Amino acid mutations PB1-V719M and PA-N444D combined with PB2-627K contribute to the pathogenicity of H7N9 in mice.

H7N9 subtype avian influenza viruses (AIVs) cause 1567 human infections and have high mortality, posing a significant threat to public health. Previously, we reported that two avian-derived H7N9 isolates (A/chicken/Eastern China/JTC4/2013 and A/chicken/Eastern China/JTC11/2013) exhibit different pathogenicities in mice. To understand the genetic basis for the differences in virulence, we constructed a series of mutant viruses based on reverse genetics. We found that the PB2-E627K mutation alone was not sufficient to increase the virulence of H7N9 in mice, despite its ability to enhance polymerase activity in mammalian cells. However, combinations with PB1-V719M and/or PA-N444D mutations significantly enhanced H7N9 virulence. Additionally, these combined mutations augmented polymerase activity, thereby intensifying virus replication, inflammatory cytokine expression, and lung injury, ultimately increasing pathogenicity in mice. Overall, this study revealed that virulence in H7N9 is a polygenic trait and identified novel virulence-related residues (PB2-627K combined with PB1-719M and/or PA-444D) in viral ribonucleoprotein (vRNP) complexes. These findings provide new insights into the molecular mechanisms underlying AIV pathogenesis in mammals, with implications for pandemic preparedness and intervention strategies.

Sludge biolysis pretreatment to reduce antibiotic resistance genes (ARGs): Insight into the relationship between potential ARGs hosts and BALOs' preferred prey.

As an important reservoir of antibiotic resistance genes (ARGs), the sludge discharged from wastewater treatment plants is the key intermediate for ARG transport into the environment. Bdellovibrio-and-like organisms (BALOs) are predatory bacteria that are expected to attack antibiotic-resistant bacteria (ARB). In this study, the screened BALOs (C3 & D15) were mixed with the sludge for biolysis to achieve the satisfying removal efficiencies of six tet genes, two sul genes, and one mobile genetic element (intl 1). Among them, tet(Q) demonstrated the highest reduction rate in relative abundance at 87.3 ± 1.0 %, while tet(X) displayed the lowest of 11.7 ± 0.2 %. The microorganisms, including Longilinea, Methanobacterium, Acetobacterium, Sulfurimonas, allobaculum, Gaiella, AAP99, Ellin6067, Rhodoferax, Ferruginibacter and Thermomonas, were expected to play a dual role in the reduction of ARGs by serving as ARB and BALOs' preferred prey. Meanwhile, BALOs consortium improved ARGs reduction efficiency via the expansion of the prey profile. Additionally, BALOs decreased the relative abundance of not only pathogens (Shinella, Rickettsia, Burkholderia, Acinetobacter, Aeromonas, Clostridium, Klebsiella and Pseudomonas), but also the ARGs' host pathogens (Mycobacterium, Plesiocystis, Burkholderia, and Bacteroides). Therefore, the application of BALOs for sludge biolysis are promising to decrease the sludge's public health risks via limiting the spread of ARGs and pathogens into the environment.

Evaluation of the passive mast cell activation test for identifying allergens in perioperative anaphylaxis: a study protocol for a prospective diagnostic accuracy study.

INTRODUCTION: Perioperative anaphylaxis (POA) can lead to significant complications. Therefore, accurate identification of allergens for POA patients is critical to ensure the safety of future surgical and anaesthetic procedures. Existing perioperative allergen detection methods face challenges in sensitivity and specificity. The passive mast cell activation test (pMAT) has recently emerged as a potential diagnostic tool. Our study aims to evaluate the diagnostic efficacy of pMAT for identifying perioperative allergens, with a focus on non-depolarising neuromuscular blocking agents, the most common culprits of POA. METHODS AND ANALYSIS: This prospective diagnostic accuracy study will measure the diagnostic accuracy of pMAT in POA patients. Participants will undergo skin testing (ST), basophil activation testing (BAT) and pMAT. The diagnostic validity of pMAT will be assessed based on the results of ST and BAT. The assessment of diagnostic accuracy will include sensitivity, specificity, likelihood ratios, and false-positive and false-negative rates while measurement of the consistency rate will assess reliability. ETHICS AND DISSEMINATION: This study has been approved by the Institutional Review Board of China-Japan Friendship Hospital (2023-KY-247). Results will be disseminated through academic presentations and peer-reviewed journal publications and will provide valuable scientific data and some new insights into the diagnostic accuracy of pMAT.

Association between different triglyceride glucose index-related indicators and depression in premenopausal and postmenopausal women: NHANES, 2013-2016.

BACKGROUND AND AIM: The association between the Triglyceride-glucose (TyG) index and depression has been observed, yet its confirmation within peri- and postmenopausal demographics remains elusive. Consequently, the principal aim of this investigation is to explore the nexus between TyG-related indicators and depressive symptoms among pre- and postmenopausal women. METHODS: The data utilized in this study were obtained from the National Health and Nutrition Examination Survey (NHANES) conducted from 2013 to 2016. The patients were divided into three groups based on TyG, Triglyceride-Glucose-Body Mass Index (TyG-BMI), Triglyceride-Glucose-Waist Circumference (TyG-WC), and Triglyceride-Glucose-Waist-to-Height Ratio (TyG-WHtR): Q1 (1st quintile), Q2 (2nd quintile), and Q3 (3rd quintile). Further exploration of the differences between these groups was conducted. Employing logistic regression, stratified analysis, restricted cubic splines, and subgroup analyses, we scrutinized the correlation between TyG-related indicators and depressive symptoms in both premenopausal and postmenopausal women. Furthermore, sensitivity analyses were conducted to assess the durability and uniformity of this relationship. RESULTS: In premenopausal women, there was a consistent independent positive correlation between TyG-BMI, TyG-WC, and TyG-WHtR with depressive symptoms across all three models, while TyG itself did not show a significant association. In Models 1 and 2, TyG-BMI exhibited a higher odds ratio (OR) value than the other two indicators [Model 1, Q3 OR (95 % confidence interval, CI) = 3.37 (1.91-5.94); Model 2, Q3 OR (95 % CI) = 3.03 (1.67-5.52)]. In Models 3, TyG-WHtR demonstrates a more significant association with depressive symptoms [Model 3, Q3 OR (95 % CI) = 2.85 (1.55-5.27)]. This correlation does not manifest in menopausal women. CONCLUSIONS: In premenopausal women, TyG-BMI, TyG-WC, and TyG-WHtR exhibited a positive and linear relationship with depressive symptoms. Furthermore, the analysis revealed that the combined measures of TyG-BMI, TyG-WC, and TyG-WHtR offered greater precision and sensitivity in assessing this association compared to TyG alone.

The Association of Infant Birth Sizes and Anemia under Five Years Old: A Population-Based Prospective Cohort Study in China.

Infant birth sizes are vital clinical parameters to predict poor growth and micronutrient deficiency in early life. However, their effects on childhood anemia remain unclear. We aimed to explore the associations between birth weight, crown-heel length, and head circumference with anemia in early childhood, as well as potential modification factors. This population-based prospective cohort study included 204,556 participants with singleton live births delivered at gestational ages of 28-42 weeks. A logistic regression model was used to estimate the associations of the measures of infant birth size and their Z-score with anemia under five years old. There were 26,802 (13.10%) children under five years old who were diagnosed has having anemia. Compared with children who did not have anemia, children who had anemia had a lower birth weight and smaller head circumference and a longer crown-heel length (all p-values < 0.05). After adjusting for confounders, not only birth weight (ß coefficient, -0.008; 95% CI, -0.011--0.004; p < 0.001) and head circumference (ß coefficient, -0.004; 95% CI, -0.007--0.001; p = 0.009), but also the related Z-scores were negatively associated with childhood anemia, while the trends for crown-heel length were the opposite. We further found significant interactions of folic acid use and maternal occupation with infant birth sizes. In conclusion, infants having abnormal sizes at birth are significantly associated with the risk for childhood anemia, which can be modified by folic acid use during pregnancy and maternal occupation.

The haemagglutinin-neuraminidase protein of velogenic Newcastle disease virus enhances viral infection through NF-κB-mediated programmed cell death.

The haemagglutinin-neuraminidase (HN) protein, a vital membrane glycoprotein, plays a pivotal role in the pathogenesis of Newcastle disease virus (NDV). Previously, we demonstrated that a mutation in the HN protein is essential for the enhanced virulence of JS/7/05/Ch, a velogenic variant NDV strain originating from the mesogenic vaccine strain Mukteswar. Here, we explored the effects of the HN protein during viral infection in vitro using three viruses: JS/7/05/Ch, Mukteswar, and an HN-replacement chimeric NDV, JS/MukHN. Through microscopic observation, CCK-8, and LDH release assays, we demonstrated that compared with Mukteswar and JS/MukHN, JS/7/05/Ch intensified the cellular damage and mortality attributed to the mutant HN protein. Furthermore, JS/7/05/Ch induced greater levels of apoptosis, as evidenced by the activation of caspase-3/8/9. Moreover, JS/7/05/Ch promoted autophagy, leading to increased autophagosome formation and autophagic flux. Subsequent pharmacological experiments revealed that inhibition of apoptosis and autophagy significantly impacted virus replication and cell viability in the JS/7/05/Ch-infected group, whereas less significant effects were observed in the other two infected groups. Notably, the mutant HN protein enhanced JS/7/05/Ch-induced apoptosis and autophagy by suppressing NF-κB activation, while it mitigated the effects of NF-κB on NDV infection. Overall, our study offers novel insights into the mechanisms underlying the increased virulence of NDV and serves as a reference for the development of vaccines.

Plasma Kidney Injury Molecule-1 for Preoperative Prediction of Renal Cell Carcinoma Versus Benign Renal Masses, and Association With Clinical Outcomes.

PURPOSE: Both clear cell and papillary renal cell carcinomas (RCCs) overexpress kidney injury molecule-1 (KIM-1). We investigated whether plasma KIM-1 (pKIM-1) may be a useful risk stratification tool among patients with suspicious renal masses. METHODS: Prenephrectomy pKIM-1 was measured in two independent cohorts of patients with renal masses. Cohort 1, from the prospective K2 trial, included 162 patients found to have clear cell RCC (cases) and 162 patients with benign renal masses (controls). Cohort 2 included 247 patients with small (cT1a) renal masses from an academic biorepository, of whom 184 had RCC. We assessed the relationship between pKIM-1, surgical pathology, and clinical outcomes. RESULTS: In Cohort 1, pKIM-1 distinguished RCC versus benign masses with area under the receiver operating curve (AUC-ROC, 0.81 [95% CI, 0.76 to 0.86]). In Cohort 2 (cT1a only), pKIM-1 distinguished RCC versus benign masses (AUC-ROC, 0.74 [95% CI, 0.67 to 0.80]) and the addition of pKIM-1 to an established nomogram for predicting malignancy improved the model AUC-ROC (0.65 [95% CI, 0.57 to 0.74] v 0.78 [95% CI, 0.72 to 0.85]). A pKIM-1 cutpoint identified using Cohort 2 demonstrated sensitivity of 92.5% and specificity of 60% for identifying RCC in Cohort 1. In long-term follow-up of RCC cases (Cohort 1), higher prenephrectomy pKIM-1 was associated with worse metastasis-free survival (multivariable MFS hazard ratio [HR] 1.29 per unit increase in log pKIM-1, 95% CI, 1.10 to 1.53) and overall survival (multivariable OS HR 1.31 per unit increase in log pKIM-1, 95% CI, 1.10 to 1.54). In long-term follow-up of Cohort 2, no metastatic events occurred, consistent with the favorable prognosis of resected cT1a RCC. CONCLUSION: Among patients with renal masses, pKIM-1 is associated with malignant pathology, worse MFS, and risk of death. pKIM-1 may be useful for selecting patients with renal masses for intervention versus surveillance.

Pt-S bond stabilized DNAzyme nanosensor with thiol-resistance enabling high-fidelity biosensing.

Gold nanoparticles (Au NPs) have been widely utilized in developing DNAzyme-functionalized nanosensors, most of which were engineered by attaching the thiolated DNAzymes to Au NPs via Au-S bonding. However, the Au NP-DNAzyme nanosensors always suffer from signal distortion when applied in complex environment with abundant thiols, which poses challenge for practical applications. Here, we focus on addressing the root cause of the issue and propose to decorate the Au NPs with a thin layer of platinum, thus facilitating the conjugation of DNAzymes through Pt-S bonding, a thiol-resistant cross-linking. The Pt-S bond stabilized DNAzyme nanosensor effectively minimized false positive signals when detecting l-histidine in infant formulas, as compared to the Au-S stabilized counterpart. This innovative strategy holds promise for high-fidelity biosensing, improving the practical applicability of Au NP-based DNAzyme nanosensor.

CPT1C-positive cancer-associated fibroblast facilitates immunosuppression through promoting IL-6-induced M2-like phenotype of macrophage.

Cancer-associated fibroblasts (CAFs) exhibit remarkable phenotypic heterogeneity, with specific subsets implicated in immunosuppression in various malignancies. However, whether and how they attenuate anti-tumor immunity in gastric cancer (GC) remains elusive. CPT1C, a unique isoform of carnitine palmitoyltransferase pivotal in regulating fatty acid oxidation, is briefly indicated as a protumoral metabolic mediator in the tumor microenvironment (TME) of GC. In the present study, we initially identified specific subsets of fibroblasts exclusively overexpressing CPT1C, hereby termed them as CPT1C+CAFs. Subsequent findings indicated that CPT1C+CAFs fostered a stroma-enriched and immunosuppressive TME as they correlated with extracellular matrix-related molecular features and enrichment of both immunosuppressive subsets, especially M2-like macrophages, and multiple immune-related pathways. Next, we identified that CPT1C+CAFs promoted the M2-like phenotype of macrophage in vitro. Bioinformatic analyses unveiled the robust IL-6 signaling between CPT1C+CAFs and M2-like phenotype of macrophage and identified CPT1C+CAFs as the primary source of IL-6. Meanwhile, suppressing CPT1C expression in CAFs significantly decreased IL-6 secretion in vitro. Lastly, we demonstrated the association of CPT1C+CAFs with therapeutic resistance. Notably, GC patients with high CPT1C+CAFs infiltration responded poorly to immunotherapy in clinical cohort. Collectively, our data not only present the novel identification of CPT1C+CAFs as immunosuppressive subsets in TME of GC, but also reveal the underlying mechanism that CPT1C+CAFs impair tumor immunity by secreting IL-6 to induce the immunosuppressive M2-like phenotype of macrophage in GC.

BC-QNet: A quantum-infused ELM model for breast cancer diagnosis.

The timely and accurate diagnosis of breast cancer is pivotal for effective treatment, but current automated mammography classification methods have their constraints. In this study, we introduce an innovative hybrid model that marries the power of the Extreme Learning Machine (ELM) with FuNet transfer learning, harnessing the potential of the MIAS dataset. This novel approach leverages an Enhanced Quantum-Genetic Binary Grey Wolf Optimizer (Q-GBGWO) within the ELM framework, elevating its performance. Our contributions are twofold: firstly, we employ a feature fusion strategy to optimize feature extraction, significantly enhancing breast cancer classification accuracy. The proposed methodological motivation stems from optimizing feature extraction for improved breast cancer classification accuracy. The Q-GBGWO optimizes ELM parameters, demonstrating its efficacy within the ELM classifier. This innovation marks a considerable advancement beyond traditional methods. Through comparative evaluations against various optimization techniques, the exceptional performance of our Q-GBGWO-ELM model becomes evident. The classification accuracy of the model is exceptionally high, with rates of 96.54 % for Normal, 97.24 % for Benign, and 98.01 % for Malignant classes. Additionally, the model demonstrates a high sensitivity with rates of 96.02 % for Normal, 96.54 % for Benign, and 97.75 % for Malignant classes, and it exhibits impressive specificity with rates of 96.69 % for Normal, 97.38 % for Benign, and 98.16 % for Malignant classes. These metrics are reflected in its ability to classify three different types of breast cancer accurately. Our approach highlights the innovative integration of image data, deep feature extraction, and optimized ELM classification, marking a transformative step in advancing early breast cancer detection and enhancing patient outcomes.

Objective Noninvasive Measurement of the Volumizing Effect of a Dermal Filler: An In Vivo Study.

BACKGROUND: Information about the volumizing effects of dermal fillers is critical for physicians' understanding of product features and prudent decision-making in clinical practice. It is important for material engineers to develop and optimize new dermal fillers, especially when comparing the physiochemical properties of a new product with those of existing fillers that are used worldwide. OBJECTIVE: This study aimed to establish a reliable, noninvasive method for in vivo quantitative evaluation of the filling effect in order to predict possible effectiveness after filler injection and to evaluate the degradation trend over time. METHODS: A rabbit model of ear injection with dermal fillers was established. Hyaluronic acid (HA) filler was injected into the subcutaneous layer of rabbit ears, resulting in a stable skin bulge. Ultrasonography was used to noninvasively measure the skin bulge for volume calculation; the volume change was analyzed periodically until 38 weeks. Pathological examination, the gold standard, was performed to confirm degradation. RESULTS: The immediate volumizing effect of HA filler injection was macroscopically observed as a local skin bulge. Ultrasound was able to precisely detect the shape of the filler and calculate the length, width, and height of the skin bulge at each time point. The degree of uplift and amount of residual samples in the pathological evaluation were consistent with the results of morphological observation using ultrasound. CONCLUSION: Evaluation of the volume impact of dermal filler through the rabbit ear injection model evaluation enables material science evaluation in the early stage of material development, and has certain clinical reference value. LEVEL OF EVIDENCE I: 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 .

Breast cancer diagnosis using support vector machine optimized by improved quantum inspired grey wolf optimization.

A prompt diagnosis of breast cancer in its earliest phases is necessary for effective treatment. While Computer-Aided Diagnosis systems play a crucial role in automated mammography image processing, interpretation, grading, and early detection of breast cancer, existing approaches face limitations in achieving optimal accuracy. This study addresses these limitations by hybridizing the improved quantum-inspired binary Grey Wolf Optimizer with the Support Vector Machines Radial Basis Function Kernel. This hybrid approach aims to enhance the accuracy of breast cancer classification by determining the optimal Support Vector Machine parameters. The motivation for this hybridization lies in the need for improved classification performance compared to existing optimizers such as Particle Swarm Optimization and Genetic Algorithm. Evaluate the efficacy of the proposed IQI-BGWO-SVM approach on the MIAS dataset, considering various metric parameters, including accuracy, sensitivity, and specificity. Furthermore, the application of IQI-BGWO-SVM for feature selection will be explored, and the results will be compared. Experimental findings demonstrate that the suggested IQI-BGWO-SVM technique outperforms state-of-the-art classification methods on the MIAS dataset, with a resulting mean accuracy, sensitivity, and specificity of 99.25%, 98.96%, and 100%, respectively, using a tenfold cross-validation datasets partition.

Neural Stem Cell-Derived Small Extracellular Vesicles: key Players in Ischemic Stroke Therapy - A Comprehensive Literature Review.

Ischemic stroke, being a prominent contributor to global disability and mortality, lacks an efficacious therapeutic approach in current clinical settings. Neural stem cells (NSCs) are a type of stem cell that are only found inside the nervous system. These cells can differentiate into various kinds of cells, potentially regenerating or restoring neural networks within areas of the brain that have been destroyed. This review begins by providing an introduction to the existing therapeutic approaches for ischemic stroke, followed by an examination of the promise and limits associated with the utilization of NSCs for the treatment of ischemic stroke. Subsequently, a comprehensive overview was conducted to synthesize the existing literature on the underlying processes of neural stem cell-derived small extracellular vesicles (NSC-sEVs) transplantation therapy in the context of ischemic stroke. These mechanisms encompass neuroprotection, inflammatory response suppression, and endogenous nerve and vascular regeneration facilitation. Nevertheless, the clinical translation of NSC-sEVs is hindered by challenges such as inadequate targeting efficacy and insufficient content loading. In light of these limitations, we have compiled an overview of the advancements in utilizing modified NSC-sEVs for treating ischemic stroke based on current methods of extracellular vesicle modification. In conclusion, examining NSC-sEVs-based therapeutic approaches is anticipated to be prominent in both fundamental and applied investigations about ischemic stroke.

Quantitative proteomics reveals the dynamic proteome landscape of zebrafish embryos during the maternal-to-zygotic transition.

Maternal-to-zygotic transition (MZT) is central to early embryogenesis. However, its underlying molecular mechanisms are still not well described. Here, we revealed the expression dynamics of 5,000 proteins across four stages of zebrafish embryos during MZT, representing one of the most systematic surveys of proteome landscape of the zebrafish embryos during MZT. Nearly 700 proteins were differentially expressed and were divided into six clusters according to their expression patterns. The proteome expression profiles accurately reflect the main events that happen during the MZT, i.e., zygotic genome activation (ZGA), clearance of maternal mRNAs, and initiation of cellular differentiation and organogenesis. MZT is modulated by many proteins at multiple levels in a collaborative fashion, i.e., transcription factors, histones, histone-modifying enzymes, RNA helicases, and P-body proteins. Significant discrepancies were discovered between zebrafish proteome and transcriptome profiles during the MZT. The proteome dynamics database will be a valuable resource for bettering our understanding of MZT.

Innate immune activation restricts priming and protective efficacy of the radiation-attenuated PfSPZ malaria vaccine.

A systems analysis was conducted to determine the potential molecular mechanisms underlying differential immunogenicity and protective efficacy results of a clinical trial of the radiation-attenuated whole-sporozoite PfSPZ vaccine in African infants. Innate immune activation and myeloid signatures at prevaccination baseline correlated with protection from P. falciparum parasitemia in placebo controls. These same signatures were associated with susceptibility to parasitemia among infants who received the highest and most protective PfSPZ vaccine dose. Machine learning identified spliceosome, proteosome, and resting DC signatures as prevaccination features predictive of protection after highest-dose PfSPZ vaccination, whereas baseline circumsporozoite protein-specific (CSP-specific) IgG predicted nonprotection. Prevaccination innate inflammatory and myeloid signatures were associated with higher sporozoite-specific IgG Ab response but undetectable PfSPZ-specific CD8+ T cell responses after vaccination. Consistent with these human data, innate stimulation in vivo conferred protection against infection by sporozoite injection in malaria-naive mice while diminishing the CD8+ T cell response to radiation-attenuated sporozoites. These data suggest a dichotomous role of innate stimulation for malaria protection and induction of protective immunity by whole-sporozoite malaria vaccines. The uncoupling of vaccine-induced protective immunity achieved by Abs from more protective CD8+ T cell responses suggests that PfSPZ vaccine efficacy in malaria-endemic settings may be constrained by opposing antigen presentation pathways.

Innovations in Breaking Barriers: Liposomes as Near-Perfect Drug Carriers in Ischemic Stroke Therapy.

Liposomes, noted for their tunable particle size, surface customization, and varied drug delivery capacities, are increasingly acknowledged in therapeutic applications. These vesicles exhibit surface flexibility, enabling the incorporation of targeting moieties or peptides to achieve specific targeting and avoid lysosomal entrapment. Internally, their adaptable architecture permits the inclusion of a broad spectrum of drugs, contingent on their solubility characteristics. This study thoroughly reviews liposome fabrication, surface modifications, and drug release mechanisms post-systemic administration, with a particular emphasis on drugs crossing the blood-brain barrier (BBB) to address lesions. Additionally, the review delves into recent developments in the use of liposomes in ischemic stroke models, offering a comparative evaluation with other nanocarriers like exosomes and nano-micelles, thereby facilitating their clinical advancement.

Electroacupuncture reduced airway inflammation by activating somatosensory-sympathetic pathways in allergic asthmatic rats.

BACKGROUND: Electroacupuncture (EA) treatment is efficacious in patients with respiratory disorders, although the mechanisms of its action in lung-function protection are poorly understood. This study aimed to explore the neuroanatomical mechanisms of EA stimulation at the BL13 acupoint (Feishu, EA-BL13) improvement in asthma. METHODS: Allergic asthma was induced by intranasal 2.0% ovalbumin (OVA) instillation combined with intraperitoneal injection of the 10.0% OVA. The levels of interleukin (IL)-4 and IL-5 were detected by enzyme-linked immunosorbent assay. Hematoxylin and eosin and periodic acid-schiff stain were used to evaluate inflammatory cell infiltration and mucus secretion. Cellular oncogene fos induction in neurons after EA stimulation was detected by immunofluorescent staining. The mRNA expression levels of adrenergic receptors were quantified with real-time polymerase chain reaction. RESULTS: EA improved airway inflammation and mucus secretion mainly by activating somatosensory-sympathetic pathways (P <0.001). Briefly, the intermediolateral (IML) nuclei of the spinal cord received signals from somatic EA stimulation and then delivered the information via the sympathetic trunk to the lung. Excited sympathetic nerve endings in lung tissue released large amounts of catecholamines that specifically activated the ß2 adrenergic receptor (ß2AR) on T cells (P <0.01) and further decreased the levels of IL-4 and IL-5 (P <0.001) through the cyclic adenosine monophosphate/protein kinase A signaling pathway. CONCLUSION: This study provided a new explanation and clinical basis for the use of EA-BL13 as a treatment for allergic asthma in both the attack and remission stages and other respiratory disorders related to airway inflammation.

Relationship of mTORC1 and ferroptosis in tumors.

Ferroptosis is a novel form of programmed death, dependent on iron ions and oxidative stress, with a predominant intracellular form of lipid peroxidation. In recent years, ferroptosis has gained more and more interest of people in the treatment mechanism of targeted tumors. mTOR, always overexpressed in the tumor, and controlling cell growth and metabolic activities, has an important role in both autophagy and ferroptosis. Interestingly, the selective types of autophay plays an important role in promoting ferroptosis, which is related to mTOR and some metabolic pathways (especially in iron and amino acids). In this paper, we list the main mechanisms linking ferroptosis with mTOR signaling pathway and further summarize the current compounds targeting ferroptosis in these ways. There are growing experimental evidences that targeting mTOR and ferroptosis may have effective impact in many tumors, and understanding the mechanisms linking mTOR to ferroptosis could provide a potential therapeutic approach for tumor treatment.

Automatic high-throughput and non-invasive selection of sperm at the biochemical level.

BACKGROUND: Sperm selection, a key step in assisted reproductive technology (ART), has long been restrained at the preliminary physical level (morphology or motility); however, subsequent fertilization and embryogenesis are complicated biochemical processes. Such an enormous "gap" poses tough problems for couples dealing with infertility, especially patients with severe/total asthenozoospermia . METHODS: We developed a biochemical-level, automatic-screening/separation, smart droplet-TO-hydrogel chip (BLASTO-chip) for sperm selection. The droplet can sense the pH change caused by sperm's respiration products and then transforms into a hydrogel to be selected out. FINDINGS: The BLASTO-chip system can select biochemically active sperm with an accuracy of over 90%, and its selection efficiency can be flexibly tuned by nearly 10-fold. All the substances in the system were proven to be biosafe via evaluating mice fertilization and offspring health. Live sperm down to 1% could be enriched by over 76-fold to 76%. For clinical application to patients with severe/total asthenozoospermia, the BLASTO-chip could select live sperm from human semen samples containing 10% live but 100% immotile sperm. The rates of fertilization, cleavage, early embryos, and blastocysts were drastically elevated from 15% to 70.83%, 10% to 62.5%, 5% to 37.5%, and 0% to 16.67%, respectively. CONCLUSIONS: The BLASTO-chip represents a real biochemical-level technology for sperm selection that is completely independent of sperm's motility. It can be a powerful tool in ART, especially for patients with severe/total asthenozoospermia. FUNDING: This work was funded by the Ministry of Science and Technology of China, the Ministry of Education of China, and the Shenzhen-Hong Kong Hetao Cooperation Zone.

TopDIA: A Software Tool for Top-Down Data-Independent Acquisition Proteomics.

Top-down mass spectrometry is widely used for proteoform identification, characterization, and quantification owing to its ability to analyze intact proteoforms. In the last decade, top-down proteomics has been dominated by top-down data-dependent acquisition mass spectrometry (TD-DDA-MS), and top-down data-independent acquisition mass spectrometry (TD-DIA-MS) has not been well studied. While TD-DIA-MS produces complex multiplexed tandem mass spectrometry (MS/MS) spectra, which are challenging to confidently identify, it selects more precursor ions for MS/MS analysis and has the potential to increase proteoform identifications compared with TD-DDA-MS. Here we present TopDIA, the first software tool for proteoform identification by TD-DIA-MS. It generates demultiplexed pseudo MS/MS spectra from TD-DIA-MS data and then searches the pseudo MS/MS spectra against a protein sequence database for proteoform identification. We compared the performance of TD-DDA-MS and TD-DIA-MS using Escherichia coli K-12 MG1655 cells and demonstrated that TD-DIA-MS with TopDIA increased proteoform and protein identifications compared with TD-DDA-MS.