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Background To figure out the efficacy, effects, safety and patient’s subjective perceptions of phacoemulsification with the active-fluidics system (AFS).Patients and methods This was a prospective, randomized, double-masked, controlled clinical study. Age-related cataract patients were recruited and randomly assigned to the AFS group and gravity-fluidics system (GFS) group in a ratio of 1:1 to have phacoemulsification. Participants were followed up at one day, one week, one month and three months postoperatively (Chinese Clinical Trial Registry, ChiCTR2100044409).Results The overall included participants were 107 finally. The total aspiration time of the AFS group was significantly less than that of the GFS group (p = .020), while no significant difference existed in cumulative dissipated energy and estimated fluid usage between the two groups. The best corrected visual acuity was significantly better in the AFS group at one day and one week postoperatively (p = .002, p = .038 respectively). The recovery of central corneal thickening and macular superficial vasculature increase was earlier in the AFS group. The central retinal thickness was significantly higher in the GFS group at one month and three months postoperatively (p = .029, p = .016 respectively). The incidence of corneal adverse events was higher in GFS group (p = .035). No serious adverse events occurred in either group. Pain scores and the scores of Cat-PROM5 questionnaire of the AFS group were significantly lower than that of the GFS group (p = .011, p = .002 respectively).Conclusion AFS improves the efficiency, effects, safety and patients’ subjective perceptions of phacoemulsification compared with GFS. It is worthwhile to promote its application in cataract surgery.KEY MESSAGESThe active-fluidics system automatically detects and maintains stable intraocular pressure at the set value.The active-fluidics system improves the efficiency, effects, safety and patients’ subjective perceptions in phacoemulsification.

Abstract The shelf-stability issue, originating from the ZnO-induced positive aging effect, poses a significant challenge to industrializing the display technology based on solution-processed quantum-dot light-emitting diodes (QLEDs). Currently, none of the proposed solutions can simultaneously inhibit exciton quenching caused by the ZnO-based electron-transporting layer (ETL) and retain other advantages of ZnO. Here in this work, we propose a bilayer design of ETL in which a buffer layer assembled of SnO2 nanoparticles (NPs) suppresses the QD-ETL exciton quenching and tunes charge balance while ZnO NPs provide high electron conductivity. As a result, the bottom-emitting QLED combining capped ZnO and SnO2 buffer exhibit a maximum luminance over 100,000 cd m−2 and a T 95 operational lifetime averaging 6200 h at 1000 cd m−2 on the premise of entirely inhibiting positive aging.

Abstract Objectives Nonvalvular atrial fibrillation (NVAF) concomitant with coronary artery disease (CAD) may increase the risk of thromboembolism. Antithrombotic therapy for NVAF patients with percutaneous coronary intervention (PCI) remains contradictory and challenging. This study aimed to assess the safety and efficacy of left atrial appendage closure (LAAC) in a cohort of patients with NVAF and PCI. Methods A total of 109 patients undergoing LAAC procedures between March 2017 and December 2020 were categorized into 2 groups, Group I included 36 patients with PCI while group II included 73 patients without. Peri-procedural and long-term complications, as well as ischemia and bleeding events, were retrospectively analyzed. Results Group I had more diabetes mellitus (55.6% vs. 26.0%; p = 0.003), higher CHA2DS2-VASc scores (5.44 ± 1.85 vs. 4.22 ± 1.64; p = 0.002) and HAS-BLED scores (3.39 ± 0.93 vs. 2.74 ± 1.05; p = 0.003) compared to Group II. Procedure-related complications within 7 days were similar in both groups (8.3% vs. 8.2%; P = 1.000). Over a median follow-up period of 20.9 months, there were no significant differences between two subgroups with regard to cardiovascular death (2.8% vs. 0%, p = 0.330), stroke/transient ischemic attack (2.8% vs. 5.5%, p = 1.000), major bleeding (0% vs. 2.7%, p = 1.000) and device-related thrombus (8.3% vs. 1.4%, p = 0.104). The observed annualized thromboembolic and major bleeding events determined by Kaplan–Meier analysis decreased by 82.4% and 100% in group I, 55.9% and 75.8% in group II, respectively. Conclusion LAAC is a safe and effective option for stroke prevention in NVAF patients with PCI.

Quantum dimer models are known to host topological quantum spin liquid phases, and it has recently become possible to simulate related $${{\mathbb{Z}}}_{2}$$ Z 2 gauge theories with Rydberg atoms. Yan et al. compute the phase diagram of an experimentally motivated quantum dimer model on a triangular lattice with fluctuating dimer density.

Abstract Background Successful implantation is a complex process that is influenced by embryo quality, endometrial receptivity, immune factors, and the specific type of in vitro fertilization protocol used. DNA topoisomerase IIα (TOP2A) is a well-known protein involved in cell proliferation; however, its expression and effect on the endometrium in recurrent implantation failure (RIF) have not been fully elucidated. Methods The human endometrial tissues of healthy controls and patients with RIF were collected. A proteomic analysis was performed to evaluate the differentially expressed proteins between the RIF group and the fertile control group. The expression patterns of TOP2A in the human preimplantation endometrium of the patients with RIF were determined by immunohistochemical staining, Western blotting and qRT-PCR. TOP2A knockdown (sh-TOP2A) T-HESCs were generated using lentiviruses. The expression of TOP2A in T-HESCs was manipulated to investigate its role in decidualization. The TOP2A-related changes in decidualization were screened by mRNA sequencing in decidualized TOP2A knockdown and control T-HESCs and then confirmed by Western blotting and immunofluorescence staining. TOP2A-deficient mice were generated by injection of TOP2A-interfering adenovirus on GD2.5 and GD3.5. Results We performed a proteomic analysis of endometrial tissues to investigate the potential pathogenesis of RIF by comparing the patients with RIF and the matched controls and found that TOP2A might be a key protein in RIF. TOP2A is ubiquitously expressed in both stromal and glandular epithelial cells of the endometrium. The data indicate that TOP2A expression is significantly lower in the mid-secretory endometrium of women with RIF. TOP2A expression was downregulated under stimulation by 8-bromo-cAMP and MPA. Ablation of TOP2A resulted in upregulated expression of decidual biomarkers and morphological changes in the cells. Mechanistic analysis revealed that TOP2A regulates the NF-κB signaling pathway in decidualized T-HESCs. The TOP2A-deficient mice exhibited lower fetal weights. Conclusions Our findings revealed that abnormal expression of TOP2A affects decidualization and changes the “window of implantation”, leading to RIF. TOP2A participates in the processes of decidualization and embryo implantation, functioning at least in part through the NF-κB pathway. Regulating the expression of TOP2A in the endometrium may become a new strategy for the prevention and treatment of RIF.

IntroductionOverweight and obese are important factors leading to the occurrence of long-term complications in women with polycystic ovary syndrome (PCOS). There has been controversy over whether dissatisfaction with pregnancy outcomes in PCOS patients is influenced by chronic inflammatory status or obesity. This retrospective study analyzed the levels of inflammatory factors in PCOS patients with different body mass index (BMI) groups and effective predictors of in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) pregnancy outcomes.MethodsThere were 273 women with PCOS diagnosed who completed serum inflammatory factors test between January 2017 and June 2022 were selected. The data of 7,649 infertility PCOS patients who received their first IVF/ICSI treatment in the Reproductive Center of Peking University Third Hospital during the period of the study were collected. Finally, 92 PCOS patients were included in the high BMI group, while 97 patients were included in the normal BMI group. Baseline characteristics were collected and the pregnancy outcomes were compared among the two groups. Then, serum inflammatory factors’ effect on IVF/ICSI pregnancy outcomes were analyzed with age, anti-Mullerian Hormone (AMH) and BMI adjusted.ResultsPCOS patients in the high BMI group significantly had a lower number of oocytes retrieved and good quality embryos. The high BMI group PCOS patients had higher levels of IL-6 and lower cumulative clinical pregnancy and live birth rates. The level of GM-CSF was higher in the first cycle transfer and cumulative miscarriage group. High TNF-α was negatively correlated with the first transfer cycle and cumulative clinical pregnancy rates after age, AMH and high BMI adjusted. In addition, the cumulative live birth rate was negatively correlated with high IL-6, but the first cycle transfer and cumulative live birth rates were positively correlated with high IL-1β.DiscussionFor PCOS patients, in addition to BMI, attention should also be paid to inflammatory indicators. High levels of TNF-α and IL-6 were negatively correlated with pregnancy outcomes, but high IL-1β was positively correlated with live birth rates among PCOS patients. The level of GM-CSF was higher in miscarriage PCOS patients.

Background Potentially inappropriate prescribing (PIP) is common in primary care and is associated with adverse outcomes. Knowledge of the risk factors of PIP can be critical in designing PIP interventions, especially in guiding our understanding on how PIP occurs in primary care. Objective This systematic review examined factors associated with PIP, specific to primary care. Methods We searched PubMed, Embase, CINAHL, Web of Science, Scopus and PsycINFO for studies related to ‘older persons’, ‘primary care’ and ‘inappropriate prescribing’. Two reviewers conducted study selection, data extraction and quality appraisal. Factors associated with PIP were narratively synthesized. Results Of the 1017 articles identified, we included 25 articles and a total of 2,893,925 participants, with average age of 70.4–84.0 years. Risk factors of PIP could be classified into patient, physician and system factors. Patient factors were related to patient demographics (advanced age, lower education level and lower socioeconomic status), medical comorbidities (polypharmacy and multimorbidity) and lifestyle factors (unhealthy habits and use of over-the-counter medications). Physician and system factors included older, male, solo general practitioner (GP), higher number of visits of pharmaceutical sales representatives to GP, centrally located GP practice, and smaller number of older patients following up with GP, and medication source from public health system. Conclusions The findings provide contextual information to guide our understanding of PIP in primary care. Factors identified in this review can inform the design of complex interventions for PIP, as well as be used to develop risk prediction tools to identify high-risk groups who may require further interventions related to PIP.

BackgroundPolymyalgia rheumatica (PMR) is a common inflammatory disease in elderly persons whose mechanism of pathogenesis has not been elucidated. Glucocorticoids are the main first-line treatments but result in numerous side effects. Therefore, there is a need to explore pathogenetic factors and identify possible glucocorticoid-sparing agents. We aimed to study the pathogenetic features of the disease and assess the efficacy and safety of Janus tyrosine kinase (JAK)-inhibitor tofacitinib in patients with PMR.Methods and findingsWe recruited treatment-naïve PMR patients from the First Affiliated Hospital, Zhejiang University School of Medicine, between September 2020 and September 2022. In the first cohort, we found that the gene expression patterns of peripheral blood mononuclear cells (PBMCs) in 11 patients (10 female, 1 male, age 68.0 ± 8.3) with newly diagnosed PMR were significantly different from 20 healthy controls (17 female, 3 male, age 63.7 ± 9.8) by RNA sequencing. Inflammatory response and cytokine-cytokine receptor interaction were the most notable pathways affected. We observed marked increases in expression of IL6R, IL1B, IL1R1, JAK2, TLR2, TLR4, TLR8, CCR1, CR1, S100A8, S100A12, and IL17RA, which could trigger JAK signaling. Furthermore, tofacitinib suppressed the IL-6R and JAK2 expression of CD4+T cells from patients with PMR in vitro. In the second cohort, patients with PMR were randomized and treated with tofacitinib or glucocorticoids (1/1) for 24 weeks. All PMR patients underwent clinical and laboratory examinations at 0, 4, 8, 12, 16, 20, and 24 weeks, and PMR activity disease scores (PMR-AS) were calculated. The primary endpoint was the proportion of patients with PMR-AS ≤10 at weeks 12 and 24. Secondary endpoints: PMR-AS score, c-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) at weeks 12 and 24. Thirty-nine patients with newly diagnosed PMR received tofacitinib, and 37 patients received glucocorticoid. Thirty-five patients (29 female, 6 male, age 64.4 ± 8.4) and 32 patients (23 female, 9 male, age 65.3 ± 8.7) patients completed the 24-week intervention, respectively. There were no statistically significant differences in primary or secondary outcomes. At weeks 12 and 24, all patients in both groups had PMR-AS ConclusionsWe found that JAK signaling was involved in the pathogenesis of PMR. Tofacitinib effectively treated patients with PMR as glucocorticoid does in this randomized, monocenter, open-label, controlled trial (ChiCTR2000038253).Trial registrationThis investigator-initiated clinical trial (IIT) had been registered on the website (http://www.chictr.org.cn/, ChiCTR2000038253).

Study region: Poyang lake wetland Study focus: Evapotranspiration (ET) is a critical parameter in the hydrologic and energy budget, and it is important for understanding spatio-temporal variations in ET in large lake wetlands. Monthly ET in the Poyang Lake wetland during 2008–2017 was estimated by the remote sensing ET retrieval model based on a Nonparametric approach (RS-NP). And the spatio-temporal variation of ET and the influencing factors were analyzed. New hydrological insights for the region: The validation revealed the usefulness of the RS-NP model in a moist region and yielded a relative error of 6 % (12 %) in the wet (dry) season. Temporally, the average yearly ET was 884 mm with ET/P (precipitation) of 55 %− 65 %. The monthly ET/P ratio increased significantly from 40 %− 50 % from January to May to 90 %− 130 % from July to October. ET in June was lower by over 20 % than that in May and July with the lowest ET/P value (33 %). Spatially, relatively larger and lower ET occurred in the northern and southern parts, respectively. The main factors affecting ET variability were downwelling shortwave radiation (∼2/3 contribution) and water area (∼1/3 contribution) at the monthly scale. Precipitation and surface temperature dominantly controlled the hysteresis effects with a lag of one month and regulated LE monthly variations. This study improves our understanding of complicated water-atmosphere interactions and their linkages with environmental factors in large lake systems.

With a shift towards plant-based diets for human and planetary health, monitoring the mineral content of staple crops is important to ensure population nutrient requirements can be met. This review aimed to explore changes in the iron content of unprocessed wheat and rice in Australia over time. A comprehensive systematic search of four electronic databases and the gray literature was conducted. A total of 25 papers published between 1930 and 2023 that measured the iron content of unprocessed wheat and rice were included. Triticum aestivum was the most common wheat type studied, including 26 cultivars; iron content ranged from 40 to 50 µg/g in the 1930s and 1970s and was more variable after this time due to the introduction of modern cultivars, with most values between 25 and 45 µg/g. The iron content of rice (Oryza sativa) was more consistent at 10–15 µg/g between the 1980s and 2020s. Variations over the years may be attributed to environmental, biological, and methodological factors but these were not well documented across all studies, limiting the interpretation of findings. As the number of individuals following plant-based diets continues to rise, the ongoing monitoring of the mineral content in commonly consumed plant-based foods is warranted.

Thin, supported inorganic mesoporous membranes are used for the removal of salts, small molecules (PFAS, dyes, and polyanions) and particulate species (oil droplets) from aqueous sources with high flux and selectivity. Nanofiltration membranes can reject simple salts with 80–100% selectivity through a space charge mechanism. Rejection by size selectivity can be near 100% since the membranes can have a very narrow size distribution. Mesoporous membranes have received particular interest due to their (potential) stability under operational conditions and during defouling operations. More recently, membranes with extreme stability became interesting with the advent of in situ fouling mitigation by means of ultrasound emitted from within the membrane structure. For this reason, we explored the stability of available and new membranes with accelerated lifetime tests in aqueous solutions at various temperatures and pH values. Of the available ceria, titania, and magnetite membranes, none were actually stable under all test conditions. In earlier work, it was established that mesoporous alumina membranes have very poor stability. A new nanofiltration membrane was made of cubic zirconia membranes that exhibited near-perfect stability. A new ultrafiltration membrane was made of amorphous silica that was fully stable in ultrapure water at 80 °C. This work provides details of membrane synthesis, stability characterization and data and their interpretation.

(1) Background: Diabetic cardiomyopathy (DCM) is a unique form of cardiomyopathy that develops as a consequence of diabetes and significantly contributes to heart failure in patients. Esaxerenone, a selective non-steroidal mineralocorticoid receptor antagonist, has demonstrated potential in reducing the incidence of cardiovascular and renal events in individuals with chronic kidney and diabetes disease. However, the exact protective effects of esaxerenone in the context of DCM are still unclear. (2) Methods: The DCM model was successfully induced in mice by administering streptozotocin (55 mg/kg per day) for five consecutive days. After being fed a normal diet for 16 weeks, echocardiography was performed to confirm the successful establishment of the DCM model. Subsequent sequencing and gene expression analysis revealed significant differences in gene expression in the DCM group. These differentially expressed genes were identified as potential targets for DCM. By utilizing the Swiss Target Prediction platform, we employed predictive analysis to identify the potential targets of esaxerenone. A protein–protein-interaction (PPI) network was constructed using the common targets of esaxerenone and DCM. Enrichment analysis was conducted using Metascape. (3) Results: Compared to the control, the diabetic group exhibited impaired cardiac function and myocardial fibrosis. There was a total of 36 common targets, with 5 key targets. Enrichment analysis revealed that the chemokine and PI3K-Akt signaling pathway was considered a crucial pathway. A target-pathway network was established, from which seven key targets were identified. All key targets exhibited good binding characteristics when interacting with esaxerenone. (4) Conclusion: The findings of this study suggest that esaxerenone exhibits a favorable therapeutic effect on DCM, primarily by modulating the chemokine and PI3K-Akt signaling pathway.

In this paper, we propose a novel liquid metal microheater utilizing a textured structure. This microheater effectively solves the problem of the liquid metal in the PDMS flow channel fracturing at a certain temperature and significantly increases the maximum operating temperature that can be achieved by the current liquid metal microheater. Experimental results demonstrate that this new structured microheater can achieve a maximum operating temperature exceeding 300 °C. To explain the performance improvement and the reasons behind liquid metal fracture, corresponding experiments were conducted, and explanations were provided based on the experimental results. Subsequently, we verified the mechanical flexibility of the microheater and found that it exhibits excellent tensile and bending resistance. Finally, utilizing its good mechanical flexibility, the microheater was successfully attached to the side wall of a cup, resulting in the boiling of water.

Abstract Background As one of the severe complications of diabetes mellitus, diabetic retinopathy (DR) is the leading cause of blindness in the working age worldwide. Although panretinal photocoagulation (PRP) was standard treatment, PRP-treated DR still has a high risk of progression. Hence, this study aimed to assess the risk factors and establish a model for predicting worsening diabetic retinopathy (DR-worsening) within five years after PRP. Methods Patients who were diagnosed with severe non-proliferative diabetic retinopathy or proliferative diabetic retinopathy and treated with PRP were included, and those patients were randomly assigned to either a training or validation cohort. The multivariate logistic regression analysis was used to screen potential risk factors for DR-worsening in the training cohort. Then the model was established after including significant independent risk factors and further validated using discrimination and calibration. Results A total of 271 patients were included, and 56.46% of patients had an outcome of DR-worsening. In the training cohort (n = 135), age (odds ratio [OR] = 0.94, 95% confidence interval [CI] 0.90–0.98), baseline best corrected visual acuity (logMAR) (OR = 10.74, 95% CI 1.84–62.52), diabetic nephropathy (OR = 9.32, 95% CI 1.49–58.46), and hyperlipidemia (OR = 3.34, 95% CI 1.05–10.66) were screened out as the independent risk factors, which were incorporated into the predictive model. The area under the receiver operating characteristic curve and calibration slope in the training and validation cohort were 0.79, 0.96 (95% CI 0.60–1.31), and 0.79, 1.00 (95% CI 0.66–1.34), respectively. Two risk groups were developed depending on the best cut-off value of the predicted probability, and the actual probability was 34.90% and 82.79% in the low-risk and high-risk groups, respectively (P

Abstract We develop a nonequilibrium increment method in quantum Monte Carlo simulations to obtain the Rényi entanglement entropy of various quantum many-body systems with high efficiency and precision. To demonstrate its power, we show the results on a few important yet difficult (2 + 1)d quantum lattice models, ranging from the Heisenberg quantum antiferromagnet with spontaneous symmetry breaking, the quantum critical point with O(3) conformal field theory (CFT) to the toric code $${{\mathbb{Z}}}_{2}$$ Z 2 topological ordered state and the Kagome $${{\mathbb{Z}}}_{2}$$ Z 2 quantum spin liquid model with frustration and multi-spin interactions. In all these cases, our method either reveals the precise CFT data from the logarithmic correction or extracts the quantum dimension in topological order, from the dominant area law in finite-size scaling, with very large system sizes, controlled errorbars, and minimal computational costs. Our method, therefore, establishes a controlled and practical computation paradigm to obtain the difficult yet important universal properties in highly entangled quantum matter.

Objective To explore the relationship between the distributions of traditional Chinese medicine (TCM) constitutional types of patients with mammary cancer and their anxiety and depression status. Methods A total of 507 patients with mammary cancer who were admitted and treated in Yunnan Cancer Hospital from July 2019 to July 2020 were selected. Baseline data were collected through questionnaires, and the Constitution in Chinese Medicine Questionnaire (CCMQ) was used to identify their TCM constitutions. Hospital Anxiety and Depression Scale (HADS) was used for assessing the anxiety and depression status of patients. Results Totally 398 patients with mammary cancer were screened. Most of the mammary cancer patients had normal constitution, 136(34. 17%) in total, followed by 80(20. 10%) cases with yang-deficiency constitution, 39(9. 80%) cases with yin-deficiency constitution and 38 (9. 55%)cases with qi depression constitution. There were 75(18. 84%) patients with depression and 89(22. 36%) patients with anxiety. Patients who had normal constitutional types were control group. Except for dampness-heat constitution and yang-deficiency constitution, the other six biased constitutions were all risk factors for the onset of depression. Among them, the top three are blood stasis constitution (OR=14. 71, P

Objective To explore the characteristics of macroautophagy and molecular chaperone-mediated autophagy (CMA) in the oxidative stress injury of human umbilical vein endothelial cells (HUVECs). Methods After HUVECs were treated with oxidized low density lipoprotein (OX-LDL) at different concentrations(0、20、50、100、200 μg/mL), the production of reactive oxygen species (ROS) was measured to screen the optimal concentration to induce HUVECs oxidative stress. The cells were divided into 4 groups: control group (without any treatment), macroautophagy inhibition group (treated with 10 mmol/L 3-MA, specific inhibitor of macroautophagy), oxidative stress group (treated with 50 μg/mL OX-LDL), and macroautophagy inhibition-oxidative stress group (treated with 10 mmol/L 3-MA+50 μg/mL OX-LDL). The expression levels of proliferation marker protein PCNA, apoptosis marker Caspase-3, macroautophagy marker Beclin-1, and CMA markers Hsc70 and Lamp-2 were detected in each group with Western blotting. The proliferation, apoptosis, 2 kinds of autophagy under different treatments were evaluated respectively. After the cells of the oxidative stress group and macroautophagy inhibition-oxidative stress group were treated for different duration (1, 3, 6, 12 and 48 h), the proliferation and apoptosis of HUVECs were tested by CCK-8 assay and Annexin-V/PI double staining, respectively. Western blotting was adopted to determine the protein levels of Beclin-1, Hsc70 and Lamp-2. Finally, the time regulation characteristics of the 2 autophagy pathways before and after macroautophagy inhibition were analyzed. Results Under OX-LDL induced oxidative stress, the ROS level was elevated with the increase of OX-LDL concentration, and 50 μg/mL was finally selected as the appropriate concentration for subsequent experiments. As compared with the control group, the levels of Caspase-3, Beclin-1, Hsc70 and Lamp-2 were up-regulated, while that of PCNA was down-regulated in the oxidative stress group (P < 0.05). With the prolongation of treatment time, proliferation inhibition rate, overall apoptotic rate and Lamp-2 level were increased within 48 h, Hsc70 level was elevated after 6 h, and that of Beclin-1 was improved within 12 h in the oxidative stress group (P < 0.05). In the macroautophagy inhibition-oxidative stress group, the expression levels of Caspase-3, Hsc70 and Lamp-2 were also up-regulated, that of PCNA down-regulated (P < 0.05), those of Hsc70 and Lamp-2 were increased at the same time and that of Hsc70 was in an elevation after 3 h of treatment (P < 0.05). Conclusion Macroautophagy and CMA are activated successively during the process of oxidative stress, and CMA can be enhanced after macroautophagy inhibition. The early activation contributes to attenuate oxidative stress-induced damage to endothelial cells.

PurposeTo explore fecal immune-related proteins that can be used for colorectal cancer (CRC) diagnosis.Patients and methodsThree independent cohorts were used in present study. In the discovery cohort, which included 14 CRC patients and 6 healthy controls (HCs), label-free proteomics was applied to identify immune-related proteins in stool that could be used for CRC diagnosis. Exploring potential links between gut microbes and immune-related proteins by 16S rRNA sequencing. The abundance of fecal immune-associated proteins was verified by ELISA in two independent validation cohorts and a biomarker panel was constructed that could be used for CRC diagnosis. The validation cohort I included 192 CRC patients and 151 HCs from 6 different hospitals. The validation cohort II included 141 CRC patients, 82 colorectal adenoma (CRA) patients, and 87 HCs from another hospital. Finally, the expression of biomarkers in cancer tissues was verified by immunohistochemistry (IHC).ResultsIn the discovery study, 436 plausible fecal proteins were identified. And among 67 differential fecal proteins (|log2 fold change| > 1, P< 0.01) that could be used for CRC diagnosis, 16 immune-related proteins with diagnostic value were identified. The 16S rRNA sequencing results showed a positive correlation between immune-related proteins and the abundance of oncogenic bacteria. In the validation cohort I, a biomarker panel consisting of five fecal immune-related proteins (CAT, LTF, MMP9, RBP4, and SERPINA3) was constructed based on the least absolute shrinkage and selection operator (LASSO) and multivariate logistic regression. The biomarker panel was found to be superior to hemoglobin in the diagnosis of CRC in both validation cohort I and validation cohort II. The IHC result showed that protein expression levels of these five immune-related proteins were significantly higher in CRC tissue than in normal colorectal tissue.ConclusionA novel biomarker panel consisting of fecal immune-related proteins can be used for the diagnosis of CRC.

This study aims to investigate the souvenir-person-place bonding for sustaining cultural heritage. Previous studies acknowledge souvenirs could represent a place; however, how people perceive souvenirs as representative of the place still needs to be studied. This study comprehends the traditional craft by identifying the dimensions of place-based craft souvenirs and exploring the connections between souvenirs, craft, and place. A qualitative approach was employed. In-depth interviews, participant and non-participant observations were conducted in Jinan, China, a long-history city with many traditional crafts. Thirty documents were imported into ATLAS.ti software for analysis. The ‘place-based craft souvenir’, ‘evaluation of souvenir’, ‘place meaning’, and ‘satisfaction’ emerged as the four main themes of ‘souvenir-person-place bonding’. These ‘souvenir-people-place’ bonding motivate individuals’ understanding of traditional craft and place, contributing to the sustainability of the traditional craft.

Temperature variation structures the composition and diversity of gut microbiomes in ectothermic animals, key regulators of host physiology, with potential benefit to host or lead to converse results (i.e., negative). So, the significance of either effect may largely depend on the length of time exposed to extreme temperatures and how rapidly the gut microbiota can be altered by change in temperature. However, the temporal effects of temperature on gut microbiota have rarely been clarified. To understand this issue, we exposed two juvenile fishes (Cyprinus carpio and Micropterus salmoides), which both ranked among the 100 worst invasive alien species in the world, to increased environmental temperature and sampled of the gut microbiota at multiple time points after exposure so as to determine when differences in these communities become detectable. Further, how temperature affects the composition and function of microbiota was examined by comparing predicted metagenomic profiles of gut microbiota between treatment groups at the final time point of the experiment. The gut microbiota of C. carpio was more plastic than those of M. salmoides. Specifically, communities of C. carpio were greatly altered by increased temperature within 1 week, while communities of M. salmoides exhibit no significant changes. Further, we identified 10 predicted bacterial functional pathways in C. carpio that were temperature-dependent, while none functional pathways in M. salmoides was found to be temperature-dependent. Thus, the gut microbiota of C. carpio was more sensitive to temperature changes and their functional pathways were significantly changed after temperature treatment. These results showed the gut microbiota of the two invasive fishes differ in response to temperature change, which may indicate that they differ in colonization modes. Broadly, we have confirmed that the increased short-term fluctuations in temperatures are always expected to alter the gut microbiota of ectothermic vertebrates when facing global climate change.

To investigate differences in fresh leaves of tea plants at different ages in gene expression, metabolism, and dried tea quality, and to provide references to a deep exploration on metabolite differential accumulation of fresh leaves of tea plants at different ages as well as the regulation mechanism, two groups of fresh leaves from tea plants at different ages (group JP: 20-, 200-, and 1,200-year tea plants; group YX: 50-, 100-, and 400-year tea plants) were chosen as materials, and their differences in gene expression, metabolites, and metabolic regulatory network were investigated by transcriptomics and metabolomics. A total of 12,706 differentially expressed genes (DEGs) were screened from the fresh tea leaves in the JP group, of which tea-20 vs. tea-200 had the largest number of DEGs, up to 9,041 (4,459 down-regulated genes, 4,582 up-regulated genes). A total of 644 common genes in the fresh leaves of three different ages of tea plants in the JP group were differentially expressed. A total of 8,971 DEGs were screened from the fresh leaf samples of tea plants in the YX group, of which the number of DEGs obtained in the tea-50 vs. tea-400 comparison combination was the largest with a total of 3,723 (1,722 up-regulated genes and 2,001 down-regulated genes). A total of 147 common genes were differentially expressed in the fresh leaves of three different tree ages in the YX group. The pathway enrichment analysis showed that most up-regulated DEGs and their related metabolic pathways were similar in the two groups, and that the metabolic pathways of common significant enrichment included flavonoid biosynthesis, phenylpropane biosynthesis, carbon metabolism, amino acid biosynthesis, and plant pathogen interaction. The metabolomics results showed that 72 and 117 different metabolites were screened from the JP and YX groups, respectively. Most of the different metabolites in the two groups were flavonoids, phenolic acids, amino acids, and their derivatives. Among them, the number of down-regulated flavonoids in older tea plants is generally higher than the number of up-regulated flavonoids. Moreover, according to the sensory evaluation results of dried tea of fresh leaves from tea plants of different ages, tea-1200 and tea-400 showed the highest sensory evaluation scores in their groups. With increase in plant age, the fragrance of the tea was more elegant, and it changed from a dense scent to a faint scent; the tea tasted sweet and its freshness increased, while the sense of astringency was weakened and the concentration declined. Therefore, the quality difference of tea of different tree ages is mainly related to secondary metabolic pathways such as the flavonoid biosynthesis pathway. With increase in tea age, a large number of gene expression in the flavonoid biosynthesis pathway is down-regulated, which reduces the content of bitter flavonoid substances in fresh leaves and makes tea soup more mellow.

Biodiversity is essential for the provision of multiple ecosystem functions simultaneously (ecosystem multifunctionality EMF). Yet, it remains unclear whether and how dominant plant species impact EMF. Here, we aimed at disentangling the direct from indirect above- and belowground pathways by which dominant plant species influence EMF. We evaluated the effects of two dominant plant species (Dasiphora fruticosa, and the toxic perennial plant Ligularia virgaurea) with expected positive and negative impacts on the abiotic environment (soil water content and pH), surrounding biological communities (plant and nematode richness, biomass, and abundance in the vicinity), and on the EMF of alpine meadows, respectively. We found that the two dominant plants enhanced EMF, with a positive effect of L. virgaurea on EMF greater than that of D. fruticosa. We also observed that dominant plants impacted on EMF through changes in soil water content and pH (indirect abiotic effects), but not through changes in biodiversity of surrounding plants and nematodes (indirect biotic pathway). Our study suggests that dominant plants may play an important role in promoting EMF, thus expanding the pervasive mass-ratio hypothesis originally framed for individual functions, and could mitigate the negative impacts of vegetation changes on EMF in the alpine meadows.

Background: Extracorporeal cardiopulmonary resuscitation (ECPR) represents last-line salvage therapy for poisoning-induced cardiac arrest but no review has focused on this specific area. Objective: This scoping review sought to evaluate the survival outcomes and characteristics of published cases of ECPR for toxicological arrest, with the aim of highlighting the potential and limitations of ECPR in toxicology.Eligibility Criteria.We searched PubMed and Cochrane for eligible papers from database inception to October 1, 2022 using the keywords “toxicology”, “ECLS” and “CPR”. References of included publications were searched to identify additional relevant articles. Qualitative synthesis was used to summarize the evidence. Results: 85 articles were chosen: 15 case series, 58 individual cases and 12 other publications that were analyzed separately due to ambiguity. ECPR may improve survival outcomes in selected poisoned patients, although the extent of benefit is unclear. As ECPR for poisoning-induced arrest may have better prognosis compared to from other aetiologies, it is likely reasonable to apply ELSO ECPR consensus guideline recommendations to toxicological arrest.Out-of-hospital cardiac arrest alone may not be sufficient grounds to deny ECPR if effective resuscitation had been promptly instituted. Poisonings involving membrane-stabilizing agents and cardio-depressive drugs, and cardiac arrests with shockable rhythms appear to have better outcomes. ECPR may permit excellent neurologically-intact recovery despite prolonged low-flow time of up to four hours. Early ECLS activation and pre-emptive catheter placement can significantly shorten time-to-ECPR and possibly improve survival. Conclusion: As effects of poisoning may be reversible, ECPR can potentially support poisoned patients through the critical peri-arrest state.

Background: Anemia combined with increased serum sedimentation (ESR) can be secondary to many diseases and may be ignored when the patient had few clinical symptoms. We report a case of persistent anemia combined with ESR for more than 2 years firstly misdiagnosed as lymphoma. When she received a chest CT scan multiple enlarged lymph nodes were found. Methods: The chest contrast-enhanced CT scan and endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) in the right hilum enlarged lymph nodes were performed for diagnosis. Results: The chest CT scan and EBUS showed multiple enlarged right hilum and mediastinum lymph nodes without calcification. Pathology of EBUS-TBNA showed multiple granulomas; Zeihl-Neelsen acid-fast stain was positive. Conclusions: Systemic lymph node tuberculosis is rarely seen in adult patients. In a young patient who has anemia combined with increased ESR should be excluded if those changes are secondary to tuberculosis. [ABSTRACT FROM AUTHOR]

The origin of pseudogap in high-T c superconductors remains a big puzzle. Here, the authors report numerical evidence of pseudogap behavior employing Quantum Monte Carlo algorithm emerging from pairing fluctuations in a quantum-critical non-Fermi liquid, similar to the pseudogap phase observed in cuprate superconductors.

Abstract Background To identify the potential biological target molecules and the corresponding interaction networks in primary open-angle glaucoma (POAG) development. Methods The microarray datasets of GSE138125 and GSE27276 concerning lncRNA and mRNA expression profiles in trabecular meshwork of POAG were downloaded from the Gene Expression Omnibus database. The R software was applied to identify differentially expressed (DE) lncRNAs and mRNAs in POAG, and to perform GO and KEGG functional enrichment analysis. Protein–protein interaction (PPI) network and module analysis, and lncRNA-miRNA-mRNA competing endogenous RNA (ceRNA) network were performed by Cytoscape software. Results A total of 567 DE-mRNAs were identified from GSE138125 and GSE27276, including 298 up-regulated and 269 down-regulated mRNAs, which were found enriching in biological processes of extracellular matrix organization and epidermis development, respectively. KEGG pathway enrichment analysis further revealed that module genes in PPI network were primarily involved in the AGE-PAGE, PI3K-Akt and TGF-β signaling pathways. Moreover, 897 up-regulated and 1036 down-regulated DE-lncRNAs were identified from GSE138125. Through literature review and databases searching, we obtained 712 lncRNA-miRNA and 337 miRNA-mRNA pairs based on the selected eight POAG-related miRNAs. After excluding 702 lncRNAs and 284 mRNAs that were not comprised in the DE-lncRNA and DE-mRNAs, a total of 53 lncRNA nodes, eight miRNA nodes, 10 mRNA nodes, and 78 edges were included in the final ceRNA network. Conclusions This study demonstrated the lncRNA and mRNA expression profiles of trabecular meshwork in POAG patients and the normal controls, and identified potentially ceRNAs and pathways which might improve the pathogenic understanding of this ocular disease.

Abstract Introduction The burden of chronic kidney disease (CKD) is rising globally including in Singapore. Primary care is the first point of contact for most patients with early stages of CKD. However, several barriers to optimal CKD management exist. Knowing healthcare professionals’ (HCPs) perspectives is important to understand how best to strengthen CKD services in the primary care setting. Integrating a theory-based framework, we explored HCPs’ perspectives on the facilitators of and barriers to CKD management in primary care clinics in Singapore. Methods In-depth interviews were conducted on a purposive sample of 20 HCPs including 13 physicians, 2 nurses and 1 pharmacist from three public primary care polyclinics, and 4 nephrologists from one referral hospital. Interviews were audio recorded, transcribed verbatim and thematically analyzed underpinned by the Theoretical Domains Framework (TDF) version 2. Results Numerous facilitators of and barriers to CKD management identified. HCPs perceived insufficient attention is given to CKD in primary care and highlighted several barriers including knowledge and practice gaps, ineffective CKD diagnosis disclosure, limitations in decision-making for nephrology referrals, consultation time, suboptimal care coordination, and lack of CKD awareness and self-management skills among patients. Nevertheless, intensive CKD training of primary care physicians, structured CKD-care pathways, multidisciplinary team-based care, and prioritizing nephrology referrals with risk-based assessment were key facilitators. Participants underscored the importance of improving awareness and self-management skills among patients. Primary care providers expressed willingness to manage early-stage CKD as a collaborative care model with nephrologists. Our findings provide valuable insights to design targeted interventions to enhance CKD management in primary care in Singapore that may be relevant to other countries. Conclusions The are several roadblocks to improving CKD management in primary care settings warranting urgent attention. Foremost, CKD deserves greater priority from HCPs and health planners. Multipronged approaches should urgently address gaps in care coordination, patient-physician communication, and knowledge. Strategies could focus on intensive CKD-oriented training for primary care physicians and building novel team-based care models integrating structured CKD management, risk-based nephrology referrals coupled with education and motivational counseling for patients. Such concerted efforts are likely to improve outcomes of patients with CKD and reduce the ESKD burden.

Abstract Introduction In vitro fertilisation (IVF) is an effective infertility treatment but the live birth rate remains unsatisfactory. Ovarian stimulation by follicle-stimulating hormone (FSH) is routinely used in IVF and the resulting high serum estradiol levels may impair oocyte/embryo quality and endometrial receptivity. Letrozole, an aromatase inhibitor, can reduce serum estradiol levels following ovarian stimulation. We aim to test the hypothesis that co-treatment with letrozole reduces supraphysiological serum estradiol levels and improves endometrial receptivity, leading to a higher live birth rate of IVF. We are conducting a randomised controlled trial (RCT) to evaluate whether letrozole as an adjunct to FSH in IVF is superior to FSH alone in the live birth rate of fresh embryo transfer. Methods/design This is an open-label randomised controlled superiority trial being performed in two assisted reproduction centres in China. Infertile women who have antral follicle count (AFC) before ovarian stimulation or on day 5 of ovarian stimulation ≥15 are randomly allocated in a 1:1 ratio to receive either letrozole and FSH or FSH alone in a GnRH antagonist protocol. Recruited women follow the standard operating procedures of the two centres. The primary outcome is the live birth rate of the fresh embryo transfer. Stimulation parameters, maternal side effects and obstetric and perinatal complications are secondary outcomes. The planned sample size is 900, i.e. 450 per group. Discussion The present study is the first multicentre randomised study to compare the live birth rate of the fresh embryo transfer following ovarian stimulation by letrozole and FSH versus FSH alone in women with anticipated high ovarian responses. Trial registration ClinicalTrials.gov NCT02912988 . Registered on September 23, 2016. This trial protocol is version 2.0.

Ampelopsis grossedentata (AG) is mainly distributed in Chinese provinces and areas south of the Yangtze River Basin. It is mostly concentrated or scattered in mountainous bushes or woods with high humidity. Approximately 57 chemical components of AG have been identified, including flavonoids, phenols, steroids and terpenoids, volatile components, and other chemical components. In vitro studies have shown that the flavone of AG has therapeutic properties such as anti-bacteria, anti-inflammation, anti-oxidation, enhancing immunity, regulating glucose and lipid metabolism, being hepatoprotective, and being anti-tumor with no toxicity. Through searching and combing the related literature, this paper comprehensively and systematically summarizes the research progress of AG, including morphology, traditional and modern uses, chemical composition and structure, and pharmacological and toxicological effects, with a view to providing references for AG-related research.

High-strength large-volume marine concrete is a critical material required for the construction of large-span sea-crossing bridges. However, the widespread issue of cracking in this concrete type significantly impacts the durability and load-bearing capacity of concrete structures. Dealing with these cracks not only delays construction schedules but also increases project costs. Addressing these pressing technical issues, this project proposes the use of newly developed high-modulus heat-shrinkable fibers (polyethylene terephthalate fiber, also known as PET fiber) from the textile industry. These fibers utilize the heat generated during the hydration of large-volume concrete to trigger its contraction, applying three-dimensional micro-prestressing stress to enhance its crack resistance, while simultaneously incorporating prewetted aggregates with high-performance micro-porous structures and utilizing their internal curing effect to reduce concrete shrinkage. This helps to minimize the loss of micro-prestressing stress caused by concrete shrinkage and creep. This synergistic approach aims to improve the crack resistance of high-strength large-volume marine concrete. By employing modern testing and simulation analysis techniques, this study aims to uncover the mechanism by which the heat-shrinkable fibers exert micro-prestressing stress on concrete and the water release mechanism of internal curing aggregates during the temperature rise and fall stages of large-volume concrete. It seeks to elucidate the cooperative regulation of the microstructure and performance enhancement mechanisms of high-strength large-volume marine concrete by the heat-shrinkable fibers and internal curing aggregates. This research will lead to the development of novel methods for the design and crack control of high-strength large-volume marine concrete, which will be validated through engineering demonstrations. The outcomes of this study will provide theoretical foundations and technical support for the preparation of the crack-resistant large-volume marine concrete used in large-span bridges.

Hemorrhagic fever with renal syndrome (HFRS) is a zoonotic disease transmitted by several rodent species. We obtained clinical data of HFRS patients from the medical records of the People’s Hospital of Xiangyun County in Dali Prefecture from July 2019 to August 2021. We collected epidemiological data of HFRS patients through interviews and investigated host animals using the night clip or night cage method. We systematically performed epidemiological analyses of patients and host animals. The differences in the presence of rodent activity at home (χ2 = 8.75, p = 0.031 < 0.05), of rodent-proof equipment in the food (χ2 = 9.19, p = 0.025 < 0.05), and of rodents or rodent excrement in the workplace (χ2 = 10.35, p = 0.014 < 0.05) were statistically different in the four clinical types, including mild, medium, severe, and critical HFRS-associated diseases. Furthermore, we conducted molecular detection of orthohantavirus in host animals. The total orthohantavirus infection rate of rodents was 2.72% (9/331); the specific infection rate of specific animal species was 6.10% (5/82) for the Apodemus chevrieri, 100% (1/1) for the Rattus nitidus, 3.77% (2/53) for the Rattus norvegicus, and 12.50% (1/8) for the Crocidura dracula. In this study, a total of 21 strains of orthohantavirus were detected in patients and rodents. The 12 orthohantavirus strains from patients showed a closer relationship with Seoul orthohantavirus (SEOOV) L0199, DLR2, and GZRn60 strains; the six orthohantavirus strains from Rattus norvegicus and Apodemus chevrieri were closely related to SEOOV GZRn60 strain. One strain (XYRn163) from Rattus norvegicus and one strain (XYR.nitidus97) from Rattus nitidus were closely related to SEOOV DLR2 strain; the orthohantavirus strain from Crocidura dracula was closely related to the Luxi orthohantavirus (LUXV) LX309 strain. In conclusion, patients with HFRS in Xuangyun County of Dali Prefecture are predominantly affected by SEOOV, with multiple genotypes of orthohantavirus in host animals, and, most importantly, these orthohantavirus strains constantly demonstrated zoonotic risk in humans.

Abnormal tendons are rarely ever repaired to the natural structure and morphology of normal tendons. To better guide the repair and regeneration of injured tendons through a tissue engineering method, it is necessary to have insights into the internal morphology, organization, and composition of natural tendons. This review summarized recent researches on the structure and function of the extracellular matrix (ECM) components of tendons and highlight the application of multiple detection methodologies concerning the structure of ECMs. In addition, we look forward to the future of multi-dimensional biomaterial design methods and the potential of structural repair for tendon ECM components. In addition, focus is placed on the macro to micro detection methods for tendons, and current techniques for evaluating the extracellular matrix of tendons at the micro level are introduced in detail. Finally, emphasis is given to future extracellular matrix detection methods, as well as to how future efforts could concentrate on fabricating the biomimetic tendons.

A resurging interest in targeted covalent inhibitors (TCIs) focus on compounds capable of irreversibly reacting with nucleophilic amino acids in a druggable target. p97 is an emerging protein target for cancer therapy, viral infections and neurodegenerative diseases. Extensive efforts were devoted to the development of p97 inhibitors. The most promising inhibitor of p97 was in phase 1 clinical trials, but failed due to the off-target-induced toxicity, suggesting the selective inhibitors of p97 are highly needed. We report herein a new type of TCIs (i.e., FL-18) that showed proteome-wide selectivity towards p97. Equipped with a Michael acceptor and a basic imidazole, FL-18 showed potent inhibition towards U87MG tumor cells, and in proteome-wide profiling, selectively modified endogenous p97 as confirmed by in situ fluorescence scanning, label-free quantitative proteomics and functional validations. FL-18 selectively modified cysteine residues located within the D2 ATP site of p97. This covalent labeling of cysteine residue in p97 was verified by LC‒MS/MS-based site-mapping and site-directed mutagenesis. Further structure–activity relationship (SAR) studies with FL-18 analogs were established. Collectively, FL-18 is the first known small-molecule TCI capable of covalent engagement of p97 with proteome-wide selectivity, thus providing a promising scaffold for cancer therapy.

The Knowledge graph, a multi-relational graph that represents rich factual information among entities of diverse classifications, has gradually become one of the critical tools for knowledge management. However, the existing knowledge graph still has some problems which form hot research topics in recent years. Numerous methods have been proposed based on various representation techniques. Graph Neural Network, a framework that uses deep learning to process graph-structured data directly, has significantly advanced the state-of-the-art in the past few years. This study firstly is aimed at providing a broad, complete as well as comprehensive overview of GNN-based technologies for solving four different KG tasks, including link prediction, knowledge graph alignment, knowledge graph reasoning, and node classification. Further, we also investigated the related artificial intelligence applications of knowledge graphs based on advanced GNN methods, such as recommender systems, question answering, and drug-drug interaction. This review will provide new insights for further study of KG and GNN.

Abstract Background Fishes are the one of the most diverse groups of animals with respect to their modes of sex determination, providing unique models for uncovering the evolutionary and molecular mechanisms underlying sex determination and reversal. Here, we have investigated how sex is determined in a species of both commercial and ecological importance, the Siamese fighting fish Betta splendens. Results We conducted association mapping on four commercial and two wild populations of B. splendens. In three of the four commercial populations, the master sex determining (MSD) locus was found to be located in a region of ~ 80 kb on LG2 which harbours five protein coding genes, including dmrt1, a gene involved in male sex determination in different animal taxa. In these fish, dmrt1 shows a male-biased gonadal expression from undifferentiated stages to adult organs and the knockout of this gene resulted in ovarian development in XY genotypes. Genome sequencing of XX and YY genotypes identified a transposon, drbx1, inserted into the fourth intron of the X-linked dmrt1 allele. Methylation assays revealed that epigenetic changes induced by drbx1 spread out to the promoter region of dmrt1. In addition, drbx1 being inserted between two closely linked cis-regulatory elements reduced their enhancer activities. Thus, epigenetic changes, induced by drbx1, contribute to the reduced expression of the X-linked dmrt1 allele, leading to female development. This represents a previously undescribed solution in animals relying on dmrt1 function for sex determination. Differentiation between the X and Y chromosomes is limited to a small region of ~ 200 kb surrounding the MSD gene. Recombination suppression spread slightly out of the SD locus. However, this mechanism was not found in the fourth commercial stock we studied, or in the two wild populations analysed, suggesting that it originated recently during domestication. Conclusions Taken together, our data provide novel insights into the role of epigenetic regulation of dmrt1 in sex determination and turnover of SD systems and suggest that fighting fish are a suitable model to study the initial stages of sex chromosome evolution.

Grade (G) 3B follicular lymphoma (FL) is a rare FL subtype which exists on a histological continuum between ‘lowgrade’ (Grade 1, 2 and 3A FL) and diffuse large B-cell lymphoma (DLBCL) appearing to share features with each. Clinical characteristics and outcomes are poorly understood due to lack of adequate representation in prospective trials and large-scale analyses. We analyzed 157 G3BFL cases from 18 international centers, and two comparator groups; G3AFL (n=302) and DLBCL (n=548). Composite histology with DLBCL or low-grade FL occurred in approximately half of the G3BFL cases. With a median of 5 years follow-up, the overall survival and progression-free survival of G3BFL patients was better than that of DLBCL patients (P

This work proposes an “N2-1” sacrificial strategy to help to improve the accuracy of the bonding technique from the existing level. The target micropattern is copied N2 times, and (N2-1) of them are sacrificed to obtain the most accurate alignment. Meanwhile, a method for manufacturing auxiliary solid alignment lines on transparent materials is proposed to visualize auxiliary marks and facilitate the alignment. Though the principle and procedure of alignment are straightforward, the alignment accuracy substantially improved compared to the original method. With this technique, we have successfully fabricated a high-precision 3D electroosmotic micropump just using a conventional desktop aligner. Because of the high precision during the alignment, the flow velocity is up to 435.62 μm/s at a driven voltage of 40 V, which far exceeds the previous similar reports. Thus, we believe that it has great potential for high precision microfluidic device fabrications.

BackgroundAt present, intensive care unit acquired weakness (ICU-AW) has become an important health care issue. The aim of this study was to develop and validate an ICU-AW prediction model for adult patients in intensive care unit (ICU) to provide a practical tool for early clinical diagnosis.MethodsAn observational cohort study was conducted including 400 adult patients admitted from September 2021 to June 2022 at an ICU with four ward at a medical university affiliated hospital in China. The Medical Research Council (MRC) scale was used to assess bedside muscle strength in ICU patients as a diagnostic basis for ICUAW. Patients were divided into the ICU-AW group and the no ICU-AW group and the clinical data of the two groups were statistically analyzed. A risk prediction model was then developed using binary logistic regression. Sensitivity, specificity, and the area under the curve (AUC) were used to evaluate the predictive ability of the model. The Hosmer-Lemeshow test was used to assess the model fit. The bootstrap method was used for internal verification of the model. In addition, the data of 120 patients in the validation group were selected for external validation of the model.ResultsThe prediction model contained five risk factors: gender (OR: 4.31, 95% CI: 1.682–11.042), shock (OR: 3.473, 95% CI: 1.191–10.122), mechanical ventilation time (OR: 1.592, 95% CI: 1.317–1.925), length of ICU stay (OR: 1.085, 95% CI: 1.018–1.156) and age (OR: 1.075, 95% CI: 1.036–1.115). The AUC of this model was 0.904 (95% CI: 0.847–0.961), with sensitivity of 87.5%, specificity of 85.8%, and Youden index of 0.733. The AUC of the model after resampling is 0.889. The model verification results showed that the sensitivity, specificity and accuracy were 71.4, 92.9, and 92.9%, respectively.ConclusionAn accurate, and readily implementable, risk prediction model for ICU-AW has been developed. This model uses readily obtained variables to predict patient ICU-AW risk. This model provides a tool for early clinical screening for ICU-AW.

Zinc exposure has been linked with disordered glucose metabolism and type 2 diabetes mellitus (T2DM) development. However, the underlying mechanism remains unclear. We conducted population-based studies and in vitro experiments to explore potential role of microRNAs (miRNAs) in zinc-related hyperglycemia and T2DM. In the discovery stage, we identified plasma miRNAs expression profile for zinc exposure based on 87 community residents from the Wuhan-Zhuhai cohort through next-generation sequencing. MiRNAs profiling for T2DM was also performed among 9 pairs newly diagnosed T2DM-healthy controls. In the validating stage, plasma miRNA related to both of zinc exposure and T2DM among the discovery population was measured by qRT-PCR in 161 general individuals derived from the same cohort. Furthermore, zinc treated HepG2 cells with mimic or inhibitor were used to verify the regulating role of miR-144-3p. Based on the discovery and validating populations, we observed that miR-144-3p was positively associated with urinary zinc, hyperglycemia, and risk of T2DM. In vitro experiments confirmed that zinc-induced increase in miR-144-3p expression suppressed the target gene Nrf2 and downstream antioxidant enzymes, and aggravated insulin resistance. Our findings provided a novel clue for mechanism underlying zinc-induced glucose dysmetabolism and T2DM development, emphasizing the important role of miR-144-3p dysregulation.

Coronavirus disease (COVID-19), a highly contagious and rapidly spreading disease with significant fatality in the elderly population, has swept across the world since 2019. Since its first appearance, the causative agent, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has undergone multiple mutations, with Omicron as the predominant circulating variant of concern at the moment. The gold standard for diagnosis of COVID-19 by real-time polymerase chain reaction (RT-PCR) to detect the virus is laborious and requires well-trained personnel to perform sophisticated procedures. Also, the genetic variants of SARS-CoV-2 that arise regularly could result in false-negative detection. Meanwhile, the current COVID-19 treatments such as conventional medicine, complementary and alternative medicine, passive antibody therapy, and respiratory therapy are associated with adverse effects. Thus, there is an urgent need to discover novel diagnostic and therapeutic approaches against SARS-CoV-2 and its variants. Over the past 30 years, nucleic acid-based aptamers have gained increasing attention and serve as a promising alternative to the antibodies in the diagnostic and therapeutic fields with their uniqueness of being small, nonimmunogenicity, and thermally stable. Aptamer targeting the SARS-CoV-2 structural proteins or the host receptor proteins represent a powerful tool to control COVID-19 infection. In this review, challenges faced by currently available diagnostic and therapeutic tools for COVID-19 are underscored, along with how aptamers can shed a light on the current COVID-19 pandemic, focusing on the critical factors affecting the discovery of high-affinity aptamers and their potential applications to control COVID-19 infection.