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1.
Chem Sci ; 15(20): 7643-7650, 2024 May 22.
Article in English | MEDLINE | ID: mdl-38784741

ABSTRACT

Attaining meticulous dominion over the binding milieu of catalytic metal sites remains an indispensable pursuit to tailor product selectivity and elevate catalytic activity. By harnessing the distinctive attributes of a Zr4+-anchored thiacalix[4]arene (TC4A) metalloligand, we have pioneered a methodology for incorporating catalytic Ag1+ sites, resulting in the first Zr-Ag bimetallic cluster, Zr2Ag7, which unveils a dualistic configuration embodying twin {ZrAg3(TC4A)2} substructures linked by an {AgSal} moiety. This cluster unveils a trinity of discrete Ag sites: a pair ensconced within {ZrAg3(TC4A)2} subunits and one located between two units. Expanding the purview, we have also crafted ZrAg3 and Zr2Ag2 clusters, meticulously mimicking the two Ag site environment inherent in the {ZrAg3(TC4A)2} monomer. The distinct structural profiles of Zr2Ag7, ZrAg3, and Zr2Ag provide an exquisite foundation for a precise comparative appraisal of catalytic prowess across three Ag sites intrinsic to Zr2Ag7. Remarkably, Zr2Ag7 eclipses its counterparts in the electroreduction of CO2, culminating in a CO faradaic efficiency (FECO) of 90.23% at -0.9 V. This achievement markedly surpasses the performance metrics of ZrAg3 (FECO: 55.45% at -1.0 V) and Zr2Ag2 (FECO: 13.09% at -1.0 V). Utilizing in situ ATR-FTIR, we can observe reaction intermediates on the Ag sites. To unveil underlying mechanisms, we employ density functional theory (DFT) calculations to determine changes in free energy accompanying each elementary step throughout the conversion of CO2 to CO. Our findings reveal the exceptional proficiency of the bridged-Ag site that interconnects paired {ZrAg3(TC4A)2} units, skillfully stabilizing *COOH intermediates, surpassing the stabilization efficacy of the other Ag sites located elsewhere. The invaluable insights gleaned from this pioneering endeavor lay a novel course for the design of exceptionally efficient catalysts tailored for CO2 reduction reactions, emphatically underscoring novel vistas this research unshrouds.

2.
Virulence ; 15(1): 2350775, 2024 12.
Article in English | MEDLINE | ID: mdl-38736041

ABSTRACT

OBJECTIVES: The translocation of intestinal flora has been linked to the colonization of diverse and heavy lower respiratory flora in patients with septic ARDS, and is considered a critical prognostic factor for patients. METHODS: On the first and third days of ICU admission, BALF, throat swab, and anal swab were collected, resulting in a total of 288 samples. These samples were analyzed using 16S rRNA analysis and the traceability analysis of new generation technology. RESULTS: On the first day, among the top five microbiota species in abundance, four species were found to be identical in BALF and throat samples. Similarly, on the third day, three microbiota species were found to be identical in abundance in both BALF and throat samples. On the first day, 85.16% of microorganisms originated from the throat, 5.79% from the intestines, and 9.05% were unknown. On the third day, 83.52% of microorganisms came from the throat, 4.67% from the intestines, and 11.81% were unknown. Additionally, when regrouping the 46 patients, the results revealed a significant predominance of throat microorganisms in BALF on both the first and third day. Furthermore, as the disease progressed, the proportion of intestinal flora in BALF increased in patients with enterogenic ARDS. CONCLUSIONS: In patients with septic ARDS, the main source of lung microbiota is primarily from the throat. Furthermore, the dynamic trend of the microbiota on the first and third day is essentially consistent.It is important to note that the origin of the intestinal flora does not exclude the possibility of its origin from the throat.


Subject(s)
Bacteria , Bronchoalveolar Lavage Fluid , Microbiota , Pharynx , RNA, Ribosomal, 16S , Respiratory Distress Syndrome , Sepsis , Humans , Male , Female , Respiratory Distress Syndrome/microbiology , Middle Aged , Pharynx/microbiology , RNA, Ribosomal, 16S/genetics , Bronchoalveolar Lavage Fluid/microbiology , Aged , Sepsis/microbiology , Bacteria/classification , Bacteria/isolation & purification , Bacteria/genetics , Pulmonary Alveoli/microbiology , Adult , Intensive Care Units , Gastrointestinal Microbiome
3.
Transfusion ; 2024 May 16.
Article in English | MEDLINE | ID: mdl-38752406

ABSTRACT

BACKGROUND: Fetal and neonatal exposure to lead is associated with irreversible adverse effects on neural development. There is no reliable threshold for lead effect, so limiting exposure is recommended. A significant correlation has been reported between post-transfusion blood lead level (BLL) in infants and lead levels in transfused RBC units. We measured levels of lead, mercury, and cadmium, in Canadian donor blood to investigate if concerning levels for neonatal transfusion exist. STUDY DESIGN AND METHODS: Whole blood samples from blood donors (n = 2529) were shipped cold within 7 days of donation. All permanent blood donation clinics across Canada were sampled. Twelve of these permanent clinics and 8 mobile clinics with a greater potential for having higher lead or mercury levels were oversampled. Heavy metals were measured by inductively coupled plasma mass spectrometry. RESULTS: Of all donations, 2.2% (lead) and 0.4% (mercury) had levels higher than the recommended thresholds for safe neonatal transfusion. BLLs were higher in males but there was no significant difference in the blood mercury levels of males versus females. Cadmium levels were higher in females. There was a positive correlation between donor age and levels of heavy metals, with lead having the strongest correlation (r = 0.47, p < .0001). Three clinics in close proximity to two lead-producing mines were among the clinics with the highest BLLs. Significantly higher blood mercury levels were observed in coastal clinics. CONCLUSION: Our data on donor blood heavy metal levels supports considering blood transfusion as an exposure source to heavy metals and encourages informed selection of blood units for transfusion to vulnerable groups.

4.
Cell Mol Biol Lett ; 29(1): 79, 2024 May 23.
Article in English | MEDLINE | ID: mdl-38783169

ABSTRACT

BACKGROUND: Postoperative cognitive dysfunction (POCD) is a common complication after anesthesia/surgery, especially among elderly patients, and poses a significant threat to their postoperative quality of life and overall well-being. While it is widely accepted that elderly patients may experience POCD following anesthesia/surgery, the exact mechanism behind this phenomenon remains unclear. Several studies have indicated that the interaction between silent mating type information regulation 2 homologue 1 (SIRT1) and brain-derived neurotrophic factor (BDNF) is crucial in controlling cognitive function and is strongly linked to neurodegenerative disorders. Hence, this research aims to explore how SIRT1/BDNF impacts cognitive decline caused by anesthesia/surgery in aged mice. METHODS: Open field test (OFT) was used to determine whether anesthesia/surgery affected the motor ability of mice, while the postoperative cognitive function of 18 months old mice was evaluated with Novel object recognition test (NORT), Object location test (OLT) and Fear condition test (FC). The expressions of SIRT1 and other molecules were analyzed by western blot and immunofluorescence staining. The hippocampal synaptic plasticity was detected by Golgi staining and Long-term potentiation (LTP). The effects of SIRT1 and BDNF overexpression as well as chemogenetic activation of glutamatergic neurons in hippocampal CA1 region of 18 months old vesicular glutamate transporter 1 (VGLUT1) mice on POCD were further investigated. RESULTS: The research results revealed that older mice exhibited cognitive impairment following intramedullary fixation of tibial fracture. Additionally, a notable decrease in the expression of SIRT1/BDNF and neuronal excitability in hippocampal CA1 glutamatergic neurons was observed. By increasing levels of SIRT1/BDNF or enhancing glutamatergic neuron excitability in the CA1 region, it was possible to effectively mitigate synaptic plasticity impairment and ameliorate postoperative cognitive dysfunction. CONCLUSIONS: The decline in SIRT1/BDNF levels leading to changes in synaptic plasticity and neuronal excitability in older mice could be a significant factor contributing to cognitive impairment after anesthesia/surgery.


Subject(s)
Brain-Derived Neurotrophic Factor , CA1 Region, Hippocampal , Down-Regulation , Neuronal Plasticity , Neurons , Postoperative Cognitive Complications , Sirtuin 1 , Animals , Sirtuin 1/metabolism , Sirtuin 1/genetics , Brain-Derived Neurotrophic Factor/metabolism , Brain-Derived Neurotrophic Factor/genetics , Mice , Neurons/metabolism , Postoperative Cognitive Complications/metabolism , Postoperative Cognitive Complications/etiology , CA1 Region, Hippocampal/metabolism , Male , Mice, Inbred C57BL , Long-Term Potentiation , Glutamic Acid/metabolism , Cognitive Dysfunction/etiology , Cognitive Dysfunction/metabolism , Cognitive Dysfunction/physiopathology
5.
PeerJ ; 12: e17352, 2024.
Article in English | MEDLINE | ID: mdl-38784390

ABSTRACT

Background: The Yunnan section of the Nujiang River (YNR) Basin in the alpine-valley area is one of the most critical areas of debris flow in China. Methods: We analyzed the applicability of three machine learning algorithms to model of susceptibility to debris flow-Random Forest (RF), the linear kernel support vector machine (Linear SVM), and the radial basis function support vector machine (RBFSVM)-and compared 20 factors to determine the dominant controlling in debris flow occurrence in the region. Results: We found that (1) RF outperformed RBFSVM and Linear SVM in terms of accuracy, (2) topographic conditions were prerequisites, and geology, precipitation, vegetation, and anthropogenic influence were critical to forming debris flows. Also, the relative elevation difference was the most prominent evaluation factor of debris flow susceptibility, and (3) susceptibility maps based on RF's debris flow susceptibility (DFS) showed that zones with very high susceptibility were distributed along the mainstream of the Nujiang River. These findings provide methodological guidance and reference for improvement of DFS assessment. It enriches the content of DFS studies in the alpine-valley areas.


Subject(s)
Machine Learning , Rivers , China , Rivers/chemistry , Environmental Monitoring/methods , Support Vector Machine , Algorithms
6.
J Immunother ; 2024 May 29.
Article in English | MEDLINE | ID: mdl-38809517

ABSTRACT

The infiltration of CD8+ T cells in the tumor microenvironment is associated with better survival and immunotherapy response. However, their roles in gastric cancer have not been explored so far. In here, the profiles of GC gene expression were collected from The Cancer Genome Atlas database. Single-cell transcriptomic data originated from GSE134520. Cell clustering, annotation, and CD8+ T-cell differential genes were from the TISCH database. We determined 896 CD8+ T-cell differential genes by scRNA-seq analysis. After integrating immune-related genes, 174 overlapping genes were obtained and a novel risk model was subsequently built. The performance of CD8+ T-cell-associated gene signature was assessed in the training and external validation sets. The gene signature showed independent risk factors of overall survival for GC. A quantitative nomogram was built to enhance the clinical efficacy of this signature. Furthermore, low-risk individuals showed higher mutation status, higher immune checkpoint expression, low Tumour Immune Dysfunction and Exclusion (TIDE) scores, and higher IPS-PD-1 combined IPS-CTLA4 scores, indicating a greater response to immunotherapy. In addition, analysis of IMvigor210 immunotherapy cohort demonstrated that low-risk individuals had a favorable response to prognosis and immunotherapy. In conclusion, we generated a CD8+ T-cell-related signature that can serve as a promising tool for personalized prognosis prediction and guiding decisions regarding immunotherapy in GC patients.

7.
Adv Mater ; : e2405178, 2024 May 19.
Article in English | MEDLINE | ID: mdl-38762788

ABSTRACT

Graphyne (GY) and graphdiyne (GDY)-based monolayers represent the next generation 2D carbon-rich materials with tunable structures and properties surpassing those of graphene. However, the detection of band formation in atomically thin GY/GDY analogues has been challenging, as both long-range order and atomic precision have to be fulfilled in the system. The present work reports direct evidence of band formation in on-surface synthesized metallated Ag-GDY sheets with mesoscopic (≈1 µm) regularity. Employing scanning tunneling and angle-resolved photoemission spectroscopies, energy-dependent transitions of real-space electronic states above the Fermi level and formation of the valence band are respectively observed. Furthermore, density functional theory (DFT) calculations corroborate the observations and reveal that doubly degenerate frontier molecular orbitals on a honeycomb lattice give rise to flat, Dirac and Kagome bands close to the Fermi level. DFT modeling also indicates an intrinsic band gap for the pristine sheet material, which is retained for a bilayer with h-BN, whereas adsorption-induced in-gap electronic states evolve at the synthesis platform with Ag-GDY decorating the (111) facet of silver. These results illustrate the tremendous potential for engineering novel band structures via molecular orbital and lattice symmetries in atomically precise 2D carbon materials.

8.
J Dig Dis ; 25(4): 238-247, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38779802

ABSTRACT

OBJECTIVES: As a serious complication of moderately severe acute pancreatitis (MSAP) and severe acute pancreatitis (SAP), infected pancreatic necrosis (IPN) can lead to a prolonged course of interventional therapy. Most predictive models designed to identify such patients are complex or lack validation. The aim of this study was to develop a predictive model for the early detection of IPN in MSAP and SAP. METHODS: A total of 594 patients with MSAP or SAP were included in the study. To reduce dimensionality, least absolute shrinkage and selection operator regression analysis was used to screen potential predictive variables, a nomogram was then constructed using logistic regression analysis. The receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA) were used to evaluate the discrimination, accuracy, and clinical efficacy of the model. External data were also obtained to further validate the constructed model. RESULTS: There were 476, 118, and 82 patients in the training, internal validation, and external validation cohorts, respectively. Platelet count, hematocrit, albumin/globulin, severity of acute pancreatitis, and modified computed tomography severity index score were independent factors for predicting IPN in MSAP and SAP. The area under the ROC curves were 0.923, 0.940, and 0.817, respectively, in the three groups. There was a good consistency between the actual probabilities and the predicted probabilities. DCA revealed excellent clinical utility. CONCLUSION: The constructed nomogram is a simple and feasible model that has good clinical predictive value and efficacy in clinical decision-making for IPN in MSAP and SAP.


Subject(s)
Nomograms , Pancreatitis, Acute Necrotizing , Severity of Illness Index , Humans , Male , Female , Middle Aged , Pancreatitis, Acute Necrotizing/complications , Pancreatitis, Acute Necrotizing/diagnosis , Adult , ROC Curve , Aged , Predictive Value of Tests , Tomography, X-Ray Computed , Retrospective Studies , Pancreatitis/diagnosis , Pancreatitis/complications
9.
Animals (Basel) ; 14(9)2024 Apr 24.
Article in English | MEDLINE | ID: mdl-38731282

ABSTRACT

The negative energy balance occurring in the periparturient period of cows will impede their health and postpartum performance. To target this issue, L-tryptophan was supplied to the prepartum cows. The results showed that L-tryptophan supplementation significantly increased the serum melatonin level and was accompanied with increases in SOD activity, IL-10 and colostrum IgA levels as well as decreases in MDA and IL-6 levels compared to the control cows. The incidence of postpartum diseases was significantly lower and the pregnancy rate was significantly higher in cows fed L-tryptophan than in the control group. A striking observation was that prepartum L-tryptophan supplementation not only improved the milk production but also the quality compared to the control cows. In general, supplementation with L-tryptophan in the prepartum period can improve the postpartum reproduction and lactation performance of cows to some extent.

10.
Mil Med Res ; 11(1): 28, 2024 May 06.
Article in English | MEDLINE | ID: mdl-38711073

ABSTRACT

BACKGROUND: Intervertebral disc degeneration (IVDD) is a multifaceted condition characterized by heterogeneity, wherein the balance between catabolism and anabolism in the extracellular matrix of nucleus pulposus (NP) cells plays a central role. Presently, the available treatments primarily focus on relieving symptoms associated with IVDD without offering an effective cure targeting its underlying pathophysiological processes. D-mannose (referred to as mannose) has demonstrated anti-catabolic properties in various diseases. Nevertheless, its therapeutic potential in IVDD has yet to be explored. METHODS: The study began with optimizing the mannose concentration for restoring NP cells. Transcriptomic analyses were employed to identify the mediators influenced by mannose, with the thioredoxin-interacting protein (Txnip) gene showing the most significant differences. Subsequently, small interfering RNA (siRNA) technology was used to demonstrate that Txnip is the key gene through which mannose exerts its effects. Techniques such as colocalization analysis, molecular docking, and overexpression assays further confirmed the direct regulatory relationship between mannose and TXNIP. To elucidate the mechanism of action of mannose, metabolomics techniques were employed to pinpoint glutamine as a core metabolite affected by mannose. Next, various methods, including integrated omics data and the Gene Expression Omnibus (GEO) database, were used to validate the one-way pathway through which TXNIP regulates glutamine. Finally, the therapeutic effect of mannose on IVDD was validated, elucidating the mechanistic role of TXNIP in glutamine metabolism in both intradiscal and orally treated rats. RESULTS: In both in vivo and in vitro experiments, it was discovered that mannose has potent efficacy in alleviating IVDD by inhibiting catabolism. From a mechanistic standpoint, it was shown that mannose exerts its anti-catabolic effects by directly targeting the transcription factor max-like protein X-interacting protein (MondoA), resulting in the upregulation of TXNIP. This upregulation, in turn, inhibits glutamine metabolism, ultimately accomplishing its anti-catabolic effects by suppressing the mitogen-activated protein kinase (MAPK) pathway. More importantly, in vivo experiments have further demonstrated that compared with intradiscal injections, oral administration of mannose at safe concentrations can achieve effective therapeutic outcomes. CONCLUSIONS: In summary, through integrated multiomics analysis, including both in vivo and in vitro experiments, this study demonstrated that mannose primarily exerts its anti-catabolic effects on IVDD through the TXNIP-glutamine axis. These findings provide strong evidence supporting the potential of the use of mannose in clinical applications for alleviating IVDD. Compared to existing clinically invasive or pain-relieving therapies for IVDD, the oral administration of mannose has characteristics that are more advantageous for clinical IVDD treatment.


Subject(s)
Cell Cycle Proteins , Glutamine , Intervertebral Disc Degeneration , Mannose , Intervertebral Disc Degeneration/drug therapy , Mannose/pharmacology , Mannose/therapeutic use , Animals , Rats , Glutamine/pharmacology , Glutamine/metabolism , Male , Rats, Sprague-Dawley , Humans , Nucleus Pulposus/drug effects , Nucleus Pulposus/metabolism
11.
Int J Ophthalmol ; 17(4): 761-766, 2024.
Article in English | MEDLINE | ID: mdl-38638243

ABSTRACT

AIM: To evaluate scleral buckling (SB) surgery using a non-contact wide-field viewing system and 23-gauge intraocular illumination for the treatment of rhegmatogenous retinal detachment in silicone oil (SO)-filled eyes. METHODS: Totally 9 patients (9 eyes) with retinal detachment in SO-filled eyes were retrospectively analyzed. All patients underwent non-contact wide-field viewing system-assisted buckling surgery with 23-gauge intraocular illumination. SO was removed at an appropriate time based on recovery. The patients were followed up for at least 3mo after SO removal. Retinal reattachment, complications, visual acuity and intraocular pressure (IOP) before and after surgery were observed. RESULTS: Patients were followed up for a mean of 8.22mo (3-22mo) after SO removal. All patients had retinal reattachment. At the final follow-up, visual acuity showed improvement for 8 patients, and no change for 1 patient. The IOP was high in 3 patients before surgery, but it stabilized after treatment; it was not affected in the other patients. None of the patients had infections, hemorrhage, anterior ischemia, or any other complication. CONCLUSION: This new non-contact wide-field viewing system-assisted SB surgery with 23-gauge intraocular illumination is effective and safe for retinal detachment in SO-filled eyes.

12.
Huan Jing Ke Xue ; 45(5): 2767-2779, 2024 May 08.
Article in Chinese | MEDLINE | ID: mdl-38629540

ABSTRACT

The external spatiotemporal evolution and intrinsic impact mechanisms of ecosystem service value are of great significance for understanding regional ecosystem issues and enhancing human ecological well-being. Based on grid data, this study used the equivalent factor method and NDVI to measure the ecosystem service value of the Yellow River Basin, analyzed the spatial-temporal evolution of urban ecosystem service value along the basin, and established a GWR model to explore the spatial heterogeneity of each influencing factor on the basis of determining the main influencing factors via geographic detector. The results showed that:① The ecosystem service value of the Yellow River Basin increased first, then decreased, and finally increased from 2000 to 2020, showing a spatial distribution pattern of "the south was higher than the north;" "the lower reaches were lower, and the upper and middle reaches were higher;" and the regulation service contributed the most to the ecosystem service value of the basin. ② The results of geographical exploration showed that the degree of influence of various factors was different. Social factors played the strongest role in explaining the ecosystem service value of the Yellow River Basin, followed by economic factors, and natural factors played the weakest role. The high value areas in the upper reaches were mainly related to rivers and lakes, and the high value areas in the middle reaches were mainly related to mountains. ③ The results of the GWR model showed that population density and land reclamation rate were negatively correlated with ecosystem service value, whereas average annual precipitation was positively correlated, and the effects increased from east to west. The GDP per unit area was negatively correlated with the overall ecosystem service value but positively correlated in the upstream region.

13.
Front Biosci (Landmark Ed) ; 29(4): 139, 2024 Apr 03.
Article in English | MEDLINE | ID: mdl-38682178

ABSTRACT

BACKGROUND: Hypoxic-ischaemic encephalopathy (HIE) is a major cause of neonatal disability and mortality. Although hypothermia therapy offers some neuroprotection, the recovery of neurological function is limited. Therefore, new synergistic therapies are necessary to improve the prognosis. Mesenchymal stem cell-based therapy is emerging as a promising treatment option for HIE. In this study, we studied the therapeutic efficacy of human placenta-derived mesenchymal stem cells (PD-MSCs) in the HIE rat model and analyzed the underlying therapeutic mechanisms. METHODS: Rats were divided into 6 groups (n = 9 for each) as follows: control, HIE model, HIE + normal saline, and HIE + PD-MSC transplantation at days 7, 14 and 28 postpartum. Following PD-MSC transplantation, neurological behavior was evaluated using rotarod tests, traction tests, and the Morris water maze test. The degree of brain tissue damage was assessed by histological examination and Nissl staining. Expression levels of apoptosis-related proteins and inflammatory factors were quantified by Western blotting and enzyme-linked immunosorbent assays. Immunofluorescence was used to investigate the ability of PD-MSCs to repair the morphology and function of hippocampal neurons with hypoxic-ischaemic (HI) injury. RESULTS: PD-MSC transplantation enhanced motor coordination and muscle strength in HIE rats. This treatment also improved spatial memory ability by repairing pathological damage and preventing the loss of neurons in the cerebral cortex. The most effective treatment was observed in the HIE + PD-MSC transplantation at day 7 group. Expression levels of microtubule-associated protein-2 (MAP-2), B-cell lymphoma-2 (BCL-2), interleukin (IL)-10, and transforming growth factor (TGF -ß1) were significantly higher in the HIE + PD-MSC treatment groups compared to the HIE group, whereas the levels of BCL-2-associated X protein (BAX), BCL-2-associated agonist of cell death (BAD), IL-1ß and tumour necrosis factor α (TNF-α) were significantly lower. CONCLUSIONS: We demonstrated that intravenous injection of PD-MSC at 7, 14 and 28 days after intrauterine HI damage in a rat model could improve learning, memory, and motor function, possibly by inhibiting apoptosis and inflammatory damage. These findings indicate that autologous PD-MSC therapy could have potential application for the treatment of HIE.


Subject(s)
Apoptosis , Hypoxia-Ischemia, Brain , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells , Placenta , Rats, Sprague-Dawley , Animals , Female , Mesenchymal Stem Cell Transplantation/methods , Pregnancy , Hypoxia-Ischemia, Brain/therapy , Humans , Placenta/cytology , Mesenchymal Stem Cells/cytology , Rats , Disease Models, Animal , Hippocampus/metabolism , Inflammation/therapy , Neurons/metabolism , Male
14.
Cell Biochem Funct ; 42(3): e4017, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38603595

ABSTRACT

Chromosomal instability (CIN), caused by errors in the segregation of chromosomes during mitosis, is a hallmark of many types of cancer. The fidelity of chromosome segregation is governed by a sophisticated cellular signaling network, one crucial orchestrator of which is Heterochromatin protein 1 (HP1). HP1 dynamically localizes to distinct sites at various stages of mitosis, where it regulates key mitotic events ranging from chromosome-microtubule attachment to sister chromatid cohesion to cytokinesis. Our evolving comprehension of HP1's multifaceted role has positioned it as a central protein in the orchestration of mitotic processes.


Subject(s)
Chromobox Protein Homolog 5 , Mitosis
15.
Pancreas ; 2024 Mar 27.
Article in English | MEDLINE | ID: mdl-38530976

ABSTRACT

OBJECTIVES: Acute pancreatitis (AP) has a high incidence of hospitalizations, morbidity, and mortality worldwide. A growing number of studies on AP pathogenesis are based on caerulein-induced experimental model, which simulates human AP in vivo. It has been demonstrated that both pancreatic acinar cells and peritoneal macrophages are involved in pancreatic inflammation and damage. However, their connection has not been well understood. METHODS: A caerulein-induced AP model was established on the pancreatic acinar cell line AR42J. Rat macrophages were isolated from the peritoneal cavity. The effects of caerulein-induced pancreatic exosomes on the peritoneal macrophage and pancreas in vivo and in vitro were examined. The underlying molecular mechanism was investigated by exploring the regulatory role of downstream molecules. RESULTS: We found that exosomes derived from caerulein-treated AR42J cells induced rat peritoneal macrophage M1 polarization and pyroptosis. miR-24-3p was upregulated in caerulein-stimulated exosomes, whereas the miR-24-3p inhibitor counteracted the effect of pancreatic exosomes on peritoneal macrophage M1 polarization and pyroptosis. Furthermore, miR-24-3p inhibited March3 expression, whereas MARCH3 mediated NLRP3 ubiquitination in rat peritoneal macrophages, which, in turn, contributed to the apoptosis, reactive oxygen species production, and inflammation in AR42J cells. CONCLUSIONS: Exosomes derived from caerulein-stimulated pancreatic acinar cells mediate peritoneal macrophage M1 polarization and pyroptosis via an miR-24-3p/MARCH3/NLRP3 axis in AP.

16.
Org Biomol Chem ; 22(15): 3068-3072, 2024 Apr 17.
Article in English | MEDLINE | ID: mdl-38546264

ABSTRACT

Allylphosphine oxide compounds are important building blocks with broad applications in organic synthesis and pharmaceutical science. Herein, we report an unprecedented palladium-catalyzed allylation of phosphine oxides with vinylethylene carbonates, producing various phosphorus allyl alcohols in excellent yields with high Z-selectivity. In addition, gram-scale synthesis and further functional group transformations demonstrate the practical utility of this synthetic method.

17.
Front Surg ; 11: 1307460, 2024.
Article in English | MEDLINE | ID: mdl-38486796

ABSTRACT

Introduction: The Tarlov cysts are pathological enlargements of the cerebrospinal fluid spaces between the endoneurium and perineurium, which can cause intolerable sciatic pain, motor impairment of lower limbs, and bladder/bowel dysfunction. Currently, the treatment results are unsatisfactory due to the low cure rates and extensive surgical trauma. Thus, there is an ongoing exploration of surgical techniques for Tarlov treatment. In the current study, we present a novel neuroendoscopic-assisted technique that combines the fenestration, leakage sealing, and tamponade of the Tarlov cyst. Methods: Between January 2020 and December 2021, a total of 32 Tarlov patients were enrolled and received neuroendoscopic-assisted surgery. Their pre- and post-surgical Visual Analogue Scale (VAS) scores, major complaints, and MR imaging were recorded for comparison. Results: 27 of 32 patients (84.4%) patients demonstrated immediate pain relief as their VAS scores decreased from 5.6 ± 1.5 to 2.5 ± 1.1 (p < 0.01) on the first day after surgery. At the 3-month follow-up, the patients' average VAS score continued to decrease (1.94 ± 0.8). Meanwhile, saddle paresthesia, urinary incontinence, and constipation were relieved in 6 (50%), 4 (80%), and 5 (41.7%), respectively, according to patients self-report. No surgical-related complication was observed in any of the cases. Discussion: We conclude that neuroendoscopic-assisted surgery is an effective surgical method for symptomatic Tarlov cysts with minimized complications.

18.
Transfusion ; 64(4): 705-715, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38420746

ABSTRACT

BACKGROUND: Donors possess heterogeneous red cell concentrates (RCCs) in terms of the biological age of their red blood cells (RBCs) as a direct result of various donor-dependent factors influencing rates of erythropoiesis. This study aimed to estimate the median biological age of RBCs in RCCs based on donor age and sex to investigate inherent differences in blood products' biological ages over hypothermic storage using estimated median densities (EMDs). STUDY DESIGN: Sixty RCCs were collected from four donor groups; male and female teenagers (17-19 years old) and seniors (75+ years old). A Percoll density-based separation approach was used to quantify the EMDs indicative of biological age. EMD and mean corpuscular hemoglobin (MCHC) were compared by correlation analyses. RESULTS: Differences in the median biological age of RCC units were observed with male donors having significantly higher EMDs compared to females (p < .001). Teen male donors possessed the highest EMDs with significantly elevated levels of biologically aged RBCs compared to both female donor groups, regardless of storage duration (p < .05). Throughout most of the 42-day storage period, senior donors, particularly senior females, demonstrated the strongest correlation between EMD and MCHC (R2 > 0.5). CONCLUSIONS: This study provides further evidence that there are inherent differences between the biological age profiles of RBCs between blood donors of different sex and age. Our findings further highlight that biological age may contribute to RBC quality during storage and that donor characteristics need to be considered when evaluating transfusion safety and efficacy.


Subject(s)
Erythrocytes , Sex Characteristics , Adolescent , Humans , Male , Female , Aged , Young Adult , Adult , Blood Donors , Erythrocyte Transfusion , Aging , Blood Preservation
19.
World J Clin Cases ; 12(4): 820-827, 2024 Feb 06.
Article in English | MEDLINE | ID: mdl-38322681

ABSTRACT

BACKGROUND: Human epidermal growth factor receptor-2 (HER-2) plays a vital role in tumor cell proliferation and metastasis. However, the prognosis of HER2-positive gastric cancer is poor. Inetetamab, a novel anti-HER2 targeting drug independently developed in China, exhibits more potent antibody-dependent cell-mediated cytotoxicity than trastuzumab, which is administered as the first-line treatment for HER2-positive gastric cancer in combination with chemotherapy. In this case, the efficacy and safety of inetetamab combined with tegafur was investigated as a second-line treatment for HER2-positive gastric cancer. CASE SUMMARY: A 52-year-old male patient with HER2-positive gastric cancer presented with abdominal distension, poor appetite, and fatigue two years after receiving six cycles of oxaliplatin combined with tegafur as first-line treatment after surgery, followed by tegafur monotherapy for six months. The patient was diagnosed with postoperative recurrence of gastric adenocarcinoma. He received 17 cycles of a combination of inetetamab, an innovative domestically developed anti-HER2 monoclonal antibody, and tegafur chemotherapy as the second-line treatment (inetetamab 200 mg on day 1, every 3 wk combined with tegafur twice daily on days 1-14, every 3 wk). Evaluation of the efficacy of the second-line treatment revealed that the patient achieved a stable condition and progression-free survival of 17 months. He tolerated the treatment well without exhibiting any grade 3-4 adverse events. CONCLUSION: Inetetamab combined with chemotherapy for the treatment of metastatic HER2-positive gastric cancer demonstrates significant survival benefits and acceptable safety.

20.
Vox Sang ; 119(5): 417-427, 2024 May.
Article in English | MEDLINE | ID: mdl-38418415

ABSTRACT

BACKGROUND AND OBJECTIVES: Donor factors influence the quality characteristics of red cell concentrates (RCCs) and the lesions that develop in these heterogeneous blood products during hypothermic storage. Teen male donors' RCCs contain elevated levels of biologically old red blood cells (RBCs). The aim of this study was to interrogate the quality of units of different donor ages and sexes to unravel the complex interplay between donor characteristics, long-term cold storage and, for the first time, RBC biological age. MATERIALS AND METHODS: RCCs from teen males, teen females, senior males and senior females were density-separated into less-dense/young (Y-RBCs) and dense/old RBCs (O-RBCs) throughout hypothermic storage for testing. The unseparated and density-separated cells were tested for haematological parameters, stress (oxidative and osmotic) haemolysis and oxygen affinity (p50). RESULTS: The O-RBCs obtained from teen donor samples, particularly males, had smaller mean corpuscular volumes and higher mean corpuscular haemoglobin concentrations. While biological age did not significantly affect oxygen affinity, biologically aged O-RBCs from stored RCCs exhibited increased oxidative haemolysis and decreased osmotic fragility, with teenage male RCCs exhibiting the highest propensity to haemolyse. CONCLUSION: Previously, donor age and sex were shown to have an impact on the biological age distribution of RBCs within RCCs. Herein, we demonstrated that RBC biological age, particularly O-RBCs, which are found more prevalently in male teens, to be a driving factor of several aspects of poor blood product quality. This study emphasizes that donor factors should continue to be considered for their potential impacts on transfusion outcomes.


Subject(s)
Blood Donors , Blood Preservation , Erythrocytes , Humans , Male , Erythrocytes/cytology , Erythrocytes/metabolism , Adolescent , Blood Preservation/methods , Female , Adult , Hemolysis , Middle Aged , Age Factors , Aged , Cellular Senescence
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