Endolysosomal trafficking controls yolk granule biogenesis in vitellogenic Drosophila oocytes.

Endocytosis and endolysosomal trafficking are essential for almost all aspects of physiological functions of eukaryotic cells. As our understanding on these membrane trafficking events are mostly from studies in yeast and cultured mammalian cells, one challenge is to systematically evaluate the findings from these cell-based studies in multicellular organisms under physiological settings. One potentially valuable in vivo system to address this challenge is the vitellogenic oocyte in Drosophila, which undergoes extensive endocytosis by Yolkless (Yl), a low-density lipoprotein receptor (LDLR), to uptake extracellular lipoproteins into oocytes and package them into a specialized lysosome, the yolk granule, for storage and usage during later development. However, by now there is still a lack of sufficient understanding on the molecular and cellular processes that control yolk granule biogenesis. Here, by creating genome-tagging lines for Yl receptor and analyzing its distribution in vitellogenic oocytes, we observed a close association of different endosomal structures with distinct phosphoinositides and actin cytoskeleton dynamics. We further showed that Rab5 and Rab11, but surprisingly not Rab4 and Rab7, are essential for yolk granules biogenesis. Instead, we uncovered evidence for a potential role of Rab7 in actin regulation and observed a notable overlap of Rab4 and Rab7, two Rab GTPases that have long been proposed to have distinct spatial distribution and functional roles during endolysosomal trafficking. Through a small-scale RNA interference (RNAi) screen on a set of reported Rab5 effectors, we showed that yolk granule biogenesis largely follows the canonical endolysosomal trafficking and maturation processes. Further, the data suggest that the RAVE/V-ATPase complexes function upstream of or in parallel with Rab7, and are involved in earlier stages of endosomal trafficking events. Together, our study provides s novel insights into endolysosomal pathways and establishes vitellogenic oocyte in Drosophila as an excellent in vivo model for dissecting the highly complex membrane trafficking events in metazoan.

HAP40 is a conserved central regulator of Huntingtin and a potential modulator of Huntington's disease pathogenesis.

Perturbation of huntingtin (HTT)'s physiological function is one postulated pathogenic factor in Huntington's disease (HD). However, little is known how HTT is regulated in vivo. In a proteomic study, we isolated a novel ~40kDa protein as a strong binding partner of Drosophila HTT and demonstrated it was the functional ortholog of HAP40, an HTT associated protein shown recently to modulate HTT's conformation but with unclear physiological and pathologic roles. We showed that in both flies and human cells, HAP40 maintained conserved physical and functional interactions with HTT. Additionally, loss of HAP40 resulted in similar phenotypes as HTT knockout. More strikingly, HAP40 strongly affected HTT's stability, as depletion of HAP40 significantly reduced the levels of endogenous HTT protein while HAP40 overexpression markedly extended its half-life. Conversely, in the absence of HTT, the majority of HAP40 protein were degraded, likely through the proteasome. Further, the affinity between HTT and HAP40 was not significantly affected by polyglutamine expansion in HTT, and contrary to an early report, there were no abnormal accumulations of endogenous HAP40 protein in HD cells from mouse HD models or human patients. Lastly, when tested in Drosophila models of HD, HAP40 partially modulated the neurodegeneration induced by full-length mutant HTT while showed no apparent effect on the toxicity of mutant HTT exon 1 fragment. Together, our study uncovers a conserved mechanism governing the stability and in vivo functions of HTT and demonstrates that HAP40 is a central and positive regulator of endogenous HTT. Further, our results support that mutant HTT is toxic regardless of the presence of its partner HAP40, and implicate HAP40 as a potential modulator of HD pathogenesis through its multiplex effect on HTT's function, stability and the potency of mutant HTT's toxicity.

Exploring genetic associations between vitiligo and mental disorders using Mendelian randomization.

Although a large number of existing studies have confirmed that people with vitiligo are prone to mental disorders, these observational studies may be subject to confounding factors and reverse causality, so the true causal relationship is inconclusive. We conducted a bidirectional Mendelian randomization (MR) analysis to assess the causality between vitiligo and mental disorders, namely depression, anxiety, insomnia, schizophrenia, bipolar disorder, obsessive-compulsive disorder (OCD) and attention-deficit hyperactivity disorder (ADHD). Summary statistics from large available genome-wide association study (GWAS) datasets for generalized vitiligo (n = 44 266), depression (n = 173 005), anxiety (n = 17 310), insomnia (n = 386 988), schizophrenia (n = 130 644), bipolar disorder (n = 413 466), OCD (n = 9725) and ADHD (n = 225 534) were utilized. Inverse-variance weighted (IVW), MR-Egger and weighted median were employed to estimate causal effects. Sensitivity analysis and MR Pleiotropy Residual Sum and Outliers (MR PRESSO) were conducted to assess heterogeneity and pleiotropy, ensuring the robustness of the results. Additionally, we corrected for estimating bias that might be brought on by sample overlap using MRlap. In our findings, none of the rigorous bidirectional MR analyses uncovered a significant causal association. Even after applying the MRlap correction, the effect sizes remained statistically nonsignificant, thereby reinforcing the conclusions drawn via IVW. In summary, our genetic-level investigation did not reveal a causal link between generalized vitiligo and mental disorders.

Prediction of Hydrogen Abstraction Rate Constants at the Allylic Site between Alkenes and OH with Multiple Machine Learning Models.

Hydrogen abstraction reactions between hydrocarbons and hydroxyl radicals are important propagation steps in radical chain reactions, playing a crucial role in atmospheric and combustion chemistry. This study focuses on predicting the rate constants of the prototype of the reaction class of hydrogen abstractions, i.e., the primary allylic hydrogen abstraction from alkenes by the OH radical, via utilizing machine learning (ML) methods. Specifically, three distinct models, namely, feedforward neural network (FNN), support vector regression (SVR), and Gaussian process regression (GPR), have been employed to construct robust ML models for prediction. We proposed a novel strategy that seamlessly integrates descriptor preprocessing, a pairwise linear correlation analysis, and a model-specific Wrapper method to enhance the effectiveness of the feature selection procedure. The selected feature subset was then evaluated using two cross-validation techniques, i.e., leave-one-group-out (LOGO) and K-fold cross-validations, for each of the three ML models (FNN, SVR, and GPR) to assess their predictive and stability performance. The results demonstrate that the FNN model, trained with seven representative descriptors, achieves superior performance compared to the other two methods. For the FNN model, the average percentage deviation is 39.06% on the test set by performing LOGO cross-validation, while the repeated 10-fold cross-validation achieves a percentage prediction deviation of 19.1%. Two larger alkenes with 10 carbons were selected to test the prediction performance of the trained FNN model on primary allylic hydrogen abstraction. Results show that the kinetic predictions follow well the modified three-parameter Arrhenius equation, indicating the reliable performance of FNN in predicting hydrogen abstraction rate constants, especially for the primary allylic site. Hopefully, this work can shed useful light on the application of ML in generating chemical kinetic parameters of hydrocarbon combustion chemistry.

The plasma levels of Dickkopf-1 elevated in patients with Juvenile Idiopathic Arthritis.

BACKGROUND: To explore the role of two major inhibitors of Wnt signal pathway, Dickkopf-1(DKK-1) and Sclerostin (SOST), in the pathogenesis of juvenile idiopathic arthritis (JIA). METHODS: 88 patients with JIA, which including 49 patients with enthesitis-related arthritis (ERA), 21 oligoarthritis (oJIA) and 18 polyarthritis (pJIA), and 36 age-and sex-matched children as healthy controls (HC) were enrolled in this study. The plasma levels of DKK-1 and SOST, measured using commercially available ELISA kits, were analyzed the correlation between the levels of DKK-1/SOST and JIA, and were analyzed in 14 patients with JIA during before and after treatment. RESULTS: Plasma levels of DKK-1 were significantly higher in the patients with JIA than that in HC, the elevation of DKK-1 level was positively correlated with HLA-B27 positive JIA. DKK-1 levels dropped significantly in patient with JIA after treatment (P < 0.05). There was no significant change in SOST levels among different subtypes of JIA, patients with JIA during before and after treatment, and HC. CONCLUSION: It was suggested that the DKK-1 may have a certain correlation with the pathogenesis of JIA, and DKK-1 levels are more closely related to the HLA-B27 positive-ERA. IMPACT: The abnormally elevated levels of Dickkopf-1 (DKK-1) may be involved in the pathogenesis of juvenile idiopathic arthritis (JIA). DKK-1 levels were more closely related to the HLA-B27 positive-enthesitis-related arthritis (ERA). DKK-1 is an inhibitor of Wnt signaling pathway that promotes osteoblastic new bone formation; it is very rare for pediatric patients with HLA-B27 positive-ERA to manifest typical spondylitis, while sacroiliac arthritis is relatively common, which may be related to the high levels of DKK-1, which is consistent with the early stage of ankylosing spondylitis (AS).

Okicamelliaside targets the N-terminal chaperone pocket of HSP90 disrupts the chaperone protein interaction of HSP90-CDC37 and exerts antitumor activity.

Heat shock protein 90 (HSP90) has been recognized as a crucial target in cancer cells. However, various toxic reactions targeting the ATP binding site of HSP90 may not be the best choice for HSP90 inhibitors. In this paper, an ellagic acid derivative, namely, okicamelliaside (OCS), with antitumor effects was found. To identify potential anti-cancer mechanisms, an OCS photosensitive probe was applied to target fishing and tracing. Chemical proteomics and protein-drug interaction experiments have shown that HSP90 is a key target for OCS, with a strong binding affinity (KD = 6.45 µM). Mutation analysis of the target protein and molecular dynamics simulation revealed that OCS could competitively act on the key Glu-47 site at the N-terminal chaperone pocket of HSP90, where the co-chaperone CDC37 binds to HSP90, affect its stability and reduce the ∆Gbind of HSP90-CDC37. It was demonstrated that OCS destroys the protein-protein interactions of HSP90-CDC37; selectively affects downstream kinase client proteins of HSP90, including CDK4, P-AKT473, and P-ERK1/2; and exerts antitumor effects on A549 cells. Furthermore, tumor xenograft experiments demonstrated high antitumor activity and low toxicity of OCS in the same way. Our findings identified a novel N-terminal chaperone pocket natural inhibitor of HSP90, that is, OCS, which selectively inhibits the formation of the HSP90-CDC37 protein complex, and provided further insight into HSP90 inhibitors for anti-cancer candidate drugs.

Inception of Carbonaceous Nanostructures via Hydrogen-Abstraction Phenylacetylene-Addition Mechanism.

Sufficient experimental evidence has suggested that polycyclic aromatic hydrocarbons are the building blocks of carbonaceous nanostructures in combustion and circumstellar envelops of carbon-rich stars, but their fundamental formation mechanisms remain elusive. By exploring the reaction kinetics of phenylacetylene with 1-naphthyl/4-phenanthryl radicals, we provide compelling theoretical and experimental evidence for a novel and self-consistent hydrogen-abstraction phenylacetylene-addition (HAPaA) mechanism. HAPaA operates efficiently at both low and high temperatures, leading to the formation, expansion, and nucleation of peri-condensed aromatic hydrocarbons (PCAHs), which are otherwise difficult to synthesis via traditional hydrogen-abstraction acetylene/vinylacetylene-addition pathways. The HAPaA mechanism can be generalized to other α-alkynyl PCAHs and thus provides an alternative covalent bond bridge for PCAH combination via an acetylene linker. The proposed HAPaA mechanism may contribute toward a comprehensive understanding of soot formation, carbonaceous nanomaterials synthesis, and the origin and evolution of carbon in our galaxy.

A HY5-COL3-COL13 regulatory chain for controlling hypocotyl elongation in Arabidopsis.

CONSTANS-LIKE (COL) family members are commonly implicated in light signal transduction during early photomorphogenesis. However, some of their functions remain unclear. Here, we propose a role for COL13 in hypocotyl elongation in Arabidopsis thaliana. We found that COL13 RNA accumulates at high levels in hypocotyls and that a disruption in the COL13 function via a T-DNA insertion or RNAi led to the formation of longer hypocotyls of Arabidopsis seedlings under red light. On the contrary, overexpression of COL13 resulted in the formation of shorter hypocotyls. Using various genetic, genomic, and biochemical assays, we proved that another COL protein, COL3, directly binds to the promoter of COL13, and the promoter region of COL3 was targeted by the transcription factor LONG HYPOCOTYL 5 (HY5), to form an HY5-COL3-COL13 regulatory chain for regulating hypocotyl elongation under red light. Additionally, further study demonstrated that COL13 interacts with COL3, and COL13 promotes the interaction between COL3 and CONSTITUTIVE PHOTOMORPHOGENIC1 (COP1), suggesting a possible COP1-dependent COL3-COL13 feedback pathway. Our results provide new information regarding the gene network in mediating hypocotyl elongation.

Predictive Combustion Kinetics of OH Radical Reactions with a C5 Unsaturated Alcohol: The Competitive H-Abstraction and OH-Addition Reactions of 2-Methyl-3-buten-2-ol.

2-Methyl-3-buten-2-ol (MBO232) is a potential biofuel and renewable fuel additive. In a combustion environment, the consumption of MBO232 is mainly through the reaction with a OH radical, one of the most important oxidants. Here, we predict the intricate reactions of MBO232 and OH radicals under a broad range of combustion conditions, that is, 230-2500 K and 0.01-1000 atm. The potential energy surfaces of H-abstraction and OH-addition have been investigated at the CCSD(T)/CBS//M06-2X/def2-TZVP level, and the rate constants were calculated via Rice-Ramsperger-Kassel-Marcus/master equation (RRKM/ME) theory. The decomposition reactions of the critical intermediates from the OH-addition reactions have also been studied. Our results show that OH-addition reactions are dominant below 850 K, while H-abstraction reactions, especially the channel-abstracting H atoms from the methyl groups, are more competitive at higher temperatures. We found that it is necessary to discriminate H atoms attached to the same C atom, as their abstraction rates can differ by up to 1 order of magnitude. The calculated results show good agreement with the reported experimental data. We have provided the modified Arrhenius expressions for rate constants of the dominant channels. The kinetic data determined in this work are of much value for constructing the combustion models of MBO232 and understanding the combustion kinetics and mechanism of other unsaturated alcohols.

Micelles self-assembled by 3-O-ß-D-glucopyranosyl latycodigenin enhance cell membrane permeability, promote antibiotic pulmonary targeting and improve anti-infective efficacy.

BACKGROUND: Nanoparticle-based pulmonary drug delivery systems are commonly developed and applied for drug-targeted delivery. They exhibit significant advantages compared to traditional pulmonary drug delivery systems. However, developing the formulation of each drug is a time-consuming and laborious task. RESULTS: In this study, a universal lung-targeting nanoparticle was designed and constructed. The self-assembled micelles were composed of a platycodon secondary saponin, 3-O-ß-D-glucopyranosyl platycodigenin 682 (GP-682), based on its specific amphiphilic structure. The GP-682 micelles exhibited a relatively stable zeta potential with a particle size between 60 and 90 nm, and the critical micelle concentration (CMC) value was approximately 42.3 µg/mL. Preincubation of GP-682 micelles markedly enhanced their cell membrane permeability and improved drug uptake in vitro. The results were visualized using fluorescent dye tracing, transmission electron microscopy (TEM) observations and the lactate dehydrogenase (LDH) release assay. The obtained benefits enhanced the distribution of levofloxacin (Lev) in mouse lung tissue and reduced antibiotics overdosing. The acute lung injury mouse model induced by the Pseudomonas aeruginosa PA 14 strain demonstrated that preinjection of GP-682 micelles before antibiotic administration resulted in a higher survival rate and anti-infective efficacy in vivo. It also caused reductions in pulmonary injury, bacterial invasion and cytokine expression compared with treatment with Lev alone. CONCLUSIONS: GP-682 micelles are another nanoparticle-based pulmonary drug delivery system and provide a new lung-targeting therapy option.

Efficacy and Safety of Botulinum Toxin Type A Injection in Patients with Bilateral Trapezius Hypertrophy.

OBJECTIVE: To evaluate aesthetic outcomes in patients with bilateral trapezius hypertrophy treated by botulinum toxin type A (BTxA) injection for aesthetic reconstruction of the upper trapezius. METHODS: From May 2015 to May 2016, 30 women with a short neck shape resulting from bilateral trapezius hypertrophy were treated with botulinum toxin type A (BTxA) injection at the most affected area of the upper trapezius. Pre- and postoperative values of SACDF (irregularly shaped area of the four points A, C, D, and F) and SACDE (irregularly shaped area of the four points A, C, D, and E), responses to patients' and doctors' Global Aesthetic Improvement Scale (GAIS) questionnaires for neck aesthetic assessment, as well as reported adverse events, were recorded and analyzed. RESULTS: Duration of follow-up ranged from 4 to 12 months. Subjects experienced non-severe adverse events and complete recovery after a single BTxA injection. In patients' GAIS questionnaires, "very much improved" accounted for 53%, "much improved" accounted for 13%, and "improved" accounted for 27%. In doctors' GAIS questionnaires, "very much improved" accounted for 27%, "much improved" accounted for 33%, "improved" accounted for 33%, and "no change" accounted for 7%. The overall degree of improvement was high. Statistically significant differences were observed with respect to the "very much improved" response to GAIS questionnaires between patients and doctors (P = 0.035). CONCLUSION: A single injection of BTxA for aesthetic reconstruction of the upper trapezius is safe and effective in patients with bilateral trapezius hypertrophy. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

[Percentages of peripheral blood γδ T cells and regulatory T cells and expression of associated cytokines in infants with human cytomegalovirus infection].

OBJECTIVE: To investigate the percentages of peripheral blood γδ T cells and regulatory T cells (Treg) and the expression of associated cytokines, interleukin 17 (IL-17) and transforming growth factor-ß1 (TGF-ß1), in infants with human cytomegalovirus (HCMV) infection. METHODS: Twenty-two infants with HCMV infection (HCMV group) and 22 healthy infants who underwent physical examination (control group) were enrolled in this study. The percentages of peripheral blood γδ T cells and Treg cells were determined by flow cytometry. The levels of IL-17 and TGF-ß1 in plasma were measured using ELISA. RESULTS: Compared with the control group, the HCMV group had significantly higher percentage of γδ T cells and IL-17 level (P<0.01) and significantly lower percentage of Treg cells and TGF-ß1 level (P<0.01). In the HCMV group, the percentage of γδ T cells was negatively correlated with the percentage of Treg cells and TGF-ß1 level (P<0.05), but positively correlated with IL-17 level (P<0.05); the percentage of Treg cells was positively correlated with TGF-ß1 level (P<0.05), but negatively correlated with IL-17 level (P<0.05); there was no correlation between IL-17 level and TGF-ß1 level (P>0.05). CONCLUSIONS: There is an imbalance between γδ T cells and Treg cells in the peripheral blood of infants with HCMV infection, and γδ T cells may be involved in the secretion of IL-17.

Theoretical Kinetic and Mechanistic Studies on the Reactions of CF3CBrCH2 (2-BTP) with OH and H Radicals.

CF3CBrCH2 (2-bromo-3,3,3-trifluoropropene, 2-BTP) is a potential replacement for CF3Br; however, it shows conflicted inhibition and enhancement behaviors under different combustion conditions. To better understand the combustion chemistry of 2-BTP, a theoretical study has been performed on its reactions with OH and H radicals. Potential energy surfaces were exhaustively explored by using B3LYP/aug-cc-pVTZ for geometry optimizations and CCSD(T)/aug-cc-pVTZ for high level single point energy refinements. Detailed kinetics of the major pathways were predicted by using RRKM/master-equation methodology. The present predictions imply that the -C(Br)=CH2 moiety of 2-BTP is most likely to be responsible for its fuel-like property. For 2-BTP + OH, the addition to the initial adduct (CF3CBrCH2OH) is the dominant channel at low temperatures, while the substitution reaction (CF3COHCH2 + Br) and H abstraction reaction (CF3CBrCH + H2O) dominates at high temperatures and elevated pressures. For 2-BTP + H, the addition to the initial adduct (CF3CBrCH3) also dominates the overall kinetics at low temperatures, while Br abstraction reaction (CF3CCH2 + HBr) and ß-scission of the adduct forming CF3CHCH2 + Br dominates at high temperatures and elevated pressures. Compared to 2-BTP + OH, the 2-BTP + H reaction tends to have a larger effect on flame suppression, given the fact that it produces more inhibition species.

FAM172A is a tumor suppressor in colorectal carcinoma.

The present study was designed to elucidate the regulatory role of a novel protein FAM172A in carcinogenesis of colorectal carcinoma (CRC). Investigation of clinical samples using Western blotting showed that expression of FAM172A is significantly lower in cancerous tissues than in adjacent tissues. Furthermore, we constructed in vitro model for continuous overexpression and silencing of FAM172A with a retroviral vector system. FAM172A suppressed the proliferative and invasive potentials of LOVO cells as shown in MTT test, transwell migration assay, wound healing assay, 3D-culture morphologic study, and xenograft experiment. RT-PCR and Western blotting showed that FAM172A overexpression inhibited expressions of Cyclin D1, CDK2, MMP-2, MMP-9, PERK, elF2α, ATF6, XBP1, and GRP78, while FAM172A silencing induced their expressions. FAM172A might regulate ERS through PERK-elF2α, ATF6-XBP1-GRP78 signal pathway. The results implicated that FAM172A functioned as a tumor suppressor in colorectal carcinoma.

Digital Health Interventions for Quality Improvements in Chronic Kidney Disease Primary Care: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Chronic kidney disease (CKD) is a significant public health issue globally. The importance of its timely identification and early intervention is paramount. However, a systematic approach for early CKD management in the primary care setting is currently lacking, receiving less attention compared to upstream risk factors such as diabetes and hypertension. This oversight may lead to a failure in meeting quality-of-care indicators. Digital health interventions (DHIs), which leverage digital tools to enhance healthcare delivery, have shown effectiveness in managing chronic diseases and improving the quality, safety, and efficiency of primary care. Our research aimed to evaluate the effectiveness of DHIs in the care process, focusing on their reach, uptake, and feasibility. METHODS: In this systematic review and meta-analysis, we searched PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, and ClinicalTrials.gov for randomized controlled trials (RCTs) assessing DHIs' effectiveness in CKD patient care among adults in primary care settings. The search, conducted on 30 June 2023, included studies published in English from 1 January 2009. Screening was conducted using Covidence, adhering to Cochrane's guidelines for data extraction. We primarily evaluated changes in care processes (testing, documentation, medication use, etc.) and the use of renin-angiotensin-aldosterone system inhibitors (RAASi), referrals, among others. Multilevel meta-analysis was employed to address within-study clustering, and meta-regression analyzed the impact of study characteristics on heterogeneity in effect sizes. Clinical endpoints were recorded where available. Bias risk was assessed using the Cochrane Risk of Bias 2 tool. Data on reach, uptake, and feasibility were narratively summarized. The study is registered with PROSPERO (CRD42023449098). RESULTS: From 679 records, 12 RCTs were included in the narrative synthesis, and 6 studies (encompassing 7 trials) in the meta-analysis. The trials indicated a -0.85% change (95%CI, -5.82% to 4.11%) in the proportion of patients receiving desired care. This result showed considerable heterogeneity (I2 = 91.9%). One study characteristic (co-intervention, education) correlated with larger effects. Although including co-intervention in multivariable meta-regression was significant, it did not diminish heterogeneity. The reported reach varied and was not high, while the uptake was relatively high. Most studies did not explicitly address feasibility, though some statements implied its evaluation. CONCLUSIONS: The current literature on the impact of DHIs in community-based CKD care is limited. The studies suggest a non-significant effect of DHIs on enhancing CKD management in community settings, marked by significant heterogeneity. Future research should focus on rigorous, methodologically sound implementations to better assess the effectiveness of DHIs in the primary care management of CKD.

Supported transitional care applied to stroke survivors: A meta-analysis.

BACKGROUND: This meta-analysis aims to assess the outcomes of supported intervention transitional care compared to traditional care for stroke survivors. MATERIAL AND METHODS: A systematic literature review was accomplished and 4,437 stroke patients were recruited for the current study; 2,211 of them were treated with transitional care and 2,226 with traditional care. The inclusion criteria of the current study recruited only randomized clinical trials up until November 2023. A random analysis model was used to analyze the continuous and dichotomous models. RESULTS: Supported intervention transitional care (early supported discharge) for stroke survivors showed a significant (p = 0.002) impact regarding the functional status of patients as expressed by the Barthel index (mean difference (MD) = 0.57, 95% confidence interval (95% CI): 0.20-0.94, I² = 93.72%). On the other hand, there were no considerable (p > 0.05) differences regarding other outcomes such as activities of daily living, the Caregiver Strain Index (CSI), the modified Rankin scale (mRS), and mortality (MD = 0.29, 95% CI: -0.12-0.69, I² = 94.5%; MD = -0.13, 95% CI: -0.40-0.14, I² = 68.65%; MD = -0.13, 95% CI: -0.49-0.23, I² = 83.33%; and MD = -0.19, 95% CI: -0.58-0.17, I² = 0%; respectively). CONCLUSION: Supported transitional care allowed stroke survivors to succeed in enhancing their functional status outcomes compared with controls, while there was no significant impact regarding mortality rate. Further investigations and multicenter studies are required to enhance the evidence.

The relationship between lactate dehydrogenase to albumin ratio and all-cause mortality during ICU stays in patients with sepsis: A retrospective cohort study with propensity score matching.

Background: Sepsis is a prevalent and severe medical condition which is frequently observed in the intensive care unit (ICU). Although numerous biomarkers have been identified to predict the prognosis of sepsis, the lactate dehydrogenase to albumin ratio (LDH/ALB ratio) has not been extensively investigated. The principal objective of this study is to assess the relationship between LDH/ALB ratio and all-cause mortality in patients with sepsis. Methods: This study included all adult critically ill patients with sepsis from the Medical Information Mart for Intensive Care IV (MIMIC-IV, version 2.0) database. Propensity score matching (PSM) analysis was conducted to mitigate bias, and Kaplan-Meier curves were performed to evaluate the cumulative survival across different groups. The association between the LDH/ALB ratio and mortality was examined through restricted cubic spline (RCS) analysis and Cox regression analysis. The robustness of the findings was confirmed through subgroup analyses. Additionally, the prognostic capability of the LDH/ALB ratio was further evaluated using receiver operating characteristic (ROC) curve analysis. Results: There were 6059 adult patients with sepsis enrolled in the final analysis. RCS revealed a non-linear relationship between the LDH/ALB ratio and an increased risk of ICU all-cause mortality (χ2 = 46.900, P < 0.001). Following PSM analysis, 1553 matched pairs were obtained. As comparison to the low LDH/ALB ratio group, the mortality rate in the high LDH/ALB ratio group was significantly higher (P < 0.001). Kaplan-Meier curves, both before and after PSM, revealed that the ICU cumulative survival rate for patients with sepsis was significantly lower in the high LDH/ALB ratio group compared to the low LDH/ALB ratio group (χ2 = 93.360, P < 0.001; χ2 = 14.400, P < 0.001). Even after adjusting for a range of potential confounders, multivariate Cox regression analysis indicated that an elevated LDH/ALB ratio was a significant predictor of all-cause mortality in these patients. ROC curve analysis demonstrated that the LDH/ALB ratio had an area under the ROC curve (AUC) of 0.688 for predicting ICU mortality, with a sensitivity of 69.2% and a specificity of 58.6%. Conclusions: An elevated LDH/ALB ratio (≥10.57) was associated with all-cause mortality in critically ill patients with sepsis, and it might serve as a prognostic marker. Clinicians should pay closer attention to sepsis patients presenting with an LDH/ALB ratio of 10.57 or higher.

Online characterization of isomeric/isobaric components in the gas phase of mainstream cigarette smoke by tunable synchrotron radiation vacuum ultraviolet photoionization time-of-flight mass spectrometry and photoionization efficiency curve simulation.

A newly developed, qualitative and quantitative method based on tunable synchrotron radiation vacuum ultraviolet photoionization time-of-flight mass spectrometry (SR-VUV-PI-TOFMS) and photoionization efficiency (PIE) curve simulation was applied for the online analysis of isomers and isobaric compounds in the gas phase of mainstream cigarette smoke. After blocking the particulate phase components by the Cambridge filter pad, a puff of fresh gas-phase cigarette smoke was immediately introduced into a vacuum ionization chamber through a heated capillary, then was photoionized, and analyzed by a TOF mass spectrometer. The PIE curves for the mass peaks up to m/z = 106 were measured between 8.0 and 10.7 eV. Some components could be directly identified by their discriminated ionization energies (IEs) on the PIE curve. By simulating the PIE curve with the sum of scaled absolute photoionization cross sections (PICSs), complex isomeric/isobaric compounds along with their mole fractions could be obtained when the best-fitting was realized between experimental and simulated PIE curves. A series of reported toxic compounds for quantification, such as 1,3-butadiene (m/z = 54), 1,3-cyclopentadiene (m/z = 66), benzene (m/z = 78), xylene (m/z = 106), 2-propenal (m/z = 56), acetone and propanal (m/z = 58), crotonaldehyde (m/z = 70), furan and isoprene (m/z = 68), were all found to have other isomers and/or isobaric compounds with considerable abundances. Some isomers have never been reported previously in cigarette smoke, like C5H6 isomers 1-penten-3-yne, 3-penten-1-yne, and 1-penten-4-yne at m/z = 66. Isomeric/isobaric compounds characterization for the mass peaks and mole fraction calculations were discussed in detail below 10.7 eV, an energy value covering several conventional used VUV light sources.

Feasibility study of semiconductor sequencing for noninvasive prenatal detection of fetal aneuploidy.

BACKGROUND: Noninvasive prenatal detection of common fetal aneuploidies with cell-free DNA from maternal plasma has been achieved with high-throughput next-generation sequencing platforms. Turnaround times for previously tested platforms are still unsatisfactory for clinical applications, however, because of the time spent on sequencing. The development of semiconductor sequencing technology has provided a way to shorten overall run times. We studied the feasibility of using semiconductor sequencing technology for the noninvasive detection of fetal aneuploidy. METHODS: Maternal plasma DNA from 13 pregnant women, corresponding to 4 euploid, 6 trisomy 21 (T21), 2 trisomy 18 (T18), and 1 trisomy 13 (T13) pregnancies, were sequenced on the Ion Torrent Personal Genome Machine sequencer platform with 318 chips. The data were analyzed with the T statistic method after correcting for GC bias, and the T value was calculated as an indicator of fetal aneuploidy. RESULTS: We obtained a mean of 3 524 401 high-quality reads per sample, with an efficiency rate of 77.9%. All of the T21, T13, and T18 fetuses could be clearly distinguished from euploid fetuses, and the time spent on library preparation and sequencing was 24 h. CONCLUSIONS: Semiconductor sequencing represents a suitable technology for the noninvasive prenatal detection of fetal aneuploidy. With this platform, sequencing times can be substantially reduced; however, a further larger-scale study is needed to determine the imprecision of noninvasive fetal aneuploidy detection with this system.

Data-driven prediction of the equivalent sand-grain roughness.

Surface roughness affects the near-wall fluid velocity profile and surface drag, and is commonly quantified by the equivalent sand-grain roughness [Formula: see text]. It is essential to estimate [Formula: see text] for accurate fluid dynamic problem modeling. While numerous roughness correlation formulas have been proposed to predict [Formula: see text] in the fully rough regime, most of them are restricted to certain roughness types, with various geometric parameters considered in each case, leading to ongoing disagreements regarding its parameterization and lack of universality. In this study, a Particle Swarm Optimized Backpropagation (PSO-BP) method is proposed to predict [Formula: see text] based on the selected surface parameters from previous DNS, LES, and experimental results for flow behavior over various surface roughness. The PSO-BP model's ability to predict [Formula: see text] in the fully rough region is evaluated and compared with both the existing roughness correction formulas as well as the traditional BP model. An optimized polynomial function is also proposed to serve as a 'white box' for predicting [Formula: see text]. It turns out that the PSO-BP method has better performance in the evaluation metrics compared to other methods, yielding a Mean Absolute Error (MAE) of 0.0390, a Mean Squared Error (MSE) of 0.0026 and a Mean Absolute Percentage Error (MAPE) of 28.12%. This novel approach for estimating [Formula: see text] has practical applicability and holds promise for improving the precision and efficiency of calculations related to equivalent sand-grain roughness, and thus provides more accurate and effective solutions for CFD and other engineering applications.