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1.
Int J Mol Sci ; 25(9)2024 Apr 27.
Article in English | MEDLINE | ID: mdl-38732019

ABSTRACT

Thrombosis is the pathological clot formation under abnormal hemodynamic conditions, which can result in vascular obstruction, causing ischemic strokes and myocardial infarction. Thrombus growth under moderate to low shear (<1000 s-1) relies on platelet activation and coagulation. Thrombosis at elevated high shear rates (>10,000 s-1) is predominantly driven by unactivated platelet binding and aggregating mediated by von Willebrand factor (VWF), while platelet activation and coagulation are secondary in supporting and reinforcing the thrombus. Given the molecular and cellular level information it can access, multiscale computational modeling informed by biology can provide new pathophysiological mechanisms that are otherwise not accessible experimentally, holding promise for novel first-principle-based therapeutics. In this review, we summarize the key aspects of platelet biorheology and mechanobiology, focusing on the molecular and cellular scale events and how they build up to thrombosis through platelet adhesion and aggregation in the presence or absence of platelet activation. In particular, we highlight recent advancements in multiscale modeling of platelet biorheology and mechanobiology and how they can lead to the better prediction and quantification of thrombus formation, exemplifying the exciting paradigm of digital medicine.


Subject(s)
Blood Platelets , Hemostasis , Thrombosis , Humans , Thrombosis/metabolism , Blood Platelets/metabolism , Hemostasis/physiology , Platelet Activation , Animals , Platelet Adhesiveness , Platelet Aggregation
2.
ACS Nano ; 18(20): 12981-12993, 2024 May 21.
Article in English | MEDLINE | ID: mdl-38717035

ABSTRACT

Aqueous aluminum-ion batteries (AAIBs) are considered as a promising alternative to lithium-ion batteries due to their large theoretical capacity, high safety, and low cost. However, the uneven deposition, hydrogen evolution reaction (HER), and corrosion during cycling impede the development of AAIBs, especially under a harsh environment. Here, a hydrated eutectic electrolyte (AATH40) composed of Al(OTf)3, acetonitrile (AN), triethyl phosphate (TEP), and H2O was designed to improve the electrochemical performance of AAIBs in a wide temperature range. The combination of molecular dynamics simulations and spectroscopy analysis reveals that AATH40 has a less-water-solvated structure [Al(AN)2(TEP)(OTf)2(H2O)]3+, which effectively inhibits side reactions, decreases the freezing point, and extends the electrochemical window of the electrolyte. Furthermore, the formation of a solid electrolyte interface, which effectively inhibits HER and corrosion, has been demonstrated by X-ray photoelectron spectroscopy, X-ray diffraction tests, and in situ differential electrochemical mass spectrometry. Additionally, operando synchrotron Fourier transform infrared spectroscopy and electrochemical quartz crystal microbalance with dissipation monitoring reveal a three-electron storage mechanism for the Al//polyaniline full cells. Consequently, AAIBs with this electrolyte exhibit improved cycling stability within the temperature range of -10-50 °C. This present study introduces a promising methodology for designing electrolytes suitable for low-cost, safe, and stable AAIBs over a wide temperature range.

3.
Biochem Pharmacol ; 224: 116229, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38643904

ABSTRACT

Prostate cancer causes numerous male deaths annually. Although great progress has been made in the diagnosis and treatment of prostate cancer during the past several decades, much about this disease remains unknown, especially its pathobiology. The kinesin superfamily is a pivotal group of motor proteins, that contains a microtubule-based motor domain and features an adenosine triphosphatase activity and motility characteristics. Large-scale sequencing analyses based on clinical samples and animal models have shown that several members of the kinesin family are dysregulated in prostate cancer. Abnormal expression of kinesins could be linked to uncontrolled cell growth, inhibited apoptosis and increased metastasis ability. Additionally, kinesins may be implicated in chemotherapy resistance and escape immunologic cytotoxicity, which creates a barrier to cancer treatment. Here we cover the recent advances in understanding how kinesins may drive prostate cancer progression and how targeting their function may be a therapeutic strategy. A better understanding of kinesins in prostate cancer tumorigenesis may be pivotal for improving disease outcomes in prostate cancer patients.


Subject(s)
Disease Progression , Kinesins , Prostatic Neoplasms , Humans , Kinesins/metabolism , Kinesins/genetics , Kinesins/physiology , Male , Prostatic Neoplasms/metabolism , Prostatic Neoplasms/pathology , Animals
4.
Int J Oncol ; 64(5)2024 05.
Article in English | MEDLINE | ID: mdl-38551160

ABSTRACT

YTHDF1, an N6­methyladenosine (m6A)­binding protein, is significantly upregulated in glioma tissues. The present study investigated the molecular mechanism underlying the regulatory effects of YTHDF1 on the viability, invasion and self­renewal of glioma stem cells (GSCs). Glioma and normal brain tissues were collected, and reverse transcription­quantitative PCR and western blotting were used to measure the gene and protein expression levels, respectively. Methylated RNA immunoprecipitation­PCR was used to assess the m6A modification level of the target gene. Subsequently GSCs were induced, and YTHDF1 and LINC00900 gene regulation was carried out using lentiviral infection. The viability, invasion and self­renewal of GSCs were assessed by Cell Counting Kit­8, Transwell and sphere formation assays, respectively. Binding between YTHDF1 and LINC00900 was verified by RNA immunoprecipitation and RNA pull­down assays. The targeted binding of microRNA (miR)­1205 to the LINC00900/STAT3 3'­UTR was verified using a luciferase reporter assay. The results revealed that YTHDF1 and LINC00900 expression levels were significantly upregulated in glioma tissues, and a high m6A modification level in LINC00900 transcripts was detected in glioma tissues. Overexpression of YTHDF1 promoted GSC viability, invasion and self­renewal, whereas knockdown of YTHDF1 had the opposite effects. In addition, YTHDF1 maintained the stability of LINC00900 and upregulated its expression through binding to it, thereby promoting GSC viability, invasion and self­renewal. Furthermore, LINC00900 promoted GSC viability, invasion, self­renewal and tumor growth by regulating the miR­1205/STAT3 axis. In conclusion, YTHDF1 promotes GSC viability and self­renewal by regulating the LINC00900/miR­1205/STAT3 axis.


Subject(s)
Brain Neoplasms , Glioma , MicroRNAs , Neoplastic Stem Cells , Humans , Brain Neoplasms/pathology , Cell Line, Tumor , Cell Proliferation/genetics , Gene Expression Regulation, Neoplastic , Glioma/pathology , MicroRNAs/metabolism , Neoplastic Stem Cells/pathology , RNA-Binding Proteins/genetics , RNA-Binding Proteins/metabolism
5.
J Virol ; 98(3): e0181523, 2024 Mar 19.
Article in English | MEDLINE | ID: mdl-38421179

ABSTRACT

Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging tick-borne bunyavirus with high pathogenicity. There has been a gradual increase in the number of reported cases in recent years, with high morbidity and mortality rates. The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway plays an important role in the innate immune defense activated by viral infection; however, the role of the cGAS-STING signaling pathway during SFTSV infection is still unclear. In this study, we investigated the relationship between SFTSV infection and cGAS-STING signaling. We found that SFTSV infection caused the release of mitochondrial DNA into the cytoplasm and inhibits downstream innate immune signaling pathways by activating the cytoplasmic DNA receptor cGAS. We found that the SFTSV envelope glycoprotein Gn was a potent inhibitor of the cGAS-STING pathway and blocked the nuclear accumulation of interferon regulatory factor 3 and p65 to inhibit downstream innate immune signaling. Gn of SFTSV interacted with STING to inhibit STING dimerization and inhibited K27-ubiquitin modification of STING to disrupt the assembly of the STING-TANK-binding kinase 1 complex and downstream signaling. In addition, Gn was found to be involved in inducing STING degradation, further inhibiting the downstream immune response. In conclusion, this study identified the important role of the glycoprotein Gn in the antiviral innate immune response and revealed a novel mechanism of immune escape for SFTSV. Moreover, this study increases the understanding of the pathogenic mechanism of SFTSV and provides new insights for further treatment of SFTS. IMPORTANCE: Severe fever with thrombocytopenia syndrome virus (SFTSV) is a newly discovered virus associated with severe hemorrhagic fever in humans. However, the role of the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway during SFTSV infection is still unclear. We found that SFTSV infection inhibits downstream innate immune signaling pathways by activating the cytoplasmic DNA receptor cGAS. In addition, SFTSV Gn blocked the nuclear accumulation of interferon regulatory factor 3 and p65 to inhibit downstream innate immune signaling. Moreover, we determined that Gn of SFTSV inhibited K27-ubiquitin modification of STING to disrupt the assembly of the STING-TANK-binding kinase 1 complex and downstream signaling. We found that the SFTSV envelope glycoprotein Gn is a potent inhibitor of the cGAS-STING pathway. In conclusion, this study highlights the crucial function of the glycoprotein Gn in the antiviral innate immune response and reveals a new method of immune escape of SFTSV.


Subject(s)
NF-kappa B , Severe Fever with Thrombocytopenia Syndrome , Humans , NF-kappa B/metabolism , Interferon Regulatory Factor-3/metabolism , Signal Transduction/genetics , Immunity, Innate/genetics , Nucleotidyltransferases/metabolism , Interferons/metabolism , Antiviral Agents , Ubiquitins/metabolism , Protein Serine-Threonine Kinases/metabolism
7.
Br J Nutr ; 131(10): 1720-1729, 2024 May 28.
Article in English | MEDLINE | ID: mdl-38275085

ABSTRACT

This study aimed to investigate the association between n-3 PUFA and lung function. First, a cross-sectional study was conducted based on the National Health and Nutrition Examination Survey (NHANES) 2007-2012 data. n-3 PUFA intake was obtained from 24-h dietary recalls. A multivariable linear regression model was used to assess the observational associations of n-3 PUFA intake with lung function. Subsequently, a two-sample Mendelian randomisation (MR) was performed to estimate the potential causal effect of n-3 PUFA on lung function. Genetic instrumental variables were extracted from published genome-wide association studies. Summary statistics about n-3 PUFA was from UK Biobank. Inverse variance weighted was the primary analysis approach. The observational study did not demonstrate a significant association between n-3 PUFA intake and most lung function measures; however, a notable exception was observed with significant findings in the highest quartile for forced vital capacity (FVC) and % predicted FVC. The MR results also showed no causal effect of circulating n-3 PUFA concentration on lung function (forced expiratory volume in one second (FEV1), ß = 0·01301, se = 0·01932, P = 0·5006; FVC, ß = -0·001894, se = 0·01704, P = 0·9115; FEV1:FVC, ß = 0·03118, se = 0·01743, P = 0·07359). These findings indicate the need for further investigation into the impact of higher n-3 PUFA consumption on lung health.


Subject(s)
Fatty Acids, Omega-3 , Lung , Mendelian Randomization Analysis , Nutrition Surveys , Humans , Fatty Acids, Omega-3/administration & dosage , Fatty Acids, Omega-3/blood , Lung/physiology , Male , Cross-Sectional Studies , Female , Middle Aged , Vital Capacity , Adult , Forced Expiratory Volume , Diet , Genome-Wide Association Study , Aged , Respiratory Function Tests
8.
Cancer Lett ; 585: 216613, 2024 Mar 31.
Article in English | MEDLINE | ID: mdl-38211649

ABSTRACT

Several studies have indicated that circular RNAs (circRNAs) play vital roles in the progression of various diseases, including bladder cancer (BCa). However, the underlying mechanisms by which circRNAs drive BCa malignancy remain unclear. In this study, we identified a novel circRNA, circPSMA7 (circbaseID:has_circ_0003456), showing increased expression in BCa cell lines and tissues, by integrating the reported information with circRNA-seq and qRT-PCR. We revealed that circPSMA7 is associated with a higher tumor grade and stage in BCa. M6A modification was identified in circPSMA7, and IGF2BP3 recognized this modification and stabilized circPSMA7, subsequently increasing the circPSMA7 expression. In vitro and in vivo experiments showed that circPSMA7 promoted BCa proliferation and metastasis by regulating the cell cycle and EMT processes. CircPSMA7 acted as a sponge for miR-128-3p, which showed antitumor effects in BCa cell lines, increasing the expression of MAPK1. The tumor proliferation and metastasis suppression induced by silencing circPSMA7 could be partly reversed by miR-128-3p inhibition. Thus, the METTL3/IGF2BP3/circPSMA7/miR-128-3p/MAPK1 axis plays a critical role in BCa progression. Furthermore, circPSMA7 may be a potential diagnostic biomarker and novel therapeutic target for patients with BCa.


Subject(s)
MicroRNAs , Urinary Bladder Neoplasms , Humans , MicroRNAs/genetics , MicroRNAs/metabolism , RNA, Circular/genetics , Cell Line, Tumor , Cell Proliferation/genetics , Urinary Bladder Neoplasms/pathology , Gene Expression Regulation, Neoplastic , Cell Movement/genetics , Methyltransferases/metabolism , Mitogen-Activated Protein Kinase 1/metabolism
9.
J Med Internet Res ; 26: e47508, 2024 Jan 31.
Article in English | MEDLINE | ID: mdl-38294856

ABSTRACT

BACKGROUND: The COVID-19 pandemic raised wide concern from all walks of life globally. Social media platforms became an important channel for information dissemination and an effective medium for public sentiment transmission during the COVID-19 pandemic. OBJECTIVE: Mining and analyzing social media text information can not only reflect the changes in public sentiment characteristics during the COVID-19 pandemic but also help the government understand the trends in public opinion and reasonably control public opinion. METHODS: First, this study collected microblog comments related to the COVID-19 pandemic as a data set. Second, sentiment analysis was carried out based on the topic modeling method combining latent Dirichlet allocation (LDA) and Bidirectional Encoder Representations from Transformers (BERT). Finally, a machine learning linear regression (ML-LR) model combined with a sparse matrix was proposed to explore the evolutionary trend in public opinion on social media and verify the high accuracy of the model. RESULTS: The experimental results show that, in different stages, the characteristics of public emotion are different, and the overall trend is from negative to positive. CONCLUSIONS: The proposed method can effectively reflect the characteristics of the different times and space of public opinion. The results provide theoretical support and practical reference in response to public health and safety events.


Subject(s)
COVID-19 , Social Media , Humans , Public Opinion , Pandemics , Sentiment Analysis , China
10.
World Neurosurg ; 184: e17-e24, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38070738

ABSTRACT

BACKGROUND: To evaluate the reliability of descending neurogenic evoked potentials (DNEP) monitoring in spinal deformity surgery under inhaled anesthesia. METHODS: A total of 180 consecutive patients who underwent spinal deformity surgery in our scoliosis center from July 2014 to August 2016 were reviewed. Intraoperative monitoring including somatosensory evoked potentials (SEP), motor evoked potentials (MEP), and DNEP was conducted routinely throughout operation. Patients were divided into 2 groups according to anesthesia methods: group A (n = 72, inhaled anesthesia, SEP/DNEP) and group B (n = 108, total intravenous anesthesia, SEP/MEP/DNEP). Intraoperative monitoring data were collected and analyzed. RESULTS: Positive alerts were observed in 26 patients (14.5%), of whom 18 (10%) were confirmed as true-positive events in the study population. No false-negative events were recorded. In group A, the sensitivity and specificity of SEP and DNEP were 100% and 93.8% and 100% and 98.5%, respectively. For group B, the sensitivity and specificity of SEP/MEP and DNEP were 100% and 95.9% and 100% and 98%, respectively. CONCLUSIONS: DNEP monitoring seemed to be effective for the detection and prevention of iatrogenic neurologic deficits during spinal deformity surgery. This study indicates that DNEP was an effective alternative in spinal deformity surgery under inhaled anesthesia.


Subject(s)
Evoked Potentials, Motor , Evoked Potentials, Somatosensory , Humans , Reproducibility of Results , Retrospective Studies , Evoked Potentials, Somatosensory/physiology , Evoked Potentials, Motor/physiology , Anesthesia, General
11.
Adv Mater ; 36(11): e2310623, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38088907

ABSTRACT

The practical implementation of aqueous zinc-ion batteries (AZIBs) encounters challenges such as dendrite growth, parasitic reactions, and severe decay in battery performance under harsh environments. Here, a novel hydrated eutectic electrolyte (HEE) composed of Zn(ClO4 )2 ·6H2 O, ethylene glycol (EG), and InCl3 solution is introduced to effectively extend the lifespan of AZIBs over a wide temperature range from -50 to 50 °C. Molecular dynamics simulations and spectroscopy analysis demonstrate that the H2 O molecules are confined within the liquid eutectic network through dual-interaction, involving coordination with Zn2+ and hydrogen bonding with EG, thus weakening the activity of free water and extending the electrochemical window. Importantly, cryo-transmission electron microscopy and spectroscopy techniques reveal that HEE in situ forms a zincophobic/zincophilic bilayer interphase by the dissociation-reduction of eutectic molecules. Specifically, the zincophilic interphase reduces the energy barrier for Zn nucleation, promoting uniform Zn deposition, while the zincophobic interphase prevents active water from contacting the Zn surface, thus inhibiting the side reactions. Furthermore, the relationships between the structural evolution of the liquid eutectic network and interfacial chemistry at electrode/electrolyte interphase are further discussed in this work. The scalability of this design strategy can bring benefits to AZIBs operating over a wide temperature range.

12.
J Orthop Surg Res ; 18(1): 950, 2023 Dec 11.
Article in English | MEDLINE | ID: mdl-38082370

ABSTRACT

OBJECTIVE: Although spinal endoscopic techniques have shown great advantages in the treatment of single-segment lumbar disk herniation (LDH), the therapeutic advantages for double-segment LDH are controversial. To compare the outcomes of percutaneous endoscopic interlaminar discectomy (PEID) versus conventional open lumbar discectomy (COLD) for the treatment of L4/5 and L5/S1 double-segmental LDH. METHODS: From January 2016 to September 2021, we included 50 patients with double-segmental LDH who underwent PEID (n = 25) or COLD (n = 25). The clinical outcomes between the two groups were evaluated using the visual analog scale (VAS), the Oswestry disability index (ODI), and the modified MacNab criteria. Moreover, the incision length, operation time, intraoperative fluoroscopy time, postoperative bedtime, hospital stays, and complications were also recorded and compared after surgery. RESULTS: In both groups, the VAS and ODI scores at different timepoints postoperatively were significantly improved compared with those preoperatively (P < 0.05) According to the modified MacNab criteria, the excellent or good outcome rate was 92% in the PEID group and 88% in the COLD group. The PEID group had shorter incision length, postoperative bedtime, and hospital stays than the COLD group. However, the operation time was shorter and intraoperative fluoroscopy time was fewer in the COLD group. In addition, there was no significant difference between the two groups in terms of surgical complications during the postoperative follow-up period. CONCLUSIONS: Both PEID and COLD have good efficacy and high safety for management of L4/5 and L5/S1 double-segmental LDH. Compared with the COLD group, the PEID group had more operative time as well as more intraoperative fluoroscopy, but it had a more minimally invasive surgical incision as well as faster postoperative recovery.


Subject(s)
Diskectomy, Percutaneous , Intervertebral Disc Displacement , Humans , Intervertebral Disc Displacement/diagnostic imaging , Intervertebral Disc Displacement/surgery , Lumbar Vertebrae/diagnostic imaging , Lumbar Vertebrae/surgery , Retrospective Studies , Endoscopy/methods , Diskectomy, Percutaneous/methods , Diskectomy/methods , Treatment Outcome
13.
ACS Appl Mater Interfaces ; 15(46): 53651-53664, 2023 Nov 22.
Article in English | MEDLINE | ID: mdl-37944056

ABSTRACT

The special structure of perovskite-like compounds allows the existence of some open spaces in the crystals that play an important role in their crystal function enhancement and can accommodate active oxygen, which helps to solve some problems in the field of corrosion prevention. The magnetic lanthanum cuprate was obtained through the doping of Co2+ and Sr2+, and compared with La2CuO4 and epoxy resin, its corrosion resistance was improved by 215.2 and 566.7%, respectively. The micromagnetic field in the crystal interfered with the state of motion of the electrons and prolonged their transport path. High concentration doping and substitution of unequal states led to the formation of oxygen vacancy defects, which could trap active oxygen molecules and inhibit cathodic corrosion reactions. The unique alternating interlayer structure of perovskite-like compounds was conducive to the release of Cu2+, thus forming a more stable passivator on the surface of the coating. La1.96Sr0.04Cu0.98Co0.02O4 had both magnetic properties and structural advantages, which enhanced the shielding property of epoxy resin and expanded the application of perovskite-like compounds in the field of corrosion prevention.

14.
J Nanobiotechnology ; 21(1): 453, 2023 Nov 28.
Article in English | MEDLINE | ID: mdl-38017517

ABSTRACT

BACKGROUND: Cell transplantation has been demonstrated as a promising approach in tissue regeneration. However, the reactive oxygen species (ROS) accumulation and inflammation condition establish a harsh microenvironment in degenerated tissue, which makes the transplanted cells difficult to survive. METHODS: In this study, we constructed a keep-charging hydrogel microsphere system to enable cells actively proliferate and function in the degenerated intervertebral disc. Specifically, we combined Mg2+ to histidine-functionalized hyaluronic acid (HA-His-Mg2+) through coordination reaction, which was further intercrossed with GelMA to construct a double-network hydrogel microsphere (GelMA/HA-His-Mg2+, GHHM) with microfluidic methods. In vitro, the GHHM loaded with nucleus pulposus cells (GHHM@NPCs) was further tested for its ability to promote NPCs proliferation and anti-inflammatory properties. In vivo, the ability of GHHM@NPCs to promote regeneration of NP tissue and rescue intervertebral disc degeneration (IVDD) was evaluated by the rat intervertebral disc acupuncture model. RESULTS: The GHHM significantly enhanced NPCs adhesion and proliferation, providing an ideal platform for the NPCs to grow on. The loaded NPCs were kept active in the degenerative intervertebral disc microenvironment as charged by the Mg2+ in GHHM microspheres to effectively support the loaded NPCs to reply against the ROS-induced inflammation and senescence. Moreover, we observed that GHHM@NPCs effectively alleviated nucleus pulposus degeneration and promoted its regeneration in the rat IVDD model. CONCLUSION: In conclusion, we constructed a keep charging system with a double-network hydrogel microsphere as a framework and Mg2+ as a cell activity enhancer, which effectively maintains NPCs active to fight against the harsh microenvironment in the degenerative intervertebral disc. The GHHM@NPCs system provides a promising approach for IVDD management.


Subject(s)
Intervertebral Disc Degeneration , Nucleus Pulposus , Rats , Animals , Intervertebral Disc Degeneration/therapy , Intervertebral Disc Degeneration/metabolism , Microspheres , Hydrogels/pharmacology , Reactive Oxygen Species/metabolism , Inflammation/metabolism
15.
Exp Ther Med ; 26(1): 335, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37383374

ABSTRACT

To assess the clinical and radiographic effectiveness of unilateral and bilateral percutaneous kyphoplasty (PKP) in the treatment of osteoporotic vertebral compression fractures (OVCF) associated with scoliosis, 52 patients with OVCF associated with scoliosis who underwent PKP were retrospectively analysed. The patients were divided into the unilateral PKP group (n=26) and the bilateral PKP group (n=26). The operation time, bone cement injection volume and frequency of intraoperative fluoroscopy were recorded and compared between the groups. Additionally, visual analogue scale (VAS) and Oswestry disability index (ODI) scores, as well as postoperative complications, including bone cement leakage and adjacent vertebral fractures, were also assessed. The operation time, bone cement injection volume and intraoperative fluoroscopy frequency were significantly lower in the unilateral compared with the bilateral group (P<0.001). The VAS score, ODI score, average vertebral body height and kyphotic angle (KA) were improved after surgery in each group with no difference in these clinical parameters between the two groups both before and after surgery. Furthermore, the proportion of cases with bone cement leakage in the unilateral group was significantly lower compared with that in the bilateral group (P<0.05). During the follow-up, there were three cases (11.5%) in the unilateral group and two cases (7.7%) in the bilateral group who suffered adjacent vertebral fractures, but there was no statistically significant difference between the two groups (P>0.05). For treating patients with OVCF accompanied by scoliosis, both unilateral and bilateral PKP could effectively relieve the acute back pain and correct the KA. However, unilateral PKP presents more advantages, such as a short operation duration and reduced intraoperative fluoroscopy frequency and bone cement leakage.

16.
Proc Natl Acad Sci U S A ; 120(6): e2217607120, 2023 02 07.
Article in English | MEDLINE | ID: mdl-36730189

ABSTRACT

The spleen clears altered red blood cells (RBCs) from circulation, contributing to the balance between RBC formation (erythropoiesis) and removal. The splenic RBC retention and elimination occur predominantly in open circulation where RBCs flow through macrophages and inter-endothelial slits (IESs). The mechanisms underlying and interconnecting these processes significantly impact clinical outcomes. In sickle cell disease (SCD), blockage of intrasplenic sickled RBCs is observed in infants splenectomized due to acute splenic sequestration crisis (ASSC). This life-threatening RBC pooling and organ swelling event is plausibly triggered or enhanced by intra-tissular hypoxia. We present an oxygen-mediated spleen-on-a-chip platform for in vitro investigations of the homeostatic balance in the spleen. To demonstrate and validate the benefits of this general microfluidic platform, we focus on SCD and study the effects of hypoxia on splenic RBC retention and elimination. We observe that RBC retention by IESs and RBC-macrophage adhesion are faster in blood samples from SCD patients than those from healthy subjects. This difference is markedly exacerbated under hypoxia. Moreover, the sickled RBCs under hypoxia show distinctly different phagocytosis processes from those non-sickled RBCs under hypoxia or normoxia. We find that reoxygenation significantly alleviates RBC retention at IESs, and leads to rapid unsickling and fragmentation of the ingested sickled RBCs inside macrophages. These results provide unique mechanistic insights into how the spleen maintains its homeostatic balance between splenic RBC retention and elimination, and shed light on how disruptions in this balance could lead to anemia, splenomegaly, and ASSC in SCD and possible clinical manifestations in other hematologic diseases.


Subject(s)
Anemia, Sickle Cell , Spleen , Humans , Microfluidics , Erythrocytes , Hypoxia
17.
Adv Mater ; 35(17): e2210082, 2023 Apr.
Article in English | MEDLINE | ID: mdl-36738238

ABSTRACT

Sustainable organic electrode materials, as promising alternatives to conventional inorganic electrode materials for sodium-ion batteries (SIBs), are still challenging to realize long-lifetime and high-rate batteries because of their poor conductivity, limited electroactivity, and severe dissolution. It is also urgent to deeply reveal their electrochemical mechanism and evolution processes. A porous organic polymer (POP) with a conjugated and hierarchical structure is designed and synthesized here. The unique molecule and structure endow the POP with electron delocalization, high ionic diffusivity, plentiful active sites, exceptional structure stability, and limited solubility in electrolytes. When evaluated as an anode for SIBs, the POP exhibits appealing electrochemical properties regarding reversible capacity, rate behaviors, and long-duration life. Importantly, using judiciously combined experiments and theoretical computation, including in situ transmission electron microscopy (TEM), and ex situ spectroscopy, we reveal the Na-storage mechanism and dynamic evolution processes of the POP, including 12-electron reaction process with Na, low volume expansion (125-106% vs the initial 100%), and stable composition and structure evolution during repeating sodiation/de-sodiation processes. This quantitative design for ultrafast and highly durable sodium storage in the POP could be of immediate benefit for the rational design of organic electrode materials with ideal electrochemical properties.

18.
ACS Nano ; 2023 Jan 03.
Article in English | MEDLINE | ID: mdl-36594407

ABSTRACT

Aqueous zinc-ion batteries (AZIBs) have attracted attention for their low cost and environmental friendliness. Unfortunately, commercialization has been hampered by several problems with dendrite growth and side reactions. Herein, we select sodium tartrate (TA-Na) as a dual-functional electrolyte additive to enhance the reversibility of AZIBs. The tartrate anions are preferentially adsorbed on the Zn surface, and then the highly nucleophilic carboxylate will coordinate with Zn2+ to promote the desolvation of [Zn(H2O)6]2+, leading to uniform Zn deposition on the beneficial (002) plane and inhibiting side reactions and dendrite growth. Consequently, the Zn|Zn cells show a long-term cycling stability of over 1500 cycles at 0.5 mA cm-2. Moreover, the Ta-Na additive improves the performance of Zn||MnO2 full cells, evidenced by a cycling life of 1000 cycles at 1 A g-1 under practical conditions with a limited Zn anode (negative/positive capacity ratio of 10/1) and controlled electrolyte (electrolyte/capacity ratio of 20 µL mAh-1).

19.
Mater Today Bio ; 18: 100519, 2023 Feb.
Article in English | MEDLINE | ID: mdl-36590983

ABSTRACT

The periosteum on the skeletal surface creates a unique micro-environment for cortical bone homeostasis, but how this micro-environment is formed remains a mystery. In our study, we observed the cells in the periosteum presented elongated spindle-like morphology within the aligned collagen fibers, which is in accordance with the differentiated osteoblasts lining on the cortical surface. We planted the bone marrow stromal cells(BMSCs), the regular shaped progenitor cells, on collagen-coated aligned fibers, presenting similar cell morphology as observed in the natural periosteum. The aligned collagen topology induced the elongation of BMSCs, whichfacilitated the osteogenic process. Transcriptome analysis suggested the aligned collagen induced the regular shaped cells to present part of the periosteum derived stromal cells(PDSCs) characteristics by showing close correlation of the two cell populations. In addition, the elevated expression of PDSCs markers in the cells grown on the aligned collagen-coated fibers further indicated the function of periosteal topology in manipulating cells' behavior. Enrichment analysis revealed cell-extracellular matrix interaction was the major pathway initiating this process, which created an osteo-friendly micro-environment as well. At last, we found the aligned topology of collagen induced mechano-growth factor expression as the result of Igf1 alternative splicing, guiding the progenitor cells behavior and osteogenic process in the periosteum. This study uncovers the key role of the aligned topology of collagen in the periosteum and explains the mechanism in creating the periosteal micro-environment, which gives the inspiration for artificial periosteum design.

20.
Phys Chem Chem Phys ; 25(1): 847-856, 2022 Dec 21.
Article in English | MEDLINE | ID: mdl-36511817

ABSTRACT

In this work, we systematically investigate the photocatalytic mechanism of g-C3N4/BiOI (001) through hybrid functional calculations based on first-principles theory. The staggered band structure is observed in the g-C3N4/BiOI (001); meanwhile, a built-in electric field exists from the g-C3N4 monolayer to the BiOI surface at the interface. BiOI has lower band edges, which bend downward at the interface; whereas g-C3N4 has higher band edges, which bend upward. With Coulomb interaction and the built-in electric field, photo-generated electrons in the conduction bands (CB) of BiOI recombine with photo-generated holes in the valence bands (VB) of g-C3N4. Meanwhile, the stronger reduction capacity for photo-excited electrons in the g-C3N4's CB and the stronger oxidation capacity for photo-generated holes in the BiOI (001)'s VB are retained. Therefore, a direct Z-scheme heterostructure character is presented. As a result, the electrons and holes generated by the photons can be separated and migrate highly effectively at the interface. The separated electrons and holes can effectively participate in the redox reactions with water/pollutants to produce the photocatalytically reactive species superoxide ions (˙O2-) and hydroxyl radicals (˙OH), respectively. This is consistent with the experimental results. It is also worth noting that the g-C3N4/BiOI (001) heterostructure shows a larger difference in the effective mass of carriers. Therefore, the direct Z-scheme charge transfer and separation mechanism and the larger effective mass difference of carriers lead to the superior photocatalytic activity of the g-C3N4/BiOI (001) in experiments. A few speculations and controversies that arose from the experiments are clarified.

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