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In recent years, offshore wind farms have frequently encountered engineering geological disasters such as seabed liquefaction and scouring. Consequently, in situ monitoring has become essential for the safe siting, construction, and operation of these installations. Current technologies are hampered by limitations in single-parameter monitoring and insufficient probe-penetration depth, hindering comprehensive multi-parameter dynamic monitoring of seabed sediments. To address these challenges, we propose a foldable multi-sensor probe and establish an underwater adaptive continuous penetration system capable of concurrently measuring seabed elevation changes and sediment pore water pressure profiles. The reliability of the equipment design is confirmed through static analysis of the frame structure and sealed cabin. Furthermore, laboratory tests validate the stability and accuracy of the electrical and mechanical sensor measurements. Preliminary tests conducted in a harbor environment demonstrate the system's effectiveness.
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Chemical Exchange Saturation Transfer (CEST) is a technique that uses specific off-resonance saturation pulses to pre-saturate targeted substances. This process influences the signal intensity of free water, thereby indirectly providing information about the pre-saturated substance. Among the clinical applications of CEST, Amide Proton Transfer (APT) is currently the most well-established. APT can be utilized for the preoperative grading of gliomas. Tumors with higher APTw signals generally indicate a higher likelihood of malignancy. In predicting preoperative molecular typing, APTw values are typically lower in tumors with favorable molecular phenotypes, such as isocitrate dehydrogenase (IDH) mutations, compared to IDH wild-type tumors. For differential diagnosis, the average APTw values of meningiomas are significantly lower than those of high-grade gliomas. Various APTw measurement indices assist in distinguishing central nervous system lesions with similar imaging features, such as progressive multifocal leukoencephalopathy, central nervous system lymphoma, solitary brain metastases, and glioblastoma. Regarding prognosis, APT effectively differentiates between tumor recurrence and treatment effects, and also possesses predictive capabilities for overall survival (OS) and progression-free survival (PFS).
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Immobilized microalgae biotechnologies can conserve water and space by low-carbon wastewater treatment and resource recovery in a recirculating aquaculture system (RAS). However, technical process parameters have been unoptimized considering the mutual interaction between factors. In this study, machine learning optimized the parameters of alginate-immobilized Chlorella vulgaris (C. vulgaris), that is, 474 µmol/(m2·s) of light intensity, 23 × 106 cells/mL for initial cell number, and 2.07 mm particle size. Importantly, under continuous illumination, the immobilized C. vulgaris and microalgal-bacterial consortium improved water purification and biomass reutilization. Transcriptomics of C. vulgaris showed enhanced nitrogen removal by increasing pyridine nucleotide and lipid accumulation via enhanced triacylglycerol synthesis. Symbiotic bacteria upregulated genes for nitrate reduction and organic matter degradation, which stimulated biomass accumulation through CO2 fixation and starch synthesis. The recoverable microalgae (1.94 g/L biomass, 47 % protein, 26.23 % lipids), struvite (64.79 % phosphorus), and alginate (79.52 %) every two weeks demonstrates a low-carbon resource recovery in RAS.
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Alginatos , Acuicultura , Biomasa , Carbono , Chlorella vulgaris , Aprendizaje Automático , Aguas Residuales , Purificación del Agua , Chlorella vulgaris/metabolismo , Acuicultura/métodos , Carbono/metabolismo , Purificación del Agua/métodos , Alginatos/química , Microalgas/metabolismo , Células Inmovilizadas/metabolismo , Nitrógeno/metabolismoRESUMEN
BACKGROUND: Human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) can profoundly affect the mental health of the people living with HIV (PLWH), with higher rates of anxiety, depression, and sleep disturbances. The disparities in neuropsychological problems evaluated by physicians and self-assessed by patients are still unknown. METHODS: A total of 5000 PLWH and 500 physicians from 167 hospitals were enrolled in this cross-sectional study from September 2022 to February 2023. 4-Item Patient Health Questionnaire (PHQ-4) was used for the evaluation of depressive issues and anxiety issues by PLWH. Each physician assessed 10 PLWH under their care for the presence of depressive or anxiety issues. The primary outcomes of this study are the concordance rates on the depressive issues and anxiety issues evaluation between physicians and PLWH. The Cohen's kappa test was used to assess the agreement between physicians and PLWH. RESULTS: The concordance rate for the evaluation of depressive issues is 73.84% (95% confidence interval [CI]: 72.60-75.04%), and it is significantly different from the expected rate of 80% (P <0.001). Similarly, the concordance rate for the evaluation of anxiety issues is 71.74% (95% CI: 70.47-72.97%), which is significantly different from the expected rate of 80% as per the null hypothesis (P <0.001). The overestimation rate by physicians on depressive issues is 12.20% (95% CI: 11.32-13.14%), and for anxiety issues is 12.76% (95% CI: 11.86-13.71%). The mismatch rate for depressive issues is 26.16% (95% CI: 24.96-27.40%), and for anxiety issues is 28.26% (95% CI: 27.02-29.53%). The underestimation rate by physicians on depressive issues is 13.96% (95% CI: 13.03-14.95%), and for anxiety issues is 15.50% (95% CI: 14.52-16.53%). For the treatment regiments, PLWH sustained on innovative treatment regimen (IR) related to a lower prevalence of depressive issues (odds ratio [OR] = 0.71, 95% CI: 0.59-0.87, P = 0.003) and a lower prevalence of anxiety issues (OR = 0.63, 95% CI: 0.52-0.76, P <0.001). PLWH switch from conventional treatment regimen (CR) to IR also related to a lower prevalence of depressive issues (OR = 0.79, 95% CI: 0.64-0.98) and a lower prevalence of anxiety issues (OR = 0.81, 95% CI: 0.67-0.99). CONCLUSION: Nearly one in three PLWH had their condition misjudged by their physicians. The findings underscore the need for improved communication and standardized assessment protocols in the care of PLWH, especially during the acute phase of HIV infection.
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Piglet birth weight is associated with preweaning survival, and its related traits have been included in the breeding program. Thus, understanding its genetic basis is essential. This study identified four birth weight-associated genomic regions on chromosomes 2, 4, 5, and 7 through genome-wide association study analysis in 7286 pigs from three different pure breeds using the FarmCPU model. The genetic and phenotypic variance explained by the four candidate regions is 8.42% and 1.85%, respectively. Twenty-eight candidate genes were detected, of which APPL2, TGFBI, MACROH2A1, and SEC22B have been reported to affect body growth or development. In addition, 21 H3K4me3-enriched peaks overlapped with the birth weight-associated genomic regions were identified by integrating the genome-wide association study results with our previous ChIP-seq and RNA-seq data generated in the pig placenta, a fetal organ relevant to birth weight, and three of the regulatory regions influence TGFBI, MACROH2A1, and SEC22B expression. This study provides new insights into understanding the mechanisms for birth weight. Further investigating the variants in the regulatory regions would help identify the functional variants for birth weight in pigs.
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Localized surface plasmon resonance (LSPR) of noble metal nanoparticles can focus surrounding light onto the particle surface to boost photochemical reactions and solar energy utilization. However, the rarity and high cost of noble metals limit their applications in plasmonic photocatalysis, forcing researchers to seek low-cost alternatives. Recently, some heavily doped semiconductors with high free carrier density have garnered attention due to their metal-like LSPR properties. However, plasmonic semiconductors have complex surface structures characterized by the presence of a depletion layer, which poses challenges for active site exposure and hot carrier transfer, resulting in low photocatalytic activity. In this review, we introduce the essential characteristics and types, synthesis methods, and characterization techniques of full-spectrum plasmonic semiconductors, elucidate the mechanism of full-spectrum nonmetallic plasmonic photocatalysis, including the local electromagnetic field, hot carrier generation and transfer, the photothermal effect, and the solutions for the surface depletion layer, and summarize the applications of plasmonic semiconductors in photocatalytic environmental remediation, CO2 reduction, H2 generation, and organic transformations. Finally, we provide a perspective on full-spectrum plasmonic photocatalysis, aiming to guide the design and development of plasmonic photocatalysts.
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As methicillin-resistant Staphylococcus aureus (MRSA) exhibits formidable resistance to many drugs, the imperative for alternative therapeutic strategies becomes increasingly evident. At the heart of our study is the identification of a novel inhibitor through fluorescence anisotropy assays, specifically targeting the crucial multiple gene regulator A (MgrA) regulatory network in S. aureus. Isorhapontigenin (Iso), a natural compound, exhibits outstanding inhibitory efficacy, modulating bacterial virulence pathways without exerting direct bactericidal activity. This suggests a paradigm shift toward attenuating virulence instead of purely focusing on bacterial elimination. Through comprehensive in vitro and in vivo evaluations, we elucidated the complex interplay between Iso and MgrA, leading to reduced S. aureus adhesion, and overall virulence. At the cellular level, Iso offers significant protection to A549 cells infected with S. aureus, reducing cellular damage. Importantly, Iso augments the chemotaxis of neutrophils, curtailing the immune evasion capabilities of S. aureus. Furthermore, in vivo investigations highlight the notable effectiveness of Iso against MRSA-induced pneumonia and within the Galleria mellonella infection model, underscoring its pivotal role in the evolving realm of antibacterial drug discovery. Significantly, when Iso is used in combination with vancomycin, it outperforms its solo application, indicating a more pronounced therapeutic impact. This seminal research emphasizes Iso's potential as a primary defense against the surge of multidrug-resistant pathogens, heralding new prospects in antimicrobial therapy.
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Antibacterianos , Staphylococcus aureus Resistente a Meticilina , Estilbenos , Animales , Humanos , Ratones , Células A549 , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Proteínas Bacterianas/metabolismo , Proteínas Bacterianas/genética , Redes Reguladoras de Genes/efectos de los fármacos , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Staphylococcus aureus Resistente a Meticilina/patogenicidad , Pruebas de Sensibilidad Microbiana , Neutrófilos/efectos de los fármacos , Infecciones Estafilocócicas/tratamiento farmacológico , Infecciones Estafilocócicas/microbiología , Virulencia/efectos de los fármacos , Estilbenos/farmacologíaRESUMEN
BACKGROUND: Trichinella spiralis (T. spiralis) is a parasitic helminth that causes a globally prevalent neglected zoonotic disease, and worms at different developmental stages (muscle larvae, adult worms, newborn larvae) induce immune attack at different infection sites, causing serious harm to host health. Several innate immune cells release extracellular traps (ETs) to entrap and kill most pathogens that invade the body. In response, some unicellular pathogens have evolved a strategy to escape capture by ETs through the secretion of nucleases, but few related studies have investigated multicellular helminths. RESULTS: In the present study, we observed that ETs from neutrophils capture adult worms of T. spiralis, while ETs from macrophages trap muscle larvae and newborn larvae, and ETs had a killing effect on parasites in vitro. To defend against this immune attack, T. spiralis secretes plancitoxin-1, a DNase II-like protein, to degrade ETs and escape capture, which is essential for the survival of T. spiralis in the host. CONCLUSIONS: In summary, these findings demonstrate that T. spiralis escapes ET-mediated capture by secreting deoxyribonuclease as a potential conserved immune evasion mechanism, and plancitoxin-1 could be used as a potential vaccine candidate.
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Trampas Extracelulares , Evasión Inmune , Trichinella spiralis , Animales , Trampas Extracelulares/inmunología , Trampas Extracelulares/metabolismo , Proteínas del Helminto/metabolismo , Larva/inmunología , Larva/parasitología , Trichinella spiralis/fisiología , Trichinella spiralis/inmunologíaRESUMEN
Clonorchis sinensis is a significant zoonotic food-borne parasite that causes a range of hepatobiliary diseases, which in severe cases can even lead to cholangiocarcinoma. To explore new diagnostic and treatment strategies, the dynamic RNA regulatory processes across different developmental stages of C. sinensis were analyzed by using whole-transcriptome sequencing. The chromosomal-level genome of C. sinensis was used for sequence alignment and annotation. In this study, we identified a total of 59,103 RNAs in the whole genome, including 2,384 miRNAs, 25,459 mRNAs, 27,564 lncRNAs and 3,696 circRNAs. Differential expression analysis identified 6,556 differentially expressed mRNAs, 2,231 lncRNAs, 877 miRNAs and 20 circRNAs at different developmental stages. Functional enrichment analysis highlighted the critical role of microtubule-related biological processes in the growth and development of C. sinensis. And coexpression analysis revealed 97 lncRNAs and 85 circRNAs that were coexpressed with 42 differentially expressed mRNAs that associated with microtubules at different developmental stages of C. sinensis. The expression of the microtubule-related genes dynein light chain 2 (DLC2) and dynein light chain 4 (DLC4) increased with C. sinensis development, and DLC2/4 could be inhibited by albendazole. Finally, by constructing competing endogenous RNA (ceRNA) networks, the lncRNA-miRNA-mRNA and circRNA-miRNA-mRNA regulatory relationships were constructed, and the ceRNA networks of MSTRG.14258.5-novel_miR_2287-newGene_28215 and MSTRG.14258.5-novel_miR_2216-CSKR_109340 were verified. This study suggests, through whole transcriptome sequencing, that the context of microtubule regulation may play an essential role in the development and growth of C. sinensis.
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Clonorchis sinensis , Microtúbulos , Transcriptoma , Clonorchis sinensis/genética , Clonorchis sinensis/crecimiento & desarrollo , Animales , Microtúbulos/metabolismo , Microtúbulos/genética , MicroARNs/genética , MicroARNs/metabolismo , Perfilación de la Expresión Génica , ARN no Traducido/genética , Clonorquiasis/parasitología , ARN Mensajero/genética , ARN Mensajero/metabolismo , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismoRESUMEN
OBJECTIVE: To investigate the associations between parity (the number of offspring a female has borne) and cognitive function, depression, and chronic comorbidity in Western China. METHODS: A total of 846 women aged 50-55 years were included in the current analysis. Cognitive status was measured using a 10-item short portable mental status questionnaire (SPMSQ). Depressive symptoms were assessed using the 15-item geriatric depression scale (GDS-15). Other characteristics were self-reported. The associations between parity and cognitive decline, depression, and chronic comorbidity were analyzed using univariable and multivariable models. Multivariable models were adjusted for age, ethnic group, occupation, marital status, educational level, lifestyle factors, and sleeping time. RESULTS: Among the enrolled women, 26.71% were either childless or had one child, 47.40% had two children, 18.32% had three children, and 7.57% had ≥4 children. Compared to women with low parity, women with two or more children exhibited a higher risk of cognitive decline. Moreover, having four or more children was significantly associated with depression and chronic comorbidity. After adjusting covariates, women with three or more children exhibited a higher risk of cognitive decline than those with low parity. However, high parity was not significantly associated with depression or chronic comorbidity after adjustment for covariates. CONCLUSION: Our study showed that ≥3 children was associated with cognitive decline in women. Longitudinal studies are needed to evaluate this conclusion and to investigate the mechanisms involved. More importantly, families and societies should pay more attention to women's long-term health outcomes related to fertility.
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OBJECTIVE: To compare the ability of gadolinium ethoxybenzyl dimeglumine (Gd-EOB-DTPA) and gadobenate dimeglumine (Gd-BOPTA) to display the 3 major features recommended by the Liver Imaging Reporting and Data System (LI-RADS 2018v) for diagnosing hepatocellular carcinoma (HCC). MATERIALS AND METHODS: In this retrospective study, we included 98 HCC lesions that were scanned with either Gd-EOB-DTPA-MR or Gd-BOPTA-M.For each lesion, we collected multiple variables, including size and enhancement pattern in the arterial phase (AP), portal venous phase (PVP), transitional phase (TP), delayed phase (DP), and hepatobiliary phase (HBP). The lesion-to-liver contrast (LLC) was measured and calculated for each phase and then compared between the 2 contrast agents. A P value < .05 was considered statistically significant. The display efficiency of the LLC between Gd-BOPTA and Gd-EOB-DTPA for HCC features was evaluated by receiver operating characteristic (ROC) curve analysis. RESULTS: Between Gd-BOPTA and Gd-EOB-DTPA, significant differences were observed regarding the display efficiency for capsule enhancement and the LLC in the AP/PVP/DP (P < .05), but there was no significant difference regarding the LLC in the TP/HBP. Both Gd-BOPTA and Gd-EOB-DTPA had good display efficiency in each phase (AUCmin > 0.750). When conducting a total evaluation of the combined data across the 5 phases, the display efficiency was excellent (AUC > 0.950). CONCLUSION: Gd-BOPTA and Gd-EOB-DTPA are liver-specific contrast agents widely used in clinical practice. They have their own characteristics in displaying the 3 main signs of HCC. For accurate noninvasive diagnosis, the choice of agent should be made according to the specific situation.
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Carcinoma Hepatocelular , Medios de Contraste , Gadolinio DTPA , Neoplasias Hepáticas , Imagen por Resonancia Magnética , Meglumina , Compuestos Organometálicos , Curva ROC , Humanos , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/diagnóstico por imagen , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Masculino , Femenino , Meglumina/análogos & derivados , Persona de Mediana Edad , Anciano , Estudios Retrospectivos , Adulto , Aumento de la Imagen/métodos , Anciano de 80 o más AñosRESUMEN
OBJECTIVE: To compare the ability to depict MRI features of hepatobiliary agents in microvascular infiltration (MVI) of hepatocellular carcinoma (HCC) during different stages of dynamic enhancement MRI. MATERIALS AND METHODS: A retrospective study included 111 HCC lesions scanned with either Gd-EOB-DTPA or Gd-BOPTA. All cases underwent multiphase dynamic contrast-enhanced scanning before surgery, including arterial phase (AP), portal venous phase (PVP), transitional phase (TP), delayed phase (DP), and hepatobiliary phase (HBP). Two abdominal radiologists independently evaluated MRI features of MVI in HCC, such as peritumoral hyperenhancement, incomplete capsule, non-smooth tumor margins, and peritumoral hypointensity. Finally, the results were reviewed by the third senior abdominal radiologist. Chi-square (χ2) Inspection for comparison between groups. P < 0.05 is considered statistically significant. Receiver operating characteristic (ROC) curve was used to evaluate correlation with pathology, and the area under the curve (AUC) and 95% confidence interval (95% CI) were calculated. RESULTS: Among the four MVI evaluation signs, Gd-BOPTA showed significant differences in displaying two signs in the HBP (P < 0.05:0.000, 0.000), while Gd-EOB-DTPA exhibited significant differences in displaying all four signs (P < 0.05:0.005, 0.006, 0.000, 0.002). The results of the evaluations of the two contrast agents in the DP phase with incomplete capsulation showed the highest correlation with pathology (AUC: 0.843, 0.761). By combining the four MRI features, Gd-BOPTA and Gd-EOB-DTPA have correlated significantly with pathology, and Gd-BOPTA is better (AUC: 0.9312vs0.8712). CONCLUSION: The four features of hepatobiliary agent dynamic enhancement MRI demonstrate a good correlation with histopathological findings in the evaluation of MVI in HCC, and have certain clinical significance.
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Carcinoma Hepatocelular , Medios de Contraste , Gadolinio DTPA , Neoplasias Hepáticas , Imagen por Resonancia Magnética , Meglumina , Humanos , Carcinoma Hepatocelular/diagnóstico por imagen , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/patología , Masculino , Femenino , Estudios Retrospectivos , Imagen por Resonancia Magnética/métodos , Persona de Mediana Edad , Anciano , Meglumina/análogos & derivados , Compuestos Organometálicos , Adulto , Microvasos/diagnóstico por imagen , Microvasos/patología , Aumento de la Imagen/métodosRESUMEN
Clonorchis sinensis is an important food-borne zoonotic parasite that is highly associated with liver fibrosis and cholangiocarcinoma. Further understanding of the pathogenesis of C. sinensis, especially liver fibrosis, could help us develop novel strategies for controlling clonorchiasis. Poly (ADP-ribose) polymerase-1 (PARP-1) can induce cellular parthanatos which is reported to be involved in liver fibrosis. Currently, whether C. sinensis could activate PARP-1 signaling to induce parthanatos or whether parthanatos play a role in C. sinensis-induced liver fibrosis is not clear. In the present study, the expression of PARP-1 and parthanatos indicators were detected in C. sinensis-infected mouse liver and in human intrahepatic biliary epithelial cells (HiBEpiCs) incubated with excretory/secretory products (ESPs) of C. sinensis. To explore the role of PARP-1 in C. sinensis infection, PARP-1 inhibitor NMS-P118 was used to block PARP-1 expression in vivo and vitro. The mortality rate, body weight, worm load, liver and bile duct lesions as well as PARP-1 and parthanatos indicators in C57BL/6 mice infected with C. sinensis, or in HiBEpiCs incubated with C. sinensis ESPs and NMS-P118 were analyzed and compared to the group without NMS-P118. The results showed that C. sinensis infection induced the activation of PARP-1 signaling as well as the translocation of AIF and MIF into the nucleus in mouse liver. ESPs of C. sinensis could induce PARP-1 up-regulation, ATP depletion and DNA damage in HiBEpiCs, indicating that C. sinensis could induce parthanatos. Inhibiting PARP-1 with NMS-P118 significantly reduced liver fibrosis and the number of larvae, increased the survival rate and body weight gain of the mice infected with C. sinensis. In addition, NMS-P118 decreased the expression of PARP-1 and alleviated ATP depletion as well as DNA damage in HiBEpiCs incubated with ESPs of C. sinensis. Our data indicated that C. sinensis and its ESPs could activate PARP-1 signaling to induce cellular parthanatos. NMS-P118 treatment alleviated liver fibrosis and promoted survival of the mice by inhibiting PARP-1, which suggested that PARP-1 could be used as a potential therapeutic target against clonorchiasis.
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Clonorquiasis , Clonorchis sinensis , Daño del ADN , Cirrosis Hepática , Parthanatos , Poli(ADP-Ribosa) Polimerasa-1 , Transducción de Señal , Animales , Humanos , Masculino , Ratones , Clonorquiasis/parasitología , Clonorchis sinensis/fisiología , Hígado/parasitología , Hígado/patología , Cirrosis Hepática/parasitología , Poli(ADP-Ribosa) Polimerasa-1/metabolismo , Poli(ADP-Ribosa) Polimerasa-1/genéticaRESUMEN
Background: In 2022, the European Society for Clinical Nutrition and Metabolism (ESPEN) and the European Association for the Study of Obesity (EASO) launched a consensus on the diagnostic methods for sarcopenic obesity (SO). The study aimed to identify the prevalence and diagnostic agreement of SO using different diagnostic methods in a cohort of subjects from West China aged at least 50 years old. Methods: A large multi-ethnic sample of 4,155 participants from the West China Health and Aging Trend (WCHAT) study was analyzed. SO was defined according to the newly published consensus of the ESPEN/EASO. Furthermore, SO was diagnosed as a combination of sarcopenia and obesity. The criteria established by the Asian Working Group for Sarcopenia 2019 (AWGS2019) were used to define sarcopenia. Obesity was defined by four widely used indicators: percent of body fat (PBF), visceral fat area (VFA), waist circumference (WC), and body mass index (BMI). Cohen's kappa was used to analyze the diagnostic agreement of the above five diagnostic methods. Results: A total of 4,155 participants were part of the study, including 1,499 men (63.76 ± 8.23 years) and 2,656 women (61.61 ± 8.20 years). The prevalence of SO was 0.63-7.22% with different diagnostic methods. The diagnosis agreement of five diagnostic methods was poor-to-good (κ: 0.06-0.67). The consensus by the ESPEN/EASO had the poorest agreement with other methods (κ: 0.06-0.32). AWGS+VFA had the best agreement with AWGS+WC (κ = 0.67), and consensus by the ESPEN/EASO had the best agreement with AWGS+ PBF (κ = 0.32). Conclusion: The prevalence and diagnostic agreement of SO varies considerably between different diagnostic methods. AWGS+WC has the highest diagnostic rate in the diagnosis of SO, whereas AWGS+BMI has the lowest. AWGS+VFA has a relatively good diagnostic agreement with other diagnostic methods, while the consensus of the ESPEN/EASO has a poor diagnostic agreement. AWGS+PBF may be suitable for the alternative diagnosis of the 2022 ESPEN/EASO.
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Índice de Masa Corporal , Vida Independiente , Obesidad , Sarcopenia , Humanos , Masculino , Femenino , China/epidemiología , Persona de Mediana Edad , Sarcopenia/diagnóstico , Sarcopenia/epidemiología , Obesidad/diagnóstico , Obesidad/epidemiología , Anciano , Prevalencia , Circunferencia de la Cintura , Pueblos del Este de AsiaRESUMEN
Purpose: This study aimed to analyze the current medication treatment status for women with osteoporosis (OP) based on real-world prescription data from 2016 to 2021 in Chinese nine cities' tertiary Grade A hospital and systematically describe the medication treatment patterns in women with OP. Methods: Prescription information for female OP patients in nine cities (Beijing, Shanghai, Guangzhou, Hangzhou, Tianjin, Zhengzhou, Chengdu, Shenyang, Harbin) was extracted from the Hospital Prescription Analysis Collaboration Project Database of the Hospital Pharmacy Professional Committee of the Chinese Pharmaceutical Association. Statistical analysis was conducted to evaluate demographic characteristics and medication treatment patterns. Results: A total of 669,505 prescriptions for medication treatment of female OP patients were included in this study. The majority of patients were aged 60 to 99 years (69.79 %) followed by 50 to 59 years (18.81 %) and 40 to 49 years (6.69 %). Geographically, the highest concentration of patients was in North China (Beijing, Tianjin) (43.05 %) followed by East China (Shanghai, Hangzhou) (31.43 %). The top three prescribed medications were active vitamin D and its analogs (40.78 %), calcium supplements (32.51 %), and bisphosphonates (18.75 %). The prescription frequency of menopausal hormone therapy (MHT) was 0.31 %. The proportion of female OP patients receiving monotherapy and two drug combinations therapy is equivalent (about 37 %). Conclusion: The diagnosis and treatment of female OP patients in China showed regional variations. The most commonly prescribed medications for this population were calcitriol, calcium carbonate with vitamin D3, and alendronate sodium with vitamin D3. The use of MHT was relatively limited.
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Archaea produce unique membrane-spanning lipids (MSLs), termed glycerol dialkyl glycerol tetraethers (GDGTs), which aid in adaptive responses to various environmental challenges. GDGTs can be modified through cyclization, cross-linking, methylation, hydroxylation, and desaturation, resulting in structurally distinct GDGT lipids. Here, we report the identification of radical SAM proteins responsible for two of these modifications-a glycerol monoalkyl glycerol tetraether (GMGT) synthase (Gms), responsible for covalently cross-linking the two hydrocarbon tails of a GDGT to produce GMGTs, and a GMGT methylase (Gmm), capable of methylating the core hydrocarbon tail. Heterologous expression of Gms proteins from various archaea in Thermococcus kodakarensis results in the production of GMGTs in two isomeric forms. Further, coexpression of Gms and Gmm produces mono- and dimethylated GMGTs and minor amounts of trimethylated GMGTs with only trace GDGT methylation. Phylogenetic analyses reveal the presence of Gms homologs in diverse archaeal genomes spanning all four archaeal superphyla and in multiple bacterial phyla with the genetic potential to synthesize fatty acid-based MSLs, demonstrating that GMGT production may be more widespread than previously appreciated. We demonstrate GMGT production in three Gms-encoding archaea, identifying an increase in GMGTs in response to elevated temperature in two Archaeoglobus species and the production of GMGTs with up to six rings in Vulcanisaeta distributa. The occurrence of such highly cyclized GMGTs has been limited to environmental samples and their detection in culture demonstrates the utility of combining genetic, bioinformatic, and lipid analyses to identify producers of distinct archaeal membrane lipids.
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Archaea , Proteínas Arqueales , Filogenia , Proteínas Arqueales/metabolismo , Proteínas Arqueales/genética , Archaea/metabolismo , Archaea/genética , Thermococcus/metabolismo , Thermococcus/genética , Éteres de Glicerilo/metabolismo , Lípidos de la Membrana/metabolismo , Lípidos de la Membrana/biosíntesisRESUMEN
Hyperactivation of pro-inflammatory type 1 cytokines (e.g., tumor necrosis factor alpha [TNF-α] and interferon gamma [IFN-γ]) mirrors the inflammation of coronavirus disease 2019. Helminths could alleviate excessive immune responses. Here, helminth Trichinella spiralis (Ts) infection was shown to protect against TNF-α- and IFN-γ-induced shock. Mechanistically, Ts-induced protection was interleukin-9 (IL-9) dependent but not IL-4Rα. Recombinant IL-9 treatment not only improved the survival of wild-type mice with TNF-α- and IFN-γ-induced shock but also that of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected K18-human angiotensin-converting enzyme 2 (hACE2) mice, emphasizing the significance of IL-9 in alleviating cytokine storm syndromes during SARS-CoV-2 infection. Interestingly, Ts excretory/secretory (TsES)-induced protection was also observed in SARS-CoV-2 infection, indicating that identifying anti-inflammatory molecules from TsES could be a novel way to mitigate adverse pathological inflammation during pathogen infection.IMPORTANCESevere coronavirus disease 2019 (COVID-19) is linked to cytokine storm triggered by type 1 pro-inflammatory immune responses. TNF-α and IFN-γ shock mirrors cytokine storm syndromes, including COVID-19. Helminths (e.g., Trichinella spiralis, Ts) can potently activate anti-inflammatory type 2 immune response. Here, we found that helminth Ts-induced protection against TNF-α and IFN-γ shock was IL-9 dependent. Treatment with recombinant IL-9 could protect against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in K18-hACE2 mice. Helminth Ts excretory/secretory (TsES) products also ameliorated SARS-CoV-2 infection-related cytokine storm. In conclusion, our study emphasizes the significance of IL-9 in protecting from cytokine storm syndromes associated with SARS-CoV-2 infection. Anti-inflammatory molecules from TsES could be a new source to mitigate adverse pathological inflammation associated with infections, including COVID-19.
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COVID-19 , Síndrome de Liberación de Citoquinas , Interleucina-9 , SARS-CoV-2 , Trichinella spiralis , Animales , COVID-19/inmunología , Ratones , Síndrome de Liberación de Citoquinas/inmunología , Síndrome de Liberación de Citoquinas/tratamiento farmacológico , Trichinella spiralis/inmunología , SARS-CoV-2/inmunología , Humanos , Interleucina-9/metabolismo , Interleucina-9/inmunología , Interferón gamma/inmunología , Interferón gamma/metabolismo , Citocinas/metabolismo , Citocinas/inmunología , Factor de Necrosis Tumoral alfa/metabolismo , Factor de Necrosis Tumoral alfa/inmunología , Modelos Animales de Enfermedad , Triquinelosis/inmunología , Femenino , Ratones Endogámicos C57BL , Enzima Convertidora de Angiotensina 2/metabolismo , Enzima Convertidora de Angiotensina 2/genéticaRESUMEN
Plasmonic semiconductors with broad spectral response hold significant promise for sustainable solar energy utilization. However, the surface inertness limits the photocatalytic activity. Herein, a novel approach is proposed to improve the body crystallinity and increase the surface oxygen vacancies of plasmonic tungsten oxide by the combination of hydrochloric acid (HCl) regulation and light irradiation, which can promote the adsorption of tert-butyl alcohol (TBA) on plasmonic tungsten oxide and overcome the hindrance of the surface depletion layer in photocatalytic alcohol dehydration. Additionally, this process can concentrate electrons for strong plasmonic electron oscillation on the near surface, facilitating rapid electron transfer within the adsorbed TBA molecules for C-O bond cleavage. As a result, the activation barrier for TBA dehydration is significantly reduced by 93% to 6.0 kJ mol-1, much lower than that of thermocatalysis (91 kJ mol-1). Therefore, an optimal isobutylene generation rate of 1.8 mol g-1 h-1 (selectivity of 99.9%) is achieved. A small flow reaction system is further constructed, which shows an isobutylene generation rate of 12 mmol h-1 under natural sunlight irradiation. This work highlights the potential of plasmonic semiconductors for efficient photocatalytic alcohol dehydration, thereby promoting the sustainable utilization of solar energy.
RESUMEN
Splicing factor mutations are common in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), but how they alter cellular functions is unclear. We show that the pathogenic SRSF2P95H/+ mutation disrupts the splicing of mitochondrial mRNAs, impairs mitochondrial complex I function, and robustly increases mitophagy. We also identified a mitochondrial surveillance mechanism by which mitochondrial dysfunction modifies splicing of the mitophagy activator PINK1 to remove a poison intron, increasing the stability and abundance of PINK1 mRNA and protein. SRSF2P95H-induced mitochondrial dysfunction increased PINK1 expression through this mechanism, which is essential for survival of SRSF2P95H/+ cells. Inhibition of splicing with a glycogen synthase kinase 3 inhibitor promoted retention of the poison intron, impairing mitophagy and activating apoptosis in SRSF2P95H/+ cells. These data reveal a homeostatic mechanism for sensing mitochondrial stress through PINK1 splicing and identify increased mitophagy as a disease marker and a therapeutic vulnerability in SRSF2P95H mutant MDS and AML.
Asunto(s)
Leucemia Mieloide Aguda , Mitocondrias , Mitofagia , Proteínas Quinasas , Factores de Empalme Serina-Arginina , Animales , Humanos , Ratones , Sustitución de Aminoácidos , Línea Celular Tumoral , Neoplasias Hematológicas/genética , Neoplasias Hematológicas/patología , Neoplasias Hematológicas/metabolismo , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patología , Leucemia Mieloide Aguda/metabolismo , Mitocondrias/genética , Mitocondrias/metabolismo , Mitocondrias/patología , Mitofagia/genética , Mutación Missense , Síndromes Mielodisplásicos/genética , Síndromes Mielodisplásicos/patología , Síndromes Mielodisplásicos/metabolismo , Proteínas Quinasas/genética , Proteínas Quinasas/metabolismo , Empalme del ARN , Factores de Empalme Serina-Arginina/genética , Factores de Empalme Serina-Arginina/metabolismoRESUMEN
Sepsis is a disorder of immune regulation caused by pathogenic microorganisms. A large number of inflammatory factors and inflammatory mediators are released, resulting in systemic inflammatory response disorder and acute lung injury (ALI). Helminths infection activate Th2 cytokines and immunomodulatory pathways, which have the function of anti-infection effector molecules. The early infection of Trichinella spiralis (T. spiralis) was mainly intestinal phase. In this study, we explored the effect of intestinal phase infection of T. spiralis on LPS-induced ALI. Compared with control mice, the serum and lung tissues of T. spiralis infected mice had a significant decrease of Th1 inflammatory cytokines, a significant increase of Th2 anti-inflammatory cytokines, and a significant decrease of inflammatory cell infiltration in lung tissue. These results suggest that T. spiralis during the intestinal phase can act on distal organs (lung) and reduce LPS-induced lung inflammation, providing evidence for a potential new pathway for immune-mediated disease in helminths and a possible role for intestinal worms in the gut-lung axis.