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BACKGROUND: Vector flow mapping (VFM) is a new echocardiographic technology that can effectively evaluate systolic and diastolic hemodynamic function. However, little is known about the prognostic value of VFM-related parameters. In this paper we aimed to investigate whether left ventricular energy loss (EL) parameters as assessed by VFM enhance prediction of adverse events in patients with chronic kidney disease with preserved ejection fraction. METHODS: One hundred thirty-nine prospectively recruited patients (66% male, 58% on dialysis) with CKD stage 3-5 with normal left ventricular ejection fraction (LVEF) made up the study cohort. Global longitudinal strain (GLS) was calculated using 2-dimensional speckle tracking, and the LV EL during one cardiac cycle for each period was measured using VFM technology. Participants were followed for 4.17 ± 1.58 years for the primary end point of overall mortality and major adverse cardiovascular events (MACE). RESULTS: Forty-five (32%) patients had a primary endpoint event. The EL during each period especially during the ejection stage (Ej-EL) was significantly higher in patients with adverse events than in those without, meanwhile the LV GLS were lower. The Ej-EL (HR: 1.11; 95% CI: 1.06-1.15) and LV GLS (HR: 0.87; 95% CI: 0.81-0.94) (all P < .001) were independent predictors for the primary end point. Increased Ej-EL (≥6.13, 10-3 J/m s) and impaired GLS (<15.52, %) were associated with a higher risk of overall mortality death and MACE (log rank χ2 = 26.94, 7.19; P < .001, =0.007), and DeLong tests showed that Ej-EL (AUC = 0.823) has a slight advantage in predicting adverse events compared to GLS (AUC = 0.681). Furthermore, the addition of Ej-EL to a model with conventional parameters did more to improve the model's discrimination compared to GLS. CONCLUSIONS: Increased Ej-EL as determined by VFM is associated with a higher risk of overall death and MACE in CKD patients with preserved EF.
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BACKGROUND: A variety of congenital or acquired conditions can cause craniomaxillofacial bone defects, resulting in a heavy financial burden and psychological stress. Guided bone self-generation with periosteum-preserved has great potential for reconstructing large bone defects. METHODS: A swine model of guided bone regeneration with occlusive periosteum was established, the rib segment was removed, and the periosteum was sutured to form a closed regeneration chamber. Hematoxylin and eosin staining, Masson's staining, and Safranine O-Fast Green staining were done. Nine-time points were chosen for collecting the periosteum and regenerated bone tissue for gene sequencing. The expression level of each secreted frizzled-related protein (SFRP) member and the correlations among them were analyzed. RESULTS: The process of bone regeneration is almost complete 1 month after surgery, and up to 1 week after surgery is an important interval for initiating the process. The expression of each SFRP family member fluctuated greatly. The highest expression level of all members ranged from 3 days to 3 months after surgery. The expression level of SFRP2 was the highest, and the difference between 2 groups was the largest. Secreted frizzled-related protein 2 and SFRP4 showed a notable positive correlation between the control and model groups. Secreted frizzled-related protein 1, SFRP2, and SFRP4 had a significant spike in fold change at 1 month postoperatively. Secreted frizzled-related protein 1 and SFRP2 had the strongest correlation. CONCLUSIONS: This study revealed the dynamic expression of the SFRP family in guided bone regeneration with occlusive periosteum in a swine model, providing a possibility to advance the clinical application of bone defect repair.
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Regeneração Óssea , Periósteo , Animais , Suínos , Regeneração Óssea/genética , Perfilação da Expressão Gênica , Regeneração Tecidual Guiada/métodos , Modelos Animais , Peptídeos e Proteínas de Sinalização IntracelularRESUMO
Environmental microorganisms commonly inhabit dense multispecies biofilms, fostering mutualistic relationships and co-evolution. However, the mechanisms underlying biofilm formation and microbial interactions within the Baijiu fermentation microecosystem remain poorly understood. Hence, the objective of this study was to investigate the composition, structure, and interactions of microorganisms residing in biofilms on environmental surfaces in Baijiu production. The results revealed a shift in the bacteria-fungi interaction network following fermentation, transitioning from a cooperative/symbiotic relationship to a competitive/antagonistic dynamic. Core microbiota within the biofilms comprised lactic acid bacteria (LAB), yeast, and filamentous fungi. From the environmental surface samples, we isolated two strains of LAB (Lactiplantibacillus pentosus EB27 and Pediococcus pentosaceus EB35) and one strain of yeast (Pichia kudriavzevii EF8), all displaying remarkable biofilm formation and fermentation potential. Co-culturing LAB and yeast demonstrated a superior capacity for dual-species biofilm formation compared to mono-species biofilms. The dual-species biofilm displayed a two-layer structure, with LAB in the lower layer and serving as the foundation for the yeast community in the upper layer. The upper layer exhibited a dense distribution of yeast, enhancing aerobic respiration. Metabolic activities in the dual-species biofilm, such as ABC transporter, oxidative phosphorylation, citric acid cycle, sulfur metabolism, glycine, serine, threonine metabolism, lysine degradation, and cysteine and methionine metabolism, showed significant alterations compared to LAB mono-species biofilms. Moreover, bacterial chemotaxis, starch, and sucrose metabolism in the dual-species biofilm exhibited distinct patterns from those observed in the yeast mono-species biofilm. This study demonstrated that a core microbiota with fermentation potential may exist in the form of a biofilm on the surface of a Baijiu brewing environment. These findings provide a novel strategy for employing synthetic stable microbiotas in the intelligent brewing of Baijiu.
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Biofilmes , Fermentação , Interações Microbianas , Biofilmes/crescimento & desenvolvimento , Interações Microbianas/fisiologia , Microbiologia de Alimentos , Cerveja/microbiologia , Microbiota/fisiologia , Técnicas de Cocultura , Lactobacillales/metabolismo , Lactobacillales/fisiologia , Fungos/metabolismo , Fungos/fisiologia , Pediococcus pentosaceus/metabolismoRESUMO
The spontaneous Baijiu fermentation system harbors a complex microbiome that is highly dynamic in time and space and varies depending on the Jiuqu starters and environmental factors. The intricate microbiota presents in the fermentation environment is responsible for carrying out various reactions. These reactions necessitate the interaction among the core microbes to influence the community function, ultimately shaping the distinct Baijiu styles through the process of spontaneous fermentation. Numerous studies have been conducted to enhance our understanding of the diversity, succession, and function of microbial communities with the aim of improving fermentation manipulation. However, a comprehensive and critical assessment of the core microbes and their interaction remains one of the significant challenges in the Baijiu fermentation industry. This paper focuses on the fermentation properties of core microbes. We discuss the state of the art of microbial traceability, highlighting the crucial role of environmental and starter microbiota in the Baijiu brewing microbiome. Also, we discuss the various interactions between microbes in the Baijiu production system and propose a potential conceptual framework that involves constructing predictive network models to simplify and quantify microbial interactions using co-culture models. This approach offers effective strategies for understanding the core microbes and their interactions, thus beneficial for the management of microbiota and the regulation of interactions in Baijiu fermentation processes.
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Fermentação , Microbiologia de Alimentos , Microbiota , Microbiota/fisiologia , Interações Microbianas/fisiologia , Cerveja/microbiologia , Bactérias/metabolismo , Bactérias/classificaçãoRESUMO
While there is significant potential for DNA machine-built enzyme-free fluorescence biosensors in the imaging analysis of live biological samples, they persist certain shortcomings. These encompass a deficiency of signal enrichment within a singular interface, uncontrolled premature activation during bio-delivery, and a slow reaction rate due to free nucleic acid collisions. In this contribution, we are committed to resolving the above challenges. Firstly, a single-interface-integrated domino-like driving amplification is constructed. In this conception, a specific target acts as the domino promotor (namely the energy source), initiating a cascading chain reaction that grafts onto a singular interface. Next, an 808 nm near-infrared (NIR) light-excited up-converting luminescence-induced light-activatable biosensing technique is introduced. By locking the target-specific identification segment with a photo-cleavage connector, the up-converted ultraviolet emission can activate target binding in a completely controlled manner. Moreover, a fast reaction rate is achieved by confining nucleic acid collisions within the surface of a DNA wire nano-scaffold, leading to a substantial enhancement in local contact concentration (30.8-fold increase, alongside a 15 times elevation in rate). When a non-coding microRNA (miRNA-221) is positioned as the model low-abundance target for proof-of-concept validation, our intelligent DNA machine demonstrates ultra-high sensitivity (with a limit of detection down to 62.65 fM) and good specificity for this hepatic malignant tumor-associated biomarker in solution detection. Going further, it is worth highlighting that the biosensing system can be employed to carry out high-performance imaging analysis in live bio-samples (ranging from the cellular level to the nude mouse body), thereby propelling the field of DNA machines in disease diagnosis.
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Técnicas Biossensoriais , DNA , Raios Infravermelhos , MicroRNAs , Técnicas Biossensoriais/métodos , Humanos , DNA/química , DNA/genética , MicroRNAs/análise , MicroRNAs/genética , Animais , Camundongos , Técnicas de Amplificação de Ácido Nucleico/métodos , Imagem Óptica/métodos , Nanoestruturas/químicaRESUMO
Ochratoxin A (OTA) is a notorious mycotoxin commonly contaminating food products worldwide. In this study, an OTA-degrading strain Brevundimonas diminuta HAU429 was isolated by using hippuryl-L-phenylalanine as the sole carbon source. The biodegradation of OTA by strain HAU429 was a synergistic effect of intracellular and extracellular enzymes, which transformed OTA into ochratoxin α (OTα) through peptide bond cleavage. Cytotoxicity tests and cell metabolomics confirmed that the transformation of OTA into OTα resulted in the detoxification of its hepatotoxicity since OTA but not OTα disturbed redox homeostasis and induced oxidative damage to hepatocytes. Genome mining identified nine OTA hydrolase candidates in strain HAU429. They were heterologously expressed in Escherichia coli, and three novel amidohydrolase BT6, BT7 and BT9 were found to display OTA-hydrolyzing activity. BT6, BT7 and BT9 showed less than 45 % sequence identity with previously identified OTA-degrading amidohydrolases. BT6 and BT7 shared 60.9 % amino acid sequence identity, and exhibited much higher activity towards OTA than BT9. BT6 and BT7 could completely degrade 1 µg mL-1 of OTA within 1 h and 50 min, while BT9 hydrolyzed 100 % of OTA in the reaction mixture by 12 h. BT6 was the most thermostable retaining 38 % of activity after incubation at 70 °C for 10 min, while BT7 displayed the highest tolerance to ethanal remaining 76 % of activity in the presence of 6 % ethanol. This study could provide new insights towards microbial OTA degradation and promote the development of enzyme-catalyzed OTA detoxification during food processing.
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Caulobacteraceae , Ocratoxinas , Ocratoxinas/metabolismo , Ocratoxinas/toxicidade , Caulobacteraceae/metabolismo , Caulobacteraceae/genética , Biodegradação Ambiental , Amidoidrolases/metabolismo , Amidoidrolases/genética , Contaminação de AlimentosRESUMO
Allergic asthma is characterized by the polarization of Th2 cells and impaired immune regulation. Macrophages occupy the largest proportion of airway immune cells. This study aims to discover the mechanism that hinders the immune regulatory functions of airway macrophages. In this study, macrophages were isolated from cells in bronchoalveolar lavage fluids (BALF) collected from asthma patients and normal control (NC) subjects. The results indicated that macrophages occupied the largest portion of the cellular components in BALF. The frequency of IL-10+ macrophage was significantly lower in asthma patients than in NC subjects. The expression of IL-10 in macrophages of BALF was associated with the levels of asthma-related parameters. The immune-suppressive functions of BALF M0 cells were defective in asthma patients. The inducibility of IL-10 expression was impaired in BALF macrophages of asthma patients, which could be restored by exposing to CpG. In conclusion, the induction of IL-10 in macrophages of BALF in asthma patients was impaired, and it could be restored by exposure to CpG.
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Asma , Líquido da Lavagem Broncoalveolar , Interleucina-10 , Oligodesoxirribonucleotídeos , Humanos , Asma/imunologia , Oligodesoxirribonucleotídeos/farmacologia , Oligodesoxirribonucleotídeos/imunologia , Líquido da Lavagem Broncoalveolar/imunologia , Líquido da Lavagem Broncoalveolar/citologia , Feminino , Masculino , Interleucina-10/metabolismo , Adulto , Macrófagos/imunologia , Macrófagos/metabolismo , Pessoa de Meia-Idade , Macrófagos Alveolares/imunologia , Células Cultivadas , Células Th2/imunologiaRESUMO
SUMMARY: Nasal reconstruction in pediatric patient is very challenging and it requires consideration of later nasal development. Herein, we introduce an innovative preauricular free flap pedicled with retrograde vascular (PFFPRV) for pediatric nasal reconstruction. In this PFFPRV technique, the retrograde superficial temporal vessels were used as the flap pedicle. The lateral alar artery and angular vein were used as vessels of the nasal recipient zone. The flap vessels were anastomosed directly to the recipient area vessels without additional vessel transplantation. Eight pediatric patients with nasal defects underwent this operation. All patients were followed up for more than 2 years. Patients' medical history data were retrospectively analyzed. Preoperative and postoperative facial photos were compared and analyzed. The satisfaction of patient's parents with the aesthetic results was assessed. All patients were successfully operated without intraoperative complications. None of the procedures required additional blood vessel grafts. One patient developed a vascular crisis the next day after the surgery and underwent vascular exploration operation. The free flaps of all patients survived without wound infection or necrosis. The color difference of flap gradually became unobvious. The transplanted flap did not show obvious contracture or retraction, and the nose was symmetrical and developed well. The parents of all patients were satisfied with the surgical results. We think this PFFPRV technique can be a reasonable alternative strategy for reconstruction of pediatric nasal defect, with no adverse effect on nasal development and no need of vascular transplantation. LEVEL OF EVIDENCE: Level IV, therapeutic study.
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To explore the effect of refined psychological pain nursing combined with information-motivation-behavioral (IMB) care model on the pain, sleep and quality of life of patients after cervical cancer surgery, so as to provide reference and basis for the nursing of patients after cervical cancer surgery. The clinical data of 798 postoperative cervical cancer patients who were nursing in our hospital from January 2018 to December 2022 were included in this retrospective study and divided into the control group (nâ =â 382) and observation group (nâ =â 416) according to the different care methods. The control group used refined psychological pain nursing, and on this basis, the observation group used IMB nursing to observe and compare the differences in pain, sleep and quality of life between the 2 groups. There was no significant difference in pain between the 2 groups before nursing (Pâ >â .05). After nursing, the pain of both groups was significantly improved. The scores of NRS, VAS, and PSEQ of the observation group were significantly better than those of the control group (Pâ <â .001). After nursing, the quality of life scores such as emotion, cognition, society, and overall health were significantly higher in the observation group than those of the control group, while physical, fatigue, nausea, vomiting, and pain were significantly lower than those of the control group (Pâ <â .05). The negative emotion score of the observation group was significantly lower than that of the control group (Pâ <â .001). The residual urine volume and urinary tract infection rate of the observation group were significantly lower than those of the control group (Pâ <â .05). The bladder function was significantly better than that of the control group (Pâ <â .05). The analgesic effect of refined psychological pain nursing combined with IMB nursing on patients after cervical cancer surgery is better than that of refined psychological pain nursing alone, which can promote pain recovery and further improve the quality of life and sleep quality of patients.
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Motivação , Neoplasias do Colo do Útero , Humanos , Feminino , Qualidade de Vida , Estudos Retrospectivos , Neoplasias do Colo do Útero/cirurgia , Sono , DorRESUMO
Purpose: Premenstrual syndrome (PMS) is a cyclical psychosomatic disorder prevalent among women of reproductive age. However, research on the potential impact of PMS on routine nursing schedules and activities is limited. This study aims to identify the prevalence of PMS among female nursing staff and to examine the relationship between PMS and missed nursing care (MNC). Method: Between November 1, 2022, and April 30, 2023, this study was conducted among female nursing staff working in nine inpatient departments at Sun Yat-sen University Cancer Center. This study used a cross-sectional design. The participants were recruited through convenience sampling. Data were collected using the standardized Menstrual Distress Questionnaire, the Oncology Missed Nursing Care self-rating scale, and a sociodemographic questionnaire. One-way analysis of variance, Fisher's least significant difference test for post-hoc comparisons, and Spearman's correlation coefficient were utilized for data analysis. A trend test was also performed to explore patterns in the severity of PMS and MNC over time. Results: We collected a total of 224 questionnaires, with 154 (68.7%) female nursing staff reporting PMS. The most common symptoms were low back pain (91.1%), abdominal discomfort (90.6%), cold hands and feet (87.1%), and lethargy (87.1%). Moreover, 91.5% of the 224 female nursing staff reported at least one MNC activity. The nursing activities most frequently missed or left incomplete were liquid intake and output monitoring as ordered (43.3%), medication administration within 30 min before or after the scheduled time (43.3%), and electrocardiogram monitoring as ordered (42.9%). "Abdominal discomfort" from the Menstrual Distress Questionnaire was significantly correlated with the majority of MNC activities (p < 0.001). Conclusions: This study provides evidence for a strong association between PMS and MNC among female nursing staff, suggesting that administrators should take the premenstrual conditions of female nursing staff into consideration. It is necessary to provide appropriate understanding and support to mitigate the impact on patient care and safety.
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BACKGROUND: CpG oligodeoxynucleotide (CpG-ODN; CpG, in short) has been employed as an adjuvant in allergen specific immunotherapy (AIT) to treat allergic diseases. The underlying mechanism needs to be further explained. The aim of this study is to examine the mechanism by which CpG and dust mite extracts (DME, a specific antigen) alleviate experimental airway allergy. METHODS: DME was used as the specific allergen to establish an airway allergy mouse model. The mice were directly exposed to DME and CpG through nasal instillations (the CpG.DME therapy). The response of DCs and allergic responses in the airways were assessed using immunological approaches. RESULTS: The airway allergy reaction was effectively suppressed by CpG.DME therapy. The administration of CpG or DME alone did not have any significant suppressive effects on the airway allergic response. Direct exposure to CpG.DME induced type 1 DCs (DC1s) and plasmacytoid DCs (pDCs), while CpG alone induced DC1s and DME alone induced DC2s in the airway tissues. Both DC1s and pDCs were required for the induction of type 1 regulatory T cells in the airway tissues by CpG.DME therapy. Depletion of either pDCs or DC1s abolished the induction of Tr1 cells, and abolished the suppressive effects on airway allergic response by the CpG.DME therapy. CONCLUSIONS: Direct exposure to CpG.DME induces DC1s and pDCs in the airway tissues. DC1s in synergy with pDCs induce type 1 regulatory T cells. The CpG.DME therapy is effective in suppressing allergic responses in mice with airway allergy.
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Células Dendríticas , Camundongos Endogâmicos BALB C , Oligodesoxirribonucleotídeos , Hipersensibilidade Respiratória , Animais , Células Dendríticas/imunologia , Células Dendríticas/efeitos dos fármacos , Oligodesoxirribonucleotídeos/farmacologia , Camundongos , Hipersensibilidade Respiratória/imunologia , Hipersensibilidade Respiratória/terapia , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/efeitos dos fármacos , Feminino , Adjuvantes Imunológicos/farmacologia , Alérgenos/imunologia , Antígenos de Dermatophagoides/imunologia , Hipersensibilidade/imunologia , Camundongos Endogâmicos C57BL , Modelos Animais de Doenças , Pyroglyphidae/imunologiaRESUMO
This study was to investigate the potential mechanisms of treatment with metformin (Met) combined with kaempferol (Kae) against postmenopausal osteoporosis. Experiments were conducted in both ovariectomy (OVX)-induced osteoporosis rats and in vitro using RAW264.7 cells, MC3T3-E1 cells, and HUVECs. Results demonstrated the therapeutic effect of Met combined with Kae on osteoporosis. In vivo, Kae alone and in combination with Met treatments enhanced tibial trabecular microstructure, bone mineral density (BMD), and mechanical properties in OVX rats without causing hepatotoxicity and nephrotoxicity. It also reduced bone resorption markers (CTX-1 and TRAP) and increased the bone formation marker (PINP) level in the serum of OVX rats. The expression of bone resorption marker TRAP was reduced, while bone formation markers Runx2 and ALP were enhanced in the bone tissue of OVX rats. Furthermore, Met combined with Kae also promoted the expression of angiogenesis-related markers CD31 and VEGF in OVX rats. In vitro, MC3T3-E1s cells treated with Met combined with Kae showed higher expression of ALP, Runx2, and VEGF. Interestingly, the treatment did not directly promote HUVECs migration and angiogenesis, but enhanced osteoblast-mediated angiogenesis by upregulating VEGF levels. Additionally, Met combined with Kae treatment promoted VEGF secretion in MC3T3-E1, and activated the Notch intracelluar pathway by upregulating HES1 and HEY1 in HUVECs. Meantime, their stimulation on CD31 expression were inhibited by DAPT, a Notch signaling inhibitor. Overall, this study demonstrates the positive effects of Met combined with Kae on osteoporotic rats by promoting osteogenesis-angiogenesis coupling, suggesting their potential application in postmenopausal osteoporosis.
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Reabsorção Óssea , Osteoporose Pós-Menopausa , Osteoporose , Feminino , Humanos , Ratos , Animais , Osteogênese , Osteoporose Pós-Menopausa/tratamento farmacológico , Subunidade alfa 1 de Fator de Ligação ao Core , Fator A de Crescimento do Endotélio Vascular/farmacologia , Quempferóis/farmacologia , Quempferóis/uso terapêutico , Angiogênese , Osso e Ossos/metabolismo , Osteoporose/tratamento farmacológico , Osteoporose/prevenção & controle , Osteoporose/metabolismo , Reabsorção Óssea/tratamento farmacológico , OvariectomiaRESUMO
Bifid nose is a rare congenital malformation, and few cases have been reported due to its low incidence. Herein, we report a new surgical procedure to treat patients with excess dorsal nasal tissue and an underfilled tip. A total of 22 patients with bifid nose deformities underwent surgery at our institution between 2012 and 2022. They were characterized by a broad nasal dorsum and a missing or underdeveloped nasal tip. We designed an innovative island flap of nasal dorsum as a new surgical method for treating this bifid nose deformity. Nasal length, tip projection, and photographs of nose morphology were obtained before and after the surgery. Outcomes, complications, indications, and patient satisfaction were analyzed and interviewed. The follow-up time ranges from 6 to 33 months (8.7 ± 5.5 months). The deformity was successfully corrected with an improved nasal appearance. Nasal length increased from initially 4.2 ± 0.3 mm to 4.6 ± 0.3 mm. Tip projection reached 19.9 ± 4.0 mm, which was 15.7 ± 2.9 mm before surgery. No severe complications were observed except poor venous reflux within postoperative 72 hours in four cases. Six patients (27.3%) got moderate healing and acceptable scars, and 14 patients (63.6%) got good healing. Most patients were very satisfied with the outcome (93.9%). The newly designed nasal dorsum island flap is a safe and effective technical approach to correct nose deformity featured by broad nasal dorsum and a missing or underdeveloped nasal tip.
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Cottonseed meal (CSM) is the major by-product of the cottonseed oil extraction process with high protein content. However, the presence of free gossypol (FG) in CSM severely restricts its utilization in the food and animal feed industries. The development of a biological strategy for the effective removal of FG in CSM has become an urgent need. In this study, three bacterial laccases including CotA from Bacillus licheniformis, CueO from Escherichia coli, and LcLac from Loigolactobacillus coryniformis were heterologously expressed and investigated for their FG degradation ability. The results showed that CotA laccase displayed the highest FG-degrading capacity among the three laccases, achieving 100% FG degradation at 37 °C and pH 7.0 in 1 h without the addition of a redox mediator. Moreover, in vitro and in vivo studies confirmed that the hepatotoxicity of FG was effectively eliminated after oxidative degradation by CotA laccase. Furthermore, the addition of CotA laccase could achieve 87% to 98% FG degradation in defatted CSM within 2 h. In conclusion, CotA laccase can be developed as an effective biocatalyst for the detoxification of FG in CSM.
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OBJECTIVE: To describe the cerebrospinal fluid (CSF) metabolomic pattern of pituitary stalk lesions. METHODS: CSF was collected from patients with different pituitary stalk lesions treated at Peking Union Medical College Hospital: germ cell tumor (GCT, n = 27); hypophysitis (n = 10); and Langerhans cell histiocytosis (LCH) or Erdheim-Chester disease (ECD) (LCH + ECD, n = 10). The CSF metabolome profiles were characterized by liquid chromatography-mass spectrometry (LC-MS). RESULTS: There were 44 metabolites that significantly differed between patients with GCT and those with hypophysitis (P < .05). Between patients with GCT with CSF level of beta subunit of human chorionic gonadotrophin (ß-hCG) < 5â mIU/mL and those with hypophysitis, there were 15 differential metabolites (P < .05, fold change > 1.5 or < 1/1.5). All of the metabolites had an area under the curve (AUC) above 0.7. There were 9 metabolites that significantly differed between patients with GCT and those with LCH + ECD (P < .05) and 7 metabolites had significant differences between GCT (CSF ß-hCG < 5â mIU/mL) and LCH + ECD (P < .05, fold change > 1.5 or < 1/1.5). We found 6 metabolites that were significantly different between patients with hypophysitis and those with LCH + ECD (P < .05) and 5 of these had fold change more than 1.5 or less than 1/1.5. Three metabolites, 5-deoxydiplosporin, cloversaponin I, and phytosphingosine, showed excellent capabilities to differentiate the 3 disease categories. Furthermore, we identified 67 metabolites associated with clinical test results (ρ > 0.2, P < .05) and 29 metabolites showed strong correlation (ρ > 0.4, P < .05). CONCLUSION: Our study is the first to systematically investigate the metabolomics of CSF in different pituitary stalk lesions. CSF metabolomics is a useful strategy for biomarker discovery.
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Doença de Erdheim-Chester , Histiocitose de Células de Langerhans , Hipofisite , Neoplasias Embrionárias de Células Germinativas , Humanos , Doença de Erdheim-Chester/complicações , Doença de Erdheim-Chester/tratamento farmacológico , Doença de Erdheim-Chester/patologia , Hipófise/patologiaRESUMO
Riboswitches are regulatory elements found in the untranslated regions (UTRs) of certain mRNA molecules. They typically comprise two distinct domains: an aptamer domain that can bind to specific small molecules, and an expression platform that controls gene expression. Riboswitches work by undergoing a conformational change upon binding to their specific ligand, thus activating or repressing the genes downstream. This mechanism allows gene expression regulation in response to metabolites or small molecules. To systematically summarise riboswitch structures and their related ligand binding functions, we present Ribocentre-switch, a comprehensive database of riboswitches, including the information as follows: sequences, structures, functions, ligand binding pockets and biological applications. It encompasses 56 riboswitches and 26 orphan riboswitches from over 430 references, with a total of 89 591 sequences. It serves as a good resource for comparing different riboswitches and facilitating the identification of potential riboswitch candidates. Therefore, it may facilitate the understanding of RNA structural conformational changes in response to ligand signaling. The database is publicly available at https://riboswitch.ribocentre.org.
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Bases de Dados de Ácidos Nucleicos , Riboswitch , Ligantes , Conformação de Ácido Nucleico , Sequências Reguladoras de Ácido Nucleico , Transdução de SinaisRESUMO
Nanocarriers play an important role in enhancing the efficacy of antibiotics against biofilms by improving their penetration and prolonging retention in pathogenic biofilms. Herein, the multifunctional nanocarriers including nanospheres (NS) and nanotubes (NT) with a high biocompatibility and biodegradability were prepared through self-assembly of partially hydrolyzed α-lactalbumin. The effects of these two different shaped nanocarriers on the delivery of antibiotics for biofilm treatment were examined by conducting in vitro antibiofilm experiment and in vivo infected wound model. The strong affinity of NS and NT for the bacterial surface allows antibiotics to be concentrated in the bacteria. Notably, the high permeability of NT into biofilms facilitates deeper penetration and the easier diffusion of loaded antibiotics within the biofilm. Furthermore, the acidic biofilm environment triggers the release of antibiotics from the NT, resulting in the accumulation of high local antibiotic concentrations. Therefore, NT could efficiently clean and inhibit the biofilm formation while also destroying the mature biofilms. In a S. aureus infected wound animal model, treatment with antibiotic-loaded NT demonstrated accelerated healing of S. aureus infected wounds when compared to free antibiotic treatment. These findings indicate that NT nanocarrier strategy is promising for treating bacterial biofilm infections, offering the potential for lower antibiotics dosages and preventing the overuse of antibiotics.
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Infecções Bacterianas , Staphylococcus aureus , Animais , Portadores de Fármacos/farmacologia , Antibacterianos , Biofilmes , Infecções Bacterianas/tratamento farmacológico , Bactérias , Testes de Sensibilidade MicrobianaRESUMO
BACKGROUND: Bifid nose is a rare congenital deformity and the etiology is unknown. The purpose of this study was to report genetic variation in family of patients with bifid nose. METHODS: Twenty-three consecutive patients who were diagnosed with mild bifid nose were operated with z-plasty from 2009 to 2021. Three underage patients (a pair of twins and a girl) from two family lines, who came to our hospital for surgical treatment, were enrolled. Whole exome sequencing and Sanger sequencing were conducted. Z-shaped flaps were created and the cartilago alaris major were re-stitched. Photographs and CT scan before and after surgery were obtained. Clinical outcomes, complications and patients' satisfaction were evaluated and analyzed. The follow-up time ranges from 2 to 3 years (2.4 ± 1.2 years). RESULTS: Most patients were satisfied with the outcome (96.2%). The nasal deformities were corrected successfully with z-plasty technique in one-stage. FREM1 c.870_876del and c.2 T > C were detected with Whole exome sequencing, which have not been reported before. The results of Sanger sequencing were consistent with those of Whole exome sequencing. CONCLUSIONS: The newly detected mutations of FREM1 have a certain heritability, and are helpful to make an accurate diagnosis and provide a better understanding of bifid nose mechanism. Z-plasty technique can be an effective technical approach for correcting mild bifid nose deformity.
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Doenças Nasais , Nariz , Feminino , Humanos , Mutação , Nariz/anormalidades , Nariz/cirurgia , Doenças Nasais/diagnóstico , Doenças Nasais/cirurgia , Tomografia Computadorizada por Raios XRESUMO
This paper reports a correction scheme to address the problem of modulation nonlinearity and optical switch crosstalk simultaneously for the multi-site optical converged network. Based on the optical link encoding and exclusive-or operation for the received signal, the present spectrum usage can be obtained among the confusion with interferences containing the modulated harmonic distortion and the crosstalk leakage from other sites. The proof-of-concept experiment is performed on various interferences involving the linear frequency modulated (LFM) waveform and the quadrature amplitude modulation (QAM) signal. The corrected spectrum has realized an improved signal-to-noise ratio (SNR) of over 22â dB compared to the uncorrected counterpart. Furthermore, it consistently maintains a superior SNR, surpassing the single impairment-corrected scenario by an impressive margin of at least 15.9â dB. Besides, the implementation would not introduce additional noise, making the corrected result agree well with the ideal case. Without any increase in hardware complexity, the presented scheme provides an effective technique to meet the correction challenge of large-scale and complicated optical networks with multiple optoelectronic devices.
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INTRODUCTION: Little is known about the effectiveness of immunotherapy alone or with chemotherapy for patients with non-small cell lung cancer (NSCLC) and programmed death ligand 1 (PD-L1) expression <50 %. We examined the outcomes of PD-L1 therapy vs. PD-L1 therapy in combination with chemotherapy as first-line treatment among NSCLC patients with PD-L1 score <50 %. METHODS: We used administrative claims and prior authorization data of a national insurer from November 2015 to July 2021. We selected patients with Stage IIIb/IV NSCLC and PD-L1 expression <50 %. Each patient was required to have ≥1 claim of a PD-L1 or PD-1 inhibitor. Treatment groups were propensity-score matched 1:1 on baseline characteristics. We measured PD-L1 therapy duration, incident immune-related adverse events (irAEs), healthcare utilization, costs, and overall survival (OS). RESULTS: In the matched sample totaling 176 patients, mean duration of PD-L1 therapy was similar (4.1 [SD 3.3] months combination vs. 4.0 [SD 4.9] months monotherapy, p = 0.800). IrAEs were similar, both for FDA-recognized irAEs (48.9 % combination, 48.9 % monotherapy, p = 0.710) and other types (34.1 % combination, 39.8 % monotherapy, p = 0.473). The combination group had more all-cause inpatient stays, ER visits, and outpatient visits (all p < 0.001). Total adjusted all-cause medical cost was $112,833 (95 % CI $5,548-$251,973) higher for combination therapy. We saw no difference in OS (adjusted hazard ratio 1.09 [95 % CI 0.72-1.65]). CONCLUSION: This study found no difference in adverse drug effects or survival between PD-L1 monotherapy compared to combination therapy for patients with Stage IIIb/IV NSCLC and PD-L1 expression <50 %, though the combination therapy cohort had higher healthcare utilization and costs. MICROABSTRACT: Use of immunotherapy alone or combined with chemotherapy for patients with non-small cell lung cancer and programmed death ligand 1 expression <50 % is understudied. Our observational study using claims and authorization data from a matched sample of 176 patients found no difference in survival or the rate of adverse drug effects between groups, although the chemo-immunotherapy cohort generated higher overall healthcare costs.