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1.
Exp Neurol ; : 115044, 2024 Nov 04.
Artículo en Inglés | MEDLINE | ID: mdl-39505249

RESUMEN

AIMS: Postoperative delirium (POD) is a common complication of anesthesia and surgery, with a higher incidence in elderly patients. Disruption of the blood-brain barrier (BBB) is considered one of the key mechanisms underlying POD. Therefore, the present study aimed to investigate the effects of different BBB permeability alteration pathways on POD in mice of various ages. METHODS: C57BL/6 J mice aged 4 and 16 months underwent exploratory laparotomy under sevoflurane anesthesia. Behavioral tests were conducted 24 h prior to surgery, as well as 6, 9, and 24 h postoperatively. Frontal cortex tissue was collected to detect the levels of BBB-related proteins and mRNA. RESULTS: At 6 and 9 h after anesthesia/surgery, 4-month-old mice showed poorer performance on behavioral tests than their untreated counterparts. However, 16-month-old mice exhibited worse behavioral test results at 6, 9, and 24 h after surgery. Anesthesia/surgery 6 h postoperatively increased the expression of vesicle-associated proteins, and BBB leakage in 4-month-old mice. In 16-month-old mice, anesthesia/surgery altered the expression of tight junction proteins, vesicle-associated proteins, and BBB leakage at 6 and 24 h postoperatively. CONCLUSION: Overall, our results suggest that anesthesia/surgery leads to age-dependent cognitive decline, and is associated with differences in the BBB injury pathways among mice of different ages. The transcellular pathway (transcytosis), compared to the paracellular pathway (tight junction), is more vulnerable to damage following anesthesia/surgery. This study provides new evidence for the improvement of POD through protection of the BBB.

2.
Stem Cell Reports ; 19(9): 1320-1335, 2024 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-39151429

RESUMEN

The homeostasis of human pluripotent stem cells (hPSCs) requires the signaling balance of extracellular factors. Exogenous regulators from cell culture medium have been widely reported, but little attention has been paid to the autocrine factor from hPSCs themselves. In this report, we demonstrate that extracellular signal-related kinase 5 (ERK5) regulates endogenous autocrine factors essential for pluripotency and differentiation. ERK5 inhibition leads to erroneous cell fate specification in all lineages even under lineage-specific induction. hPSCs can self-renew under ERK5 inhibition in the presence of fibroblast growth factor 2 (FGF2) and transforming growth factor ß (TGF-ß), although NANOG expression is partially suppressed. Further analysis demonstrates that ERK5 promotes the expression of autocrine factors such as NODAL, FGF8, and WNT3. The addition of NODAL protein rescues NANOG expression and differentiation phenotypes under ERK5 inhibition. We demonstrate that constitutively active ERK5 pathway allows self-renewal even without essential growth factors FGF2 and TGF-ß. This study highlights the essential contribution of autocrine pathways to proper maintenance and differentiation.


Asunto(s)
Comunicación Autocrina , Proteína Quinasa 7 Activada por Mitógenos , Proteína Homeótica Nanog , Células Madre Pluripotentes , Humanos , Diferenciación Celular , Línea Celular , Linaje de la Célula , Proliferación Celular , Autorrenovación de las Células , Factor 2 de Crecimiento de Fibroblastos/metabolismo , Factor 2 de Crecimiento de Fibroblastos/farmacología , Proteína Quinasa 7 Activada por Mitógenos/metabolismo , Proteína Quinasa 7 Activada por Mitógenos/genética , Proteína Homeótica Nanog/metabolismo , Proteína Homeótica Nanog/genética , Proteína Nodal/metabolismo , Células Madre Pluripotentes/metabolismo , Células Madre Pluripotentes/citología , Transducción de Señal , Factor de Crecimiento Transformador beta/metabolismo
3.
Stem Cell Reports ; 19(9): 1304-1319, 2024 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-39178847

RESUMEN

Effective lineage-specific differentiation is essential to fulfilling the great potentials of human pluripotent stem cells (hPSCs). In this report, we investigate how modulation of medium pH and associated metabolic changes influence mesendoderm differentiation from hPSCs. We show that daily medium pH fluctuations are critical for the heterogeneity of cell fates in the absence of exogenous inducers. Acidic environment alone leads to cardiomyocyte generation without other signaling modulators. In contrast, medium alkalinization is inhibitory to cardiac fate even in the presence of classic cardiac inducers. We then demonstrate that acidic environment suppresses glycolysis to facilitate cardiac differentiation, while alkaline condition promotes glycolysis and diverts the differentiation toward other cell types. We further show that glycolysis inhibition or AMPK activation can rescue cardiac differentiation under alkalinization, and glycolysis inhibition alone can drive cardiac cell fate. This study highlights that pH changes remodel metabolic patterns and modulate signaling pathways to control cell fate.


Asunto(s)
Diferenciación Celular , Glucólisis , Miocitos Cardíacos , Células Madre Pluripotentes , Humanos , Diferenciación Celular/efectos de los fármacos , Células Madre Pluripotentes/metabolismo , Células Madre Pluripotentes/citología , Células Madre Pluripotentes/efectos de los fármacos , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/citología , Miocitos Cardíacos/efectos de los fármacos , Concentración de Iones de Hidrógeno , Acidosis/metabolismo , Endodermo/citología , Endodermo/metabolismo , Linaje de la Célula/efectos de los fármacos , Mesodermo/citología , Mesodermo/metabolismo , Medios de Cultivo/farmacología , Medios de Cultivo/química , Transducción de Señal/efectos de los fármacos , Línea Celular , Proteínas Quinasas Activadas por AMP/metabolismo
4.
Nat Genet ; 56(7): 1503-1515, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38834904

RESUMEN

Unlike megabats, which rely on well-developed vision, microbats use ultrasonic echolocation to navigate and locate prey. To study ultrasound perception, here we compared the auditory cortices of microbats and megabats by constructing reference genomes and single-nucleus atlases for four species. We found that parvalbumin (PV)+ neurons exhibited evident cross-species differences and could respond to ultrasound signals, whereas their silencing severely affected ultrasound perception in the mouse auditory cortex. Moreover, megabat PV+ neurons expressed low levels of complexins (CPLX1-CPLX4), which can facilitate neurotransmitter release, while microbat PV+ neurons highly expressed CPLX1, which improves neurotransmission efficiency. Further perturbation of Cplx1 in PV+ neurons impaired ultrasound perception in the mouse auditory cortex. In addition, CPLX1 functioned in other parts of the auditory pathway in microbats but not megabats and exhibited convergent evolution between echolocating microbats and whales. Altogether, we conclude that CPLX1 expression throughout the entire auditory pathway can enhance mammalian ultrasound neurotransmission.


Asunto(s)
Corteza Auditiva , Vías Auditivas , Proteínas del Tejido Nervioso , Transmisión Sináptica , Animales , Masculino , Ratones , Corteza Auditiva/metabolismo , Vías Auditivas/metabolismo , Ecolocación , Ratones Endogámicos C57BL , Proteínas del Tejido Nervioso/genética , Proteínas del Tejido Nervioso/metabolismo , Neuronas/metabolismo , Parvalbúminas/metabolismo , Parvalbúminas/genética
5.
Molecules ; 29(11)2024 May 24.
Artículo en Inglés | MEDLINE | ID: mdl-38893360

RESUMEN

Thioethers are critical in the fields of pharmaceuticals and organic synthesis, but most of the methods for synthesis alkyl thioethers employ foul-smelling thiols as starting materials or generate them as by-products. Additionally, most thiols are air-sensitive and are easily oxidized to produce disulfides under atmospheric conditions; thus, a novel method for synthesizing thioethers is necessary. This paper reports a simple, effective, green method for synthesizing dialkyl or alkyl aryl thioether derivatives using odorless, stable, low-cost ROCS2K as a thiol surrogate. This transformation offers a broad substrate scope and good functional group tolerance with excellent selectivity. The reaction likely proceeds via xanthate intermediates, which can be readily generated via the nucleophilic substitution of alkyl halides or aryl halides with ROCS2K under transition-metal-free and base-free conditions.

6.
Pharmaceuticals (Basel) ; 17(5)2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38794206

RESUMEN

Astragalus polysaccharide (APS) derived from A. membranaceus plays a crucial role in traditional Chinese medicine. These polysaccharides have shown antitumor effects and are considered safe. Thus, they have become increasingly important in cancer immunotherapy. APS can limit the spread of cancer by influencing immune cells, promoting cell death, triggering cancer cell autophagy, and impacting the tumor microenvironment. When used in combination with other therapies, APS can enhance treatment outcomes and reduce toxicity and side effects. APS combined with immune checkpoint inhibitors, relay cellular immunotherapy, and cancer vaccines have broadened the application of cancer immunotherapy and enhanced treatment effectiveness. By summarizing the research on APS in cancer immunotherapy over the past two decades, this review elaborates on the anticancer mechanism of APS and its use in cancer immunotherapy and clinical trials. Considering the multiple roles of APS, this review emphasizes the importance of using APS as an adjunct to cancer immunotherapy and compares other polysaccharides with APS. This discussion provides insights into the specific mechanism of action of APS, reveals the molecular targets of APS for developing effective clinical strategies, and highlights the wide application of APS in clinical cancer therapy in the future.

7.
Int Immunopharmacol ; 135: 112290, 2024 Jun 30.
Artículo en Inglés | MEDLINE | ID: mdl-38796964

RESUMEN

Anesthesia and surgery activate matrix metalloproteinase 9 (MMP9), leading to blood-brain barrier (BBB) disruption and postoperative delirium (POD)-like behavior, especially in the elderly. Aged mice received intraperitoneal injections of either the MMP9 inhibitor SB-3CT, melatonin, or solvent, and underwent laparotomy under 3 % sevoflurane anesthesia(anesthesia/surgery). Behavioral tests were performed 24 h pre- and post-operatively. Serum and cortical tissue levels of interleukin (IL)-1ß, IL-6, and tumor necrosis factor-α (TNF-α) were measured using ELISA. Levels of PDGFRß, MMP9, tight junction, Mfsd2a, caveolin-1, synaptophysin, and postsynaptic densin (PSD)-95 proteins in the prefrontal cortex were assayed using Western blotting. BBB permeability was assessed by detecting IgG in the prefrontal cortex and serum S100ß levels. Anesthesia/surgery-induced peripheral inflammation activated MMP9, which in turn injured pericytes and tight junctions and increased transcytosis, thereby disrupting the BBB. Impaired BBB allowed the migration of peripheral inflammation into the central nervous system (CNS), thereby inducing neuroinflammation, synaptic dysfunction, and POD-like behaviors. However, MMP9 inhibition reduced pericyte and tight junction injury and transcytosis, thereby preserving BBB function and preventing the migration of peripheral inflammation into the CNS, thus attenuating synaptic dysfunction and POD-like behavior. In addition, to further validate the above findings, we showed that melatonin exerted similar effects through inhibition of MMP9. The present study shows that after anesthesia/surgery, inflammatory cytokines upregulation is involved in regulating BBB permeability in aged mice through activation of MMP9, suggesting that MMP9 may be a potential target for the prevention of POD.


Asunto(s)
Barrera Hematoencefálica , Metaloproteinasa 9 de la Matriz , Melatonina , Enfermedades Neuroinflamatorias , Sevoflurano , Animales , Metaloproteinasa 9 de la Matriz/metabolismo , Barrera Hematoencefálica/metabolismo , Barrera Hematoencefálica/efectos de los fármacos , Masculino , Ratones , Sevoflurano/farmacología , Enfermedades Neuroinflamatorias/inmunología , Melatonina/farmacología , Envejecimiento , Ratones Endogámicos C57BL , Corteza Prefrontal/metabolismo , Corteza Prefrontal/efectos de los fármacos , Citocinas/metabolismo , Complicaciones Posoperatorias , Anestesia , Conducta Animal/efectos de los fármacos , Laparotomía/efectos adversos , Uniones Estrechas/metabolismo , Uniones Estrechas/efectos de los fármacos , Compuestos Heterocíclicos con 1 Anillo , Sulfonas
8.
Int J Biol Macromol ; 270(Pt 2): 132229, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38734337

RESUMEN

In this study, the effect of hydrothermal treatment with different temperatures (120-180 °C) on the rheological properties of xanthan gum was evaluated. When the temperature of hydrothermal treatment was relatively low (120 °C), the rheological properties of the hydrothermally treated xanthan gum was similar to the untreated xanthan gum (pseudoplastic and solid-like/gel-like behavior). However, as the temperature of hydrothermal treatment was higher, the rheological properties of the hydrothermally treated xanthan gum changed greatly (e.g., a wider range of Newtonian plateaus in flow curves, existence of a critical frequency between the storage modulus (G') and the loss modulus (G") in the dynamic viscoelasticity measurement, variation of complex viscosity). Although the hydrothermal treatment showed little influence on the functional groups of xanthan gum, it altered the micromorphology of xanthan gum from uneven and rough lump-like to thinner and smoother flake-like. In addition, higher concentration (2 %) of hydrothermally treated xanthan gum made its viscosity close to that of the untreated xanthan gum (1 %). Besides, hydrothermal treatment also affected the effect of temperature and salt (CaCl2) adding on the rheological properties of xanthan gum. Overall, this study can provide some useful information on the rheological properties of xanthan gum after hydrothermal treatment.


Asunto(s)
Polisacáridos Bacterianos , Reología , Temperatura , Polisacáridos Bacterianos/química , Viscosidad , Agua/química
9.
BMC Ophthalmol ; 24(1): 57, 2024 Feb 05.
Artículo en Inglés | MEDLINE | ID: mdl-38317124

RESUMEN

BACKGROUND: In Asian patients with severe ptosis,the use of conjoint fascia sheath (CFS) suspension or levator aponeurosis fascia complex shortening surgery can correct the ptosis. During these surgery, a significant amount of levator aponeurosis fascia shortening is performed, which often leads to serious complications such as conjunctival prolapse.This study compares two surgical approaches for correcting severe blepharoptosis:Conjoint fascial sheath (CFS) + levator aponeurosis and muller's muscle complex (LM complex) suspension and conjoint fascial sheath (CFS) + LM complex+conjunctival suspension.The postoperative efficacy and the incidence of complications such as conjunctival prolapse are investigated for both procedures. METHODS: This study retrospectively analyzed 70 patients (77eyes) with severe blepharoptosis from January 2019 to December 2021. The patients were divided into the experimental group (34 cases, 38 eyes) and the control group (36 cases, 39 eyes). The experimental group was treated with CFS+LM complex + conjunctival suspension, and the control group was treated with CFS+LM complex suspension.The curative effect of blepharoptosis, the incidence of complications such as conjunctival prolapse and patient satisfaction were compared between the two different surgical methods. RESULTS: There was no significant difference in the correction effective rate between the experimental group (84.21%) and the control group (82.05%) (P > 0.05). There was no significant difference in the total incidence of complications between the experimental group (23.68%) and the control group (38.46%) (P > 0.05), but in the complication of conjunctival prolapse, the incidence of conjunctival prolapse in the experimental group was significantly lower than that in the control group. The difference was statistically significant (P < 0.05). In the survey of patient satisfaction rate, the satisfaction rate of the experimental group was significantly higher than that of the control group,which was statistically significant (P < 0.05). CONCLUSIONS: Compared to CFS+LM complex suspension surgery, the CFS+LM complex + conjunctival suspension has a definite effect in preventing postoperative conjunctival prolapse .The procedure has a high feasibility, good corrective effect, and improves patient satisfaction after surgery.


Asunto(s)
Blefaroplastia , Blefaroptosis , Humanos , Blefaroptosis/cirugía , Blefaroplastia/métodos , Estudios Retrospectivos , Prolapso , Párpados/cirugía , Músculos Oculomotores/cirugía , Resultado del Tratamiento
10.
Chem Commun (Camb) ; 60(9): 1140-1143, 2024 Jan 25.
Artículo en Inglés | MEDLINE | ID: mdl-38189083

RESUMEN

Herein, we developed a synthetic strategy for the direct construction of C-S bonds to obtain biologically active sulfur-containing compounds and a methodology involving the reductive sulfuration of aldehydes or ketones to obtain diverse substituted thiol, disulfide, and thioester derivatives. EtOCS2K is demonstrated as a potential substitute for the Berzelius reagent or Lawesson's reagent for the construction of C-S bonds.

11.
Natl Sci Rev ; 11(1): nwad256, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38288368

RESUMEN

Nausea and vomiting are important defensive responses to cope with pathogens and toxins that invade the body. The nucleus of the solitary tract (NTS) is important for initiating these responses. However, the molecular heterogeneities and cellular diversities of the NTS occlude a better understanding of these defensive responses. Here, we constructed the single-nucleus transcriptomic atlas of NTS cells and found multiple populations of NTS neurons that may be involved in these defensive responses. Among these, we identified Calbindin1-positive (Calb1+) NTS neurons that are molecularly distinct from Tac1+ neurons. These Calb1+ neurons are critical for nausea and retching induced by cereulide; an emetic toxin secreted by Bacillus Cereus. Strikingly, we found that cereulide can directly modulate vagal sensory neurons that innervate Calb1+ NTS neurons, a novel mechanism distinct from that for nausea and retching induced by Staphylococcal enterotoxin A. Together, our transcriptomic atlas of NTS neurons and the functional analyses revealed the neural mechanism for cereulide-induced retching-like behavior. These results demonstrate the molecular and cellular complexities in the brain that underlie defensive responses to the diversities of pathogens and toxins.

12.
Cell ; 186(26): 5892-5909.e22, 2023 12 21.
Artículo en Inglés | MEDLINE | ID: mdl-38091994

RESUMEN

Different functional regions of brain are fundamental for basic neurophysiological activities. However, the regional specification remains largely unexplored during human brain development. Here, by combining spatial transcriptomics (scStereo-seq) and scRNA-seq, we built a spatiotemporal developmental atlas of multiple human brain regions from 6-23 gestational weeks (GWs). We discovered that, around GW8, radial glia (RG) cells have displayed regional heterogeneity and specific spatial distribution. Interestingly, we found that the regional heterogeneity of RG subtypes contributed to the subsequent neuronal specification. Specifically, two diencephalon-specific subtypes gave rise to glutamatergic and GABAergic neurons, whereas subtypes in ventral midbrain were associated with the dopaminergic neurons. Similar GABAergic neuronal subtypes were shared between neocortex and diencephalon. Additionally, we revealed that cell-cell interactions between oligodendrocyte precursor cells and GABAergic neurons influenced and promoted neuronal development coupled with regional specification. Altogether, this study provides comprehensive insights into the regional specification in the developing human brain.


Asunto(s)
Encéfalo , Transcriptoma , Humanos , Neuronas Dopaminérgicas , Neuronas GABAérgicas , Mesencéfalo , Neocórtex , Encéfalo/crecimiento & desarrollo , Encéfalo/metabolismo
13.
Front Oncol ; 13: 1280900, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38023183

RESUMEN

Background: In the era of anti-HER2 targeted therapy, the potential clinical feasibility of considering HER2-overexpressing breast cancer cases presenting with 1-3 positive axillary lymph nodes as low-risk, and thereby contemplating postoperative radiotherapy reduction, remains an important subject for in-depth examination. The aim of this retrospective study was to evaluate the effectiveness of de-escalated radiotherapy in T1-2N1M0 HER2-overexpressing breast cancer patients receiving anti-HER2 targeted therapy. Specifically, omitting regional lymph node irradiation (RNI) after breast-conserving surgery and only performing whole-breast irradiation or omitting postmastectomy radiation therapy. Methods: A retrospective analysis was conducted on 429 patients with stage T1-2N1M0 primary invasive HER2-overexpressing breast cancer from our center between 2004 and 2018. Patients who received anti-HER2 targeted therapy were divided into an RNI group and a no RNI group to assess the role of RNI. The prognostic role of RNI was investigated via the Kaplan-Meier method and Cox proportional hazards modeling. Results: The median follow-up time was 46.8 months (range 7.1-225.8 months). In the anti-HER2 targeted therapy group RNI yielded no significant improvements in invasive disease-free survival (IDFS) (p = 0.940), local-regional recurrence-free survival (p = 0.380), distant metastases-free survival (p = 0.698), or overall survival (p = 0.403). Estrogen receptor (ER) status (hazard ratio [HR] 0.105, 95% confidence interval [CI] 0.023-0.749, p = 0.004) and lymph vascular invasion status (LVI) (HR 5.721, 95% CI 1.586-20.633, p = 0.008) were identified as independent prognostic factors for IDFS, and ER-positive and LVI-negative patients exhibited better prognoses. Conclusion: Omitting RNI may be a safe option in T1-2N1 HER2-overexpressing breast cancer patients receiving standardized anti-HER2 targeted therapy; particularly in ER-positive or LVI-negative subgroups.

14.
BMC Anesthesiol ; 23(1): 337, 2023 10 06.
Artículo en Inglés | MEDLINE | ID: mdl-37803259

RESUMEN

BACKGROUND: EEG monitoring techniques are receiving increasing clinical attention as a common method of reflecting the depth of sedation in the perioperative period. The influence of depth of sedation indices such as the bispectral index (BIS) generated by the processed electroencephalogram (pEEG) machine to guide the management of anesthetic depth of sedation on postoperative outcome remains controversial. This research was designed to decide whether an anesthetic agent exposure determined by raw electroencephalogram (rEEG) can influence anesthetic management and cause different EEG patterns and affect various patient outcomes. METHODS: A total of 141 participants aged ≥ 60 years undergoing abdominal major surgery were randomized to rEEG-guided anesthesia or routine care group. The rEEG-guided anesthesia group had propofol titrated to keep the rEEG waveform at the C-D sedation depth during surgery, while in the routine care group the anesthetist was masked to the patient's rEEG waveform and guided the anesthetic management only through clinical experience. The primary outcome was the presence of postoperative complications, the secondary outcomes included intraoperative anesthetic management and different EEG patterns. RESULTS: There were no statistically significant differences in the occurrence of postoperative respiratory, circulatory, neurological and gastrointestinal complications. Further EEG analysis revealed that lower frontal alpha power was significantly associated with a higher incidence of POD, and that rEEG-guidance not only reduced the duration of deeper anesthesia in patients with lower frontal alpha power, but also allowed patients with higher frontal alpha power to receive deeper and more appropriate depths of anesthesia than in the routine care group. CONCLUSIONS: In elderly patients undergoing major abdominal surgery, rEEG-guided anesthesia did not reduce the incidence of postoperative respiratory, circulatory, neurological and gastrointestinal complications. rEEG-guided anesthesia management reduced the duration of intraoperative BS in patients and the duration of over-deep sedation in patients with lower frontal alpha waves under anesthesia, and there was a strong association between lower frontal alpha power under anesthesia and the development of POD. rEEG-guided anesthesia may improve the prognosis of patients with vulnerable brains by improving the early identification of frail elderly patients and providing them with a more effective individualized anesthetic managements.


Asunto(s)
Anestesia , Anestésicos , Enfermedades Gastrointestinales , Propofol , Anciano , Humanos , Electroencefalografía/métodos , Anestesia General/métodos
15.
Aging Cell ; 22(11): e13982, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37681451

RESUMEN

Although immunosenescence may result in increased morbidity and mortality, many mammals have evolved effective immune coping strategies to extend their lifespans. Thus, the immune systems of long-lived mammals present unique models to study healthy longevity. To identify the molecular clues of anti-immunosenescence, we first built high-quality reference genome for a long-lived myotis bat, and then compared three long-lived mammals (i.e., bat, naked mole rat, and human) versus the short-lived mammal, mouse, in splenic immune cells at single-cell resolution. A close relationship between B:T cell ratio and immunosenescence was detected, as B:T cell ratio was much higher in mouse than long-lived mammals and significantly increased during aging. Importantly, we identified several iron-related genes that could resist immunosenescence changes, especially the iron chaperon, PCBP1, which was upregulated in long-lived mammals but dramatically downregulated during aging in all splenic immune cell types. Supportively, immune cells of mouse spleens contained more free iron than those of bat spleens, suggesting higher level of ROS-induced damage in mouse. PCBP1 downregulation during aging was also detected in hepatic but not pulmonary immune cells, which is consistent with the crucial roles of spleen and liver in organismal iron recycling. Furthermore, PCBP1 perturbation in immune cell lines would result in cellular iron dyshomeostasis and senescence. Finally, we identified two transcription factors that could regulate PCBP1 during aging. Together, our findings highlight the importance of iron homeostasis in splenic anti-immunosenescence, and provide unique insight for improving human healthspan.


Asunto(s)
Quirópteros , Inmunosenescencia , Humanos , Animales , Ratones , Quirópteros/genética , Bazo/metabolismo , Envejecimiento , Mamíferos/fisiología , Homeostasis
16.
Am J Transl Res ; 15(8): 5216-5227, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37692958

RESUMEN

OBJECTIVE: To investigate the effect of sodium bicarbonated Ringer's solution (BRS) on lactate metabolism, acid-base balance, and clinical outcomes in elderly patients undergoing gastrointestinal surgery. METHODS: A total of 60 elderly patients undergoing gastrointestinal surgery were enrolled in this prospective, randomized controlled study. The participants were randomly assigned to the BRS group (n = 30) or sodium lactated Ringer's solution (LRS) group (n = 30) where they received goal-directed fluid therapy with BRS or LRS, respectively. The primary outcome was the incidence of postoperative hyperlactatemia, whereas the secondary outcomes included pH, bicarbonate, base excess (BE), liver function, and postoperative complications within 30 days. Linear regression was conducted to screen the factors affecting lactate concentration. RESULTS: After fluid therapy, the probability of hyperlactatemia was lower in the BRS group than in the LRS group (3.3% vs. 40.0%, P < 0.001). No significant difference in bicarbonate, pH, and BE was observed between the groups (P > 0.05). Furthermore, the incidence of major complications and the length of hospital stay were not significantly different (P > 0.05). However, the BRS group had a lower risk of minor complications than the LRS group (50.0% vs. 76.7%, P = 0.032), particularly in terms of impaired liver function (16.7% vs. 43.3%, P = 0.024). Diabetes, hypotension, and volume of LRS infused were highly correlated with lactate concentration. CONCLUSION: BRS is more beneficial to the reduction of the incidence of postoperative hyperlactatemia and the risk of minor postoperative complications in elderly patients undergoing gastrointestinal surgery. Therefore, BRS may be a better option for perioperative fluid therapy in elderly patients undergoing gastrointestinal surgery.

17.
Ecol Evol ; 13(9): e10511, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37701023

RESUMEN

Whether conifers can withstand environmental changes especially temperature fluctuations has been controversial. Epigenetic analysis may provide new perspectives for solving the issue. Pseudotaxus chienii is an endangered gymnosperm species endemic to China. In this study, we have examined the genetic and epigenetic variations in its natural populations aiming to disentangle the synergistic effects of climate and soil on its population (epi)genetic differentiation by using amplified fragment length polymorphism (AFLP) and methylation-sensitive AFLP (MSAP) techniques. We identified 23 AFLP and 26, 7, and 5 MSAP outliers in P. chienii. Twenty-one of the putative adaptive AFLP loci were found associated with climate and/or soil variables including precipitation, temperature, K, Fe, Zn, and Cu, whereas 21, 7, and 4 MSAP outliers were significantly related to precipitation of wettest month (Bio13), precipitation driest of month (Bio14), percent tree cover (PTC), and soil Fe, Mn, and Cu compositions. Total precipitation and precipitation in the driest seasons were the most influential factors for genetic and epigenetic variation, respectively. In addition, a high full-methylation level and a strong correlation between genetic and epigenetic variation were detected in P. chienii. Climate is found of greater importance than soil in shaping adaptive (epi)genetic differentiation, and the synergistic effects of climate and climate-soil variables were also observed. The identified climate and soil variables should be considered when applying ex situ conservation.

18.
Am J Transl Res ; 15(5): 3476-3488, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37303623

RESUMEN

OBJECTIVE: This study aimed to compare the ability of three frailty assessments to predict adverse outcomes after elective gastrointestinal surgery and analyze how frailty assessments impact the American Society of Anesthesiologists (ASA) risk prediction model. METHODS: Frailty was measured using the FRAIL scale, Fried Phenotype (FP), and Clinical Frailty Scale (CFS), alongside ASA assessments before surgery. Univariate and logistic regression analyses were used to determine the predictive value of each method. The predictive abilities of the tools were assessed by the area under the receiver operating characteristic curves (AUCs) and their 95% confidence intervals (CIs). RESULTS: After adjusting for age and other risk factors, logistic regression analysis revealed significant positive associations between preoperative frailty and postoperative total adverse systemic complications (odds ratios [ORs] [95% CIs]: FRAIL, 1.297 [0.943-1.785]; FP, 1.317 [0.965-1.798]; CFS, 2.046 [1.413-3.015]; P < 0.001). The CFS was the best predictor of any adverse systemic complications (AUC, 0.696; 95% CI, 0.640-0.748). The predictive abilities of the FRAIL scale (AUC, 0.613; 95% CI, 0.555-0.669) and FP (AUC, 0.615; 95% CI, 0.557-0.671) were similar. The CFS and ASA assessment combined (AUC, 0.697; 95% CI, 0.641-0.749) had a statistically improved AUC compared to the ASA assessment alone (AUC, 0.636; 95% CI, 0.578-0.691), illustrating their value for predicting any adverse systemic complications. CONCLUSION: Frailty instruments enhance the accuracy of predicting postoperative outcome in older adults. Clinicians should add frailty assessments before preoperative ASA, particularly the CFS, given its ease of use and clinical feasibility.

19.
J Environ Manage ; 339: 117933, 2023 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-37080099

RESUMEN

Sewage sludge (SS) has been extensively used as an alternative fertilizer in forest plantations, which are beneficial in supplying timbers and mitigating climate change. However, whether the extra nitrogen (N) applied by SS would enhance the soil nitrous oxide (N2O) emission, an important greenhouse gas, in forest plantations have not been well understood. The objective of this study is to evaluate the ecological effects of SS application on soils, by investigating the soil N2O emission and the toxicity of the potentially toxic elements (PTEs) in soil. A field fertilization experiment was conducted in Eucalyptus plantations with four fertilization rates (0 kg m-2, 1.5 kg m-2, 3.0 kg m-2, and 4.5 kg m-2). The soil N2O emissions were monitored at a soil depth of 0-10 cm using static chamber method, soil chemical properties, and PTEs were determined at soil depths of 0-10 cm, 10-20 cm, and 20-40 cm. The average soil N2O emission rate was 8.1 µg N2O-N h-1 m-2 in plots without SS application (control). The application of SS significantly increased the soil N2O emissions by 7-10 times as to control. The increased N2O emissions were positively related to the soil total phosphorus and nitrogen and negatively correlated with copper and zinc, which increased with the SS application. However, the potential ecological risk index (Ei) and the comprehensive potential ecological risk index (RI) of PTEs were lower than 40 and 150 respectively, which indicating a low toxicity of PTEs to soil health. After seven months of SS application, the priming effects of SS on soil N2O emissions gradually diminished. These findings suggest that the application of SS may increase N2O emissions at the initial stages of application (<7 months) and may have a low PTEs pollution risk, even at a high SS addition rate (4.5 kg m-2).


Asunto(s)
Eucalyptus , Metales Pesados , Suelo/química , Aguas del Alcantarillado , Nitrógeno/análisis , Fertilizantes/análisis , Óxido Nitroso/análisis , Agricultura , China
20.
J Cosmet Dermatol ; 22(9): 2528-2533, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-36992574

RESUMEN

BACKGROUND: Bromhidrosis, also known as body odor, is a common disease in life, which often occurs in young adults. The histological basis of bromhidrosis is the hyperplasia of apocrine sweat glands. OBJECTIVE: To compare the effects of different methods of endoscopy in microdynamic axillary osmidrosis removal on curative effect, complications, and surgical efficiency. METHODS: A total of 149 patients with axillary osmidrosis were treated in our hospital from January 2020 to December 2021. They were treated with endoscopic assistance in the whole process of operation (Group A) and endoscope-assisted exploration after blind rotary cutter suction (Group B), respectively, and the curative effect, complication rate, and surgical efficiency were evaluated. RESULTS: There was no significant difference in the curative effect and complication rate between the two groups, but the endoscope-assisted exploration group after suction with rotary cutter (Group B) had higher surgical efficiency. CONCLUSION: On the basis of professional use of rotary cutter, it is efficient to choose endoscope to check the excision of sweat gland in the operation area and stop bleeding in time after blind suction.


Asunto(s)
Hiperhidrosis , Enfermedades de las Glándulas Sudoríparas , Adulto Joven , Humanos , Olor Corporal , Enfermedades de las Glándulas Sudoríparas/cirugía , Glándulas Apocrinas/cirugía , Succión/métodos , Axila/cirugía , Endoscopios , Odorantes , Hiperhidrosis/cirugía
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