ABSTRACT
Filamentous fungi can produce raw-starch-degrading enzyme, however, regulation of production of raw-starch-degrading enzyme remains poorly understood thus far. Here, two novel transcription factors raw-starch-degrading enzyme regulator D (RsrD) and raw-starch-degrading enzyme regulator E (RsrE) were identified to participate in the production of raw-starch-degrading enzyme in Penicillium oxalicum. Individual knockout of rsrD and rsrE in the parental strain Δku70 resulted in 31.1%-92.9% reduced activity of raw-starch-degrading enzyme when cultivated in the presence of commercial starch from corn. RsrD and RsrE contained a basic leucine zipper and a Zn2Cys6-type DNA-binding domain, respectively, but with unknown functions. RsrD and RsrE dynamically regulated the expression of genes encoding major amylases over time, including raw-starch-degrading glucoamylase gene PoxGA15A and α-amylase gene amy13A. Interestingly, RsrD and RsrE regulated each other at transcriptional level, through binding to their own promoter regions; nevertheless, both failed to bind to the promoter regions of PoxGA15A and amy13A, as well as the known regulatory genes for regulation of amylase gene expression. RsrD appears to play an epistatic role in the module RsrD-RsrE on regulation of amylase gene expression. This study reveals a novel regulatory pathway of fungal production of raw-starch-degrading enzyme.IMPORTANCETo survive via combating with complex extracellular environment, filamentous fungi can secrete plant polysaccharide-degrading enzymes that can efficiently hydrolyze plant polysaccharide into glucose or other mono- and disaccharides, for their nutrients. Among the plant polysaccharide-degrading enzymes, raw-starch-degrading enzymes directly degrade and convert hetero-polymeric starch into glucose and oligosaccharides below starch gelatinization temperature, which can be applied in industrial biorefinery to save cost. However, the regulatory mechanism of production of raw-starch-degrading enzyme in fungi remains unknown thus far. Here, we showed that two novel transcription factors raw-starch-degrading enzyme regulator D (RsrD) and raw-starch-degrading enzyme regulator E (RsrE) positively regulate the production of raw-starch-degrading enzyme by Penicillium oxalicum. RsrD and RsrE indirectly control the expression of genes encoding enzymes with amylase activity but directly regulate each other at transcriptional level. These findings expand diversity of gene expression regulation in fungi.
Subject(s)
Fungal Proteins , Gene Expression Regulation, Fungal , Penicillium , Starch , Transcription Factors , Penicillium/genetics , Penicillium/enzymology , Penicillium/metabolism , Transcription Factors/metabolism , Transcription Factors/genetics , Starch/metabolism , Fungal Proteins/genetics , Fungal Proteins/metabolism , Amylases/metabolism , Amylases/genetics , Promoter Regions, GeneticABSTRACT
BACKGROUND: By combining high-frequency and contrast-enhanced ultrasound (CEUS), the position of the severed end of a finger extensor tendon injury and the injury classification can be determined as part of a comprehensive preoperative evaluation in clinical practice. However, there have been no reports of high-frequency ultrasound combined with CEUS for the preoperative diagnosis of human finger extensor tendon injury. CASES PRESENTATION: One case of complete rupture of the extensor tendon was diagnosed by ultrasound, which was completely consistent with the surgery; one case of incomplete rupture was ultimately confirmed clinically; and one case of distal phalangeal bone base avulsion fracture with tendon contusion and missed diagnosis on the first radiographic examination was confirmed by follow-up radiographic examination. CONCLUSIONS: Different types of finger extensor tendon injuries exhibit distinctive contrast-enhanced ultrasonography findings. Combined high-frequency and contrast-enhanced ultrasound can accurately locate the position of the severed end of the finger extensor tendon injury before surgery while observing the contrast agent filling area to clarify injury classification, providing a reliable imaging basis for clinical practice and ultimately developing personalized diagnosis and treatment plans for patients to ensure minimal trauma and pain, as well as optimal treatment effects.
ABSTRACT
Filamentous fungi produce polysaccharide-degrading enzymes, which is controlled by poorly understood transcriptional circuits. Here we show that a circuit comprising RsrC-RsrA-RsrB (Rsr: production of raw-starch-degrading enzyme regulator) that positively regulates production of raw starch-degrading enzymes in Penicillium oxalicum. Transcription factor (TF) RsrA is essential for biosynthesis of raw starch-degrading enzymes. RsrB and RsrC containing Zn2Cys6- and C2H2-zinc finger domains, act downstream and upstream of RsrA, respectively. RsrA activates rsrB transcription, and three nucleotides (G-286, G-287 and G-292) of rsrB promoter region are required for RsrA, in terms of TF, for binding. RsrB165-271 binds to DNA sequence 5'-TCGATCAGGCACGCC-3' in the promoter region of the gene encoding key raw-starch-degrading enzyme PoxGA15A. RsrC specifically binds rsrA promoter, but not amylase genes, to positively regulate the expression of rsrA and the production of raw starch-degrading enzymes. These findings expand complex regulatory network of fungal raw starch-degrading enzyme biosynthesis.
Subject(s)
Fungal Proteins , Gene Expression Regulation, Fungal , Penicillium , Transcription Factors , Penicillium/genetics , Penicillium/metabolism , Penicillium/enzymology , Fungal Proteins/genetics , Fungal Proteins/metabolism , Transcription Factors/metabolism , Transcription Factors/genetics , Promoter Regions, Genetic , Polysaccharides/metabolism , Polysaccharides/biosynthesis , Gene Regulatory NetworksABSTRACT
Background: Pediatric acute myeloid leukemia (AML) has poor prognosis and high rate of relapse and mortality, and exploration of new treatment options is still critically needed. Objectives: To summarize the outcome of our new treatment strategies for pediatric AML, which is characterized by dual induction and acute lymphoblastic leukemia (ALL) elements consolidation. Design: Retrospective, single-arm study. Methods: From July 2012 to December 2019, an intensive chemotherapy protocol was used for newly diagnosed children with AML, which contains dual induction, three courses of consolidations based on high-dose cytarabine, and two courses of consolidations composed of high-dose methotrexate, vincristine, asparaginase, and mercaptopurine (ALL-like elements). Blasts were monitored by bone marrow smears at intervals, and two lumbar punctures were performed during chemotherapy. We retrospectively analyzed the efficacy and safety of this study. The last follow-up was on 26 May 2023. Results: A total of 70 pediatric AMLs were included. The median age at diagnosis was 6.7 (0.5-16.0) years. The median initial WBC count was 23.74 × 109/L, 11 of whom ⩾100 × 109/L. After dual induction, there were 62 cases of complete remission (CR), 5 cases of partial remission, and 3 cases of nonremission. The CR rate was 88.57%. The median follow-up time was 5.8 (0.2-9.4) years, the 5-year overall survival was 78.2% ± 5%, the event-free survival (EFS) was 71.2% ± 5.6%, and the cumulative recurrence rate was 27.75%. The 5-year EFS of patients with initial WBC < 100 × 109/L (n = 59) and ⩾100 × 109/L (n = 11) were 76.4% ± 5.7% and 45.5% ± 15% (p = 0.013), respectively. A total of 650 hospital infections occurred. The main causes of infection were respiratory tract infection (26.92%), septicemia (18.46%), stomatitis (11.85%), and skin and soft-tissue infection (10.46%). Conclusion: This intensive treatment protocol with dual induction and ALL-like elements is effective and safe for childhood AML. Initial WBC ⩾ 100 × 109/L was the only independent risk factor in this cohort. Trial registration: It is a retrospective study, and no registration on ClinicalTrials.gov.
ABSTRACT
Proteins and peptides play vital roles in different biological processes in vivo. As a dynamic hydrolysis system, milk is rich in proteins and proteases and provides a constant supply of endogenous bioactive peptides to newborn mammals. Previous studies have primarily focused on researching bioactive peptides by adding exogenous enzymes to milk samples. However, such an approach overlooks the significance of endogenous peptides and parent proteins that naturally exist in milk. Herein, we analyzed and compared parent proteins and their releasing peptides in human colostrum (HC), bovine colostrum (BC), and donkey colostrum (DC). The predominant proteins and hydrolyzed peptides in the three types of milk were identified. Among them, peptides were found to possess common bioactivities, including ACE inhibitory, antioxidant, antibacterial and immunomodulatory properties in HC, BC, and DC. Furthermore, the biological functions of these parent proteins were clarified using bioinformatics. These insights offer a novel perspective on natural bioactive peptides and the potential utilization of specific parent proteins and peptides to develop infant formulae derived from diverse milk sources.
Subject(s)
Colostrum , Equidae , Milk Proteins , Peptides , Proteolysis , Colostrum/chemistry , Animals , Humans , Cattle , Milk Proteins/metabolism , Milk Proteins/chemistry , Peptides/metabolism , Peptides/analysis , Female , Milk, Human/chemistryABSTRACT
The rise of antibiotic resistance poses a significant public health crisis, particularly due to limited antimicrobial options for the treatment of infections with Gram-negative pathogens. Here, an antimicrobial peptide (AMP) SR25 is characterized, which effectively kills both Gram-negative and Gram-positive bacteria through a unique dual-targeting mechanism without detectable resistance. Meanwhile, an SR25-functionalized hydrogel is developed for the efficient treatment of infected diabetic wounds. SR25 is obtained through genome mining from an uncultured bovine enteric actinomycete named Nonomuraea Jilinensis sp. nov. Investigations reveal that SR25 has two independent cellular targets, disrupting bacterial membrane integrity and restraining the activity of succinate:quinone oxidoreductase (SQR). In a diabetic mice wound infection model, the SR25-incorporated hydrogel exhibits high efficacy against mixed infections of Escherichia coli (E. coli) and methicillin-resistant Staphylococcus aureus (MRSA), accelerating wound healing. Overall, these findings demonstrate the therapeutic potential of SR25 and highlight the value of mining drugs with multiple mechanisms from uncultured animal commensals for combating challenging bacterial pathogens.
Subject(s)
Diabetes Mellitus, Experimental , Disease Models, Animal , Wound Healing , Animals , Mice , Wound Healing/drug effects , Diabetes Mellitus, Experimental/drug therapy , Methicillin-Resistant Staphylococcus aureus/drug effects , Antimicrobial Peptides/pharmacology , Wound Infection/drug therapy , Wound Infection/microbiology , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Escherichia coli/drug effects , Microbial Sensitivity TestsABSTRACT
Radiotherapy is a pivotal means of cancer treatment, but it often leads to radiation dermatitis, a skin injury caused by radiation-induced excess reactive oxygen species (ROS). Scavenging free radicals in the course of radiation therapy will be an effective means to prevent radiation dermatitis. This study demonstrates a novel double network hydrogel doped with MoS2 nanosheets for the prevention of radiation-induced dermatitis. The resultant SPM hydrogel constructed from polyacrylamide (PAM) and sodium alginate (SA) nanofiber presented favorable mechanical and adhesion properties. It could conform well to the human body's irregular contours without secondary dressing fixation, making it suitable for skin protection applications. The in vitro and in vivo experiments showed that the antioxidant properties conferred by MoS2 nanosheets enable SPM to effectively mitigate excessive ROS and reduce oxidative stress, thereby preventing radiation dermatitis caused by oxidative damage. Biosafety assessments indicated good biocompatibility of the composite hydrogel, suggesting SPM's practicality and potential as an external dressing for skin radiation protection.
Subject(s)
Alginates , Antioxidants , Hydrogels , Radiodermatitis , Hydrogels/chemistry , Hydrogels/pharmacology , Antioxidants/chemistry , Antioxidants/pharmacology , Radiodermatitis/prevention & control , Radiodermatitis/drug therapy , Animals , Alginates/chemistry , Alginates/pharmacology , Humans , Acrylic Resins/chemistry , Acrylic Resins/pharmacology , Mice , Molybdenum/chemistry , Molybdenum/pharmacology , Disulfides/chemistry , Disulfides/pharmacology , Reactive Oxygen Species/metabolism , Adhesives/chemistry , Adhesives/pharmacology , Particle SizeABSTRACT
Crack-based flexible strain sensors with ultra-high sensitivity under tiny strain are highly desired for environmental perception and motion detection of novel flexible and miniature robots. However, previously reported methods for fabricating crack patterns have often sacrificed the cyclic stability of the sensor, leading to a trade-off relationship between the sensitivity and the cyclic stability. Here, a universal and simple strategy based on fatigue loading with an ultra-large cumulative strain of up to â¼1.2 × 107%, rather than the traditionally quasi-static pre-overloading methods, is proposed to introduce channel cracks in the sensing layer without sacrificing the cyclic stability. The developed flexible strain sensors exhibit high strain-sensitivity (gauge factor = 5798) under tiny strain (< 3%), high cyclic stability (15 000 cycles) and a low strain detecting limit (0.02%). Furthermore, a leaf-like mechanosensor is developed using the fatigue crack-based strain sensor for the realization of multifunctional applications in environment perception and micro-motion detection. Brilliant airflow sensing performance with a wide sensing range (0.93-11.93 m s-1) and a fast response time (0.28 s) for amphibious applications is demonstrated. This work provides a new strategy for overcoming limits of crack-based flexible strain sensors and the developed leaf-like mechanosensor shows great application potential in miniature and flexible reconnaissance robots.
ABSTRACT
Objective: To analyze the correlation between body mass index (BMI) and clinicopathological factors of papillary thyroid cancer (PTC). Methods: The clinical data of patients with PCT who were hospitalized in the Department of Thyroid Surgery of the Affiliated Hospital of Guizhou Medical University from March 2023 to September 2023 were retrospectively collected, including age, gender, height, weight, BMI, v-raf murine sarcoma viral oncogene homolog B (BRAF) gene mutation, tumor size, multifocus, Hashimoto's thyroiditis, lymph node metastasis and other clinicopathological factors. According to the World Health Organization (WHO) definition for Asian population, BMI≥25kg/m2 was obese group, 23≤BMI≤24.9kg/m2 was overweight group, 18.5≤BMI≤22.9kg/m2 was normal weight group, and BMI≤18.5kg/m2 was low weight group. The clinicopathological factors of overweight and obese patients with PTC were analyzed. Results: A total of 164 PTC patients were included, with an average BMI of (24.44±3.57) kg/m2. Age of overweight and obese PTC patients (Z=1.978, p=0.083); Gender of overweight and obese PTC patients (χ2 value: 11.570, p=0.004); Tumor size in overweight and obese PTC patients (Z=0.894, p=0.411); BRAF gene mutation in overweight and obese PTC patients (χ2 value: 1.452, p =0.623); Multifocal lesions were found in overweight and obese patients (χ2 value: 1.653, p =0.201). Hashimoto's thyroiditis was found in overweight and obese PTC patients (χ2 value: 1.147, p=0.298). Overweight and obese patients with PTC had lymph node metastasis (χ2 value: 1.690, p =0.251). Conclusion: Overweight and obesity in PTC patients are correlated with male, but not with age, tumor size, BRAF mutation, multifocality, Hashimoto's thyroiditis and lymph node metastasis.
ABSTRACT
BACKGROUND: Hyperarousal plays an essential role in the initiation and maintenance of insomnia, highlighting the need for a tool that measure the hyperarousal state during the early course of insomnia. Pre-sleep Arousal Scale (PSAS) is a self-report questionnaire to evaluate subjective pre-sleep arousal of insomnia. The aim of this study was to examine the psychometric properties of the PSAS among patients with acute insomnia disorder (AID) using Rasch analysis. METHODS: Totally 170 patients with AID from 31 public hospitals in China were recruited and completed the test. The psychometric properties of the PSAS were tested using Rasch analysis by Winsteps v5.4.1.0, including unidimensionality, local item independence, item fit, category diagnostics, reliability, item-person maps and differential item functioning (DIF) by age and gender. RESULTS: According to Rasch analysis, somatic and cognitive subscales were unidimensional and basically demonstrated good item-fit statistics. 4-point Likert scale may be more appropriate for PSAS. All items have a good reliability and separation. No gender and age bias were detected for the scale. However, the person arousal level is not well matched to item difficulty. CONCLUSION: The present study further reveals appropriate psychometric properties of the PSAS in patients with AID and provides suggestions for refinements and supplements to the PSAS.
Subject(s)
Arousal , Psychometrics , Sleep Initiation and Maintenance Disorders , Humans , Sleep Initiation and Maintenance Disorders/diagnosis , Sleep Initiation and Maintenance Disorders/physiopathology , Male , Female , Arousal/physiology , Adult , Reproducibility of Results , Middle Aged , Surveys and Questionnaires , China , Self Report , Sleep/physiologyABSTRACT
2-Methylisoborneol (2-MIB) is a common and widely distributed off-flavor compound in water. However, the toxic mechanisms of 2-MIB on aquatic organisms remain largely unexplored. In this study, grass carp larvae were exposed to different concentrations (0, 5, and 20 µg L-1) of 2-MIB for 96 h. The accumulation of 2-MIB in the dorsal muscle was measured. Histological analysis, ultrastructure observations, and transcriptomic sequencing were conducted on the liver tissues. The results showed that 2-MIB accumulated significantly in the fish muscle, with the accumulation increasing as the exposure concentration increased through gas chromatography-mass spectrometry (GC-MS) detection. Histological and ultrastructure observations indicated that 2-MIB caused concentration-dependent inflammatory infiltration and mitochondrial damage in the liver. Transcriptomic analysis revealed lipid metabolism disorders induced by exposure to 2-MIB in grass carp. Additionally, 5 µg L-1 2-MIB affected the neurodevelopment and cardiovascular system of grass carp larvae through extracellular matrix (ECM)-receptor interaction and focal adhesion pathway. Furthermore, several pathways related to the digestive system were significantly enriched, implying that 2-MIB may impact pancreatic secretion function, protein digestion and absorption processes. These findings provide new insights into the potential toxicological mechanisms of 2-MIB.
Subject(s)
Carps , Inflammation , Transcriptome , Water Pollutants, Chemical , Animals , Water Pollutants, Chemical/toxicity , Inflammation/chemically induced , Transcriptome/drug effects , Gene Expression Profiling , Camphanes/toxicity , Liver/drug effects , Liver/pathology , Larva/drug effectsABSTRACT
Due to the decomposition temperature of Polyamide 66 (PA66) in the environment is close to its thermoforming temperature, it is difficult to construct porous scaffolds of PA66/nanohydroxyapatite (PA66/HAp) by fused deposition modeling (FDM) three-dimensional (3D) printing. In this study, we demonstrated for the first time a method for 3D printing PA66/HAp composites at room temperature, prepared PA66/HAp printing ink using a mixed solvent of formic acid/dichloromethane (FA/DCM), and constructed a series of composite scaffolds with varying HAp content. This printing system can print composite materials with a high HAp content of 60 wt %, which is close to the mineral content in natural bone. The physicochemical evaluation presented that the hydroxyapatite was uniformly distributed within the PA66 matrix, and the PA66/HAp composite scaffold with 30 wt % HAp content exhibited optimal mechanical properties and printability. The results of in vitro cell culture experiments indicated that the incorporation of HAp into the PA66 matrix significantly improved the cell adhesion, proliferation, and osteogenic differentiation of bone marrow stromal cells (BMSCs) cultured on the scaffold. In vivo animal experiments suggested that the PA66/HAp composite material with 30 wt % HAp content had the best structural maintenance and osteogenic performance. The three-dimensional PA66/HAp composite scaffold prepared by low temperature printing in the current study holds great potential for the repair of large-area bone defects.
Subject(s)
Durapatite , Mesenchymal Stem Cells , Nylons , Printing, Three-Dimensional , Tissue Scaffolds , Durapatite/chemistry , Tissue Scaffolds/chemistry , Nylons/chemistry , Animals , Mesenchymal Stem Cells/cytology , Mesenchymal Stem Cells/drug effects , Bone Regeneration/drug effects , Osteogenesis/drug effects , Tissue Engineering/methods , Cell Proliferation/drug effects , Cell Differentiation/drug effects , Temperature , Cell AdhesionABSTRACT
Plant-associated microbiomes play important roles in plant health and productivity. However, despite fruits being directly linked to plant productivity, little is known about the microbiomes of fruits and their potential association with fruit health. Here, by integrating 16S rRNA gene, ITS high-throughput sequencing data, and microbiological culturable approaches, we reported that roots and fruits (pods) of peanut, a typical plant that bears fruits underground, recruit different bacterial and fungal communities independently of cropping conditions and that the incidence of pod disease under monocropping conditions is attributed to the depletion of Bacillus genus and enrichment of Aspergillus genus in geocarposphere. On this basis, we constructed a synthetic community (SynCom) consisting of three Bacillus strains from geocarposphere soil under rotation conditions with high culturable abundance. Comparative transcriptome, microbiome profiling, and plant phytohormone signaling analysis reveal that the SynCom exhibited more effective Aspergillus growth inhibition and pod disease control than individual strain, which was underpinned by a combination of molecular mechanisms related to fungal cell proliferation interference, mycotoxins biosynthesis impairment, and jasmonic acid-mediated plant immunity activation. Overall, our results reveal the filter effect of plant organs on the microbiome and that depletion of key protective microbial community promotes the fruit disease incidence.
Subject(s)
Arachis , Fruit , Microbiota , Plant Diseases , Plant Roots , RNA, Ribosomal, 16S , Soil Microbiology , Fruit/microbiology , Plant Diseases/microbiology , Plant Diseases/prevention & control , RNA, Ribosomal, 16S/genetics , Plant Roots/microbiology , Arachis/microbiology , Aspergillus/genetics , Aspergillus/isolation & purification , Bacillus/genetics , Bacillus/isolation & purification , Plant Growth Regulators/metabolism , Fungi/genetics , Fungi/classification , Fungi/isolation & purification , Bacteria/genetics , Bacteria/classification , Bacteria/isolation & purificationABSTRACT
BACKGROUND: Several studies have suggested that transcutaneous vagus nerve stimulation (tVNS) may be effective for the treatment of epilepsy. However, auricular acupoint therapy (including auricular acupuncture and auricular point-sticking therapy), a method of stimulating the vagus nerve, has been poorly reviewed. This systematic review is the first to categorize auricular acupoint therapy as transcutaneous auricular vagus nerve stimulation (taVNS), aiming to assess the efficacy of taVNS in patients with epilepsy (PWE), and to analyse the results of animal experiments on the antiepileptic effects of taVNS. METHODS: We searched MEDLINE, EMBASE, Web of Science, Scopus, and various Chinese databases from their inception to June 10, 2023 and found nine clinical studies (including a total of 788 PWE) and eight preclinical studies. We performed a meta-analysis and systematic review of these articles to assess the efficacy of taVNS in PWE and the association between taVNS and electroencephalogram (EEG) changes. We also analysed the effects on epileptic behaviour, latency of the first seizure, and seizure frequency in epileptic animals. The PRISMA 2020 checklist provided by the EQUATOR Network was used in this study. RESULTS: taVNS had a higher response rate in PWE than the control treatment (OR = 2.94, 95 % CI = 1.94 - 4.46, P < 0.05). The analysis showed that the taVNS group showed wider EEG changes than the control group (OR = 2.17, 95 % CI 1.03 to 4.58, P < 0.05). The preclinical studies analysis revealed significant differences in epileptic behaviour (SMD = -4.78, 95 % CI -5.86 to -3.71, P < 0.05) and seizure frequency (SMD = -5.06, 95 % CI -5.96 to -4.15, P < 0.05) between the taVNS and control groups. No statistical difference was found in the latency of the first seizure between the two groups (SMD =13.54; 95 % CI 7.76 to 19.33, P < 0.05). CONCLUSION: Based on the available data, PWE may benefit from the use of taVNS. taVNS is an effective procedure for improving epileptic behaviour in animal models.
Subject(s)
Epilepsy , Transcutaneous Electric Nerve Stimulation , Vagus Nerve Stimulation , Humans , Vagus Nerve Stimulation/methods , Epilepsy/therapy , Epilepsy/physiopathology , Transcutaneous Electric Nerve Stimulation/methods , AnimalsABSTRACT
STUDY OBJECTIVES: To investigate the cost-effectiveness of cognitive behavioral therapy for insomnia (CBTI), with an additional focus on digital CBTI (dCBTI) in adults with insomnia. METHODS: We searched eight electronic databases for economic evaluations of CBTI: PubMed, Scopus, Web of Science, psycINFO, Cochrane, Library, CINAHL, ProQuest, and National Health Service Economic Evaluation Database. Meta-analyses were performed to investigate the effects and costs between CBTI and control groups (no treatment, other treatments included hygiene education and treatment as usual). Subgroup analyses for dCBTI were conducted. RESULTS: Twelve randomized controlled trial studies between 2004 and 2023 were included in our systematic review and meta-analyses. The incremental cost-utility ratios and incremental cost-effectiveness ratios showed that the CBTI and dCBTI groups were more cost-effective than controls, from healthcare perspective and societal perspective, respectively. Compared to controls, CBTI demonstrated significantly better efficacy within 12 months. Healthcare costs were significantly higher in the CBTI groups compared to the controls within 6 months but there was no difference at 12 months. Additionally, dCBTI was associated with significantly lower presenteeism costs compared to controls at 6 months. CONCLUSIONS: Our findings suggest that CBTI is more cost-effective than other treatments or no treatment for adults with insomnia. It may bring more economic benefits in the long term, especially in long-lasting efficacy and cost reduction. In addition, dCBTI is one of the cost-effective options for insomnia. PROSPERO REGISTRATION NUMBER: CRD42â 022â 383â 440. URL: www.crd.york.ac.uk/PROSPERO. NAME FOR PROSPERO REGISTRATION: Cost-effectiveness of cognitive behavioral therapy for insomnia (CBTI): a systematic review with meta-analysis.
Subject(s)
Cognitive Behavioral Therapy , Cost-Benefit Analysis , Sleep Initiation and Maintenance Disorders , Humans , Sleep Initiation and Maintenance Disorders/therapy , Sleep Initiation and Maintenance Disorders/economics , Cognitive Behavioral Therapy/economics , Cognitive Behavioral Therapy/methods , Health Care Costs/statistics & numerical dataABSTRACT
Resistance to glucocorticoids (GCs), the common agents for remission induction in pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL), poses a significant therapeutic hurdle. Therefore, dissecting the mechanisms shaping GC resistance could lead to new treatment modalities. Here, we showed that CD9- BCP-ALL cells were preferentially resistant to prednisone and dexamethasone over other standard cytotoxic agents. Concordantly, we identified significantly more poor responders to the prednisone prephase among BCP-ALL patients with a CD9- phenotype, especially for those with adverse presenting features including older age, higher white cell count and BCR-ABL1. Furthermore, gain- and loss-of-function experiments dictated a definitive functional linkage between CD9 expression and GC susceptibility, as demonstrated by the reversal and acquisition of relative GC resistance in CD9low and CD9high BCP-ALL cells, respectively. Despite physical binding to the GC receptor NR3C1, CD9 did not alter its expression, phosphorylation or nuclear translocation but potentiated the induction of GC-responsive genes in GCresistant cells. Importantly, the MEK inhibitor trametinib exhibited higher synergy with GCs against CD9- than CD9+ lymphoblasts to reverse drug resistance in vitro and in vivo. Collectively, our results elucidate a previously unrecognized regulatory function of CD9 in GC sensitivity, and inform new strategies for management of children with resistant BCP-ALL.
ABSTRACT
A new loach species, Oreonectesandongensissp. nov. is described from the Guangxi Zhuang Autonomous Region, China. The new species can be differentiated from other members of the genus by combinations of characters: a developed posterior chamber of the swim bladder, 13-14 branched caudal-fin rays, 8-16 lateral-line pores, body width 12-15% of standard length (SL), interorbital width 42-47% of head length (HL), and caudal peduncle length 11-16% of SL. Bayesian inference phylogenetic analysis based on mitochondrial Cyt b provided strong support for validity of O.andongensissp. nov. (uncorrected p-distance 6.0-7.5%).
ABSTRACT
Clostridium perfringens (C. perfringens) infection is recognized as one of the most challenging issues threatening food safety and perplexing agricultural development. To date, the molecular mechanisms of the interactions between C. perfringens and the host remain poorly understood. Here, we show that stimulator of interferon genes (STING)-dependent trained immunity protected against C. perfringens infection through mTOR signaling. Heat-killed Candida albicans (HKCA) training elicited elevated TNF-α and IL-6 production after LPS restimulation in mouse peritoneal macrophages (PM). Although HKCA-trained PM produced decreased levels of TNF-α and IL-6, the importance of trained immunity was demonstrated by the fact that HKCA training resulted in enhanced bacterial phagocytic ability and clearance in vivo and in vitro during C. perfringens infection. Interestingly, HKCA training resulted in the activation of STING signaling. We further demonstrate that STING agonist DMXAA is a strong inducer of trained immunity and conferred host resistance to C. perfringens infection in PM. Importantly, corresponding to higher bacterial burden, reduction in cytokine secretion, phagocytosis, and bacterial killing were shown in the absence of STING after HKCA training. Meanwhile, the high expression levels of AKT/mTOR/HIF1α were indeed accompanied by an activated STING signaling under HKCA or DMXAA training. Moreover, inhibiting mTOR signaling with rapamycin dampened the trained response to LPS and C. perfringens challenge in wild-type (WT) PM after HKCA training. Furthermore, STINGdeficient PM presented decreased levels of mTOR signaling-related proteins. Altogether, these results support STING involvement in trained immunity which protects against C. perfringens infection via mTOR signaling.
Subject(s)
Clostridium Infections , Animals , Mice , Clostridium Infections/veterinary , Clostridium perfringens , Interleukin-6 , Lipopolysaccharides , TOR Serine-Threonine Kinases , Trained Immunity , Tumor Necrosis Factor-alpha/metabolismABSTRACT
To elucidate the effects of long-term (20 years) afforestation with different woody plant species on the soil microenvironment in coal gangue polymetallic contaminated areas. This study analyzed the soil physicochemical properties, soil enzyme activities, soil ionophore, bacterial community structure, soil metabolite, and their interaction relationships at different vertical depths. Urease, sucrase, and acid phosphatase activities in the shallow soil layers increased by 4.70-7.45, 3.83-7.64, and 3.27-4.85 times, respectively, after the restoration by the four arboreal plant species compared to the plant-free control soil. Additionally, it reduced the content of available elements in the soil and alleviated the toxicity stress for Cd, Ni, Co, Cr, As, Fe, Cu, U, and Pb. After the long-term restoration of arboreal plants, the richness and Shannon indices of soil bacteria significantly increased by 4.77-23.81% and 2.93-7.93%, respectively, broadening the bacterial ecological niche. The bacterial community structure shaped by different arboreal plants exhibited high similarity, but the community similarity decreased with increasing vertical depth. Soils Zn, U, Sr, S, P, Mg, K, Fe, Cu, Ca, Ba, and pH were identified as important influencing factors for the community structure of Sphingomonas, Pseudarthrobacter, Nocardioides, and Thiobacillus. The metabolites such as sucrose, raffinose, L-valine, D-fructose 2, 6-bisphosphate, and oxoglutaric acid were found to have the greatest effect on the bacterial community in the rhizosphere soils for arboreal plants. The results of the study demonstrated that long-term planting for woody plants in gangue dumps could regulate microbial abundance and symbiotic patterns through the accumulation of rhizosphere metabolites in the soil, increase soil enzyme activity, reduce heavy metal levels, and improve the soil environment in coal gangue dumps.