MECP2 directly interacts with RNA polymerase II to modulate transcription in human neurons.

Mutations in the methyl-DNA-binding protein MECP2 cause the neurodevelopmental disorder Rett syndrome (RTT). How MECP2 contributes to transcriptional regulation in normal and disease states is unresolved; it has been reported to be an activator and a repressor. We describe here the first integrated CUT&Tag, transcriptome, and proteome analyses using human neurons with wild-type (WT) and mutant MECP2 molecules. MECP2 occupies CpG-rich promoter-proximal regions in over four thousand genes in human neurons, including a plethora of autism risk genes, together with RNA polymerase II (RNA Pol II). MECP2 directly interacts with RNA Pol II, and genes occupied by both proteins showed reduced expression in neurons with MECP2 patient mutations. We conclude that MECP2 acts as a positive cofactor for RNA Pol II gene expression at many neuronal genes that harbor CpG islands in promoter-proximal regions and that RTT is due, in part, to the loss of gene activity of these genes in neurons.

MYT1L deficiency impairs excitatory neuron trajectory during cortical development.

Mutations that reduce the function of MYT1L, a neuron-specific transcription factor, are associated with a syndromic neurodevelopmental disorder. Furthermore, MYT1L is routinely used as a proneural factor in fibroblast-to-neuron transdifferentiation. MYT1L has been hypothesized to play a role in the trajectory of neuronal specification and subtype specific maturation, but this hypothesis has not been directly tested, nor is it clear which neuron types are most impacted by MYT1L loss. In this study, we profiled 313,335 nuclei from the forebrains of wild-type and MYT1L-deficient mice at two developmental stages: E14 at the peak of neurogenesis and P21, when neurogenesis is complete, to examine the role of MYT1L levels in the trajectory of neuronal development. We found that MYT1L deficiency significantly disrupted the relative proportion of cortical excitatory neurons at E14 and P21. Significant changes in gene expression were largely concentrated in excitatory neurons, suggesting that transcriptional effects of MYT1L deficiency are largely due to disruption of neuronal maturation programs. Most effects on gene expression were cell autonomous and persistent through development. In addition, while MYT1L can both activate and repress gene expression, the repressive effects were most sensitive to haploinsufficiency, and thus more likely mediate MYT1L syndrome. These findings illuminate the intricate role of MYT1L in orchestrating gene expression dynamics during neuronal development, providing insights into the molecular underpinnings of MYT1L syndrome.

Validation of a new non-hyperemic physiological index: the constant-resistance ratio (cRR).

OBJECTIVES: The instantaneous wave-free ratio (iwFR) has limited availability. A new resting index called the constant-resistance ratio (cRR), which dynamically identifies cardiac intervals with constant and minimum resistance, has been developed; however, its diagnostic performance is unknown. The aim of this study was to validate the cRR by retrospectively calculating the cRR values from raw pressure waveforms of 2 publicly available datasets and compare them with those of the iwFR. METHODS: Waveform data from the CONTRAST and VERIFY 2 studies were used. The primary endpoint was Bland-Altman bias between cRR and iwFR. Secondary endpoints included diagnostic agreement, correlation, receiver operating characteristic (ROC) analysis, and success rates of cRR and iwFR. RESULTS: Among the 1036 waveforms, 871 were successful in determining paired cRR and iwFR values, while cRR was 6% more successful than iwFR (P less than .0001). The mean bias between cRR and iwFR was 0.003, with 95% limits of agreement [-0.021,0.028]. These 2 indices were highly correlated (r = 0.991; P less than .0001). Using an iwFR of 0.89 or less as the reference standard, the optimal cRR cutoff was 0.89, with an area under the ROC curve of 0.991 (P less than .001) and a diagnostic accuracy of 96.9% (95% CI [96%, 98%]). CONCLUSIONS: The cRR, a new resting index for identifying dynamic cardiac intervals with constant and minimum resistance, demonstrated high numerical agreement, diagnostic consistency, and a higher success rate than the iwFR based on the 2 publicly available datasets.

A novel intracoronary hypothermia device reduces myocardial reperfusion injury in pigs.

BACKGROUND: Hypothermia therapy has been suggested to attenuate myocardial necrosis; however, the clinical implementation as a valid therapeutic strategy has failed, and new approaches are needed to translate into clinical applications. This study aimed to assess the feasibility, safety, and efficacy of a novel selective intracoronary hypothermia (SICH) device in mitigating myocardial reperfusion injury. METHODS: This study comprised two phases. The first phase of the SICH was performed in a normal porcine model for 30 minutes ( n = 5) to evaluate its feasibility. The second phase was conducted in a porcine myocardial infarction (MI) model of myocardial ischemia/reperfusion was performed by balloon occlusion of the left anterior descending coronary artery for 60 minutes and maintained for 42 days. Pigs in the hypothermia group ( n = 8) received hypothermia intervention onset reperfusion for 30 minutes and controls ( n = 8) received no intervention. All animals were followed for 42 days. Cardiac magnetic resonance analysis (5 and 42 days post-MI) and a series of biomarkers/histological studies were performed. RESULTS: The average time to lower temperatures to a steady state was 4.8 ± 0.8 s. SICH had no impact on blood pressure or heart rate and was safely performed without complications by using a 3.9 F catheter. Interleukin-6 (IL-6), tumor necrosis factor-α, C-reactive protein (CRP), and brain natriuretic peptide (BNP) were lower at 60 min post perfusion in pigs that underwent SICH as compared with the control group. On day 5 post MI/R, edema, intramyocardial hemorrhage, and microvascular obstruction were reduced in the hypothermia group. On day 42 post MI/R, the infarct size, IL-6, CRP, BNP, and matrix metalloproteinase-9 were reduced, and the ejection fraction was improved in pigs that underwent SICH. CONCLUSIONS: The SICH device safely and effectively reduced the infarct size and improved heart function in a pig model of MI/R. These beneficial effects indicate the clinical potential of SICH for treatment of myocardial reperfusion injury.

Are baseline conditions of coronary arteries sufficient for calculating angio-based index of microcirculatory resistance and fractional flow reserve?

Background: Angio-based index of microcirculatory resistance (IMR) and fractional flow reserve (FFR) have been developed, however, the differences between baseline and hyperemic data and their effects on their computation have not yet been discussed. This study aimed to compare the diagnostic performance of a novel method for calculating IMR and FFR from coronary angiography under baseline and hyperemic conditions. Methods: We performed a retrospective study to investigate the diagnostic performance of angiography-derived IMR (AccuIMR) and FFR (AccuFFRangio) computed from the hyperemic condition (AccuIMRhyp, AccuFFRangiohyp) and baseline condition (AccuIMRbase, AccuFFRangiobase) in 101 consecutive patients with chronic coronary syndrome (CCS) who underwent measurements of IMR and FFR at a single center, using wire-based IMR and FFR as the reference standard. Results: AccuIMRhyp showed much better correlation with IMR than AccuIMRbase (r=0.77 vs. 0.47, P<0.001). The diagnostic accuracy and area under the curve (AUC) for identifying significant microvascular dysfunction was higher for AccuIMRhyp than AccuIMRbase [92.1% (95% CI: 85.0-96.5%) vs. 83.2% (95% CI: 74.4-89.9%), P=0.012; 0.942 (95% CI: 0.877-0.979) vs. 0.815 (95% CI: 0.726-0.886), P=0.003]. The computed AccuFFRangio showed good correlations with FFR and good diagnostic performance under both hyperemic and baseline conditions [r=0.68 vs. 0.68, P>0.99; diagnostic accuracy =95.9% (95% CI: 89.8-98.9%) vs. 94.9% (95% CI: 88.4-98.3%), P=0.728; AUC =0.989 (95% CI: 0.942-1.000) vs. 0.973 (95% CI: 0.919-0.995), P=0.381]. The net reclassification index (NRI) demonstrated that hyperemic group had improved reclassification ability compared to the baseline group in identification of IMR >25 (NRI =0.20, P<0.001) and FFR ≤0.8 (NRI =0.11, P<0.001). Conclusions: By comparing the calculated angio-derived IMR and FFR under the baseline and hyperemic conditions, this study demonstrates that AccuIMR calculation is more accurate using the hyperemic condition, while AccuFFRangio calculation is accurate under both conditions.

Current development of pyrazole-azole hybrids with anticancer potential.

Chemotherapy is a critical treatment modality for cancer patients, but multidrug resistance remains one of the major challenges in cancer therapy, creating an urgent need for the development of novel potent chemical entities. Azoles, particularly pyrazole, could interact with different biological targets and exhibit diverse biological properties including anticancer activity. Many clinically used anticancer agents own an azole moiety, demonstrating that azoles are privileged and pivotal templates in the discovery of novel anticancer chemotherapeutics. The present article is an attempt to highlight the recent advances in pyrazole-azole hybrids with anticancer potential and discuss the structure-activity relationships, covering articles published from 2018 to present, to facilitate the rational design of more effective anticancer candidates.

The Association Between Angiographically Derived Radial Wall Strain and the Risk of Acute Myocardial Infarction.

BACKGROUND: The radial wall strain (RWS) is a novel angiography-based method to assess the biomechanical property of the coronary artery and whether it can predict future acute myocardial infarction (AMI) events remains to be elucidated. OBJECTIVES: This study aimed to investigate the association between angiography-derived RWS and future AMI events in mild to intermediate lesions. METHODS: We performed a matched case-control analysis nested in a retrospective cohort of patients who had received prior angiography (the index procedure) at least 1 month before and were hospitalized again for repeat angiography. Patients with at least 1 de novo mild to intermediate lesion identified at the index procedure and eligible for RWS analysis were enrolled. The study identified cases with target lesion-related AMI diagnosed at the repeat angiography, matching each case to 3 control subjects without AMI. RESULTS: Altogether 44 patients with lesion-related AMI and 132 matched controls were enrolled. The median diameter stenosis of the overall interrogated lesions was 34.0%. The baseline maximum RWS (RWSmax), which was defined as the highest RWS in the stenotic segment, was significantly higher in lesions responsible for AMI than those that remained quiescent (median 13% vs 10%; P < 0.001). RWSmax was predictive of lesion-related AMI, with an area under the curve of 0.83 (95% CI: 0.76-0.90; P < 0.001) and an optimal cutoff >12%. RWSmax >12% was found to be independently associated with subsequent AMI events with a risk ratio of 7.25 (95% CI: 3.94-13.37; P < 0.001). CONCLUSIONS: Among angiographically mild to intermediate lesions, a high-strain pattern identified by angiography-derived RWS was associated with an increased risk of AMI events.

Dynamic perfusion SPECT for functional evaluation in symptomatic patients with myocardial bridging.

BACKGROUND: The aim of this study was to investigate the feasibility and diagnostic value of myocardial flow reserve (MFR) assessed by rest/stress myocardial perfusion imaging with dynamic single-photon emission computed tomography (SPECT) in the functional evaluation of myocardial bridge (MB). METHODS: From May 2017 to July 2021, patients with angiographically confirmed isolated MB on the left anterior descending artery (LAD) who underwent dynamic SPECT myocardial perfusion imaging were retrospectively included. The assessment of semiquantitative indices of myocardial perfusion (summed stress scores, SSS) and quantitative parameters (MFR) was performed. RESULTS: A total of 49 patients were enrolled. The mean age of the subjects was 61.0 ± 9.0 years. All of the patients were symptomatic, and 16 cases (32.7%) presented with typical angina. SPECT-derived MFR showed a borderline significantly negative correlation with SSS (r = 0.261, P = .070). There was a trend of higher prevalence of impaired myocardial perfusion defined as MFR < 2 than as SSS ≥ 4 (42.9% vs 26.5%; P = .090). CONCLUSION: Our data support that SPECT MFR may be a useful parameter for the functional assessment of MB. In patients with MB, the use of dynamic SPECT could be a potential method for hemodynamic assessment.

The standard versus prolonged dual antiplatelet therapy after the XINSORB bioresorbable scaffold implantation (SPARTA) trial: study protocol for a randomized controlled trial.

BACKGROUND: Dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 inhibitor is the standard of care after coronary stenting, including coronary stenting involving bioresorbable scaffolds (BRSs). Current clinical guidelines recommend at least 12 months of DAPT after BRS implantation. However, the correlation between prolonged DAPT and net clinical benefits remains unknown. METHODS: The SPARTA trial is designed to be a prospective, randomized, parallel-group, clinical trial. It aims to compare the benefits and risks of DAPT applied for either 12 or 36 months after XINSORB BRS implantation. The primary endpoints are the incidence of the composite endpoint of major adverse cardiac events (MACEs), including all-cause death, any myocardial infarction (MI), and all revascularizations, as well as Bleeding Academic Research Consortium Definition (BARC) type 3 or 5 bleeding events. The secondary endpoints of the study include the device-oriented composite endpoint of target lesion failure (defined as cardiac death, target vessel-related MI, or ischemia-driven target lesion revascularization), target vessel failure (defined as cardiac death, MI, or ischemia-driven target vessel revascularization), scaffold thrombosis, and minor bleeding events. This trial will enroll 2106 subjects treated with the XINSORB BRS only. All subjects will receive DAPT after the index procedure for 12 (± 1) months. Subjects without MACEs or major bleeding will be randomized to receive either 24 additional months of DAPT or aspirin alone. DISCUSSION: This trial is designed to investigate the impact of extending the duration of DAPT up to 3 years after XINSORB BRS implantation by investigating the balance of risks and benefits in a broad population of treated patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT04501900 . Registered on 6 August 2020.

Drug-coated balloon for the treatment of small vessel disease: 9 months of angiographic results and 12 months of clinical outcomes of the PEPCAD China SVD study.

BACKGROUND: Whether the drug-coated balloons (DCBs)-alone strategy was superior to plain old balloon angioplasty (POBA) in treating SVD remains unknown. AIMS: We aimed to evaluate the efficacy and safety of DCBs for the treatment of coronary de novo small vessel disease (SVD) and provide further evidence for extending the clinical indications of DCBs. (ChiCTR1800014966). METHODS: Eligible patients were randomized at a 2:1 ratio to receive DCB treatment or POBA in this prospective, multicenter clinical trial. The reference vessel diameter of lesions was visually assessed to be 2.0 to 2.75 mm. The primary endpoint of the study was angiographic in-segment late luminal loss (LLL) at the 9-month follow-up to demonstrate the superiority of DCB treatment to POBA in SVD. The composite clinical endpoints included clinically driven target lesion revascularization (CD-TLR), target lesion failure (TLF), major adverse cardiac events (MACEs), and thrombosis at the 12-month follow-up. RESULTS: A total of 270 patients were enrolled (181 for DCB, 89 for POBA) at 18 centers in China. The primary endpoint of 9-month in-segment LLL in the intention-to-treat population was 0.10 ± 0.33 mm with DCB and 0.25 ± 0.38 mm with POBA (p = 0.0027). This difference indicated significant superiority of DCB treatment (95% CI: -0.22, -0.04, psuperiority = 0.0068). The rates of the clinical endpoints-CD-TLR, TLF, and MACEs-were comparable between groups. No thrombosis events were reported. CONCLUSIONS: DCB treatment of de novo SVD was superior to POBA with lower 9-month in-segment LLL. The rates of clinical events were comparable between the two devices.

A TEMPOL and rapamycin loaded nanofiber-covered stent favors endothelialization and mitigates neointimal hyperplasia and local inflammation.

An increased level of reactive oxygen species (ROS) plays a major role in endothelial dysfunction and vascular smooth muscle cell (VSMC) proliferation during in-stent thrombosis and restenosis after coronary artery stenting. Herein, we report an electrospun core-shell nanofiber coloaded with 4-hydroxy-2,2,6,6-tetramethylpiperidine 1-oxyl (TEMPOL) and rapamycin (RAPA) that correspondingly serves as an ROS scavenger and VSMC inhibitor. This system has the potential to improve the biocompatibility of current drug-eluting stent (DES) coatings with the long-term and continuous release of TEMPOL and rapamycin. Moreover, the RAPA/TEMPOL-loaded membrane selectively inhibited the proliferation of VSMCs while sparing endothelial cells (ECs). This membrane demonstrated superior ROS-scavenging, anti-inflammatory and antithrombogenic effects in ECs. In addition, the membrane could maintain the contractile phenotype and mitigate platelet-derived growth factor BB (PDGF-BB)-induced proliferation of VSMCs. In vivo results further revealed that the RAPA/TEMPOL-loaded covered stents promoted rapid restoration of vascular endothelium compared with DES and persistently impeded inflammation and neointimal hyperplasia in porcine models.

Structural Feature Analyzation Strategies toward Discovery of Orally Bioavailable PROTACs of Bruton's Tyrosine Kinase for the Treatment of Lymphoma.

Bruton's tyrosine kinase proteolysis-targeting chimeras (BTK-PROTACs) have emerged as a promising approach to address the limitations of BTK inhibitors. However, conducting the rational discovery of orally bioavailable BTK-PROTACs presents significant challenges. In this study, dimensionality reduction analysis and model molecule validation were utilized to identify some key structural features for improving the oral absorption of BTK-PROTACs. The results were applied to optimize the newly discovered BTK-PROTACs B1 and B2. Compound C13 was discovered with improved oral bioavailability, high BTK degradation activity, and selectivity. It exhibited inhibitory effects against different hematologic cancer cells and attenuated the BTK-related signaling pathway. The oral administration of C13 effectively reduced BTK protein levels and suppressed tumor growth. This study led to the discovery of a new orally bioavailable BTK-PROTAC for the treatment of lymphoma, and we hope that the strategy will find wide utility.

Structure-based rational design enables efficient discovery of a new selective and potent AKT PROTAC degrader.

AKT and associated signaling pathways have been recognized as promising therapeutic targets for decades, and growing evidence indicates that inhibition or degradation of cellular AKT are viable strategies to treat cancer. Guided by an in silico modeling approach for rational linker design and based on our previous work in this field, we herein efficiently synthesized a small group of cereblon-recruiting AKT PROTAC molecules and identified a highly potent AKT degrader B4. Compared to the existing AKT degraders, B4 has a structurally unique AKT targeting warhead derived from the pyrazole-furan conjugated piperidine derivatives. It induces selective degradation of all three isoforms of AKT and exhibits efficacious anti-proliferation against several human hematological cancers. Notably, B4 demonstrates potent inhibition of AKT downstream signaling superior to its parental inhibitor. Together with its active analogs, B4 expands the arsenal of AKT chemical degraders as a valuable probe to uncover AKTs new functions and as a potential drug candidate to treat cancer.

Functional comparison of different jailed balloon techniques in treating non-left main coronary bifurcation lesions.

BACKGROUND: There is a paucity of data comparing functional difference between active jailed balloon technique (A-JBT) and conventional jailed balloon technique (C-JBT) in treating non-left main coronary bifurcation lesions (CBLs). METHODS: In this retrospective cohort study, we consecutively enrolled 232 patients with non-left main CBLs who underwent percutaneous coronary intervention (PCI) using JBTs between January 2018 and March 2019. Among them, 191 patients entered the final analysis with 12-months angiographic follow-up. We stratified patients into A-JBT group (130 patients) and C-JBT group (61 patients). The functional analysis by Murray law-based quantitative flow ratio (µQFR) and Seattleanginaquestionnaire (SAQ) were performed to compare the two techniques. RESULTS: Compared with C-JBT group, A-JBT group observed a lower abrupt (0.8% vs. 11.1%, p = 0.002) and final SB occlusion (0 vs. 7.9%, p = 0.005). Meanwhile, A-JBT group had a significantly higher µQFR of side branch (SB) both post-PCI and 12-months follow-up (median [interquartile range (IQR)]: 0.91 (0.86-0.96) vs. 0.82 (0.69-0.92), p < 0.001; median [IQR]: 0.95 (0.89-0.98) vs. 0.85 (0.74-0.93), p < 0.001) than C-JBT group. Besides, A-JBT group gained a µQFR improvement at follow-up period compared with post-PCI data (median [IQR]: 0.95 [0.89-0.98] vs. 0.91[0.86-0.96] of SB, p < 0.001) and a higher SAQ scores at 12-months follow-up compared with C-JBT group (p < 0.001). CONCLUSIONS: Compared with C-JBT, A-JBT provided excellent SB protection during MV stenting and improved the SB functional blood flow as well as the angina relief even after 12 months.

The current scenario on anticancer activity of artemisinin metal complexes, hybrids, and dimers.

Cancer, the most significant cause of morbidity and mortality, has already posed a heavy burden on health care systems globally. In recent years, cancer treatment has made a significant breakthrough, but cancer cells inevitably acquire resistance, and the efficacy of the treatment is greatly reduced as the tumor progresses. To overcome the above issues, novel chemotherapeutics are needed urgently. Artemisinin and its derivatives-sesquiterpene lactone compounds possessing a unique peroxy bridge moiety-exhibit excellent safety and tolerability profiles. Mechanistically, artemisinin derivatives can promote cancer cell apoptosis, induce cell cycle arrest and autophagy, and inhibit cancer cell invasion and migration. Accordingly, artemisinin derivatives demonstrate promising anticancer efficacy both in vitro and in vivo, and even in clinical Phase I/II trials. The purpose of the present review article is to provide an emphasis on the current scenario (January 2017-January 2022) of artemisinin derivatives with potential anticancer activity, inclusive of artemisinin metal complexes, hybrids, and dimers. The structure-activity relationships and mechanisms of action are also discussed to facilitate the further rational design of more effective candidates.

Diagnostic Accuracy of Serum Amyloid A in Acute Appendicitis: A Systematic Review and Meta-Analysis.

Background: Serum amyloid A has been widely reported as a useful biochemical marker in the diagnoses of acute appendicitis. The aim of this study was to appraise the diagnostic accuracy of serum amyloid A in the diagnosis of acute appendicitis. Methods: A systematic search of several databases was conducted. The search time was from the beginning of the databases creation to March 1, 2021, and the languages were restricted to English and Chinese. Clinical studies using serum amyloid A for the diagnosis of acute appendicitis were included. The overall sensitivity and specificity were calculated by using a bivariable mixed effects model. Heterogeneity was tested using I2 statistics. This study has been registered on the International Prospective Register of Systematic Reviews (PROSPERO; no. CRD42021241343). Results: Five studies comprising 668 participants were eligible for inclusion. The overall sensitivity and specificity of serum amyloid A in diagnosing acute appendicitis were 0.87 (95% confidence interval [CI], 0.79-0.92) and 0.74 (95% CI, 0.59-0.85), respectively. The positive and negative likelihood were 3.3 (95% CI, 2.1-5.4) and 0.18 (95% CI, 0.11-0.28), respectively. The area under the summary receiver operating characteristic curves was 0.89 (95% CI, 0.86-0.91). The heterogeneity was significant (I2 = 82%; 95% CI [63%-100%]). Conclusions: Serum amyloid A has good diagnostic accuracy for acute appendicitis. It is expected that serum amyloid A could be helpful in the early clinical diagnosis of acute appendicitis.

Validation of a Novel Renal Denervation System With Cryoablation: A Preclinical Study and Case Series.

Recently, we designed a renal denervation with cryoablation (Cryo-RDN) system using liquid nitrogen and proved its short-term safety and effectiveness. In this study, we first conducted a 6-month follow-up in a swine model. Renal sympathetic nerve activity remained at a significantly lower level than that of the control group after 6 months. In patients with resistant hypertension, Cryo-RDN demonstrated preliminary safety. Renal function fluctuations and vascular-related complications were not detected. In addition, the average 24-hour systolic and diastolic blood pressure decreased by 12.17 ± 8.35 mm Hg and 8.50 ± 3.83 mm Hg at the 6-month follow-up, respectively, compared with their baseline values.

Discovery of phenyl-linked symmetric small molecules as inhibitors of the programmed cell death-1/programmed cell death-ligand 1 interaction.

Programmed cell death-1/programmed cell death ligand 1 (PD-1/PD-L1) is one of the most promising targets in the field of immune checkpoint blockade therapy. Beginning with our exploration of linkers and structure-activity relationship research, we found that the aromatic ring could replace the linker and aryl group to maintain the satisfactory activity of classic triaryl scaffold inhibitor. Based on previous studies, we designed and synthesized a series of C2-symmetric phenyl-linked compounds, and further tail optimization afforded the inhibitors, which displayed promising inhibitory activity against the PD-1/PD-L1 interaction with IC50 value at the single nanomolar range (C13-C15). Further cell-based PD-1/PD-L1 blockade bioassays indicated that these C2-symmetric molecules could significantly inhibit the PD-1/PD-L1 interaction at the cellular level and restore T cells' immune function at the safety concentrations. The discovery of these phenyl-linked symmetric small molecules showed the potential of simplified-linker and C2-symmetric strategy and provided a basis for developing symmetric small molecule inhibitors of PD-1/PD-L1 interaction. Moreover, C13 and C15 performed stable binding modes to PD-L1 dimeric after computational docking and dynamic simulation, which may serve as a good starting point for further development.

Novel Fe(III)-Polybasic acid coordination polymer nanoparticles with targeted retention for photothermal and chemodynamic therapy of tumor.

The development of Fe-coordination polymer-based nanoparticles, with safe and high anti-tumor effects, for the treatment of tumor is facing challenges such as limited resources and poor targeting. In this study, we prepared Fe-polyhydroxy coordination polymer nanoparticles (TA-Fe@MNPs), based on tartaric acid (TA)-Fe(III) coordination polymer as the new photothermal agent, mannose (M) as the target, and bovine serum albumin (BSA) and polyethyleneimine (PEI) as the carrier materials, and investigated them for targeting the multifunctional therapy of tumors. The TA-Fe@MNPs synthesized via a simple coordination of Fe3+ with TA, bovine serum albumin, and polyethyleneimine under ambient conditions exhibited an appropriate size (~125 nm), electrically neutral surfaces, good biocompatibility, and low normal cell toxicity. The TA-Fe@MNPs are the first to exhibit a remarkable photothermal performance. They also showed a pH-sensitive Fenton-like response that was further enhanced via glutathione response. Interestingly, after a single injection, the TA-Fe@MNPs could be retained at the tumor site for 36 h with an effective photothermal dose, which was attributed to the reduced protein adsorption and slow elimination in tumor cells with the aid of M modification and carrier materials, while that for the TA-Fe@NPs did so for only 2 h. Tumor ablation was demonstrated by in vivo photothermal and chemokinetic therapy using TA-Fe@MNPs, and their safety was evident from the weight changes and blood parameters. These results indicated that the TA-Fe@MNPs, as new photothermal and CDT agents, have the potential to be used in clinical tumor therapy nanoplatforms.

Feasibility and Safety of the Novel Vivolight Frequency Domain Optical Coherence Tomography System: A Multicenter Study.

OBJECTIVE: The study sought to assess the effectiveness and safety of the novel P60 Vivolight frequency-domain optical coherence tomography (OCT) system (Shenzhen Vivolight Medical Device & Technology). METHODS: A total of 90 patients were enrolled from 3 institutions. The pullbacks were performed with both the P60 Vivolight OCT system and the Ilumien Optis OCT system (Abbott Vascular). The primary endpoint was the clear stent length (CSL). Device safety was assessed by the record of serious procedure-related or postprocedure adverse events. The secondary endpoints were the average lumen area of stent, clear image length (CIL), system stability, and imaging catheter operability. RESULTS: The mean relative errors of CSL were 3.30% (95% confidence interval [CI], -0.71 to 7.31) in the full analysis set (FAS) and 0.83% (95% CI, -1.79 to 3.45) in the per-protocol set (PPS). The mean relative errors of the average lumen area of stent were 2.20% (95% CI, 0.70 to 3.80) in the FAS and 1.55% (95% CI, 0.30 to 2.80) in the PPS. No difference was observed in the percentage of obtaining >24 mm of CIL (93.18% in the P60 Vivolight group vs 95.45% in the Ilumien Optis group; P=.48). There were no serious procedure-related or postprocedure adverse events. CONCLUSIONS: The feasibility and safety of the novel Vivolight OCT system is equivalent to that of the Ilumien Optis OCT system.