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1.
J Am Chem Soc ; 146(1): 646-659, 2024 Jan 10.
Article in English | MEDLINE | ID: mdl-38151051

ABSTRACT

Among the various metal-organic framework (MOF) adsorbents, diamine-functionalized Mg2(dobpdc) (dobpdc4- = 4,4-dioxidobiphenyl-3,3'-dicarboxylate) shows remarkable carbon dioxide removal performance. However, applying diamine-functionalized Mg2(dobpdc) in practical applications is premature because it shows persistent performance degradation under real flue gas conditions containing water vapor owing to diamine loss during wet cycles. To address this issue, we employed hydrophobic carbonate compounds to protect diamine groups in een-Mg2(dobpdc) (een-MOF, een = N-ethylethylenediamine). tert-Butyl dicarbonate (Boc) reacted rapidly with diamines at the pore openings of MOF particles to form dense secondary and tertiary hydrophobic amines, effectively preventing moisture ingress. The Boc-protected een-MOF-Boc1 maintained excellent CO2 adsorption even under simulated flue gas conditions containing 10% H2O. This observation indicates that Boc protection renders een groups intact during repeated wet cycles, suggesting that Boc-protected een groups are resistant to replacement by water molecules. To increase the practicability of the MOF adsorbent, we fabricated een-MOF/PAN-Boc1 composite beads by shaping MOF particles with polyacrylonitrile (PAN). Notably, the composite beads maintained their CO2 adsorption performance even after repeating the temperature swing adsorption process more than 150 times in 10% water vapor. Furthermore, breakthrough tests showed that the dynamic CO2 separation performance was retained under humid conditions. These results demonstrate that Boc protection provides an easy and effective way to develop promising adsorbents with high CO2 adsorption capacity, long-term durability, and the properties required for postcombustion applications.

2.
J Am Chem Soc ; 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38953459

ABSTRACT

Direct air capture (DAC) shows considerable promise for the effective removal of CO2; however, materials applicable to DAC are lacking. Among metal-organic framework (MOF) adsorbents, diamine-Mg2(dobpdc) (dobpdc4- = 4,4-dioxidobiphenyl-3,3'-dicarboxylate) effectively removes low-pressure CO2, but the synthesis of the organic ligand requires high temperature, high pressure, and a toxic solvent. Besides, it is necessary to isolate the ligand for utilization in the synthesis of the framework. In this study, we synthesized a new variant of extended MOF-74-type frameworks, M2(hob) (M = Mg2+, Co2+, Ni2+, and Zn2+; hob4- = 5,5'-(hydrazine-1,2-diylidenebis(methanylylidene))bis(2-oxidobenzoate)), constructed from an azine-bonded organic ligand obtained through a facile condensation reaction at room temperature. Functionalization of Mg2(hob) with N-methylethylenediamine, N-ethylethylenediamine, and N,N'-dimethylethylenediamine (mmen) enables strong interactions with low-pressure CO2, resulting in top-tier adsorption capacities of 2.60, 2.49, and 2.91 mmol g-1 at 400 ppm of CO2, respectively. Under humid conditions, the CO2 capacity was higher than under dry conditions due to the presence of water molecules that aid in the formation of bicarbonate species. A composite material combining mmen-Mg2(hob) and polyvinylidene fluoride, a hydrophobic polymer, retained its excellent adsorption performance even after 7 days of exposure to 40% relative humidity. In addition, the one-pot synthesis of Mg2(hob) from a mixture of the corresponding monomers is achieved without separate ligand synthesis steps; thus, this framework is suitable for facile large-scale production. This work underscores that the newly synthesized Mg2(hob) and its composites demonstrate significant potential for DAC applications.

3.
Clin Endocrinol (Oxf) ; 100(2): 116-123, 2024 02.
Article in English | MEDLINE | ID: mdl-38146598

ABSTRACT

OBJECTIVE: Metabolic dysfunction-associated steatotic liver disease (MASLD) affects many populations, and screening out the high-risk populations at an early stage is a challenge. As a sarcopenia index, the relationship between creatinine to cystatin C ratio (CCR) and MASLD remains unclear. This cross-sectional, prospective study aimed to explore the relationship between CCR and MASLD. Design Firstly, explored the correlation between CCR and MASLD in cross-sectional analyses. Then excluded the population with baseeline diagnosis of MASLD and analyzed the association with baseline CCR levels and the onset of MASLD in the population with available follow-up data. Univariate and multivariate logistic regression analyses were used to calculate odds ratios (ORs) to evaluate the association between CCR levels and MASLD. PATIENTS AND MEASUREMENTS: This study included 368,634 participants from the UK Biobank for cross-sectional and prospective analyses. The demographic characteristics and laboratory measurements of all participants were obtained from the UK Biobank. MASLD was diagnosed according to the multi-society consensus nomenclature. Hepatic steatosis was defined as FLI  ≥60. RESULTS: We grouped the study participants according to CCR tertiles. In cross-sectional analyses, participants in CCR tertile 1 had the highest MASLD risk (OR: 1.070, 95% CI: 1.053-1.088, p < .001). And the similar association was observed in the prospective analyses (CCR tertile 1 OR: 1.340, 95% CI: 1.077-1.660, p = .009; CCR tertile 2 OR: 1.217, 95% CI: 1.021-1.450, p = .029, respectively). After stratification by gender, the significant association between CCR and the onset of MASLD was only observed in males (CCR tertile 1 OR: 1.639, 95% CI: 1.160-2.317, p = .005; CCR tertile 2 OR: 1.322, 95% CI: 1.073-1.628, p = .005, respectively). CONCLUSION: Our results indicated that lower CCR was significantly associated with higher risk of MASLD, based on which predictive models can be developed to screen populations at high risk of developing MASLD.


Subject(s)
Cystatin C , Fatty Liver , Male , Humans , Prospective Studies , Creatinine , Cross-Sectional Studies , Biological Specimen Banks , UK Biobank
4.
Osteoporos Int ; 35(4): 679-689, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38221591

ABSTRACT

Previously observational studies did not draw a clear conclusion on the association between fatty liver diseases and bone mineral density (BMD). Our large-scale studies revealed that MAFLD and hepatic steatosis had no causal effect on BMD, while some metabolic factors were correlated with BMD. The findings have important implications for the relationship between fatty liver diseases and BMD, and may help direct the clinical management of MAFLD patients who experience osteoporosis and osteopenia. PURPOSE: Liver and bone are active endocrine organs with several metabolic functions. However, the link between metabolic dysfunction-associated fatty liver disease (MAFLD) and bone mineral density (BMD) is contradictory. METHODS: Using the UK Biobank and National Health and Nutrition Examination Survey (NHANES) dataset, we investigated the association between MAFLD, steatosis, and BMD in the observational analysis. We performed genome-wide association analysis to identify single-nucleotide polymorphisms associated with MAFLD. Large-scale two-sample Mendelian randomization (TSMR) analyses examined the potential causal relationship between MAFLD, hepatic steatosis, or major comorbid metabolic factors, and BMD. RESULTS: After adjusting for demographic factors and body mass index, logistic regression analysis demonstrated a significant association between MAFLD and reduced heel BMD. However, this association disappeared after adjusting for additional metabolic factors. MAFLD was not associated with total body, femur neck, and lumbar BMD in the NHANES dataset. Magnetic resonance imaging-measured steatosis did not show significant associations with reduced total body, femur neck, and lumbar BMD in multivariate analysis. TSMR analyses indicated that MAFLD and hepatic steatosis were not associated with BMD. Among all MAFLD-related comorbid factors, overweight and type 2 diabetes showed a causal relationship with increased BMD, while waist circumference and hyperlipidemia had the opposite effect. CONCLUSION: No causal effect of MAFLD and hepatic steatosis on BMD was observed in this study, while some metabolic factors were correlated with BMD. This has important implications for understanding the relationship between fatty liver disease and BMD, which may help direct the clinical management of MAFLD patients with osteoporosis.


Subject(s)
Diabetes Mellitus, Type 2 , Elasticity Imaging Techniques , Non-alcoholic Fatty Liver Disease , Osteoporosis , Humans , Bone Density/genetics , Genome-Wide Association Study , Mendelian Randomization Analysis , Nutrition Surveys , Osteoporosis/genetics
5.
BMC Cancer ; 24(1): 246, 2024 Feb 22.
Article in English | MEDLINE | ID: mdl-38388861

ABSTRACT

BACKGROUND: Artificial intelligence (AI)-assisted clinical trial screening is a promising prospect, although previous matching systems were developed in English, and relevant studies have only been conducted in Western countries. Therefore, we evaluated an AI-based clinical trial matching system (CTMS) that extracts medical data from the electronic health record system and matches them to clinical trials automatically. METHODS: This study included 1,053 consecutive inpatients primarily diagnosed with hepatocellular carcinoma who were referred to the liver tumor center of an academic medical center in China between January and December 2019. The eligibility criteria extracted from two clinical trials, patient attributes, and gold standard were decided manually. We evaluated the performance of the CTMS against the established gold standard by measuring the accuracy, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and run time required. RESULTS: The manual reviewers demonstrated acceptable interrater reliability (Cohen's kappa 0.65-0.88). The performance results for the CTMS were as follows: accuracy, 92.9-98.0%; sensitivity, 51.9-83.5%; specificity, 99.0-99.1%; PPV, 75.7-85.1%; and NPV, 97.4-98.9%. The time required for eligibility determination by the CTMS and manual reviewers was 2 and 150 h, respectively. CONCLUSIONS: We found that the CTMS is particularly reliable in excluding ineligible patients in a significantly reduced amount of time. The CTMS excluded ineligible patients for clinical trials with good performance, reducing 98.7% of the work time. Thus, such AI-based systems with natural language processing and machine learning have potential utility in Chinese clinical trials.


Subject(s)
Artificial Intelligence , Carcinoma, Hepatocellular , Liver Neoplasms , Patient Selection , Humans , Carcinoma, Hepatocellular/diagnosis , Carcinoma, Hepatocellular/therapy , China/epidemiology , Liver Neoplasms/diagnosis , Liver Neoplasms/therapy , Reproducibility of Results , Retrospective Studies , Clinical Trials as Topic , Hospitalization
6.
J Clin Periodontol ; 51(1): 24-32, 2024 01.
Article in English | MEDLINE | ID: mdl-37872750

ABSTRACT

AIM: To compare the implant accuracy, safety and morbidity between robot-assisted and freehand dental implant placement. MATERIALS AND METHODS: Subjects requiring single-site dental implant placement were recruited. Patients were randomly allocated to freehand implant placement and robot-assisted implant placement. Differences in positional accuracy of the implant, surgical morbidity and complications were assessed. The significance of intergroup differences was tested with an intention-to-treat analysis and a per-protocol (PP) analysis (excluding one patient due to calibration error). RESULTS: Twenty patients (with a median age of 37, 13 female) were included. One subject assigned to the robotic arm was excluded from the PP analysis because of a large calibration error due to the dislodgement of the index. For robot-assisted and freehand implant placement, with the PP analysis, the median (25th-75th percentile) platform global deviation, apex global deviation and angular deviation were 1.23 (0.9-1.4) mm/1.9 (1.2-2.3) mm (p = .03, the Mann-Whitney U-test), 1.40 (1.1-1.6) mm/2.1 (1.7-3.9) mm (p < .01) and 3.0 (0.9-6.0)°/6.7 (2.2-13.9)° (p = .08), respectively. Both methods showed limited damage to the alveolar ridge and had similar peri- and post-operative morbidity and safety. CONCLUSIONS: Robot-assisted implant placement enabled greater positional accuracy of the implant compared to freehand placement in this pilot trial. The robotic system should be further developed to simplify surgical procedures and improve accuracy and be validated in properly sized trials assessing the full spectrum of relevant outcomes.


Subject(s)
Dental Implants , Robotics , Surgery, Computer-Assisted , Humans , Female , Pilot Projects , Haptic Technology , Dental Implantation, Endosseous/methods , Cone-Beam Computed Tomography , Computer-Aided Design
7.
Clin Oral Implants Res ; 35(6): 598-608, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38517053

ABSTRACT

OBJECTIVES: To systematically analyze the accuracy of robotic surgery for dental implant placement. MATERIALS AND METHODS: PubMed, Embase, and Cochrane CENTRAL were searched on October 25, 2023. Model studies or clinical studies reporting the accuracy of robotic surgery for dental implant placement among patients with missing or hopeless teeth were included. Risks of bias in clinical studies were assessed. Meta-analyses were undertaken. RESULTS: Data from 8 clinical studies reporting on 109 patients and 242 implants and 13 preclinical studies were included. Positional accuracy was measured by comparing the implant plan in presurgery CBCT and the actual implant position in postsurgery CBCT. For clinical studies, the pooled (95% confidence interval) platform deviation, apex deviation, and angular deviation were 0.68 (0.57, 0.79) mm, 0.67 (0.58, 0.75) mm, and 1.69 (1.25, 2.12)°, respectively. There was no statistically significant difference between the accuracy of implants placed in partially or fully edentulous patients. For model studies, the pooled platform deviation, apex deviation, and angular deviation were 0.72 (0.58, 0.86) mm, 0.90 (0.74, 1.06) mm, and 1.46 (1.22, 1.70)°, respectively. No adverse event was reported. CONCLUSION: Within the limitation of the present systematic review, robotic surgery for dental implant placement showed suitable implant positional accuracy and had no reported obvious harm. Both robotic systems and clinical studies on robotic surgery for dental implant placement should be further developed.


Subject(s)
Dental Implantation, Endosseous , Dental Implants , Robotic Surgical Procedures , Humans , Robotic Surgical Procedures/methods , Dental Implantation, Endosseous/methods , Cone-Beam Computed Tomography
8.
Eur Spine J ; 2024 May 31.
Article in English | MEDLINE | ID: mdl-38819738

ABSTRACT

PURPOSE: The minimally invasive oblique lumbar interbody fusion (MI-OLIF) L5-S1 was introduced to overcome the limitations of conventional fusion techniques, however, MI-OLIF is not possible using the standard method due to vascular structures in some cases. We aimed to introduce the "lateral corridor" and report the details of the surgical technique with a clinical case series. METHODS: We utilized the lateral access route of the left common iliac vein and named it the "lateral corridor", to distinguish the technique from the standard technique (central corridor). The type and frequency of branch vessels that required additional manipulations were reviewed, and the frequency of intraoperative vascular injury was investigated. RESULTS: Among the 107 patients who underwent MI-OLIF L5-S1, 26 patients (24.3%) who received the "lateral corridor" technique were included. Branch vessel ligation was required in 42.3% of the patients. The types of branch vessels that required ligation were seven cases (26.9%) of the iliolumbar vein (ILV) and six cases (23.1%) of ascending lumbar vein (ALV). The ILV and ALV were ligated in two cases. None of the patients developed intraoperative vascular injuries. CONCLUSION: We introduced the "lateral corridor" as an alternative approach for MI-OLIF L5-S1, implemented it in 24.3% of the patient cohort, and reported favorable outcomes devoid of vascular complications. The "lateral corridor" necessitated ligation of the ILV or ALV in 42.3% of cases. The "lateral corridor" approach appears to be a promising surgical technique, offering feasibility even in instances where the vascular anatomy precludes the employment of the conventional approach.

9.
Environ Toxicol ; 39(6): 3473-3480, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38450827

ABSTRACT

Cholelithiasis is a common digestive disease that drives a myriad of adverse complications. The correlation between sarcopenia and various digestive disorders has been extensively researched, whereas its association with cholelithiasis remains unreported. We aimed to investigate the association through prospective and Mendelian randomization (MR) analyses and establish a quantitative score reflecting the impact of sarcopenia-related markers on cholelithiasis. The prospective study involved 448 627 participants from the UK Biobank. Cox proportional hazard models were employed to investigate the correlation between sarcopenia-related markers and cholelithiasis. To quantitatively assess cholelithiasis risk, the SARCHO score was derived from a multivariable Cox model. Bidirectional two-sample MR analysis was conducted to validate the causal association. A total of 16 738 individuals developed cholelithiasis during a median follow-up of 12 years. Hazard ratios (HRs) of cholelithiasis decreased stepwise over skeletal muscle index tertiles (highest tertile: reference; middle tertile: 1.23, p < .001; lowest tertile: 1.33, p < .001). The tertiles of grip strength showed a similar pattern. Individuals with slow walking pace had a higher risk of cholelithiasis compared to those with normal walking pace (HR 1.23; p < .001). Our SARCHO score better quantifies the risk of cholelithiasis. MR analysis showed a causal relationship between muscle mass and cholelithiasis (OR 0.81; p < .001). No causal effect of cholelithiasis on lean mass was observed. Prospective and MR analyses have consistently demonstrated an increased risk of cholelithiasis in individuals with decreased muscle mass. Additionally, SARCHO score further quantified the cholelithiasis occurrence risk. These findings provide compelling evidence for muscle strengthening in preventing cholelithiasis.


Subject(s)
Cholelithiasis , Mendelian Randomization Analysis , Sarcopenia , Humans , Sarcopenia/epidemiology , Cholelithiasis/epidemiology , Prospective Studies , Female , Male , Middle Aged , Biomarkers/blood , Aged , Adult , Proportional Hazards Models , Risk Factors
10.
Sensors (Basel) ; 24(3)2024 Jan 23.
Article in English | MEDLINE | ID: mdl-38339435

ABSTRACT

Needle electromyogram (EMG) research has suggested that endplate noise (EPN) is a characteristic of myofascial trigger points (MTrPs). Although several studies have observed MTrPs through ultrasonography, whether they are hyperechoic or hypoechoic in ultrasound images is still controversial. Therefore, this study determined the echogenicity of MTrP ultrasonography. In stage 1, the MTrP of rat masseter muscle was identified through palpation and marked. Needle EMG was performed to detect the presence of EPN. When EPN was detected, ultrasound scans and indwelling needles were used to identify the nodule with a different grayscale relative to that of its surrounding tissue, and the echogenicity of the identified MTrP was determined. In stage 2, these steps were reversed. An ultrasound scan was performed to detect the nodule at the marked site, and an EMG needle was inserted into the nodule to detect EPN. There were 178 recordings in each stage, obtained from 45 rats. The stage 1 results indicate that the MTrPs in ultrasound images were hypoechoic with a 100% sensitivity of assessment. In stage 2, the accuracy and precision of MTrP detection through ultrasonography were 89.9% and 89.2%, respectively. The results indicate that ultrasonography produces highly accurate and precise MTrP detection results.


Subject(s)
Myofascial Pain Syndromes , Trigger Points , Rats , Animals , Myofascial Pain Syndromes/diagnostic imaging , Ultrasonography , Electromyography , Needles
11.
J Neuroradiol ; 51(1): 59-65, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37247754

ABSTRACT

PURPOSE: In the endovascular era, postcoiling recanalization of cerebral aneurysms is occurring with greater frequency. Repeat coiling is usually done to prevent rebleeding, although long-term outcomes of re-embolization have yet to be adequately investigated. The present study was undertaken to assess clinical and radiographic outcomes of re-embolization in recanalized aneurysms, focusing on procedural safety, efficacy, and durability. METHOD: In this retrospective review, we examined 308 patients with 310 recurrent aneurysms. All lesions were re-coiled, once major recanalization (after initial coil embolization) was established. Medical records and radiologic data amassed during extended follow-up were then subject to review. Cox proportional hazards regression analysis was undertaken to identify risk factors for subsequent recurrence. RESULT: During a lengthy follow-up (mean, 40.2 ± 33.0 months), major recanalization developed again in 87 aneurysms (28.1%). Multivariable Cox regression analysis linked re-recanalization to initial saccular neck width (p=.003) and autosomal dominant polycystic kidney disease (ADPKD; p<.001). Stent implantation (p=.038) and successful occlusion at second coiling (p=.012) were protective against later recanalization in this setting. The more recent the second embolization was performed, the lower the risk of further recurrence (p=.023). Procedure-related complications included asymptomatic thromboembolism (n = 9), transient ischemic neurologic deficits (n = 2), procedural bleeding (n = 1), and coil migration (n = 1), but there were no residual effects or deaths. CONCLUSION: Repeat coil embolization is a safe therapeutic option for recanalized cerebral aneurysms. Wide-necked status and ADPKD emerged as risks for subsequent recanalization, whereas successful occlusion and stent implantation seemed to reduce the likelihood of recurrence after re-embolization procedures.


Subject(s)
Embolization, Therapeutic , Intracranial Aneurysm , Polycystic Kidney, Autosomal Dominant , Humans , Intracranial Aneurysm/diagnostic imaging , Intracranial Aneurysm/therapy , Intracranial Aneurysm/etiology , Treatment Outcome , Follow-Up Studies , Polycystic Kidney, Autosomal Dominant/etiology , Polycystic Kidney, Autosomal Dominant/therapy , Cerebral Angiography , Stents , Embolization, Therapeutic/methods , Retrospective Studies
12.
Angew Chem Int Ed Engl ; 63(21): e202400855, 2024 May 21.
Article in English | MEDLINE | ID: mdl-38503692

ABSTRACT

Postsynthetic modifications (PSMs) of metal-organic frameworks (MOFs) play a crucial role in enhancing material performance through open metal site (OMS) functionalization or ligand exchange. However, a significant challenge persists in preserving open metal sites during ligand exchange, as these sites are inherently bound by incoming ligands. In this study, for the first time, we introduced alkoxides by exchanging bridging chloride in Ni2Cl2BTDD (BTDD=bis (1H-1,2,3,-triazolo [4,5-b],-[4',5'-i]) dibenzo[1,4]dioxin) through PSM. Rietveld refinement of synchrotron X-ray diffraction data indicated that the alkoxide oxygen atom bridges Ni(II) centers while the OMSs of the MOF are preserved. Due to the synergy of the existing OMS and introduced functional group, the alkoxide-exchanged MOFs showed CO2 uptakes superior to the pristine MOF. Remarkably, the tert-butoxide-substituted Ni_T exhibited a nearly threefold and twofold increase in CO2 uptake compared to Ni2Cl2BTDD at 0.15 and 1 bar, respectively, as well as high water stability relative to the other exchanged frameworks. Furthermore, the Grand Canonical Monte Carlo simulations for Ni_T suggested that CO2 interacts with the OMS and the surrounding methyl groups of tert-butoxide groups, which is responsible for the enhanced CO2 capacity. This work provides a facile and unique synthetic strategy for realizing a desirable OMS-incorporating MOF platform through bridging ligand exchange.

13.
Physiol Genomics ; 55(2): 90-100, 2023 02 01.
Article in English | MEDLINE | ID: mdl-36645668

ABSTRACT

Bone marrow mesenchymal stem cells (BMSCs) exert pivotal roles in suppressing immune rejection in organ transplantation. However, the function of BMSCs on immune rejection in renal transplantation remains unclear. This study aimed to evaluate the effect and underlying mechanism of BMSCs on immune rejection in renal transplantation. Following the establishment of the renal allograft mouse model, the isolated primary BMSCs were injected intravenously into the recipient mice. Enzyme-linked immunosorbent assay, flow cytometry, hematoxylin-eosin staining, and Western blot assays were conducted to investigate BMSCs' function in vivo and in vitro. Mechanistically, the underlying mechanism of BMSCs on immune rejection in renal transplantation was investigated in in vivo and in vitro models. Functionally, BMSCs alleviated the immune rejection in renal transplantation mice and facilitated B cell activation and the production of IL-10+ regulatory B cells (Bregs). Furthermore, the results of mechanism studies revealed that BMSCs induced the production of IL-10+ Bregs by facilitating a proliferation-inducing ligand (APRIL) phosphorylation to enhance immunosuppression and repressed renal transplant rejection by promoting APRIL phosphorylation to induce IL-10+ Bregs. BMSCs prevent renal transplant rejection by facilitating APRIL phosphorylation to induce IL-10+ Bregs.


Subject(s)
B-Lymphocytes, Regulatory , Kidney Transplantation , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells , Mice , Animals , Interleukin-10 , Graft Rejection , Phosphorylation , Mesenchymal Stem Cell Transplantation/methods , Bone Marrow Cells
14.
Cancer Immunol Immunother ; 72(7): 2299-2308, 2023 Jul.
Article in English | MEDLINE | ID: mdl-36884079

ABSTRACT

BACKGROUND: There is still no specific real-world data regarding the clinical activity of immune checkpoint inhibitors in the elderly with liver cancer. Our study aimed to compare the efficacy and safety of immune checkpoint inhibitors between patients aged ≥ 65 years and the younger group, while exploring their differences in genomic background and tumor microenvironment. METHODS: This retrospective study was conducted at two hospitals in China and included 540 patients treated with immune checkpoint inhibitors for primary liver cancer between January 2018 and December 2021. Patients' medical records were reviewed for clinical and radiological data and oncologic outcomes. The genomic and clinical data of patients with primary liver cancer were extracted and analyzed from TCGA-LIHC, GSE14520, and GSE140901 datasets. RESULTS: Ninety-two patients were classified as elderly and showed better progression-free survival (P = 0.027) and disease control rate (P = 0.014). No difference was observed in overall survival (P = 0.69) or objective response rate (P = 0.423) between the two age groups. No significant difference was reported concerning the number (P = 0.824) and severity (P = 0.421) of adverse events. The enrichment analyses indicated that the elderly group was linked to lower expression of oncogenic pathways, such as PI3K-Akt, Wnt, and IL-17. The elderly had a higher tumor mutation burden than younger patients. CONCLUSIONS: Our results indicated that immune checkpoint inhibitors might exhibit better efficacy in the elderly with primary liver cancer, with no increased adverse events. Differences in genomic characteristics and tumor mutation burden may partially explain these results.


Subject(s)
Antineoplastic Agents, Immunological , Liver Neoplasms , Aged , Humans , Retrospective Studies , Cohort Studies , Immune Checkpoint Inhibitors/adverse effects , Antineoplastic Agents, Immunological/therapeutic use , Phosphatidylinositol 3-Kinases , Liver Neoplasms/drug therapy , Liver Neoplasms/genetics , Tumor Microenvironment
15.
Small ; 19(41): e2303640, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37287400

ABSTRACT

In reticular chemistry, topology is a powerful concept for defining the structures of covalent organic frameworks (COFs). However, due to the lack of diversity in the symmetry and reaction stoichiometry of the monomers, only 5% of the two-dimensional topologies have been reported to be COFs. To overcome the limitations of COF connectivity and pursue novel topologies in COF structures, two aminal-linked COFs, KUF-2 and KUF-3, are prepared, with dumbbell-shaped secondary building units. Linear dialdehydes and piperazine are condensed at a ratio of 1:2 to construct an aminal linkage, leading to unreported hxl-a (KUF-2) and quasi-hcb (KUF-3) structures. Notably, KUF-3 displays top-tier C2 H6 /C2 H4 selectivity and C2 H6 uptake at 298 K, outperforming most porous organic materials. The intrinsic aromatic ring-rich and Lewis basic pore environments, and appropriate pore widths enable the selective adsorption of C2 H6 , as confirmed by Grand Canonical Monte Carlo simulations. Dynamic breakthrough curves revealed that C2 H6 can be selectively separated from a gas mixture of C2 H6 and C2 H4 . This study suggests that topology-based design of aminal-COFs is an effective strategy for expanding the field of reticular chemistry and provides the facile integration of strong Lewis basic sites for selective C2 H6 /C2 H4 separation.

16.
Small ; 19(35): e2301905, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37093175

ABSTRACT

The development of adsorbents for Kr and Xe separation is essential to meet industrial demands and for energy conservation. Although a number of previous studies have focused on Xe-selective adsorbents, stimuli-responsive Xe/Kr-selective adsorbents still remain underdeveloped. Herein, a Hofmann-type framework Co(DABCO)[Ni(CN)4 ] (referred to as CoNi-DAB; DABCO = 1,4-diazabicyclo[2,2,2]octane) that provides a temperature-dependent switchable Xe/Kr separation performance is reported. CoNi-DAB showed high Kr/Xe (0.8/0.2) selectivity with significant Kr adsorption at 195 K as well as high Xe/Kr (0.2/0.8) selectivity with superior Xe adsorption at 298 K. Such adsorption features are associated with the temperature-dependent rotational configuration of the DABCO ligand, which affects the kinetic gate-opening temperature of Xe and Kr. The packing densities of Xe (2.886 g cm-3 at 298 K) and Kr (2.399 g  cm-3 at 195 K) inside the framework are remarkable and comparable with those of liquid Xe (3.057 g cm-3 ) and liquid Kr (2.413 g cm-3 ), respectively. Breakthrough experiments confirm the temperature-dependent reverse separation performance of CoNi-DAB at 298 K under dry and wet (88% relative humidity) conditions and at 195 K under dry conditions. The unique adsorption behavior is also verified through van der Waals (vdW)-corrected density functional theory (DFT) calculations and nudged elastic band (NEB) simulations.

17.
Small ; 19(30): e2300707, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37058091

ABSTRACT

Silica is regarded as a promising anode material for lithium-ion batteries (LIBs) because of its high theoretical capacity. However, large volume variation and poor electrical conductivity are limiting factors for the development of SiO2 anode materials. To solve this problem, combining SiO2 with a conductive phase and designing hollow porous structures are effective ways. In this work, The Co(II)-EDTA chelate on the surface of diatom biosilica (DBS) frustules and obtained DBS@C-Co composites decorated with Co nanoparticles by calcination without a reducing atmosphere is first precipitated. The unique three-dimensional structure of diatom frustules provides enough space for the volume change of silica during lithiation/delithiation. Co nanoparticles effectively improve the electrical conductivity and electrochemical activity of silica. Through the synergistic effect of the hollow porous structure, carbon layer and Co nanoparticles, the DBS@C-Co-60 composite delivers a high reversible capacity of >620 mAh g-1 at 100 mA g-1 after 270 cycles. This study provides a new method for the synthesis of metal/silica composites and an opportunity for the development of natural resources as advanced active materials for LIBs.

18.
J Transl Med ; 21(1): 69, 2023 02 02.
Article in English | MEDLINE | ID: mdl-36732815

ABSTRACT

BACKGROUND: Recurrence is common in glioblastoma multiforme (GBM) because of the infiltrative, residual cells in the tumor margin. Standard therapy for GBM consists of surgical resection followed by chemotherapy and radiotherapy, but the median survival of GBM patients remains poor (~ 1.5 years). For recurrent GBM, anti-angiogenic treatment is one of the common treatment approaches. However, current anti-angiogenic treatment modalities are not satisfactory because of the resistance to anti-angiogenic agents in some patients. Therefore, we sought to identify novel prognostic biomarkers that can predict the therapeutic response to anti-angiogenic agents in patients with recurrent glioblastoma. METHODS: We selected patients with recurrent GBM who were treated with anti-angiogenic agents and classified them into responders and non-responders to anti-angiogenic therapy. Then, we performed proteomic analysis using liquid-chromatography mass spectrometry (LC-MS) with formalin-fixed paraffin-embedded (FFPE) tissues obtained from surgical specimens. We conducted a gene-ontology (GO) analysis based on protein abundance in the responder and non-responder groups. Based on the LC-MS and GO analysis results, we identified potential predictive biomarkers for anti-angiogenic therapy and validated them in recurrent glioblastoma patients. RESULTS: In the mass spectrometry-based approach, 4957 unique proteins were quantified with high confidence across clinical parameters. Unsupervised clustering analysis highlighted distinct proteomic patterns (n = 269 proteins) between responders and non-responders. The GO term enrichment analysis revealed a cluster of genes related to immune cell-related pathways (e.g., TMEM173, FADD, CD99) in the responder group, whereas the non-responder group had a high expression of genes related to nuclear replisome (POLD) and damaged DNA binding (ERCC2). Immunohistochemistry of these biomarkers showed that the expression levels of TMEM173 and FADD were significantly associated with the overall survival and progression-free survival of patients with recurrent GBM. CONCLUSIONS: The candidate biomarkers identified in our protein analysis may be useful for predicting the clinical response to anti-angiogenic agents in patients with recurred GBM.


Subject(s)
Brain Neoplasms , Glioblastoma , Humans , Glioblastoma/drug therapy , Glioblastoma/genetics , Glioblastoma/metabolism , Proteomics , Brain Neoplasms/drug therapy , Brain Neoplasms/genetics , Brain Neoplasms/pathology , Neoplasm Recurrence, Local/genetics , Angiogenesis Inhibitors/pharmacology , Angiogenesis Inhibitors/therapeutic use , Biomarkers , Xeroderma Pigmentosum Group D Protein
19.
Mol Psychiatry ; 27(12): 5235-5243, 2022 12.
Article in English | MEDLINE | ID: mdl-35974140

ABSTRACT

We previously developed a novel machine-learning-based brain age model that was sensitive to amyloid. We aimed to independently validate it and to demonstrate its utility using independent clinical data. We recruited 650 participants from South Korean memory clinics to undergo magnetic resonance imaging and clinical assessments. We employed a pretrained brain age model that used data from an independent set of largely Caucasian individuals (n = 757) who had no or relatively low levels of amyloid as confirmed by positron emission tomography (PET). We investigated the association between brain age residual and cognitive decline. We found that our pretrained brain age model was able to reliably estimate brain age (mean absolute error = 5.68 years, r(650) = 0.47, age range = 49-89 year) in the sample with 71 participants with subjective cognitive decline (SCD), 375 with mild cognitive impairment (MCI), and 204 with dementia. Greater brain age was associated with greater amyloid and worse cognitive function [Odds Ratio, (95% Confidence Interval {CI}): 1.28 (1.06-1.55), p = 0.030 for amyloid PET positivity; 2.52 (1.76-3.61), p < 0.001 for dementia]. Baseline brain age residual was predictive of future cognitive worsening even after adjusting for apolipoprotein E e4 and amyloid status [Hazard Ratio, (95% CI): 1.94 (1.33-2.81), p = 0.001 for total 336 follow-up sample; 2.31 (1.44-3.71), p = 0.001 for 284 subsample with baseline Clinical Dementia Rating ≤ 0.5; 2.40 (1.43-4.03), p = 0.001 for 240 subsample with baseline SCD or MCI]. In independent data set, these results replicate our previous findings using this model, which was able to delineate significant differences in brain age according to the diagnostic stages of dementia as well as amyloid deposition status. Brain age models may offer benefits in discriminating and tracking cognitive impairment in older adults.


Subject(s)
Alzheimer Disease , Cognitive Dysfunction , Humans , Aged , Middle Aged , Aged, 80 and over , Child, Preschool , Amyloid beta-Peptides/metabolism , Brain/metabolism , Cognition , Positron-Emission Tomography/methods , Magnetic Resonance Imaging , Apolipoprotein E4
20.
World J Urol ; 41(11): 3065-3074, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37787942

ABSTRACT

PURPOSE: Despite advances in technology, such as advent of laser enucleation and minimally invasive surgical therapies, transurethral resection of the prostate (TURP) remains the most widely performed surgical technique for benign prostatic hyperplasia (BPH). We evaluated resection volume (RV)-derived parameters and analyzed the effect of RV on post-TURP outcomes. METHODS: This observational study used data from patients who underwent TURP at two institutions between January 2011 and December 2021 Data from patients with previous BPH surgical treatment, incomplete data, and underlying disease affecting voiding function were excluded. The collected data included age, prostate-specific antigen, transrectal ultrasound (TRUS)- and uroflowmetry-derived parameters, RV, perioperative laboratory values, perioperative International Prostatic Symptom Score (IPSS), follow-up period, retreatment requirements and interval between the first TURP and retreatment. RESULTS: In 268 patients without prior BPH medication, there were no differences in prostate volume (PV), transitional zone volume (TZV), or RV according to IPSS. A total of 60 patients started retreatment, including medical or surgical treatment, within the follow-up period. There was a significant difference in RV/PV between the groups without and with retreatment respectively (0.56 and 0.37; p = 0.008). However, preoperative TRUS- and uroflowmetry-derived parameters did not differ between the two groups. Multiple linear regression analysis showed that RV (p = 0.003) and RV/TZV (p = 0.006) were significantly associated with differences in perioperative IPSS. In the multivariate logistic regression analysis, only RV/PV was correlated with retreatment (p = 0.010). CONCLUSION: Maximal TURP leads to improved postoperative outcomes and reduced retreatment rate, it may gradually become a requirement rather than an option.


Subject(s)
Prostatic Hyperplasia , Transurethral Resection of Prostate , Male , Humans , Prostate/diagnostic imaging , Prostate/surgery , Transurethral Resection of Prostate/methods , Prostatic Hyperplasia/complications , Urination , Treatment Outcome , Retreatment
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