Temporal shifts in 24 notifiable infectious diseases in China before and during the COVID-19 pandemic.

The coronavirus disease 2019 (COVID-19) pandemic, along with the implementation of public health and social measures (PHSMs), have markedly reshaped infectious disease transmission dynamics. We analysed the impact of PHSMs on 24 notifiable infectious diseases (NIDs) in the Chinese mainland, using time series models to forecast transmission trends without PHSMs or pandemic. Our findings revealed distinct seasonal patterns in NID incidence, with respiratory diseases showing the greatest response to PHSMs, while bloodborne and sexually transmitted diseases responded more moderately. 8 NIDs were identified as susceptible to PHSMs, including hand, foot, and mouth disease, dengue fever, rubella, scarlet fever, pertussis, mumps, malaria, and Japanese encephalitis. The termination of PHSMs did not cause NIDs resurgence immediately, except for pertussis, which experienced its highest peak in December 2023 since January 2008. Our findings highlight the varied impact of PHSMs on different NIDs and the importance of sustainable, long-term strategies, like vaccine development.

Gas6/AXL Alleviates Hepatic Ischemia/Reperfusion Injury by Inhibiting Ferroptosis via the PI3K/AKT Pathway.

BACKGROUND: Hepatic ischemia/reperfusion (I/R) injury is a major cause of complications in clinical liver surgery. AXL receptor tyrosine kinase (AXL) is a member of the TAM receptor tyrosine kinase family (TYRO3, AXL, and MERTK). Our previous study has shown that AXL expression was markedly upregulated in liver transplantation patients. However, the underlying mechanism of AXL in hepatic I/R injury remains unclear. METHODS: A mouse liver warm I/R model and a primary hepatocyte hypoxia/reoxygenation model were established to investigate the role of AXL activation and ferroptosis in hepatic I/R injury by pretreating with recombinant mouse growth arrest-specific protein 6 (AXL activator) or R428 (AXL inhibitor). Moreover, we used LY294002 (phosphatidylinositol 3-kinase [PI3K] inhibitor) to evaluate the relationship between the PI3K/AKT (the Ser and Thr kinase AKT) pathway and ferroptosis in hepatic I/R injury. RESULTS: Hepatic I/R injury decreased phosphorylation AXL expression and enhanced ferroptosis in liver transplantation patients and hepatic I/R-subjected mice. AXL activation attenuated lipid peroxidation and ferroptosis in hepatic I/R injury in vivo and in vitro. Inhibition of AXL activation exacerbated liver pathological damage and liver dysfunction, as well as iron accumulation and lipid peroxidation in hepatic I/R injury. Mechanistically, activated growth arrest-specific protein 6/AXL and its downstream PI3K/AKT signaling pathway inhibited ferroptosis during hepatic I/R injury. CONCLUSIONS: AXL activation protects against hepatic I/R injury by preventing ferroptosis through the PI3K/AKT pathway. This study is the first investigation on the AXL receptor and ferroptosis, and activating AXL to mitigate ferroptosis may be an innovative therapeutic strategy to combat hepatic I/R injury.

Neurotoxicity of tetramethylammonium ion on larval and juvenile zebrafish: Effects on neurobehaviors and multiple biomarkers.

Tetramethylammonium hydroxide (TMAH) is an important compound that utilized and released by the rapidly expanding semiconductor industry, which could hardly be removed by the conventional wastewater treatment techniques. As a cholinergic agonist, the tetramethylammonium ion (TMA+) has been reported to induce toxicity to muscular and respiratory systems of mammals and human, however the toxicity on aquatic biota remains poorly known. We investigated the neurotoxic effects of TMA+ exposure on zebrafish, based on neurobehavior tests and a series of biomarkers. Significant inhibitions on the swimming distance of zebrafish larvae were observed when the exposure level exceeded 50 mg/L, and significant alterations on swimming path angles (straight and deflective movements) occurred even at 10 mg/L. The tested neurobehavioral endpoints of zebrafish larvae were significantly positively correlated with reactive oxygen species (ROS) and malondialdehyde (MDA), significantly negatively related with the activities of antioxidant enzymes, but not significantly correlated with the level of acetylcholinesterase (AChE). Such relationship indicates that the observed neurotoxic effects on swimming behavior of zebrafish larvae is mainly driven by oxidative stress, rather than the alterations of neurotransmitter. At the highest exposure concentration (200 mg/L), TMA+ evoked more severe toxicity on zebrafish juveniles, showing significantly stronger elevation on the MDA activity, and greater inhibitions on the activities of antioxidant enzymes and AChE, suggesting juveniles were more susceptible to TMA+ exposure than larval zebrafish.

Study on the Freeze-Thaw Resistance of Concrete Pavements in Seasonally Frozen Regions.

In seasonally frozen regions, concrete pavement is exposed to cycles of freeze-thaw and erosion from de-icing salt, which can lead to unfavorable service conditions and vulnerability to damage. This paper examines the compressive strength, flexural-tensile strength, abrasion resistance, permeability, and spacing factor of concrete, taking into account the impact of various curing conditions, de-icing salt solutions, and mass fractions on the concrete's freeze-thaw resistance. Two test methods, the single-face method and the fast-freezing method, were used to comparatively analyze the freeze-thaw resistance of concrete. The analysis was based on the surface scaling, water absorption rate, mass loss rate, relative dynamic elastic modulus, and relative durability index. The results indicate that the presence of salt solution significantly worsened the degree of concrete damage caused by freeze-thaw cycles. The use of freeze-thaw media, specifically sodium chloride (NaCl), calcium chloride (CaCl2), and potassium acetate (KAc) at mass fractions of 5%, 4.74%, and 5%, respectively, had the greatest impact on the surface scaling of concrete. However, their effect on the water absorption rate was inconsistent. When the freeze-thaw medium was water, the concrete's relative dynamic elastic modulus and relative durability index were 9.6% and 75.3% higher, respectively, for concrete cured in 20 °C-95% RH conditions compared to those cured in 0 °C-50% RH conditions. We propose a comprehensive relative durability index (DFw) by combining the results of two methods of freeze-thaw tests. The DFw of concrete cured in 0 °C-50% RH conditions was 83.8% lower than that of concrete cured in 20 °C-95% RH conditions when exposed to a freeze-thaw medium of 5% mass fraction NaCl solution. To evaluate the salt freeze-thaw resistance of concrete pavement, it is recommended to use surface scaling and DFw together.

Endoplasmic reticulum stress-related genes as prognostic and immunogenic biomarkers in prostate cancer.

BACKGROUND: The metastasis and aggressive nature of prostate cancer (PCa) has become a major malignancy related threat that concerns men's health. The efficacy of immune monotherapy against PCa is questionable due to its lymphocyte-suppressive nature. METHOD: Endoplasmic reticulum stress- (ERS-) and PCa-prognosis-related genes were obtained from the Molecular Signatures Database and the Cancer Genome Atlas database. The expression, prognosis and immune infiltration values of key genes were explored by "survival R package", "rms", "xCELL algorithm", and univariate-multivariate Cox and LASSO regression analyses. The "consensus cluster plus R package" was used for cluster analysis. RESULT: As ERS-related genes, ERLIN2 and CDK5RAP3 showed significant expressional, prognostic and clinic-pathologic values. They were defined as the key genes significantly correlated with immune infiltration and response. The nomogram was constructed with T-stage and primary treatment outcome, and the risk-prognostic model was constructed in the following way: Riskscore = (- 0.1918) * ERLIN2 + (0.5254) * CDK5RAP3. Subsequently, prognostic subgroups based on key genes classified the high-risk group as a pro-cancer subgroup that had lower mutation rates of critical genes (SPOP and MUC16), multiple low-expression immune-relevant molecules, and differences in macrophages (M1 and M2) expressions. Finally, ERLIN2 as an anti-oncogene and CDK5RAP3 as a pro-oncogene were further confirmed by cell phenotype assays and immunohistochemistry. CONCLUSION: We identified ERLIN2 and CDK5RAP3 as ERS-related genes with important prognostic and immunologic values, and classified patients between high- and low-risk subgroups, which provided new prognostic markers, immunotherapeutic targets, and basis for prognostic assessments.

A Sequentially Activated Probe for Imaging of Superoxide Anion and Peroxynitrite in PC12 Cells under Oxidative Stress.

Superoxide anion (O2·-) and peroxynitrite (ONOO-), two important oxidants under oxidative stress, coexist in complex cell and organism systems, playing crucial roles in various physiological and pathological processes, particularly in neurodegenerative diseases. Despite the absence of robust molecular tools capable of simultaneously visualizing O2·- and ONOO- in biosystems, the relationship between these two species remains understudied. Herein, we present sequentially activated fluorescent probe, DHX-SP, which exhibits exceptional selectivity and sensitivity toward O2·- and ONOO-. This probe enables precise imaging of these species in living PC12 cells under oxidative stress conditions using distinct fluorescence signal combinations. Furthermore, the probe DHX-SP has the ability to visualize changes in O2·- and ONOO- levels during ferroptosis of PC12 cells and in the Parkinson's disease model. These findings establish a connection between the crosstalk of the phosphorus group of O2·- and ONOO- in PC12 cells under oxidative stress.

Efficacy of acupuncture as an adjunctive treatment to patients with stable COPD: a multicenter, randomized, sham-controlled trial protocol.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a common respiratory disease and the third leading cause of death worldwide. Previous evidence has shown that acupuncture may be an effective complementary alternative therapy for stable COPD. However, large-sample, rigorously designed long-term follow-up studies still need to be completed. Notably, the relationship between the frequency of acupuncture and clinical efficacy in studies on acupuncture for stable COPD still needs further validation. This study aims to evaluate the efficacy and safety of acupuncture for stable COPD and further investigate the dose-effect relationship of acupuncture. METHODS/DESIGN: This is a multicenter, randomized, controlled trial that uses central randomization to randomly allocate 550 participants in a 1:1:1:1:1 ratio to once a week acupuncture group, twice a week acupuncture group, three times a week acupuncture group, sham acupuncture group and waiting-list control group. The sham acupuncture group will receive placebo acupuncture treatments three times per week, and the waiting-list control group will not receive any form of acupuncture intervention. The study consists of a 2-week baseline, 12-week of treatment, and 52-week of follow-up. Patients with COPD between 40 to 80 years old who have received stable Western medication within the previous 3 months and have had at least 1 moderate or severe acute exacerbation within the past 1 year will be included in the study. Basic treatment will remain the same for all participants. The primary outcome is the proportion of responders at week 12. Secondary outcomes include the proportion of responders at week 64, change in the St. George's Respiratory Questionnaire (SGRQ) Scale, change in the Modified-Medical Research Council (mMRC) Scale, change in the COPD Assessment Test (CAT) Scale, change in the Lung Function Screening Indicators (LFSI), change in the 6-min walk distance (6-MWD), change in Short-Form 36 Health Survey (SF-36) Scale, the number of moderate and severe acute exacerbations and adverse event rate during the follow-up period. DISCUSSION: This study will provide robust evidence on whether acupuncture is safe and effective for treating stable COPD. Meanwhile, comparing the differences in efficacy between different acupuncture frequencies will further promote the optimization of acupuncture for stable COPD. TRIAL REGISTRATION: This study was registered in the Chinese Clinical Trial Registry (ChiCTR2200058757), on April 16, 2022.

Dust-phase phthalates in university dormitories in Beijing, China: pollution characteristics, potential sources, and non-dietary oral exposure.

This study aimed to determine dust-phase phthalate levels in 112 dormitories of 14 universities during autumn and winter, investigate their potential sources, and estimate phthalate exposure via dust ingestion. Twelve phthalates were detected, among which di-(2-ethylhexyl) phthalate (DEHP) and dicyclohexyl phthalate (DCHP) were the most abundant, followed by di-isobutyl phthalate (DiBP) and di-n-butyl phthalate (DnBP). The median concentrations and contributions of DCHP and DEHP were the highest. The contributions of di-n-octyl phthalate and di-nonyl phthalate were higher in winter than in autumn. Potential sources included iron furniture, chemical fiber textiles, clothes, and personal care products. Medium-density fiberboard furniture is a potential sink for phthalates. In two seasons, DEHP, DCHP, DiBP, and DnBP were the main phthalates ingested by college students . The median oral exposure of ten phthalates was higher in females than in males. College students have a high risk of exposure to DEHP in dormitories.

A Multiparametric MRI-based Radiomics Model for Stratifying Postoperative Recurrence in Luminal B Breast Cancer.

This study aims to develop an MRI-based radiomics model to assess the likelihood of recurrence in luminal B breast cancer. The study analyzed medical images and clinical data from 244 patients with luminal B breast cancer. Of 244 patients, 35 had experienced recurrence and 209 had not. The patients were randomly divided into the training set (51.5 ± 12.5 years old; n = 171) and the test set (51.7 ± 11.3 years old; n = 73) in a ratio of 7:3. The study employed univariate and multivariate Cox regression along with the least absolute shrinkage and selection operator (LASSO) regression methods to select radiomics features and calculate a risk score. A combined model was constructed by integrating the risk score with the clinical and pathological characteristics. The study identified two radiomics features (GLSZM and GLRLM) from DCE-MRI that were used to calculate a risk score. The AUCs were 0.860 and 0.868 in the training set and 0.816 and 0.714 in the testing set for 3- and 5-year recurrence risk, respectively. The combined model incorporating the risk score, pN, and endocrine therapy showed improved predictive power, with AUCs of 0.857 and 0.912 in the training set and 0.943 and 0.945 in the testing set for 3- and 5-year recurrence risk, respectively. The calibration curve of the combined model showed good consistency between predicted and measured values. Our study developed an MRI-based radiomics model that integrates clinical and radiomics features to assess the likelihood of recurrence in luminal B breast cancer. The model shows promise for improving clinical risk stratification and treatment decision-making.

Association between baseline glycated hemoglobin level and atrial fibrillation recurrence following cryoballoon ablation among patients with and without diabetes.

OBJECTIVES: The study aims to assess the effect of baseline glycated hemoglobin (HbA1c) levels on atrial fibrillation (AF) recurrence following cryoballoon ablation in patients with and without diabetes. METHODS: Consecutive AF patients receiving first cryoballoon ablation between April 2018 and April 2021 were included. AF recurrence and other clinical outcomes were recorded for a minimum of 12 months post-ablation, with regular assessments at 3, 6, and 12 months, followed by annual check-ups. The primary outcome was AF recurrence after ablation at longest follow-up. Multivariate Cox proportional hazards regression models were utilized to calculate the hazard ratio (HR) and 95% CI per standard deviation (SD) increase of baseline HbA1c level. RESULTS: 335 patients were included in the analysis. The mean age was 61.7 years, 61.8% were male. 12.8% had type 2 diabetes, and 81.7% of patients had paroxysmal AF. The median level of HbA1c was 5.3%, and the mean CHA2DS2-VASc score was 1.8. All cryoballoon ablation procedures, utilizing a 28-mm balloon, achieved successful pulmonary vein isolation. Over a median follow-up of 18 months, 105 patients (31.3%) experienced AF recurrence. In multivariate Cox proportional hazards analysis, a higher HbA1c level, persistent AF (HR 1.91, 95% CI 1.08 to 3.39, P = 0.026), alcohol consumption (HR 2.67, 95% CI 1.33 to 5.37, P = 0.006), and Nadir RSPV (HR 1.04, 95% CI 1.00 to 1.08, P = 0.005) were significant predictors of AF recurrence. Per-SD increase of HbA1c was associated with a 1.75-fold increase risk of AF recurrence (HR 1.75, 95% CI 1.39 to 2.21, P < 0.001). Subgroup analysis revealed that a higher HbA1c level was associated with a higher risk of AF recurrence in patients with and without diabetes, and in patients with paroxysmal and persistent AF. CONCLUSION: Baseline HbA1c level was an independent predictor of AF recurrence following cryoablation, both in patients with and without diabetes.

Magnetic resonance imaging-based radiomics was used to evaluate the level of prognosis-related immune cell infiltration in breast cancer tumor microenvironment.

PURPOSE: The tumor immune microenvironment is a valuable source of information for predicting prognosis in breast cancer (BRCA) patients. To identify immune cells associated with BRCA patient prognosis from the Cancer Genetic Atlas (TCGA), we established an MRI-based radiomics model for evaluating the degree of immune cell infiltration in breast cancer patients. METHODS: CIBERSORT was utilized to evaluate the degree of infiltration of 22 immune cell types in breast cancer patients from the TCGA database, and both univariate and multivariate Cox regressions were employed to determine the prognostic significance of immune cell infiltration levels in BRCA patients. We identified independent prognostic factors for BRCA patients. Additionally, we obtained imaging features from the Cancer Imaging Archive (TCIA) database for 73 patients who underwent preoperative MRI procedures, and used the Least Absolute Shrinkage and Selection Operator (LASSO) to select the best imaging features for constructing an MRI-based radiomics model for evaluating immune cell infiltration levels in breast cancer patients. RESULTS: According to the results of Cox regression analysis, M2 macrophages were identified as an independent prognostic factor for BRCA patients (HR = 32.288, 95% CI: 3.100-357.478). A total of nine significant features were selected to calculate the radiomics-based score. We established an intratumoral model with AUCs (95% CI) of 0.662 (0.495-0.802) and 0.678 (0.438-0.901) in the training and testing cohorts, respectively. Additionally, a peritumoral model was created with AUCs (95% CI) of 0.826 (0.710-0.924) and 0.752 (0.525-0.957), and a combined model was established with AUCs (95% CI) of 0.843 (0.723-0.938) and 0.744 (0.491-0.965). The peritumoral model demonstrated the highest diagnostic efficacy, with an accuracy, sensitivity, and specificity of 0.773, 0.727, and 0.818, respectively, in its testing cohort. CONCLUSION: The MRI-based radiomics model has the potential to evaluate the degree of immune cell infiltration in breast cancer patients, offering a non-invasive imaging biomarker for assessing the tumor microenvironment in this disease.

The impact of different soluble endogenous proteins and their combinations with ß-glucan on the in vitro digestibility, microstructure, and physicochemical properties of highland barley starch.

The impacts of protein types and its interaction with ß-glucan on the in vitro digestibility of highland barley starch were investigated through analyzing physicochemical and microstructural properties of highland barley flour (HBF) after sequentially removing water- (WP), salt- (SP), alcohol- (AP) and alkali-soluble (AlkP) proteins. Resistant starch (RS) increased significantly in HBF after removing WP and SP, and RS of HBF was lower than that of without ß-glucan. After removing WP, SP and AP, swelling powers of HBF without ß-glucan (9.33-9.77) were higher than those of HBF (12.09-15.95). Trends of peak viscosity and peak temperature (thermal degradation temperature) were similar as swelling power, and HBF without AP showed the highest peak temperature (310.33 °C). Removals of different proteins improved the crystalline structure and short-range order of starch. There was a blue shift in T2 values and an opposite change in free water proportion. The matrix on starch surface was mainly formed by AP and AlkP, which could be aggregated by ß-glucan. But, the inhibitory effect of AP or AlkP was stronger than that of proteins combined with ß-glucan. These results help in the development of starch-based foods with different digestive properties by combining different protein types with ß-glucan.

Short-term effectiveness of single-dose intranasal spray COVID-19 vaccine against symptomatic SARS-CoV-2 Omicron infection in healthcare workers: a prospective cohort study.

Background: The pivotal phase 3 efficacy clinical trial has demonstrated that a two-dose regimen of dNS1-RBD (Beijing Wantai Biological Pharmacy Enterprise, Beijing, China) is well-tolerated and provides wide protection against SARS-CoV-2 infection. However, the effectiveness of a single-dose regimen is still unknown. We aimed to estimate the effectiveness of one-dose of dNS1-RBD against symptomatic Omicron infections in real-world conditions. Methods: This prospective cohort study was conducted during an Omicron outbreak among healthcare workers in Xiamen, China, from December 22, 2022 to January 16, 2023. Participants chose to receive single-dose of dNS1-RBD or remain unvaccinated based on personal preference. Healthcare workers daily validated their SARS-CoV-2 infection status, using either RT-PCR or rapid antigen test. A survey questionnaire was conducted to gather information on acute symptoms from individuals infected with SARS-CoV-2. The primary outcome was the symptomatic SARS-CoV-2 infections after enrollment in the dNS1-RBD recipients or the control group among all participants and by prior COVID-19 vaccination status. Findings: On December 22, 2022, a total of 1391 eligible participants without a history of prior SARS-CoV-2 infection were enrolled. Among them, 550 received single-dose of dNS1-RBD, while 841 remained unvaccinated. In the total cohort, the range of follow-up time was 1∼26 days. During the study period, a total of 880 symptomatic SARS-CoV-2 infections were identified in the total cohort. The adjusted vaccine effectiveness against symptomatic SARS-CoV-2 infections and the infections requiring medical attention were 19.0% (95% CI: 6.7, 29.7, P = 0.004) and 59.4% (95% CI: 25.1, 78.0, P = 0.004) in the total cohort, 11.6% (95% CI: -2.4, 23.7, P = 0.100) and 55.3% (95% CI: 15.3, 76.4, P = 0.014) in the participants with inactivated COVID-19 vaccination history, as well as 87.0% (95% CI: 72.6, 93.9, P < 0.001) and 84.2% (95% CI: -41.8, 98.2, P = 0.099) in the naïve participants, respectively. Interpretation: When administered as a booster to individuals with a history of inactivated COVID-19 vaccination, a single-dose of dNS1-RBD provides protection against infections requiring medical attention at least in the short-term after vaccination. The data also showed that a single-dose of dNS1-RBD is protective against symptomatic SARS-CoV-2 infections as a primary immunization for individuals without prior exposure, but due to the limited sample size of naïve participants, further research with a larger sample size is needed to make a solid conclusion. Funding: Xiamen Science and Technology Bureau 2022 General Science and Technology Plan Project and the Bill & Melinda Gates Foundation.

In vitro and in silico analyses reveal the interaction between LysM receptor-like kinase3 of Solanum tuberosum and the carbohydrate elicitor Riclin octaose.

As a carbohydrate elicitor, Riclin octaose (Rioc) activates the pattern-triggered immunity of Solanum tuberosum L., while how the plant perceives Rioc is unknown. Here, a pattern recognition receptor StLYK3 (LysM receptor-like kinase3) whose transcription level was significantly up-regulated after Rioc elicitation was investigated in vitro and in silico. The nucleotide that encoded the ectodomain of StLYK3 (StLYK3-ECD) was heterologously expressed in the Pichia pastoris strain GS115. The purified StLYK3-ECD had the molecular weight of 25.08 kDa and pI of 5.69. Afterwards interaction between StLYK3-ECD and Rioc was analyzed by isothermal titration calorimetry. The molar ratio of ligand to receptor, dissociation constant, and enthalpy were 1.28 ± 0.04, 26.7 ± 3.1 µM, and -45.0 ± 1.8 kJ mol-1 , respectively. Besides, molecular dynamics results indicated that StLYK3-ECD contained three carbohydrate-binding motifs and the first two motifs probably contributed to the interaction with Rioc via hydrogen bond and van de Waals' forces. Amino acids containing hydroxyl, amidic, and sulfhydryl groups took the main portion in the docking site. Moreover, replacing the 92nd threonyl (T) of StLYK3-ECD with valyl (V) resulted in the alteration of the preferred docking site. The dissociation constant drastically increased to 841.6 ± 232.4 µM. In conclusion, StLYK3 was a potential receptor of Rioc.

A Propolis-Derived Small Molecule Tectochrysin Ameliorates Type 2 Diabetes in Mice by Activating Insulin Receptor ß.

SCOPE: Propolis has been found to decrease glucose levels and increase insulin sensitivity in type 2 diabetes. However, the active ingredient responsible for these effects and its regulating mechanism are not fully understood. METHODS AND RESULTS: To address this, molecular docking screening is used to screen the effective hypoglycemic ingredient in propolis and found that tectochrysin (TEC) has a high affinity to the insulin receptor (IR), highlighting its potential for glycemic control. In vivo tests show that TEC decreases glucose levels and enhances insulin sensitivity in db/db mice. By hyperinsulinemic euglycemic clamp test, this study further finds that TEC promotes glucose uptake in adipose tissue and skeletal muscle, as well as inhibits hepatic gluconeogenesis. Moreover, it finds that TEC promotes glucose uptake and adipocytes differentiation in 3T3-L1 cells like insulin, suggesting that TEC exerts an insulin mimetic effect. Mechanistically, pharmacology inhibition of IRß abolishes the effects of TEC on glucose uptake and the phosphorylation of IR. The study further demonstrates that TEC binds to and activates IRß by targeting its E1077 and M1079. CONCLUSION: Therefore, this study sheds light on the mechanism underlying propolis' potential for ameliorating type 2 diabetes, offering a natural food-derived compound as a promising therapeutic option.

Application of adaptive laboratory evolution to improve the tolerance of Rhodotorula strain to methanol in crude glycerol and development of an effective method for cell lysis.

Rhodotorula toruloides can utilize crude glycerol as the low-cost carbon source for lipid production, but its growth is subjected to inhibition by methanol in crude glycerol. Here, transcriptome profiling demonstrated that 1004 genes were significantly regulated in the strain R. toruloides TO2 under methanol stress. Methanol impaired the function of membrane transport and subsequently weakened the utilization of glycerol, activities of the primary metabolism and functions of nucleus and ribosome. Afterwards the tolerance of TO2 to methanol was improved by using two-round adaptive laboratory evolution (ALE). The final strain M2-ale had tolerance up to 3.5% of methanol. 1 H NMR-based metabolome analysis indicated that ALE not only improved the tolerance of M2-ale to methanol but also tuned the carbon flux towards the biosynthesis of glycerolipid-related metabolites. The biomass and lipid titer of M2-ale reached 14.63 ± 0.45 g L-1 and 7.06 ± 0.44 g L-1 at 96 h in the crude glycerol medium, which increased up to 17.69% and 31.39%, respectively, comparing with TO2. Afterwards, an effective method for cell lysis was developed by combining sonication and enzymatic hydrolysis (So-EnH). The lytic effect of So-EnH was validated by using confocal imaging and flow cytometry. At last, lipid recovery rate reached 95.4 ± 2.7% at the optimized condition.

CPFTransformer: transformer fusion context pyramid medical image segmentation network.

Introduction: The application of U-shaped convolutional neural network (CNN) methods in medical image segmentation tasks has yielded impressive results. However, this structure's single-level context information extraction capability can lead to problems such as boundary blurring, so it needs to be improved. Additionally, the convolution operation's inherent locality restricts its ability to capture global and long-distance semantic information interactions effectively. Conversely, the transformer model excels at capturing global information. Methods: Given these considerations, this paper presents a transformer fusion context pyramid medical image segmentation network (CPFTransformer). The CPFTransformer utilizes the Swin Transformer to integrate edge perception for segmentation edges. To effectively fuse global and multi-scale context information, we introduce an Edge-Aware module based on a context pyramid, which specifically emphasizes local features like edges and corners. Our approach employs a layered Swin Transformer with a shifted window mechanism as an encoder to extract contextual features. A decoder based on a symmetric Swin Transformer is employed for upsampling operations, thereby restoring the resolution of feature maps. The encoder and decoder are connected by an Edge-Aware module for the extraction of local features such as edges and corners. Results: Experimental evaluations on the Synapse multi-organ segmentation task and the ACDC dataset demonstrate the effectiveness of our method, yielding a segmentation accuracy of 79.87% (DSC) and 20.83% (HD) in the Synapse multi-organ segmentation task. Discussion: The method proposed in this paper, which combines the context pyramid mechanism and Transformer, enables fast and accurate automatic segmentation of medical images, thereby significantly enhancing the precision and reliability of medical diagnosis. Furthermore, the approach presented in this study can potentially be extended to image segmentation of other organs in the future.

MMGan: a multimodal MR brain tumor image segmentation method.

Computer-aided diagnosis has emerged as a rapidly evolving field, garnering increased attention in recent years. At the forefront of this field is the segmentation of lesions in medical images, which is a critical preliminary stage in subsequent treatment procedures. Among the most challenging tasks in medical image analysis is the accurate and automated segmentation of brain tumors in various modalities of brain tumor MRI. In this article, we present a novel end-to-end network architecture called MMGan, which combines the advantages of residual learning and generative adversarial neural networks inspired by classical generative adversarial networks. The segmenter in the MMGan network, which has a U-Net architecture, is constructed using a deep residual network instead of the conventional convolutional neural network. The dataset used for this study is the BRATS dataset from the Brain Tumor Segmentation Challenge at the Medical Image Computing and Computer Assisted Intervention Society. Our proposed method has been extensively tested, and the results indicate that this MMGan framework is more efficient and stable for segmentation tasks. On BRATS 2019, the segmentation algorithm improved accuracy and sensitivity in whole tumor, tumor core, and enhanced tumor segmentation. Particularly noteworthy is the higher dice score of 0.86 achieved by our proposed method in tumor core segmentation, surpassing those of stateof-the-art models. This study improves the accuracy and sensitivity of the tumor segmentation task, which we believe is significant for medical image analysis. And it should be further improved by replacing different loss functions such as cross-entropy loss function and other methods.

Loss of ZBED6 Protects Against Sepsis-Induced Muscle Atrophy by Upregulating DOCK3-Mediated RAC1/PI3K/AKT Signaling Pathway in Pigs.

Sepsis-induced muscle atrophy often increases morbidity and mortality in intensive care unit (ICU) patients, yet neither therapeutic target nor optimal animal model is available for this disease. Here, by modifying the surgical strategy of cecal ligation and puncture (CLP), a novel sepsis pig model is created that for the first time recapitulates the whole course of sepsis in humans. With this model and sepsis patients, increased levels of the transcription factor zinc finger BED-type containing 6 (ZBED6) in skeletal muscle are shown. Protection against sepsis-induced muscle wasting in ZBED6-deficient pigs is further demonstrated. Mechanistically, integrated analysis of RNA-seq and ChIP-seq reveals dedicator of cytokinesis 3 (DOCK3) as the direct target of ZBED6. In septic ZBED6-deficient pigs, DOCK3 expression is increased in skeletal muscle and myocytes, activating the RAC1/PI3K/AKT pathway and protecting against sepsis-induced muscle wasting. Conversely, opposite gene expression patterns and exacerbated muscle wasting are observed in septic ZBED6-overexpressing myotubes. Notably, sepsis patients show increased ZBED6 expression along with reduced DOCK3 and downregulated RAC1/PI3K/AKT pathway. These findings suggest that ZBED6 is a potential therapeutic target for sepsis-induced muscle atrophy, and the established sepsis pig model is a valuable tool for understanding sepsis pathogenesis and developing its therapeutics.