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Abstract Epithelial ovarian cancer (EOC) is a deadly disease with limited diagnostic biomarkers and therapeutic targets. Here we conduct a comprehensive proteomic profiling of ovarian tissue and plasma samples from 813 patients with different histotypes and therapeutic regimens, covering the expression of 10,715 proteins. We identify eight proteins associated with tumor malignancy in the tissue specimens, which are further validated as potential circulating biomarkers in plasma. Targeted proteomics assays are developed for 12 tissue proteins and 7 blood proteins, and machine learning models are constructed to predict one-year recurrence, which are validated in an independent cohort. These findings contribute to the understanding of EOC pathogenesis and provide potential biomarkers for early detection and monitoring of the disease. Additionally, by integrating mutation analysis with proteomic data, we identify multiple proteins related to DNA damage in recurrent resistant tumors, shedding light on the molecular mechanisms underlying treatment resistance. This study provides a multi-histotype proteomic landscape of EOC, advancing our knowledge for improved diagnosis and treatment strategies.

Abstract To non‐destructively resolve and diagnose the degradation mechanisms of lithium‐ion batteries (LIBs), it is necessary to cross‐scale decouple complex kinetic processes through the distribution of relaxation times (DRT). However, LIBs with low interfacial impedance render DRT unreliable without data processing and closed‐loop validation. This study proposes a hierarchical analytical framework to enhance timescale resolution and reduce uncertainty, including interfacial impedance reconstruction and multi‐dimensional DRT analysis. Interfacial impedance is reconstructed by eliminating simulated inductive and diffusive impedance based on a high‐fidelity frequency‐domain model. Multi‐dimensional DRT decouples solid electrolyte interphase (SEI) and charge transfer (CT) processes by the reversibility of electrochemical reactions with state of charge (SOC) to characterize electrode kinetic evolution driven by SOC and temperature through timescales and peak area. The findings reveal that reconstructed impedance improves the accuracy of identified time constants by ≈20%. Cross‐scale DRT results reveal that SOCs below 10% at 25 °C effectively distinguish electrode kinetics due to the high correlation between cathodic CT and SOC. Kinetic metrics characterize that anodic SEI or CT are different control steps limiting the low‐temperature performance of different cells. This work underscores the potential of the proposed framework for non‐destructive diagnostics of kinetic evolution.

Abstract Background Highly resilient adolescents with type 1 diabetes have been proved to achieve within-target glycemic outcomes and experience high quality of life. The ecological resilience model for adolescents with type 1 diabetes was developed in this study. It aims to increase our understanding of how resilience is both positively and negatively affected by internal and environmental ecological factors. Methods This cross-sectional study surveyed 460 adolescents with type 1 diabetes from 36 cities in 11 provinces, China. Participants completed self-report questionnaires on resilience, family functioning, peer support, peer stress, coping style, and demographics. Standard glycated hemoglobin tests were performed on the adolescents. Structural equation modeling was applied to analyze the data. Results The ecological resilience model for adolescents with type 1 diabetes was a good model with a high level of variance in resilience (62%). Family functioning was the most important predictor of resilience, followed by peer support, positive coping, and peer stress. Moreover, positive coping was the mediator of the relationship between family functioning and resilience. Positive coping and peer stress co-mediated the association between peer support and resilience. Conclusions Family functioning, peer relationships, and positive coping are interrelated, which may jointly influence resilience. The findings provide a theoretical basis for developing resilience-promotion interventions for adolescents with type 1 diabetes, which may lead to health improvements during a vulnerable developmental period.

Abstract Background Adolescents with type 1 diabetes mellitus suffer from diabetes distress and poor health-related quality of life (HRQOL) since living with the condition that differentiates them from their peers. The present study investigated the effects of peer support and stress on diabetes distress and HRQOL and whether positive coping mediated the effects. Methods We used a prospective study design. A total of 201 adolescents with type 1 diabetes mellitus from 20 cities in 4 provinces were recruited.Participants complete two separate surveys at approximately 18-month intervals. The scales employed at both Time 1 and Time 2 included the Diabetes-Specific Peer Support Measure, Diabetes Stress Questionnaire for Youths, Simplified Coping Style Questionnaire, 5-item Problem Areas in Diabetes Scale, and the Diabetes Quality of Life for Youth scale. Results Baseline peer stress directly predicted diabetes distress and HRQOL at 18 months, even controlling for age, gender, and peer support. However, the direct effect of baseline peer support on 18-month diabetes distress and HRQOL was insignificant. Baseline peer support indirectly affected diabetes distress and HRQOL at 18 months through positive coping, indicating that positive coping plays a mediating role. Conclusion The findings suggest that peer social relationships, especially peer stress, and positive coping are promising intervention targets for adolescents facing challenges in psychosocial adaptation.

Summary: This study investigated host responses to long COVID by following up with 89 of the original 144 cohorts for 1-year (N = 73) and 2-year visits (N = 57). Pulmonary long COVID, characterized by fibrous stripes, was observed in 8.7% and 17.8% of patients at the 1-year and 2-year revisits, respectively, while renal long COVID was present in 15.2% and 23.9% of patients, respectively. Pulmonary and renal long COVID at 1-year revisit was predicted using a machine learning model based on clinical and multi-omics data collected during the first month of the disease with an accuracy of 87.5%. Proteomics revealed that lung fibrous stripes were associated with consistent down-regulation of surfactant-associated protein B in the sera, while renal long COVID could be linked to the inhibition of urinary protein expression. This study provides a longitudinal view of the clinical and molecular landscape of COVID-19 and presents a predictive model for pulmonary and renal long COVID.

IntroductionVariability in microbial residues within soil aggregates are becoming progressively essential to the nutritive and sustainability of soils, and are therefore broadly regarded as an indispensable part of soil organic matter. It is unexplored how the widespread implementation of microbial fertilisers in agricultural production impacts soil organic nutrients, in particular the microbial residue fraction.MethodsWe performed a three-year field experiment to verify the distinct impacts of microbial and organic fertilizers on carbon accumulation in soil microbial leftovers among aggregate fractions.ResultsMicrobial residual carbon was shown to decrease insignificantly during the application of microbial fertilizer and to rise marginally afterwards with the utilization of organic fertilizer. However, the combined effects of the two fertilizers had substantial impacts on the accumulation of microbial residual carbon. Changes in the structure of the fungi and bacteria shown in this study have implications for the short-term potential of microbial fertilizer shortages to permanent soil carbon sequestration. Additionally, our findings revealed variations in microbial residue accumulation across the microbial fertilizers, with Azotobacter chroococcum fertilizer being preferable to Bacillus mucilaginosus fertilizer due to its higher efficiency. In this scenario of nutrient addition, fungal residues may serve as the primary binding component or focal point for the production of new microaggregates, since the quantity of SOC provided by fungal residues increased while that supplied by bacterial residues decreased.DiscussionOur findings collectively suggested that the mechanisms behind the observed bacterial and fungal MRC (microbial residue carbon) responses to microbial fertilizer or organic fertilizer in bamboo forest soils are likely to be distinct. The application of microbial fertilizers for a limited duration led to a decline soil stable carbon pool, potentially influencing the regulation of soil nutrients in such hilly bamboo forests.

Immunotherapy has emerged as the primary treatment modality for patients with advanced Hepatocellular carcinoma (HCC). However, its clinical efficacy remains limited, benefiting only a subset of patients, while most exhibit immune tolerance and face a grim prognosis. The infiltration of immune cells plays a pivotal role in tumor initiation and progression. In this study, we conducted an analysis of immune cell infiltration patterns in HCC patients and observed a substantial proportion of CD8+T cells. Leveraging the weighted gene co-expression network analysis (WGCNA), we identified 235 genes associated with CD8+T cell and constructed a risk prediction model. In this model, HCC patients were stratified into a high-risk and low-risk group. Patients in the high-risk group exhibited a lower survival rate, predominantly presented with intermediate to advanced stages of cancer, displayed compromised immune function, showed limited responsiveness to immunotherapy, and demonstrated elevated expression levels of the Notch signaling pathway. Further examination of clinical samples demonstrated an upregulation of the Notch1+CD8+T cell exhaustion phenotype accompanied by impaired cytotoxicity and cytokine secretion functions that worsened with increasing Notch activation levels. Our study not only presents a prognostic model but also highlights the crucial involvement of the Notch pathway in CD8+T cell exhaustion—a potential target for future immunotherapeutic interventions.

Background Prediabetes leads to declines in physical function in older adults, but the impact of prediabetes progression or regression on physical function is unknown. This study assessed this longitudinal association, with physical function objectivelymeasured by grip strength, walking speed, and standing balance, based on the Health and Retirement Study enrolling United States adults aged >50 years. Methods Participants with prediabetes were followed-up for 4-year to ascertain prediabetes status alteration (maintained, regressed, or progressed), and another 4-year to assess their impacts on physical function. Weak grip strength was defined as

High‐grade serous ovarian carcinoma (HGSOC) is the most common subtype of ovarian cancer with 5‐year survival rates below 40%. Neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS) is recommended for patients with advanced‐stage HGSOC unsuitable for primary debulking surgery (PDS). However, about 40% of patients receiving this treatment exhibited chemoresistance of uncertain molecular mechanisms and predictability. Here, we built a high‐quality ovary‐specific spectral library containing 130 735 peptides and 10 696 proteins on Orbitrap instruments. Compared to a published DIA pan‐human spectral library (DPHL), this spectral library provides 10% more ovary‐specific and 3% more ovary‐enriched proteins. This library was then applied to analyze data‐independent acquisition (DIA) data of tissue samples from an HGSOC cohort treated with NACT, leading to 10 070 quantified proteins, which is 9.73% more than that with DPHL. We further established a six‐protein classifier by parallel reaction monitoring (PRM) to effectively predict the resistance to additional chemotherapy after IDS (Log‐rank test, P = 0.002). The classifier was validated with 57 patients from an independent clinical center (P = 0.014). Thus, we have developed an ovary‐specific spectral library for targeted proteome analysis, and propose a six‐protein classifier that could potentially predict chemoresistance in HGSOC patients after NACT‐IDS treatment.

Background: /purpose: The quality of the hybrid layer is of great importance for dentin bonding. The purpose of this study was to develop a novel copper-based pretreatment and investigate the effect of the pretreatment combined with universal adhesives on the dentin bond strength. Materials and methods: Etch-and-rinse adhesive Single Bond 2 (SB2) and two universal adhesives Prime Bond Universal (PBU) and Single Bond Universal (SBU) were selected. The dentin surfaces were pretreated with CuSO4 solution and K2HPO4 solution in turn (Cu–P pretreatment), and the adhesive was applied following the manufacturer's instructions. There were four groups of Cu–P pretreatment: HH-Cu (1.5 mol/L CuSO4 + 1.0 mol/L K2HPO4); H–Cu (0.15 mol/L CuSO4 + 0.1 mol/L K2HPO4); L-Cu (0.015 mol/L CuSO4 + 0.01 mol/L K2HPO4); and LL-Cu (0.0015 mol/L CuSO4 + 0.001 mol/L K2HPO4). The microtensile bond strength (μ-TBS) and fracture mode were determined. The dentin surface after pretreatment and the antimicrobial properties of the pretreatment agent were also evaluated. Results: The minimum inhibitory concentration and minimum bactericidal concentration of Cu–P pretreatment were 0.012 mol/L CuSO4 + 0.008 mol/L K2HPO4. Combined with SB2, the H–Cu and L-Cu groups showed a higher μ-TBS (P

Key Clinical Message The second distobuccal canal in the maxillary first molar is often missed because of the low prevalence rate (0%–4%). The article reports this kind of variation in one case. Promising outcomes have continued up to the present (2‐year follow‐up).

Integrating genetic information with circulating proteomics can help understand mechanisms of disease. Here, the authors conduct genome-wide association analyses of the serum proteome in 2,958 Han Chinese individuals, uncovering proteins which may contribute to ancestry differences in cardiometabolic disease susceptibility.

Lipase-catalyzed stereoselective resolution of cis-(±)-dimethyl 1-acetylpiperidine-2,3-dicarboxylate (cis-(±)-1) is an attractive route for the synthesis of (S,S)-2,8-diazobicyclo[4.3.0]nonane, an important chiral intermediate of the fluoroquinolone antibiotic, moxifloxacin. In our previous study, a lipase from Sporisorium reilianum (SRL) was identified to possess excellent thermostability and pH stability. However, the low enzymatic activity of the SRL is a challenge that must be addressed. A rational design was initially employed for SRL tailoring according to the engineered Candida antarctica lipase B (CALB), resulting in a beneficial variant called SRL-I194N/V195L. Subsequently, two key amino acid residues in loop 6, L145 and L154, which might modulate the lid conformation between open and closed, were identified. A tetra-site variant, SRL-I194N/V195L/L145V/L154G (V13), with a significantly enhanced activity of 87.8 U∙mg−1 was obtained; this value was 2195-fold higher than that of wild-type SRL. Variant V13 was used to prepare optically pure (2S,3R)-dimethyl 1-acetylpiperidine-2,3-dicarboxylate ((2S,3R)-1), resolving 1 mol∙L−1 cis-(±)-1 with a conversion of 49.9% in 2 h and absolute stereoselectivity (E > 200). Excellent stability with a half-life of 92.5 h was also observed at 50 °C. Overall, the study findings reveal a lipase with high activity toward cis-(±)-1 at an industrial level and may offer a general strategy for enhancing the enzyme activity of other lipases and other classes of enzymes with a lid moiety.

Abstract Background Emotional expression has been suggested to affect the well-being of individuals with unintentional injuries. However, few studies have investigated it as a heterogeneous phenomenon. The purpose of this study was to characterize the patterns of emotional expression among patients with unintentional injuries using latent profile analysis, and to examine the relationship among these latent profiles and cognitive processing, posttraumatic growth, and posttraumatic stress disorder. Methods A cross-sectional study was carried out at two general hospitals in Wenzhou, China. In total, 352 patients with unintentional injuries completed the socio-demographic questionnaire, Berkeley Expressivity Questionnaire, Ambivalence Over Emotional Expression Questionnaire, Event-Related Rumination Inventory, the Posttraumatic Growth Inventory, and PTSD Checklist-Civilian Version. Results Three unique profiles were identified: high emotional expressivity (n = 238, 67.6%), moderate emotional expressivity (n = 45, 12.8%), and low emotional expressivity (n = 69, 19.6%). The ANOVA and chi-square tests demonstrated significant differences among the three groups concerning deliberate rumination and posttraumatic growth. Multinomial logistic regression analysis indicated that monthly income and time since injury significantly predicted profile membership. Conclusions Most patients showed high emotional expressivity after an unintentional injury. Emotional expression profiles were associated with deliberate rumination and posttraumatic growth. Emotional expression interventions tailored for different profiles are warranted after an unintentional injury.

Biodegradable suture anchors based on Mg-Nd-Zn-Zr alloy were developed for ligament-to-bone fixation in rotator cuff surgeries. The Mg alloy anchors were designed with structural features of narrow tooth and wide tooth, and simulated through finite element analysis (FEA). Meanwhile, the corrosion behaviors of the Mg alloy anchors were studied by immersion test and the mechanical properties were investigated by measuring the maximum torque and pull-out force. The simulation result showed that the wide-tooth anchor exhibited more a uniform stress distribution and lower shear stress in the torsion process, suggesting a satisfactory torsional resistance of this structure. Meanwhile, the wide-tooth anchor exhibited a lower Von-Mises stress after applying the same pull-out force in the simulation, indicating a higher resistance to pull-out failure of the anchor. The result of the immersion test indicated that the wide-tooth anchor exhibited a slightly slower corrosion rate in Hank’s solution after 14-day immersion, which was beneficial to enhance the structural and mechanical stability of the biodegradable suture anchor. Furthermore, the results of the mechanical properties test demonstrated that the wide-tooth anchor showed superior performance with higher maximum torques and axial pull-out forces before and after corrosion. More importantly, the axial pull-out force and maximum torque for the wide-tooth anchor decreased by 5.86% and 8.64% after corrosion, which were significantly less than those for the narrow-tooth anchor. Therefore, the wide-tooth suture anchor with lower corrosion rate, higher mechanical properties and structural stability is a promising candidate for ligament-bone fixation in the repair of rotator cuff injuries.

Abstract Determination of malignancy in thyroid nodules remains a major diagnostic challenge. Here we report the feasibility and clinical utility of developing an AI-defined protein-based biomarker panel for diagnostic classification of thyroid nodules: based initially on formalin-fixed paraffin-embedded (FFPE), and further refined for fine-needle aspiration (FNA) tissue specimens of minute amounts which pose technical challenges for other methods. We first developed a neural network model of 19 protein biomarkers based on the proteomes of 1724 FFPE thyroid tissue samples from a retrospective cohort. This classifier achieved over 91% accuracy in the discovery set for classifying malignant thyroid nodules. The classifier was externally validated by blinded analyses in a retrospective cohort of 288 nodules (89% accuracy; FFPE) and a prospective cohort of 294 FNA biopsies (85% accuracy) from twelve independent clinical centers. This study shows that integrating high-throughput proteomics and AI technology in multi-center retrospective and prospective clinical cohorts facilitates precise disease diagnosis which is otherwise difficult to achieve by other methods.

Abstract Little is known regarding why a subset of COVID-19 patients exhibited prolonged positivity of SARS-CoV-2 infection. Here, we found that patients with long viral RNA course (LC) exhibited prolonged high-level IgG antibodies and higher regulatory T (Treg) cell counts compared to those with short viral RNA course (SC) in terms of viral load. Longitudinal proteomics and metabolomics analyses of the patient sera uncovered that prolonged viral RNA shedding was associated with inhibition of the liver X receptor/retinoid X receptor (LXR/RXR) pathway, substantial suppression of diverse metabolites, activation of the complement system, suppressed cell migration, and enhanced viral replication. Furthermore, a ten-molecule learning model was established which could potentially predict viral RNA shedding period. In summary, this study uncovered enhanced inflammation and suppressed adaptive immunity in COVID-19 patients with prolonged viral RNA shedding, and proposed a multi-omic classifier for viral RNA shedding prediction.

Background Creatinine-to-cystatin C ratio is recently suggested to be a surrogate marker for sarcopenia. However, little is known about its association with diabetes. This study aimed to fill in this gap based on a large-scale prospective cohort. Methods A population-based representative sample of 5,055 participants aged ≥45 years from the China Health and Retirement Longitudinal Study was enrolled between 2011 and 2012 and followed at least once during the subsequent surveys at 2013, 2015, or 2018. Creatinine-to-cystatin C ratio was calculated and normalized by body weight. Incident diabetes was ascertained by plasma glucose, glycosylated hemoglobin, self-reported history, or use of anti-diabetic drugs. Logistic regression analysis and mediation analysis were employed. Results During follow-up, 634 participants developed diabetes. The risk of diabetes was gradually and significantly decreased with increased normalized creatinine–cystatin C ratio. The multivariable-adjusted odds ratio for diabetes was 0.91 (95% confidence interval, 0.83 to 0.99) per 1 standard deviation higher of normalized creatinine-to-cystatin C ratio, and this relationship remained significant after controlling for muscle strength. The risk reduction in diabetes was significantly larger in participants with normal-weight and high normalized creatinine-to-cystatin C ratio compared with those with overweight/obesity and high normalized creatinine-to-cystatin C ratio (Pinteraction=0.01). Insulin resistance and inflammation appeared to be key mediators accounting for the observed relationship between normalized creatinine-to-cystatin C ratio and risk of diabetes, with their mediating effect being 93.1% and 22.0%, respectively. Conclusion High normalized creatinine-to-cystatin C ratio is associated with reduced risk of diabetes in middle-aged and older adults.

A thermosensitive optoelectronic upconversion device based on integrated microscale LED and photodiode structures, with temperature dependent of spectral shift and intensity change.

Thyroid nodules occur in about 60% of the population. A major challenge in thyroid nodule diagnosis is to distinguish between follicular adenoma (FA) and carcinoma (FTC). Here, we present a comprehensive thyroid spectral library covering five types of thyroid tissues. This library includes 121 960 peptides and 9941 protein groups. This spectral library can be used to quantify up to 7863 proteins from thyroid tissues, and can also be used to develop parallel reaction monitoring (PRM) assays for targeted protein quantification. Next, to stratify follicular thyroid tumours, we compared the proteomes of 24 FA and 22 FTC samples, and identified 204 differentially expressed proteins (DEPs). Our data suggest altered ferroptosis pathways in malignant follicular carcinoma. In all, 31 selected proteins effectively distinguished follicular tumours. Of those DEPs, nine proteins were further verified by PRM in an independent cohort of 18 FA and 19 FTC. Together, we present a comprehensive spectral library for DIA and targeted proteomics analysis of thyroid tissue specimens, and identified nine proteins that could potentially distinguish FA and FTC.

Abstract Necrotizing enterocolitis (NEC) is a multifactorial and complex disease. Our knowledge of the cellular and genetic basis of NEC have expanded considerably as new molecular mechanisms have been identified. This article will focus on the current understanding of the molecular pathogenesis of NEC with a focus on the inflammatory, immune, infectious, and genetic mechanisms that drive disease development.

Abstract Background Prediabetes progression is associated with increased mortality while its regression decreases it. It is unclear whether muscle strength is related to prediabetes progression or regression. This study investigated the associations of muscle strength, assessed by grip strength and chair‐rising time, with prediabetes progression and regression based on the China Health and Retirement Longitudinal Study (CHARLS) enrolling middle‐aged and older adults. Methods We included 2623 participants with prediabetes from CHARLS, who were followed up 4 years later with blood samples collected for measuring fasting plasma glucose and haemoglobin A1c. Grip strength (normalized by body weight) and chair‐rising time were assessed at baseline and categorized into tertiles (low, middle, and high groups). Prediabetes at baseline and follow‐up was defined primarily using the American Diabetes Association (ADA) criteria and secondarily using the World Health Organization (WHO) and International Expert Committee (IEC) criteria. Multinomial logistic regression analysis was applied to obtain the odds ratios (ORs) and 95% confidence intervals (CIs). Results The mean age of included participants was 59.0 ± 8.6 years, and 46.6% of them were males. During follow‐up, 1646 participants remained as prediabetes, 379 progressed to diabetes, and 598 regressed to normoglycaemia based on ADA criteria. Participants who progressed to diabetes had lower normalized grip strength than those who remained as prediabetes (0.49 ± 0.15 vs. 0.53 ± 0.15, P

Simultaneous neural activation and inhibition in the same brain region of animals is highly desirable. Here the authors report a wireless, dual-colour optogenetic probe with the co-expression of two spectrally distinct opsins to allow for bidirectional neuronal activity manipulation in a rodent model.

Background/Aims Older adults are vulnerable to central obesity, while the association of changes in central fatness with risk of diabetes and metabolic control has not been investigated among this particular population. This study was aimed to address these issues. Methods A total of 1,815 adults aged ≥ 60 years without diabetes at baseline were followed for 4 years. Incident diabetes was ascertained based on plasma glucose, hemoglobin A1c, medical history, and/or the use of anti-diabetic drugs. Central fatness was assessed by waist circumference (WC), waist-height ratio (WHtR), and body roundness index (BRI). Logistic regression analyses were used to assess the association of changes in central fatness with risk of diabetes, along with dose-response and mediation analyses. Results During the 4-year follow-up, 177 participants developed diabetes. The risk of diabetes was increased by 42%, 41%, and 40% per 1 standard deviation increases in WC, WHtR, and BRI, respectively, in multivariable-adjusted models (all p < 0.01). Moreover, these relationships were all linearly-shaped (all pnonlinearity ≥ 0.11). Increases in WC, WHtR, and BRI correlated with increases in hemoglobin A1c, triglycerides-and-glucose index, triglycerides, white blood cell, and C-reactive protein (all p ≤ 0.04). Yet only changes in hemoglobin A1c and triglycerides-and-glucose index were identified as the possible mediators for risk of diabetes, with their mediating effect being about 35% and 21%, respectively. Conclusions Increases in central fatness were related to elevated risk of diabetes, and this association might be partly explained by the worsening of glycemic control and insulin resistance in older adults.

Aims. Metabolic syndrome (MetS) affects approximately one-third of the global population. Visit-to-visit variability of blood pressure (VVV-BP) constitutes a substantial risk factor for numerous chronic conditions. Thus, this study aimed to assess the relationship between VVV-BP and MetS and identify potential moderating factors between these. Methods. Data were obtained from the China Health and Retirement Longitudinal Study, a nationally representative study. Multiple logistic regression analyses were utilized to explore the association between VVV-BP and MetS while incorporating moderation analyses. MetS was defined according to the criteria outlined in the Joint Interim Statement. VVV-BP was expressed by the standard deviation, coefficient of variation, average real variability, and root mean square error. Results. Individuals with the highest levels of VVV of systolic blood pressure (SBP) exhibited a 70% increased risk of MetS compared to those with the lowest levels (OR = 1.70, 95% CI = 1.31–2.21). In addition, they had a 41% increased risk of VVV of diastolic blood pressure (DBP) (OR = 1.41, 95% CI = 1.09–1.81). Notably, weight change status significantly influenced the relationship between VVV-BP and MetS (Pinteraction = 0.01). Conclusions. VVV-BP is a significant contributor to the risk of developing MetS. Importantly, individuals who experienced weight loss during the follow-up period did not face a significantly higher risk of developing MetS.

Winter oil rapeseed ‘18 R-1’ (Brassica rapa L.) is a new variety that can survive in northern China where the extreme low temperature is −20 °C to −32 °C. It is different from traditional B. rapa and Brassica napus. In this study, the complete chloroplast (cp) genome of ‘18 R-1’ was sequenced and analyzed to assess the genetic relationship. The size of cp genome is 153,494 bp, including one large single copy (LSC) region of 83,280 bp and one small single copy (SSC) region of 17,776 bp, separated by two inverted repeat (IR) regions of 26,219 bp. The GC content of the whole genome is 36.35%, while those of LSC, SSC, and IR are 34.12%, 29.20%, and 42.32%, respectively. The cp genome encodes 132 genes, including 87 protein-coding genes, eight rRNA genes, and 37 tRNA genes. In repeat structure analysis, 288 simple sequence repeats (SSRs) were identified. Cp genome of ‘18 R-1’ was closely related to Brassica chinensis, B. rapa and Brassica pekinesis.

Abstract Background The polyene macrocyclic compound amphotericin B (AmB) is an important antifungal antibiotic for the clinical treatment of invasive fungal infections. To rationally guide the improvement of AmB production in the main producing strain Streptomyces nodosus, comparative metabolomics analysis was performed to investigate the intracellular metabolic changes in wild-type S. nodosus ZJB20140315 with low-yield AmB production and mutant S. nodosus ZJB2016050 with high-yield AmB production, the latter of which reached industrial criteria on a pilot scale. Results To investigate the relationship of intracellular metabolites, 7758 metabolites were identified in mutant S. nodosus and wildtype S. nodosus via LC–MS. Through analysis of metabolism, the level of 26 key metabolites that involved in carbon metabolism, fatty acids metabolism, amino acids metabolism, purine metabolism, folate biosynthesis and one carbon pool by folate were much higher in mutant S. nodosus. The enrichment of relevant metabolic pathways by gene overexpression strategy confirmed that one carbon pool by folate was the key metabolic pathway. Meanwhile, a recombinant strain with gene metH (methionine synthase) overexpressed showed 5.03 g/L AmB production within 120 h fermentation, which is 26.4% higher than that of the mutant strain. Conclusions These results demonstrated that comparative metabolomics analysis was an effective approach for the improvement of AmB production and could be applied for other industrially or clinically important compounds as well.

Inflammation is one of the main causes of impaired health in livestock and some of its processes weaken animal productivity and impact human health. The present study was conducted to evaluate the effect of echinacea extract (cichoric acid – CA) on yak peripheral blood mononuclear cells (PBMCs), inflammatory-related factors, and the toll-like receptor (TLR)4 signalling pathway induced by lipopolysaccharide (LPS) in these PBMCs.

ObjectiveEmergency patients are in severe and urgent condition. If the patient is obese, the traditional lumbar puncture method is more difficult. This study was to observe the comparison of ultrasound-guided and landmark-guided lumbar puncture for obese patients in the emergency department.MethodsSixty patients suspected of intracranial infection, subarachnoid hemorrhage, and intraventricular hemorrhage from January 2018 to June 2020 were selected in the Department of Emergency Medicine, Shengjing Hospital of China Medical University. They were randomly assigned to two groups according to the order of enrollment: Group A (Landmark-guided group, n = 30) and Group B (Ultrasound-guided group, n = 30). Follow-up assessments were performed to observe lumbar puncture time, the number of bloody CSF, Visual Analog Scale (VAS), the complications, and satisfaction.ResultsCompared with group A, group B had less lumbar puncture time, lower puncture attempts, and a higher first puncture success rate (P 0.05). Compared with group A, the postprocedural VAS in group B was lower, and the difference was statistically significant (P

BackgroundAlthough pediatric resilience plays a significant role in resisting negative moods and improving glycaemic control, little research exists regarding resilience among the parents of adolescents with Type 1 diabetes.ObjectiveTo investigate parental resilience's correlations with parental depressive symptoms, parental diabetes distress, and pediatric glycaemic control.MethodsThis cross-sectional study recruited adolescents with Type 1 diabetes and their parents from two hospitals. The parents completed questionnaires. The 10-item Connor-Davidson Resilience Scale measured resilience; the Problem Areas in Diabetes Survey-Parent Revised version measured diabetes distress; the Patient Health Questionnaire-9 measured depressive symptoms. Standard glycated hemoglobin tests were performed on the adolescents.ResultsData from 224 parents (77.2% female, Mage = 39.88 [SD = 5.02], age range = 30–56 years) of adolescents (50.9% boys, Mage = 13.54 years [SD = 2.48], age range = 10–19 years) were available. More than half (52.7%) of parents exceeded the criterion score for high resilience. Parental resilience was significantly negatively associated with parental depressive symptoms and diabetes distress. Parents from the high-resilience group reported fewer depressive symptoms than those from the low-resilience group. In multivariate regressions, greater parental resilience is consistently related to better pediatric glycaemic control beyond parental psychological risk factors.ConclusionsThis study highlights the importance of parental resilience for parental mental health and glycaemic control among adolescents with Type 1 diabetes. The appropriate resilience support programme might be developed for parents, especially for those existing depressive symptoms and diabetes distress.

To address the increasing need for detecting and validating protein biomarkers in clinical specimens, mass spectrometry (MS)-based targeted proteomic techniques, including the selected reaction monitoring (SRM), parallel reaction monitoring (PRM), and massively parallel data-independent acquisition (DIA), have been developed. For optimal performance, they require the fragment ion spectra of targeted peptides as prior knowledge. In this report, we describe a MS pipeline and spectral resource to support targeted proteomics studies for human tissue samples. To build the spectral resource, we integrated common open-source MS computational tools to assemble a freely accessible computational workflow based on Docker. We then applied the workflow to generate DPHL, a comprehensive DIA pan-human library, from 1096 data-dependent acquisition (DDA) MS raw files for 16 types of cancer samples. This extensive spectral resource was then applied to a proteomic study of 17 prostate cancer (PCa) patients. Thereafter, PRM validation was applied to a larger study of 57 PCa patients and the differential expression of three proteins in prostate tumor was validated. As a second application, the DPHL spectral resource was applied to a study consisting of plasma samples from 19 diffuse large B cell lymphoma (DLBCL) patients and 18 healthy control subjects. Differentially expressed proteins between DLBCL patients and healthy control subjects were detected by DIA-MS and confirmed by PRM. These data demonstrate that the DPHL supports DIA and PRM MS pipelines for robust protein biomarker discovery. DPHL is freely accessible at https://www.iprox.org/page/project.html?id=IPX0001400000.

Summary: Implantable devices and systems have been emerging as powerful tools for neuroscience research and medical applications. Here we report a wireless, dual-channel optoelectronic system for functional optogenetic interrogation of superior colliculus (SC), a layered structure pertinent to defensive behaviors, in rodents. Specifically, a flexible and injectable probe comprises two thin-film microscale light-emitting diodes (micro-LEDs) at different depths, providing spatially resolved optical illuminations within the tissue. Under remote control, these micro-LEDs interrogate the intermediate layer and the deep layer of the SC (ILSC and DLSC) of the same mice, and deterministically evoke distinct freezing and flight behaviors, respectively. Furthermore, the system allows synchronized optical stimulations in both regions, and we discover that the flight response dominates animals' behaviors in our experiments. In addition, c-Fos immunostaining results further elucidate the functional hierarchy of the SC. These demonstrations provide a viable route to unraveling complex brain structures and functions.

Formalin‐fixed, paraffin‐embedded (FFPE), biobanked tissue samples offer an invaluable resource for clinical and biomarker research. Here, we developed a pressure cycling technology (PCT)‐SWATH mass spectrometry workflow to analyze FFPE tissue proteomes and applied it to the stratification of prostate cancer (PCa) and diffuse large B‐cell lymphoma (DLBCL) samples. We show that the proteome patterns of FFPE PCa tissue samples and their analogous fresh‐frozen (FF) counterparts have a high degree of similarity and we confirmed multiple proteins consistently regulated in PCa tissues in an independent sample cohort. We further demonstrate temporal stability of proteome patterns from FFPE samples that were stored between 1 and 15 years in a biobank and show a high degree of the proteome pattern similarity between two types of histological regions in small FFPE samples, that is, punched tissue biopsies and thin tissue sections of micrometer thickness, despite the existence of a certain degree of biological variations. Applying the method to two independent DLBCL cohorts, we identified myeloperoxidase, a peroxidase enzyme, as a novel prognostic marker. In summary, this study presents a robust proteomic method to analyze bulk and biopsy FFPE tissues and reports the first systematic comparison of proteome maps generated from FFPE and FF samples. Our data demonstrate the practicality and superiority of FFPE over FF samples for proteome in biomarker discovery. Promising biomarker candidates for PCa and DLBCL have been discovered.

Treatment of glioblastoma (GBM) remains a challenge using conventional chemotherapy, such as temozolomide (TMZ), and is often ineffective as a result of drug resistance. We have assessed a novel nitrone-based agent, OKN-007, and found it to be effective in decreasing tumor volumes and increasing survival in orthotopic GBM xenografts by decreasing cell proliferation and angiogenesis and increasing apoptosis. In this study, we assessed combining OKN-007 with TMZ in vivo in a human G55 GBM orthotopic xenograft model and in vitro in TMZ-resistant and TMZ-sensitive human GBM cell lines. For the in vivo studies, magnetic resonance imaging was used to assess tumor growth and vascular alterations. Percent animal survival was also determined. For the in vitro studies, cell growth, IC50 values, RNA-seq, RT-PCR, and ELISA were used to assess growth inhibition, possible mechanism-of actions (MOAs) associated with combined OKN-007 + TMZ versus TMZ alone, and gene and protein expression levels, respectively. Microarray analysis of OKN-007–treated rat F98 glioma tumors was also carried out to determine possible MOAs of OKN-007 in glioma-bearing animals either treated or not treated with OKN-007. OKN-007 seems to elicit its effect on GBM tumors via inhibition of tumorigenic TGF-β1, which affects the extracellular matrix. When combined with TMZ, OKN-007 significantly increases percent survival, decreases tumor volumes, and normalizes tumor blood vasculature in vivo compared to untreated tumors and seems to affect TMZ-resistant GBM cells possibly via IDO-1, SUMO2, and PFN1 in vitro. Combined OKN-007 + TMZ may be a potentially potent treatment strategy for GBM patients.

Medical data security is facing great challenges in medical applications due to the open internet and the semi-trusted cloud. For the sake of privacy protection and the security of medical images, this paper proposes a secure and high visual-quality framework for medical images. In this framework, a novel reversible data hiding (RDH) based on lesion extraction embeds privacy data into medical images for privacy protection and image quality improvement, homomorphic encryption based on chaotic map encrypts images for medical image security. The experiments have shown that the proposed framework increases the security of medical data and improves the visual quality of medical images significantly. The proposed RDH in this framework outperforms the other RDH methods with contrast enhancement and the proposed encryption scheme increases image security well.

Aim: Diabetic peripheral neuropathy (DPN) is a common, severe microvascular complication of diabetes. Our study was to assess prevalence and risk factors for DPN in subjects with type 2 diabetes from 14 different countries.Methods: A total of 2,733 subjects with type 2 diabetes aged 18–65 years (45.3% men, mean duration of diabetes = 8.8 years) were included to perform this International Prevalence and Treatment of Diabetes and Depression (INTERPRET-DD) study in 14 countries. After a structured questionnaire was used in face-to-face interviews to collect sociodemographic characteristics and medical records of the participating subjects, laboratory tests were carried out for clinical measurement. Depressive symptoms were diagnosed and measured using the Patient Health Questionnaire-9. The potential risk factors for DPN were determined by multilevel mixed-effects logistic regression, accounting for clustering of participants within the country. Robustness of the estimates was assessed by sensitivity analysis.Results: The overall prevalence of DPN across different countries was 26.71%, whereas country-specific prevalences showed considerable variation. Multivariate analysis revealed that duration of diabetes (OR: 1.08 per 1-year increase, 95% CI: 1.06–1.09), poor glycemic control (OR: 1.11 per 1% increase in HbA1c, 95% CI: 1.05–1.18), and history of hypertension (OR: 1.58, 95% CI: 1.18–2.12), cardiovascular disease (OR: 2.07, 95% CI: 1.55–2.78) and depressive symptoms (OR: 1.92, 95% CI: 1.43–2.58) were independently and positively associated with the risk of DPN. Sensitivity analyses including or excluding patients from countries with extreme low or high prevalence of DPN yielded similar estimates in terms of trend and magnitude.Conclusions: This international study illustrates that more than a quarter of individuals with type 2 diabetes developed DPN. The prevalence was positively associated with the duration of diabetes, poor glycemic control, and history of hypertension, cardiovascular disease and depressive symptoms.

Background: Early screening for colorectal cancer (CRC) is essential to improve its prognosis. Liquid biopsies are increasingly being considered for diagnosing cancer due to low invasiveness and high reproducibility. In addition, circulating extracellular vesicles (crEVs, extracellular vesicles isolated from plasma) expressing tumour-specific proteins are potential biomarkers for various cancers. Here, we present a data-independent acquisition (DIA)-mass spectrometry (MS)-based diagnostic method for liquid biopsies. Methods: Extracellular vesicles (EVs) were isolated from culture supernatants of human CRC cell lines, and plasma of patients with CRC at different tumour stages, by overnight ultracentrifugation coupled with sucrose density gradient centrifugation. Tumour-specific EV proteins were prioritized using Tandem Mass Tag (TMT)-based shotgun proteomics and phosphoproteomics. The results were verified in a second independent cohort and a mouse tumour-bearing model using Western blotting (WB). The candidate biomarkers were further validated in a third cohort by DIA-MS. Finally, the DIA-MS methodology was accelerated to permit high-throughput detection of EV biomarkers in another independent cohort of patients with CRC and healthy controls. Results: High levels of total and phosphorylated fibronectin 1 (FN1) in crEVs, haptoglobin (HP), S100A9 and fibrinogen α chain (FGA) were significantly associated with cancer progression. FGA was the most dominant biomarker candidate. Analysis of the human CRC cell lines and the mouse model indicated that FGA+ crEVs were likely released by CRC cells. Furthermore, fast DIA-MS and parallel reaction monitoring (PRM)-MS both confirmed that FGA+ crEVs could distinguish colon adenoma with an area of curve (AUC) in the receiver operating characteristic (ROC) curve of 0.949 and patients with CRC (AUC of ROC is 1.000) from healthy individuals. The performance outperformed conventional tumour biomarkers. The DIA-MS quantification of FGA+ crEVs among three groups agreed with that from PRM-MS. Conclusion: DIA-MS detection of FGA+ crEVs is a potential rapid and non-invasive screening tool to identify early stage CRC. Abbreviations: FGA: fibrinogen α chain; CRC: colorectal cancer; crEVs: circulating extracellular vesicles; EV: extracellular vesicles;MS: mass spectrometry; WB: Western blotting; ROC: receiver operating characteristic; PRM: Parallel Reaction Monitoring; GPC1: Glypican-1; GO: Gene ontology; TEM: transmission electron microscopy; FN1: Fibronectin 1; HP: haptoglobin; TMT: Tandem Mass Tag; LC-MS/MS: liquid chromatography coupled to tandem mass spectrometry; DIA: data-independent acquisition; DDA: data-dependent acquisition; CiRT: Common internal Retention Time standards;AGC: Automatic gain control; AUC: area under curve.

Abstract Background and aims Exercise training is considered a cornerstone in the management of type 2 diabetes, which is associated with impaired endothelial function. However, the association of exercise training with endothelial function in type 2 diabetes patients has not been fully understood. This meta-analysis aimed to investigate their associations with focus on exercise types. Methods Databases were searched up to January 2018 for studies evaluating the influences of exercise training with durations ≥ 8 weeks on endothelial function assessed by flow-mediated dilation (FMD) among type 2 diabetes patients or between type 2 diabetics and non-diabetics. Data were pooled using random-effects models to obtain the weighted mean differences (WMDs) and 95% confidence intervals (CIs). Results Sixteen databases were included. Exercise training resulted in an overall improvement in FMD by 1.77% (95% CI 0.94–2.59%) in type 2 diabetes patients. Specifically, both aerobic and combined aerobic and resistance exercise increased FMD by 1.21% (95% CI 0.23–2.19%) and 2.49% (95% CI 1.17–3.81%), respectively; but resistance exercise only showed a trend. High-intensity interval aerobic exercise did not significantly improve FMD over moderate-intensity continuous exercise. Notably, the improvement in FMD among type 2 diabetes patients was smaller compared with non-diabetics in response to exercise training (WMD − 0.72%, 95% CI − 1.36 to − 0.08%) or specifically to aerobic exercise (WMD − 0.65%, 95% CI − 1.31 to 0.01%). Conclusions Exercise training, in particular aerobic and combined exercise, improves endothelial function in type 2 diabetes patients, but such an improvement appears to be weakened compared with non-diabetics. Trial registration PROSPERO CRD42018087376

Background: Although step counters are popularly employed for physical rehabilitation in chronic obstructive pulmonary disease (COPD) patients, their effectiveness is inconsistent and even questioned. This meta-analysis aimed to investigate whether step counter use increases physical activity or improves exercise capacity in COPD patients. Methods: Electronic databases were searched for randomized controlled trials that assessed the efficacy of step counter use in increasing physical activity or in improving exercise capacity. Data were aggregated using a random-effects model to get the overall effect sizes [standard mean difference (SMD) with 95% confidence interval (CI)], and subgroup analyses were performed. Results: A total of 15 trials enrolling 1316 patients with moderate to severe COPD were included. Step counter use increased physical activity compared with controls (SMD = 0.57, 95% CI 0.31–0.84), which is equal to a magnitude of 1026 steps/day in daily steps. It also enhanced exercise capacity with an effect size of 0.30 (95% CI 0.16–0.45), approximating to a magnitude of 11.6 m in the 6-min walking distance. Step counter use could augment physical activity (SMD = 0.64, 95% CI 0.19–1.08) and exercise capacity (SMD = 0.32, 95% CI 0.01–0.62) for patients receiving pulmonary rehabilitation. Yet it cannot enhance physical activity or exercise capacity in patients with severe COPD or among studies with intervention durations ⩾6 months (both p > 0.50). Conclusions: Step counter use increases physical activity and improves exercise capacity in COPD patients, at least in the short term, which supports the notion of recommending step counter use in COPD management.

Vigorous to maximal aerobic interval training (INT) has received remarkable interest in improving cardiometabolic outcomes for type 2 diabetes patients recently, yet with inconsistent findings. This meta-analysis was aimed to quantify its effectiveness in type 2 diabetes. Randomized controlled trials (RCTs) were identified by searches of 3 databases to October 2017, which evaluated the effects of INT with a minimal training duration of 8 weeks vs. moderate-intensity continuous training (MICT) or non-exercise training (NET) among type 2 diabetes patients on outcomes including cardiorespiratory fitness, glycemic control, body composition, blood pressure, and lipid profiles. Weighted mean differences with 95% confidence intervals (CIs) were calculated with the random-effects model. Nine datasets from 7 RCTs with 189 patients were included. Compared with MICT, INT improved maximal oxygen consumption (VO2max) by 2.60 ml/kg/min (95% CI: 1.32 to 3.88 ml/kg/min, P

Background: Increased physical activity (PA) is a key element in the management of patients with nonalcoholic fatty liver disease (NAFLD); however, its association with NAFLD risk has not been systematically assessed. This meta-analysis of observational studies was to quantify this association with dose–response analysis. Methods: Electronic databases were searched to January 2017 for studies of adults reporting the risk of NAFLD in relation to PA with cohort or case-control designs. Studies that reported sex-specific data were included as separate studies. The overall risk estimates were pooled using a random-effects model, and the dose–response analysis was conducted to shape the quantitative relationship. Results: A total of 6 cohort studies from 5 articles with 32,657 incident NAFLD cases from 142,781 participants, and 4 case-control studies from 3 articles with 382 NAFLD cases and 302 controls were included. Compared with the lowest PA level, the highest PA level was associated with a risk reduction of NAFLD in cohort [RR (risk ratio) 0.79, 95% CI (confidence interval) 0.71–0.89] and case-control studies [OR (odds ratio) 0.43, 95% CI 0.27–0.68]. For cohort studies, both highest and moderate PA levels were superior to the light one in lowering NAFLD risk ( p for interaction = 0.006 and 0.02, respectively), and there was a log-linear dose–response association ( p for nonlinearity = 0.10) between PA and NAFLD risk [RR 0.82 (95% CI 0.73–0.91) for every 500 metabolic equivalent (MET)-minutes/week increment in PA]. Conclusions: Increased PA may lead to a reduced risk of NAFLD in a dose-dependent manner, and the current guideline-recommended minimum PA level that approximates to 500 MET-minutes/week is able to moderately reduce the NAFLD risk.

BackgroundHeart rate recovery (HRR) is a noninvasive assessment of autonomic dysfunction and has been implicated with risk of cardiovascular events and all‐cause mortality. However, evidence has not been systematically assessed. We performed a meta‐analysis of prospective cohort studies to quantify these associations in the general population. Methods and ResultsA literature search using 3 databases up to August 2016 was conducted for studies that reported hazard ratios with 95% CIs for the association between baseline HRR and outcomes of interest. The overall hazard ratios were calculated using a random‐effects model. There were 9 eligible studies in total, with 5 for cardiovascular events enrolling 1061 cases from 34 267 participants, and 9 for all‐cause mortality enrolling 2082 cases from 41 600 participants. The pooled hazard ratios associated with attenuated HRR versus fast HRR that served as the referent were 1.69 (95% CI 1.05–2.71) for cardiovascular events and 1.68 (95% CI 1.51–1.88) for all‐cause mortality. For every 10 beats per minute decrements in HRR, the hazard ratios were 1.13 (95% CI 1.05–1.21) and 1.09 (95% CI 1.01–1.19), respectively. Further analyses suggested that the associations observed between attenuated HRR and risk of fatal cardiovascular events and all‐cause mortality were independent of traditional metabolic factors for cardiovascular disease (all P

Diabetic retinopathy (DR) is one of the major complications of diabetes. Although great efforts have been made to uncover the mechanisms underlying the pathology of DR, the exact causes of DR remain largely unknown. Because of multifactor involvement in DR etiology, currently no effective therapeutic treatments for DR are available. In this paper, we review the pathology of DR, commonly used animal models, and novel therapeutic approaches. Perspectives and future directions for DR treatment are discussed.

Regular physical activity (PA) is a key element in the prevention and management of type 2 diabetes mellitus (T2DM). Participation in regular PA improves blood glucose control and can prevent or delay T2DM and its complications, along with positively affecting lipids, blood pressure, cardiovascular events, mortality, and quality of life. However, most people with T2DM are not active and show poor adherence. This paper reviews the possible barriers to PA and strategies to improve the adherence to PA. Based on the currently available literature, it is concluded that self-efficacy and social support from family, friends, and health care providers play the important role in adoption and maintenance of regular PA. Here we also highlight some new modern and innovative interventions that facilitate exercise participation and improve the adherence.

Cerium oxide nanoparticles, nanoceria, are inorganic antioxidants that have catalytic activities which mimic those of the neuroprotective enzymes superoxide dismutase and catalase. We have previously shown that nanoceria preserve retinal morphology and prevent loss of retinal function in a rat light damage model. In this study, the homozygous tubby mutant mouse, which exhibits inherited early progressive cochlear and retinal degeneration, was used as a model to test the ability of nanoceria to slow the progression of retinal degeneration. Tubby mice were injected systemically, intracardially, with 20 μl of 1 mM nanoceria in saline, at postnatal day 10 and subsequently at P20 and P30 whereas saline injected and uninjected wild type (or heterozygous tubby) served as injected and uninjected controls, respectively. Assays for retinal function, morphology and signaling pathway gene expression were performed on P34 mice. Our data demonstrate that nanoceria protect the retina by decreasing Reactive Oxygen Species (ROS), up-regulating the expression of neuroprotection-associated genes; down-regulating apoptosis signaling pathways and/or up-regulating survival signaling pathways to slow photoreceptor degeneration. These data suggest that nanoceria have significant potential as global agents for therapeutic treatment of inherited retinal degeneration and most types of ocular diseases.