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1.
Neural Regen Res ; 20(7): 1883-1899, 2025 Jul 01.
Article in English | MEDLINE | ID: mdl-39254548

ABSTRACT

Various nanoparticle-based drug delivery systems for the treatment of neurological disorders have been widely studied. However, their inability to cross the blood-brain barrier hampers the clinical translation of these therapeutic strategies. Liposomes are nanoparticles composed of lipid bilayers, which can effectively encapsulate drugs and improve drug delivery across the blood-brain barrier and into brain tissue through their targeting and permeability. Therefore, they can potentially treat traumatic and nontraumatic central nervous system diseases. In this review, we outlined the common properties and preparation methods of liposomes, including thin-film hydration, reverse-phase evaporation, solvent injection techniques, detergent removal methods, and microfluidics techniques. Afterwards, we comprehensively discussed the current applications of liposomes in central nervous system diseases, such as Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, traumatic brain injury, spinal cord injury, and brain tumors. Most studies related to liposomes are still in the laboratory stage and have not yet entered clinical trials. Additionally, their application as drug delivery systems in clinical practice faces challenges such as drug stability, targeting efficiency, and safety. Therefore, we proposed development strategies related to liposomes to further promote their development in neurological disease research.

2.
Heliyon ; 10(17): e37388, 2024 Sep 15.
Article in English | MEDLINE | ID: mdl-39290272

ABSTRACT

Netrin-1 (NTN1) is involved in psychological alterations caused by central nerve system diseases. The primary objective of this research was to investigate whether a deficiency of neuron-derived NTN1 in the remote brain regions affects SCI outcomes. To examine the roles and mechanisms of neuron-derived NTN1 during SCI, Western blots, Nissl staining, immunochemical technique, RNA-sequence, and related behavioral tests were conducted in the study. Our study revealed that mice lacking NTN1 exhibited normal morphological structure of the spinal cords, hippocampus, and neurological function. While neuron-derived NTN1deletion mechanistically disrupted neuronal regeneration and aggregates neuronal apoptosis and ferroptosis in the intermediate phase following SCI. Additionally, neuroinflammation was significantly enhanced in the early phase, which could be related to activation of the NF-κB signaling pathway. Overall, our findings indicate that the deletion of neuron-derived NTN1 leads to the activation of the NF-κB pathway, contributing to the promotion of neuronal apoptosis and ferroptosis, and the pathological progression of SCI.

3.
World J Clin Cases ; 12(26): 5983-5989, 2024 Sep 16.
Article in English | MEDLINE | ID: mdl-39286392

ABSTRACT

BACKGROUND: A sclerosing epithelioid fibrosarcoma (SEF) is a rare malignant fibroblastic soft tissue tumor that rarely occurs in intra-abdominal organs. A case of a SEF in the pancreatic head is reported herein, including its clinical manifestations, preoperative imaging features, gross specimen and pathological findings. CASE SUMMARY: A 33-year-old male patient was admitted to Peking Union Medical College Hospital in December 2023 due to a one-year history of intermittent upper abdominal pain and the discovery of a pancreatic mass. The patient underwent an enhanced computed tomography scan of the abdomen, which revealed a well-defined, round mass with clear borders and calcifications in the pancreatic head. The mass exhibited progressive, uneven mild enhancement, measuring approximately 6.6 cm × 6.3 cm. The patient underwent laparoscopic pylorus-preserving pancreaticoduodenectomy. Postoperative pathological examination revealed that the lesion was consistent with a SEF. At the 3-month postoperative follow-up, the patient did not report any short-term complications, and there were no signs of tumor recurrence. CONCLUSION: SEFs are rare malignant fibrous soft tissue tumors. SEFs rarely develop in the pancreas, and its preoperative diagnosis depends on imaging findings, with confirmation depending on pathological examination and immunohistochemistry. Currently, only four cases of pancreatic SEF have been reported in studies written in English. This case is the first reported case of a pancreatic SEF by a clinical physician.

4.
Nanomaterials (Basel) ; 14(18)2024 Sep 14.
Article in English | MEDLINE | ID: mdl-39330650

ABSTRACT

Boron carbide ceramics are potentially ideal candidates for lightweight bulletproof armor, but their use is currently limited by their low fracture toughness. Recent experimental results have shown that sintered samples with high twin densities exhibit high fracture toughness, but the toughening mechanism and associated crack propagation process of nanotwinned boron carbide at the atomic scale remain a mystery. Reported here are molecular dynamics simulations with a reactive force field potential to investigate how nanoscale twins affect the fracture toughness of boron carbide ceramics. The results show that the strength disparity on either side of a twin boundary is the fundamental reason for the toughening effect; the twin boundary impedes crack propagation only when the crack moves to a region of higher fracture strength. The fracture toughness of nanotwinned boron carbide is greatly affected by the angle between the twin boundary and the prefabricated crack. At an angle of 120°, the twin boundary provides the maximum toughening effect, enhancing the toughness by 32.72%. Moreover, phase boundaries-another common structure in boron carbide ceramics-have no toughening effect. This study provides new insights into the design of boron carbide ceramics with high fracture toughness.

5.
Colloids Surf B Biointerfaces ; 245: 114208, 2024 Sep 03.
Article in English | MEDLINE | ID: mdl-39255749

ABSTRACT

Implant-associated infections (IAIs), triggered by pathogenic bacteria, are a leading cause of implant failure. The design of functionalized coatings on biomedical materials is crucial to address IAIs. Herein, a multifunctional coating with good antifouling effect and antibacterial photothermal therapy (aPTT) performance was developed. The copper tannate nanosheets (CuTA NSs) were formed via coordination bonding of Cu2+ ions and tannic acid (TA). The CuTA NSs were then integrated into the TA and poly(ethylene glycol) (PEG) network to form the TCP coating for deposition on the titanium (Ti) substrates via surface adhesion of TA and gravitational effect. The resulting Ti-TCP substrate exhibited good antifouling property, reactive oxygen species (ROS) scavenging capability and cytocompatibility. The TCP coating exhibited antifouling efficacy in conjunction with aPTT, curtailing the surface adhesion and biofilm formation of pathogens, such as Staphylococcus aureus and Escherichia coli. Notably, the Ti-TCP substrate also exhibited the ability to prevent bacterial infection in vivo in a subcutaneous implantation model. The present work demonstrated a promising approach in designing high-performance antifouling and photothermal bactericidal coatings to combat IAIs.

6.
Front Neuroinform ; 18: 1400702, 2024.
Article in English | MEDLINE | ID: mdl-39239071

ABSTRACT

Purpose: This study aimed to develop a radiomic model based on non-contrast computed tomography (NCCT) after interventional treatment to predict the clinical prognosis of acute ischemic stroke (AIS) with large vessel occlusion. Methods: We retrospectively collected 141 cases of AIS from 2016 to 2020 and analyzed the patients' clinical data as well as NCCT data after interventional treatment. Then, the total dataset was divided into training and testing sets according to the subject serial number. The cerebral hemispheres on the infarct side were segmented for radiomics signature extraction. After radiomics signatures were standardized and dimensionality reduced, the training set was used to construct a radiomics model using machine learning. The testing set was then used to validate the prediction model, which was evaluated based on discrimination, calibration, and clinical utility. Finally, a joint model was constructed by incorporating the radiomics signatures and clinical data. Results: The AUCs of the joint model, radiomics signature, NIHSS score, and hypertension were 0.900, 0.863, 0.727, and 0.591, respectively, in the training set. In the testing set, the AUCs of the joint model, radiomics signature, NIHSS score, and hypertension were 0.885, 0.840, 0.721, and 0.590, respectively. Conclusion: Our results provided evidence that using post-interventional NCCT for a radiomic model could be a valuable tool in predicting the clinical prognosis of AIS with large vessel occlusion.

7.
J Mater Chem B ; 12(37): 9238-9248, 2024 Sep 25.
Article in English | MEDLINE | ID: mdl-39171692

ABSTRACT

Surface modification of biomedical materials and devices using versatile nanocomposite coatings holds great promise for improving functionalities to defend against life-threatening bacterial infections. In this study, a one-step surface modification strategy was developed to deposit gold nanorods (AuNRs)- and curcumin (CUR)-encapsulated zeolitic imidazolate framework-8 (ZIF-8) nanoparticles (AuNRs-ZIF-CUR NPs or AZC) onto phytic acid (PA)-ε-polylysine (Ply) network coatings. In the solution mixture of PA, Ply and AZC, PA interacted with Ply via electrostatic interactions, and can also bind to AZC via metal chelation. The as-formed AZC-PA-Ply aggregates could be deposited onto various substrates via surface adhesion of PA and gravitational effects. The physicochemical and antibacterial properties of the AZC-PA-Ply network coatings on polydimethylsiloxane (PDMS) substrates were evaluated. The sustained release of zinc ions and CUR, as well as the contact-killing ability of Ply, endowed the AZC-PA-Ply network coatings with good antibacterial chemotherapeutic effects. In addition, the embedded AuNRs in the AZC-PA-Ply network coatings exhibited excellent photothermal conversion efficiency for the ablation of bacteria. Upon near-infrared (NIR) laser irradiation, the AZC-PA-Ply-coated PDMS surfaces exhibited strong antibacterial effects by disrupting the membrane integrity and cellular functions of the adhered bacteria. Thus, the AZC-PA-Ply network coatings displayed combined antibacterial chemotherapeutic and photothermal therapeutic effects. Furthermore, the AZC-PA-Ply-coated PDMS substrates exhibited effective bacterial infection prevention and good biocompatibility in an in vivo implant model. Hence, the versatile AZC-PA-Ply network coatings are potentially useful as a multi-modal antibacterial platform to eliminate infectious bacterial pathogens in biomedical applications.


Subject(s)
Anti-Bacterial Agents , Curcumin , Gold , Metal-Organic Frameworks , Metal-Organic Frameworks/chemistry , Metal-Organic Frameworks/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemical synthesis , Gold/chemistry , Gold/pharmacology , Curcumin/chemistry , Curcumin/pharmacology , Staphylococcus aureus/drug effects , Photothermal Therapy , Surface Properties , Microbial Sensitivity Tests , Animals , Polylysine/chemistry , Polylysine/pharmacology , Particle Size , Mice , Polymers/chemistry , Polymers/pharmacology , Nanotubes/chemistry , Coated Materials, Biocompatible/chemistry , Coated Materials, Biocompatible/pharmacology , Escherichia coli/drug effects , Bacterial Infections/drug therapy
8.
ACS Appl Mater Interfaces ; 16(36): 48113-48125, 2024 Sep 11.
Article in English | MEDLINE | ID: mdl-39215692

ABSTRACT

Monolayer MXenes are a novel class of two-dimensional transition metal carbides/nitrides with fascinating physicochemical properties. Despite recent advances in the study of MXenes' mechanical properties, a comprehensive understanding of the fundamental physical mechanisms that affect fracture due to surface terminations and vacancy defects in MXenes under nanoindentation remains largely unexplored. Here, we address this gap using molecular dynamics simulations and nanoindentation theory to investigate the effects of surface terminations and vacancy defects on the fracture behavior of Ti3C2Tx MXenes. By inducing the rupture of monolayer MXenes through nanoindentation, we find that bare Ti3C2 exhibits brittle fracture behavior. The presence of surface terminations and vacancy defects reduces the load-carrying capacity and flexibility of MXenes. Interestingly, surface terminations increase the stiffness of the structure, while vacancy defects have the opposite effect. We also find that high concentrations of surface oxidation impart ductile fracture characteristics to MXenes and increase the maximum crack length at failure. Additionally, defects exceeding the critical concentration can effectively prevent brittle crack propagation by causing frequent crack deflection and blunting crack tips. Combining these findings, we propose a new strategy to synergistically enhance the fracture toughness of MXenes through high concentrations of surface oxidation and vacancy defects exceeding the critical concentration without significantly affecting strength and stiffness, thereby avoiding catastrophic failure in MXene monolayers due to brittle fracture. This work provides fundamental insights into the mechanical properties and fracture mechanisms of monolayer MXenes.

9.
Int J Biol Macromol ; 277(Pt 4): 134562, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39116982

ABSTRACT

Antifreeze proteins (AFPs) can inhibit ice crystal growth. The ice-binding mechanism of AFPs remains unclear, yet the hydration shells of AFPs are thought to play an important role in modulating the binding of AFPs and ice. Here, we performed all-atom molecular dynamics simulations of an AFP from Choristoneura fumiferana (CfAFP) at four different temperatures, with a focus on analysis at 240 and 300 K, to investigate the dynamic and thermodynamic characteristics of hydration shells around ice-binding surfaces (IBS) and non-ice-binding surfaces (NIBS). Our results revealed that the dynamics of CfAFP hydration shells were highly heterogeneous, with its IBS favoring a less dense and more tetrahedral solvation shell, and NIBS hydration shells having opposite features to those of the IBS. The IBS of nine typical hyperactive AFPs were found to be in pure low-entropy hydration shell region, indicating that low-entropy hydration shell region of IBS and the tetrahedral arrangements of water molecules around them mediate the ice-binding mechanism of AFPs. It is because the entropy increase of the low-entropy hydration shell around IBS, while the higher entropy water molecules at NIBS most likely prevent ice crystal growth. These findings provide new mechanistic insights into the ice-binding of AFPs.


Subject(s)
Antifreeze Proteins , Insect Proteins , Moths , Antifreeze Proteins/chemistry , Antifreeze Proteins/metabolism , Moths/chemistry , Moths/metabolism , Insect Proteins/chemistry , Insect Proteins/metabolism , Ice , Entropy , Animals , Adsorption , Computer Simulation
10.
Animals (Basel) ; 14(16)2024 Aug 19.
Article in English | MEDLINE | ID: mdl-39199936

ABSTRACT

The present study was designed to assess the impact of Alhagi honey small-molecule sugars (AHAS) on Hu lambs. Therefore, in this study, AHAS low-dose (AHAS-L, 200 mg/ kg per day), AHAS medium-dose (AHAS-M, 400 mg/kg per day), and AHAS high-dose (AHAS-H, 800 mg/kg per day) were administered to Hu lambs to investigate the regulatory effects of AHAS on growth performance, oxidation index, immune system enhancement, and intestinal microbiota. The results showed that lambs in the AHAS-H group exhibited significantly increased in average daily weight gain, and growth performance compared to those in the control group (p < 0.05). Moreover, AHAS-H supplementation resulted in increased levels of serum antioxidant enzymes (SOD, GSH-Px, and T-AOC), serum antibodies (IgA, IgG, and IgM), and cytokines (IL-4, 10,17, IFN-γ, and TNF-α) compared with the control group (p < 0.05). Additionally, it increased the quantity and richness of beneficial bacteria at such as Sphingomonas, Ralstonia, and Flavobacterium, activating various metabolic pathways and promoting the production of various short-chain fatty acids. In summary, our findings highlight the potential of AHAS-H treatment in enhancing intestinal health of lambs by improving intestinal function, immunity, and related metabolic pathways. Consequently, these results suggest that AHAS holds promising potential as a valuable intervention for optimizing growth performance and intestinal health in lambs.

11.
Front Surg ; 11: 1414870, 2024.
Article in English | MEDLINE | ID: mdl-39108285

ABSTRACT

Background: Lymph node involvement is recognized as a prognostic factor for patients with gallbladder cancer. However, the N stage varied from different editions of the American Joint Committee on Cancer (AJCC) TNM Classification. Our objective was to investigate the impact of lymph node involvement on overall survival in elderly patients with non-metastatic gallbladder adenocarcinoma. Methods: Patients older than 65 years with non-metastatic gallbladder adenocarcinoma were identified from the SEER data. We used Cox proportional hazard regression analysis to select the independent risk factor. A nomogram was built to identify the 1-, 3-, and 5-years' prognostic impact. Univariate and multivariate models were used to examine the correlation of overall survival (OS) with the number of metastatic nodes. Results: A total of 1,654 patients (706 with and 948 without nodal involvement) were included. Cox proportional hazard regression analyses found that age, gender, tumor size, lymph node involvement, and surgical options were risk factors for the prognosis and were integrated into the nomogram. After adjustment, OS was compromised for patients who receive surgery with nodal involvement [hazard ratio (HR), 2.238; P < 0.01]. Furthermore, after adjustment the presence of more than two metastatic lymph nodes was associated with decreased OS (HR, 3.305; P < 0.01). Conclusions: Our results suggest that lymph node involvement is associated with compromised survival in elderly patients. A nomogram was developed to predict the prognosis of gallbladder cancer. A change point of more than two metastatic lymph nodes seems to carry prognostic significance, calling for closer monitoring of elderly patients with gallbladder cancer with involvement of increased number of lymph nodes.

12.
Age Ageing ; 53(7)2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38984695

ABSTRACT

PURPOSE: This study aimed to develop a normal brain ageing model based on magnetic resonance imaging and radiomics, therefore identifying radscore, an imaging indicator representing white matter heterogeneity and exploring the significance of radscore in detecting people's cognitive changes. METHODS: Three hundred sixty cognitively normal (CN) subjects from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database and 105 CN subjects from the Parkinson's Progression Markers Initiative database were used to develop the model. In ADNI, 230 mild cognitive impairment (MCI) subjects were matched with 230 CN old-aged subjects to evaluate their heterogeneity difference. One hundred four MCI subjects with 48 months of follow-up were divided into low and high heterogeneity groups. Kaplan-Meier survival curve analysis was used to observe the importance of heterogeneity results for predicting MCI progression. RESULTS: The area under the receiver operating characteristic curve of the model in the training, internal test and external test sets was 0.7503, 0.7512 and 0.7514, respectively. There was a significantly positive correlation between age and radscore of CN subjects (r = 0.501; P < .001). The radscore of MCI subjects was significantly higher than that of matched CN subjects (P < .001). The median radscore ratios of MCI to CN from four age groups (66-70y, 71-75y, 76-80y and 81-85y) were 1.611, 1.760, 1.340 and 1.266, respectively. The probability to progression of low and high heterogeneity groups had a significant difference (P = .002). CONCLUSION: When radscore is significantly higher than that of normal ageing, it is necessary to alert the possibility of cognitive impairment and deterioration.


Subject(s)
Aging , Cognitive Dysfunction , Disease Progression , Magnetic Resonance Imaging , Humans , Cognitive Dysfunction/diagnostic imaging , Cognitive Dysfunction/diagnosis , Aged , Male , Female , Aged, 80 and over , Aging/psychology , Brain/diagnostic imaging , Brain/pathology , Risk Factors , Age Factors , Predictive Value of Tests , Cognition , Databases, Factual , Case-Control Studies , Risk Assessment , White Matter/diagnostic imaging , White Matter/pathology , Radiomics
13.
ACS Appl Mater Interfaces ; 16(28): 36628-36636, 2024 Jul 17.
Article in English | MEDLINE | ID: mdl-38954707

ABSTRACT

Real-time detection of harmful gases at room temperature has become a serious problem in public health and environmental monitoring. Two-dimensional materials with semiconductor properties BiOCl is a promising gas-sensitive material due to its large specific surface area and adjustable band gap as well as outstanding safety characteristics. However, limited by the weak gas adsorption sites and sluggish charge-transfer ability, the performance of BiOCl could not be fully exploited. Oxygen vacancy (Vo) engineering can introduce lattice defects, thereby significantly increasing the local charge density and enhancing the adsorption of gases, which is an effective strategy to enhance the gas-sensing performance. In this work, we composite BiOCl with a vacancy (Vo-BiOCl) and reduced graphene oxide (rGO) to construct a Vo-BiOCl/rGO heterostructure with enhanced gas adsorption sites. Experimental and theoretical calculations show that Vo can enhance the adsorption of gases and the introduction of rGO forms a high-quality heterostructure with BiOCl, which can effectively reduce the band gap of BiOCl and promote electron transfer, thereby improving the sensitivity of the sensor. Benefiting from above, Vo-BiOCl/rGO achieves the ability to detect low concentrations of NO2/NH3 at room temperature, with high sensitivity (55% at 1 ppm of NO2 and -28% at 1 ppm of NH3), fast response time (40 s at 1 ppm of NO2 and 2 s at 1 ppm of NH3), good stability (over 150 days), and fully recoverable gas sensitivity.

15.
World J Surg Oncol ; 22(1): 165, 2024 Jun 25.
Article in English | MEDLINE | ID: mdl-38918808

ABSTRACT

BACKGROUND: The purpose of this study was to compare safety and efficacy outcomes between immediate breast reconstruction (IBR) and mastectomy alone in locally advanced breast cancer patients. METHODS: We conducted a comprehensive literature search of PUBMED, EMBASE, and Cochrane databases. The primary outcomes evaluated were overall survival, disease-free survival, and local recurrence. The secondary outcome was the incidence of surgical complications. All data were analyzed using Review Manager 5.3. RESULTS: Sixteen studies, involving 15,364 participants were included in this meta-analysis. Pooled data demonstrated that patients underwent IBR were more likely to experience surgical complications than those underwent mastectomy alone (HR: 3.96, 95%CI [1.07,14.67], p = 0.04). No significant difference was found in overall survival (HR: 0.94, 95%CI [0.73,1.20], p = 0.62), disease-free survival (HR: 1.03, 95%CI [0.83,1.27], p = 0.81), or breast cancer specific survival (HR: 0.93, 95%CI [0.71,1.21], p = 0.57) between IBR group and Non-IBR group. CONCLUSIONS: Our study demonstrates that IBR after mastectomy does not affect the overall survival and disease-free survival of locally advanced breast cancer patients. However, IBR brings with it a nonnegligible higher risk of complications and needs to be fully evaluated and carefully decided.


Subject(s)
Breast Neoplasms , Mammaplasty , Mastectomy , Postoperative Complications , Humans , Female , Breast Neoplasms/surgery , Breast Neoplasms/pathology , Breast Neoplasms/mortality , Mastectomy/adverse effects , Mastectomy/methods , Mammaplasty/methods , Mammaplasty/adverse effects , Postoperative Complications/etiology , Postoperative Complications/epidemiology , Prognosis , Neoplasm Recurrence, Local/pathology , Neoplasm Recurrence, Local/epidemiology , Neoplasm Recurrence, Local/etiology , Survival Rate
16.
World J Clin Cases ; 12(17): 3206-3213, 2024 Jun 16.
Article in English | MEDLINE | ID: mdl-38898831

ABSTRACT

BACKGROUND: Function-preserving pancreatectomy can improve the long-term quality of life of patients with benign or low-grade malignant tumors, such as intraductal papillary mucinous neoplasms (IPMNs) and mucinous cystic neoplasms. However, there is limited literature on laparoscopic spleen-preserving total pancreatectomy (L-SpTP) due to technical difficulties. CASE SUMMARY: Patient 1 was a 51-year-old male diagnosed with IPMN based on preoperative imaging, showing solid nodules in the pancreatic head and diffuse dilation of the main pancreatic duct with atrophy of the distal pancreas. We performed L-SpTP with preservation of the splenic vessels, and the postoperative pathology report revealed IPMN with invasive carcinoma. Patient 2 was a 60-year-old male with multiple cystic lesions in the pancreatic head and body. L-SpTP was performed, and intraoperatively, the splenic vein was injured and required ligation. Postoperative pathology revealed a mucinous cystic tumor of the pancreas with low-grade dysplasia. Both patients were discharged on postoperative day 7, and there were no major complications during the perioperative period. CONCLUSION: We believe that L-SpTP is a safe and feasible treatment for low-grade malignant pancreatic tumors, but more case studies are needed to evaluate its safety, efficacy, and long-term outcomes.

17.
Nano Lett ; 24(26): 8098-8106, 2024 Jul 03.
Article in English | MEDLINE | ID: mdl-38913786

ABSTRACT

The development of multifunctional MXene-based fabrics for smart textiles and portable devices has garnered significant attention. However, very limited studies have focused on their structure design and associated mechanical properties. Here, the supertough MXene fiber felts composed of MXene/sodium alginate (SA) fibers were fabricated. The fracture strength and bending stiffness of felts can be up to 97.8 MPa and 1.04 N mm2, respectively. Besides, the fracture toughness of felts was evaluated using the classic Griffith theory, yielding to a critical stress intensity factor of 1.79 MPam. In addition, this kind of felt presents outstanding electrothermal conversion performance (up to 119 °C at a voltage of 2.5 V), high cryogenic and high-temperature tolerance of photothermal conversion performance (-196 to 160 °C), and excellent electromagnetic interference (EMI) shielding effectiveness (54.4 dB in the X-band). This work provides new structural design concepts for high-performance MXene-based textiles, broadening their future applications.

18.
Discov Oncol ; 15(1): 218, 2024 Jun 10.
Article in English | MEDLINE | ID: mdl-38856944

ABSTRACT

The role of cathepsin K (CTSK) expression in the pathogenesis and progression of gastric cancer (GC) remains unclear. Hence, the primary objective of this study is to elucidate the precise expression and biological role of CTSK in GC by employing a combination of bioinformatics analysis and in vitro experiments. Our findings indicated a significant upregulation of CTSK in GC. The bioinformatics analysis revealed that GC patients with a high level of CTSK expression exhibited enrichment of hallmark gene sets associated with angiogenesis, epithelial-mesenchymal transition (EMT), inflammatory response, KRAS signaling up, TNFα signaling via KFκB, IL2-STAT5 signaling, and IL6-JAK-STAT3 signaling. Additionally, these patients demonstrated elevated levels of M2-macrophage infiltration, which was also correlated with a poorer prognosis. The results of in vitro experiments provided confirmation that the over-expression of CTSK leads to an increase in the proliferative and invasive abilities of GC cells. However, further evaluation was necessary to determine the impact of CTSK on the migration capability of these cells. Our findings suggested that CTSK has the potential to facilitate the initiation and progression of GC by augmenting the invasive capacity of GC cells, engaging in tumor-associated EMT, and fostering the establishment of an immunosuppressive tumor microenvironment (TME).

19.
Surg Obes Relat Dis ; 20(10): 962-969, 2024 Oct.
Article in English | MEDLINE | ID: mdl-38782612

ABSTRACT

BACKGROUND: Bile acids can stimulate the secretion of glucagon-like peptide-1 (GLP-1) and be mostly reabsorbed in the ileum. OBJECTIVES: We aimed to investigate whether ileum excision could reverse the glucose improvement after biliopancreatic diversion with duodenal switch (BPD/DS). SETTING: Peking Union Medical College Hospital. METHODS: Thirty diabetic rats were randomly divided into the BPD/DS group, BPD/DS plus ileectomy (BDI) group, and control group. The fasting blood glucose, bile acids, and glucagon-like peptide-1(GLP-1) levels in plasma samples were analyzed. RESULTS: In postoperative week 20, the fasting blood glucose level in the BDI group was significantly higher than that in the BPD/DS group (11.5 ± 1.4 mmol/L versus 7.6 ± 1.0 mmol/L, P < .001), and the AUCOGTT value was also significantly higher than that in the BPD/DS group (2186.1 ± 237.2 mmol/L·min versus 1551.2 ± 136.9 mmol/L·min, P < .001). The plasma level of bile acids in the BDI group was lower than that in the BPD/DS group (P = .012) and was not significantly different from that in the control group (P = .629). The plasma level of GLP-1 in the BDI group was lower than that in the BPD/DS group (P = .009) and was not significantly different from that in the control group (P = .530). Moreover, the intestinal TGR5 expression in the BDI group was significantly lower than that in the BPD/DS group (P < .001). CONCLUSIONS: The results show that excision of the ileum can partially reverse the improvement in glucose metabolism after BPD/DS.


Subject(s)
Bile Acids and Salts , Biliopancreatic Diversion , Blood Glucose , Diabetes Mellitus, Experimental , Duodenum , Glucagon-Like Peptide 1 , Ileum , Animals , Biliopancreatic Diversion/methods , Ileum/surgery , Ileum/metabolism , Rats , Male , Diabetes Mellitus, Experimental/surgery , Diabetes Mellitus, Experimental/metabolism , Duodenum/surgery , Duodenum/metabolism , Blood Glucose/metabolism , Glucagon-Like Peptide 1/metabolism , Glucagon-Like Peptide 1/blood , Bile Acids and Salts/metabolism , Bile Acids and Salts/blood , Rats, Sprague-Dawley , Random Allocation
20.
Nat Commun ; 15(1): 4512, 2024 May 27.
Article in English | MEDLINE | ID: mdl-38802369

ABSTRACT

In higher plants, mature male gametophytes have distinct apertures. After pollination, pollen grains germinate, and a pollen tube grows from the aperture to deliver sperm cells to the embryo sac, completing fertilization. In rice, the pollen aperture has a single-pore structure with a collar-like annulus and a plug-like operculum. A crucial step in aperture development is the formation of aperture plasma membrane protrusion (APMP) at the distal polar region of the microspore during the late tetrad stage. Previous studies identified OsINP1 and OsDAF1 as essential regulators of APMP and pollen aperture formation in rice, but their precise molecular mechanisms remain unclear. We demonstrate that the Poaceae-specific OsSRF8 gene, encoding a STRUBBELIG-receptor family 8 protein, is essential for pollen aperture formation in Oryza sativa. Mutants lacking functional OsSRF8 exhibit defects in APMP and pollen aperture formation, like loss-of-function OsINP1 mutants. OsSRF8 is specifically expressed during early anther development and initially diffusely distributed in the microsporocytes. At the tetrad stage, OsSRF8 is recruited by OsINP1 to the pre-aperture region through direct protein-protein interaction, promoting APMP formation. The OsSRF8-OsINP1 complex then recruits OsDAF1 to the APMP site to co-regulate annulus formation. Our findings provide insights into the mechanisms controlling pollen aperture formation in cereal species.


Subject(s)
Gene Expression Regulation, Plant , Oryza , Plant Proteins , Pollen , Oryza/genetics , Oryza/metabolism , Oryza/growth & development , Plant Proteins/metabolism , Plant Proteins/genetics , Pollen/metabolism , Pollen/genetics , Pollen/growth & development , Mutation , Pollination , Cell Membrane/metabolism , Plants, Genetically Modified , Pollen Tube/metabolism , Pollen Tube/growth & development , Pollen Tube/genetics
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