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Alzheimer's disease (AD) is an advanced and incurable neurodegenerative disease. Genetic variations are intrinsic etiological factors contributing to the abnormal expression of brain function and structure in AD patients. A new multimodal feature fusion called "magnetic resonance imaging (MRI)-p value" was proposed to construct 3D fusion images by introducing genes as a priori knowledge. Moreover, a new deep joint learning diagnostic model was constructed to fully learn images features. One branch trained a residual network (ResNet) to learn the features of local pathological regions. The other branch learned the position information of brain regions with different changes in the different categories of subjects' brains by introducing attention convolution, and then obtained the discriminative probability information from locations via convolution and global average pooling. The feature and position information of the two branches were linearly interacted to acquire the diagnostic basis for classifying the different categories of subjects. The diagnoses of AD and health control (HC), AD and mild cognitive impairment (MCI), HC and MCI were performed with data from the Alzheimer's Disease Neuroimaging Initiative (ADNI). The results showed that the proposed method achieved optimal results in AD-related diagnosis. The classification accuracy (ACC) and area under the curve (AUC) of the three experimental groups were 93.44% and 96.67%, 89.06% and 92%, and 84% and 81.84%, respectively. Moreover, a total of six novel genes were found to be significantly associated with AD, namely NTM, MAML2, NAALADL2, FHIT, TMEM132D and PCSK5, which provided new targets for the potential treatment of neurodegenerative diseases., (© 2024. The Author(s).)

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.

Objective: This study utilized lung ultrasound to investigate whether lung protective ventilation reduces pulmonary atelectasis and improves intraoperative oxygenation in infants undergoing laparoscopic surgery., Methods: Eighty young infants (aged 1-6 months) who received general anesthesia for more than 2 h during laparoscopic surgery were randomized into the lung protective ventilation group (LPV group) and the conventional ventilation group (control group). The LPV group received mechanical ventilation starting at 6 mL/kg tidal volume, 5 cmH 2 O PEEP, 60% inspired oxygen fraction, and half-hourly alveolar recruitment maneuvers. Control group ventilation began with 8-10 mL/kg tidal volume, 0 cmH 2 O PEEP, and 60% inspired oxygen fraction. Lung ultrasound was conducted five times-T1 (5 min post-intubation), T2 (5 min post-pneumoperitoneum), T3 (at the end of surgery), T4 (post-extubation), and T5 (prior to discharge from the PACU)-for each infant. Simultaneous arterial blood gas analysis was performed at T1, T2, T3, and T4., Results: Statistically significant differences were observed in pulmonary atelectasis incidence, lung ultrasound scores, and the PaO 2 , PaCO 2 , PaO 2 /FiO 2 ratios at T2, T3, and T4. However, at T5, no statistically significant differences were noted in terms of lung ultrasound scores (4.30 ± 1.87 vs. 5.00 ± 2.43, 95% CI: -1.67 to 0.27, p  = 0.153) or the incidence of pulmonary atelectasis (32.5% vs. 47.5%, p  = 0.171)., Conclusion: In infants aged 1-6 months, lung protective ventilation during laparoscopy under general anesthesia significantly reduced the incidence of pulmonary atelectasis and enhanced intraoperative oxygenation and dynamic lung compliance compared to conventional ventilation. However, these benefits did not persist; no differences were observed in lung ultrasound scores or the incidence of pulmonary atelectasis at PACU discharge., Clinical Trial Registration: http://www.chictr.org.cn/, identifier: ChiCTR2200058653., 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 Yue, Wang, Wu, Sun, Xia and Chen.)

We prepared biocompatible and environment-friendly zinc oxide nanoparticles (ZnO NPs) with upconversion properties and catalase-like nanozyme activity. Photodynamic therapy (PDT) application is severely limited by the poor penetration of UV-Visible light and a hypoxic tumor environment. Here, we used ZnO NPs as a carrier for the photosensitizer chlorin e6 (Ce6) to construct zinc oxide-chlorin e6 nanoparticles (ZnO-Ce6 NPs), simultaneously addressing both problems. In terms of penetration, ZnO NPs convert 808 nm near-infrared light into 401 nm visible light to excite Ce6, achieving deep-penetrating photodynamic therapy under long-wavelength light. Interestingly, the ability to emit short-wavelength light under long-wavelength light is usually observed in upconversion nanoparticles. As nanozymes, ZnO NPs can catalyze the decomposition of hydrogen peroxide in tumors, providing oxygen for photodynamic action and relieving hypoxia. The enhanced photodynamic action produces a large amount of reactive oxygen species, which overactivate autophagy and trigger immunogenic cell death (ICD), leading to antitumor immunotherapy. In addition, even in the absence of light, ZnO and ZnO-Ce6 NPs can induce ferroptosis of tumor cells and exert antitumor effects., Competing Interests: The authors have no conflicts of interest to declare., (© 2024 The Authors.)

Rationale and Objectives: Medulloblastoma (MB) and Ependymoma (EM) in children, share similarities in age group, tumor location, and clinical presentation. Distinguishing between them through clinical diagnosis is challenging. This study aims to explore the effectiveness of using radiomics and machine learning on multiparametric magnetic resonance imaging (MRI) to differentiate between MB and EM and validate its diagnostic ability with an external set., Materials and Methods: Axial T2 weighted image (T2WI) and contrast-enhanced T1weighted image (CE-T1WI) MRI sequences of 135 patients from two centers were collected as train/test sets. Volume of interest (VOI) was manually delineated by an experienced neuroradiologist, supervised by a senior. Feature selection analysis and the least absolute shrinkage and selection operator (LASSO) algorithm identified valuable features, and Shapley additive explanations (SHAP) evaluated their significance. Five machine-learning classifiers-extreme gradient boosting (XGBoost), Bernoulli naive Bayes (Bernoulli NB), Logistic Regression (LR), support vector machine (SVM), linear support vector machine (Linear SVC) classifiers were built based on T2WI (T2 model), CE-T1WI (T1 model), and T1 + T2WI (T1 + T2 model). A human expert diagnosis was developed and corrected by senior radiologists. External validation was performed at Sun Yat-Sen University Cancer Center., Results: 31 valuable features were extracted from T2WI and CE-T1WI. XGBoost demonstrated the highest performance with an area under the curve (AUC) of 0.92 on the test set and maintained an AUC of 0.80 during external validation. For the T1 model, XGBoost achieved the highest AUC of 0.85 on the test set and the highest accuracy of 0.71 on the external validation set. In the T2 model, XGBoost achieved the highest AUC of 0.86 on the test set and the highest accuracy of 0.82 on the external validation set. The human expert diagnosis had an AUC of 0.66 on the test set and 0.69 on the external validation set. The integrated T1 + T2 model achieved an AUC of 0.92 on the test set, 0.80 on the external validation set, achieved the best performance. Overall, XGBoost consistently outperformed in different classification models., Conclusion: The combination of radiomics and machine learning on multiparametric MRI effectively distinguishes between MB and EM in childhood, surpassing human expert diagnosis in training and testing sets., Competing Interests: Declaration of Competing Interest The authors declare that they have no identified economic or personal conflicts that would have seemed to have an impact on the research presented in this study. Competing Interest The authors affirm that they have no identified economic or personal conflicts that would have seemed to impact the research presented in this study., (Copyright © 2024 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Burn wounds often bring high risks of delayed healing process and even death. Reactive oxygen species (ROS) play a crucial role in burn wound repair. However, the dynamic process in wound healing requires both the generation of ROS to inhibit bacteria and the subsequent reduction of ROS levels to initiate and promote tissue regeneration, which calls for a more intelligent ROS regulation dressing system. Hence, a dual-layered hydrogel (Dual-Gel) tailored to the process of burn wound repair is designed: the inner layer hydrogel (Gel 2) first responds to bacterial hyaluronidase (Hyal) to deliver aggregation-induced emission photosensitizer functionalized adipose-derived stem cell nanovesicles, which generate ROS upon light irradiation to eliminate bacteria; then the outer layer hydrogel (Gel 1) continuously starts a long-lasting consumption of excess ROS at the wound site to accelerate tissue regeneration. Simultaneously, the stem cell nanovesicles trapped in the burns wound also provide nutrients and mobilize neighboring tissues to thoroughly assist in inflammation regulation, cell proliferation, migration, and angiogenesis. In summary, this study develops an intelligent treatment approach on burn wounds by programmatically regulating ROS and facilitating comprehensive wound tissue repair., (© 2024 Wiley‐VCH GmbH.)

Background: The neutrophil-to-lymphocyte ratio (NLR) and systemic inflammation response index (SIRI) at admission are independent diagnostic biomarkers in stroke-associated pneumonia (SAP). Our study aimed to investigate the association between NLR, SIRI, specifically follow-up NLR and SIRI, and SAP, as well as their relationship with functional outcomes., Patients and Methods: We retrospectively included 451 consecutive intracerebral hemorrhage patients from May 2017 to May 2019. We conducted univariate and multivariable analyses to identify the factors independently associated with SAP and poor functional outcomes., Results: Compared to 127 (28.16%) patients diagnosed with SAP, those without SAP had both lower baseline and follow-up NLR and SIRI values ( P <0.001). After adjustments, we found that baseline NLR [OR, 1.039 (95% CI, 1.003-1.077); P =0.036] and follow-up NLR [OR, 1.054 (95% CI, 1.011-1.098); P =0.012] were independently associated with SAP. The follow-up NLR was also associated with a higher mRS [OR, 1.124 (95% CI, 1.025-1.233); P =0.013] and lower ADL-MBI score [OR, 1.167 (95% CI, 1.057-1.289); P =0.002] at discharge. Multivariable analysis indicated that advanced age and nasogastric tube feeding were independently associated with SAP ( P <0.05). We constructed a dynamic nomogram to identify SAP risk. Further subgroup analysis revealed that baseline NLR [OR, 1.062 (95% CI, 1.007-1.120); P =0.026] is independently associated with SAP in the nasogastric feeding group, while follow-up NLR [OR, 1.080 (95% CI, 1.024-1.139); P =0.005] was associated with the occurrence of SAP in non-nasogastric feeding patients., Conclusions: We found elevated baseline and follow-up NLR values were associated with SAP occurrence, and increasing follow-up NLR indicated poor functional outcomes. Inflammatory markers at different stages may offer individualized guidance for patients receiving various treatments., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Both genetic and lifestyle factors contribute to myocardial infarction (MI) and stroke, including ischaemic stroke (IS) and intracerebral haemorrhage (ICH). We explored how and the extent to which a healthy lifestyle, by considering a comprehensive list, could counteract the genetic risk of those diseases, respectively., Methods: 315 044 participants free of stroke and MI at baseline were identified from the UK Biobank. Genetic risk scores (GRS) for those diseases were constructed separately and categorised as low, intermediate and high by tertile. Lifestyle risk scores (LRS) were constructed separately using smoking, alcohol intake, physical activity, dietary patterns and sleep patterns. Similarly, participants were categorised into low, intermediate and high LRS. The data were analysed using Cox proportional hazard models., Results: Over a median follow-up of 12.8 years, 4642, 1046 and 9485 participants developed IS, ICH and MI, respectively. Compared with participants with low levels of GRS and LRS, the HRs of those with high levels of GRS and LRS were 3.45 (95% CI 2.71 to 4.41), 2.32 (95% CI 1.40 to 3.85) and 4.89 (95% CI 4.16 to 5.75) for IS, ICH and MI, respectively. Moreover, among participants with high GRS, the standardised 14-year rates of IS events were 4.40% (95% CI 3.45% to 5.36%) among those with high LRS. In contrast, it is only 1.78% (95% CI 1.63% to 1.94%) among those with low LRS. Similarly for MI, the high LRS group had standardised rates of 8.60% (95% CI 7.38% to 9.81%), compared with 3.34% (95% CI 3.12% to 3.56%) in low LRS. Among the high genetic risk group of ICH, the rate is reduced by about half compared low LRS to high LRS, although the rate was low for both (0.36% (95% CI 0.31% to 0.42%) and 0.71% (95% CI 0.36% to 1.05%), respectively)., Conclusion: Healthy lifestyles were substantially associated with a reduction in the risk of IS, ICH and MI and attenuated the genetic risk of IS, ICH and MI by at least half, respectively., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Low-cost nanocomposite metasurfaces have demonstrated attractive potential to replace the equivalent dielectric metasurfaces for light engineering. However, the resonance characteristics of embedded structures in nanocomposite metasurfaces have not been further analyzed beyond the effective refractive index. Herein, we have proposed customizable polarization-selective narrowband meta-filters using ultraviolet-curable (UV) nanocomposites. As an additional degree of freedom, near-field effects between highly concentrated doped nanoparticles can enhance the Mie resonance of the low aspect ratio (AR = 0.2) meta-units. The surface lattice resonances (SLRs) of meta-filters can be coupled with enhanced Mie resonances of individual meta-units to realize tunable narrowband (FWHM ∼0.007λ) reflections with intensities near unity. Meanwhile, the polarization-selective properties of the reflection peaks can be tuned by optimizing the asymmetric lattice. Such proposed new-generation customizable meta-filters will offer, to our knowledge, novel strategies for filtering specific near-infrared polarized fluorescence in the integrated imaging systems.

Background: Diabetes Mellitus is a long duration disease, and if a person with diabetes is infected with a blood-borne infectious disease and proper syringe disposal practices are not followed, they run the danger of transmitting the infection to others for a very long period. Whereas fewer research has been done in China on the handing of sharp objects at home. Therefore, there is a need to translate and localize the Knowledge-Attitude-Practice Questionnaire regarding sharp disposal for diabetic patients to assess the current level of patient knowledge, attitudes, and practices and to improve the basis for promoting safe sharps handling practices., Methods: This investigation was a cross-sectional study. The Knowledge-Attitude-Practice Questionnaire regarding sharp disposal was localized and debugged and tested for reliability and validity, and then 334 patients were investigated by General Characteristics Questionnaire, Knowledge- Attitude-Practice Questionnaire regarding sharp disposal, and the influencing factors of practice level regarding sharp disposal of patients were analyzed., Results: The Cronbach's α value of the attitude section was 0.864 and the content validity index was 0.923. The knowledge and practice sections are in line with continental language conventions and are easy to understand without any ambiguity. The majority (52%) of the participants had poor knowledge and a neutral attitude toward disposing of sharp objects. Sharps disposal practices among diabetes mellitus patients were poor since about 90% of patients dispose of their used sharps directly into the household waste. Furthermore, we found that level of education, knowledge and attitude were the major predictors of practices regarding sharps disposal among diabetic patients ( R 2  = 0.573, p  < 0.001)., Conclusion: The Chinese version of the Knowledge-Attitude-Practice Questionnaire regarding sharp disposal has applicability in China. In China, current practice of disposing used sharps is improper. Additionally, the majority of the subjects had low levels of knowledge and attitudes. To raise awareness and encourage diabetic patients to follow appropriate sharps disposal practices, there needs to be ongoing education and a locally tailored safe sharp disposal alternative accessible., 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 Zan, Liu, Meng and Wang.)

Purpose: Atherosclerosis (AS) is a chronic inflammatory vascular disease and the predominant cause of ischemic stroke (IS). AS is a potential pathogenetic factor in IS. However, the processes by which they interact remain unknown. The purpose of this paper was to investigate the shared gene signatures and putative molecular processes in AS and IS., Methods: Gene Expression Omnibus (GEO) data for AS and IS microarrays were retrieved. The co-expression modules associated with AS and IS were identified using the Weighted Gene Co-Expression Network Analysis (WGCNA). We constructed an interaction network of shared differentially expressed genes in AS and IS and conducted an enrichment analysis using ClueGO software. We validated the results in a separate cohort through differential gene analysis. Additionally, we retrieved AS and IS-related miRNAs from the Human microRNA Disease Database (HMDD) and predicted their target genes using miRWalk. We then built a network of miRNAs-mRNAs-KEGG pathways using the shared genes., Results: Through WGCNA, we identified five modules and six modules as significant in AS and IS, respectively. A ClueGO enrichment analysis of common genes showed that highly active CCR1 chemokine receptor binding is critical to AS and IS pathogenesis. The differential analysis expression results in another cohort closely matched these findings. The miRNA-mRNA network suggested that hsa-miR-330-5p, hsa-miR-143-3p, hsa-miR-16-5p, hsa-miR-152-3p might regulate the shared gene KRAS, which could be a key player in AS and IS., Conclusion: We integrated ischemic stroke and carotid atherosclerosis public database data and found that ATF3, CCL3, CCL4, JUNB, KRAS, and ZC3H12A may affect both, making them novel biomarkers or therapeutic target genes. Clinical samples and expression trends supported our analyses of pivotal genes., Competing Interests: The authors declare that there is no conflict of interest in this work., (© 2024 Ban et al.)

Background: Whether asthma patients could benefit from home monitoring for fractional exhaled nitric oxide (flow of 50 mL/s, Fe NO50 ) is unknown. We explore the application value of home monitoring Fe NO50 in daily asthma management., Methods: Twenty-two untreated, uncontrolled asthma patients were selected. Medical history, blood and sputum samples, pulmonary function, Asthma Control Test (ACT), and other clinical data of the subjects were collected. All subjects underwent daily monitoring for four weeks using a Fe NO50 monitor and mobile spirometry (mSpirometry). The diurnal differences and dynamic changes were described. Compare the effect-acting time and the relative plateau of treatment between Fe NO50 and mSpirometry monitoring., Results: In the first two weeks, the morning median (IQR) level of Fe NO50 was 44 (35, 56) ppb, which was significantly higher than the evening median level [41 (32, 53) ppb, P = 0.028]. The median (IQR) effect-acting time assessed by Fe NO50 was 4 (3, 5) days, which was significantly earlier than each measure of mSpirometry (P < 0.05). Fe NO50 reached the relative plateau significantly earlier than FEV 1 (15 ± 2 days vs. 21 ± 3 days, P < 0.001). After treatment, the daily and weekly variation rates of Fe NO50 showed a gradually decreasing trend (P < 0.05). The ACT score, sputum eosinophils, and blood eosinophils also significantly improved (P ≤ 0.01)., Conclusions: The daily home monitoring of Fe NO50 in asthmatic patients showed significant circadian rhythm, and the sensitivity of Fe NO50 in evaluating the response to treatment was higher than mSpirometry. The daily and weekly variation rates of Fe NO50 change dynamically with time, which may be used to assess the condition of asthma., (© 2024. The Author(s).)

Background: Carotid atherosclerosis (CAS) is a complication of atherosclerosis (AS). PAN-optosome is an inflammatory programmed cell death pathway event regulated by the PAN-optosome complex. CAS's PAN-optosome-related genes (PORGs) have yet to be studied. Hence, screening the PAN-optosome-related diagnostic genes for treating CAS was vital., Methods: We introduced transcriptome data to screen out differentially expressed genes (DEGs) in CAS. Subsequently, WGCNA analysis was utilized to mine module genes about PANoptosis score. We performed differential expression analysis (CAS samples vs. standard samples) to obtain CAS-related differentially expressed genes at the single-cell level. Venn diagram was executed to identify PAN-optosome-related differential genes (POR-DEGs) associated with CAS. Further, LASSO regression and RF algorithm were implemented to were executed to build a diagnostic model. We additionally performed immune infiltration and gene set enrichment analysis (GSEA) based on diagnostic genes. We verified the accuracy of the model genes by single-cell nuclear sequencing and RT-qPCR validation of clinical samples, as well as in vitro cellular experiments., Results: We identified 785 DEGs associated with CAS. Then, 4296 module genes about PANoptosis score were obtained. We obtained the 7365 and 1631 CAS-related DEGs at the single-cell level, respectively. 67 POR-DEGs were retained Venn diagram. Subsequently, 4 PAN-optosome-related diagnostic genes ( CNTN4 , FILIP1 , PHGDH , and TFPI2 ) were identified via machine learning. Cellular function tests on four genes showed that these genes have essential roles in maintaining arterial cell viability and resisting cellular senescence., Conclusion: We obtained four PANoptosis-related diagnostic genes ( CNTN4 , FILIP1 , PHGDH , and TFPI2 ) associated with CAS, laying a theoretical foundation for treating CAS., 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 Song, Lou, Wang, Zhang, Xia, Ban, Zhao, Sun, Wang, Lin, Guo, Zhou and Xia.)

Kauralexin A1 (KA1) is a key intermediate of the kauralexin A series metabolites of maize phytoalexins. However, their application is severely limited by their low abundance in maize. In this study, an efficient biosynthetic pathway was constructed to produce KA1 in Saccharomyces cerevisiae . Also, metabolic and enzyme engineering strategies were applied to construct the high-titer strains, such as chassis modification, screening synthases, the colocalization of enzymes, and multiple genomic integrations. First, the KA1 precursor ent -kaurene was synthesized using the efficient diterpene synthase GfCPS/KS from Fusarium fujikuroi , and optimized to reach 244.36 mg/L in shake flasks, which displayed a 200-fold increase compared to the initial strain. Then, the KA1 was produced under the catalysis of ZmCYP71Z18 from Zea mays and SmCPR1 from Salvia miltiorrhiza , and the titer was further improved by integrating the fusion protein into the genome. Finally, an ent -kaurene titer of 763.23 mg/L and a KA1 titer of 42.22 mg/L were achieved through a single-stage fed-batch fermentation in a 5 L bioreactor. This is the first report of the heterologous biosynthesis of maize diterpene phytoalexins in S. cerevisiae , which lays a foundation for further pathway reconstruction and biosynthesis of the kauralexin A series maize phytoalexins.

Early endosomes (EEs) are crucial in cargo sorting within vesicular trafficking. While cargoes destined for degradation are retained in EEs and eventually transported to lysosomes, recycled cargoes for the plasma membrane (PM) or the Golgi undergo segregation into specialized membrane structures known as EE buds during cargo sorting. Despite this significance, the molecular basis of the membrane expansion during EE bud formation has been poorly understood. In this study, we identify a protein complex comprising SHIP164, an ATPase RhoBTB3, and a retromer subunit Vps26B, which promotes the formation of EE buds at Golgi-EE contacts. Our findings reveal that Vps26B acts as a novel Rab14 effector, and Rab14 activity regulates the association of SHIP164 with EEs. Depletion of SHIP164 leads to enlarged Rab14 + EEs without buds, a phenotype rescued by wild-type SHIP164 but not the lipid transfer-defective mutants. Suppression of RhoBTB3 or Vps26B mirrors the effects of SHIP164 depletion. Together, we propose a lipid transport-dependent pathway mediated by the RhoBTB3-SHIP164-Vps26B complex at Golgi-EE contacts, which is essential for EE budding., (© 2024. The Author(s).)

Objectives: While dysregulation of DSCC1 (DNA Replication And Sister Chromatid Cohesion 1) has been established in breast cancer and colorectal cancer, its associations with other tumors remain unclear. Therefore, this study was launched to explore the role of DSCC1 in pan-cancer., Methodology: In this study, we investigate the biological functions of DSCC1 across 33 solid tumors, elucidating its role in promoting oncogenesis and progression in various cancers through comprehensive analysis of multi-omics data., Results: We conducted a comprehensive analysis of DSCC1 expression using RNA-seq data from TCGA and GTEx databases across 30 cancer types. Striking variations were observed, with significant overexpression of DSCC1 identified in numerous cancers. Elevated DSCC1 level was strongly associated with poorer prognosis, shorter survival, and advanced tumor stages in kidney renal papillary cell carcinoma (KIRP), liver hepatocellular carcinoma (LIHC), lung adenocarcinoma (LUAD), as indicated by Kaplan-Meier curves and GEPIA2 analysis. Further investigation into the molecular mechanisms revealed reduced DNA methylation in the DSCC1 promoter region in KIRP, LIHC, and LUAD, supporting enhanced RNA transcription. Protein expression analysis via the Human Protein Atlas (HPA) corroborated mRNA expression findings, showcasing elevated DSCC1 protein in KIRP, LIHC, and LUAD tissues. Mutational analysis using cBioPortal revealed alterations in 0.4% of KIRP, 17% of LIHC, and 5% of LUAD samples, predominantly characterized by amplification. Immune cell infiltration analysis demonstrated robust positive correlations between DSCC1 expression and CD8+ T cells, CD4+ T cells, and B cells, influencing the tumor microenvironment. STRING and gene enrichment analyses unveiled DSCC1's involvement in critical pathways, emphasizing its multifaceted impact. Notably, drug sensitivity analysis highlighted a significant correlation between DSCC1 mRNA expression and responses to 78 anticancer treatments, suggesting its potential as a predictive biomarker and therapeutic target for KIRP, LIHC, and LUAD. Finally, immunohistochemistry staining of clinical samples validated computational results, confirming elevated DSCC1 protein expression., Conclusion: Overall, this study provides comprehensive insights into the pivotal role of DSCC1 in KIRP, LIHC, and LUAD initiation, progression, and therapeutic responsiveness, laying the foundation for further investigations and personalized treatment strategies., Competing Interests: None., (AJTR Copyright © 2024.)

Little is known about below-ground competition in mixed-species plantations under increasing nitrogen (N) deposition. This study aims to determine the effects of N addition on root competition in coniferous and broad-leaved species mixed plantations. A pot experiment was conducted using the coniferous species Cunninghamia lanceolata and the broad-leaved species Phoebe chekiangensis planted in mixed plantations with different competition intensities under N addition (0 or 45 kg N ha -1  yr -1 ). Biomass allocation, root morphology, root growth level, and competitive ability were determined after five months of treatment. Our findings indicated that root interactions in mixed plantations did not influence biomass allocation in either C. lanceolata or P. chekiangensis but promoted growth in C. lanceolata when no N was added. However, N addition decreased biomass accumulation in both species in the mixed plantation and had a negative effect on the root growth of C. lanceolata due to intensified competition. Addition of N increased the relative importance of root predatory competition in P. chekiangensis, and increased the allelopathic competitive advantage in C. lanceolata. This suggests that N addition causes a shift in the root competitive strategy from tolerance to competition. Overall, these findings highlight the significant impact that the addition of N can have on plant interactions in mixed plantations. Our results provide implications for the mechanisms of root competition in response to increasing atmospheric N deposition in mixed plantations., (© 2024 Scandinavian Plant Physiology Society.)

Human health is greatly threatened by bacterial infection, which raises the risk of serious illness and death in humans. For early screening and accurate treatment of bacterial infection, there is a strong desire to undertake ultrasensitive detection and effective killing of pathogenic bacteria. Herein, a novel surface-enhanced Raman scattering (SERS) biosensor based on sandwich structure consisting of capture probes/bacteria/SERS tags was established for specific identification, capture and photothermal killing of Escherichia coli (E. coli). Finite-difference time-domain (FDTD) technique was used to simulate the electromagnetic field distribution of capture probes, SERS tags and sandwich-type SERS substrate, and a possible SERS enhancement mechanism based on sandwich structure was presented and discussed. Sandwich-type SERS biosensor successfully achieved distinctive identification and magnetic beneficiation of E. coli. In addition, a single SERS substrate, including capture probes and SERS tags, could also achieve outstanding photothermal effects as a consequence of localized surface plasmon resonance (LSPR) effect. Intriguingly, sandwich-type SERS biosensor demonstrated a higher photothermal conversion efficiency (50.03 %) than the single substrate, which might be attributed to the formation of target bacterial clusters. The superior biocompatibility and the low toxicity of the sandwich-type biosensor were confirmed. Our approach offers a fresh method for constructing sandwich-type biosensor with multiple SERS hotspots based on extremely effective hybrid plasmonic nanoparticles, and has a wide range of potential applications in the recognition and treatment of bacteria., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Anaplastic lymphoma kinase (ALK) rearrangement is a well-known driver oncogene detected in approximately 5% of non-small cell lung cancer. However, ALK rearrangement is much less frequent in other solid tumors outside the lungs, such as colorectal cancer (CRC); thus, the optimal management of CRC with ALK rearrangements has yet to be established. In this report, we describe 2 cases of ALK-positive CRC, both of which benefited from ALK tyrosine kinase inhibitor (ALK-TKI) therapy. Case 1 was a postoperative patient with poorly differentiated colon adenocarcinoma, who was diagnosed with metastatic relapse shortly after surgery. Both fluorouracil, leucovorin, and oxaliplatin (FOLFOX) and bevacizumab combined with 5-fluorouracil, l-leucovorin, and irinotecan (FOLFIRI) proved ineffective against the disease. The patient was then treated with ensartinib, as the CAD-ALK fusion gene was detected by genomic analysis. The patient was initially treated with ensartinib monotherapy for 9 months, then with ensartinib combined with local radiotherapy and fruquintinib for another 4 months for isolated hilar hepatic lymph node metastasis. The patient experienced disease progression with an acquired ALK G1202R resistance mutation that responded well to lorlatinib. Case 2 involved a 72-year-old man with advanced colon cancer (pT4bN2aM1b, stage IV) harboring an EML4-ALK fusion. The patient underwent resection of the right colon tumor due to intestinal obstruction, but the disease continued to progress after 12 courses of FOLFIRI and bevacizumab chemotherapy. However, the patient responded remarkably well to alectinib. Our report emphasizes the importance of gene detection in the treatment of malignant tumors, and the significance of ALK mutations in CRC., (© The Author(s) 2024. Published by Oxford University Press.)

Type 2 diabetes (T2D) is a chronic condition that can lead to significant harm, such as heart disease, kidney disease, nerve damage, and blindness. Although T2D-related genes have been identified through Genome-wide association studies (GWAS) and various computational methods, the biological mechanism of T2D at the cell type level remains unclear. Exploring cell type-specific genes related to T2D is essential to understand the cellular mechanisms underlying the disease. To address this issue, we introduce DiGCellNet (predicting Disease Genes with Cell type specificity based on biological Networks), a model that integrates graph convolutional network (GCN) and multi-task learning (MTL) to predict T2D-associated cell type-specific genes based on the biological network. Our work represents the first attempt to predict cell type-specific disease genes using GCN and MTL. We evaluate our approach by predicting genes specific to four cell types and demonstrate that the proposed DiGCellNet outperforms other models that combine node embeddings with traditional machine learning algorithms. Moreover, DiGCellNet successfully identifies CALM1 as a gene specific to beta cell type in T2D cases, and this association is confirmed using an independent dataset. The code is available at https://github.com/23AIBox/23AIBox-DiGCellNet., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest regarding the publication of this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Multifunctional nanoparticles are of significant importance for synergistic multimodal antitumor activity. Herein, zinc oxide (ZnO) was used as pH-sensitive nanoparticles for loading the chemotherapy agent doxorubicin (DOX) and the photosensitizer agent indocyanine green (ICG), and biocompatible low-molecular-weight heparin (LMHP) was used as the gatekeepers for synergistic photothermal therapy/photodynamic therapy/chemotherapy/immunotherapy. ZnO was decomposed into cytotoxic Zn 2+ ions, leading to a tumor-specific release of ICG and DOX. ZnO simultaneously produced oxygen (O 2 ) and reactive oxygen species (ROS) for photodynamic therapy (PDT). The released ICG under laser irradiation produced ROS for PDT and raised the tumor temperature for photothermal therapy (PTT). The released DOX directly caused tumor cell death for chemotherapy. Both DOX and ICG also induced immunogenic cell death (ICD) for immunotherapy. The in vivo and in vitro results presented a superior inhibition of tumor progression, metastasis and recurrence. Therefore, this study could provide an efficient approach for designing multifunctional nanoparticles for synergistic multimodal antitumor therapy.

Physically unclonable function (PUF) methods have high security, but their wide application is limited by complex encoding, large database, advanced external characterization equipment, and complicated comparative authentication. Therefore, we creatively propose the physically unclonable holographic encryption and anticounterfeiting based on the light propagation of complex medium and fluorescent labels. As far as we know, this is the first holographic encryption and anticounterfeiting method with a fluorescence physically unclonable property. The proposed method reduces the above requirements of traditional PUF methods and significantly reduces the cost. The angle-multiplexed PUF fluorescent label is the physical secret key. The information is encrypted as computer-generated holograms (CGH). Many physical parameters in the system are used as the parameter secret keys. The Diffie-Hellman key exchange algorithm is improved to transfer parameter secret keys. A variety of complex medium hologram generation methods are proposed and compared. The effectiveness, security, and robustness of the method are studied and analyzed. Finally, a graphical user interface (GUI) is designed for the convenience of users. The advantages of this method include lower PUF encoding complexity, effective reduction of the database size, lower requirements for characterization equipment, and direct use of decrypted information without complicated comparative authentication to reduce misjudgment. It is believed that the method proposed in this paper will pave the way for the popularization and application of PUF-based anticounterfeiting and encryption methods.

Background: The knee joint anatomical structure is susceptible to external forces, which can lead to functional break down, profoundly affecting the quality of life and daily functioning of individuals., Objective: To investigate the effects of continuous nursing intervention on walking function, quality of life, and treatment satisfaction in patients undergoing unicondylar knee replacement., Methods: This prospective study included 90 patients who underwent unicondylar knee arthroplasty due to unicondylar osteoarthritis. Participants were divided into two groups based on their nursing methods: the control group (n= 45) and the observation group (n= 45)., Results: Three months post-intervention, the observation group demonstrated significant improvements in knee joint range of motion, Hospital for Special Surgery Knee Score score, and Lysholm knee joint score compared to the control group (P< 0.05). The observation group also had a shorter completion time for the Timed Up and Go test and significantly higher SF-36 scores (P< 0.05 for both). Additionally, Knee Injury and Osteoarthritis Outcome Score scores in the observation group were significantly higher after three months of intervention (P< 0.05). And the observation group reported higher satisfaction rates and lower dissatisfaction rates compared to the control group (P< 0.05)., Conclusion: Early postoperative rehabilitation guidance, regular reviews, and rehabilitation exercise guidance result in better rehabilitation outcomes, enhanced knee joint function, improved walking ability, and overall quality of life for patients undergoing unicondylar knee replacement.

The transcription factor (TF)-mediated regulatory network controlling lincomycin production in Streptomyces lincolnensis is yet to be fully elucidated despite several types of associated TFs having been reported. SLCG&#95;2919, a tetracycline repressor (TetR)-type regulator, was the first TF to be characterized outside the lincomycin biosynthetic cluster to directly suppress the lincomycin biosynthesis in S. lincolnensis. In this study, improved genomic systematic evolution of ligands by exponential enrichment (gSELEX), an in vitro technique, was adopted to capture additional SLCG&#95;2919-targeted sequences harboring the promoter regions of SLCG&#95;6675, SLCG&#95;4123-4124, SLCG&#95;6579, and SLCG&#95;0139-0140. The four DNA fragments were confirmed by electrophoretic mobility shift assays (EMSAs). Reverse-transcription quantitative polymerase chain reaction (RT-qPCR) showed that the corresponding target genes SLCG&#95;6675 (anthranilate synthase), SLCG&#95;0139 (LysR family transcriptional regulator), SLCG&#95;0140 (beta-lactamase), SLCG&#95;6579 (cytochrome P450), SLCG&#95;4123 (bifunctional DNA primase/polymerase), and SLCG&#95;4124 (magnesium or magnesium-dependent protein phosphatase) in ΔSLCGL&#95;2919 were differentially increased by 3.3-, 4.2-, 3.2-, 2.5-, 4.6-, and 2.2-fold relative to those in the parental strain S. lincolnensis LCGL. Furthermore, the individual inactivation of these target genes in LCGL reduced the lincomycin yield to varying degrees. This investigation expands on the known DNA targets of SLCG&#95;2919 to control lincomycin production and lays the foundation for improving industrial lincomycin yields via genetic engineering of this regulatory network., (© 2023 Wiley-VCH GmbH.)

Nowadays, people give more importance and pay closer attention to the condition of their eyelids and lid margins. This increased recognition of eyelid hygiene is due to the growing awareness that improper eyelid cleaning might lead to various ocular surface diseases such as blepharitis and meibomian gland dysfunction. These ocular surface diseases can greatly affect people's quality of life. This article reviews the latest procedures for proper eyelid cleaning, including indications, methods, tools, detergents, and clinical applications, to maintain a healthy ocular surface and assist in the treatment of dry eye and blepharitis., (Copyright © 2023 Copyright: © 2023 Indian Journal of Ophthalmology.)

High-capacity optical data storage and information encryption by using glass substrates are fascinating due to merits of expanding the functionality and applicability of the optoelectronic field. However, the development of glass substrate-based multi-dimensional information encryption methods has remained a challenge because of the high hardness, brittleness and melting temperature of glasses. Herein, inspired by the unique natural structure of plant leaves, multicolor micro-texture-based physical unclonable functions (PUFs) fluorescence glass labels (MTPLs) are exploited by using ultraviolet photocurable silica nanocomposites and soft replication method. It is the first time that simultaneous rare-earth ion (RE 3+ ) space-selective doping and bionic micro-texture replication onto transparent glass have been realized, in which the doping position and fluorescence color of RE 3+ and height information of unclonable micro-texture can be selectively equipped for multilevel information encryption. The prepared micro-scale MTPLs are endowed with tunable multilevel authentication models, including macro-scale multicolor fluorescent 2D patterns, micro-scale pattern, color 3D information and intelligence authentication. A high-performance anti-counterfeiting platform with interactive authentication is also established based on the high robustness and security of MTPLs. Such unclonable bionic MTPLs based on RE 3+ space-selective doping and micro-texture duplication provide an effective and potentially universal approach for multilevel encryption and intelligent authentication., (© 2023 Wiley-VCH GmbH.)

Identifying the binding affinity between a drug and its target is essential in drug discovery and repurposing. Numerous computational approaches have been proposed for understanding these interactions. However, most existing methods only utilize either the molecular structure information of drugs and targets or the interaction information of drug-target bipartite networks. They may fail to combine the molecule-scale and network-scale features to obtain high-quality representations. In this study, we propose CSCo-DTA, a novel cross-scale graph contrastive learning approach for drug-target binding affinity prediction. The proposed model combines features learned from the molecular scale and the network scale to capture information from both local and global perspectives. We conducted experiments on two benchmark datasets, and the proposed model outperformed existing state-of-art methods. The ablation experiment demonstrated the significance and efficacy of multi-scale features and cross-scale contrastive learning modules in improving the prediction performance. Moreover, we applied the CSCo-DTA to predict the novel potential targets for Erlotinib and validated the predicted targets with the molecular docking analysis., (© The Author(s) 2024. Published by Oxford University Press.)

Aim: To investigate how nurses' psychological resilience affects their work engagement and the resulting pathways, namely, the intermediary effect of career identity and quality of work life., Background: Psychological resilience is the ability to adapt to new circumstances and overcome difficulties. Work engagement is a positive, perfect emotional and cognitive state in the work process, which has a positive effect on nurses' physical and mental health and career development. The importance of psychological resilience in nursing is growing in popularity. However, few studies have explored the relationship between psychological resilience and nurses' work engagement., Design: This is a cross-sectional study., Methods: From March to April 2023, 356 nurses in the First Affiliated Hospital of Jinzhou Medical University in China received valid questionnaires. The study was surveyed using the Connor-Davidson, Resilience Scale, the Nursing Career Identity Scale, the Work-Related Quality of Life Scale, and the 15-item Utrecht Work Engagement Scale. Process version 3.5 plug-in SPSS 25 was used to test the mediating effect., Results: (1) Psychological resilience was significantly and positively correlated with career identity, quality of work life, and work engagement ( r = 0.702-0.803, p < 0.001). (2) Career identity and quality of work life partially mediated the relationship between psychological resilience and work engagement, with effect sizes of 0.2382 and 0.0958, respectively. (3) There was a chain mediation model between psychological resilience and work engagement that had a value of 0.1219., Conclusion: Career identity and quality of work life played a chain-mediating role between psychological resilience and work engagement. Thus, in order to enhance the work engagement of clinical nurses, it is necessary for nursing managers to take measures to enhance not only psychological resilience but also their career identity and the quality of work life., 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 © 2023 Meng, Zhang, Zan and Wang.)

CDK4/6 inhibitors (CDK4/6i) plus endocrine therapy are now standard first-line therapy for advanced HR + /HER2 - breast cancer, but developing resistance is just a matter of time in these patients. Here, we report that a cyclin E1-interacting lncRNA (EILA) is up-regulated in CDK4/6i-resistant breast cancer cells and contributes to CDK4/6i resistance by stabilizing cyclin E1 protein. EILA overexpression correlates with accelerated cell cycle progression and poor prognosis in breast cancer. Silencing EILA reduces cyclin E1 protein and restores CDK4/6i sensitivity both in vitro and in vivo. Mechanistically, hairpin A of EILA binds to the carboxyl terminus of cyclin E1 protein and hinders its binding to FBXW7, thereby blocking its ubiquitination and degradation. EILA is transcriptionally regulated by CTCF/CDK8/TFII-I complexes and can be inhibited by CDK8 inhibitors. This study unveils the role of EILA in regulating cyclin E1 stability and CDK4/6i resistance, which may serve as a biomarker to predict therapy response and a potential therapeutic target to overcome resistance.

Objective: To identify the risk factors related to lifestyle behaviors that affect the incidence of lung cancer, to build a lung cancer risk prediction model to identify, in the population, individuals who are at high risk, and to facilitate the early detection of lung cancer., Methods: The data used in the study were obtained from the UK Biobank, a database that contains information collected from 502 389 participants between March 2006 and October 2010. Based on domestic and international guidelines for lung cancer screening and high-quality research literature on lung cancer risk factors, high-risk population identification criteria were determined. Univariate Cox regression was performed to screen for risk factors of lung cancer and a multifactor lung cancer risk prediction model was constructed using Cox proportional hazards regression. Based on the comparison of Akaike information criterion and Schoenfeld residual test results, the optimal fitted model assuming proportional hazards was selected. The multiple factor Cox proportional hazards regression was performed to consider the survival time and the population was randomly divided into a training set and a validation set by a ratio of 7:3. The model was built using the training set and the performance of the model was internally validated using the validation set. The area under the receiver operating characteristic (ROC) curve ( AUC ) was used to evaluate the efficacy of the model. The population was categorized into low-risk, moderate-risk, and high-risk groups based on the probability of occurrence of 0% to <25%, 25% to <75%, and 75% to 100%. The respective proportions of affected individuals in each risk group were calculated., Results: The study eventually covered 453 558 individuals, and out of the cumulative follow-up of 5 505 402 person-years, a total of 2 330 cases of lung cancer were diagnosed. Cox proportional hazards regression was performed to identify 10 independent variables as predictors of lung cancer, including age, body mass index (BMI), education, income, physical activity, smoking status, alcohol consumption frequency, fresh fruit intake, family history of cancer, and tobacco exposure, and a model was established accordingly. Internal validation results showed that 8 independent variables (all the 10 independent variables screened out except for BMI and fresh fruit intake) were significant influencing factors of lung cancer ( P <0.05). The AUC of the training set for predicting lung cancer occurrence at one year, five years, and ten years were 0.825, 0.785, and 0.777, respectively. The AUC of the validation set for predicting lung cancer occurrence at one year, five years, and ten years were 0.857, 0.782, and 0.765, respectively. 68.38% of the individuals who might develop lung cancer in the future could be identified by screening the high-risk population., Conclusion: We established, in this study, a model for predicting lung cancer risks associated with lifestyle behaviors of a large population. Showing good performance in discriminatory ability, the model can be used as a tool for developing standardized screening strategies for lung cancer., (Copyright© by Editorial Board of Journal of Sichuan University (Medical Sciences).)

Wound repair is a complex problem for both clinical practitioners and scientific investigators. Conventional approaches to wound repair have been associated with several limitations, including prolonged treatment duration, high treatment expenses, and significant economic and psychological strain on patients. Consequently, there is a pressing demand for more efficacious and secure treatment modalities to enhance the existing treatment landscapes. In the field of wound repair, cell-free therapy, particularly the use of mesenchymal stem cell-derived exosomes (MSC-Exos), has made notable advancements in recent years. Exosomes, which are small lipid bilayer vesicles discharged by MSCs, harbor bioactive constituents such as proteins, lipids, microRNA (miRNA), and messenger RNA (mRNA). These constituents facilitate material transfer and information exchange between the cells, thereby regulating their biological functions. This article presents a comprehensive survey of the function and mechanisms of MSC-Exos in the context of wound healing, emphasizing their beneficial impact on each phase of the process, including the regulation of the immune response, inhibition of inflammation, promotion of angiogenesis, advancement of cell proliferation and migration, and reduction of scar formation., 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 © 2023 Qin, He, Wang, Wang, Yang and Chen.)

Objectives: To evaluate the compliance of postoperative gastric cancer patients with oral nutritional calcium supplementation and explore its influencing factors, in order to provide a reference for formulating relevant nursing interventions., Methods: A total of 269 postoperative patients with gastric cancer admitted to the third department of surgery of the Fourth Hospital of Hebei Medical University from February to July 2020 were selected retrospectively through convenient sampling. A general information questionnaire and the Chinese version of the modified medication adherence eight-item scale were used to conduct a cross-sectional survey, in order to evaluate the compliance of postoperative gastric cancer patients with oral nutritional supplementation., Results: A total of 269 questionnaires were distributed in this study, and 228 valid questionnaires were finally recovered. The compliance score for oral nutritional calcium supplements in postoperative patients with gastric cancer was (6.43±0.21). The results of multiple linear regression analysis showed that the patients' education level, family monthly average income, postoperative time, medication belief and social support were factors influencing postoperative compliance with oral nutritional supplementation (P<0.05)., Conclusions: The compliance of postoperative gastric cancer patients with oral nutritional calcium supplements is at a medium to low level. Patients' education level, family monthly average income, postoperative time, medication belief, and social support are the main influencing factors. It is necessary to formulate and implement relevant interventions to improve compliance., Competing Interests: None., (AJTR Copyright © 2023.)

The randomized, double-blinded, multi-center, phase III GEMSTONE-302 ( NCT03789604 ) study evaluated the efficacy and safety of sugemalimab versus placebo in combination with chemotherapy as first-line treatment for metastatic non-small-cell lung cancer (NSCLC). In this study, 479 treatment-naive patients with stage IV squamous or non-squamous NSCLC without known EGFR sensitizing mutations, ALK, ROS1 or RET fusions were randomized (2:1) to receive 1,200 mg of sugemalimab (n = 320) or placebo (n = 159) every 3 weeks in combination with platinum-based chemotherapy for up to four cycles, followed by maintenance therapy with sugemalimab or placebo for squamous NSCLC and sugemalimab or placebo plus pemetrexed for non-squamous NSCLC. Placebo-treated patients could cross over to receive sugemalimab monotherapy on disease progression. The primary endpoint was investigator-assessed progression-free survival (PFS) and the secondary endpoints included overall survival (OS) and objective response rate. Sugemalimab plus chemotherapy has demonstrated significant PFS prolongation in the primary analysis as reported previously. As of 22 November 2021, the prespecified interim OS analysis showed significant improvement with the addition of sugemalimab to chemotherapy (median OS = 25.4 versus 16.9 months; hazard ratio = 0.65; 95% confidence interval = 0.50-0.84; P = 0.0008). Sugemalimab plus chemotherapy provided superior PFS and OS compared to placebo plus chemotherapy, supporting the use of sugemalimab as a first-line treatment option for metastatic NSCLC., (© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Background: Hyperglycemia is a characteristic feature of diabetes that often results in neuropsychological complications such as depression. Diabetic individuals are more vulnerable to experience depression compared to the normal population. Thus, novel treatment approaches are required to reduce depressive symptoms among diabetic individuals. Traditional Chinese medicines (TCMs) such as Shengmai San (SMS) and Radix puerariae (R) are usually widely used to treat ailments such as neurological complications since ancient time., Methods: In this study, SMS was combined with R to prepare an R-SMS formulation and screened for their antidepressant activity in diabetic rats. The antidepressant potential of the prepared combination was evaluated behaviorally using open field test, novelty-induced hypophagia, and forced swim test in diabetic rats with biochemical and protein expression (PI3K, BDNF [brain-derived neurotrophic factor], and SYN [presynaptic vesicle protein]) analysis., Results: Diabetic rats (streptozotocin, 45 mg/kg) showed elevated fasting blood glucose (FBG) >12 mM with depressive symptoms throughout the study. Treatment with R-SMS (0.5, 1.5, and 4.5 g/kg) significantly reverted depressive symptoms in diabetic rats as evinced by significantly (p < 0.05) reduced immobility time with an increased tendency to eat food in a novel environment. Treatment with R-SMS also significantly increased the protein expression of PI3K, BDNF, and SYN protein, which play a crucial role in depression., Conclusion: This study showed that R-SMS formulation antagonized depressive symptoms in diabetic rats; thus, this formulation might be studied further to develop as an antidepressant., (© 2023 The Authors. Animal Models and Experimental Medicine published by John Wiley & Sons Australia, Ltd on behalf of The Chinese Association for Laboratory Animal Sciences.)

Two novel arsenotungstate species, [As 4 W 48 O 168 ] 36- ( 1a ) and [As 2 W 21 O 77 (H 2 O) 3 ] 22- ( 2a ), have been successfully isolated under a one-pot synthetic method. 1a is the second largest arsenotungstate cluster and is constructed from four {AsW 12 } clusters combined together. 2a can be described as lacunary sites of {As 2 W 19 } filled by {W 2 O 8 } units. Compounds 1 and 2 exhibit proton conductivity properties, and the conductivity value of 1 is 5.0 × 10 -3 S cm -1 at 98% relative humidity and 75 °C. This work proves that the lattice water molecules and polyoxoanions can participate in the formation of a hydrogen bond, acting as effective pathway for intermolecular proton conduction.

Abnormal or excessive accumulation of adipose tissue leads to a condition called obesity. Long-term positive energy balance arises when energy intake surpasses energy expenditure, which increases the risk of metabolic and other chronic diseases, such as atherosclerosis. In industrialized countries, the prevalence of coronary heart disease is positively correlated with the human development index. Atherosclerotic cardiovascular disease (ACD) is among the primary causes of death on a global scale. There is evidence to support the notion that individuals from varied socioeconomic origins may experience varying mortality effects as a result of high blood pressure, high blood sugar, raised cholesterol levels, and high body mass index (BMI). However, it is believed that changes in the concentration of trace elements in the human body are the main contributors to the development of some diseases and the transition from a healthy to a diseased state. Metal trace elements, non-metal trace elements, and the sampling site will be examined to determine whether trace elements can aid in the diagnosis of atherosclerosis. This article will discuss whether trace elements, discussed under three sections of metal trace elements, non-metal trace elements, and the sampling site, can participate in the diagnosis of atherosclerosis., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2023 The Author(s). Published by IMR Press.)

Wound healing is a complex biological process involving multiple cell types with their critical functions. The diabetic wounds show delayed wound healing, while the anagen wounds display accelerated wound closure. However, the mechanisms underlying the effect of cellular heterogeneity on wound healing are still unclear. CD34 + cells exhibit high heterogeneity in wound skins and improve wound healing. Herein, we investigated the phenotypic and functional heterogeneity of CD34 + cells in normal, anagen, and diabetic wounds. We obtained CD34 lineage tracing mice, constructed distinct wound models, collected CD34 + cells from wound edges, and performed single-cell RNA sequencing. We identified 10 cell clusters and 6 cell types of CD34 + cells, including endothelial cells, fibroblasts, keratinocytes, neutrophils, macrophages, and T cells. 5 subclusters were defined as fibroblasts. The CD34 + fibroblasts C2 highly expressed papillary fibroblastic markers took up the largest proportion in anagen wounds and were associated with inflammation and extracellular matrix. Increased CD34 + endothelial cells, fibroblasts C4, and neutrophils as well as decreased fibroblasts C1 were discovered in diabetic wounds. We also filtered out differentially expressed genes (DEGs) of each cell cluster in anagen wounds and diabetic wounds. Functional enrichment analysis was performed on these DEGs to figure out the enriched pathways and items for each cell cluster. Pseudotime analysis of CD34 + fibroblasts was next carried out indicating fibroblast C4 mainly with low differentiation. Our results have important implications for understanding CD34 + cell type-specific roles in anagen and diabetic wounds, provide the possible mechanisms of wound healing from a new perspective, and uncover potential therapeutic approaches to treating wounds., 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 © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Ferroptosis is an iron-dependent cell death mode and closely linked to various cancers, including skin cutaneous melanoma (SKCM). Although attempts have been made to construct ferroptosis-related gene (FRG) signatures for predicting the prognosis of SKCM, the prognostic impact of ferroptosis-related genetic mutations in SKCM remains lacking. This study aims to develop a prediction model to explain the relationship between ferroptosis-related genetic mutations and clinical outcomes of SKCM patients and to explore the potential value of ferroptosis in SKCM treatment. Methods: FRGs which significantly correlated with the prognosis of SKCM were firstly screened based on their single-nucleotide variant (SNV) status by univariate Cox regression analysis. Subsequently, the least absolute shrinkage and selection operator (LASSO) and Cox regressions were performed to construct a new ferroptosis-related genetic mutation risk (FerrGR) model for predicting the prognosis of SKCM. We then illustrate the survival and receiver operating characteristic (ROC) curves to evaluate the predictive power of the FerrGR model. Moreover, independent prognostic factors, genomic and clinical characteristics, immunotherapy, immune infiltration, and sensitive drugs were compared between high-and low-FerrGR groups. Results: The FerrGR model was developed with a good performance on survival and ROC analysis. It was a robust independent prognostic indicator and followed a nomogram constructed to predict prognostic outcomes for SKCM patients. Besides, FerrGR combined with tumor mutational burden (TMB) or MSI (microsatellite instability) was considered as a combined biomarker for immunotherapy response. The high FerrGR group patients were associated with an inhibitory immune microenvironment. Furthermore, potential drugs target to high FerrGR samples were predicted. Conclusion: The FerrGR model is valuable to predict prognosis and immunotherapy in SKCM patients. It offers a novel therapeutic option for SKCM., 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 © 2023 He, Huang, Li, Wang, Nie, Li, Wang, Cao, Chen and Wang.)

CDK4/6 inhibitors are the standard treatment in advanced HR+/HER2- breast cancer patients. Nevertheless, the resistance to CDK4/6 inhibitors is inevitable and the strategies to overcome resistance are of great interest. Here, we show that the palbociclib-resistant breast cancer cells expressed significantly higher levels of Cyclin D1 and CDK4 proteins because of upregulated protein synthesis. Silencing Cyclin D1 or CDK4 led to cell cycle arrest while silencing Cyclin E1 or CDK2 restored the sensitivity to palbociclib. Furthermore, PI3K/mTOR pathway was hyper-activated in palbociclib-resistant cells, leading to more phosphorylated 4E-BP1 and higher levels of Cyclin D1 and CDK4 translation. Targeting PI3K/mTOR pathway with a specific PI3Kα inhibitor (BYL719) or an mTOR inhibitor (everolimus) reduced the protein levels of Cyclin D1 and CDK4, and restored the sensitivity to palbociclib. The tumor samples expressed significantly higher levels of Cyclin D1, CDK4, p-AKT and p-4E-BP1 after progression on palbociclib treatment. In conclusion, our findings suggest that overexpressed Cyclin D1 and CDK4 proteins lead to the resistance to CDK4/6 inhibitor and PI3K/mTOR inhibitors are able to restore the sensitivity to CDK4/6 inhibitors, which provides the biomarker and rationale for the combinational use of CDK4/6 inhibitors and PI3K/mTOR inhibitors after CDK4/6 inhibitor resistance in breast cancer., (© 2022. Science China Press and Springer-Verlag GmbH Germany, part of Springer Nature.)

Motivation: Drug-food interactions (DFIs) occur when some constituents of food affect the bioaccessibility or efficacy of the drug by involving in drug pharmacodynamic and/or pharmacokinetic processes. Many computational methods have achieved remarkable results in link prediction tasks between biological entities, which show the potential of computational methods in discovering novel DFIs. However, there are few computational approaches that pay attention to DFI identification. This is mainly due to the lack of DFI data. In addition, food is generally made up of a variety of chemical substances. The complexity of food makes it difficult to generate accurate feature representations for food. Therefore, it is urgent to develop effective computational approaches for learning the food feature representation and predicting DFIs., Results: In this article, we first collect DFI data from DrugBank and PubMed, respectively, to construct two datasets, named DrugBank-DFI and PubMed-DFI. Based on these two datasets, two DFI networks are constructed. Then, we propose a novel end-to-end graph embedding-based method named DFinder to identify DFIs. DFinder combines node attribute features and topological structure features to learn the representations of drugs and food constituents. In topology space, we adopt a simplified graph convolution network-based method to learn the topological structure features. In feature space, we use a deep neural network to extract attribute features from the original node attributes. The evaluation results indicate that DFinder performs better than other baseline methods., Availability and Implementation: The source code is available at https://github.com/23AIBox/23AIBox-DFinder., Supplementary Information: Supplementary data are available at Bioinformatics online., (© The Author(s) 2022. Published by Oxford University Press.)

In metazoans the endoplasmic reticulum (ER) undergoes extensive remodeling during the cell cycle. The endosomal sorting complexes required for transport (ESCRT) protein CHMP7 coordinates ESCRT-III dependent nuclear envelope reformation during mitotic exit. However, potential roles of ER-associated CHMP7 at non-mitotic stages remain unclear. Here we discovered a new role of CHMP7 in mediating three-way ER and ER-mitochondrial membrane contact sites (MCSs). We showed that CHMP7 localizes to multiple cellular membranes including the ER, mitochondrial-associated membranes (MAMs) and the outer mitochondrial membrane (OMM) via its N-terminal membrane-binding domain. CHMP7 undergoes dynamic assembly at three-way ER junctions and ER-mitochondrial MCSs through hydrophobic interactions among α helix-1 and α helix-2 of the C-terminal CHMP-like domain, which was required for tethering different organelles in vivo. Furthermore, CHMP7 mediates the formation of three-way ER junctions in parallel with Atlastins (ATLs). Importantly, CHMP7 also regulates ER-mitochondrial interactions and its depletion affects mitochondrial division independently of ESCRT complex. Taken together, our results suggest a direct role of CHMP7 in the formation of the ER contacts in interphase., (© 2022. The Author(s), under exclusive licence to ADMC Associazione Differenziamento e Morte Cellulare.)

To discover new potential pesticide candidates, recently, structural modification of natural bioactive products has received much attention. In this work, a series of new piperine-type ester derivatives were regio- and stereoselectively synthesized based on a natural alkaloid piperine isolated from Piper nigrum . Their structures were characterized by IR, mp, 1 H NMR ( 13 C NMR), and high-resolution mass spectrometry (HRMS). Against Tetranychus cinnabarinus Boisduval (Acari: Tetranychidae), compounds 4e , 4f , 4u , and 4v displayed the most significant acaricidal activity with LC 50 values of 0.155, 0.117, 0.177, and 0.164 mg/mL, respectively. Particularly, compound 4f showed >120-fold higher acaricidal activity than piperine (LC 50 : 14.198 mg/mL). Notably, the acaricidal activity of 4f was equivalent to that of the commercial acaricide spirodiclofen (LC 50 : 0.115 mg/mL). Additionally, against Eriosoma lanigerum Hausmann (Hemiptera: Aphididae), compounds 4w and 4b' showed 1.8-fold aphicidal activity of piperine. Furthermore, via the scanning electron microscope (SEM) imaging method, the obvious destruction of the construction of the cuticle layer of 4f- treated T. cinnabarinus was observed. Compound 4f could be further studied as a lead acaricidal agent.

The cost-effective biomass-derived carbon with high electrochemical performance is highly desirable for the sustainable development of advanced energy storage devices. In this manuscript, Typha angustifolia with a large output and loose porous characteristics was selected as the raw material of biomass. In the synthesis process, KHCO 3 , which is more environmentally friendly, is used as a pore-forming agent, and the low-cost, easy-to-clean fluxing agent NaCl is used to assist the pore-forming process. Based on the analysis of thermogravimetric-infrared test results, the calcination procedure of porous carbon was designed reasonably, so that the functions of the pore-forming agent and fluxing agent could be fully exerted. Its high electrochemical performance is attributed to combined contributions from high surface area and hierarchical porous structures. The as-prepared carbon also showed an outstanding capacitance of 317.2 F/g at a current density of 1 A g -1 and a high capacitance retention of over 97.83% after 5000 cycles at a current density of 4 A g -1 . This work provides an outstanding renewable candidate and a feasible route design strategy for the fabrication of high-performance electrodes., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

Glycine transporter 1 (GlyT1) is responsible for the reuptake of glycine, which regulates glutamate signaling as a co-agonist with N-methyl-D-aspartic acid (NMDA) receptors in the excitatory synapse and has been proposed to be a potential target in the development of therapies for a broad range of disorders of the central nervous system. Despite significant progress in characterizing structure and transport mechanism of the transporter, the regulation of transport function through oligomerization remains to be understood. In the present work, association of two forms of GlyT1 into dimers and higher order oligomers was detected by coimmunoprecipitation. To investigate functional properties of dimers of a GlyT1 cysteine mutant L288C, we performed oxidative cross-linking of the positioned cysteine residues in extracellular loop 3 (EL3) near the extracellular end of TM6. By analyzing the effect of copper phenanthroline (CuP)-induced dimerization on transport function, cross-linking of L288C was found to inhibit transport activity. In addition, an intramolecular ion pair Lys286-Glu289 was revealed to be critical for stabilizing EL3 in a conformation that modulates CuP-induced dimerization and transport function of the GlyT1 L288C mutant. Furthermore, the influence of transporter conformation on GlyT1 L288C dimerization was investigated. The substrate glycine, in the presence of both Na + and Cl - , significantly reduced oxidative cross-linking, suggesting a large-scale rotation of the bundle domain during substrate transport impairs interfacial interactions between L288C protomers. The present study provides new insights into structural and functional elements regulating GlyT1 transport activity through its dimerization or oligomerization.

Triple-negative breast cancer (TNBC) is the most malignant subtype of breast cancer. In the absence of effective molecular markers for TNBC, there is an urgent clinical need for promising therapeutic target for TNBC. Histone deacetylases (HDACs), key regulators for chromatin remodeling and gene expression, have been suggested to play critical roles in cancer development. However, little is known ~the functions and implications of HDACs in TNBC treatment in the future. By analyzing the expression and prognostic significance of HDAC family members in TNBC through TCGA and METABRIC databases, HDAC7 was found to be downregulated in TNBC samples and the survival of patients with lower expression of HDAC7 was shorter. Furthermore, HDAC7 was negatively associated with NudC domain containing 1 (NudCD1) and γ-glutamyl hydrolase (GGH). Loss of NudCD1 or GGH predicted improved overall survival time (OS) of patients with TNBC. In vitro experiments showed that silencing of HDAC7 enhanced TNBC cell proliferation, while overexpression HDAC7 inhibited TNBC cell proliferation. The results of functional experiments confirmed that HDAC7 negatively modulated GGH and NudCD1 expression. Furthermore, decrease of NudCD1 or GGH inhibited cell proliferation. Notably, the HDAC7-NudCD1/GGH axis was found to be associated with NK cell infiltration. Overall, the present study revealed a novel role of HDAC7-NudCD1/GGH axis in TNBC, which might provide a promising treatment strategy for patients with TNBC., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Zhu et al.)

Background: Keloid is characterized by excessive collagen accumulation and fibroblast growth, which are fibroproliferative disorders of injured skin, causing functional limitations. Studies have shown that adipose-derived stem cells (ADSCs) inhibit the bioactivity and fibrosis of keloid fibroblasts. However, the molecular mechanism of this effect of ADSCs on keloid formation has not been fully elucidated., Methods: This in vitro study used fibroblasts obtained from keloids. A consensus gene co-expression network was constructed to focus on identifying consensus gene co-expression modules associated with keloid fibroblasts. Differentially expressed genes (DEGs) were identified between keloid fibroblasts and normal dermal fibroblasts. A functional enrichment analysis was also performed with the DAVID database. A weighted gene co-expression network analysis (WGCNA) was used to screen keloid-related modules using the "WGCNA" R package, followed by hub gene selection in modules from the Protein-protein interaction network through the STRING database. Keloid fibroblasts and ADSCs were extracted and cultured. Proliferation and apoptosis were examined using a 5-ethynyl-2-deoxyuridine (Edu) kit and flow cytometry., Results: We identified 302 DEGs overlapping with a consensus analysis of clusters and a differential expression analysis between keloid fibroblasts and normal dermal fibroblasts. Most of these were involved in collagen binding, extracellular matrix organization, and the PI3K-Akt signaling pathway. WGCNA analysis selected a keloid-associated brown module. ITGA2 was identified as a novel marker in hub genes from the PPI network based on the degree and function of collagen modulation. Furthermore, the proliferation ability of keloid fibroblasts cultured in ADSC medium was inhibited while apoptosis was dramatically increased. Overexpression of ITGA2 reversed the decrease in ADSC-induced apoptosis and increased ADSC-reduced proliferation., Conclusion: Our study demonstrated that activation of ITGA2 plays a crucial role in ADSC-induced keloid fibroblast apoptosis and anti-proliferation effects. These results also improved our understanding of the molecular mechanism of the pathogenesis of keloid in response to ADSCs and may contribute to the further development of keloid therapy.

Various metal oxide nanomaterials have been widely used as carriers to prepare pH-sensitive nanomedicines to respond to the acidic tumor microenvironment promoting antitumor efficiency. Herein, we used zinc oxide nanoparticles (ZnO NPs) as metal oxide nanomaterial coated with low-molecular-weight heparin (LMHP) and doxorubicin (DOX) complex (LMHP-DOX) to prepare ZnO-LD NPs for controllable pH-triggered DOX release on the targeted site. Our results indicated that the released DOX from ZnO-LD NPs was pH-sensitive. The oxygen produced by ZnO-LD NPs in H 2 O 2 solution was observed in in vitro experiment. The ZnO-LD NPs entered into both PC-3M and 4T1 tumor cells via clathrin-mediated endocytosis and micropinocytosis pathway. The intracellular reactive oxygen species (ROS) generated by ZnO-LD NPs could significantly increase the caspase 3/7 level, leading to tumor cell apoptosis. The in vitro and in vivo antitumor activity was confirmed in PC-3M and 4T1 cell lines or tumor-bearing mice models. The in vivo and in vitro tumor images via second-order nonlinearity of ZnO-LD NPs indicated that ZnO-LD NPs could penetrate deep into the tumor tissues. Therefore, the ZnO-LD NPs developed in our study could provide an efficient approach for the preparation of pH-sensitive nano delivery systems suitable for tumor therapy and imaging.