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After the cancellation of COVID-19 epidemic control measures in 2023, cases of pediatric bronchiolitis caused by Mycoplasma pneumoniae (MP) have been reported successively, with some children experiencing residual bronchiolitis obliterans (BO). Currently, the diagnosis of bronchiolitis Mycoplasma pneumoniae pneumonia (MPP) primarily relies on high-resolution computed tomography (HRCT). To establish a predictive model for bronchiolitis MPP, a retrospective analysis was conducted. The patients were randomly divided into a training cohort and a validation cohort. The nomogram model was constructed in the training cohort. Finally, the differential, calibration, and clinical applicability of the prediction model were evaluated using both the training and validation cohorts. Logistic stepwise regression analysis identified age, atopy, wheezing, hypoxemia, and pleural effusion as independent predictors of bronchiolitis MPP. These factors were used to construct a nomogram model. This nomogram model serves as a useful tool for predicting the risk of bronchiolitis MPP, which may facilitate individualized early intervention., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethics approval and consent to participate: The studies involving humans were approved by the Medical Ethics Committee of Xiamen University Affiliated First Hospital (institutional review board numbers: 2023-094). The studies were conducted in accordance with local legislation and institutional requirements. Written informed consent for participation in this study was provided by the participants’ legal guardians/next of kin., (© 2024. The Author(s).)

New combinations or alternative therapies for major depressive disorder (MDD) are necessary. Intradermal acupuncture (IA) shows promise but requires further investigation regarding its efficacy, safety, and mechanisms. Conducted across 3 centers from November 2022 to January 2024, our randomized controlled trial included 120 participants with moderate to severe MDD, divided into the selective serotonin reuptake inhibitors (SSRIs), SSRIs plus sham IA (SSRIs + SIA), and SSRIs plus active IA (SSRIs + AIA) groups. Acupuncture groups received 10 sessions over 6 weeks at Shenmen (HT7), Neiguan (PC6), Sanyinjiao (SP6) and Taichong (LR3) bilaterally, followed by a 4-week follow-up. The primary outcome was changes in Hamilton Depression Rating Scale-17 (HAMD-17) scores at week 6. Furthermore, healthy controls (HCs) and MDD patients underwent magnetic resonance imaging (MRI) scans for functional connectivity (FC) analysis. After 6 weeks of treatment, the SSRIs + AIA group showed a greater reduction in HAMD-17 score than the SSRIs + SIA group (MD, -4.9 [CI, -7.6 to -2.2], P < 0.001) and SSRIs group (MD, -5.1 [CI, -7.8 to -2.3], P < 0.001). No serious adverse events occurred. SSRIs + AIA resulted in lower incidences of palpitations (vs.SSRIs + SIA: OR, 0.1% [CI, 0.0-1.0%]; vs. SSRIs: OR, 0.1% [CI, 0.0-0.7%]; P < 0.05), somnolence (vs.SSRIs + SIA: OR, 0.1% [CI, 0.0-0.9%]; vs.SSRIs: OR, 0.1% [CI, 0.0-0.7%]; P < 0.05), and nausea (vs.SSRIs + SIA: OR, 0.1% [CI, 0.0-1.0%]; vs. SSRIs: OR, 0.1% [CI, 0.0-0.9%]; P < 0.05). MDD patients showed abnormal FCs, and IA enhanced FCs between striatum and frontal&#95;inf&#95;tri, and striatum and cerebellum in the MRI study. Overall, IA as adjunctive therapy provides clinical efficacy and safety for MDD, and it may exert antidepressant effects by modulating striatal FCs., Competing Interests: Competing interests: The authors declare no competing interests. Ethics approval and consent to participate: This study complied with the declaration of Helsinki and was approved by the Medical Ethics Committee of the Third Affiliated Hospital of Zhejiang Chinese Medical University, and all participants provided written informed consent., (© 2024. The Author(s).)

This study aimed to investigate the benefits of using three-dimensional (3D)-printed hip joint fixators after intra-arterial chemotherapy (IAC) by inguinal femoral artery puncture in children with retinoblastoma. Overall, 79 cases of retinoblastoma who had undergone IAC through the femoral artery were selected and divided into an observation group of 50 cases and an intervention group of 29 cases according to the hemostasis method employed. The patients in the observation group were treated with sandbags for hemostasis, while those in the intervention group were given 3D-printed hip joint fixators to help immobilize the hips and sandbags. We used the Face, Legs, Activity, Cry and Consolability scale (FLACC), the Wong-Baker Facial Expression Pain Scale, and self-made questionnaires to evaluate demographics, clinical characteristics, pain, complications, satisfaction, and other indicators of the two groups. There were no significant differences in general data, such as age, gender, height, weight, manual compression time, diseased eye, tumor stage, platelet count, puncture times, pain distribution, and total score, between the groups. There was a positive correlation between FLACC pain and the total Wong-Baker pain score (r = 0.599, p < 0.001). During the 2 h of sandbag compression, sandbags were dislodged in the observation group as many as ten times, which was significantly higher than that in the intervention group (up to four times; p < 0.001). This was correlated with a very high score of satisfaction (92.34 ± 19.96 out of 100). The 3D-printed hip fixator is easy to operate, has a low incidence of complications, and saves time and effort. It effectively reduces the incidence of sandbags falling off after IAC in children with retinoblastoma and does not increase the patient's pain. It is a method that could improve hemostasis in young children undergoing IAC by inguinal femoral artery., Competing Interests: Competing interests The authors declare no competing interests. Consent for publication Not applicable. Ethics approval and consent to participate Our study is carried out under the ethical principles of the Declaration of Helsinki and was approved by the ethics committee of the Institutional Review Board of the Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine (approval number: SH9H-2019-T277-4).The parents of all included children provided written, informed consent for the study., (© 2024. The Author(s).)

This study investigated the effect of household air pollution on pregnant women with GDM, and assessed the modifying effect of a healthy lifestyle on this relationship. Household solid fuel exposure was defined as using solid fuels (coal, crop residue, and wood) for cooking and heating. Four individually modifiable lifestyle factors were assessed in early pregnancy: body mass index, diet, sleep, and vitamin D supplementation. Multifactorial logistic regression modeling was used to assess the relationship between household air pollution and GDM. A stratified analysis and additive interaction tested the effects of healthy lifestyle scores. After adjusting for potential confounders, we found that using solid fuels for heating was significantly associated with an increased risk of GDM (adjusted OR = 1.60, 95% CI 1.18-2.18). GDM risk showed a decreasing trend in the medium versus the high score group when compared to the low score group, with a consistent trend regardless of household fuel type used (adjusted OR = 0.39, 95% CI 0.27-0.57) (adjusted OR = 0.12, 95% CI 0.05-0.28), respectively. Importantly, when the healthy lifestyle score increased, exposure to household air pollution was no longer associated with a higher GDM risk. There was a negative additive interaction between exposure to household solid fuels exposure and a healthy lifestyle (FERI: -5.10 [-16.48, -2.04]; AP: -1.29 [-2.80, -0.39]; SI: -0.37 [-0.20, -0.67]). We determined that exposure to household air pollution may be an important GDM risk factor. In addition, A healthy lifestyle may have a protective effect on women with GDM exposed to indoor fuel air pollution., (© 2024. The Author(s).)

In the field of human action recognition, it is a long-standing challenge to characterize the video-level spatio-temporal features effectively. This is attributable in part to the inability of CNN to model long-range temporal information, especially for actions that consist of multiple staged behaviors. In this paper, a novel attention-based spatio-temporal VLAD network (AST-VLAD) with self-attention model is developed to aggregate the informative deep features across the video according to the adaptive deep feature selected. Moreover, an overall automatic approach to adaptive video sequences optimization (AVSO) is proposed through shot segmentation and dynamic weighted sampling, the AVSO increase in the proportion of action-related frames and eliminate the redundant intervals. Then, based on the optimized video, a self-attention model is introduced in AST-VLAD to modeling the intrinsic spatio-temporal relationship of deep features instead of solving the frame-level features in an average or max pooling manner. Extensive experiments are conducted on two public benchmarks-HMDB51 and UCF101 for evaluation. As compared to the existing frameworks, results show that the proposed approach performs better or as well in the accuracy of classification on both HMDB51 (73.1% ) and UCF101 (96.0%) datasets., (© 2024. The Author(s).)

The differentiation of developmental cell lineages is associated with genome-wide modifications in histone H3 methylation. However, the causal role of histone H3 methylation in transcriptional regulation and cell differentiation has been difficult to test in mammals. The experimental overexpression of histone H3 mutants carrying lysine-to-methionine (K-to-M) substitutions has emerged as an alternative tool for inhibiting the endogenous levels of histone H3 methylation at specific lysine residues. Here, we leverage the use of histone K-to-M mutants by creating Enhanced Episomal Vectors that enable the simultaneous depletion of multiple levels of histone H3 lysine 4 (H3K4) or lysine 9 (H3K9) methylation in projection neurons of the mouse cerebral cortex. Our approach also facilitates the simultaneous depletion of H3K9 and H3K27 trimethylation (H3K9me3 and H3K27me3, respectively) in cortical neurons. In addition, we report a tamoxifen-inducible Cre-FLEX system that allows the activation of mutant histones at specific developmental time points or in the adult cortex, leading to the depletion of specific histone marks. The tools presented here can be implemented in other experimental systems, such as human in vitro models, to test the combinatorial role of histone methylations in developmental fate decisions and the maintenance of cell identity., (© 2024. The Author(s).)

Bruton tyrosine kinase inhibitor (BTKi) combined with rituximab-based chemotherapy benefits diffuse large B-cell lymphoma (DLBCL) patients. However, drug resistance is the major cause of relapse and death of DLBCL. In this study, we conducted a comprehensive analysis BTKi-resistance related genes (BRRGs) and established a 10-gene (CARD16, TRIP13, PSRC1, CASP1, PLBD1, CARD6, CAPG, CACNA1A, CDH15, and NDUFA4) signature for early identifying high-risk DLBCL patients. The resistance scores based on the BRRGs signature were associated with prognosis. Furthermore, we developed a nomogram incorporating the BRRGs signature, which demonstrated excellent performance in predicting the prognosis of DLBCL patients. Notably, tumor immune microenvironment, biological pathways, and chemotherapy sensitivity were different between high- and low-resistance score groups. Additionally, we identified TRIP13 as a key gene in our model. TRIP13 was found to be overexpressed in DLBCL and BTKi-resistant DLBCL cell lines, knocking down TRIP13 suppresses cell proliferation, promotes cell apoptosis, and enhances the apoptosis effect of BTKi on DLBCL cells by regulating the Wnt/β-catenin pathway. In conclusion, our study presents a novel BRRGs signature that could serve as a promising prognostic marker in DLBCL, and TRIP13 might be a potential therapeutic target for resistant DLBCL., (© 2024. The Author(s).)

Prostate cancer bone metastasis is a predominant cause of death for prostate cancer (PCa) patients. However, the underlying mechanisms are poorly understood. Here, we report that high levels of RNF41 are associated with metastatic human prostate cancer. RNF41 silencing inhibits prostate cancer cell growth, cell migration and invasion in vitro and in vivo. Mechanistically, we identify that RNF41 induces K27- and K63-linked noncanonical polyubiquitination of MYO1C to enhance its stability and induce actin remodeling, which promotes PCa bone metastasis. RNF41 was significantly upregulated in metastatic prostate cancer tissues and positively associated with MYO1C expression. Furthermore, we show in intraarterial injected-bone metastasis xenograft model that targeting MYO1C stability by inhibition of RNF41 markedly suppressed PCa bone metastasis. Collectively, our findings identify RNF41 is an important regulator of prostate cancer cell growth and metastasis and targeting RNF41/MYO1C could be a valuable strategy to ameliorate prostate cancer progression and metastasis., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

The treatment, disposal, and resource utilization of waste mud are challenges for engineering construction. This study investigates the road performance of waste mud-solidified soil and explains how solidifying materials influence the strength and deformation characteristics of waste mud. Unconfined compressive strength tests, consolidated undrained triaxial shear tests, resonant column tests, and consolidation compression tests were conducted to evaluate the solidification effect. The test results show that with an increase in cement content from 5 to 9%, the unconfined compressive strength of the waste mud-solidified soil increased by over 100%, the curing time was extended from 3 to 28 days, and the unconfined compressive strength increased by approximately 70%. However, an increase in initial water content from 40 to 60% reduced the unconfined compressive strength by 50%. With the increase of cement content from 5 to 9%, the cohesion and friction angles increased by approximately 78% and 24%, respectively. The initial shear modulus under dynamic shear increased by approximately 38% and the shear strain corresponding to a damping ratio decay to 70% of the initial shear modulus decreased by nearly 11%. The compression coefficient decreased by approximately 55%. Scanning electron microscopy and X-ray diffraction tests showed that a higher cement content led to the formation of more hydration reaction products, especially an increase in the content of AlPO 4 , which can effectively fill the pores between soil particles, enhance the bonding between soil particles, and form a skeleton with soil particles to improve compactness. Consequently, the strength of the waste mud-solidified soil increased significantly while its compressibility decreased. This study can provide data support for dynamic characteristics of waste mud solidified soil subgrade., (© 2024. The Author(s).)

Multiple myeloma (MM) is an incurable hematological malignancy with poor survival. Accumulating evidence reveals that lactylation modification plays a vital role in tumorigenesis. However, research on lactylation-related genes (LRGs) in predicting the prognosis of MM remains limited. Differentially expressed LRGs (DELRGs) between MM and normal samples were investigated from the Gene Expression Omnibus database. Univariate Cox regression and LASSO Cox regression analysis were applied to construct gene signature associated with overall survival. The signature was validated in two external datasets. A nomogram was further constructed and evaluated. Additionally, Enrichment analysis, immune analysis, and drug chemosensitivity analysis between the two groups were investigated. qPCR and immunofluorescence staining were performed to validate the expression and localization of PFN1. CCK-8 and flow cytometry were performed to validate biological function. A total of 9 LRGs (TRIM28, PPIA, SOD1, RRP1B, IARS2, RB1, PFN1, PRCC, and FABP5) were selected to establish the prognostic signature. Kaplan-Meier survival curves showed that high-risk group patients had a remarkably worse prognosis in the training and validation cohorts. A nomogram was constructed based on LRGs signature and clinical characteristics, and showed excellent predictive power by calibration curve and C-index. Moreover, biological pathways, immunologic status, as well as sensitivity to chemotherapy drugs were different between high- and low-risk groups. Additionally, the hub gene PFN1 is highly expressed in MM, knocking down PFN1 induces cell cycle arrest, suppresses cell proliferation and promotes cell apoptosis. In conclusion, our study revealed that LRGs signature is a promising biomarker for MM that can effectively early distinguish high-risk patients and predict prognosis., (© 2024. The Author(s).)

The verified text data of wheat varieties is an important component of wheat germplasm information. To automatically obtain a structured description of the phenotypic and genetic characteristics of wheat varieties, the aim at solve the issues of fuzzy entity boundaries and overlapping relationships in unstructured wheat variety approval data, WGIE-DCWF (joint extraction model of wheat germplasm information entity relationship based on deep character and word fusion) was proposed. The encoding layer of the model deeply fused word semantic information and character information using the Transformer encoder of BERT. This allowed for the cascading fusion of contextual semantic feature information to achieve rich character vector representation and improve the recognition ability of entity features. The triple extraction layer of the model established a cascading pointer network, extracted the head entity, extracted the tail entity according to the relationship category, and decoded the output triplet. This approach improved the model's capability to extract overlapping relationships. The experimental results demonstrated that the WGIE-DCWF model performed exceptionally well on both the WGD (wheat germplasm dataset) and the public dataset DuIE. The WGIE-DCWF model not only achieved high performance on the evaluation datasets but also demonstrated good generalization. This provided valuable technical support for the construction of a wheat germplasm information knowledge base and is of great significance for wheat breeding, genetic research, cultivation management, and agricultural production., (© 2024. The Author(s).)

Immune checkpoint inhibitors targeting the programmed cell death-1 (PD-1) protein significantly improve survival in patients with advanced non-small-cell lung cancer (NSCLC), but its impact on early-stage ground-glass opacity (GGO) lesions remains unclear. This is a single-arm, phase II trial (NCT04026841) using Simon's optimal two-stage design, of which 4 doses of sintilimab (200 mg per 3 weeks) were administrated in 36 enrolled multiple primary lung cancer (MPLC) patients with persistent high-risk (Lung-RADS category 4 or had progressed within 6 months) GGOs. The primary endpoint was objective response rate (ORR). T/B/NK-cell subpopulations, TCR-seq, cytokines, exosomal RNA, and multiplexed immunohistochemistry (mIHC) were monitored and compared between responders and non-responders. Finally, two intent-to-treat (ITT) lesions (pure-GGO or GGO-predominant) showed responses (ORR: 5.6%, 2/36), and no patients had progressive disease (PD). No grade 3-5 TRAEs occurred. The total response rate considering two ITT lesions and three non-intent-to-treat (NITT) lesions (pure-solid or solid-predominant) was 13.9% (5/36). The proportion of CD8 + T cells, the ratio of CD8 + /CD4 + , and the TCR clonality value were significantly higher in the peripheral blood of responders before treatment and decreased over time. Correspondingly, the mIHC analysis showed more CD8 + T cells infiltrated in responders. Besides, responders' cytokine concentrations of EGF and CTLA-4 increased during treatment. The exosomal expression of fatty acid metabolism and oxidative phosphorylation gene signatures were down-regulated among responders. Collectively, PD-1 inhibitor showed certain activity on high-risk pulmonary GGO lesions without safety concerns. Such effects were associated with specific T-cell re-distribution, EGF/CTLA-4 cytokine compensation, and regulation of metabolism pathways., (© 2024. The Author(s).)

Electrical cables, often referred to as 'blood vessels' and 'nerves' of the industry, play a vital role in the connection of electrical devices. However, traditional cables that lack distributed filtering functions are usually the primary coupling path for electromagnetic compatibility (EMC) problems. An innovative design for a filtering cable, which incorporates insulated electrical wires coated with a specific defected conductor layer (DCL), enables it to achieve distributed filtering advantages along its axis. Microwave network analysis is employed to build the two-port network model of filtering cable, which efficiently analyzes the cascading characteristics of periodic or aperiodic filtering cables. To validate, the flexible printed circuit board (FPCB) with sawtooth dumbbell-shaped DCL and mounted by capacitors is wrapped around the stripped section of the coaxial cable to manufacture a multi-stopband filtering cable. Simulated and measured results demonstrate that the proposed filtering cable can be effectively suppressed in the stopband, which can be adjusted by changing the values of capacitors., (© 2024. The Author(s).)

Objectives: To characterize choroidal vascular changes in children with different refractive status., Methods: A study including 5864 children aged 6-9 years was performed to investigate the choroidal vascular index (CVI) in myopic, emmetropic and hyperopic eyes. Each participant had a comprehensive ocular examination with cycloplegic autorefraction performed, axial length (AL) measured and Swept Source-Optical Coherence Tomography (SS-OCT) scans acquired. Choroidal thickness (ChT) was measured by built-in software, and CVI was calculated using a previously validated self-developed algorithm., Results: The mean ChT and CVI were 275.88 ± 53.34 μm and 34.91 ± 3.83 in the macula region, and 191.96 ± 46.28 μm and 32.35 ± 4.21 in the peripapillary region. CVI was significantly lowest for myopes, followed by emmetropes and hyperopes (P < 0.001). CVI varied between different sectors separated by the Early Treatment of Diabetic Retinopathy Study (ETDRS) grid (P < 0.001). Macular CVI decreased horizontally from nasal to temporal quadrant with lowest in center fovea, and vertically from superior to inferior quadrants. Peripapillary CVI was highest in the nasal and lowest in the inferior sector. Multiple regression showed that spherical equivalent (SE), AL, intraocular pressure (IOP), ChT, age, and gender were significantly related to CVI (P < 0.05)., Conclusions: In children, the distribution of CVI in the posterior pole is not uniform. A decreased CVI was observed from hyperopia to myopia and was associated with decreased SE, elongated AL, and choroidal thinning. Further study of changes in CVI during myopia onset and progression is required to better understand the role of the choroidal vasculature in myopia development., (© 2023. The Author(s).)

The endoplasmic reticulum (ER) functions as a quality-control organelle for protein homeostasis, or "proteostasis". The protein quality control systems involve ER-associated degradation, protein chaperons, and autophagy. ER stress is activated when proteostasis is broken with an accumulation of misfolded and unfolded proteins in the ER. ER stress activates an adaptive unfolded protein response to restore proteostasis by initiating protein kinase R-like ER kinase, activating transcription factor 6, and inositol requiring enzyme 1. ER stress is multifaceted, and acts on aspects at the epigenetic level, including transcription and protein processing. Accumulated data indicates its key role in protein homeostasis and other diverse functions involved in various ocular diseases, such as glaucoma, diabetic retinopathy, age-related macular degeneration, retinitis pigmentosa, achromatopsia, cataracts, ocular tumors, ocular surface diseases, and myopia. This review summarizes the molecular mechanisms underlying the aforementioned ocular diseases from an ER stress perspective. Drugs (chemicals, neurotrophic factors, and nanoparticles), gene therapy, and stem cell therapy are used to treat ocular diseases by alleviating ER stress. We delineate the advancement of therapy targeting ER stress to provide new treatment strategies for ocular diseases., (© 2023. West China Hospital, Sichuan University.)

Diabetic cardiomyopathy (DCM), a common complication of diabetes, is defined as ventricular dysfunction in the absence of underlying heart disease. Noncoding RNAs (ncRNAs), including long noncoding RNAs (lncRNAs) and microRNAs (miRNAs), play a crucial role in the development of DCM. Weighted Gene Co-Expression Network Analysis (WGCNA) was used to identify key modules in DCM-related pathways. DCM-related miRNA-mRNA network and DCM-related ceRNA network were constructed by miRNA-seq to identify hub genes in these modules. We identified five hub genes that are associated with the onset of DCM, including Troponin C1 (Tnnc1), Phospholamban (Pln), Fatty acid binding proteins 3 (Fabp3), Popeye domain containing 2 (Popdc2), and Tripartite Motif-containing Protein 63 (Trim63). miRNAs that target the hub genes were mainly involved in TGF-β and Wnt signaling pathways. GO BP enrichment analysis found these miRNAs were involved in the signaling of TGF-β and glucose homeostasis. Q-PCR results found the gene expressions of Pln, Fabp3, Trim63, Tnnc1, and Popdc2 were significantly increased in DCM. Our study identified five hub genes (Tnnc1, Pln, Fabp3, Popdc2, Trim63) whose associated ceRNA networks are responsible for the onset of DCM., (© 2023. The Author(s).)

The coronavirus disease 2019 (COVID-19) brought a healthy crisis all around the world. It's not only affected healthcare utilization, but also some disease's incidence. We collected pre-hospital emergency data in Chengdu from January 2016 to December 2021, and studied the demand for emergency medical services (EMSs), emergency response times (ERTs), and the disease spectrum in the city proper of Chengdu as a whole. A total of 1,122,294 prehospital emergency medical service (EMS) instances met the inclusion criteria. Under the influence of COVID-19, notably in 2020, the epidemiological characteristics of prehospital emergency services in Chengdu were considerably altered. However, as the pandemic was brought under control, they returned to normal or even earlier in 2021.The COVID-19 pandemic had an effect on people's medical care-seeking behavior and the performance of prehospital emergency services. Although the indicators associated with prehospital emergency services eventually recovered as the epidemic was brought under control, they remained marginally different from before the outbreak., (© 2023. The Author(s).)

Chronic pain patients often have anxiety disorders, and some of them suffer from anxiety even after analgesic administration. In this study, we investigated the role of AMPAR-mediated synaptic transmission in the ventromedial prefrontal cortex (vmPFC) in chronic pain-induced persistent anxiety in mice and explored potential drug targets. Chronic inflammatory pain was induced in mice by bilateral injection of complete Freund's adjuvant (CFA) into the planta of the hind paws; anxiety-like behaviours were assessed with behavioural tests; S-nitrosylation and AMPAR-mediated synaptic transmission were examined using biochemical assays and electrophysiological recordings, respectively. We found that CFA induced persistent upregulation of AMPAR membrane expression and function in the vmPFC of anxious mice but not in the vmPFC of non-anxious mice. The anxious mice exhibited higher S-nitrosylation of stargazin (an AMPAR-interacting protein) in the vmPFC. Inhibition of S-nitrosylation by bilaterally infusing an exogenous stargazin (C302S) mutant into the vmPFC rescued the surface expression of GluA1 and AMPAR-mediated synaptic transmission as well as the anxiety-like behaviours in CFA-injected mice, even after ibuprofen treatment. Moreover, administration of ZL006, a small molecular inhibitor disrupting the interaction of nNOS and PSD-95 (20 mg·kg -1 ·d -1 , for 5 days, i.p.), significantly reduced nitric oxide production and S-nitrosylation of AMPAR-interacting proteins in the vmPFC, resulting in anxiolytic-like effects in anxious mice after ibuprofen treatment. We conclude that S-nitrosylation is necessary for AMPAR trafficking and function in the vmPFC under chronic inflammatory pain-induced persistent anxiety conditions, and nNOS-PSD-95 inhibitors could be potential anxiolytics specific for chronic inflammatory pain-induced persistent anxiety after analgesic treatment., (© 2022. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

To improve the homogeneity of phase-change materials (PCMs) composites for thermal energy storage, the poly(ethylene glycol monomethyl ether)-based trimethylolpropane (Ymer-N120) with long side ethyoxyl chains is employed to form comb-like polyurethane which functioned as supporting materials for PCMs. And the results of Fourier transform infrared spectroscopy (FTIR), X-ray diffraction, differential scanning calorimetry, accelerated thermal cycling testing, thermogravimetric analysis and field emission scanning electron microscopy (FESEM) suggested a crosslinked polyurethane embedded with micron grade myristic acid (MA) crystals was prepared during the thermal curing process. The obtained comb-like polyurethane (YP) can provide 3D structure supporting materials for melting MA. And the long side ethyoxyl chain of Ymer-N120 promote the melting MA form micron-sized crystals. The results of thermal reliability testing confirmed the advantages of same methylene groups in side chains and suggested the maximal hold capability of YP crosslinks is about 50 wt% of composites. With the 50 wt% addition of MA, YPM50 can supply high latent heat (over 90 J/g of YPM50) with fine thermal stability (due to its initial decomposing temperature reaches 190 °C) without leakage (after 500 times of accelerated thermal cycling testing). All results indicated this structure supplies an effective solution for the leakage of PCMs, which show a promising application in TES., (© 2023. The Author(s).)

To establish a risk prediction model and make individualized assessment for the susceptible diabetic retinopathy (DR) population in type 2 diabetic mellitus (T2DM) patients. According to the retrieval strategy, inclusion and exclusion criteria, the relevant meta-analyses on DR risk factors were searched and evaluated. The pooled odds ratio (OR) or relative risk (RR) of each risk factor was obtained and calculated for β coefficients using logistic regression (LR) model. Besides, an electronic patient-reported outcome questionnaire was developed and 60 cases of DR and non-DR T2DM patients were investigated to validate the developed model. Receiver operating characteristic curve (ROC) was drawn to verify the prediction accuracy of the model. After retrieving, eight meta-analyses with a total of 15,654 cases and 12 risk factors associated with the onset of DR in T2DM, including weight loss surgery, myopia, lipid-lowing drugs, intensive glucose control, course of T2DM, glycated hemoglobin (HbA1c), fasting plasma glucose, hypertension, gender, insulin treatment, residence, and smoking were included for LR modeling. These factors, followed by the respective β coefficient was bariatric surgery (- 0.942), myopia (- 0.357), lipid-lowering drug follow-up < 3y (- 0.994), lipid-lowering drug follow-up > 3y (- 0.223), course of T2DM (0.174), HbA1c (0.372), fasting plasma glucose (0.223), insulin therapy (0.688), rural residence (0.199), smoking (- 0.083), hypertension (0.405), male (0.548), intensive glycemic control (- 0.400) with constant term α (- 0.949) in the constructed model. The area under receiver operating characteristic curve (AUC) of the model in the external validation was 0.912. An application was presented as an example of use. In conclusion, the risk prediction model of DR is developed, which makes individualized assessment for the susceptible DR population feasible and needs to be further verified with large sample size application., (© 2023. The Author(s).)

Current evidence on digital health interventions is disproportionately concerned with high-income countries and hospital settings. This scoping review evaluates the extent of use and effectiveness of digital health interventions for non-communicable disease (NCD) management in primary healthcare settings of low- and middle-income countries (LMICs) and identifies factors influencing digital health interventions' uptake. We use PubMed, Embase, and Web of Science search results from January 2010 to 2021. Of 8866 results, 52 met eligibility criteria (31 reviews, 21 trials). Benchmarked against World Health Organization's digital health classifications, only 14 out of 28 digital health intervention categories are found, suggesting critical under-use and lagging innovation. Digital health interventions' effectiveness vary across outcomes: clinical (mixed), behavioral (positively inclined), and service implementation outcomes (clear effectiveness). We further identify multiple factors influencing digital health intervention uptake, including political commitment, interactivity, user-centered design, and integration with existing systems, which points to future research and practices to invigorate digital health interventions for NCD management in primary health care of LMICs., (© 2023. The Author(s).)

Suboptimal medication adherence is a major barrier to hypertension control in Kenya, especially among informal urban settlement areas (sometimes referred to as "slums"). The few studies that have specifically explored medication adherence among this population have received discordant results, implying that additional factors which influence medication adherence merit further investigation. This study explores the relationship between family support and medication adherence among people with hypertension in informal settlements in Nairobi, Kenya. We conducted a quantitative survey followed up by semi-structured qualitative interviews. The sampling frame comprised two health facilities in informal settlement areas of the Korogocho neighborhood and participants were recruited via convenience sampling. We performed multiple logistic regressions for quantitative data and thematic analysis for qualitative data. A total of 93 people participated in the survey (mean age: 57 ± 14.7, 66% female). Most participants reported high family support (82%, n = 76) and suboptimal medication adherence (43% by the Morisky Scale; 76% by the Hill-Bone Scale), with no significant associations between family support and medication adherence. During interviews, many participants reported they lacked health knowledge and education. We suggest that the lack of health knowledge among this population may have contributed to a failure for family support to meaningfully translate into improvements in medication adherence. Our results underscore the need for further research to improve hypertension control among this uniquely disadvantaged population, especially with respect to the possible mediating influence of health education on family support and medication adherence., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

The present cross-sectional survey was performed to assess the prevalence and factors associated with fear of hypoglycemia (FoH) in hospitalized patients with type 2 diabetes (T2D). Between July and December 2020, 494 patients with T2D were evaluated via structured questionnaires containing sociodemographic information, clinical information, and the Fear of Hypoglycemia-15 scale (FH-15). Patients were divided into the FoH and non-FoH groups according to the FH-15 score. Univariate and multivariate logistic regression analyses were performed to determine factors associated with FoH. Variables with P values < 0.1 in the univariate model were included in the multivariate model. In this study, the prevalence of FoH was 17.4% (86/494). 247 (50.0%) patients experienced hypoglycemic episodes in the past year, and 15 (3.0%) patients experienced severe hypoglycemic episodes in the past year. The mean age was 60.04 ± 11.71 years old, and female patients accounted for 39.9% of the sample. The item with the highest average FH-15 scores was: how often are you afraid of having hypoglycemia while alone? Multivariate logistic regression analysis indicated that living alone (OR 2.48; 95% CI 1.20-5.14; P = 0.015), number of hypoglycemic episodes in the past year (OR 1.06; 95% CI 1.03-1.10; P < 0.001), number of severe hypoglycemic episodes in the past year (OR 2.61; 95% CI 1.20-5.69; P = 0.016), and duration of insulin use (OR 1.06; 95% CI 1.02-1.10; P = 0.006) were associated with FoH. The prevalence of FoH in hospitalized patients with T2D was high. FoH was associated with living alone, number of hypoglycemic episodes in the past year, number of severe hypoglycemic episodes in the past year, and duration of insulin use. These findings can contribute to early decision-making for preventing, identifying, and improving FoH in patients with T2D. In the future, interventions aimed at reducing FoH to improve the harmful effects of FoH are necessary, such as increasing diabetes-related knowledge and skills, increasing social support, reducing psychological fear, and minimizing risks for hypoglycemic episodes., (© 2022. The Author(s).)

Colorectal cancer (CRC) is a heterogeneous disease and one of the most prevalent malignancies worldwide. Previous research has demonstrated that mitophagy is crucial to developing colorectal cancer. This study aims to examine the association between mitophagy-related genes and the prognosis of CRC patients. Gene expression profiles and clinical information of CRC patients were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Univariate Cox regression and the least absolute shrinkage and selection operator (LASSO) regression analysis were applied to establish a prognostic signature using mitophagy related genes. Kaplan-Meier and receiver operating characteristic (ROC) curves were used to analyze patient survival and predictive accuracy. Meanwhile, we also used the Genomics of Drug Sensitivity in Cancer (GDSC) database and Tumor Immune Dysfunction and Exclusion (TIDE) algorithm to estimate the sensitivity of chemotherapy, targeted therapy and immunotherapy. ATG14 overexpression plasmid was used to regulate the ATG14 expression level in HCT116 and SW480 cell lines, and cell counting kit-8, colony formation and transwell migration assay were performed to validate the function of ATG14 in CRC cells. A total of 22 mitophagy-driven genes connected with CRC survival were identified, and then a novel prognostic signature was established based on 10 of them (AMBRA1, ATG14, MAP1LC3A, MAP1LC3B, OPTN, VDAC1, ATG5, CSNK2A2, MFN1, TOMM22). Patients were divided into high-risk and low-risk groups based on the median risk score, and the survival of patients in the high-risk group was significantly shorter in both the training cohort and two independent cohorts. ROC curve showed that the area under the curves (AUC) of 1-, 3- and 5-year survival were 0.66, 0.66 and 0.64, respectively. Multivariate Cox regression analysis confirmed the independent prognostic value of the signature. Then we constructed a Nomogram combining the risk score, age and M stage, which had a concordance index of survival prediction of 0.77 (95% CI 0.71-0.83) and more robust predictive accuracy. Results showed that CD8+ T cells, regulatory T cells and activated NK cells were significantly more enriched in the high-risk group. Furthermore, patients in the high-risk group are more sensitive to targeted therapy or chemotherapy, including bosutinib, elesclomol, lenalidomide, midostaurin, pazopanib and sunitinib, while the low-risk group is more likely to benefit from immunotherapy. Finally, in vitro study confirmed the oncogenic significance of ATG14 in both HCT116 and SW480 cells, whose overexpression increased CRC cell proliferation, colony formation, and migration. In conclusion, we developed a novel mitophagy-related gene signature that can be utilized not only as an independent predictive biomarker but also as a tool for tailoring personalizing treatment for CRC patients, and we confirmed ATG14 as a novel oncogene in CRC., (© 2022. The Author(s).)

Fast radio bursts (FRBs) are highly dispersed, millisecond-duration radio bursts 1-3 . Recent observations of a Galactic FRB 4-8 suggest that at least some FRBs originate from magnetars, but the origin of cosmological FRBs is still not settled. Here we report the detection of 1,863 bursts in 82 h over 54 days from the repeating source FRB 20201124A (ref.  9 ). These observations show irregular short-time variation of the Faraday rotation measure (RM), which scrutinizes the density-weighted line-of-sight magnetic field strength, of individual bursts during the first 36 days, followed by a constant RM. We detected circular polarization in more than half of the burst sample, including one burst reaching a high fractional circular polarization of 75%. Oscillations in fractional linear and circular polarizations, as well as polarization angle as a function of wavelength, were detected. All of these features provide evidence for a complicated, dynamically evolving, magnetized immediate environment within about an astronomical unit (AU; Earth-Sun distance) of the source. Our optical observations of its Milky-Way-sized, metal-rich host galaxy 10-12 show a barred spiral, with the FRB source residing in a low-stellar-density interarm region at an intermediate galactocentric distance. This environment is inconsistent with a young magnetar engine formed during an extreme explosion of a massive star that resulted in a long gamma-ray burst or superluminous supernova., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Cell lines have become an integral resource and tool for conducting biological experiments ever since the Hela cell line was first developed (Scherer et al. in J Exp Med 97:695-710, 1953). They not only allow detailed investigation of molecular pathways but are faster and more cost-effective than most in vivo approaches. The last decade saw many emerging model systems strengthening basic science research. However, lack of genetic and molecular tools in these newer systems pose many obstacles. Astyanax mexicanus is proving to be an interesting new model system for understanding metabolic adaptation. To further enhance the utility of this system, we developed liver-derived cell lines from both surface-dwelling and cave-dwelling morphotypes. In this study, we provide detailed methodology of the derivation process along with comprehensive biochemical and molecular characterization of the cell lines, which reflect key metabolic traits of cavefish adaptation. We anticipate these cell lines to become a useful resource for the Astyanax community as well as researchers investigating fish biology, comparative physiology, and metabolism., (© 2022. The Author(s).)

Tyrosine phosphorylation by protein tyrosine kinases (PTKs) is a type of post-translational modification. Tec kinases, which are a subfamily of non-receptor PTKs, were originally discovered in the hematopoietic system and include five members: Tec, Btk, Itk/Emt/Tsk, Etk/Bmx, and Txk/Rlk. With the progression of modern research, certain members of the Tec family of kinases have been found to be expressed outside the hematopoietic system and are involved in the development and progression of a variety of diseases. The role of Tec family kinases in cardiovascular disease is receiving increasing attention. Tec kinases are involved in the occurrence and progression of ischemic heart disease, atherosclerosis, cardiac dysfunction associated with sepsis, atrial fibrillation, myocardial hypertrophy, coronary atherosclerotic heart disease, and myocardial infarction and post-myocardial. However, no reviews have comprehensively clarified the role of Tec kinases in the cardiovascular system. Therefore, this review summarizes research on the role of Tec kinases in cardiovascular disease, providing new insights into the prevention and treatment of cardiovascular disease., (© 2022. The Author(s).)

To compare the clinical feasibility and oncological outcome of different surgical techniques for inguinal lymphadenectomy (ILND) in patients suffering from penile cancer. This study included data from 109 cN 0-2 patients diagnosed with penile cancer who received ILND. 80 laparoscopic ILND were performed on 40 patients, while 138 open surgeries were performed on 69 patients. Perioperative complications and prognosis were compared between different surgical techniques. Compared with the open surgery group, the laparoscopy group had a shorter hospital stay (8.88 ± 7.86 days vs. 13.94 ± 10.09 days, P = 0.004), and a lower wound healing delay rate (8.75% vs. 22.46%, P = 0.017), but also had longer drainage time (10.91 ± 9.66 vs. 8.70 ± 4.62, P = 0.002). There were no significant differences in terms of other intraoperative parameters, complications, and survival between open and laparoscopic group. Compared with saphenous vein ligated subgroup, preserved subgroup showed no significant reducing of complication rate. There was no significant difference among complication between different open surgery subgroup. Immediate ILND showed no prognostic advantage over delayed ILND regardless of clinical lymph node status. Compared with open surgery, the minimally invasive ILND technique has similar oncological efficiency and a lower complication rate. Saphenous vein preservation has limited value in reducing complications. Delayed lymphadenectomy might be a more reasonable option for ILND., (© 2022. The Author(s).)

There exists a consensus that combining hyperbaric oxygen (HBO) and chemotherapy promotes chemotherapy sensitivity in GBM cells. However, few studies have explored the mechanism involved. HIF1α and HIF2α are the two main molecules that contribute to GBM malignant progression by inhibiting apoptosis or maintaining stemness under hypoxic conditions. Moreover, Sox2, a marker of stemness, also contributes to GBM malignant progression through stemness maintenance or cell cycle arrest. Briefly, HIF1α, HIF2α and Sox2 are highly expressed under hypoxia and contribute to GBM growth and chemoresistance. However, after exposure to HBO for GBM, whether the expression of the above factors is decreased, resulting in chemosensitization, remains unknown. Therefore, we performed a series of studies and determined that the expression of HIF1α, HIF2α and Sox2 was decreased after HBO and that HBO promoted GBM cell proliferation through cell cycle progression, albeit with a decrease in stemness, thus contributing to chemosensitization via the inhibition of HIF1α/HIF2α-Sox2.

Alzheimer's disease is the leading cause of dementia. The long progression period in Alzheimer's disease provides a possibility for patients to get early treatment by having routine screenings. However, current clinical diagnostic imaging tools do not meet the specific requirements for screening procedures due to high cost and limited availability. In this work, we took the initiative to evaluate the retina, especially the retinal vasculature, as an alternative for conducting screenings for dementia patients caused by Alzheimer's disease. Highly modular machine learning techniques were employed throughout the whole pipeline. Utilizing data from the UK Biobank, the pipeline achieved an average classification accuracy of 82.44%. Besides the high classification accuracy, we also added a saliency analysis to strengthen this pipeline's interpretability. The saliency analysis indicated that within retinal images, small vessels carry more information for diagnosing Alzheimer's diseases, which aligns with related studies.

Fast radio bursts (FRBs) are millisecond-duration radio transients of unknown physical origin observed at extragalactic distances 1-3 . It has long been speculated that magnetars are the engine powering repeating bursts from FRB sources 4-13 , but no convincing evidence has been collected so far 14 . Recently, the Galactic magnetar SRG 1935+2154 entered an active phase by emitting intense soft γ-ray bursts 15 . One FRB-like event with two peaks (FRB 200428) and a luminosity slightly lower than the faintest extragalactic FRBs was detected from the source, in association with a soft γ-ray/hard-X-ray flare 18-21 . Here we report an eight-hour targeted radio observational campaign comprising four sessions and assisted by multi-wavelength (optical and hard-X-ray) data. During the third session, 29 soft-γ-ray repeater (SGR) bursts were detected in γ-ray energies. Throughout the observing period, we detected no single dispersed pulsed emission coincident with the arrivals of SGR bursts, but unfortunately we were not observing when the FRB was detected. The non-detection places a fluence upper limit that is eight orders of magnitude lower than the fluence of FRB 200428. Our results suggest that FRB-SGR burst associations are rare. FRBs may be highly relativistic and geometrically beamed, or FRB-like events associated with SGR bursts may have narrow spectra and characteristic frequencies outside the observed band. It is also possible that the physical conditions required to achieve coherent radiation in SGR bursts are difficult to satisfy, and that only under extreme conditions could an FRB be associated with an SGR burst.

Myopia, a leading cause of distance vision impairment, is projected to affect half of the world's population in 30 years. We analysed the relationship between certain demographic, environmental, and behavioural factors and myopia from a 2-year school-based, prospective trial conducted in Shanghai, China. This trial enrolled 6295 school-aged children at baseline and followed them up for 24 months. The relationship between abovementioned factors and myopia was examined and the role of sleep in childhood myopia development was highlighted. Our results suggest that 'sleeping late' is a risk factor for myopia prevalence at baseline (odds ratio [OR] = 1.55, p = 0.04), 2-year myopia incidence (odds ratio [OR] = 1.44, p = 0.02) and progression over 24 months (p = 0.005), after adjusting for residency area, age, gender, sleep duration, and time spent outdoors. The identification and consistency of results with late sleepers being a susceptible group to both myopia onset and progression suggests a complex relationship between circadian rhythm, indoor environment, habitual indoor activities and myopia development and progression. These results can offer new insights to future myopia aetiology studies as well as aid in decision-making of myopia prevention strategies.

Dietary quality is an important factor influencing prediabetes, but few studies have applied the Chinese Diet Balance Index (DBI-16) to evaluate the dietary quality of individuals with prediabetes and explore the associations between dietary quality and prediabetes. In our study, the lower-bound score, higher-bound score and diet quality distance, were respectively calculated to assess dietary quality based on each food group. Logistic regression was used to calculate the odds ratio (OR) and 95% confidence interval (95%CI) of unfavorable dietary quality leading to prediabetes in every subgroup. The results were shown that individuals with prediabetes had excessive intake in the categories of cereals, salt and inadequate intake in vegetables, fish and diet variety than participants without prediabetes (all P < 0.01). Unfavourable dietary quality was significantly associated with an increased risk of prediabetes (OR: 1.45, 95%CI: 1.29-1.63), especially among the subjects who lived in rural areas (OR: 1.63, 95%CI: 1.25-1.76), those who had abdominal obesity (OR: 1.58, 95%CI: 1.36-1.85), those who smoked (OR: 1.58, 95%CI: 1.30-1.93), those who consumed alcohol (OR: 1.57, 95%CI: 1.28-1.93) and those who did not drink tea (OR: 1.64, 95%CI: 1.42-1.88). In Conclusion, unfavourable dietary quality was significantly associated with an increased risk of prediabetes.

Neuroinflammation is one of the critical events in neurodegenerative diseases, whereas microglia play an important role in the pathogenesis of neuroinflammation. In this study, we investigated the effects of a natural sesquiterpene lactone, 6-O-angeloylplenolin (6-OAP), isolated from the traditional Chinese medicine Centipeda minima (L.) A.Br., on neuroinflammation and the underlying mechanisms. We showed that treatment with lipopolysaccharide (LPS) caused activation of BV2 and primary microglial cells and development of neuroinflammation in vitro, evidenced by increased production of inflammatory cytokines TNF-α and IL-1β, the phosphorylation and nuclear translocation of NF-κB, and the transcriptional upregulation of COX-2 and iNOS, leading to increased production of proinflammatory factors NO and PGE 2 . Moreover, LPS treatment induced oxidative stress through increasing the expression levels of NOX2 and NOX4. Pretreatment with 6-OAP (0.5-4 μM) dose-dependently attenuated LPS-induced NF-κB activation and oxidative stress, thus suppressed neuroinflammation in the cells. In a mouse model of LPS-induced neuroinflammation, 6-OAP (5-20 mg·kg -1 ·d -1 , ip, for 7 days before LPS injection) dose-dependently inhibited the production of inflammatory cytokines, the activation of the NF-κB signaling pathway, and the expression of inflammatory enzymes in brain tissues. 6-OAP pretreatment significantly ameliorated the activation of microglia and astrocytes in the brains. 6-OAP at a high dose caused a much stronger antineuroinflammatory effect than dexamethansone (DEX). Furthermore, we demonstrated that 6-OAP pretreatment could inhibit LPS-induced neurite and synaptic loss in vitro and in vivo. In conclusion, our results demonstrate that 6-OAP exerts antineuroinflammatory effects and can be considered a novel drug candidate for the treatment of neuroinflammatory diseases.

Outbreaks of viral infections are a global health burden. Although type I interferon (IFN-I) exerts broad-spectrum antiviral effects, its antiviral efficacy in host cells is largely restricted by viruses. How the antiviral efficacy of IFN-I can be improved remains to be explored. Here, we identified the ADP-ribosyltransferase poly(ADP-ribose) polymerase family member 11 (PARP11) as a potent regulator of IFN-I antiviral efficacy. PARP11 does not restrict IFN-I production induced by vesicular stomatitis virus or Sendai virus but inhibits the strength of IFN-I-activated signalling. Mechanistically, PARP11 mono-ADP-ribosylates the ubiquitin E3 ligase β-transducin repeat-containing protein (β-TrCP). Mono-ADP-ribosylation of β-TrCP promotes IFNα/β receptor subunit 1 (IFNAR1) ubiquitination and degradation. Moreover, PARP11 expression is upregulated by virus infections, including vesicular stomatitis virus, herpes simplex virus-1 and influenza A virus, thus promoting ADP-ribosylation-mediated viral evasion. We further highlight the potential for repurposing clinical ADP-ribosylation inhibitors. We found that rucaparib can target PARP11 to stabilize IFNAR1 and therefore exhibits efficient enhancement of IFN-I signalling and the host antiviral response. Consequently, rucaparib renders mice more resistant to viral infection. Our study updates the understanding of how β-TrCP regulates its substrates and may provide a druggable target for improving IFN antiviral efficacy.

Fractures that develop in coal seams threaten safety in many ways, but they can be predicted using fracture parameters derived from seismic data. However, the post-stack split shear waves are difficult to thoroughly separate by Alford rotation due to wavefield mixing. We propose a method of predicting fractures in a coal seam using multi-component seismic data, which was applied to coal seam 13-1 of the Huainan coalfield, China. We employed the Alford rotation to separate the split PS-waves (P-to-S converted waves) and perform interlayer travel-time inversion of the fast shear waves using geophysical logs, rock-physics parameters, and tunnel-excavation information as constraints. However, post-stack wavefield mixing of the coal seam interfered with the Alford rotation of the real post-stack seismic data. Therefore, we only performed the Alford rotation on radial and transverse component post-stack sections to derive fracture azimuths, which were then applied to the pre-stack separation of the split PS-waves. Using joint PP- and PS-wave inversion, anisotropy parameters were derived for use in fracture prediction. Finally, we predicted unsafe mining areas with a high probability of coal and gas outbursts. The application results were verified by excavation data from the mine tunnels. Our method contributes to fracture prediction on coal mine safety.

Considering the challenge of population ageing and the substantial health problem among the elderly population from falls, the purpose of this study was to verify whether it is possible to distinguish accurately between older fallers and non-fallers, based on data from wearable inertial sensors collected during a specially designed test battery. A comprehensive but practical test battery using 5 wearable inertial sensors for multifactorial fall risk assessment was designed. This was followed by an experimental study on 196 community-dwelling Korean older women, categorized as fallers (N 1  = 82) and non-fallers (N 2  = 114) based on prior history of falls. Six machine learning models (logistic regression, naïve bayes, decision tree, random forest, boosted tree and support vector machine) were proposed for faller classification. Results indicated that compared with non-fallers, fallers performed significantly worse on the test battery. In addition, the application of sensor data and support vector machine for faller classification achieved an overall accuracy of 89.4% with 92.7% sensitivity and 84.9% specificity. These findings suggest that wearable inertial sensor based systems show promise for elderly fall risk assessment, which could be implemented in clinical practice to identify "at-risk" individuals reliably to promote proactive fall prevention.

Objective: Ciliary neurotrophic factor (CNTF) has been evaluated as a candidate therapeutic agent for diabetes and its neural complications. However, its role in diabetic retinopathy has not been fully elucidated., Methods: This is a randomized unblinded animal experiment. Wistar rats with streptozocin (STZ)-induced diabetes were regularly injected with CNTF or vehicle control in their vitreous bodies beginning at 2 weeks after STZ injection. A total of five injections were used. In diabetic rats, the levels of CNTF and neurotrophin-3 (NT-3) were evaluated by enzyme-linked immunosorbent assays (ELISA) and real-time PCR. The abundance of tyrosine hydroxylase (TH) and β-III tubulin was detected by western blot. Transferase-mediated dUTP nick-end labeling staining (TUNEL) was used to detect cell apoptosis in the retinal tissue. The activation of caspase-3 was also measured., Results: The protein and mRNA levels of CNTF in diabetic rat retinas were reduced compared to control rats. In addition, retinal ganglion cells (RGCs) and dopaminergic amacrine cells appeared to undergo degeneration in diabetic rat retinas, as revealed by transferase-mediated dUTP nick-end labeling staining (TUNEL). Tyrosine hydroxylase (TH) and β-III tubulin protein levels also decreased significantly. Intraocular administration of CNTF rescued RGCs and dopaminergic amacrine cells from neurodegeneration and counteracted the downregulation of β-III tubulin and TH expression, thus demonstrating its therapeutic potential., Conclusion: Our study suggests that early diabetic retinal neuropathy involves the reduced expression of CNTF and can be ameliorated by an exogenous supply of this neurotrophin.

Na based all-solid-state batteries are a promising technology for large-scale energy storage applications owing to good safety properties and low cost. High performance solid electrolyte materials with high room temperature ionic conductivity, good electrochemical stability and facile synthesis are highly desired for the commercialization of this technology. In this work, we report the synthesis and characterization of a novel fast Na-ion conductor, cubic Na 3 SbSe 4 , with an excellent ionic conductivity of 0.85 mS cm -1 at room temperature, and a group of S doped variants. Na 3 SbSe 4 exhibits good compatibility with metallic Na and good stability in a wide voltage range. The application of this compound as solid electrolyte is demonstrated in all-solid-state Na-ion cells cycled at room temperature.

Newborn microglia rapidly replenish the whole brain after selective elimination of most microglia (>99%) in adult mice. Previous studies reported that repopulated microglia were largely derived from microglial progenitor cells expressing nestin in the brain. However, the origin of these repopulated microglia has been hotly debated. In this study, we investigated the origin of repopulated microglia by a series of fate-mapping approaches. We first excluded the blood origin of repopulated microglia via parabiosis. With different transgenic mouse lines, we then demonstrated that all repopulated microglia were derived from the proliferation of the few surviving microglia (<1%). Despite a transient pattern of nestin expression in newly forming microglia, none of repopulated microglia were derived from nestin-positive non-microglial cells. In summary, we conclude that repopulated microglia are solely derived from residual microglia rather than de novo progenitors, suggesting the absence of microglial progenitor cells in the adult brain.

We present a synthetic-wavelength based heterodyne interferometer of optical frequency combs with wide consecutive measurement range for absolute distance measurement. The synthetic wavelength is derived from two wavelengths obtained by two band-pass filters. The interferometric phase of the synthetic wavelength is used as a marker for the pulse-to-pulse alignment, which greatly improves the accuracy of traditional peak finding method. The consecutive measurement range is enlarged by using long fiber to increase the path length difference of the reference and measurement arms. The length of the long fiber is stabilized according to the interferometric phase of a CW laser. The experimental results show the present system can realize an accuracy of 75 nm in 350 mm consecutive measurement range.

Elucidating the origin of microglia is crucial for understanding their functions and homeostasis. Previous study has indicated that Nestin-positive progenitor cells differentiate into microglia and replenish the brain after depleting most brain microglia. Microglia have also shown the capacity to repopulate the retina after eliminating all retinal microglia. However, the origin(s) of repopulated retinal microglia is/are unknown. In this study, we aim to investigate the origins of repopulated microglia in the retina. Interestingly, we find that repopulated retinal microglia are not derived from Nestin-positive progenitor cells. Instead, they have two origins: the center-emerging microglia are derived from residual microglia in the optic nerve and the periphery-emerging microglia are derived from macrophages in the ciliary body/iris. Therefore, we have for the first time identified the extra-retinal origins of microglia in the adult mammalian retina by using a model of microglial repopulation, which may shed light on the target exploration of therapeutic interventions for retinal degenerative disorders., Competing Interests: The authors declare that they have no conflict of interest.

The global prevalence of hepatitis C Virus (HCV) is approximately 3% and one-fifth of all HCV carriers live in the Middle East, where Egypt has the highest global incidence of HCV infection. Quantitative structure-activity relationship (QSAR) models were used in many applications for predicting the potential effects of chemicals on human health and environment. The adaptive neuro-fuzzy inference system (ANFIS) is one of the most popular regression methods for building a nonlinear QSAR model. However, the quality of ANFIS is influenced by the size of the descriptors, so descriptor selection methods have been proposed, although these methods are affected by slow convergence and high time complexity. To avoid these limitations, the antlion optimizer was used to select relevant descriptors, before constructing a nonlinear QSAR model based on the PIC 50 and these descriptors using ANFIS. In our experiments, 1029 compounds were used, which comprised 579 HCVNS5B inhibitors (PIC 50  < ~14) and 450 non-HCVNS5B inhibitors (PIC 50  > ~14). The experimental results showed that the proposed QSAR model obtained acceptable accuracy according to different measures, where [Formula: see text] was 0.952 and 0.923 for the training and testing sets, respectively, using cross-validation, while [Formula: see text] was 0.8822 using leave-one-out (LOO).

MDM2, an E3 ubiquitin ligase, is a potent inhibitor of the p53 tumor suppressor and is elevated in many human cancers that retain wild-type p53. MDM2 SNP309G is a functional polymorphism that results in elevated levels of MDM2 (due to enhanced SP1 binding to the MDM2 promoter) thus decreasing p53 activity. Mdm2 SNP309G/G mice are more prone to spontaneous tumor formation than Mdm2 SNP309T/T mice, providing direct evidence for the impact of this SNP in tumor development. We asked whether environmental factors impact SNP309G function and show that SNP309G cooperates with ionizing radiation to exacerbate tumor development. Surprisingly, ultraviolet B light or Benzo(a)pyrene exposure of skin shows that SNP309G allele actually protects against squamous cell carcinoma susceptibility. These contrasting differences led us to interrogate the mechanism by which Mdm2 SNP309 regulates tumor susceptibility in a tissue-specific manner. Although basal Mdm2 levels were significantly higher in most tissues in Mdm2 SNP309G/G mice compared with Mdm2 SNP309T/T mice, they were significantly lower in Mdm2 SNP309G/G keratinocytes, the cell-type susceptible to squamous cell carcinoma. The assessment of potential transcriptional regulators in ENCODE ChIP-seq database identified transcriptional repressor E2F6 as a possible negative regulator of MDM2 expression. Our data show that E2F6 suppresses Mdm2 expression in cells harboring the SNP309G allele but not the SNP309T allele. Thus, Mdm2 SNP309G exhibits tissue-specific regulation and differentially impacts cancer risk.

The microstructure of a high-pressure die-cast hypereutectic A390 alloy, including PSPs, pores, α-Al grains and Cu-rich phases, was characterized using synchrotron X-ray tomography, together with SEM, TEM and EBSD. The Cu-rich phases exhibited a net morphology and distributed at the boundaries of the α-Al grains, which in turn surrounded the PSPs. Statistical analysis of the reconstructed 1000 PSPs showed that both equivalent diameter and shape factor of the PSPs exhibited a unimodal distribution with peaks corresponding to 25 μm and 0.78, respectively.) PSPs morphology with multiple twinning were observed and morphological or growth transition of the PSPs from regular octahedral shape (with a shape factor of 0.85 was mainly caused by the constraint of the Cu-rich phases. In particular, the presence of the Cu-rich phases restricted the growth of the α-Al grains, inducing stress on the internal silicon particles, which caused multiple twinning occurrence with higher growth potential and consequently led to growth transitions of the PSPs.