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Abstract This study aimed to explore psychological problems and related factors among frontline primary healthcare workers who belongs to community health service centers and directly provides medical security services to community residents during the COVID-19 in Shanghai. We used a cross-sectional data analysis design to investigate the anxiety and depression levels of 929 frontline healthcare staff (primary healthcare providers, nurses, village doctors, and public health workers) during the Shanghai epidemic.The prevalence of depression among frontline primary healthcare workers was 39.7% (369 cases) and that of anxiety was 30%(279 cases). There was a significant correlation between the depression symptoms and anxiety symptoms. And factors associated with depression were being female, advanced education, expecting psychological interventions, expecting vacations as a reward, and expecting financial rewards. Factors strongly associated with anxiety were being female, expecting psychological interventions, and expecting vacations as a reward. Psychological problems among frontline primary healthcare workers merit more attention during the COVID-19 outbreak, especially those who are vulnerable (e.g., females and those with an advanced education).

While the industry has produced sugar-derived ethanol from the conventional method of fermentation for hundreds of years, other effective routes involving the direct transformation of carbohydrates still remain extremely rare. Very recently, an innovative chemo-catalytic method driven by the aqueous-phase catalysis was created for the synthesis of cellulosic ethanol, making a great breakthrough in the common ways as it can theoretically utilize all of the carbon atoms in sugars with faster kinetics; up to now, results from the relevant studies have been accumulated to a certain extent, but the periodic conclusions in this field are unfortunately absent. For this reason, this work tries to offer an overview of the cellulosic ethanol produced by chemo-catalytic routes, highlighting the present knowledge in relation to the technical efficiency, catalytic mechanisms as well as practical applications. At first, the advanced progress on the increasing efficiency from a varied type of catalytic systems are extensively discussed, which involves the specific functions of hybrid components from different strategies; meanwhile, the general influences of processing conditions, such as the hydrothermal severity and aqueous environments, are also identified. Subsequently, possible mechanisms behind the chemo-catalytic processes are widely elaborated by analyzing a number of experimental cases associated with the reaction network and its kinetic models. After that, the actual effects of this technique on the real biomass are collected to identify the positive/negative interactions between multiple components, together with the potential solutions on the semi-continuous processes of pilot scale application. The techno-economic analysis (TEA) is also calculated and compared with other similar methods, such as fermentation and gasification. Finally, several proposals aimed at upgrading the whole chain of chemo-catalytic processes are clearly provided, which may function as a guideline for future studies on the production of bio-ethanol from lignocellulosic materials.

Abstract Background Glucagon-like peptide-1 receptor (GLP1R) agonists have been shown to reduce major cardiovascular events in diabetic patients, but their role in heart failure (HF) remains controversial. Recent evidence implies their potential benefits on cardiometabolism such as lipid metabolism, which may contribute to lowering the risk of HF. Consequently, we designed a Mendelian randomization (MR) study to investigate the causal relationships of circulating lipids mediating GLP1R agonists in HF. Methods The available cis-eQTLs for GLP1R target gene were selected as instrumental variables (IVs) of GLP1R agonism. Positive control analyses of type 2 diabetes mellitus (T2DM) and body mass index (BMI) were conducted to validate the enrolled IVs. Two-sample MR was performed to evaluate the associations between GLP1R agonism and HF as well as left ventricular ejection fraction (LVEF). Summary data for HF and LVEF were obtained from two genome-wide association studies (GWASs), which included 977,323 and 40,000 individuals of European ancestry, respectively. The primary method employed was the random-effects inverse variance weighted, with several other methods used for sensitivity analyses, including MR-Egger, MR PRESSO, and weighted median. Additionally, multivariable MR and mediation MR were applied to identify potentially causal lipid as mediator. Results A total of 18 independent IVs were included. The positive control analyses showed that GLP1R agonism significantly reduced the risk of T2DM (OR = 0.79, 95% CI = 0.75–0.85, p

Abstract Soybean is a photoperiod-sensitive staple crop. Its photoperiodic flowering has major consequences for latitudinal adaptation and grain yield. Here, we identify and characterise a flowering locus named Time of flower 4b (Tof4b), which encodes E1-Like b (E1Lb), a homologue of the key soybean floral repressor E1. Tof4b protein physically associates with the promoters of two FLOWERING LOCUS T (FT) genes to repress their transcription and delay flowering to impart soybean adaptation to high latitudes. Three E1 homologues undergo subfunctionalisation and show differential subcellular localisation. Moreover, they all possess self-repression capability and each suppresses the two homologous counterparts. Subfunctionalisation and the transcriptional regulation of E1 genes collectively finetune flowering time and high-latitude adaptation in soybean. We propose a model for the functional fate of the three E1 genes after the soybean whole-genome duplication events, refine the molecular mechanisms underlying high-latitude adaption, and provide a potential molecular-breeding resource.

Osteoporosis is linked to increased bone marrow adipocyte (BMAd) proliferation, which displaces bone-forming cells and alters the local environment. The impact of BMAd lipid droplets on bone health and osteoblast function remains unclear. This study investigates the interplay between BMAd-derived lipid droplets and osteoblast functionality, focusing on ferroptosis pathways. Osteoblast cultures were treated with conditioned media from adipocytes to simulate in vivo conditions. High-throughput mRNA sequencing and Western blot analysis were used to profile changes in gene expression and protein levels related to ferroptosis, oxidative phosphorylation, and osteogenic markers. Cellular assays assessed the direct impact of lipid droplets on osteoblast activity. Results showed that osteoblasts exposed to adipocyte-conditioned media had increased intracellular lipid droplet accumulation, upregulation of ferroptosis-related genes and proteins, and downregulation of oxidative phosphorylation and osteoblast differentiation markers. Treatment with ferroptosis inhibitors reversed the detrimental effects on osteoblasts, indicating the functional relevance of this pathway in osteoporosis. BMAd-derived lipid droplets contribute to osteoblast dysfunction through ferroptosis induction. Inhibiting ferroptosis could preserve osteoblast function and combat osteoporosis-related bone issues, suggesting that modulating lipid metabolism and redox balance in bone cells may be promising for future treatments.

BackgroundGrowing evidence emphasizes the importance of xanthophyll carotenoids and omega-3 fatty acids in eye health. However, the beneficial effects of such supplementation have not been thoroughly discussed among adults with high screen exposure. Current trial evidence on lutein bioavailability is contradictory, and the interactions of dietary intervention with host-related factors remain elusive. This study aims to investigate the comparative effectiveness of supplementation with macular xanthophylls and omega-3 fatty acids on macular pigment optical density (MPOD) and visual function, access the bioavailability of free lutein and lutein ester, and explore the complex interplay between genetic variations, intestinal microbiota, and the dietary intervention in Chinese adults with long-term exposure to digital devices.MethodsThe Lutein, Zeaxanthin, and Omega-3 (LZO) clinical trial is a 24-week multicenter, randomized, double-blind, placebo-controlled trial of 600 participants recruited from research centers, universities, and communities. Individuals are eligible to participate if they are aged over 18 years and use digital devices for over 8 h daily in the last 2 years, and will be randomized to six arms. A total of three visits will be scheduled at baseline, 12 and 24 weeks. The primary outcome is the change in MPOD over the 24-week intervention. The secondary outcomes are changes in visual function (visual acuity, best-corrected visual acuity, contrast and glare sensitivity, critical flicker fusion, reaction time, visuognosis persistence, symptoms and signs of dry eye, retinal thickness, and optical quality), and changes in serum lutein and zeaxanthin concentrations, and erythrocyte membrane omega-3 fatty acids. Genetic variations will be determined using genome-wide genotyping at baseline. 16S rRNA gene sequencing will be utilized to assess microbiome compositional changes before and after intervention.DiscussionThe trial is anticipated to establish early interventions to prevent photochemical ocular damage and delay the onset of vision impairment in young adults with long-term repeated exposure to screen-based electronic devices, and provide valuable insights for the development of precision nutrition strategies for maintaining eye health.Clinical trial registrationwww.clinicaltrials.in.th, Identifier, TCTR20220904002.

Abstract Klotho regulates many pathways in the aging process, but it remains unclear how it is physiologically regulated. Because Klotho is synthesized, cleaved, and released from the kidney; activates the chief urinary K+ secretion channel (ROMK) and stimulates urinary K+ secretion, we explored if Klotho protein is regulated by dietary K+ and the potassium-regulatory hormone, Aldosterone. Klotho protein along the nephron was evaluated in humans and in wild-type (WT) mice; and in mice lacking components of Aldosterone signaling, including the Aldosterone-Synthase KO (AS-KO) and the Mineralocorticoid-Receptor KO (MR-KO) mice. We found the specific cells of the distal nephron in humans and mice that are chief sites of regulated K+ secretion have the highest Klotho protein expression along the nephron. WT mice fed K+-rich diets increased Klotho expression in these cells. AS-KO mice exhibit normal Klotho under basal conditions but could not upregulate Klotho in response to high-K+ intake in the K+-secreting cells. Similarly, MR-KO mice exhibit decreased Klotho protein expression. Together, i) Klotho is highly expressed in the key sites of regulated K+ secretion in humans and mice, ii) In mice, K+-rich diets increase Klotho expression specifically in the potassium secretory cells of the distal nephron, iii) Aldosterone signaling is required for Klotho response to high K+ intake.

Abstract Background Exportin 1 (XPO1) is a nuclear export protein that facilitates the transportation of various substances. XPO1 promotes tumor development as a poor prognostic factor in a variety of tumors and is a therapeutic target for screening inhibitors. However, the role of XPO1 in oral squamous cell carcinoma (OSCC) has yet to be determined. Methods The expression patterns of XPO1 mRNA in OSCC were investigated using bioinformatics tools, and the expression levels of XPO1 protein in OSCC specimens were confirmed by immunohistochemical assays. Survival analysis was conducted to evaluate the impact of XPO1 on prognosis. GO and KEGG enrichment analyses were utilized to uncover the signaling pathways mediated by XPO1. Additionally, we examined the association between XPO1 and AKT/MAPK/TGFBR1 and immune infiltration. Results XPO1 mRNA and protein expression levels were significantly enhanced in OSCC and associated with OSCC severity. Enhanced XPO1 expression was indicative of poor survival. Functional analysis showed that XPO1 mediated pathways associated with cell cycle and DNA replication and reduced immune infiltration in OSCC. Additionally, XPO1 mRNA and protein expression levels had significant positive relationships with AKT/MAPK/TGFBR1. Conclusions XPO1, as a marker of poor prognosis in OSCC, can promote OSCC through AKT/MAPK/TGFBR1.

Abstract Background The duration of hospitalization, especially in the intensive care unit (ICU), for patients with diabetic ketoacidosis (DKA) is influenced by patient prognosis and treatment costs. Reducing ICU length of stay (LOS) in patients with DKA is crucial for optimising healthcare resources utilization. This study aimed to establish a nomogram prediction model to identify the risk factors influencing prolonged LOS in ICU-managed patients with DKA, which will serve as a basis for clinical treatment, healthcare safety, and quality management research. Methods In this single-centre retrospective cohort study, we performed a retrospective analysis using relevant data extracted from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. Clinical data from 669 patients with DKA requiring ICU treatment were included. Variables were selected using the Least Absolute Shrinkage and Selection Operator (LASSO) binary logistic regression model. Subsequently, the selected variables were subjected to a multifactorial logistic regression analysis to determine independent risk factors for prolonged ICU LOS in patients with DKA. A nomogram prediction model was constructed based on the identified predictors. The multivariate variables included in this nomogram prediction model were the Oxford acute severity of illness score (OASIS), Glasgow coma scale (GCS), acute kidney injury (AKI) stage, vasoactive agents, and myocardial infarction. Results The prediction model had a high predictive efficacy, with an area under the curve value of 0.870 (95% confidence interval [CI], 0.831–0.908) in the training cohort and 0.858 (95% CI, 0.799–0.916) in the validation cohort. A highly accurate predictive model was depicted in both cohorts using the Hosmer–Lemeshow (H-L) test and calibration plots. Conclusion The nomogram prediction model proposed in this study has a high clinical application value for predicting prolonged ICU LOS in patients with DKA. This model can help clinicians identify patients with DKA at risk of prolonged ICU LOS, thereby enhancing prompt intervention and improving prognosis.

Soil salinization is one of the primary factors contributing to land degradation in arid areas, severely restricting the sustainable development of agriculture and the economy. Satellite remote sensing is essential for real-time, large-scale soil salinity content (SSC) evaluation. However, some satellite images have low temporal resolution and are affected by weather conditions, leading to the absence of satellite images synchronized with ground observations. Additionally, some high-temporal-resolution satellite images have overly coarse spatial resolution compared to ground features. Therefore, the limitations of these spatiotemporal features may affect the accuracy of SSC evaluation. This study focuses on the arable land in the Manas River Basin, located in the arid areas of northwest China, to explore the potential of integrated spatiotemporal data fusion and deep learning algorithms for evaluating SSC. We used the flexible spatiotemporal data fusion (FSDAF) model to merge Landsat and MODIS images, obtaining satellite fused images synchronized with ground sampling times. Using support vector regression (SVR), random forest (RF), and convolutional neural network (CNN) models, we evaluated the differences in SSC evaluation results between synchronized and unsynchronized satellite images with ground sampling times. The results showed that the FSDAF model’s fused image was highly similar to the original image in spectral reflectance, with a coefficient of determination (R2) exceeding 0.8 and a root mean square error (RMSE) below 0.029. This model effectively compensates for the missing fine-resolution satellite images synchronized with ground sampling times. The optimal salinity indices for evaluating the SSC of arable land in arid areas are S3, S5, SI, SI1, SI3, SI4, and Int1. These indices show a high correlation with SSC based on both synchronized and unsynchronized satellite images with ground sampling times. SSC evaluation models based on synchronized satellite images with ground sampling times were more accurate than those based on unsynchronized images. This indicates that synchronizing satellite images with ground sampling times significantly impacts SSC evaluation accuracy. Among the three models, the CNN model demonstrates the highest predictive accuracy in SSC evaluation based on synchronized and unsynchronized satellite images with ground sampling times, indicating its significant potential in image prediction. The optimal evaluation scheme is the CNN model based on satellite image synchronized with ground sampling times, with an R2 of 0.767 and an RMSE of 1.677 g·kg−1. Therefore, we proposed a framework for integrated spatiotemporal data fusion and CNN algorithms for evaluating soil salinity, which improves the accuracy of soil salinity evaluation. The results provide a valuable reference for the real-time, rapid, and accurate evaluation of soil salinity of arable land in arid areas.

Macrophages, known for their phenotypic plasticity, play a critical role in maintaining homeostasis and inflammation-related pathogenesis. Although identifying diverse macrophage phenotypes holds promise for enhancing diagnoses and treatments of diseases mediated by macrophages, existing methodologies for differentiating macrophages often lack precision. They are limited by the cumbersome procedures that require large-scale equipment, such as flow cytometry and transcriptomic analysis. In this context, we have engineered fluorescent polyadenine (polyA)-mediated sticky flares that enable practical visualization of macrophages. This technology facilitates the highly sensitive detection of macrophage phenotypes through the specific recognition of intracellular mRNAs, permitting in situ imaging. Our approach demonstrates the potential for determining macrophage polarization status at the single-cell level within dynamic immune microenvironments, thereby providing crucial diagnostic and prognostic information that could guide the development of tailored treatments for macrophage-related diseases in personalized medicine.

Abstract Aim To investigate the relationship between chemoresistance in pancreatic cancer patients receiving postoperative gemcitabine adjuvant therapy and specific clinical/pathological characteristics, as well as its impact on patient prognosis. Methods From June 2018 to June 2021, clinical and pathological data of 148 pancreatic cancer patients were collected, and 101 patients were followed up for tumor recurrence/metastasis and survival status. The correlation between chemoresistance and specific clinical/pathological characteristics or patient prognosis was retrospectively analyzed. Results Of the 148 patients, 78 were in the chemoresistance group and 70 in the non‐chemoresistance group. Univariate analysis showed that the development of chemoresistance may be related to patient age, combined diabetes, preoperative CA19‐9 level, tumor size, AJCC stage, vascular invasion, and positive lymph node ratio. Furthermore, subsequent multivariate analysis incorporating these variables indicated that tumor size may be a key factor influencing chemoresistance (p 3 cm). Conclusions Patients with pancreatic cancer receiving postoperative gemcitabine adjuvant therapy are more likely to develop chemoresistance when their tumor sizes are larger (diameter >3 cm). Development of chemoresistance exacerbates the prognosis of patients with pancreatic cancer, and larger tumor size is also a risk factor for poor prognosis in these patients.

Abstract Major cereal crops have benefitted from Green Revolution traits such as shorter and more compact plants that permit high-density planting, but soybean has remained relatively overlooked. To balance ideal soybean yield with plant height under dense planting, shortening of internodes without reducing the number of nodes and pods is desired. Here, we characterized a short-internode soybean mutant, reduced internode 1 (rin1). Partial loss of SUPPRESSOR OF PHYA 105 3a (SPA3a) underlies rin1. RIN1 physically interacts with two homologs of ELONGATED HYPOCOTYL 5 (HY5), STF1 and STF2, to promote their degradation. RIN1 regulates gibberellin metabolism to control internode development through a STF1/STF2–GA2ox7 regulatory module. In field trials, rin1 significantly enhances grain yield under high-density planting conditions comparing to its wild type of elite cultivar. rin1 mutants therefore could serve as valuable resources for improving grain yield under high-density cultivation and in soybean–maize intercropping systems.

Abstract Background This study seeks to assess the utility of T1 and T2 mapping in distinguishing metastatic lymph nodes from reactive lymphadenopathy in patients with head and neck squamous cell carcinoma (HNSCC), using diffusion-weighted imaging (DWI) as a comparison. Methods Between July 2017 and November 2019, 46 HNSCC patients underwent neck MRI inclusive of T1 and T2 mapping and DWI. Quantitative measurements derived from preoperative T1 and T2 mapping and DWI of metastatic and non-metastatic lymph nodes were compared using independent samples t-test or Mann–Whitney U test. Receiver operating characteristic curves and the DeLong test were employed to determine the most effective diagnostic methodology. Results We examined a total of 122 lymph nodes, 45 (36.9%) of which were metastatic proven by pathology. Mean T2 values for metastatic lymph nodes were significantly lower than those for benign lymph nodes (p

C-reactive protein (CRP) is a potential biomarker for evaluating inflammatory responses in patients receiving coronary artery bypass graft surgery. Here, the authors depict a sensitive and reliable colorimetric approach for CRP analysis. In this method, an aptamer specifically binds with CRP and an initiator sequence is released from an arch probe to activate signal amplification. The released initiator sequence hybridizes with the toehold section in the ‘jellyfish’ probe to form a blunt terminus to induce exonuclease III-assisted signal amplification. The method exhibited a low limit of detection of 1.32 ng/ml and high intraday and interday precision for CRP detection. In summary, this colorimetric approach may provide a potential alternative tool for the evaluation of inflammation in patients receiving coronary artery bypass graft and clinical diagnostics of disease.

Water availability is an important issue all over the world, and membrane filtration technology is one of the most effective measures for remediation. As a sustainable and renewable biomass material, natural wood has a hierarchical and three-dimensional interconnected microstructure, which provides an alternative for water filter design. Longitudinal filtration could take advantage of the micropores, while the treatment speed is severely limited. This study examined a wood filter in which muddy wastewater can be transported into the microchannels and out of the vertically stacked micropores. The filter takes full advantage of the pores present in the wood without sacrificing the speed of hydraulic flow within the main transport channels, exhibiting excellent performance for mud removal. In this manner, water flux, decolorization, and turbidity are highly dependent on the groove number, groove depth, and thickness of the filter. Due to the reorientation of the water transport pathways, the clogging of micropores could be easily alleviated, thus promoting the filter lifecycle. The design of the cross-flow wood filter can provide an available platform for various wastewater treatment cases with different impurities, displaying an application prospect in the wastewater treatment field.

ObjectivesTo investigate and compare the associated factors of depression, anxiety, and other psychological differences between patients with Corona Virus Disease 2019 quarantined in square cabin hospitals (SCH) and isolation wards (IW) in China.MethodsCluster sampling method was performed during Shanghai’s Two-Month Lockdown in 2022. Hospital Anxiety and Depression Scale Depression subscale (HADS-D), 7-tiem Generalized Anxiety Disorder Scale (GAD-7), Pittsburgh sleep quality index (PSQI), and Perceived Social Support Scale (PSSS) were used to investigate psychological differences.ResultsThe HADS-D and GAD-7 scores of SCH patients were significantly higher than those in IW (p < 0.001; p = 0.0295). Sleep latency (SCH-IW = -3.76, p < 0.001), sleep duration (SCH-IW = -2.22, p < 0.05), habitual sleep efficiency (SCH-IW = -4.11, p < 0.001), sleep disturbance (SCH-IW = -3.59, p < 0.001) and use of sleep medication (SCH-IW = -5.18, p < 0.001) of SCH patients were significantly worse. Depression was the main emotional problem of quarantined patients. Patients in SCH had lower social support. Sleep disorders and the lowest oxygen saturation ≤ 93% were risk factors for depression, while social support and child status were protective factors. Myalgia and constipation were risk factors for anxiety, while marital status was the protective factor.ConclusionPatients quarantined in SCH had higher risks of depression and anxiety, lower sleep quality and social support. Somatic discomfort and sleep disorders exacerbated depression and anxiety, which could be ameliorated by social support and taken into consideration in future SCH construction.

Objective: To evaluate the image quality of low-dose temporal bone computed tomography (CT) in otitis media and mastoiditis patients by using deep learning reconstruction (DLR). Materials and methods: A total of ninety-seven temporal bones from 53 consecutive adult patients who had suspected otitis media and mastoiditis and underwent temporal bone CT were prospectively enrolled. All patients underwent high resolution CT protocol (group A) and an additional low-dose protocol (group B). In group A, high resolution data were reconstructed by filter back projection (FBP). In group B, low-dose data were reconstructed by DLR mild (B1), DLR standard (B2) and DLR strong (B3). The objective image quality was analyzed by measuring the CT value and image noise on the transverse image and calculating the signal-to-noise ratio (SNR) on incudomallear joint, retroauricular muscle, vestibule and subcutaneous fat. Subjective image quality was analyzed by using a five-point scale to evaluate nine anatomical structures of middle and inner ear. The number of temporal bone lesions which involved in five structures of middle ear were assessed in group A, B1, B2 and B3 images. Results: There were no significant differences in the CT values of the four reconstruction methods at four structures (all p > 0.05). The DLR group B1, B2 and B3 had significantly less image noise and a significantly higher SNR than group A at four structures (all p 0.05), however, the group B3 had lower subjective image quality than group A in modiolus, spiral osseous lamina and stapes (all p 0.05), however, the number of temporal bone lesions which involved in mastoid for group B3 images were significantly more than group A (p

Flowering time is a key agronomic trait that directly affect the adaptation and yield of soybean. After whole genome duplications, about 75% of genes being represented by multiple copies in soybean. There are four TERMINAL FLOWER 1 (TFL1) genes in soybean, and the TFL1b (Dt1) has been characterized as the determinant of stem growth habit. The function of other TFL1 homologs in soybean is still unclear. Here, we generated knockout mutants by CRISPR/Cas9 genome editing technology and found that the tfl1c/tfl1d double mutants flowered significantly earlier than wild-type plants. We investigated that TFL1c and TFL1d could physically interact with the bZIP transcription factor FDc1 and bind to the promoter of APETALA1a (AP1a). RNA-seq and qRT-PCR analyses indicated that TFL1c and TFL1d repressed the expressions of the four AP1 homologs and delayed the flowering time in soybean. The two genes play important roles in the regulation of flowering time in soybean and mainly act as the flowering inhibitors under long-day conditions. Our results identify novel components in the flowering-time regulation network of soybean and will be invaluable for molecular breeding of improved soybean yield.

Abstract Background Castration-resistant prostate cancer (CRPC) is currently the main challenge for prostate cancer (PCa) treatment, and there is an urgent need to find novel therapeutic targets and drugs. Prohibitin (PHB1) is a multifunctional chaperone/scaffold protein that is upregulated in various cancers and plays a pro-cancer role. FL3 is a synthetic flavagline drug that inhibits cancer cell proliferation by targeting PHB1. However, the biological functions of PHB1 in CRPC and the effect of FL3 on CRPC cells remain to be explored. Methods Several public datasets were used to analyze the association between the expression level of PHB1 and PCa progression as well as outcome in PCa patients. The expression of PHB1 in human PCa specimens and PCa cell lines was examined by immunohistochemistry (IHC), qRT-PCR, and Western blot. The biological roles of PHB1 in castration resistance and underlying mechanisms were investigated by gain/loss-of-function analyses. Next, in vitro and in vivo experiments were conducted to investigate the anti-cancer effects of FL3 on CRPC cells as well as the underlying mechanisms. Results PHB1 expression was significantly upregulated in CRPC and was associated with poor prognosis. PHB1 promoted castration resistance of PCa cells under androgen deprivation condition. PHB1 is an androgen receptor (AR) suppressive gene, and androgen deprivation promoted the PHB1 expression and its nucleus-cytoplasmic translocation. FL3, alone or combined with the second-generation anti-androgen Enzalutamide (ENZ), suppressed CRPC cells especially ENZ-sensitive CRPC cells both in vitro and in vivo. Mechanically, we demonstrated that FL3 promoted trafficking of PHB1 from plasma membrane and mitochondria to nucleus, which in turn inhibited AR signaling as well as MAPK signaling, yet promoted apoptosis in CRPC cells. Conclusion Our data indicated that PHB1 is aberrantly upregulated in CRPC and is involved in castration resistance, as well as providing a novel rational approach for treating ENZ-sensitive CRPC.

Background White matter hyperintensities (WMHs) are areas of increased signal intensity on T2‐weighted magnetic resonance imaging (MRI). WMH penumbra may be a potential target for early intervention in WMHs. We explored the relationship between angiogenesis and WMH penumbra in patients with WMHs. Methods and Results Twenty‐one patients with confluent WMHs of Fazekas grade ≥2 were included. All the participants underwent 68Ga‐NOTA‐PRGD2 positron emission tomography/magnetic resonance imaging. WMH penumbra was analyzed with masks created for the WMH and 7 normal‐appearing white matter layers; each layer was dilated away from the WMH by 2 mm. Angiogenesis array and ELISA were used to detect the serum levels of angiogenic factors, inflammatory factors, HIF‐1 alpha, and S100B. Fourteen patients with increased 68Ga‐NOTA‐PRGD2 maximum standardized uptake (>0.17) were classified into group 2. Seven patients with maximum standardized uptake ≤0.17 were classified as group 1. WMH volume and serum levels of integrin αvβ3, vascular endothelial growth factor receptor 22, and interleukin‐1β tended to be higher in group 2 than in group 1. In group 2, 68Ga‐NOTA‐PRGD2 uptake was significantly increased at the border between the WMH and normal‐appearing white matter than in WMHs (P=0.004). The structure penumbra, defined by fractional anisotropy, was wider in group 2 (8 mm) than in group 1 (2 mm). The cerebral blood flow penumbra was 12 mm in both groups. Angiogenesis showed a correlation with reduced cerebral blood flow and microstructure integrity. Conclusions Our study provides evidence that angiogenesis occurs in the WMH penumbra. Further studies are warranted to verify the effect of angiogenesis on WMH growth.

Background: Oral squamous cell carcinoma (OSCC) is one of the most common types of cancer worldwide. Although overall losses of 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) have been previously observed, a genome-wide, single-base-resolution, and simultaneous mapping of 5mC and 5hmC in OSCC is still unaccomplished. Similarly, the mechanism of how 5mC and 5hmC collectively lead to abnormal gene expression in OSCC is largely unexplored. Using parallel whole-genome bisulfite sequencing (WGBS) and whole-genome oxidative bisulfite sequencing (oxWGBS), we characterized 5mC- and 5hmC-profiles at single-nucleotide resolution in paired primary OSCC samples and their normal adjacent tissues (NATs). We also analyzed the effect of 5mC- and 5hmC-modifications on differential gene expression in OSCC using multi-omics analysis.Results: An overall reduction of both 5mC and 5hmC in various genomic regions have been observed in OSCC samples. At promoter regions, a total of 6,921 differentially methylated regions and 1,024 differentially hydroxymethylated regions were identified in OSCC. Interestingly, compared to bidirectional modification with 5mC and 5hmC, unidirectional modification with 5mC and 5hmC at the promoters is associated with bigger change in the gene expression. Additionally, genes bearing unidirectional modification with 5mC and 5hmC at the promoters are enriched in signaling pathways like cell proliferation, cell differentiation, and receptor tyrosine kinase pathway that are essential for the tumorigenesis. Finally, the grouped expression signature of top 20 genes bearing promoter-unidirectional-modification with 5mC and 5hmC tends to correlate with the clinical outcome of certain subtypes of head and neck squamous cell carcinoma.Conclusion: Using parallel WGBS and oxWGBS analyses, we observed an overall reduction of 5mC- and 5hmC-modifications at various genomic regions in OSCC. Unidirectional modification with 5mC and 5hmC at the promoters is associated with enhanced changes in gene expression in OSCC tissues. Furthermore, such differentially expressed genes bearing unidirectional modifications with 5mC and 5hmC at the promoters might have clinical relevance to the outcome of OSCC.

Abstract Since the discovery of conducting polyacetylene in the 1970s, intrinsically conducting polymers (ICPs) have attracted great attention because of their interesting structure, properties, and applications. Notably different from conventional conductors such as metals and doped semiconductors, ICPs have high mechanical flexibility and are light weight. In addition, their properties can be easily tuned by controlling the doping level, modifying the chemical structure, or forming composites with organic or inorganic materials. Their application in bioelectronics is particularly interesting because they have good biocompatibility and good mechanical matching with biological tissues. In this article, the methods to increase the mechanical stretchability of ICPs are first reviewed because high stretchability is often required for bioelectronic applications while pristine ICPs generally have limited stretchability. The application of ICPs as stretchable electrodes for epidermal biopotential detection and neural interfaces is discussed. Then, the employment of ICPs as the electrodes or sensing material of mechanical sensors is reviewed. They also have important application in controllable drug delivery. Last, their applications in the wearable energy harvesting and storage devices including thermoelectric generators and supercapacitors are also covered.

Abstract Intramuscular injection of anemoside B4 (AB4) has a superior therapeutic effect on clinical mastitis in lactating cows. Here, we explored AB4’s effect on milk whey in clinical mastitis-affected cows using proteomics. Among fifty clinical mastitis cows received AB4 administration (0.05 ml/kg/day, for 7 days), twelve healed cows were selected and marked as group T. Twelve clinically heathy cows received the same dose of saline for 7 days, marked as group C. Collected milk whey of group T before and after AB4 administration marked as T1 and T2, respectively. The milk whey of group C after saline injection marked as C1. Milk whey protein changes were detected using tandem mass tag-based quantitative proteomic. We identified 872 quantifiable proteins in the samples. Among them, 511 proteins between T1 and C1, and 361 proteins between T2 and T1 were significantly altered. T1 than C1 had significantly more proteins associated with inflammatory damage and trans-endothelial migration of leukocytes, whereas these proteins were reduced in T2 treated with AB4. Compared with C, proteins associated with fibrin clot degradation and complement system activation were downregulated in T1 but upregulated in T2. In summary, AB4 can exert its therapeutic effect on clinical mastitis in cows mainly by reducing inflammatory damage, activating the complement system, inhibiting trans-endothelial migration of leukocytes, and promoting degradation of milk fibrin clots.

Abstract Background The purpose of this study was to introduce a modified lateral approach for combined radical resection of buccal squamous cell carcinoma (BSCC) and evaluate its surgical, oncological, functional, and aesthetic outcomes in comparison with the conventional lower-lip splitting approach. Methods This single-center study retrospectively reviewed 80 patients with BSCC, of which 37 underwent the lateral approach and 43 underwent the conventional approach. Surgical, functional, oncological, and aesthetic evaluations, as well as follow-ups, were recorded and compared. Results Compared to the conventional approach group, the lateral approach group had a longer surgical time (P = 0.000), but there was no significant difference in other surgical and oncological parameters. Moreover, the scar in the head and neck had a significantly discreet appearance in the lateral approach group, whose satisfaction was better than those in the conventional approach group (P = 0.000). Other oral function parameters, postoperative mouth-opening, and 3-year survival rate were not significantly different between the two groups. Conclusion The lateral approach could provide superior aesthetic results while maintaining equal surgical, functional, and oncological outcomes compared to the conventional approach for radical resection of BSCC.

ABSTRACT Disturbance of commensal intestinal microbiota is related to chronic inflammatory dermatosis. We analyzed the diversity of the gut microbiota to characterize the biological variation of psoriasis (Ps). Significant differences of gut microbiome profiles were revealed in murine model with psoriasis by sequencing 16S rRNA V3-V4 variable region. Group comparisons included the imiquimod cream (IMQ group, n=8), the imiquimod cream and antibiotics (ATB) (PC+IMQ group, n=8) and the healthy control (CTRL group, n=8). The gut microbiota existed in Ps groups including IMQ group and PC+IMQ group encompassed less diversity than controls, which were attributed to decreased presence of several taxa. The two Ps groups were characterized by significant reduction in firmicutes. In this study, microbiota of psoriasis was defined by an increase presence of Bacteroides. After treated with ATB, we found substantial increase of Lactobacillales but significant decrease of Clostridiales and Coriobacteriales. Relative lower abundance of multiple intestinal bacteria was observed in Ps groups. Although part of genera were concomitantly reduced in both IMQ and PC+IMQ conditions, we discovered the specialty of PC+IMQ group samples was that contained lower abundance of beneficial taxa. Characteristics of gut microbiota profiles in Ps mice were comparable to profiles in patients with Ps, which were related to alteration of specific inflammatory proteins in disease groups but were significantly different from control group. Thus, this study emphasizes the role of intestinal microbiota in the pathogenesis of Ps and provides new insight for investigating association between intestinal microbes and immune inflammation.

AimsTo explore the clinical characteristics of patients with symptomatic duodenal diverticula and to generalize how to make appropriate treatment choices for this group of patients.Materials and methodsFrom January 2010 to September 2020, a total of 647 patients with duodenal diverticula (DD) were included in this study. 345 of them with relevant symptoms were divided into the symptomatic group and the other 302 patients were in the asymptomatic group.ResultsAmong all patients, most DD were located in the periampullary area,

BackgroundMarital status is a robust sociodemographic predictor of sleep. Having to live apart from spouse may have different implications than those of cohabitants or singles, especially in military personnel. Further research on this group will help provide knowledge in advance and facilitate early targeted interventions.MethodsAn online questionnaire study was conducted from July to November 2021. A total of 1,832 male military personnel completed the questionnaire. The marital status was measured by a self-reported single choice question. Pittsburgh sleep quality index (PSQI), Epworth Sleepiness Scale (ESS) and The Dysfunctional Beliefs and Attitudes about sleep scale (DBAS-16) were used to measure sleep-related outcomes. Inverse probability weighting (IPW) was applied to reduce the effects of confounding. Logistic regression was used to analyze the relationship between marital status and sleep and explore the impact of living together or not.ResultsAfter inverse probability weighting, the prevalence of poor sleep quality, sleepiness and dysfunctional beliefs were 16.1, 20.1 and 7.1%, respectively. One-way ANOVA results for the means of both groups were statistically significantly different, except for the sleep latency and sleep disturbance dimensions of PSQI. Participants who were married were more likely to have poor sleep quality (OR: 1.408, 95% CI: [1.10, 1.80]), to have daytime sleepiness (OR: 1.560, 95% CI: [1.27, 1.92]) and to develop dysfunctional beliefs and attitudes (OR: 2.497, 95% CI: [1.65, 3.80]) than those who were unmarried. Further analysis showed that the odds of developing poor sleep quality and DBAS in participants who married but living apart were significantly bigger than those unmarried (OR: 1.548 and 3.991, respectively.), while there were no significant differences in the odds of daytime sleepiness (OR: 0.738, p = 0.050). Age was a protective factor for the development of bad sleep outcomes, while family economic was an independent risk factor.ConclusionMarital status appear important for sleep quality, daytime sleepiness and sleep beliefs. The effect of living apart or not should be considered separately as an important predictor of sleep.

Objectives Cellular senescence is strongly associated with fibrosis and tumorigenesis. However, whether the epithelium of oral submucous fibrosis (OSF) undergoes premature senescence remains unclear. This study investigates the roles of senescent epithelial cells in OSF. Methods The immunohistochemistry and Sudan black B staining were performed to identify epithelium senescence in OSF tissues. Arecoline was used to induce human oral keratinocytes (HOKs) senescence. The cell morphology, senescence-associated β galactosidase activity, cell counting Kit 8, immunofluorescence, quantitative real-time PCR, and western blot assay were used to identification of senescent HOKs. The enzyme-linked immunosorbent assay was exerted to evaluate the levels of transforming growth factor β1 (TGF-β1) in the supernatants of HOKs treated with or without arecoline. Results The senescence-associated markers, p16 and p21, were overexpressed in OSF epithelium. These expressions were correlated with alpha-smooth actin (α-SMA) positively and proliferating cell nuclear antigen (PCNA) negatively. Moreover, Sudan black staining showed that there was more lipofuscin in OSF epithelium. In vitro, HOKs treated with arecoline showed senescence-associated characteristics including enlarged and flattened morphology, senescence-associated β galactosidase staining, cell growth arrest, γH2A.X foci, upregulation of p53, p21, and TGF-β1 protein levels. Moreover, senescent HOKs secreted more TGF-β1. Conclusions Senescent epithelial cells are involved in OSF progression and may become a promising target for OSF treatment.

Objective: To investigate the correlation between parameters of PET/MR and the expression level of epidermal growth factor receptor (EGFR) in head and neck squamous cell carcinoma (HNSCC) and to evaluate diagnostic efficacy of independent and combined PET/MR parameters for the expression level of EGFR. Materials and methods: 21 patients who had undergone PET/MR and been proven HNSCC pathologically were included in this retrospective study. The PET/MR sequences included 18-flurodeoxyglucose (18F-FDG) PET, T1, T2-weighted imaging, DWI, ADC and DCE. Parameters including ADCmean from DWI, Ktrans, Ve, Kep from DCE, and SUVmean, SUVmax from PET were obtained. Immunohistochemical method was used to detect the expression level of EGFR. The associations between parameters of PET/MR and EGFR expression level were analyzed by Spearman's analysis. Logistic regression was utilized to establish the diagnostic model of EGFR expression level with PET/MR parameters. The efficacy of the independent and combined diagnostic model for EGFR expression level in HNSCC was analyzed by ROC curve. P value ≤ 0.05 was considered statistically significant. Results: (1) Expression level of EGFR was correlated to SUVmean with correlation coefficient of 0.47 (p = 0.05). (2) There was significant difference of SUVmean between the EGFR high- and low-expression groups (p = 0.02). (3) Combination of PET/MR improved the diagnostic efficacy for expression level of EGFR, with AUC = 0.93. Conclusion: There were different degrees of correlation between PET/MR parameters and EGFR expression level in HNSCC. Combination of PET/MR might improve diagnostic efficacy of EGFR expression level.