Continuous quality improvement project to reduce the downtime of medical linear accelerators: A case study at Zhejiang Cancer Hospital.

Objective: To analyse and continually improve existing issues in the quality improvement process of medical linear accelerators (LINACs) and enhance the quality control management of LINACs. Methods: Data were collected from eight LINACs (sourced from three manufacturers) at Zhejiang Cancer Hospital using Excel diaries between January 2019 and December 2020. The data description and analysis were performed using the analytic hierarchy process, SPSSAU and Excel software, and mean-time-to-repair (MTTR)/mean-time-between-failure (MTBF) metrics. Continuous quality improvement was executed using the quality control circle (QCC) quality management method. Results: After quality improvement, the risk frequency of 'LINAC down' events decreased by 43.63% and downtime was reduced by 40.45%. The weight of downtime risk improved by 73.69%. The MTTR recovery value increased by 31.90%, and MTBF reliability increased by 2.97 h. The simulation results demonstrated that the proposed quality improvement measures could effectively decrease the frequency and duration of downtimes, consequently extending the normal operational time of LINACs. Conclusion: Transitioning from instant repair to preventative maintenance can enhance the operational efficiency of equipment and yield economic benefits for hospitals. The QCC method and the event risk evaluation model are effective in reducing the downtime of LINACs and improving their quality control management.

HPV16-miRNAs exert oncogenic effects through enhancers in human cervical cancer.

BACKGROUND: Cervical cancer is a human papillomavirus (HPV)-related disease. HPV type 16 (HPV16), which is the predominant cause of cervical cancer, can encode miRNAs (HPV16-miRNAs). However, the role of HPV16-miRNAs in the pathogenesis of cervical cancer remains unclear. METHODS: Human cervical cancer cell lines SiHa (HPV16-positive) and C33A (HPV-negative), and cervical cancer tissues were collected to investigate the expression levels of two HPV16-miRNAs (HPV16-miR-H1 and HPV16-miR-H6). The overexpression and knockdown of HPV16-miR-H1 and HPV16-miR-H6 were performed using the lentiviral vector system and miRNA inhibitors, respectively. RNA-sequencing (RNA-seq) analysis and H3K27ac chromatin immunoprecipitation and sequencing (CHIP-seq) experiments were utilized to explore the roles of HPV16-miR-H1 and HPV16-miR-H6 facilitated by enhancers. CCK8, EdU, transwell, and wound healing assays were performed to verify the effects of HPV16-miR-H1 and HPV16-miR-H6 on cell proliferation and migration. RESULTS: HPV16-miR-H1 and HPV16-miR-H6 were highly expressed in both SiHa cells and tissue samples from HPV16-positive cervical cancer patients. RNA-seq analysis showed that HPV16-miR-H1 and HPV16-miR-H6 induced the upregulation of numerous tumor progression-associated genes. H3K27ac CHIP-seq experiments further revealed that HPV16-miR-H1 and HPV16-miR-H6 modulated the expression of critical genes by regulating their enhancer activity. The functional study demonstrated that HPV16-miR-H1 and HPV16-miR-H6 increased the migratory capacity of SiHa cells. CONCLUSIONS: Our data shed light on the role of HPV16-encoded miRNAs in cervical cancer, particularly emphasizing their involvement in the miRNA-enhancer-target gene system. This novel regulatory mechanism of HPV16-miRNAs provides new insights and approaches for the development of therapeutic strategies by targeting HPV16-positive cervical cancer.

Tris (2-chloroethyl) phosphate presence inhibits methane production from anaerobic digestion: Alterations in organic matter transformation, cell physiological status, and microbial community.

Organophosphate flame retardants (OPFRs) are widely used in consumer products, leading to their unavoidable release into the environment, especially accumulation in anaerobic environments and posing potential risks. This study focused on Tris(2-chloroethyl) phosphate (TCEP), a representative OPFR, to investigate its effects on carbon transformation and methane production in anaerobic digestion. Increasing TCEP concentrations from control to 16 mg/L resulted in decreased cumulative methane yield (from 235.4 to 196.3 mL/g COD) and maximum daily methane yield (from 40.8 to 16.17 mL/(g COD·d)), along with an extended optimal anaerobic digestion time (from 15 to 20 days). Mechanistic analysis revealed TCEP binding to tyrosine-like proteins in extracellular polymeric substances, causing cell membrane integrity impairment. The TCEP-caused alteration of the physiological status of cells was demonstrated to be a significant contribution to the inhibited bioprocesses including acidogenesis, acetogenesis, and methanogenesis. Illumina Miseq sequencing showed TCEP decreasing the relative abundance of acidogens (58.8 % to 46.0 %) and acetogens (7.1 % to 5.0 %), partly shifting the methanogenesis pathway from acetoclastic to hydrogenotrophic methanogenesis. These findings enhance understanding of TCEP's impact on anaerobic digestion, emphasizing the environmental risk associated with its continued accumulation.

Polyacrylonitrile as an Efficient Transfer Medium for Wafer-Scale Transfer of Graphene.

The disparity between growth substrates and application-specific substrates can be mediated by reliable graphene transfer, the lack of which currently strongly hinders the graphene applications. Conventionally, the removal of soft polymers, that support the graphene during the transfer, would contaminate graphene surface, produce cracks, and leave unprotected graphene surface sensitive to airborne contaminations. In this work, it is found that polyacrylonitrile (PAN) can function as polymer medium for transferring wafer-size graphene, and encapsulating layer to deliver high-performance graphene devices. Therefore, PAN, that is compatible with device fabrication, does not need to be removed for subsequent applications. The crack-free transfer of 4 in. graphene onto SiO2/Si wafers, and the wafer-scale fabrication of graphene-based field-effect transistor arrays with no observed clear doping, uniformly high carrier mobility (≈11 000 cm2 V-1 s-1), and long-term stability at room temperature, are achieved. This work presents new concept for designing the transfer process of 2D materials, in which multifunctional polymer can be retained, and offers a reliable method for fabricating wafer-scale devices of 2D materials with outstanding performance.

Nano-optogenetics for Disease Therapies.

Optogenetic, known as the method of 21 centuries, combines optic and genetic engineering to precisely control photosensitive proteins for manipulation of a broad range of cellular functions, such as flux of ions, protein oligomerization and dissociation, cellular intercommunication, and so on. In this technique, light is conventionally delivered to targeted cells through optical fibers or micro light-emitting diodes, always suffering from high invasiveness, wide-field illumination facula, strong absorption, and scattering by nontargeted endogenous substance. Light-transducing nanomaterials with advantages of high spatiotemporal resolution, abundant wireless-excitation manners, and easy functionalization for recognition of specific cells, recently have been widely explored in the field of optogenetics; however, there remain a few challenges to restrain its clinical applications. This review summarized recent progress on light-responsive genetically encoded proteins and the myriad of activation strategies by use of light-transducing nanomaterials and their disease-treatment applications, which is expected for sparking helpful thought to push forward its preclinical and translational uses.

Effect of novel anti-tumor and anti-angiogenesis drug taurolactone on angiogenic factor AGGF1 and angiogenesis mimicry in patients with hepatocellular carcinoma.

OBJECTIVE: Our study was to investigate the impact of taurolactone, a novel anti-tumor and anti-angiogenic drug, on AGGF1, an angiogenic factor, and angiogenesis mimicry in patients diagnosed with hepatocellular carcinoma (HCC). METHODS: A total of 120 HCC patients were enrolled from the Department of Oncology and Hepatobiliary Surgery at our hospital between May 2021 and December 2022. HCC diagnoses were confirmed through imaging or tissue biopsy for all patients. The age of patients ranged from 37 to 72 years, with an average age of 64.29 ± 4.58 years. These participants were divided equally into two groups: the control group and the observation group, each consisting of 60 individuals. While the control group received standard drug treatment, the observation group was administered taurolactone treatment. Before being included in the study, all participants or their legal representatives provided signed informed consent. Patient demographic information was collected through a questionnaire survey. ELISA was used to measure the levels of VEGF and AGGF1 in patients following treatment. Western blot was applied to assess the protein expression of PDGF, Angiopoietin, and AGGF1. MRI imaging technology was utilized to assess the perfusion characteristics of tumor blood vessels in patients. Tumor vessel density was compared between patients using ultrasonography. We also conducted a comparison between the two groups in terms of progression-free survival and overall survival. RESULTS: General patient information between the two groups showed no significant differences (P > 0.05). Of note, the observation group exhibited greatly lower levels of VEGF and AGGF1 compared to the control group (P < 0.05). Moreover, the levels of PDGF, Angiopoietin, and AGGF1 protein expression were significantly reduced in the observation group compared to the control group (P < 0.05). In terms of tumor perfusion, the observation group displayed lower average and maximum perfusion volumes in tumor blood vessels compared to the control group (P < 0.05). Additionally, the observation group demonstrated delayed peak times and arrival times of tumor blood vessels in comparison to the control group (P < 0.05). Furthermore, the density of tumor blood vessels was notably lower in the observation group compared to the control group (P < 0.05). Patients in the observation group had longer progression-free survival and overall survival than the control group (P < 0.05). CONCLUSION: In HCC patients, our study highlighted the potential efficacy of taurolactone treatment as it effectively inhibited angiogenic factors and angiogenesis mimicry, ultimately leading to an improved prognosis for these patients.

Circulating metabolic biomarkers and risk of new-onset hypertension: findings from the UK Biobank.

OBJECTIVE: The evidence regarding the associations of circulating metabolic biomarkers with hypertension risk is scarce. We aimed to examine the associations between circulating metabolites and risk of hypertension. METHODS: We included 49 422 individuals free of hypertension at baseline with a mean (SD) age of 53.5 (8.0) years from the UK Biobank. Nuclear magnetic resonance spectroscopy was used to quantify 143 individual metabolites. Multivariable-adjusted Cox regression models were used to estimate hazard ratios and 95% confidence intervals (CIs). RESULTS: During a mean (SD) follow-up of 11.2 (1.8) years, 2686 incident hypertension cases occurred. Out of 143 metabolites, 76 were associated with incident hypertension, among which phenylalanine (hazard ratio: 1.40; 95% CI: 1.24-1.58) and apolipoprotein A1 (hazard ratio: 0.76; 95% CI: 0.66-0.87) had the strongest association when comparing the highest to the lowest quintile. In general, very-low-density lipoprotein (VLDL) particles were positively, whereas high-density lipoprotein (HDL) particles were inversely associated with risk of hypertension. Similar patterns of cholesterol, phospholipids, and total lipids within VLDL and HDL particles were observed. Triglycerides within all lipoproteins were positively associated with hypertension risk. Other metabolites showed significant associations with risk of hypertension included amino acids, fatty acids, ketone bodies, fluid balance and inflammation markers. Adding 10 selected metabolic biomarkers to the traditional hypertension risk model modestly improved discrimination (C-statistic from 0.745 to 0.752, P < 0.001) for prediction of 10-year hypertension incidence. CONCLUSION: Among UK adults, disturbances in metabolic biomarkers are associated with incident hypertension. Comprehensive metabolomic profiling may provide potential novel biomarkers to identify high-risk individuals.

Comparative study of the multiple wavelength lasing of nitrogen ions: the role of vibrational level-dependent photoionization.

We report on an optical amplification and energy threshold of the two most prominent emission lines, 391.4 and 427.8 nm, of the cavity-less lasing of nitrogen ions pumped by femtosecond laser pulses. It was found that the two transitions both show optical amplification under a low gas pressure condition, while the 391.4 nm emission is barely amplified under high gas pressure. Moreover, the 427.8 nm emission presents a significant lower pump laser energy threshold and a larger gain factor than the 391.4 nm emission. Numerical simulations based on a three-state coupling model suggest that the smaller ionization Franck-Condon factor from the ground state of N2 to the vibrational level ν = 1 in X 2 Σ g+ state of N2 + favors the formation of population inversion corresponding to the 427.8 nm emission. Meanwhile, the competition between the strong field ionization and excitation induced by the pumping laser requires higher laser intensity to acquire the population inversion for the 391.4 nm radiation, leading to a corresponding larger energy threshold.

[Resources and utilization of medicinal plants in countries and regions involved in "the Belt and Road" Initiative].

The protection, development, and utilization of medicinal plant resources are important cornerstones of maintaining human health. However, due to factors such as the reduction of high-quality land resources, deterioration of ecological environments, and excessive and disorderly resource development, medicinal plant resources are becoming scarce, and some of them are insufficiently supplied. With the proposal of "the Belt and Road" Initiative, the cooperation between China and "the Belt and Road" partners(the countries and regions involved in "the Belt and Road" Initiative)is increasingly close, which provides a new opportunity for carrying out trade of medicinal plant resources and alleviating the problem of imbalance and relative inadequacy of medicinal plant resources in countries. This study first determined the distribution and species information of plant resources in countries and regions involved in "the Belt and Road" Initiative by investigating the database of plant distribution and that of medicinal plant resources. Then, according to the published data from the International Union for Conservation of Nature(IUCN) and the Convention on International Trade in Endangered Species of Wild Fauna and Flora(CITES), this study identified the rare and endangered medicinal plants and the medicinal plants under trade control in countries and regions involved in "the Belt and Road" Initiative and finally sorted out the list of potential medicinal plant resources in countries and regions involved in "the Belt and Road" Initiative that can be used by China. This data resource can not only be used for the overall protection of important endangered species but also scientifically guide the development and utilization of medicinal resources, providing guidance and a theoretical basis for the sustainable development of medicinal plant resources in countries and regions involved in "the Belt and Road" Initiative.

Can cerebellar theta-burst stimulation improve balance function and gait in stroke patients? A randomized controlled trial.

BACKGROUND: The cerebellum is a key structure involved in balance and motor control, and has become a new stimulation target in brain regulation technology. Interference theta-burst simulation (iTBS) is a novel simulation mode of repetitive transcranial magnetic simulation. However, the impact of cerebellar iTBS on balance function and gait in stroke patients is still unknown. AIM: The aim of this study was to determine whether cerebellar iTBS can improve function, particularly balance and gait, in patients with post-stroke hemiplegia. DESIGN: This study is a randomized, double-blind, sham controlled clinical trial. SETTING: The study was carried out at the Department of Rehabilitation Medicine in a general hospital. POPULATION: Patients with stroke with first unilateral lesions were enrolled in the study. METHODS: Thirty-six patients were randomly assigned to the cerebellar iTBS group or sham stimulation group. The cerebellar iTBS or pseudo stimulation site is the ipsilateral cerebellum on the paralyzed side, which is completed just before daily physical therapy. The study was conducted five times a week for two consecutive weeks. All patients were assessed before the intervention (T0) and at the end of 2 weeks of treatment (T1), respectively. The primary outcome was the Berg Balance Scale (BBS), while secondary outcome measures included the Fugl Meyer Lower Limb Assessment Scale (FMA-LE), timed up and go (TUG), Barthel Index (BI), and gait analysis. RESULTS: After 2 weeks of intervention, the BBS, FMA-LE, TUG, and BI score in both the iTBS group and the sham group were significantly improved compared to the baseline (all P<0.05). Also, there was a significant gait parameter improvement including the cadence, stride length, velocity, step length compared to the baseline (P<0.05) in the iTBS group, but only significant improvement in cadence was identified in the sham group (P<0.05). Intergroup comparison showed that the BBS (P<0.001), FMA-LE (P<0.001), and BI (P=0.002) in the iTBS group were significantly higher than those in the sham group, and the TUG in the iTBS was significantly lower than that in the sham group (P=0.002). In addition, there were significant differences in cadence (P=0.029), strip length (P=0.046), gain velocity (P=0.002), and step length of affected lower limb (P=0.024) between the iTBS group and the sham iTBS group. CONCLUSIONS: Physical therapy is able to improve the functional recovery in hemiplegic patients after stroke, but the cerebellar iTBS can facilitate and accelerate the recovery, particularly the balance function and gait. Cerebellar iTBS could be an efficient and facilitative treatment for patients with stroke. CLINICAL REHABILITATION IMPACT: Cerebellar iTBS provides a convenient and efficient treatment modality for functional recovery of patients with stroke, especially balance function and gait.

Targeting PNPO to suppress tumor growth via inhibiting autophagic flux and to reverse paclitaxel resistance in ovarian cancer.

Our previous study showed that pyridoxine 5'-phosphate oxidase (PNPO) is a tissue biomarker of ovarian cancer (OC) and has a prognostic implication but detailed mechanisms remain unclear. The current study focused on PNPO-regulated lysosome/autophagy-mediated cellular processes and the potential role of PNPO in chemoresistance. We found that PNPO was overexpressed in OC cells and was a prognostic factor in OC patients. PNPO significantly promoted cell proliferation via the regulation of cyclin B1 and phosphorylated CDK1 and shortened the G2M phase in a cell cycle. Overexpressed PNPO enhanced the biogenesis and perinuclear distribution of lysosomes, promoting the degradation of autophagosomes and boosting the autophagic flux. Further, an autolysosome marker LAMP2 was upregulated in OC cells. Silencing LAMP2 suppressed cell growth and induced cell apoptosis. LAMP2-siRNA blocked PNPO action in OC cells, indicating that the function of PNPO on cellular processes was mediated by LAMP2. These data suggest the existence of the PNPO-LAMP2 axis. Moreover, silencing PNPO suppressed xenographic tumor formation. Chloroquine counteracted the promotion effect of PNPO on autophagic flux and inhibited OC cell survival, facilitating the inhibitory effect of PNPO-shRNA on tumor growth in vivo. Finally, PNPO was overexpressed in paclitaxel-resistant OC cells. PNPO-siRNA enhanced paclitaxel sensitivity in vitro and in vivo. In conclusion, PNPO has a regulatory effect on lysosomal biogenesis that in turn promotes autophagic flux, leading to OC cell proliferation, and tumor formation, and is a paclitaxel-resistant factor. These data imply a potential application by targeting PNPO to suppress tumor growth and reverse PTX resistance in OC.

Recent trends in the transfer of graphene films.

Recent years have witnessed advances in chemical vapor deposition growth of graphene films on metal foils with fine scalability and thickness controllability. However, challenges for obtaining wrinkle-free, defect-free and large-area uniformity remain to be tackled. In addition, the real commercial applications of graphene films still require industrially compatible transfer techniques with reliable performance of transferred graphene, excellent production capacity, and suitable cost. Transferred graphene films, particularly with a large area, still suffer from the presence of transfer-related cracks, wrinkles and contaminants, which would strongly deteriorate the quality and uniformity of transferred graphene films. Potential applications of graphene films include moisture barrier films, transparent conductive films, electromagnetic shielding films, and optical communications; such applications call different requirements for the performance of transferred graphene, which, in turn, determine the suitable transfer techniques. Besides the reliable transfer process, automatic machines should be well developed for the future batch transfer of graphene films, ensuring the repeatability and scalability. This mini-review provides a summary of recent advances in the transfer of graphene films and offers a perspective for future directions of transfer techniques that are compatible for industrial batch transfer.

Associations Between Beverage Consumption and Risk of Microvascular Complications Among Individuals With Type 2 Diabetes.

CONTEXT: The relationship between the consumption of different beverages and the risk of microvascular complications in individuals with type 2 diabetes (T2D) is unclear. OBJECTIVE: To investigate the association of individual beverage consumption, including artificially sweetened beverages (ASBs), sugar-sweetened beverages (SSBs), tea, coffee, natural juice, and yogurt, with the risk of microvascular complications in adults with T2D. METHODS: This cohort study included 6676 participants with T2D who were free of macrovascular and microvascular complications at baseline in the UK Biobank. Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: During a median follow-up of 11.7 years, 1116 cases of composite microvascular complications were documented. After multivariable adjustment, a linear dose-response relationship was demonstrated between the consumption of ASBs and SSBs and the risk of microvascular complications. Compared with nonconsumers, those who consumed ≥2.0 units/day of ASBs and SSBs had an HR (95% CI) of 1.44 (1.18-1.75) and 1.32 (1.00-1.76) for composite microvascular complications, respectively. In addition, higher tea consumption was associated with a lower risk of diabetic retinopathy, with an HR (95% CI) of 0.72 (0.57-0.92) for whom consuming ≥4.0 units/day. There was no significant association between individual beverage consumption and the risk of diabetic neuropathy. No significant association was observed between the consumption of coffee, natural juice, or yogurt and the risks of microvascular complications. Moreover, substituting half units/day of ASBs or SSBs with tea or coffee was associated with a 16% to 28% lower risk of microvascular complications. CONCLUSION: Higher consumption of ASBs and SSBs was linearly associated with an increased risk of microvascular complications in adults with T2D.

Octamer-binding transcription factor 4-positive circulating tumor cell predicts worse treatment response and survival in advanced cholangiocarcinoma patients who receive immune checkpoint inhibitors treatment.

BACKGROUND: Octamer-binding transcription factor 4-positive circulating tumor cell (OCT4+CTC) exhibits high stemness and invasive potential, which may influence the efficacy of immune checkpoint inhibitors (ICI). This study aimed to assess the prognostic role of OCT4+CTC in advanced cholangiocarcinoma (CCA) patients who received ICI treatment. METHODS: In total, 40 advanced CCA patients who received ICI treatment were included, and CTC and OCT4 counts were detected via a Canpatrol system and an RNA in situ hybridization method before ICI treatment. Patients were subsequently divided into none CTC, OCT4-CTC, and OCT4+CTC groups. Patients were followed up for a median of 10.4 months. RESULTS: The percentages of patients in none CTC, OCT4-CTC, and OCT4+CTC groups were 25.0%, 30.0%, and 45.0%, respectively. The proportion of patients with lymph node metastasis was highest in OCT4+CTC group, followed by none CTC group, and lowest in OCT4-CTC group (P = 0.025). The objective response rate (ORR) was lowest in OCT4+CTC group, moderate in OCT4-CTC group, and highest in none CTC group (P = 0.009), while disease control rate was not different among three groups (P = 0.293). In addition, progression-free survival (PFS) (P < 0.001) and overall survival (OS) (P = 0.001) were shorter in the OCT4+CTC group than in none CTC & OCT4-CTC group. Moreover, OCT4+CTC (versus none CTC) was independently linked with poorer PFS [hazard ratio (HR) = 6.752, P = 0.001] and OS (HR = 6.674, P = 0.003) in advanced CCA patients. CONCLUSION: OCT4+CTC relates to lymph node metastasis and shows a good predictive value for poor treatment response and survival in advanced CCA patients who receive ICI treatment.

Enhancing Rumen Fermentation and Bacteria Community in Sika Deer (Cervus nippon) through Varying Levels of Dragon Fruit Peel Polyphenolic Extract: An In Vitro Study.

The aim of this study is to investigate the effect of dragon fruit peel polyphenolic extract (DFPE) on gas production, rumen fermentation, and bacterial communities in sika deer using an in vitro technique. Three treatments with different DFPE levels (DFPE0, base diet; DFPE5, base diet + 5 mg/g DFPE; DFPE10, base diet + 10 mg/g DFPE, respectively; n = 6) were implemented. The phenolic composition of DFPE, gas production (GP), ammonia nitrogen (NH3-N), volatile fatty acid (VFA), and bacteria communities was evaluated after 24 h of incubation. The results showed that GP and NH3-N were reduced by DFPE supplementation. Total VFA, isovaleric acid, and valeric acid were increased (p < 0.05) by the addition of DFPE. No changes (p > 0.05) were observed in pH, acetic acid, propionic acid, isobutyric acid, butyric acid, and the ratio of acetic acid to propionic acid. Additionally, the alpha indexes, including Sobs, Shannon, and Ace, were increased by DFPE supplementation. Moreover, at the phylum level, DFPE supplementation increased (p = 0.01) Bacteroidota but reduced (p < 0.01) Firmicutes. At the genus level, compared to DFPE0, the DFPE10 had increased relative abundances of Rikenellaceae_RC9_gut_group (p < 0.01), norank_f_Muribaculaceae (p = 0.01), Lachnospiraceae_NK3A20_group (p < 0.01), Christensenellaceae_R-7_group (p < 0.01), and NK4A214_group (p < 0.01), decreased relative abundances of Streptococcus (p < 0.01), Oribacterium (p = 0.01), and Enterococcus (p < 0.01). Compared to DFPE0, DFPE5 had no change (p > 0.05) in all bacteria at the genus level except for decreased relative abundance of Enterococcus (p < 0.01). These results indicated that DFPE may be able to be used as a feed additive to enhance fermentation parameters and improve ruminal bacteria communities in Sika deer.

Associations of serum 25-hydroxyvitamin D and vitamin D receptor polymorphisms with risks of cardiovascular disease and mortality among patients with chronic kidney disease: a prospective study.

BACKGROUND: Evidence regarding the relationships of serum 25-hydroxyvitamin D [25(OH)D] with cardiovascular diseases (CVD) and mortality among patients with chronic kidney disease (CKD) is limited and inconsistent. OBJECTIVES: This study aimed to investigate the associations between serum 25(OH)D and CVD incidence and mortality among patients with CKD. METHODS: This prospective study included 21,507 participants with CKD and free of CVD in the UK Biobank. Incidences of total and subtypes of CVD and mortality were ascertained via electronic health records. Cox proportional hazard regression models were used to estimate the hazard ratios (HRs) and 95% confidential intervals (CIs) for CVD incidence and mortality. RESULTS: The median serum 25(OH)D concentration was 44.0 nmol/L (interquartile range: 30.1, 60.6 nmol/L). After multivariable adjustment, compared with CKD patients with serum 25(OH)D concentrations of <25 nmol/L, those with serum 25(OH)D ≥75 nmol/L had HRs (95% CIs) of 0.80 (0.71, 0.90) for total CVD incidence, 0.82 (0.69, 0.97) for ischemic heart disease, 0.56 (0.41, 0.77) for stroke, 0.64 (0.46, 0.88) for myocardial infarction, 0.62 (0.49, 0.80) for heart failure, 0.60 (0.43, 0.85) for CVD mortality, and 0.62 (0.52, 0.74) for all-cause mortality. In addition, these associations were not modified by vitamin D receptor polymorphisms, with no significant interaction detected. CONCLUSIONS: Higher serum 25(OH)D concentrations were significantly associated with lower risks of total and subtypes of CVD incidence and mortality among individuals with CKD. These findings highlight the importance of maintaining adequate vitamin D status in the prevention of CVD and mortality in patients with CKD.

Successive accumulation of biotic assemblages at a fine spatial scale along glacier-fed waters.

Glacier-fed waters create strong environmental filtering for biota, whereby different organisms may assume distinct distribution patterns. By using environmental DNA-based metabarcoding, we investigated the multi-group biodiversity distribution patterns of the Parlung No. 4 Glacier, on the Tibetan Plateau. Altogether, 642 taxa were identified from the meltwater stream and the downstream Ranwu Lake, including 125 cyanobacteria, 316 diatom, 183 invertebrate, and 18 vertebrate taxa. As the distance increased from the glacier terminus, community complexity increased via sequential occurrences of cyanobacteria, diatoms, invertebrates, and vertebrates, as well as increasing taxa numbers. The stream and lake showed different community compositions and distinct taxa. Furthermore, the correlations with environmental factors and community assembly mechanisms showed group- and habitat-specific patterns. Our results reveal the rapid spatial succession and increasing community complexity along glacial flowpaths and highlight the varying adaptivity of different organisms, while also providing insight into the ecosystem responses to global change.

Biomarker cystatin B expression correlates with pathogenesis in cervical cancer.

OBJECTIVE: Cervical cancer (CC) is one of the most common gynecologic malignancies worldwide. Although rapid improvements have been made regarding its prevention and treatment, little is known about disease pathogenesis and the clinical relevance of reliable biomarkers. The present study evaluated the expression of cystatin B (CSTB) as a potential biomarker of CC. METHODS: Tissue microarray analysis and immunohistochemical staining were performed to detect CSTB expression, while CSTB mRNA and protein expression levels of freshly isolated CC tissue were measured by quantitative real-time PCR and western blot, respectively. Bioinformatics were used to analyze the CSTB co-expression network and functional enrichments. RESULTS: We observed high CSTB mRNA and protein expression levels in CC tissues, which was confirmed by tissue microarray in a comparison with paired adjacent non-cancerous cervical tissue samples. CSTB gene enrichments and associations with co-expressed genes were also observed. Further analysis showed that elevated CSTB expression was associated with pathological progress in CC. CONCLUSION: Our data demonstrate that CSTB has the potential to be used as a tissue biomarker with clinical value in patients with CC, which may aid the development of intervention strategies.

Associations of Regional Body Fat with Risk of Cardiovascular Disease and Mortality among Individuals with Type 2 Diabetes.

OBJECTIVES: We aimed to prospectively examine the association between regional body fat and risk of cardiovascular disease (CVD) in individuals with type 2 diabetes (T2D), who often exhibit changes in relative fat distribution and have increased CVD risk. METHODS: The main analysis included 21,472 participants with T2D from the UK Biobank. Regional body fat was measured by bioelectric impedance assessment. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: Over a median of 7.7 years of follow-up, 3,976 CVD events occurred. After multivariable adjustment, upper and lower body fat were independently and oppositely associated with CVD risk among patients with T2D. Higher arm fat percentage was linearly associated with increased CVD risk (P nonlinear >0.05), while higher trunk fat percentage was nonlinearly associated with increased CVD risk (P nonlinear <0.05). In contrast, higher leg fat percentage was nonlinearly associated with lower CVD risk (P nonlinear <0.05). When comparing extreme quartiles, the multivariable-adjusted HR (95% CI) of CVD was 0.72 (0.58, 0.90) for leg fat percentage, 1.63 (1.29, 2.05) for arm fat percentage, and 1.27 (1.06, 1.52) for trunk fat percentage. Similar patterns of associations were observed for all-cause and CVD mortality. In addition, leg fat percentage, but not other regional fat percentage, was associated with CVD risk independently of traditional measures of obesity. CONCLUSIONS: Among people with T2D, arm fat and trunk fat were positively, whereas leg fat was inversely, associated with the risk of CVD and mortality. These findings highlight the importance of considering both the amount and the location of body fat when assessing CVD and mortality risk among individuals with T2D.

Neuroprotective effects of dendrobium endophytes metabolites in SH-SY5Y cells via the Nrf2/Keap1 pathway.

Recent studies have revealed that endophytes in plants can produce metabolites with activity that is comparable to or identical to the host. Dendrobine has attracted much attention in the field of neurodegenerative diseases by exhibiting anti-oxidative stress and neuroprotective effects. This study aimed to investigate the protective effects and mechanisms of metabolites of dendrobium endophytes Pseudomonas protegens CM-YJ44 and Priestia megaterium D-HT207 against H2O2-induced oxidative stress injury in SH-SY5Y cells. Results showed that there were 50 neuroprotective compounds in CM-YJ44 and 72 neuroprotective compounds in D-HT207. Those both increased significantly cell viability, decreased contents of ROS in H2O2-induced SH-SY5Y cells. It was confirmed that metabolites of CM-YJ44 and D-HT207 inhibited the H2O2-induced oxidative stress injury in SH-SY5Y cells, which mechanism is related to inhibition of ROS production, alteration of MMP, and inhibition of apoptosis and inflammatory factors expression via the Nrf2/Keap1 pathway.