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1.
Plants (Basel) ; 13(13)2024 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-38999704

RESUMEN

Chrysanthemums are among the world's most popular cut flowers, with their color being a key ornamental feature. The formation of these colors can be influenced by high temperatures. However, the regulatory mechanisms that control the fading of chrysanthemum flower color under high-temperature stress remain unclear. This study investigates the impact of high temperatures on the color and biochemical responses of purple chrysanthemums. Four purple chrysanthemum varieties were exposed to both normal and elevated temperature conditions. High-temperature stress elicited distinct responses among the purple chrysanthemum varieties. 'Zi Feng Che' and 'Chrystal Regal' maintained color stability, whereas 'Zi Hong Tuo Gui' and 'Zi lian' exhibited significant color fading, particularly during early bloom stages. This fading was associated with decreased enzymatic activities, specifically of chalcone isomerase (CHI), dihydroflavonol 4-reductase (DFR), and anthocyanidin synthase (ANS), indicating a critical period of color development under heat stress. Additionally, the color fading of 'Zi Lian' was closely related to the increased activity of the peroxidase (POD) and polyphenol oxidase (PPO). Conversely, a reduction in ß-glucosidase (ßG) activity may contribute significantly to the color steadfastness of 'Zi Feng Che'. The genes Cse_sc027584.1_g010.1 (PPO) and Cse_sc031727.1_g010.1 (POD) might contribute to the degradation of anthocyanins in the petals of 'Zi Hong Tuo Gui' and 'Zi Lian' under high-temperature conditions, while simultaneously maintaining the stability of anthocyanins in 'Zi Feng Che' and 'Chrystal Regal' at the early bloom floral stage. The findings of this research provide new insights into the physiological and biochemical mechanisms by which chrysanthemum flower color responds to high-temperature stress.

2.
Front Optoelectron ; 17(1): 12, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38689035

RESUMEN

Since their inception, frequency combs generated in microresonators, known as microcombs, have sparked significant scientific interests. Among the various applications leveraging microcombs, soliton microcombs are often preferred due to their inherent mode-locking capability. However, this choice introduces additional system complexity because an initialization process is required. Meanwhile, despite the theoretical understanding of the dynamics of other comb states, their practical potential, particularly in applications like sensing where simplicity is valued, remains largely untapped. Here, we demonstrate controllable generation of sub-combs that bypasses the need for accessing bistable regime. And in a graphene-sensitized microresonator, the sub-comb heterodynes produce stable, accurate microwave signals for high-precision gas detection. By exploring the formation dynamics of sub-combs, we achieved 2 MHz harmonic comb-to-comb beat notes with a signal-to-noise ratio (SNR) greater than 50 dB and phase noise as low as - 82 dBc/Hz at 1 MHz offset. The graphene sensitization on the intracavity probes results in exceptional frequency responsiveness to the adsorption of gas molecules on the graphene of microcavity surface, enabling detect limits down to the parts per billion (ppb) level. This synergy between graphene and sub-comb formation dynamics in a microcavity structure showcases the feasibility of utilizing microcombs in an incoherent state prior to soliton locking. It may mark a significant step toward the development of easy-to-operate, systemically simple, compact, and high-performance photonic sensors.

3.
Anaesth Crit Care Pain Med ; 43(3): 101364, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38460889

RESUMEN

BACKGROUND: Hospitals with higher septic shock case volume demonstrated lower hospital mortality. We conducted this study to investigate whether this phenomenon was only caused by the increase in the number of admissions or the need to improve the medical care capacity in septic shock at the same time. METHODS: Seven-hundred and eighty-seven hospitals from China collected in a survey from January 1, 2021 to December 31, 2021. Medical care capacity for septic shock was explored by patients with septic shock in intensive care units (ICU) divided into beds, intensivists, and nurses respectively. MAIN RESULTS: The proportion of ICU patients with septic shock was negatively associated with the patient mortality of septic shock (Estimate [95%CI], -0.2532 [-0.5038, -0.0026]) (p-value 0.048). The ratios of patients with septic shock to beds, intensivists, and nurses were negatively associated with mortality of septic shock (Estimate [95%CI], -0.370 [-0.591, -0.150], -0.136 [-0.241, -0.031], and -0.774 [-1.158, -0.389]) (p-value 0.001, 0.011 and < 0.001). Severe pneumonia, the most common infection that caused a septic shock, correlated positively with its mortality (Estimate [95%CI], 0.1002 [0.0617, 0.1387]) (p-value < 0.001). CONCLUSIONS: Hospitals with higher medical care capacity for septic shock were associated with lower hospital mortality.


Asunto(s)
Mortalidad Hospitalaria , Unidades de Cuidados Intensivos , Choque Séptico , Humanos , Choque Séptico/mortalidad , Choque Séptico/terapia , Estudios Transversales , China/epidemiología , Unidades de Cuidados Intensivos/estadística & datos numéricos , Masculino , Femenino , Persona de Mediana Edad , Capacidad de Camas en Hospitales/estadística & datos numéricos , Cuidados Críticos/estadística & datos numéricos
4.
JCI Insight ; 9(6)2024 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-38358827

RESUMEN

Mutations in the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) gene lead to CF, a life-threating autosomal recessive genetic disease. While recently approved Trikafta dramatically ameliorates CF lung diseases, there is still a lack of effective medicine to treat CF-associated liver disease (CFLD). To address this medical need, we used a recently established CF rabbit model to test whether sotagliflozin, a sodium-glucose cotransporter 1 and 2 (SGLT1/2) inhibitor drug that is approved to treat diabetes, can be repurposed to treat CFLD. Sotagliflozin treatment led to systemic benefits to CF rabbits, evidenced by increased appetite and weight gain as well as prolonged lifespan. For CF liver-related phenotypes, the animals benefited from normalized blood chemistry and bile acid parameters. Furthermore, sotagliflozin alleviated nonalcoholic steatohepatitis-like phenotypes, including liver fibrosis. Intriguingly, sotagliflozin treatment markedly reduced the otherwise elevated endoplasmic reticulum stress responses in the liver and other affected organs of CF rabbits. In summary, our work demonstrates that sotagliflozin attenuates liver disorders in CF rabbits and suggests sotagliflozin as a potential drug to treat CFLD.


Asunto(s)
Fibrosis Quística , Hepatopatías , Animales , Conejos , Fibrosis Quística/complicaciones , Fibrosis Quística/tratamiento farmacológico , Fibrosis Quística/genética , Hepatopatías/complicaciones , Glicósidos , Cirrosis Hepática/tratamiento farmacológico , Cirrosis Hepática/complicaciones
5.
Int Immunopharmacol ; 126: 111327, 2024 Jan 05.
Artículo en Inglés | MEDLINE | ID: mdl-38056198

RESUMEN

INTRODUCTION: Phospholipase A2 receptor (PLA2R)-associated membranous nephropathy (MN) is a common cause of nephrotic syndrome in nondiabetic adults who are also within the common age group for malignancy. How to treat patients with PLA2R-associated MN and malignancy effectively and safely still requires careful consideration. The aim of our study was to examine the outcomes and safety of rituximab (RTX) in these patients. METHODS: Retrospective analysis of clinical data was performed on 15 patients with PLA2R-associated MN and malignancy. Patients were followed every 1-3 months for a minimum of 24 months. Clinical data were collected, including CD19+ B cells, anti-PLA2R antibodies, 24-hour urinary protein, serum albumin, and serum creatinine. The percentage of patients who achieved clinical remission and immunological remission was also measured. RESULTS: Among these 15 patients, 14 patients with solid tumors received treatment for malignant diseases with complete resection. One patient received chemotherapy for chronic myeloid leukemia, and achieved complete remission 36 months before the diagnosis of MN. There were 6 (40.00 %) patients who achieved complete remission and 14 (93.33 %) patients who achieved complete or partial remission at the last visit after RTX treatment. At the last visit, patients were clinically improved, as evidenced by significant improvements in anti-PLA2R antibody titer [2.00 (2.00, 2.00) vs 35.25 (11.18, 91.58) RU/ml, P = 0.002], 24-hour urine protein [0.39 (0.11, 2.28) vs 9.22 (4.47, 14.73) g/d, P = 0.001], and serum albumin [38.15 (34.80, 43.20) vs 23.70 (18.70, 25.70) g/L, P = 0.001]. During the follow-up, the renal function of those patients remained stable. Recurrence of malignant tumors or the occurrence of new tumor events were not observed. CONCLUSION: In this single-center retrospective study with a small sample size, RTX therapy might be an effective and safe treatment in patients with PLA2R-associated MN and malignancy.


Asunto(s)
Glomerulonefritis Membranosa , Neoplasias , Adulto , Humanos , Glomerulonefritis Membranosa/tratamiento farmacológico , Rituximab/uso terapéutico , Estudios Retrospectivos , Receptores de Fosfolipasa A2 , Autoanticuerpos , Neoplasias/complicaciones
6.
Adv Sci (Weinh) ; : e2304580, 2023 Nov 14.
Artículo en Inglés | MEDLINE | ID: mdl-37963852

RESUMEN

Improving the utilization of thermal energy is crucial in the world nowadays due to the high levels of energy consumption. One way to achieve this is to use phase change materials (PCMs) as thermal energy storage media, which can be used to regulate temperature or provide heating/cooling in various applications. However, PCMs have limitations like low thermal conductivity, leakage, and corrosion. To overcome these challenges, PCMs are encapsulated into microencapsulated phase change materials (MEPCMs) capsules/fibers. This encapsulation prevents PCMs from leakage and corrosion issues, and the microcapsules/fibers act as conduits for heat transfer, enabling efficient exchange between the PCM and its surroundings. Microfluidics-based MEPCMs have attracted intensive attention over the past decade due to the exquisite control over flow conditions and size of microcapsules. This review paper aims to provide an overview of the state-of-art progress in microfluidics-based encapsulation of PCMs. The principle and method of preparing MEPCM capsules/fibers using microfluidic technology are elaborated, followed by the analysis of their thermal and microstructure characteristics. Meanwhile, the applications of MEPCM in the fields of building energy conservation, textiles, military aviation, solar energy utilization, and bioengineering are summarized. Finally, the perspectives on MEPCM capsules/fibers are discussed.

7.
Front Med ; 2023 Nov 22.
Artículo en Inglés | MEDLINE | ID: mdl-37991709

RESUMEN

This cohort study was performed to explore the influence of intensive care unit (ICU) quality on in-hospital mortality of veno-venous (V-V) extracorporeal membrane oxygenation (ECMO)-supported patients in China. The study involved all V-V ECMO-supported patients in 318 of 1700 tertiary hospitals from 2017 to 2019, using data from the National Clinical Improvement System and China National Critical Care Quality Control Center. ICU quality was assessed by quality control indicators and capacity parameters. Among the 2563 V-V ECMO-supported patients in 318 hospitals, a significant correlation was found between ECMO-related complications and prognosis. The reintubation rate within 48 hours after extubation and the total ICU mortality rate were independent risk factors for higher in-hospital mortality of V-V ECMO-supported patients (cutoff: 1.5% and 7.0%; 95% confidence interval: 1.05-1.48 and 1.04-1.45; odds ratios: 1.25 and 1.23; P = 0.012 and P = 0.015, respectively). Meanwhile, the V-V ECMO center volume was a protective factor (cutoff of ≥ 50 cases within the 3-year study period; 95% confidence interval: 0.57-0.83, odds ratio: 0.69, P = 0.0001). The subgroup analysis of 864 patients in 11 high-volume centers further strengthened these findings. Thus, ICU quality may play an important role in improving the prognosis of V-V ECMO-supported patients.

8.
J Inflamm Res ; 16: 4399-4411, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37822530

RESUMEN

Introduction: Rituximab (RTX) has been shown to be effective in inducing immunological remission in patients with membranous nephropathy (MN). Some patients required more than one course of RTX to achieve immunological remission. Identifying patients who need more courses of RTX to achieve immunological remission is beneficial for better physician-patient communication, the assessment of treatment course, and the evaluation of medical costs. This study aims to establish a practical model to predict the probability of immunological remission after receiving one cycle of RTX. Methods: This study enrolled 106 patients from the First Affiliated Hospital of Zhengzhou University in the modeling group and 30 patients from Henan Provincial Hospital of Traditional Chinese Medicine in the external validation group. Patients in the modeling group were divided into responders or nonresponders according to whether they achieved immunological remission or not after following up for 6 months. A nomogram was established based on the results of logistic regression analysis. The predictive performance of the nomogram was evaluated by the area under the receiver operating characteristic curve (AUC), calibration curves, and decision curve analysis (DCAs). Results: In the modeling group, 75 (70.8%) patients achieved immunological remission within 6 months after receiving one cycle of RTX. Significant differences were observed between nonresponders and responders. Risk factors used in nomogram included PLA2R antibody, hemoglobin, and gender. The AUC value of nomogram was 0.797 (95% CI 0.701-0.894, P<0.001). The calibration curves demonstrated acceptable agreement between the predicted outcomes by the nomogram and the actual values. DCA curves showed good positive net benefits in the predictive model. The external validation also demonstrated the reliability of the prediction nomogram. Conclusion: A predictive nomogram including PLA2R antibody, hemoglobin, and gender may provide a basis to predict the doses of RTX needed in MN patients.

9.
Arterioscler Thromb Vasc Biol ; 43(12): 2285-2297, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-37823268

RESUMEN

BACKGROUND: Although single-cell RNA-sequencing is commonly applied to dissect the heterogeneity in human tissues, it involves the preparation of single-cell suspensions via cell dissociation, causing loss of spatial information. In this study, we employed high-resolution single-cell transcriptome imaging to reveal rare smooth muscle cell (SMC) types in human thoracic aortic aneurysm (TAA) tissue samples. METHODS: Single-molecule spatial distribution of transcripts from 140 genes was analyzed in fresh-frozen human TAA samples with region and sex-matched controls. In vitro studies and tissue staining were performed to examine human CART prepropeptide (CARTPT) regulation and function. RESULTS: We captured thousands of cells per sample including a spatially distinct CARTPT-expressing SMC subtype enriched in male TAA samples. Immunoassays confirmed human CART (cocaine- and amphetamine-regulated transcript) protein enrichment in male TAA tissue and truncated CARTPT secretion into cell culture medium. Oxidized low-density lipoprotein, a cardiovascular risk factor, induced CARTPT expression, whereas CARTPT overexpression in human aortic SMCs increased the expression of key osteochondrogenic transcription factors and reduced contractile gene expression. Recombinant human CART treatment of human SMCs further confirmed this phenotype. Alizarin red staining revealed calcium deposition in male TAA samples showing similar localization with human CART staining. CONCLUSIONS: Here, we demonstrate the feasibility of single-molecule imaging in uncovering rare SMC subtypes in the diseased human aorta, a difficult tissue to dissociate. We identified a spatially distinct CARTPT-expressing SMC subtype enriched in male human TAA samples. Our functional studies suggest that human CART promotes osteochondrogenic switch of aortic SMCs, potentially leading to medial calcification of the thoracic aorta.


Asunto(s)
Aneurisma de la Aorta Torácica , Calcinosis , Humanos , Masculino , Transcriptoma , Aneurisma de la Aorta Torácica/metabolismo , Aorta Torácica/metabolismo , Perfilación de la Expresión Génica/métodos , Calcinosis/metabolismo , Miocitos del Músculo Liso/metabolismo
10.
J Cardiovasc Transl Res ; 16(6): 1408-1416, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37672183

RESUMEN

Acute coronary syndrome (ACS) and atrial fibrillation (AF) often coexist in clinical practice, and patients with these conditions often have a critical illness with high risk of both ischemia and bleeding. This study aims to report potential molecular markers for predicting the efficacy based on a meta-analysis of microarray data from the GEO database. In 40 patients with acute coronary syndrome (ACS) and atrial fibrillation (AF) treated with PCI, P2RX1's effects on platelet aggregation, medication resistance, and predictive value were examined. Twenty up-regulated genes in peripheral blood samples of ACS and AF patients were down-regulated after PCI, while 7 down-regulated genes were up-regulated. ACS affected eight potential genes. P2RX1, one of the four LASSO analysis-retrieved disease characteristic genes, accurately predicted AF patients' thrombosis risk and PCI's anti-thrombotic impact. Therefore, P2RX1 may be a molecular marker to predict the effect of anti-thrombotic therapy in patients with ACS and AF after PCI.


Asunto(s)
Síndrome Coronario Agudo , Fibrilación Atrial , Intervención Coronaria Percutánea , Trombosis , Humanos , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/tratamiento farmacológico , Fibrilación Atrial/genética , Inhibidores de Agregación Plaquetaria/efectos adversos , Anticoagulantes/uso terapéutico , Intervención Coronaria Percutánea/efectos adversos , Síndrome Coronario Agudo/genética , Síndrome Coronario Agudo/terapia , Trombosis/inducido químicamente , Trombosis/complicaciones , Trombosis/tratamiento farmacológico
11.
Eur J Med Res ; 28(1): 372, 2023 Sep 25.
Artículo en Inglés | MEDLINE | ID: mdl-37749658

RESUMEN

BACKGROUND: Septic shock is a global public health burden. In addition to the improvement of the level of individual care, the improvement of the overall hospital quality control management is also an essential key aspect of the Surviving Sepsis Campaign (SSC). Using of antibiotics is a cornerstone in the treatment of septic shock, so we conducted this study to investigate the influence of antibiotics and pathogenic bacteria on the mortality of septic shock at the level of overall hospital in China. METHODS: This was an observational database study in 2021 enrolled the data of 787 hospitals from 31 provinces/municipalities/autonomous regions of Mainland China collected in a survey from January 1, 2021 to December 31, 2021. RESULTS: The proportion of ICU patients with septic shock was 3.55%, while the patient mortality of septic shock was 23.08%. While carbapenem was the most preferred antibiotic medication used in 459 of the 782 hospitals, the preference for carbapenem did not show significant effect on the patient mortality in the treatment of septic shock (p-value 0.59). Compared with patients with fermenting bacteria as the most common pathogenic bacteria causing septic shock, patients with non-fermenting bacteria had a higher mortality (p-value 0.01). CONCLUSIONS: Whether using carbapenem as the preferred antibiotic or not, did not show effect on the patient mortality of septic shock. Compared with patients with fermenting bacteria as the most common pathogenic bacteria, patients of septic shock with non-fermenting bacteria had a higher mortality.


Asunto(s)
Sepsis , Choque Séptico , Humanos , Carbapenémicos/uso terapéutico , Choque Séptico/tratamiento farmacológico , Antibacterianos/uso terapéutico , China/epidemiología
12.
Cell Rep ; 42(10): 113171, 2023 10 31.
Artículo en Inglés | MEDLINE | ID: mdl-37768825

RESUMEN

Atherosclerosis, a leading health concern, stems from the dynamic involvement of immune cells in vascular plaques. Despite its significance, the interplay between chromatin remodeling and transcriptional regulation in plaque macrophages is understudied. We discovered the reduced expression of Baf60a, a component of the switch/sucrose non-fermentable (SWI/SNF) chromatin remodeling complex, in macrophages from advanced plaques. Myeloid-specific Baf60a deletion compromised mitochondrial integrity and heightened adhesion, apoptosis, and plaque development. BAF60a preserves mitochondrial energy homeostasis under pro-atherogenic stimuli by retaining nuclear respiratory factor 1 (NRF1) accessibility at critical genes. Overexpression of BAF60a rescued mitochondrial dysfunction in an NRF1-dependent manner. This study illuminates the BAF60a-NRF1 axis as a mitochondrial function modulator in atherosclerosis, proposing the rejuvenation of perturbed chromatin remodeling machinery as a potential therapeutic target.


Asunto(s)
Aterosclerosis , Factores de Transcripción , Humanos , Aterosclerosis/genética , Ensamble y Desensamble de Cromatina , Regulación de la Expresión Génica , Homeostasis , Factores de Transcripción/genética , Factores de Transcripción/metabolismo
13.
Glob Chall ; 7(9): 2300063, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37745820

RESUMEN

The remarkable control function over the functional material formation process enabled by droplet microfluidic emulsification approaches can lead to the efficient and one-step encapsulation of active substances in microparticles, with the microparticle characteristics well regulated. In comparison to the conventional fabrication methods, droplet microfluidic technology can not only construct microparticles with various shapes, but also provide excellent templates, which enrich and expand the application fields of microparticles. For instance, intersection with disciplines in pharmacy, life sciences, and others, modifying the structure of microspheres and appending functional materials can be completed in the preparation of microparticles. The as-prepared polymer particles have great potential in a wide range of applications for chemical analysis, heavy metal adsorption, and detection. This review systematically introduces the devices and basic principles of particle preparation using droplet microfluidic technology and discusses the research of functional microparticle formation with high monodispersity, involving a plethora of types including spherical, nonspherical, and Janus type, as well as core-shell, hole-shell, and controllable multicompartment particles. Moreover, this review paper also exhibits a critical analysis of the current status and existing challenges, and outlook of the future development in the emerging fields has been discussed.

14.
Medicine (Baltimore) ; 102(26): e34066, 2023 Jun 30.
Artículo en Inglés | MEDLINE | ID: mdl-37390251

RESUMEN

This study aimed to determine whether there is an association between the age at menopause (AM) and diabetic microvascular complications. This cross-sectional study included 298 postmenopausal women with type 2 diabetes mellitus. They were divided into 3 groups according to AM (in years; group 1: AM < 45 years, n = 32; group 2:45 ≤ AM < 50 years, n = 102; group 3: AM ≥ 50 years, n = 164). Clinical data related to the duration of type 2 diabetes, body mass index, smoking status, hypertension status, AM, biochemical indices, and diabetic microvascular complications (retinopathy, nephropathy, and neuropathy) were collected. Logistic regression analysis was performed to identify the association between the AM and diabetic microvascular complications. No statistical differences were observed in the prevalence of diabetic retinopathy, chronic kidney disease, or diabetic peripheral neuropathy between the groups. After adjusting for possible confounders, AM did not correlate with the presence of diabetic retinopathy (ß = 1.03, 95% confidence interval [CI]: 0.94-1.14, P = .511), chronic kidney disease (ß = 1.04, 95% CI: 0.97-1.12, P = .280), and diabetic peripheral neuropathy (ß = 1.01, 95% CI: 0.93-1.09, P = .853). Our findings suggest that early menopause (age < 45 years) was not associated with microvascular diabetic complications. Further prospective studies are needed to clarify this issue.


Asunto(s)
Diabetes Mellitus Tipo 2 , Neuropatías Diabéticas , Retinopatía Diabética , Insuficiencia Renal Crónica , Humanos , Femenino , Persona de Mediana Edad , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/epidemiología , Neuropatías Diabéticas/epidemiología , Neuropatías Diabéticas/etiología , Estudios Transversales , Retinopatía Diabética/epidemiología , Retinopatía Diabética/etiología
15.
JCI Insight ; 8(14)2023 07 24.
Artículo en Inglés | MEDLINE | ID: mdl-37289544

RESUMEN

Specific and efficient smooth muscle cell-targeted (SMC-targeted) gene deletion is typically achieved by pairing SMMHC-CreERT2-Tg mice with mice carrying the loxP-flanked gene. However, the transgene, CreERT2, is not controlled by the endogenous Myh11 gene promoter, and the codon-modified iCreERT2 exhibits significant tamoxifen-independent leakage. Furthermore, because the Cre-bearing bacterial artificial chromosome (BAC) is inserted onto the Y chromosome, the SMMHC-CreERT2-Tg mice strain can only exhibit gene deletions in male mice. Additionally, there is a lack of Myh11-driven constitutive Cre mice when tamoxifen usage is a concern. We used CRISPR/Cas9-mediated homologous recombination between a donor vector carrying the CreNLSP2A or CreERT2-P2A sequence and homologous arm surrounding the translation start site of the Myh11 gene to generate Cre-knockin mice. The P2A sequence enables the simultaneous translation of Cre and endogenous proteins. Using reporter mice, we assessed Cre-mediated recombination efficiency, specificity, tamoxifen-dependent controllability, and functionality in both sexes. Both constitutive (Myh11-CreNLSP2A) and inducible (Myh11-CreERT2-P2A) Cre mice demonstrated efficient, SMC-specific, sex-independent Cre recombinase activity without confounding endogenous gene expression. Combined with recently generated BAC transgenic Myh11-CreERT2-RAD mice and the Itga8-CreERT2 mouse models, our models will help expand the research toolbox, facilitating unbiased and comprehensive research in SMCs and SMC-dependent cardiovascular diseases.


Asunto(s)
Miocitos del Músculo Liso , Tamoxifeno , Femenino , Ratones , Masculino , Animales , Eliminación de Gen , Ratones Transgénicos , Tamoxifeno/farmacología
16.
Sci Rep ; 13(1): 6740, 2023 04 25.
Artículo en Inglés | MEDLINE | ID: mdl-37185370

RESUMEN

To evaluate the efficacy and safety of rituximab (RTX) in the treatment of primary focal segmental glomerulosclerosis (FSGS) in adults. The clinical data of patients with primary FSGS who received RTX treatment in the First Affiliated Hospital of Zhengzhou University were analyzed retrospectively. The selected patients received RTX twice or four times, with a single dose of 375 mg/m2, and the interval between two times of administration of RTX was 2-4 weeks. The treatment target is to achieve the clearance of B cells (peripheral blood B cell count < 5/µl). The primary outcome measures were remission and recurrence of renal disease, and the secondary outcome measures were adverse events and renal outcomes. A total of 14 FSGS patients were included, including 12 males, 9 with glucocorticoid-dependent or frequently relapsing nephrotic syndrome, and 3 with newly diagnosed nephrotic syndrome. After RTX treatment, 7 patients with glucocorticoid-dependent/recurrent nephrotic syndrome were completely relieved. At 6 months of follow-up, glucocorticoids were discontinued in all patients except 1 patient. The other 5 patients achieved partial remission (PR), of which 1 patient relapsed after PR, and 1 initial patient achieved complete remission. One patient progressed to end-stage renal disease (ESRD) after 4 months of follow-up. RTX in the treatment of adult glucocorticoid-dependent/relapsing FSGS can reduce the risk of recurrence and help to decline or discontinue the use of glucocorticoid and immunosuppressants.


Asunto(s)
Glomeruloesclerosis Focal y Segmentaria , Síndrome Nefrótico , Masculino , Humanos , Adulto , Rituximab/efectos adversos , Glomeruloesclerosis Focal y Segmentaria/complicaciones , Síndrome Nefrótico/tratamiento farmacológico , Síndrome Nefrótico/complicaciones , Glucocorticoides/uso terapéutico , Estudios Retrospectivos , Recurrencia , Resultado del Tratamiento
17.
Phys Rev Lett ; 130(15): 153802, 2023 Apr 14.
Artículo en Inglés | MEDLINE | ID: mdl-37115887

RESUMEN

Solitons in microresonators have spurred intriguing nonlinear optical physics and photonic applications. Here, by combining Kerr and Brillouin nonlinearities in an over-modal microcavity, we demonstrate spatial multiplexing of soliton microcombs under a single external laser pumping operation. This demonstration offers an ideal scheme to realize highly coherent dual-comb sources in a compact, low-cost and energy-efficient manner, with uniquely low beating noise. Moreover, by selecting the dual-comb modes, the repetition rate difference of a dual-comb pair could be flexibly switched, ranging from 8.5 to 212 MHz. Beyond dual-comb, the high-density mode geometry allows the cascaded Brillouin lasers, driving the co-generation of up to 5 space-multiplexing frequency combs in distinct mode families. This Letter offers a novel physics paradigm for comb interferometry and provides a widely appropriate tool for versatile applications such as comb metrology, spectroscopy, and ranging.

18.
JCI Insight ; 8(11)2023 06 08.
Artículo en Inglés | MEDLINE | ID: mdl-37079380

RESUMEN

Abdominal aortic aneurysm (AAA) is usually asymptomatic until life-threatening complications occur, predominantly involving aortic rupture. Currently, no drug-based treatments are available, primarily due to limited understanding of AAA pathogenesis. The transcriptional regulator PR domain-containing protein 16 (PRDM16) is highly expressed in the aorta, but its functions in the aorta are largely unknown. By RNA-seq analysis, we found that vascular smooth muscle cell-specific (VSMC-specific) Prdm16-knockout (Prdm16SMKO) mice already showed extensive changes in the expression of genes associated with extracellular matrix (ECM) remodeling and inflammation in the abdominal aorta under normal housing conditions without any pathological stimuli. Human AAA lesions displayed lower PRDM16 expression. Periadventitial elastase application to the suprarenal region of the abdominal aorta aggravated AAA formation in Prdm16SMKO mice. During AAA development, VSMCs undergo apoptosis because of both intrinsic and environmental changes, including inflammation and ECM remodeling. Prdm16 deficiency promoted inflammation and apoptosis in VSMCs. A disintegrin and metalloproteinase 12 (ADAM12) is a gelatinase that can degrade various ECMs. We found that ADAM12 is a target of transcriptional repression by PRDM16. Adam12 knockdown reversed VSMC apoptosis induced by Prdm16 deficiency. Our study demonstrated that PRDM16 deficiency in VSMCs promoted ADAM12 expression and aggravates AAA formation, which may provide potential targets for AAA treatment.


Asunto(s)
Aneurisma de la Aorta Abdominal , Músculo Liso Vascular , Ratones , Animales , Humanos , Músculo Liso Vascular/patología , Aneurisma de la Aorta Abdominal/metabolismo , Aorta Abdominal/patología , Inflamación/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo
19.
Sci Rep ; 13(1): 3373, 2023 02 27.
Artículo en Inglés | MEDLINE | ID: mdl-36849534

RESUMEN

Septic shock, largely caused by intestinal perforation, is a common critical disease in intensive care unit (ICU). For hospitals and health systems, a performance improvement program for sepsis was strong recommended in guidelines. Numerous studies have shown that improved quality control improves outcomes in patients with septic shock. Nevertheless, association between quality control and outcomes of septic shock caused by intestinal perforation are not fully revealed. Thus we designed this study to investigate effects of quality control on septic shock caused by intestinal perforation in China. This was a multicenter observational study. A total of 463 hospitals were enrolled in this survey, led by the China National Critical Care Quality Control Center (China-NCCQC) from January 1, 2018 to December 31, 2018. In this study, the indicators of quality control included the proportion of ICU patient bed occupancy to total inpatient bed occupancy, the proportion of ICU patients with APACHE II score ≥ 15, and the microbiology detection rate before antibiotic use. The outcome indicators included hospital stays, hospitalization costs, complications, and mortality. Generalized linear mixed models were used to analyse the association between quality control and septic shock caused by intestinal perforation. The proportion of ICU patient bed occupancy to total inpatient bed occupancy is positively correlated with hospital stays, incidence of complications (ARDS, AKI) and costs in septic shock caused by intestinal perforation (p < 0.05). The proportion of ICU patients with APACHE II score ≥ 15 was not associated with hospital stays and incidence of ARDS and AKI (p < 0.05). Increasing of the proportion of ICU patients with APACHE II score ≥ 15 decreased the costs of patients with septic shock caused by intestinal perforation (p < 0.05). The microbiology detection rate before antibiotic use was not associated with hospital stays, incidence of AKI and costs of patients with septic shock caused by intestinal perforation (p < 0.05). Surprisingly, the increase of microbiology detection rate before antibiotic use increased the incidence of ARDS in patients with septic shock caused by intestinal perforation (p < 0.05). The above three indicators of quality control were not associated with mortality of the patients with septic shock caused by intestinal perforation. On the one hand, the number of ICU patients admitted should be controlled to reduce the proportion of ICU patients out of total inpatient bed occupancy. On the other hand, intensive care unit admission of severe patients (patients with APACHE II score ≥ 15) should be encouraged to improve the proportion of patients with APACHE II score ≥ 15 in the ICU, so that ICU can focus more on the treatment of severe patients and promote the professionalization of severe patient management. It is not advisable to collect sputum specimens too frequently for patients without pneumonia.


Asunto(s)
Lesión Renal Aguda , Perforación Intestinal , Síndrome de Dificultad Respiratoria , Choque Séptico , Humanos , Choque Séptico/complicaciones , Estudios Transversales , Perforación Intestinal/complicaciones , Perforación Intestinal/epidemiología , Antibacterianos , China/epidemiología , Control de Calidad
20.
Diabetes Metab Syndr Obes ; 16: 179-186, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36760594

RESUMEN

Background: Branched chain amino acids (BCAAs) have been revealed to be closely related to insulin resistance and obesity. This study aimed to investigate if BCAA levels at baseline are related to an improvement in insulin resistance after implementing a weight loss program intervention. Methods: Stored blood samples from participants in previous trials were used for BCAA evaluation. Linear regression was used to analyze the relationship between baseline amino acid levels and changes in the insulin resistance index (HOMA-IR) and blood glucose. Results: A total of 48 participants were enrolled. After the intervention, the body weight (78.29± 12.68 vs 72.06 ± 13.30 kg, p=0.020), fasting glucose (4.76 ± 0.43 vs 4.48 ± 0.39 mmol/L, p=0.001), fasting insulin (18.41±13.58 vs 12.87±10.88, p=0.028), and HOMA-IR (4.01±3.39 vs 2.62± 2.18, p=0.018) were improved significantly. BCAA levels were related to the improvement in HOMA-IR (ß=-0.006, p=0.039), and valine was found to be the most closely related to the improvement in HOMA-IR (ß=-0.013, p=0.017). Conclusion: The baseline BCAA is related to the improvement in insulin resistance among participants after a weight loss intervention.

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