A data-driven combined prediction method for the demand for intensive care unit healthcare resources in public health emergencies.

BACKGROUND: Public health emergencies are characterized by uncertainty, rapid transmission, a large number of cases, a high rate of critical illness, and a high case fatality rate. The intensive care unit (ICU) is the "last line of defense" for saving lives. And ICU resources play a critical role in the treatment of critical illness and combating public health emergencies. OBJECTIVE: This study estimates the demand for ICU healthcare resources based on an accurate prediction of the surge in the number of critically ill patients in the short term. The aim is to provide hospitals with a basis for scientific decision-making, to improve rescue efficiency, and to avoid excessive costs due to overly large resource reserves. METHODS: A demand forecasting method for ICU healthcare resources is proposed based on the number of current confirmed cases. The number of current confirmed cases is estimated using a bilateral long-short-term memory and genetic algorithm support vector regression (BILSTM-GASVR) combined prediction model. Based on this, this paper constructs demand forecasting models for ICU healthcare workers and healthcare material resources to more accurately understand the patterns of changes in the demand for ICU healthcare resources and more precisely meet the treatment needs of critically ill patients. RESULTS: Data on the number of COVID-19-infected cases in Shanghai between January 20, 2020, and September 24, 2022, is used to perform a numerical example analysis. Compared to individual prediction models (GASVR, LSTM, BILSTM and Informer), the combined prediction model BILSTM-GASVR produced results that are closer to the real values. The demand forecasting results for ICU healthcare resources showed that the first (ICU human resources) and third (medical equipment resources) categories did not require replenishment during the early stages but experienced a lag in replenishment when shortages occurred during the peak period. The second category (drug resources) is consumed rapidly in the early stages and required earlier replenishment, but replenishment is timelier compared to the first and third categories. However, replenishment is needed throughout the course of the epidemic. CONCLUSION: The first category of resources (human resources) requires long-term planning and the deployment of emergency expansion measures. The second category of resources (drugs) is suitable for the combination of dynamic physical reserves in healthcare institutions with the production capacity reserves of corporations. The third category of resources (medical equipment) is more dependent on the physical reserves in healthcare institutions, but care must be taken to strike a balance between normalcy and emergencies.

A highly sensitive ratiometric fluorescence immunoassay based on bioorthogonal nanozymes.

We designed a novel ratiometric fluorescence immunoassay based on bioorthogonal nanozymes for carcinoembryonic antigen detection. The analytical performance of our designed immunoassay showed a wide linear range, a low detection limit, good reproducibility, selectivity and stability. Thus, bioorthogonal nanozymes hold great potential applications in clinical diagnoses.

Radiomics signature based on robust features derived from diffusion data for differentiation between benign and malignant solitary pulmonary lesions.

BACKGROUND: Classifying and characterizing pulmonary lesions are critical for clinical decision-making process to identify optimal therapeutic strategies. The purpose of this study was to develop and validate a radiomics nomogram for distinguishing between benign and malignant pulmonary lesions based on robust features derived from diffusion images. MATERIAL AND METHODS: The study was conducted in two phases. In the first phase, we prospectively collected 30 patients with pulmonary nodule/mass who underwent twice EPI-DWI scans. The robustness of features between the two scans was evaluated using the concordance correlation coefficient (CCC) and dynamic range (DR). In the second phase, 139 patients who underwent pulmonary DWI were randomly divided into training and test sets in a 7:3 ratio. Maximum relevance minimum redundancy, least absolute shrinkage and selection operator, and logistic regression were used for feature selection and construction of radiomics signatures. Nomograms were established incorporating clinical features, radiomics signatures, and ADC(0, 800). The diagnostic efficiency of different models was evaluated using the area under the curve (AUC) and decision curve analysis. RESULTS: Among the features extracted from DWI and ADC images, 42.7% and 37.4% were stable (both CCC and DR ≥ 0.85). The AUCs for distinguishing pulmonary lesions in the test set for clinical model, ADC, ADC radiomics signatures, and DWI radiomics signatures were 0.694, 0.802, 0.885, and 0.767, respectively. The nomogram exhibited the best differentiation performance (AUC = 0.923). The decision curve showed that the nomogram consistently outperformed ADC value and clinical model in lesion differentiation. CONCLUSION: Our study demonstrates the robustness of radiomics features derived from lung DWI. The ADC radiomics nomogram shows superior clinical net benefits compared to conventional clinical models or ADC values alone in distinguishing solitary pulmonary lesions, offering a promising tool for noninvasive, precision diagnosis in lung cancer.

Identification and physiological activity of (methoxymethyl)triphenylphosphonium chloride as a new phytotoxin isolated from Rhizoctonia solani AG-3 TB.

Rhizoctonia solani as a cosmopolitan fungus is the causative agent of many crop diseases and leads to significant economic losses in crop production. To explore the toxin structure and physiological activity of R. solani AG-3 TB, high-performance liquid chromatography (HPLC), infrared absorption spectrum (IR), and nuclear magnetic resonance spectrum (NMR) were required. Here, the compound (methoxymethyl)triphenylphosphonium chloride (MMC) with the molecular formula C20H20ClOP was purified and identified from R. solani AG-3 TB. The pure compound MMC treated at 20 µg/mL, 50 µg/mL, and 100 µg/mL can cause obvious necrosis on leaves, increase active oxygen species (AOS), decrease chlorophyll content, and damage cellular structure. The results enrich the understanding of toxin compounds for R. solani and provide valuable insights into the toxicology of R. solani AG-3 TB.

Adsorption of NO2, SO2, H2S, and NH3 on Os-Doped WSe2 Monolayers: A First-Principles Study.

In this study, DFT calculations are used to analyze the adsorption of industrial waste gases (NO2, SO2, H2S, and NH3) on WSe2 monolayers. The adsorption energy, energy band, density of states, charge transfer, and recovery time of the adsorption structures between the target gas molecules and the Os-doped WSe2 are studied. Compared with pure WSe2 monolayer, Os surface bonding doping WSe2 (Os-modified WSe2) and Os doping with Se vacancy of WSe2 (Os-embedded WSe2) exhibit improved gas molecule adsorption ability. Among them, the adsorption energy of the Os-modified WSe2 monolayer on NO2, SO2, H2S, and NH3 is greater than that of the WSe2 monolayer. At the same time, it is proved that the Os-embedded WSe2 can be used as a gas sensor for H2S and NH3 gas molecules at a high temperature.

CRISPR/dCas9-Mediated Specific Molecular Assembly Facilitates Genotyping of Mutant Circulating Tumor DNA.

Breakthroughs in circulating tumor DNA (ctDNA) analysis are critical in tumor liquid biopsies but remain a technical challenge due to the double-stranded structure, extremely low abundance, and short half-life of ctDNA. Here, we report an electrochemical CRISPR/dCas9 sensor (E-dCas9) for sensitive and specific detection of ctDNA at a single-nucleotide resolution. The E-dCas9 design harnesses the specific capture and unzipping of target ctDNA by dCas9 to introduce a complementary reporter probe for specific molecular assembly and signal amplification. By efficient homogeneous assembly and interfacial click reaction, the assay demonstrates superior sensitivity (up to 2.86 fM) in detecting single-base mutant ctDNA and a broad dynamic range spanning 6 orders of magnitude. The sensor is also capable of measuring 10 fg/µL of a mutated target in excess of wild-type ones (1 ng/µL), equivalent to probing 0.001% of the mutation relative to the wild type. In addition, our sensor can monitor the dynamic expression of cellular genomic DNA and allows accurate analysis of blood samples from patients with nonsmall cell lung cancer, suggesting the potential of E-dCas9 as a promising tool in ctDNA-based cancer diagnosis.

The correlation of urinary strontium with the risk of chronic kidney disease among the general United States population.

Background: This study sought to illustrate whether urinary strontium levels were related to developing chronic kidney disease (CKD) in the United States population. Methods: A total of 5,005 subjects were identified from the National Health and Nutrition Examination Survey 2011-2016. Survey-weighted logistic regression analysis, multivariate linear regression analysis, restricted cubic spline (RCS) plots curve and stratified analyses were undertaken to explicate the correlation between urinary strontium and CKD. Results: With the increase of urinary strontium, the incidence rate of CKD and urinary albumin to creatinine ratio (UACR) levels gradually decreased, and estimated glomerular filtration rate (eGFR) levels gradually increased. After controlling all confounders, only urinary strontium in the fourth quartile was correlated to a lower CKD prevalence (OR: 0.59; 95% CI, 0.44-0.79) compared to the lowest quartile. Multivariate linear regression analysis showed that urinary strontium was positively correlated with eGFR but negatively with UACR. RCS curve suggested a nonlinear relationship between urinary strontium and CKD (P for non-linearity <0.001). Stratified analyses indicated no significant difference in the correlation between urinary strontium and CKD among different subgroups. Conclusion: Urinary strontium was strongly correlated with a low risk of CKD, and this association was non-linear among the US population.

Path Analysis of Self-Efficacy, Coping Style and Resilience on Depression in Patients with Recurrent Schizophrenia.

Purpose: Based on the two mediating variables of self-efficacy and coping style, a multiple mediating model was constructed to explore the mechanism by which psychological resilience affects depression in patients with recurrent schizophrenia. Methods: A total of 210 patients with recurrent schizophrenia who were hospitalized in a tertiary hospital in Hunan Province, China, were enrolled. The Connor Davidson Resilience Scale (CD-RISC), Self-rating Depression Scale (SDS), General Self-Efficacy Energy Scale (GSES) and Simplified Coping Style Questionnaire (SCSQ) were used to evaluate resilience, self-efficacy, coping style and depression. Path analysis was performed by constructing a structural equation model, and the mediating effect between variables was verified by the bias-corrected nonparametric percentile bootstrap method. Results: Resilience, self-efficacy and positive coping together explained 53.2% of the variance in depression. (1) The total scores of self-efficacy, coping style, resilience and depression in patients with recurrent schizophrenia were 2.54±0.61, 31.73±9.62, 58.06±17.26 and 50.48±12.55, respectively. (2) Pearson analysis showed that the scores of self-efficacy, positive coping, resilience and depression were significantly correlated with depression (r=-0.24-0.51, P<0.01). (3) The path analysis showed that resilience directly affects depression (ß=-0.401); additionally, resilience indirectly affects depression through self-efficacy (ß=-0.179) and through the chain mediating effect of self-efficacy and positive coping style (ß=-0.024). Conclusion: There is a high incidence of depression in patients with recurrent schizophrenia in China, and intervention is needed. This research revealed that resilience directly affects depression in patients with recurrent schizophrenia and that self-efficacy and positive coping play a part in mediating resilience and depression in patients with recurrent schizophrenia in China. Implementing targeted interventions based on action paths to improve the level of resilience and reduce the incidence of depression has guiding significance in the field of occupational rehabilitation of patients with recurrent schizophrenia.

Adsorption and Sensing of NO2, SO2, and NH3 on a Janus MoSeTe Monolayer Decorated with Transition Metals (Fe, Co, and Ni): A First-Principles Study.

This paper reports the adsorption of toxic gases (NO2, SO2, and NH3) on a MoSeTe structure based on first principles. It was found that the gas (NO2, SO2, and NH3) adsorption on a pure MoSeTe monolayer was weak; however, the adsorption performance of these gas molecules on transition-metal-atom-supported MoSeTe monolayers (TM-MoSeTe) was better than that on pure MoSeTe monolayers. In addition, there was more charge transfer between gas molecules and TM-MoSeTe. By comparing the adsorption energy and charge transfer values, the trend of adsorption energy and charge transfer in the adsorption of NO2 and SO2 was determined to be Fe-MoSeTe > Co-MoSeTe > Ni-MoSeTe. For the adsorption of NH3, the effect trend was as follows: Co-MoSeTe > Ni-MoSeTe > Fe-MoSeTe. Finally, by comparing their response times, the better gas sensor was selected. The Ni-MoSeTe system is suitable for NO2 gas sensors, and the Fe-MoSeTe and Co-MoSeTe systems are suitable for SO2 gas sensors. The Fe-MoSeTe, Co-MoSeTe, and Ni-MoSeTe systems are all suitable for NH3 gas sensors. Janus transition-metal dichalcogenides have the potential to be used as gas-sensing and scavenging materials.

Framework Nucleic Acid-Based Multifunctional Tumor Theranostic Nanosystem for miRNA Fluorescence Imaging and Chemo/Gene Therapy.

Intelligent stimulus-responsive theranostic systems capable of specifically sensing low-abundance tumor-related biomarkers and efficiently killing tumors remain a pressing endeavor. Here, we report a multifunctional framework nucleic acid (FNA) nanosystem for simultaneous imaging of microRNA-21 (miR-21) and combined chemo/gene therapy. To achieve this, two FNA nanoarchitectures labeled with Cy5/BHQ2 signal tags were designed, each of which contained an AS1411 aptamer, two pairs of DNA/RNA hybrids, a pH-sensitive DNA catcher, and doxorubicin (DOX) intercalating between cytosine and guanine in the tetrahedral DNA nanostructure (TDN). In the acidic tumor microenvironment, the DNA catchers spontaneously triggered to form an i-motif and create an FNA dimer (dFNA) while releasing DOX molecules to exert a cytotoxic effect. In addition, the overexpressed miR-21 in tumor cells dismantled the DNA/RNA hybrids to produce vascular endothelial growth factor-associated siRNA via a toehold-mediated strand displacement reaction, thus enabling a potent RNA interfering. Also importantly, the liberated miR-21 could initiate cascade-reaction amplification to efficiently activate the Cy5 signal reporters, thereby realizing on-site fluorescence imaging of miR-21 in living cells. The exquisitely designed FNA-based nanosystem showed favorable biocompatibility and stability as well as acid-driven DOX release characteristics. Owing to the aptamer-guided targeting delivery, specific uptake of the FNA-based theranostic nanosystem by HepG2 cells was verified with confocal laser scanning microscopy and flow cytometry analyses, which therefore resulted in apoptosis of HepG2 cells while doing minimal damage to normal H9c2 and HL-7702 cells. Strikingly, both in vitro and in vivo experiments demonstrated the achievements of the FNA-enabled miR-21 imaging and synergistically enhanced chemo/gene therapy. This work thus represents a noteworthy advance on the FNA-based theranostic strategy that can effectively avoid the undesirable premature leakage of anticarcinogen and off-target of siRNA, and achieve on-demand reagents release for tumor diagnostics and treatment.

Bioorthogonal Microbubbles with Antifouling Nanofilm for Instant and Suspended Enrichment of Circulating Tumor Cells.

Integrating clinical rare cell enrichment, culture, and single-cell phenotypic profiling is currently hampered by the lack of competent technologies, which typically suffer from weak cell-interface collision affinity, strong nonspecific adsorption, and the potential uptake. Here, we report cells-on-a-bubble, a bioinspired, self-powered bioorthogonal microbubble (click bubble) that leverages a clickable antifouling nanointerface and a DNA-assembled sucker-like polyvalent cell surface, to enable instant and suspended isolation of circulating tumor cells (CTCs) within minutes. Using this biomimetic engineering strategy, click bubbles achieve a capture efficiency of up to 98%, improved by 20% at 15 times faster over their monovalent counterparts. Further, the buoyancy-activated bubble facilitates self-separation, 3D suspension culture, and in situ phenotyping of the captured single cancer cells. By using a multiantibody design, this fast, affordable micromotor-like click bubble enables suspended enrichment of CTCs in a cohort (n = 42) across three cancer types and treatment response evaluation, signifying its great potential to enable single-cell analysis and 3D organoid culture.

The prognostic effects of the geriatric nutritional risk index on elderly acute kidney injury patients in intensive care units.

Introduction: The geriatric nutritional risk index (GNRI), a nutritional screening tool specifically for the aging population, has been proven to be associated with worse outcomes in chronic kidney disease patients, especially in the hemodialysis population. However, the predictive validity of GNRI in critically ill elderly patients with acute kidney injury (AKI) is yet to be determined. This analysis sought to examine the prognostic effects of GNRI on elderly AKI patients in intensive care units (ICUs). Methods: We collected elderly AKI patient-relevant data from the Medical Information Mart for Intensive Care III database. AKI was diagnosed and staged according to the "Kidney Disease Improving Global Outcomes" criteria. In the study, 1-year mortality was considered the primary outcome, whereas in-hospital, ICU, 28-day and 90-day mortality, and prolonged length of stay in ICU and hospital were selected as the secondary outcomes. Results: In all, 3,501 elderly patients with AKI were selected for this study, with a 1-year mortality rate of 36.4%. We classified the study population into low (≤98) and high (>98) GNRI groups based on the best cutoff value. The incidence of endpoints was remarkably lower in patients with elevated GNRI (p < 0.001). When stratified by the AKI stage, patients with high GNRI at AKI stages 1, 2, and 3 had markedly lower 1-year mortality than those with low GNRI (all p < 0.05). The multivariable regression analysis identified the independent prognostic ability of GNRI on the research outcomes (all p < 0.05). Restricted cubic spline exhibited a linear correlation between GNRI and 1-year death (p for non-linearity = 0.434). The prognostic implication of GNRI on 1-year mortality was still significant in patients with the most subgroups. Conclusion: In critically ill elderly patients with AKI, elevated GNRI upon admission was strongly correlated with a lower risk of unfavorable outcomes.

The Identification of Streptococcus pasteurianus Obtained from Six Regions in China by Multiplex PCR Assay and the Characteristics of Pathogenicity and Antimicrobial Resistance of This Zoonotic Pathogen.

Streptococcus pasteurianus is a zoonotic pathogen causing meningitis and bacteremia in animals and humans. A lack of accurate and convenient detection methods hinders preventing and controlling diseases caused by S. pasteurianus. Additionally, there is limited knowledge about its pathogenicity and antimicrobial resistance characteristics, as there are only three complete genome sequences available. In this study, we established a multiplex PCR assay for the detection of S. pasteurianus, which was applied to six fecal samples from cattle with diarrhea and 285 samples from healthy pigs. Out of the samples tested, 24 were positive, including 5 from pig tonsils, 18 from pig hilar lymph nodes, and 1 from cattle feces. Two strains were isolated from positive samples, and their complete genomes were sequenced. The two strains were non-virulent in mice and multidrug-resistant by the antimicrobial susceptibility test. We first found the presence of genes tet(O/W/32/O) and lsa(E) in S. pasteurianus, leading to resistance to lincosamides and tetracyclines. The convenient and specific multiplex PCR assay provides essential technical support for epidemiological research, and the complete genome sequence of two non-virulent strains contributes to understanding this zoonotic bacterium's genomic characteristics and pathogenesis.

Bottom-Up Signal Boosting with Fractal Nanostructuring and Primer Exchange Reaction for Ultrasensitive Detection of Cancerous Exosomes.

Exosomes are emerging as promising biomarkers for cancer diagnosis, yet sensitive and accurate quantification of tumor-derived exosomes remains a challenge. Here, we report an ultrasensitive and specific exosome sensor (NPExo) that initially leverages hierarchical nanostructuring array and primer exchange reaction (PER) for quantitation of cancerous exosomes. This NPExo uses a high-curvature nanostructuring array (bottom) fabricated by single-step electrodeposition to enhance capturing of the target exosomes. The immuno-captured exosome thus provides abundant membrane sites to insert numerous cholesterol-DNA probes with a density much higher than that by immune pairing, which further allows PER-based DNA extension to assemble enzyme concatemers (up) for signal amplification. Such a bottom-up signal-boosting design imparts NPExo with ultrahigh sensitivity up to 75 particles/mL (i.e., <1 exosome per 10 µL) and a broad dynamic range spanning 6 orders of magnitude. Furthermore, our sensor allows monitoring subtle exosomal phenotypic transition and shows high accuracy in discrimination of liver cancer patients from healthy donors via blood samples, suggesting the great potential of NPExo as a promising tool in clinical diagnostics.

Diagnostic performance of diffusion-weighted imaging versus 18F-FDG PET/CT in differentiating pulmonary lesions: an updated meta-analysis of comparative studies.

OBJECTIVE: To compare the diagnostic accuracy of diffusion-weighted imaging (DWI) and 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) for differentiating pulmonary nodules and masses. METHODS: We systematically searched six databases, including PubMed, EMBASE, the Cochrane Library, and three Chinese databases, to identify studies that used both DWI and PET/CT to differentiate pulmonary nodules. The diagnostic performance of DWI and PET/CT was compared and pooled sensitivity and specificity were calculated along with 95% confidence intervals (CIs). The Quality Assessment of Diagnostic Accuracy Studies 2 was used to assess the quality of the included studies, and STATA 16.0 software was utilized to perform statistical analysis. RESULTS: Overall, 10 studies that enrolled a total of 871 patients with 948 pulmonary nodules were included in this meta-analysis. DWI had greater pooled sensitivity (0.85 [95% CI 0.77-0.90]) and specificity (0.91 [95% CI 0.82-0.96]) than PET/CT (sensitivity, 0.82 [95% CI 0.70-0.90]); specificity, (0.81, [95% CI 0.72-0.87]). The area under the curve of DWI and PET/CT were 0.94 (95% CI 0.91-0.96) and 0.87 (95% CI 0.84-0.90) (Z = 1.58, P > 0.05), respectively. The diagnostic odds ratio of DWI (54.46, [95% CI 17.98-164.99]) was superior to that of PET/CT (15.77, [95% CI 8.19-30.37]). The Deeks' funnel plot asymmetry test showed no publication bias. The Spearman correlation coefficient test revealed no significant threshold effect. Lesion diameter and reference standard could be potential causes for the heterogeneity of both DWI and PET/CT studies, and quantitative or semi-quantitative parameters used would be a potential source of bias for PET/CT studies. CONCLUSION: As a radiation-free technique, DWI may have similar performance compare with PET/CT in differentiating malignant pulmonary nodules or masses from benign ones.

An inorganic-organic-polymeric nanovehicle for targeting delivery of doxorubicin: Rational assembly, pH-stimulus release, and dual hyperthermia/chemotherapy of hepatocellular carcinoma.

Efficiently synergistic therapy of hepatocellular carcinoma (HCC) by chemotherapeutic drug and photothermal agent remains a considerable challenge. Here, we report a nanodrug that integrates specific hepatoma-targeted delivery, pH-triggered drug release, and cooperative photothermal-chemotherapy function. By grafting the easily self-assembled CuS@polydopamine (CuS@PDA) nanocapsulation with polyacrylic acid (PAA), an inorganic-organic-polymeric hybrid nanovehicle was developed as a dual photothermal agent and carrier for loading antitumor drug-doxorubicin (DOX) through electrostatic adsorption and chemical linking antibody against GPC3 commonly overexpressed in HCC, resulting in the nanodrug, CuS@PDA/PAA/DOX/GPC3. The multifunctional nanovehicle had excellent biocompatibility, stability, and high photothermal conversion efficiency, due to the rationally designed binary CuS@PDA photothermal agent. The 72-h accumulative drug release in pH 5.5 tumor microenvironment can reach up to 84%, far higher than 15% measured in pH 7.4 condition. Notably, in contrast to the merely 20% survival rate of H9c2 and HL-7702 cells exposed to free DOX, their viabilities in the nanodrug circumstance can maintain 54% and 66%, respectively, suggesting the abated toxicity to the normal cell lines. When exposed to the hepatoma-targeting nanodrug, the viability of HepG2 cells was found to be 36%, which further drastically declined to 10% plus 808-nm NIR irradiation. Moreover, the nanodrug is potent to cause tumor ablation in HCC-modeled mice, and the therapeutic efficacy can be greatly enhanced under NIR stimulus. Histology analyses reveal that the nanodrug can effectively alleviate the chemical damage to heart and liver, as compared to free DOX. This work thus offers a facile strategy for design of targeting anti-HCC nanodrug toward combined photothermal-chemotherapy.

Identification of 3-Methoxyphenylacetic Acid as a Phytotoxin, Produced by Rhizoctonia solani AG-3 TB.

Tobacco target spot disease is caused by Rhizoctonia solani AG-3 TB, which causes serious harm to the quality and yield of tobacco. In this study, thin layer chromatography (TLC), high performance liquid chromatography (HPLC), infrared absorption spectroscopy (IR), and nuclear magnetic resonance spectroscopy (NMR) were used to purify and identify the potential phytotoxin produced by R. solani AG-3 TB. The result indicated that the purified toxin compound was 3-methoxyphenylacetic acid (3-MOPAA) (molecular formula: C9H10O3). The exogenous purified compound 3-MOPAA was tested, and the results revealed that 3-MOPAA can cause necrosis in tobacco leaves. 3-MOPAA is a derivative of phenylacetic acid (PAA), which should be produced by specific enzymes, such as hydroxylase or methylase, in the presence of PAA. These results enrich the research on the pathogenic phytotoxins of R. solani and provide valuable insights into the pathogenic mechanism of AG-3 TB.

Prognostic implication of lactic dehydrogenase-to-albumin ratio in critically ill patients with acute kidney injury.

BACKGROUND: No studies have been published on the correlation between lactic dehydrogenase-to-albumin ratio (LAR) and poor prognosis of acute kidney injury (AKI) patients, warranting further research. This analysis sought to investigate the prognostic implication of LAR in critically ill patients with AKI. METHODS: The present study enrolled 11,046 and 5180 adults with AKI from the Medical Information Mart for Intensive Care III (MIMIC III) and MIMIC IV, respectively. Data from MIMIC IV were identified as the training cohort, and those from MIMIC III were identified as the validation cohort. We applied multivariate regression analysis to identify the link between LAR and all-cause mortality. Restricted cubic spline (RCS) was conducted to figure out the correlation between LAR and in-hospital mortality. Furthermore, we carried out stratification analyses to examine if the effects of LAR on in-hospital mortality were consistent across various subclasses. RESULTS: The level of LAR was remarkably higher in the in-hospital non-survivor group (p < 0.001). Furthermore, the increased LAR group presented a remarkably higher rate of in-hospital mortality at AKI stages 1, 2, and 3 compared with the decreased LAR group (all p < 0.001). Multivariate regression analyses exhibited the independent prognostic significance of LAR for all-cause mortality (all p < 0.001). MIMIC III observed concordant results. RCS indicated a non-linear correlation between LAR and in-hospital death (P for non-linearity < 0.001). The relationship between LAR and in-hospital mortality was still significant in patients with various subclasses. CONCLUSIONS: Elevated LAR at admission is a prognostic risk factor for critically ill patients with AKI.

Shenmai Injection Improves Hypertensive Heart Failure by Inhibiting Myocardial Fibrosis via TGF-ß 1/Smad Pathway Regulation.

OBJECTIVE: To study effects of Shenmai Injection on hypertensive heart failure and its mechanism for inhibiting myocardial fibrosis. METHODS: Salt-sensitive (Dahl/SS) rats were fed with normal diet (0.3% NaCl) and the high-salt diet (8% NaCl) to observe the changes in blood pressure and heart function, as the control group and the model group. Salt-insensitive rats (SS-13BN) were fed with the high-salt diet (8% NaCl) as the negative control group. After modeling, the model rats were randomly divided into heart failure (HF) group, Shenmai Injection (SMI) group and pirfenidone (PFD) group by a random number table, with 6 rats in each group. They were given sterilized water, SMI and pirfenidone, respectively. Blood pressure, cardiac function, fibrosis and related molecular expression were detected by sphygmomanometer, echocardiogram, enzyme linked immunosorbent assay (ELISA), hematoxylin-eosin staining, Masson staining, immunofluorescence and qPCR analysis. RESULTS: After high-salt feeding, compared with the control and negative control group, in the model group the blood pressure increased significantly, the left ventricular ejection fraction (LVEF) and left ventricular fraction shortening (LVFS) were significantly reduced, and the serum NT-proBNP concentration increased significantly (all P<0.05); furthermore, the arrangement of myocardial cells was disordered, the edema was severe, and the degree of myocardial fibrosis was also significantly increased (P<0.05); the protein and mRNA expressions of collagen type I (Col I) were up-regulated (P<0.05), and the mRNA expressions of transforming growth factor ß 1 (TGF- ß 1), Smad2 and Smad3 were significantly up-regulated (P<0.05). Compared with HF group, after intervention of Shenmai Injection, LVEF and LVFS increased, myocardial morphology was improved, collagen volume fraction decreased significantly (P<0.05), and the mRNA expressions of Col I, TGF- ß 1, Smad2 and Smad3, as well as Col I protein expression, were all significantly down-regulated (all P<0.05). CONCLUSION: Myocardial fibrosis is the main pathological manifestation of hypertensive heart failure, and Shenmai Injection could inhibit myocardial fibrosis and effectively improve heart failure by regulating TGF-ß 1/Smad signaling pathway.

Chromosome-level genome assembly of the European flat oyster (Ostrea edulis) provides insights into its evolution and adaptation.

The European flat oyster (Ostrea edulis) is an endangered and economically important marine bivalve species that plays a critical role in the coastal ecosystem. Here, we report a high-quality chromosome-level genome assembly of O. edulis, generated using PacBio HiFi-CCS long reads and annotated with Nanopore full-length transcriptome. The O. edulis genome covers 946.06 Mb (scaffold N50 94.82 Mb) containing 34,495 protein-coding genes and a high proportion of repeat sequences (58.49 %). The reconstructed demographic histories show that O. edulis population might be shaped by breeding habit (embryo brooding) and historical climatic change. Comparative genomic analysis indicates that transposable elements may drive lineage-specific evolution in oysters. Notably, the O. edulis genome has a Hox gene cluster rearrangement that has never been reported in bivalves, making this species valuable for evolutionary studies of molluscan diversification. Moreover, genome expansion of O. edulis is probably central to its adaptation to filter-feeding and sessile lifestyles, as well as embryo brooding and pathogen resistance, in coastal ecosystems. This chromosome-level genome assembly provides new insights into the genome feature of oysters, and presents an important resource for genetic research, evolutionary studies, and biological conservation of O. edulis.