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BACKGROUND: In radiography procedures, radiographers' suboptimal positioning and exposure parameter settings may necessitate image retakes, subjecting patients to unnecessary ionizing radiation exposure. Reducing retakes is crucial to minimize patient X-ray exposure and conserve medical resources. OBJECTIVE: We propose a Digital Radiography (DR) Pre-imaging All-round Assistant (PIAA) that leverages Artificial Intelligence (AI) technology to enhance traditional DR. METHODS: PIAA consists of an RGB-Depth (RGB-D) multi-camera array, an embedded computing platform, and multiple software components. It features an Adaptive RGB-D Image Acquisition (ARDIA) module that automatically selects the appropriate RGB camera based on the distance between the cameras and patients. It includes a 2.5D Selective Skeletal Keypoints Estimation (2.5D-SSKE) module that fuses depth information with 2D keypoints to estimate the pose of target body parts. Thirdly, it also uses a Domain expertise (DE) embedded Full-body Exposure Parameter Estimation (DFEPE) module that combines 2.5D-SSKE and DE to accurately estimate parameters for full-body DR views. RESULTS: Optimizes DR workflow, significantly enhancing operational efficiency. The average time required for positioning patients and preparing exposure parameters was reduced from 73 seconds to 8 seconds. CONCLUSIONS: PIAA shows significant promise for extension to full-body examinations.
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The yeast SWR1 complex catalyzes the exchange of histone H2A/H2B dimers in nucleosomes with Htz1/H2B dimers. We use cryoelectron microscopy to determine the structure of an enzyme-bound hexasome intermediate in the reaction pathway of histone exchange, in which an H2A/H2B dimer has been extracted from a nucleosome prior to the insertion of a dimer comprising Htz1/H2B. The structure reveals a key role for the Swc5 subunit in stabilizing the unwrapping of DNA from the histone core of the hexasome. By engineering a crosslink between an Htz1/H2B dimer and its chaperone protein Chz1, we show that this blocks histone exchange by SWR1 but allows the incoming chaperone-dimer complex to insert into the hexasome. We use this reagent to trap an SWR1/hexasome complex with an incoming Htz1/H2B dimer that shows how the reaction progresses to the next step. Taken together the structures reveal insights into the mechanism of histone exchange by SWR1 complex.
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BACKGROUND: Opioid anesthesia (OA) is currently the predominant anesthetic method. However, its associated side effects, such as nausea and vomiting, coupled with the principle of enhanced recovery after surgery (ERAS), have spurred the adoption of opioid-free anesthesia (OFA) in select surgical procedures. For small and medium-sized operations, ERAS is particularly important. The aim of this study was to investigate the effect of OFA, utilizing esketamine in combination with dexmedetomidine and sevoflurane, on postoperative recovery quality following small and medium-sized surgical interventions. METHODS: A total of 120 patients who underwent various small and medium-sized operations were randomly allocated to OFA and OA groups. The OA group received sufentanyl and sevoflurane, while the OFA group received esketamine, dexmedetomidine, and sevoflurane. The primary outcome measure was the postoperative quality of recovery-40 scores (QoR-40) 24 hours after surgery. Secondary outcomes included hemodynamic changes at different time intervals, the incidences of adverse events were recorded. RESULTS: Patients in the OFA group exhibited a higher QoR-40 score of 184.0 (182.0, 186.2) compared to 182.0 (180.0, 184.0) in the OA group (P<0.001). The disparities were particularly noble in terms of Physical comfort and Emotional status. Multivariable analysis identified postoperative nausea and vomiting (PONV) as a significant independent factor impacting QoR-40 (ß=-4.49 [-6.1, -2.87], P<0.001). Hemodynamic stability was more pronounced in the OFA than in the OA group. The incidence of PONV was substantially lower in the OFA group (one [1.6%] vs. 14 [25%], P<0.001), with a reduced need for vasoactive drugs (five [7.8%] vs. 15 [26.8%], P=0.005), and a lower incidence of respiratory depression (0 [0%] vs. six [10.7%], P=0.009). CONCLUSIONS: OFA improves the postoperative recovery quality in small and medium-sized surgical procedures, potentially attributed to decreased incidence of PONV. Additionally, OFA facilitates the maintenance of more stable hemodynamics throughout the operation.
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Periodo de Recuperación de la Anestesia , Humanos , Masculino , Femenino , Estudios Prospectivos , Persona de Mediana Edad , Adulto , Sevoflurano/administración & dosificación , Analgésicos Opioides/uso terapéutico , Dexmedetomidina/uso terapéutico , Ketamina/uso terapéutico , Ketamina/administración & dosificación , Recuperación Mejorada Después de la Cirugía , Anciano , Anestesia/métodosRESUMEN
INTRODUCTION: Immunotherapy has revolutionized the management of lung cancer and improved lung cancer survival in trials, but its real-world impact at the population level remains unclear. METHODS: Using data obtained from eight Surveillance, Epidemiology, and End Results (SEER) registries from 2004 through 2019, we addressed the long-term trends in the incidence, incidence-based mortality (IBM), and survival of lung cancer patients in the United States. RESULTS: The incidence and IBM of both non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) all significantly decreased steadily from 2004 to 2019. The 1-year survival (1-YS) of both NSCLC and SCLC improved over time, with the best improvement observed for Stage 4 NSCLC. Two significant turning points of Stage 4 NSCLC 1-YS were observed over the years: 0.63% (95% confidence interval [CI]: 0.33%-0.93%) from 2004 to 2010, 0.81% (95% CI: 0.41%-1.21%) from 2010 to 2014 and a striking 2.09% (95% CI: 1.70%-2.47%) from 2014 to 2019. The same two turning points in 1-YS were pronounced for Stage 4 NSCLC in women, which were coincident with the introduction of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) and immunotherapy. However, for Stage 4 NSCLC in men, only one significant turning point in the 1-YS starting in 2014 was found, which might only correspond to immunotherapy. Significant period effects in reduced IBM were also observed for both Stage 4 AD and Stage 4 SQCC during the period. CONCLUSION: This SEER analysis found that immunotherapy improved the survival of Stage 4 NSCLC patients at the population level in the United States. This real-world evidence confirms that immunotherapy has truly revolutionized the management of lung cancer.
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Carcinoma de Pulmón de Células no Pequeñas , Inmunoterapia , Neoplasias Pulmonares , Estadificación de Neoplasias , Programa de VERF , Humanos , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/terapia , Carcinoma de Pulmón de Células no Pequeñas/patología , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/patología , Masculino , Femenino , Estados Unidos/epidemiología , Inmunoterapia/métodos , Anciano , Persona de Mediana Edad , Tasa de Supervivencia/tendencias , IncidenciaRESUMEN
Vegetation restoration is an effective measure to cope with global climate change and promote soil carbon sequestration. However, during vegetation restoration, the turnover and properties of carbon within various aggregates change. The effects of plant source carbon input on surface soil and subsurface soil may be different. Thus, the characteristics of carbon components in aggregates are affected. Therefore, the research object of this study is the Robinia pseudoacacia forest located in 16-47a of the Loess Plateau, and compared with farmland. The change characteristics of organic carbon functional groups in 0-20 cm, 20-40 cm, and 40-60 cm soil layers were analyzed by Fourier near infrared spectroscopy, and the relationship between the chemical structure of organic carbon and the content of organic carbon components in soil aggregates was clarified, and the mechanism affecting the distribution of organic carbon components in soil aggregates was revealed in the process of vegetation restoration. The results show the following: (1) The stability of surface aggregates is sensitive, while that of deep aggregates is weak. Vegetation restoration increased the surface soil organic carbon content by 1.97~3.78 g·kg-1. (2) After vegetation restoration, the relative contents of polysaccharide functional groups in >0.25 mm aggregates were significantly reduced, while the relative contents of aromatic and aliphatic functional groups of organic carbon were significantly increased. The opposite is true for aggregates smaller than 0.25 mm. (3) With the increase in soil depth, the effect of litter on organic carbon gradually decreased, while the effect of root input on the accumulation of inert carbon in deep soil was more lasting.
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Two addition orders, i.e., the layer-by-layer (L) and mixed biopolymer (M) orders, were used to generate sodium caseinate - sugar beet pectin electrostatically stabilized o/w emulsions with 0.5% oil and varying sodium caseinate: sugar beet pectin ratios (3:1-1:3) at pH 4.5. Emulsion stability against environmental stresses (i.e., pH, salt addition, thermal treatment, storage and in vitro simulated gastrointestinal digestion) and its astaxanthin encapsulation against degradation during storage and in vitro digestion were evaluated. Results indicated that a total biopolymer concentration of 0.5% was optimal, with the preferred sodium caseinate-sugar beet pectin ratios for L and M emulsions being 1:1 and 1:3, respectively. L emulsions generally exhibited smaller droplet diameters than M emulsions across all ratios, except at 1:3. Lowering the pH to 1.5 substantially reduced the net negative charge of all emulsions, with only L emulsions precipitating at pH 3. M emulsions showed greater tolerance to salt addition, remaining stable up to 500 mM sodium and calcium concentrations, whereas L emulsions destabilized at levels exceeding 50 mM and 30 mM, respectively. All emulsions were stable when heated at 37 °C or 90 °C for 30 min. Astaxanthin degradation rates increased with prolonged storage, reaching 61.66% and 54.08% by day 7 for L and M emulsions, respectively. Encapsulation efficiency of astaxanthin in freshly prepared M emulsions (86.85%) was significantly higher compared to L emulsions (72.82%). M emulsions had 30% and 25% higher encapsulation efficiency of astaxanthin than L emulsions after in vitro digestion for 120 min and 240 min respectively. This study offers suggestions for interface design and process optimization to improve the performance of protein-polysaccharide emulsion systems, such as in beverages and dairy products, as well as their delivery effect of bioactives.
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Photocatalysis is the most promising green approach to solve antibiotic pollution in water, but the actual treatment effect is limited by photocatalytic activity. Herein, Bi and BiOCl were loaded onto the surface of Ce-MOF (metal-organic framework) using an electrostatic adsorption method, and a special ternary heterojunction of Ce/Bi/BiOCl was successfully prepared as a photocatalyst for the degradation of tetracycline (TC). FTIR demonstrated that the obtained photocatalyst contains functional groups such as -COOH belonging to Ce-MOF and characteristic crystal planes of Bi and BiOCl, indicating the successful construction of a ternary photocatalyst. The results of UV-vis absorption spectra confirm that the band gap of Ce/Bi/BiOCl heterojunction is reduced from 3.35 eV to 2.7 eV, resulting in an enhanced light absorption capability in the visible light region. The special ternary heterojunction constructed by Ce-MOF, Bi, and BiOCl could achieve a narrow band gap and reasonable band structure, thereby enhancing the separation of photogenerated charges. Consequently, the photocatalytic performance of the Ce/Bi/BiOCl ternary heterojunction was significantly enhanced compared to Ce-MOF, Bi, and BiOCl. Therefore, Ce/Bi/BiOCl can achieve a photocatalytic degradation rate of 97.7% within 20 min, which is much better than Bi (14.8%) and BiOCl (67.9%). This work successfully constructed MOF-based ternary photocatalysts and revealed the relationship between ternary heterojunctions and photocatalytic activity. This provides inspiration for constructing other heterogeneous catalysts for use in the field of photocatalysis.
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PURPOSE: This prospective study aims to evaluate the value of [18F]AlF-NOTA-fibroblast activation protein inhibitor (FAPI)-04 positron emission tomography-computed tomography (PET/CT) in predicting molecular subtypes of breast cancer. METHODS: The study consecutively recruited patients suspected of having breast cancer from a single center who were prospectively enrolled from July 2023 to May 2024 and underwent [18F]AlF-NOTA-FAPI-04 PET/CT. This study compared the differences in tracer uptake among breast cancers with different adverse prognostic factors and molecular subtypes. The classification performance for each molecular subtype of breast cancer was assessed using a receiver operating characteristic (ROC) curve. RESULTS: Fifty-three participants (mean age, 51 ± 11 years; 52 females) were evaluated. Breast cancer lesions with adverse prognostic factors showed higher tracer uptake. The five different molecular subtypes exhibited varying levels of uptake. The luminal A and luminal B (HER2-negative) subtypes had relatively low uptake, while the luminal B (HER2-positive), HER2-positive, and triple-negative subtypes had relatively high uptake. ROC analysis identified the max standardized uptake value (SUVmax) as a significant classifier (AUC = 0.912, P = 0.0005) for the luminal A subtype, with 100% sensitivity and 83% specificity. For predicting the luminal B (HER2-negative) subtype, SUVmax had an AUC of 0.770 (P = 0.0015). SUVmax, with an AUC of 0.781 (P = 0.003), was used to identify the triple-negative subtype tumors, resulting in a sensitivity of 100% and specificity of 51%. Lastly, the ROC curve showed the cut-off 15.40 (AUC = 0.921, P < 0.0001) could classify luminal A & luminal B (HER2-negative), and luminal B (HER2-positive) & HER2-positive & triple-negative, yielding a sensitivity of 94% and specificity of 79%. CONCLUSION: The uptake of [18F]AlF-NOTA-FAPI-04 is significantly correlated with the molecular subtypes of breast cancer, and [18F]AlF-NOTA-FAPI-04 PET/CT is a potential tool for noninvasive identification of luminal A subtypes and guidance of FAP-targeted therapies.
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The immunosuppressive tumor microenvironment (TME) in solid tumors often impedes the efficacy of immunotherapy. Bacterial outer membrane vesicles (OMVs), as a promising cancer vaccine that can potently stimulate immune responses, have garnered interest as a potential platform for cancer therapy. However, the low yield of OMVs limits their utilization. To address this limitation, we developed a novel approach to synthesize OMV-like multifunctional synthetic bacterial vesicles (SBVs) by pretreating bacteria with ampicillin and lysing them through sonication. Compared to OMVs, the yield of SBVs increased by 40 times. Additionally, the unique synthesis process of SBVs allows for the encapsulation of bacterial intracellular contents, endowing SBVs with the capability of delivering catalase (CAT) for tumor hypoxia relief and activating the host cyclic GMP-AMP synthase (cGAS)/stimulator of interferon genes (STING) signaling pathway. To overcome the toxicity of lipopolysaccharide (LPS) on the SBVs surface, we decorated SBVs with a biocompatible polydopamine (PDA) shell, which allowed TME reprogramming using SBVs to be conducted without adverse side effects. Additionally, the photosensitizer indocyanine green (ICG) was loaded into the PDA shell to induce immunogenic cell death and further improve the efficacy of immunotherapy. In summary, the SBVs-based therapeutic platform SBV@PDA/ICG (SBV@P/I) can synergistically elicit safe and potent tumor-specific antitumor responses through combined immunotherapy and phototherapy.
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Ferroelectric Rashba semiconductors (FRS) are highly demanded for their potential capability for nonvolatile electric control of electron spins. An ideal FRS is characterized by a combination of room temperature ferroelectricity and a strong Rashba effect, which has, however, been rarely reported. Herein, we designed a room-temperature FRS by vertically stacking a Sb monolayer on a room-temperature ferroelectric In2Se3 monolayer. Our first-principles calculations reveal that the Sb/In2Se3 heterostructure exhibits a clean Rashba splitting band near the Fermi level and a strong Rashba effect coupled to the ferroelectric order. Switching the electric polarization direction enhances the Rashba effect, and the flipping is feasible with a low energy barrier of 22 meV. This Rashba-ferroelectricity coupling effect is robust against changes of the heterostructure interfacial distance and external electric fields. Such a nonvolatile electrically tunable Rashba effect at room temperature enables potential applications in next-generation data storage and logic devices operated under small electrical currents.
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Selenium supplements are beneficial to human health, however, concerns regarding the toxicity of inorganic selenium have stimulated research on safer organic compounds. The main objective of this study was to develop a novel glucosamine-selenium compound (Se-GlcN), clarify its structure, and subsequently investigate its oral toxicity and in vitro anti-hepatitis B virus (HBV) activity. Electron microscopy, infrared, ultraviolet spectroscopy, nuclear magnetic resonance and thermogravimetric analyses revealed a unique binding mode of Se-GlcN, with the introduction of the Se-O bond at the C6 position, resulting in the formation of two carboxyl groups. In acute toxicity studies, the median lethal dose (LD50) of Se-GlcN in ICR mice was 92.31 mg/kg body weight (BW), with a 95 % confidence interval of 81.88-104.07 mg/kg BW. A 30-day subchronic toxicity study showed that 46.16 mg/kg BW Se-GlcN caused livers and kidneys damage in mice, whereas doses of 9.23 mg/kg BW and lower were safe for the livers and kidneys. In vitro studies, Se-GlcN at 1.25 µg/mL exhibited good anti-HBV activity, significantly reducing HBsAg, HBeAg, 3.5 kb HBV RNA and total HBV RNA by 45 %, 54 %, 84 %, 87 %, respectively. In conclusion, the Se-GlcN synthesized in this study provides potential possibilities and theoretical references for its use as an organic selenium supplement.
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Antivirales , Glucosamina , Virus de la Hepatitis B , Ratones Endogámicos ICR , Animales , Virus de la Hepatitis B/efectos de los fármacos , Glucosamina/química , Glucosamina/farmacología , Ratones , Antivirales/farmacología , Antivirales/síntesis química , Antivirales/química , Antivirales/toxicidad , Administración Oral , Masculino , Selenio/química , Selenio/farmacología , Hígado/efectos de los fármacos , Hígado/patología , Humanos , Femenino , Riñón/efectos de los fármacos , Riñón/patología , Células Hep G2 , Antígenos de Superficie de la Hepatitis B/metabolismoRESUMEN
Fritillaria taipaiensis P. Y. Li (F. taipaiensis) is a traditional Chinese herbal medicine that has been used for over two millennia to treat cough and expectoration. However, the increasing cultivation of F. taipaiensis has led to the spread of bulb rot diseases. In this study, pathogens were isolated from rotten F. taipaiensis bulbs. Through molecular identification, pathogenicity testing, morphological assessment, and microscopy, Fusarium solani was identified as the pathogen causing bulb rot in F. taipaiensis. The colonization of F. solani in the bulbs was investigated through microscopic observation. The rapid and accurate detection of this pathogen will contribute to better disease monitoring and control. Loop-mediated isothermal amplification (LAMP) and qPCR methods were established to quickly and specifically identify this pathogen. These results provide valuable insights for further research on the prediction, rapid detection, and effective prevention and control of bulb rot in F. taipaiensis.
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Previous research has demonstrated a robust association between osteoarthritis (OA) and psoriasis. Notably, a significant proportion of psoriasis patients exhibit symptoms of arthritis, particularly psoriatic arthritis. However, a definitive causal relationship between psoriasis, psoriatic arthritis and OA remains to be established. This study aimed to elucidate the causal relationship between psoriasis, psoriatic arthritis, and osteoarthritis using a 2-sample Mendelian randomization approach. The causal relationship between psoriasis, psoriatic arthritis and OA was rigorously investigated using a 2-sample Mendelian Randomization (MR) approach. Instrumental variables pertinent to psoriasis, psoriatic arthritis and 4 distinct types of OA (knee osteoarthritis (KOA), hand osteoarthritis (HOA), total knee replacement (TKR), and total hip replacement (THR)) were sourced from extensive, published genome-wide association studies (GWAS). To estimate the causal effects, methodologies such as inverse variance weighting (IVW), MR-Egger, and weighted median estimation (WM) were employed. Mendelian Randomization analysis suggested a potential causal effect of psoriasis on osteoarthritis (OA). For hand OA (HOA), the P value was .381 (ORâ =â 0.28); for knee OA (KOA), the P value was .725 (ORâ =â 1.46); for TKR, the P value was .488 (ORâ =â 0.274); and for THR, the P value was .454 (ORâ =â 0.216). Furthermore, we explored the causality of psoriatic arthritis on OA. For HOA, the P value was .478 (ORâ =â 0.0095); for KOA, the P value was .835 (ORâ =â 0.345); for THR, the P value was .807 (ORâ =â 0.120); and for TKR, the P value was .860 (ORâ =â 0.190). Our findings indicate that there is no evidence of a causal connection between psoriasis or psoriatic arthritis and OA, suggesting that while psoriasis may contribute to arthritis, it does not influence OA development.
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Artritis Psoriásica , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Osteoartritis , Psoriasis , Humanos , Psoriasis/genética , Psoriasis/complicaciones , Psoriasis/epidemiología , Osteoartritis/genética , Osteoartritis/epidemiología , Artritis Psoriásica/genética , Artritis Psoriásica/complicaciones , Osteoartritis de la Rodilla/genética , Osteoartritis de la Rodilla/epidemiología , Causalidad , Artroplastia de Reemplazo de Cadera , Artroplastia de Reemplazo de RodillaRESUMEN
To investigate the association between the microbiota in mothers and gut microbiota in infants from 0 to 6 months, the microbiotas in infant feces, maternal feces, and breast milk were determined by 16S rRNA gene sequencing. The contribution of each maternal microbiome to the infant was assessed using fast expectation-maximization for microbial source tracking calculations. The levels of short-chain fatty acids (SCFAs) and secretory immunoglobulin A (sIgA) in the feces of infants were also determined using gas chromatography and IDK-sIgA ELISA to gain a more comprehensive understanding of the infant gut microbiome. The results of this study showed that in addition to Firmicutes (E1) and Bifidobacterium (E2), the dominant microorganisms of the intestinal microbiota of infants aged 0-6 months include Proteobacteria, which is different from previous findings. Acetic acid, the most abundant SCFA in the infant gut, was positively correlated with Megasphaera (P < 0.01), whereas sIgA was positively correlated with Bacteroides (P < 0.05) and negatively correlated with Klebsiella and Clostridium_XVIII (P < 0.05). The maternal gut microbiota contributed more to the infant gut microbiota (43.58% ± 11.13%) than the breast milk microbiota, and significant differences were observed in the contribution of the maternal microbiota to the infant gut microbiota based on the delivery mode and feeding practices. In summary, we emphasize the key role of maternal gut health in the establishment and succession of infant gut microbiota.IMPORTANCEThis study aims to delineate the microbial connections between mothers and infants, leveraging the fast expectation-maximization for microbial source tracking methodology to quantify the contribution of maternal microbiota to the constitution of the infant's gut microbiome. Concurrently, it examines the correlations between the infant gut microbiota and two distinctive biomolecules, namely short-chain fatty acids (SCFAs) and secretory immunoglobulin A (sIgA). The findings indicate that the maternal gut microbiota exerts a greater influence on the infant's gut microbial composition than does the microbiota present in breast milk. Infants born via vaginal delivery and receiving mixed feeding display gut microbiota profiles more similar to their mothers'. Notably, the SCFA acetate displays positive associations with beneficial bacteria and inverse relationships with potentially harmful ones within the infant's gut. Meanwhile, sIgA positively correlates with Bacteroides species and negatively with potentially pathogenic bacteria. By delving into the transmission dynamics of maternal-infant microbiota, exploring the impacts of metabolic byproducts within the infant's gut, and scrutinizing how contextual factors such as birthing method and feeding practices affect the correlation between maternal and infant microbiota, this research endeavors to establish practical strategies for optimizing early-life gut health management in infants. Such insights promise to inform targeted interventions that foster healthier microbial development during the critical first 6 months of life.
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Purpose: To investigate the therapeutic efficiency of a novel drink termed "Ferment" in cases of ulcerative colitis (UC) and its influence on the gut microbiota. Method: In this study, we developed a complex of mixed fruit juice and lactic acid bacteria referred to as Ferment. Ferment was fed to mice for 35 days, before inducing UC with Dextran Sulfate Sodium Salt. We subsequently investigated the gut microbiome composition using 16S rRNA sequencing. Result: After Ferment treatment, mouse body weight increased, and animals displayed less diarrhea, reduced frequency of bloody stools, and reduced inflammation in the colon. Beneficial bacteria belonging to Ileibacterium, Akkermansia, and Prevotellacea were enriched in the gut after Ferment treatment, while detrimental organisms including Erysipelatoclostridium, Dubosiella, and Alistipes were reduced. Conclusion: These data place Ferment as a promising dietary candidate for enhancing immunity and protecting against UC.
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To illustrate the genomic and drug resistance traits of the Klebsiella pneumoniae Kpn_XM9, which harbors a transposon (Tn) As1 and was barely susceptible to ceftazidime-avibactam (CZA). Whole-genome sequencing, gene deletion, antimicrobial susceptibility, and conjugation tests were carried out to illustrate the traits of Kpn_XM9. As confirmed by whole-genome sequencing, the Kpn_XM9 harbored a 5,523,536 bp chromosome and five plasmids with lengths being 128,129, 196,512, 84,812, 43,695, and 5,596 bp, respectively. Plasmid p1_Kpn_XM9 (128,219 bp) contained four resistance genes, blaCTX-M-65, blaTEM-1B, rmtB, and two copies of blaKPC-2. Genes blaKPC-2 were bracketed by ISKpn17 and ISKpn16 within a new composite Tn3-like TnAs1. The two tandem repeats, positioned opposite each other, were spaced 93,447 bp apart in p1_Kpn_XM9. Kpn_XM9 belonged to K64 and sequence type (ST) 11. The Kpn_XM9 was resistant to amikacin, aztreonam, ticarcillin/clavulanic acid, piperacillin/tazobactam, ceftazidime, cefepime, imipenem, meropenem, tobramycin, ciprofloxacin, levofloxacin, doxycycline, minocycline, tigecycline, colistin, and trimethoprim/sulfamethoxazole; it was barely susceptible to CZA with a minimum inhibitory concentration of 8/4 µg/mL, which declined to 2/4 µg/mL after a 18,555 bp nucleotide was knocked out and one copy of blaKPC-2 was sustained on p1_Kpn_XM9. Kpn_XM9 had virulence genes encoding Types 1 and 3 fimbriae, four siderophores, and capsular polysaccharide anchoring protein but no genes upregulating capsular polysaccharide synthesis. The Kpn_XM9 presented a classical phenotype with extreme drug resistance. The emergence of double copies of blaKPC-2 in a single plasmid from the predominant ST11 K. pneumoniae represents a new therapeutic challenge.IMPORTANCEWith the wide use of ceftazidime-avibactam against carbapenem-resistant organisms, its resistance is increasingly documented; among the corresponding resistance mechanisms, mutations of blaKPC-2 or blaKPC-3 into other subtypes are dominant to date. However, more copies of blaKPC-2 may also greatly increase the minimum inhibitory concentration of ceftazidime-avibactam, which could be conferred by transposon As1 and insertion sequence 26 and should be of concern.
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Antibacterianos , Compuestos de Azabiciclo , Ceftazidima , Combinación de Medicamentos , Farmacorresistencia Bacteriana Múltiple , Infecciones por Klebsiella , Klebsiella pneumoniae , Pruebas de Sensibilidad Microbiana , Plásmidos , beta-Lactamasas , Ceftazidima/farmacología , Klebsiella pneumoniae/genética , Klebsiella pneumoniae/efectos de los fármacos , Klebsiella pneumoniae/enzimología , Compuestos de Azabiciclo/farmacología , Humanos , Infecciones por Klebsiella/microbiología , Infecciones por Klebsiella/tratamiento farmacológico , Antibacterianos/farmacología , beta-Lactamasas/genética , beta-Lactamasas/metabolismo , Farmacorresistencia Bacteriana Múltiple/genética , Plásmidos/genética , Secuenciación Completa del Genoma , Elementos Transponibles de ADN/genética , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , HospitalesRESUMEN
The rapid development of the Greater Mekong Subregion (GMS) makes it essential to understand the major mechanisms controlling the streamflow, especially for the Lancang-Mekong River (abbr. Mekong River). We used instrumental annual streamflow data (1960-2007) from Chiang Saen hydrological station and several gridded hydroclimatic datasets to explore the hydroclimatic evolution of the Mekong River, together with its driving mechanisms. We found that changes in the Mekong streamflow are consistent with precipitation changes, and the Mekong is thus a precipitation-dominated river that is susceptible to the effects of ongoing climate change. The instrumental record of Mekong annual streamflow is closely related to hydroclimatic changes, especially those related to moisture, within the area from the Hengduan Mountains to the Chiang Saen Station. Based on these gridded records, we extended the Mekong annual streamflow record to cover 1891-2021 using nested multiple linear regression fitting. The fitted streamflow explained up to 57.6 % of the instrumental changes and it indicates that the major 2019 drought was not unique over the past century. Despite extremely low precipitation and high temperatures, it is likely that the effects of drought can be mitigated via hydraulic engineering regulation. Climatological analyses showed that the Mekong annual streamflow is driven by the El Niño-Southern Oscillation (ENSO) and the Indian Ocean Dipole (IOD), which is consistent with observed quasi-interannual cycles of 3-4 years. A multi-model ensemble of CMIP6 revealed that the Mekong annual streamflow will experience an upward trend in the future, accompanied by the more extreme impacts of ENSO and the IOD.
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Excess gene dosage from chromosome 21 (chr21) causes Down syndrome (DS), spanning developmental and acute phenotypes in terminal cell types. Which phenotypes remain amenable to intervention after development is unknown. To address this question in a model of DS neurogenesis, we derived trisomy 21 (T21) human induced pluripotent stem cells (iPSCs) alongside, otherwise, isogenic euploid controls from mosaic DS fibroblasts and equipped one chr21 copy with an inducible XIST transgene. Monoallelic chr21 silencing by XIST is near-complete and irreversible in iPSCs. Differential expression reveals that T21 neural lineages and iPSCs share suppressed translation and mitochondrial pathways and activate cellular stress responses. When XIST is induced before the neural progenitor stage, T21 dosage correction suppresses a pronounced skew toward astrogenesis in neural differentiation. Because our transgene remains inducible in postmitotic T21 neurons and astrocytes, we demonstrate that XIST efficiently represses genes even after terminal differentiation, which will empower exploration of cell type-specific T21 phenotypes that remain responsive to chr21 dosage.
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Diferenciación Celular , Síndrome de Down , Dosificación de Gen , Células Madre Pluripotentes Inducidas , Neurogénesis , ARN Largo no Codificante , Síndrome de Down/genética , Humanos , Neurogénesis/genética , Células Madre Pluripotentes Inducidas/metabolismo , Células Madre Pluripotentes Inducidas/citología , ARN Largo no Codificante/genética , Diferenciación Celular/genética , Cromosomas Humanos Par 21/genética , Neuronas/metabolismoRESUMEN
Donor (D)-acceptor (A) copolymer-based organic mixed ionic-electronic conductors (OMIECs) exhibit intrinsic environmental stability for they have tailored energy levels. However, their figure-of-merit (µC*) is still falling behind the D-D polymers because of morphology deterioration during the electrochemical doping process. Herein, we developed two D-A copolymers with precisely regulated backbone curvature, namely PTBT-P and PTTBT-P. Compared to the curved PTBT-P and previously reported copolymers, PTTBT-P better keeps its backbone linear, leading to a long-range ordered doping morphology, which is revealed by the in operando X-ray technique. This optimized doping morphology enables a significantly improved operando charge mobility (µ) of 2.44 cm2 V-1 s-1 and a µC* value of 342 F cm-1 V-1 s-1, one of the highest values in D-A copolymer based on OECTs. Besides, we fabricated PTTBT-P-based electrochemical random-access memories and achieved ideal and robust conductance modulation. This study highlights the critical role of backbone curvature control in the optimization of doping morphology for efficient and robust organic electrochemical devices.
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To investigate the changes in the intestinal flora in the Chinese elderly with cardiovascular disease (CVD) and its correlation with the metabolism of trimethylamine (TMA), the intestinal flora composition of elderly individuals with CVD and healthy elderly individuals was analyzed using 16S rRNA sequencing, the TMA levels in the feces of elderly were detected using headspace-gas chromatography (HS-GC), and four kinds of characterized TMA-producing intestinal bacteria in the elderly were quantified using real-time fluorescence quantitative polymerase chain reaction (qPCR). The results showed that Firmicutes, Actinobacteria, Proteobacteria, Bacteroidetes, and Verrucomicrobia are the dominant microorganisms of the intestinal flora in the Chinese elderly. And there were significant differences in the intestinal bacteria composition between healthy elderly individuals and those with CVD, accompanied by a notable difference in the TMA content. The richness and diversity of the intestinal flora in the elderly with CVD were higher than those in the healthy elderly. Correlation analysis indicated that certain significantly different intestinal flora were associated with the TMA levels. Our findings showed a significant difference in TMA-producing intestinal flora between healthy elderly individuals and those with CVD. The TMA levels were found to be positively and significantly correlated with Klebsiella pneumoniae, suggesting that this bacterium is closely linked to the production of TMA in the elderly gut. This may have implications for the development and progression of CVD in the elderly population.