CNV., Competing Interests: Declaration of competing interest All authors assert that there are no potential conflicts of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Chitin has garnered significant attention due to its renewable, biocompatibility and biodegradability, while its practical application seriously hindered as the functionality of chitin itself can no longer meet people's increasing requirements for materials. Here, an effective method is successfully built for high-performance chitin fibers fabrication through a multi-step strategy that involved chemical pre-crosslinking, followed by wet-twisting and wet-stretching techniques, combined with physical cross-linking. The as-prepared chitin fiber exhibited a smooth surface, adjustable diameter, and mechanical strong properties (144.6 MPa). More importantly, functional chitin fiber with magnetic or conductive abilities can be easily obtained by spraying Fe 3 O 4 particles or Ag nanowire on the chemical pre-crosslinking chitin gel film before stretching and twisting. The doped functional inorganic particles exist in a continuous ribbon structure in the fiber reduced the decrease in material strength caused by uneven particles dispersion, resulting 88.4 % of stress and 91.6 % of strain retention. This work not only bestow invaluable insights into the fabrication of functional chitin fibers but also provide a novel approach to solve the problem of poor compatibility between organic and inorganic composite materials., 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.)

Introduction: Long working hours are likely associated with the decreased of kidney function, while physical activity (PA) was linked to improvements in kidney function. However, whether PA can offset the negative impact of long working hours on kidney function was unclear, which is the focus of this study., Methods: A cross-sectional study was conducted. Three approaches were adopted to distinguish the association between long working hours and regular working hours. Moderate to vigorous physical activity (PA) was assessed by a structured questionnaire. eGFR and chronic kidney disease (CKD) or not were utilized to evaluate the kidney function. Linear and logistic regression analyses were conducted to assess the association between weekly working hours, PA, and kidney function., Results: A total of 18,431 adults were enrolled in this study, including 9981 males (54.2%) and 8450 females (45.8%). The average eGFR was (99.54 ± 17.55 mL/min/1.73 m 2 ). The people worked more than 40 h/wk (98.89 ± 17.06 mL/min/1.73 m 2 ) had lower eGFR compared to those worked less than 40 h/wk (99.93 ± 17.83 mL/min/1.73 m 2 ) ( p < 0.05). Individuals working longer hours exhibited lower eGFR ( β  = -0.772, 95% CI : -1.241, -0.303, for > 40 h/wk compared to working ≤ 40 h/wk). Engagement in moderate to vigorous PA was associated with higher eGFR values ( β = 1.159, 95% CI : 0.699, 1.619) compared to low PA (< 150 minutes/wk), but this association did not reach statistical significance for the prevalence of CKD. Furthermore, PA was insufficient to reverse the decline of eGFR related to prolonged working hours., Discussion: Prolonged working hours were associated with a decline in eGFR, while PA was found to have a protective effect on kidney function. However, PA alone may not fully mitigate the negative impact of prolonged working hours on renal health. More robust measures to protect renal function should be implemented to mitigate the damage caused by prolonged working hours., 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 Yan, Nabi, Liu, Zeng, Song, Ding and Hu.)

Glycine as one of the most abundant amino acids in human proteins, with extensive applications in both life and industry, is conventionally synthesized through complex procedures or toxic feedstocks. In this study, we present a facile and benign electrochemical pathway for synthesis of glycine through reductive coupling of glyoxylic acid and nitrate over a copper-bismuth bimetal catalyst derived from a metal-organic framework (MOF) array on copper foam (Cu/Bi-C@CF). Remarkably, Cu/Bi-C@CF achieves a fantastic selectivity of 89 %, corresponding a high Faraday efficiency of 65.9 %. From control experiments, the introduction of Bi caused the binding energy of Cu shift to a lower state, which leads to a high selectivity towards the formation of key intermediate hydroxylamine rather than ammonia product, facilitating the formation of oxime and providing additional sites for subsequent hydrogenation reaction on the way to glycine. Moreover, the derivation of MOF arrays ensures the effective dispersion of Bi and enhances the stability of Cu/Bi-C@CF. This innovative approach not only presents sustainable pathways for the production of value-added organonitrogen compounds utilizing readily available carbon and nitrogen sources, but also provides novel insights into the design of multistage structural catalysts for sequential reactions., (© 2024 Wiley-VCH GmbH.)

The hyperpolarization-activated cyclic nucleotide-gated (HCN) channels play a crucial role in regulating neuronal excitability. Despite growing evidence supporting the therapeutic potential of HCN1 inhibition in treating neurological disorders, the structural basis of channel inhibition by inhibitor has remained elusive. Here, we present the cryo-electron microscopy structure of human HCN1 channel in complex with inhibitor ivabradine, the drug on the market that acts on HCN channels. Combining electrophysiology, mutagenesis, and molecular dynamics simulations, our findings reveal that ivabradine binds to a previously unidentified pocket formed between the S4, S1, and HCN domain. Furthermore, through structure-based virtual screening, we identify two Food and Drug Administration-approved drugs that can inhibit the HCN1 channel by interacting with the ivabradine-binding site. Our results not only provide insights into the structural intricacies of ivabradine-mediated inhibition, but also offer a potential pharmacological framework for developing novel drugs targeting the HCN1 channel. The elucidation of these molecular interactions serves as a foundational step in advancing therapeutic strategies for modulating HCN1 activity, contributing to the broader landscape of drug discovery and development in this area., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The hypothalamic-pituitary-ovarian (HPO) axis represents a central neuroendocrine network essential for reproductive function. Despite its critical role, the intrinsic heterogeneity within the HPO axis across vertebrates and the complex intercellular interactions remain poorly defined. This study provides the first comprehensive, unbiased, cell type-specific molecular profiling of all three components of the HPO axis in adult Lohmann layers and Liangshan Yanying chickens. Within the hypothalamus, pituitary, and ovary, seven, 12, and 13 distinct cell types were identified, respectively. Results indicated that the pituitary adenylate cyclase activating polypeptide (PACAP), follicle-stimulating hormone (FSH), and prolactin (PRL) signaling pathways may modulate the synthesis and secretion of gonadotropin-releasing hormone (GnRH), FSH, and luteinizing hormone (LH) within the hypothalamus and pituitary. In the ovary, interactions between granulosa cells and oocytes involved the KIT, CD99, LIFR, FN1, and ANGPTL signaling pathways, which collectively regulate follicular maturation. The SEMA4 signaling pathway emerged as a critical mediator across all three tissues of the HPO axis. Additionally, gene expression analysis revealed that relaxin 3 (RLN3), gastrin-releasing peptide (GRP), and cocaine- and amphetamine regulated transcripts (CART, also known as CARTPT) may function as novel endocrine hormones, influencing the HPO axis through autocrine, paracrine, and endocrine pathways. Comparative analyses between Lohmann layers and Liangshan Yanying chickens demonstrated higher expression levels of GRP , RLN3 , CARTPT , LHCGR , FSHR , and GRPR in the ovaries of Lohmann layers, potentially contributing to their superior reproductive performance. In conclusion, this study provides a detailed molecular characterization of the HPO axis, offering novel insights into the regulatory mechanisms underlying reproductive biology.

Background: The Nottingham prognostic index (NPI) has been shown to negatively impact survival in breast cancer (BC). However, its ability to predict the locoregional recurrence (LRR) of BC remains still unclear. This study aims to determine whether a higher NPI serves as a significant predictor of LRR in BC., Methods: In total, 238 patients with BC were included in this analysis, and relevant clinicopathological features were collected. Correlation analysis was performed between NPI scores and clinicopathological characteristics. The optimal nomogram model was determined by Akaike information criterion. The accuracy of the model's predictions was evaluated using receiver operating characteristic curves (ROC curves), calibration curves and goodness of fit tests. The clinical application value was assessed through decision curve analysis., Results: Six significant variables were identified, including age, body mass index (BMI), TNM stage, NPI, vascular invasion, perineural invasion ( P <0.05). Two prediction models, namely a TNM-stage-based model and an NPI-based model, were constructed. The area under the curve (AUC) for the TNM-stage- and NPI-based models were 0.843 (0.785,0.901) and 0.830 (0.766,0.893) in training set and 0.649 (0.520,0.778) and 0.728 (0.610,0.846) in validation set, respectively. Both models exhibited good calibration and goodness of fit. The F-measures were 0.761vs 0.756 and 0.556 vs 0.696, respectively. Clinical decision curve analysis showed that both models provided clinical benefits in evaluating risk judgments based on the nomogram model., Conclusions: a higher NPI is an independent risk factor for predicting LRR in BC. The nomogram model based on NPI demonstrates good discrimination and calibration, offering potential clinical benefits. Therefore, it merits widespread adoption and application., Competing Interests: The authors declared 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 Zheng, Zeng, Huang, Wu, Xiao and Li.)

Aiming at the problems of a large volume, slow processing speed, and difficult deployment in the edge terminal, this paper proposes a lightweight insulator detection algorithm based on an improved SSD. Firstly, the original feature extraction network VGG-16 is replaced by a lightweight Ghost Module network to initially achieve the lightweight model. A Feature Pyramid structure and Feature Pyramid Network (FPN+PAN) are integrated into the Neck part and a Simplified Spatial Pyramid Pooling Fast (SimSPPF) module is introduced to realize the integration of local features and global features. Secondly, multiple Spatial and Channel Squeeze-and-Excitation (scSE) attention mechanisms are introduced in the Neck part to make the model pay more attention to the channels containing important feature information. The original six detection heads are reduced to four to improve the inference speed of the network. In order to improve the recognition performance of occluded and overlapping targets, DIoU-NMS was used to replace the original non-maximum suppression (NMS). Furthermore, the channel pruning strategy is used to reduce the unimportant weight matrix of the model, and the knowledge distillation strategy is used to fine-adjust the network model after pruning, so as to ensure the detection accuracy. The experimental results show that the parameter number of the proposed model is reduced from 26.15 M to 0.61 M, the computational load is reduced from 118.95 G to 1.49 G, and the mAP is increased from 96.8% to 98%. Compared with other models, the proposed model not only guarantees the detection accuracy of the algorithm, but also greatly reduces the model volume, which provides support for the realization of visible light insulator target detection based on edge intelligence.