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1.
Medicine (Baltimore) ; 103(38): e39586, 2024 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-39312372

RESUMO

Chronic ankle pain significantly impairs daily activities and athletic performance with osteochondral lesions of the talus (OLT) in Hepple stages IV and V, which are often causative factors. This study aimed to assess the efficacy and safety of autologous osteochondral transplantation (AOT) for the treatment of these conditions. This retrospective study was conducted from May 2020 to May 2023 at Cangzhou Traditional Chinese and Western Medicine Combined Hospital, including patients with a diagnosis of Hepple stage IV or V OLT confirmed by magnetic resonance imaging (MRI) and arthroscopy. Surgical interventions involved arthroscopic debridement, followed by AOT or limited arthrotomy based on the location and size of the lesion. Preoperative and postoperative evaluations used the Visual Analog Scale, American Orthopedic Foot and Ankle Society Ankle-Hindfoot Scale, MRI-Based Cartilage Repair Tissue Scoring, and the International Knee Documentation Committee Knee Evaluation Form. Statistical analysis was conducted using paired-sample t tests to compare the preoperative and postoperative data. Twenty patients were included, revealing significant postoperative improvements in Visual Analog Scale, American Orthopedic Foot and Ankle Society, and MRI-based cartilage repair tissue scores (P < .05). The radiographic findings suggested effective cartilage regeneration. No adverse effects were observed in the donor knee sites, as confirmed by the stable pre- and postoperative International Knee Documentation Committee Knee Evaluation Form scores. Recovery of physical abilities was achieved on average within 7.3 weeks for daily activities and 13.4 weeks for sports activities. AOT effectively treats Hepple stage IV-V OLT, improves ankle function, promotes cartilage regrowth, and allows quick resumption of daily and athletic activities without compromising donor-site integrity.


Assuntos
Transplante Ósseo , Condrócitos , Ílio , Transplante Autólogo , Humanos , Estudos Retrospectivos , Feminino , Masculino , Adulto , Transplante Ósseo/métodos , Transplante Autólogo/métodos , Ílio/transplante , Condrócitos/transplante , Periósteo/transplante , Tálus/cirurgia , Pessoa de Meia-Idade , Cartilagem Articular/cirurgia , Artroplastia Subcondral/métodos , Artroscopia/métodos , Imageamento por Ressonância Magnética , Desbridamento/métodos , Resultado do Tratamento , Adulto Jovem , Articulação do Tornozelo/cirurgia , Articulação do Tornozelo/diagnóstico por imagem
2.
Org Biomol Chem ; 2024 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-39302242

RESUMO

Reported here is a rapid and versatile synthetic approach towards the specific pentacyclic carbazolelactams related to calothrixin B. The crucial transformation is an acid-promoted cascade involving a dehydration/electrocyclization/C-N bond cleavage/lactamization sequence.

3.
J Stroke Cerebrovasc Dis ; : 108029, 2024 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-39307209

RESUMO

BACKGROUND AND PURPOSE: Malnutrition is associated with poor outcomes in different diseases. Our aim was to investigate whether measures of malnutrition could be used to predict 90-day outcomes in patients with vertebrobasilar artery occlusion (VBAO) undergoing endovascular treatment (EVT). METHODS: We retrospectively analyzed patients with VBAO who received EVT at three comprehensive stroke centers. Malnutrition was assessed using the controlling nutritional status (CONUT) score, geriatric nutritional risk index (GNRI), and prognostic nutritional index (PNI). Primary outcome was good functional outcome defined as modified Rankin Scale (mRS) 0-3 measured at 90 days. RESULTS: A total of 285 patients were enrolled, of which 260 (91.22%) met the requirements. According to the CONUT, GNRI, and PNI scores, the proportions of patients classified as moderately or severely malnourished were 7.3%, 3.08%, and 35%, respectively. In the multivariate regression model after adjusting for potential confounders, malnutrition (severe risk versus normal nutritional status) was significantly associated with an increased risk of poor prognosis for CONUT scores (adjusted odds ratio [OR]14.91, 95%CI, 1.69 - 131.71; P = 0.015), GNRI scores (adjusted [OR] 10.67, 1.17 - 96.93; P =0.036) and PNI scores (adjusted [OR] 4.61, 2.28 - 9.31; P< 0.001). Similar results were obtained when malnutrition scores were analyzed as continuous variables. Adding the 3 malnutrition measures to the risk reclassification that included traditional risk factors significantly improved the predictive value of 3-month poor prognosis. CONCLUSIONS: Our study showed that malnutrition may be associated with poor prognosis within 3 months of EVT in patients with VBAO.

4.
Interv Neuroradiol ; : 15910199241270653, 2024 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-39246035

RESUMO

BACKGROUND: To investigate the association between perfusion deficit, vessel wall characteristics, and risk of recurrent ischemic events in medically treated patients with chronic symptomatic anterior circulation large vessel occlusion. METHODS: We retrospectively reviewed chronic symptomatic patients due to anterior circulation large vessel occlusion in our center. All patients received multiparametric magnetic resonance imaging (including perfusion-weighted imaging and high-resolution vessel wall imaging) within 4 weeks to 3 months after symptom onset. The association between baseline clinical or imaging variables and recurrent ischemic events was assessed in bivariate models and multivariable logistic regression to identify independent predictors of recurrence. RESULTS: Among 71 enrolled patients, 21.1% (15/71) patients had recurrent ischemic events (nine ischemic strokes and six transient ischemic attacks) during a 2-year follow-up. In bivariate models, hypertension, occlusion with hyperintense signals, the presence of intraluminal thrombus, Tmax >4 s volume, Tmax >6 s volume, Tmax >8 s volume, and Tmax >10 s volume were associated with recurrence (all p < 0.05). In multivariate analysis, hypertension (p = 0.039, OR 10.057 (95% CI, 1.123-90.048)), higher deficit volume of Tmax >4 s (p = 0.011, OR 1.012 (95% CI, 1.003-1.021)) and occlusion with hyperintense signal (p = 0.030, OR 6.732 (95% CI, 1.200-37.772)) were still independent predictors of recurrent ischemic events. CONCLUSIONS: Besides hypertension history, higher deficit volume of Tmax >4 s and occlusion with hyperintense signal determined using multiparametric MRI are strongly associated with risk for recurrent ischemic events in medically treated patients with chronic symptomatic anterior circulation large vessel occlusion. Future studies are needed to determine the utility of revascularization strategies in such high-risk patients.

5.
Clin Ther ; 2024 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-39242322

RESUMO

PURPOSE: Reduced glutathione (GSH) is extensively used in clinical therapeutics due to its antioxidative and cytoprotective properties. It is essential in the management of various chronic and acute conditions and serves as an adjunct therapy in oncology. Despite its widespread use, the physical compatibility of GSH with other intravenous drugs during Y-site administration has not been thoroughly investigated, posing risks such as reduced efficacy and adverse reactions. This study fills this critical gap by examining the physical compatibility of GSH with 44 commonly used intravenous drugs in simulated Y-site administration with 0.9% sodium chloride injection (NS) and 5% dextrose injection, aiming to enhance patient safety and clinical outcomes. METHODS: Simulated Y-site administration was conducted in vitro by mixing 24 mg/mL of GSH with equal volumes of 44 diluted intravenous drugs. Physical compatibility was assessed by observing visual changes, checking for the Tyndall effect, measuring turbidity, and monitoring pH levels at 0, 0.5, 1, 2, and 4 hours post-mixing. Physical compatibility was defined as the absence of color changes, gas evolution, particulate formation, and the Tyndall effect within 4 hours, with turbidity changes of less than 0.5 nephelometric turbidity units from baseline and pH variations of less than 10% from initial values. FINDINGS: GSH exhibited physical incompatibility with 11 of the 44 intravenous drugs evaluated, while it remained compatible with 33 drugs over 4 hours. IMPLICATIONS: This study reveals that while GSH is physically compatible with the majority of tested intravenous drugs, incompatibilities with 11 drugs under simulated Y-site conditions necessitate rigorous compatibility testing prior to co-administration in clinical settings. These findings emphasize the importance of such testing to prevent potential treatment failures and adverse effects. Further research is needed to explore chemical stability and therapeutic efficacy in clinical settings, ensuring the safe and effective use of GSH in medical treatments.

6.
Nat Commun ; 15(1): 7671, 2024 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-39227588

RESUMO

Optoelectronic synapses, leveraging the integration of classic photo-electric effect with synaptic plasticity, are emerging as building blocks for artificial vision and photonic neuromorphic computing. However, the fundamental working principles of most optoelectronic synapses mainly rely on physical behaviors while missing chemical-electric synaptic processes critical for mimicking biorealistic neuromorphic functionality. Herein, we report a photoelectrochemical synaptic device based on p-AlGaN/n-GaN semiconductor nanowires to incorporate chemical-electric synaptic behaviors into optoelectronic synapses, demonstrating unparalleled dual-modal plasticity and chemically-regulated neuromorphic functions through the interplay of internal photo-electric and external electrolyte-mediated chemical-electric processes. Electrical modulation by implementing closed or open-circuit enables switching of optoelectronic synaptic operation between short-term and long-term plasticity. Furthermore, inspired by transmembrane receptors that connect extracellular and intracellular events, synaptic responses can also be effectively amplified by applying chemical modifications to nanowire surfaces, which tune external and internal charge behaviors. Notably, under varied external electrolyte environments (ion/molecule species and concentrations), our device successfully mimics chemically-regulated synaptic activities and emulates intricate oxidative stress-induced biological phenomena. Essentially, we demonstrate that through the nanowire photoelectrochemical synapse configuration, optoelectronic synapses can be incorporated with chemical-electric behaviors to bridge the gap between classic optoelectronic synapses and biological synapses, providing a promising platform for multifunctional neuromorphic applications.

7.
Dig Liver Dis ; 2024 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-39294045

RESUMO

OBJECTIVE: Non-cirrhotic porto-mesenteric vein thrombosis (NC-PMVT) is a rare but severe clinical condition. The study aims to assess the effectiveness and safety of transjugular intrahepatic portosystemic shunt (TIPS) coupled with dual-access thrombolysis in patients with acute severe NC-PMVT. METHODS: From January 2018 to February 2023, a total of 25 patients with acute severe NC-PMVT who were treated with TIPS in conjunction with mechanical thrombectomy and dual-access thrombolysis. The period of thrombolysis was determined by the improvement of clinical symptoms and vascular recanalization. The technical success, recanalization rate, clinical success, and procedure-related complications were analyzed. RESULTS: The technical success rate was 100 %. The median duration for thrombolytic catheter removal was 5 (IQR 3.5 - 7) days. Full and partial recanalization were accomplished in 10 (40 %) and 15 (60 %) patients respectively before discharge. No significant procedure-related complications were reported. The clinical success rate was 88 %, with a mortality rate of 12 %. Over a median follow-up of 8 months, 3/22 (13.64 %) patients had a recurrence of thrombosis; 1/22 (4.54 %) patients underwent partial intestinal resection one and a half months post-discharge; the remaining patients did not experience any portal hypertensive complications. CONCLUSION: The combination of TIPS and dual-access thrombolysis appears to be safe and effective for patients with acute severe NC-PMVT.

8.
Langmuir ; 2024 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-39302707

RESUMO

The flotation separation of galena from sphalerite was commonly implemented under pH > 10.5, which led to the consumption of lime. In this paper, 2-diethylamine-4-hydroxy-1,3,5-triazine-6-thiol (DEHTT) was synthesized and introduced as a highly selective collector to perform the depressant-free flotation separation of Pb/Zn sulfide minerals. The microflotation results indicated that 8.0 × 10-7 mol/L DEHTT recovered 94.17% galena and 26.67% sphalerite from their mixture at pH 8.5 regulated by Na2CO3, and under the same conditions, sodium isobutyl xanthate (SIBX) floated out 94.94% galena and 50.41% sphalerite, deducing a superior flotation selectivity of DEHTT in comparison to SIBX. In situ AFM images displayed the more preferable adsorption of DEHTT on galena in comparison to that on sphalerite. The results of adsorption thermodynamics and kinetics inferred that the adsorption of DEHTT onto the galena surface was a spontaneous endothermic chemical process. XPS further indicated that DEHTT combined with interface Pb atoms to form the -S-Pb and -O-Pb bonds. The special affinity of DEHTT to galena achieved the selective flotation separation of galena from sphalerite without the addition of lime and depressants.

9.
Opt Lett ; 49(18): 5192-5195, 2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-39270261

RESUMO

A metal surface with controllable infrared emissivity has a wide range of applications. However, a flexible and simple fabrication method is needed. Here, a controllable femtosecond laser self-deposition technology was developed to fabricate Al@AlOx core/shell micropillars (MPs) with diverse size distribution on the aluminum surface in a single-step operation under ambient conditions. By establishing a deterministic relationship between pulse-repetition frequency (PRF) and particle size distribution (PSD), we achieved continuous control of the infrared emissivity of the surface by lower PRF, ranging from low (0.31) to high (0.93). Additionally, by using higher PRF, we attained dual-band emissivity control, featuring high emissivity in the range of 10-14 µm and near-continuous change in the range of 2.5-10 µm.

10.
Int Immunopharmacol ; 141: 112990, 2024 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-39223062

RESUMO

Inflammatory bowel diseases (IBDs) are chronic, relapsing, and inflammatory disorders of the gastrointestinal tract characterized by abnormal immune responses. Recently, STING has emerged as a promising therapeutic target for various autoinflammatory diseases. However, few STING-selective small molecules have been investigated as novel strategies for IBD. In this study, we sought to examine the effects of PROTAC-based STING degrader SP23 on acute colitis and explore its underlying mechanism. SP23 treatment notably alleviates dextran sulfate sodium (DSS)-induced colitis. Pharmacological degradation of STING significantly reduced the production of inflammatory cytokines, such as TNF-α, IL-1ß, and IL-6, and inhibited macrophage polarization towards the M1 type. Furthermore, SP23 administration decreased the loss of tight junction proteins, including ZO-1, occludin, and claudin-1, and downregulated STING and NLRP3 signaling pathways in intestinal inflammation. In vitro, STING activated NLRP3 inflammasome-mediated pyroptosis in intestinal epithelial cells, which could be abrogated by SP23 and STING siRNA intervention. In conclusion, these findings provide new evidence for STING as a novel therapeutic target for IBD, and reveal that hyperactivation of STING could exaggerate colitis by inducing NLRP3/Caspase-1/GSDMD axis mediated intestinal epithelial cells pyroptosis.


Assuntos
Colite , Sulfato de Dextrana , Macrófagos , Proteínas de Membrana , Camundongos Endogâmicos C57BL , Proteína 3 que Contém Domínio de Pirina da Família NLR , Piroptose , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Animais , Piroptose/efeitos dos fármacos , Proteínas de Membrana/metabolismo , Proteínas de Membrana/genética , Colite/tratamento farmacológico , Colite/induzido quimicamente , Colite/imunologia , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Macrófagos/metabolismo , Camundongos , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/patologia , Mucosa Intestinal/metabolismo , Mucosa Intestinal/imunologia , Transdução de Sinais/efeitos dos fármacos , Inflamassomos/metabolismo , Citocinas/metabolismo , Masculino , Humanos , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Células Epiteliais/imunologia , Modelos Animais de Doenças , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico
11.
Am J Transl Res ; 16(8): 4208-4215, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39262756

RESUMO

OBJECTIVE: To explore the diagnostic value of nanopore sequencing technology for detecting nontuberculous mycobacterial pulmonary disease (NTM-PD) in bronchial alveolar lavage fluid (BALF). METHODS: A retrospective analysis was conducted on 83 patients with suspected NTM-PD admitted to Anhui Chest Hospital from January 2021 to November 2023. All patients underwent bronchoscopic examination, and BALF samples were collected for smear acid-fast staining, mycobacterial culture, and nanopore sequencing. The diagnostic efficiencies of these three methods were compared. RESULTS: Among these patients, 27 were diagnosed with NTM-PD, 43 with pulmonary tuberculosis (PTB), and 13 with other lung diseases (OLD). The sensitivity, specificity, positive and negative predictive value of nanopore sequencing for diagnosing NTM-PD were 88.9%, 87.5%, 77.4%, and 94.2%, respectively. Nanopore sequencing demonstrated significantly higher sensitivity than smear and culture methods. The area under the receiver operating characteristic (ROC) curve (AUC) for nanopore sequencing was 0.882, significantly higher than that of smear (0.547) and culture (0.658), with P values less than 0.05. CONCLUSION: Nanopore sequencing technology has high diagnostic efficiency for NTM-PD and can directly identify bacterial species, but specificity issues should be considered in clinical application.

12.
Sci Total Environ ; 953: 176158, 2024 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-39255941

RESUMO

Per- and polyfluoroalkyl substances (PFAS), known as "forever chemicals," are synthetic chemicals which have been used since the 1940s. Given their remarkable thermostability and chemical stability, PFAS have been widely utilized in commercial products, including textiles, surfactants, food packages, nonstick coatings, and fire-fighting foams. Thus, PFAS are widely distributed worldwide and have been detected in human urine, blood, breast milk, tissues and other substances. Growing concerns over the risks of PFAS, including their toxicity and carcinogenicity, have attracted people's attention. Recent reviews have predominantly emphasized advancements in the detection, adsorption, and degradation of PFAS through their chemical structures and toxic properties; however, further examination of the literature is needed to determine the link between PFAS exposure and cancer risk. Here, we introduced different PFAS detection methods based on sensors and liquid chromatography-mass spectrometry (LC-MS). Then, we discussed epidemiological investigations on PFAS levels and cancer risks in recent years, as well as the mechanisms underlying the carcinogenesis. Finally, we proposed the "4C principles" for ongoing exploration and refinement in this field. This review highlights PFAS-cancer associations to fill knowledge gaps and provide evidence-based strategies for future research.

13.
Front Oncol ; 14: 1437493, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39239270

RESUMO

Background: Several existing studies have shown a correlation between some of the blood and urine biomarkers and oral leukoplakia (OLK). However, the causality of this relationship remains uncertain. Thus, this study aimed to examine the causal association between 35 blood and urine biomarkers and OLK. Methods: Single nucleotide polymorphisms (SNPs) associated with 35 blood and urine biomarkers were selected as instrumental variables (IVs) using a two-sample Mendelian randomization(MR) study to assess the causal relationship between the biomarkers and the risk of oral leukoplakia. We used the inverse variance weighted (IVW) method as the main analysis. Furthermore, several sensitivity analyses were performed to assess heterogeneity, horizontal pleiotropy, and stability. Results: Based on the selection criteria of the Inverse Variance Weighted (IVW) method, the analysis found that 5 blood and urine biomarkers were significantly associated with the development of leukoplakia, of which the results of IVW showed that abnormalities of Apolipoprotein B (Apo B), Cholesterol, Low-density Lipoprotein (LDL), Triglycerides (TG) promoted the development of oral leukoplakia, and Non Albumin Protein (NAP) had a protective effect on the development of oral leukoplakia. We then performed a Bonferroni correction for these results, and after correction Apo B was still causally associated with the development of oral leukoplakia (IVW P<0.0007), whereas the other four biomarkers could only provide some evidence of predisposition. Conclusion: Our two-sample Mendelian randomization study supports the existence of a causal relationship between these five blood and urine biomarkers and the occurrence of oral leukoplakia, and provides evidence for a number of risk and protective factors for the development of oral leukoplakia; however, the definitive mechanisms for the occurrence and development of oral leukoplakia still remain to be elucidated, and further studies on these relevant mechanisms are still needed.

14.
J Colloid Interface Sci ; 678(Pt B): 570-577, 2024 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-39265329

RESUMO

Lithium-oxygen batteries (LOBs) have been widely studied because of their ultra-high energy density (∼3500 Wh kg-1). However, the reversibility and stability of LOBs are greatly limited by the sluggish kinetics of oxygen reduction/evolution reactions (ORR/OER) and severely parasitic reactions on oxygen electrodes. Electrolyte in LOBs plays an important role in the transport of reactive oxygen species and Li+, which greatly affects the kinetics and reversibility of the charging and discharging processes of batteries. In this work, perfluorooctane (PFO) is used as the additive in 1.0 M LiTFSI/TEGDEM electrolyte for LOBs to regulate the kinetics of oxygen electrode reactions. Due to the strong adsorption ability of PE toward oxygen, the oxygen concentration inside the electrolyte is greatly increased after the addition of PE. In addition, the PE-added electrolyte also exhibits superior electrochemical stability and is capable of triggering solution-mediated Li2O2 growth pathway during the discharge process of the LOBs. Therefore, with the increased oxygen concentration and the optimized electrode/electrolyte interface, the ORR/OER kinetics on the oxygen electrode is significantly promoted, which enables the LOBs with excellent energy efficiency and cycling life. This work provides a new idea for the design of oxygen-rich and high-performance electrolyte for lithium-oxygen batteries.

15.
Nucleic Acids Res ; 52(17): 10717-10729, 2024 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-39189451

RESUMO

African swine fever virus (ASFV) is one of the most important causative agents of animal diseases and can cause highly fatal diseases in swine. ASFV DNA polymerase (DNAPol) is responsible for genome replication and highly conserved in all viral genotypes showing an ideal target for drug development. Here, we systematically determined the structures of ASFV DNAPol in apo, replicating and editing states. Structural analysis revealed that ASFV DNAPol had a classical right-handed structure and showed the highest similarity to the structure of human polymerase delta. Intriguingly, ASFV DNAPol has a much longer fingers subdomain, and the thumb and palm subdomain form a unique interaction that has never been seen. Mutagenesis work revealed that the loss of this unique interaction decreased the enzymatic activity. We also found that the ß-hairpin of ASFV DNAPol is located below the template strand in the editing state, which is different from the editing structures of other known B family DNAPols with the ß-hairpin above the template strand. It suggests that B family DNAPols have evolved two ways to facilitate the dsDNA unwinding during the transition from replicating into editing state. These findings figured out the working mechanism of ASFV DNAPol and will provide a critical structural basis for the development of antiviral drugs.


Assuntos
Vírus da Febre Suína Africana , Microscopia Crioeletrônica , DNA Polimerase Dirigida por DNA , Modelos Moleculares , Vírus da Febre Suína Africana/enzimologia , Vírus da Febre Suína Africana/genética , DNA Polimerase Dirigida por DNA/química , DNA Polimerase Dirigida por DNA/genética , DNA Polimerase Dirigida por DNA/metabolismo , Animais , Suínos , Proteínas Virais/química , Proteínas Virais/metabolismo , Proteínas Virais/genética , Febre Suína Africana/virologia , Sequência de Aminoácidos
16.
Hepatol Commun ; 8(9)2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-39185904

RESUMO

BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) is strongly associated with obesity. Sex and age affect MASLD prevalence and pathophysiology. The use of animal models fed Western-style diets is vital for investigating the molecular mechanisms contributing to metabolic dysregulation and for facilitating novel drug target identification. However, the sex-associated and age-associated mechanisms underlying the pathophysiology remain poorly understood. This knowledge gap limits the development of personalized sex-specific and age-specific drug treatments. METHODS: Young (7 wk) and aged (52 wk) male and female mice were fed a high-fat diet (HFD) or low-fat diet. Liver metabolome (>600 molecules) and transcriptome profiles were analyzed. RESULTS: Male and female mice fed an HFD developed obesity, glucose intolerance, and hepatic steatosis. However, fasting blood glucose, insulin, and serum alanine aminotransferase levels were higher in males fed an HFD, indicating a more severe metabolic disease. In addition, males showed significant increases in liver diacylglycerides and glycosylceramides (known mediators of insulin resistance and fibrosis), and more changes in the transcriptome: extracellular matrix organization and proinflammatory genes were elevated only in males. In contrast, no major increase in damaging lipid classes was observed in females fed an HFD. However, aging affected the liver to a greater extent in females. Acylcarnitine levels were significantly reduced, suggestive of changes in fatty acid oxidation, and broad changes in the transcriptome were observed, including reduced oxidative stress response gene expression and alterations in lipid partitioning genes. CONCLUSIONS: Here, we show distinct responses to an HFD between males and females. Our study underscores the need for using both sexes in drug target identification studies, and characterizing the molecular mechanisms contributing to the MASLD pathophysiology in aging animals.


Assuntos
Dieta Hiperlipídica , Obesidade , Animais , Feminino , Masculino , Camundongos , Dieta Hiperlipídica/efeitos adversos , Fatores Sexuais , Fatores Etários , Obesidade/metabolismo , Obesidade/fisiopatologia , Modelos Animais de Doenças , Fígado/metabolismo , Fígado/fisiopatologia , Transcriptoma , Fígado Gorduroso/metabolismo , Fígado Gorduroso/fisiopatologia , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/fisiopatologia , Hepatopatia Gordurosa não Alcoólica/etiologia , Resistência à Insulina , Metaboloma , Intolerância à Glucose/fisiopatologia , Intolerância à Glucose/metabolismo
17.
Mar Drugs ; 22(8)2024 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-39195463

RESUMO

Currently, there is an urgent need for new antibacterial and antifungal agents to combat the growing challenge of antibiotic resistance. As the largest ecosystem on Earth, the marine ecosystem includes a vast array of microorganisms (primarily bacteria and fungi), plants, invertebrates, and vertebrates, making it a rich source of various antimicrobial compounds. Notably, terpenoids, known for their complex structures and diverse bioactivities, are a significant and promising group of compounds in the battle against bacterial and fungal infections. In the past five years, numerous antimicrobial terpenoids have been identified from marine organisms such as bacteria, fungi, algae, corals, sea cucumbers, and sponges. This review article provides a detailed overview of 141 terpenoids with antibacterial and/or antifungal properties derived from marine organisms between 2019 and 2024. Terpenoids, a diverse group of natural organic compounds derived from isoprene units, are systematically categorized based on their carbon skeleton structures. Comprehensive information is provided about their names, structures, biological sources, and the extent of their antibacterial and/or antifungal effectiveness. This review aims to facilitate the rapid identification and development of prospective antimicrobials in the pharmaceutical sector.


Assuntos
Organismos Aquáticos , Terpenos , Terpenos/farmacologia , Terpenos/química , Animais , Anti-Infecciosos/farmacologia , Anti-Infecciosos/química , Bactérias/efeitos dos fármacos , Humanos , Antibacterianos/farmacologia , Antibacterianos/química , Fungos/efeitos dos fármacos , Antifúngicos/farmacologia , Antifúngicos/química
18.
Microsyst Nanoeng ; 10(1): 118, 2024 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-39187505

RESUMO

The projected speckle-based three-dimensional digital image correlation method (3D-DIC) is being increasingly used in the reliability measurement of microelectronic packaging structures because of its noninvasive nature, high precision, and low cost. However, during the measurement of the thermal reliability of packaging structures, the thermal airflow generated by heating introduces distortions in the images captured by the DIC measurement system, impacting the accuracy and reliability of noncontact measurements. To address this challenge, a thermal airflow distortion correction model based on the transformer attention mechanism is proposed specifically for the measurement of thermal warpage in microelectronic packaging structures. This model avoids the oversmoothing issue associated with convolutional neural networks and the lack of physical constraints in generative adversarial networks, ensuring the precision of grayscale gradient changes in speckle patterns and minimizing adverse effects on DIC calculation accuracy. By inputting the distorted images captured by the DIC measurement system into the network, corrected images are obtained for 3D-DIC calculations, thus allowing the thermal warpage measurement results of the sample to be acquired. Through experiments measuring topography with customized step block specimens, the effectiveness of the proposed method in improving warpage measurement accuracy is confirmed; this is particularly true when captured images are affected by thermal airflow at 140 °C and 160 °C, temperatures commonly encountered in thermal reliability testing of packaging structures. The method successfully reduces the standard deviation from 9.829 to 5.943 µm and from 12.318 to 6.418 µm, respectively. The results demonstrate the substantial practical value of this method for measuring thermal warpage in microelectronic packaging structures.

19.
Zhonghua Nan Ke Xue ; 30(6): 525-530, 2024 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-39212362

RESUMO

OBJECTIVE: To observe the effect and safety of the traditional Chinese medicine (TCM) Linggui Formula (LGF) in the treatment of asthenospermia with kidney deficiency and blood stasis. METHODS: This randomized controlled trial included 90 cases of asthenospermia with kidney deficiency and blood stasis treated in our hospital from September 2022 to September 2023, 45 by oral medication with LGF (the trial group) and the other 45 with oral levocarnitine solution (the control group), all for 12 weeks. We followed up the patients for 12 weeks, recorded the semen parameters, TCM syndrome scores, sexual hormone levels, pregnancy rates, and DNA fragmentation index (DFI) of the patients, and compared them between the two groups before and after treatment. RESULTS: Totally, 82 of the patients completed the study, 42 in the trial and 40 in the control group. After treatment, the patients in the trial group showed significant increases in the percentage of progressively motile sperm (PMS) (from ï¼»19.25±3.08ï¼½% to ï¼»38.57±4.99ï¼½%, P< 0.05), total sperm motility (from ï¼»32.29±3.64ï¼½% to ï¼»46.50±4.77ï¼½%, P< 0.05) and sperm concentration (from ï¼»83.9±37.2ï¼½ to ï¼»95.1±34.9ï¼½× 106/ml ï¼½, P< 0.05), and so did the controls in PMS (from ï¼»19.75±4.28ï¼½% to ï¼»34.46±5.07ï¼½%, P< 0.05), total sperm motility (from ï¼»33.02±4.93ï¼½% to ï¼»43.11±4.72ï¼½%, P< 0.05) and sperm concentration (from ï¼»85.2±39.7ï¼½ to ï¼»88.1±35.2ï¼½ × 106/ml , P< 0.05), all even more significant in the trial than in the control group (P< 0.05). No statistically significant difference was observed in the semen volume either in the trial (from ï¼»3.38±0.38ï¼½ to ï¼»3.24±0.45ï¼½ ml, P> 0.05) or in the control group (from ï¼»3.46±0.52ï¼½ to ï¼»3.30±0.37ï¼½ ml, P> 0.05), or between the trial and control groups (P> 0.05), or in the sexual hormone levels, pregnancy rates, and sperm DFI between the two groups before and after treatment (P> 0.05). Both groups of patients had good safety profiles without serious adverse reactions. CONCLUSION: Linggui Formula can improve the percentage of PMS in asthenospermia patients with kidney deficiency and blood stasis, potentially enhancing pregnancy rates and with a good safety.


Assuntos
Astenozoospermia , Medicamentos de Ervas Chinesas , Motilidade dos Espermatozoides , Humanos , Masculino , Medicamentos de Ervas Chinesas/uso terapêutico , Medicamentos de Ervas Chinesas/administração & dosagem , Astenozoospermia/tratamento farmacológico , Motilidade dos Espermatozoides/efeitos dos fármacos , Adulto , Medicina Tradicional Chinesa/métodos , Taxa de Gravidez , Nefropatias/tratamento farmacológico , Nefropatias/complicações , Gravidez , Fragmentação do DNA
20.
Nat Med ; 30(9): 2679-2691, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39095595

RESUMO

While single-cell technologies have greatly advanced our comprehension of human brain cell types and functions, studies including large numbers of donors and multiple brain regions are needed to extend our understanding of brain cell heterogeneity. Integrating atlas-level single-cell data presents a chance to reveal rare cell types and cellular heterogeneity across brain regions. Here we present the Brain Cell Atlas, a comprehensive reference atlas of brain cells, by assembling single-cell data from 70 human and 103 mouse studies of the brain throughout major developmental stages across brain regions, covering over 26.3 million cells or nuclei from both healthy and diseased tissues. Using machine-learning based algorithms, the Brain Cell Atlas provides a consensus cell type annotation, and it showcases the identification of putative neural progenitor cells and a cell subpopulation of PCDH9high microglia in the human brain. We demonstrate the gene regulatory difference of PCDH9high microglia between hippocampus and prefrontal cortex and elucidate the cell-cell communication network. The Brain Cell Atlas presents an atlas-level integrative resource for comparing brain cells in different environments and conditions within the Human Cell Atlas.


Assuntos
Encéfalo , Caderinas , Análise de Célula Única , Transcriptoma , Humanos , Encéfalo/citologia , Encéfalo/metabolismo , Camundongos , Animais , Caderinas/genética , Caderinas/metabolismo , Microglia/metabolismo , Microglia/citologia , Células-Tronco Neurais/metabolismo , Células-Tronco Neurais/citologia , Protocaderinas , Atlas como Assunto , Hipocampo/citologia , Hipocampo/metabolismo , Aprendizado de Máquina , Comunicação Celular/genética
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