True lumen expansion but no aortic remodeling following thoracic endografting and distal bare-stent for subacute complicated Type B aortic dissection.

BACKGROUND: The effects of thoracic endovascular aneurysm repair (TEVAR) with additional distal bare metal stents (BMSs) in patients with subacute complicated type B aortic dissection (cTBAD) are unclear and are investigated in this retrospective study. METHODS: The medical records of 67 patients who received TEVAR due to subacute cTBAD were reviewed. Areas of true lumen (TL) and false lumen at 5 levels-- pulmonary artery (PA), diaphragm, renal artery (RA), middle of the infrarenal aorta, and aortic bifurcation-were measured using computed tomography before and 3, 6, and 12 months after surgery. The TL ratio (TL area/total aortic area) and total aortic area at each time point were compared between the TEVAR+BMS (n=37) and TEVAR-only (n=30) groups. The effects of BMS use and time were evaluated using generalized estimating equations and generalized linear regression models. RESULTS: Baseline characteristics, remodeling types, and clinical outcomes did not differ significantly between the 2 groups. Postoperative TL ratios at the diaphragm and RA were significantly higher in the TEVAR+BMS group than in the TEVAR-only group (p < 0.05). BMS use and time had significant interaction effects at the PA, diaphragm, and RA (all p < 0.05), but effects on total aortic area were not significant at any of the 5 parts. TL ratios at the diaphragm and RA exhibtied greater improvement in the TEVAR+BMS group than in the TEVAR-only group at postoperative months 6 and 12 (all p < 0.001). Aortic diameters at all 5 parts were significantly smaller in the TEVAR+BMS group than in the TEVAR-only group (all p < 0.05). CONCLUSION: In patients with subacute cTBAD, TEVAR with BMS implantation effectively expands the TL from the thoracic aorta to the RA but neither enhances aortic remodeling nor elicits any change in total aortic area in whole dissected aorta relative to TEVAR only.

Assessing and optimizing the bioactivities of diverse enzyme-derived protein hydrolysates from Porphyra yezoensis: unlocking the health potential.

The interest in algae-derived bioactive compounds has grown due to their potential therapeutic efficacy against a range of diseases. These compounds, derived from proteins, exhibit diverse functions and profound pharmacological effects. Recent research has highlighted the extensive health benefits of algae-derived bioactive compounds, positioning them as potential natural antioxidants in the food, pharmaceutical, and cosmetic industries. This study focuses on extracting proteins from Porphyra yezoensis using innovative physical pre-treatment methods such as stirring, ball milling, and homogenization, under various acidic and alkaline conditions. Enzymatic hydrolysis, employing commercial enzymes at optimal temperature, pH, and enzyme-substrate ratios, produced distinct fractions according to molecular weight. Pepsin demonstrated the highest hydrolysis rate, with the fraction above 10 kDa identified as the most bioactive hydrolysate. Antioxidant activity was evaluated through DPPH, ABTS, ferrous ion chelation, and reducing power assays, demonstrating high antioxidant potential and the ability to mitigate oxidative stress. The 10 kDa fraction of pepsin hydrolysate exhibited 82.6% DPPH activity, 77.5% ABTS activity, 88.4% ferrous ion chelation activity, and higher reducing power potential (0.84 absorbance at 700 nm). Further exploration of mechanisms, amino acid profiles, and potential in vivo benefits is essential to fully exploit the medicinal potential of these algae-derived hydrolysates.

In vitro evaluation of antioxidant potential of polysaccharides and oligosaccharides extracted from three different seaweeds.

Bioactive polysaccharides and oligosaccharides were successfully extracted from three distinct seaweeds: Sargassum sp., Graciallaria sp., and Ulva sp. utilizing various extraction techniques. The obtained polysaccharides and oligosaccharides were subjected to comprehensive characterization, and their potential antioxidant properties were assessed using a Hep G2 cell model. Analysis via FTIR spectroscopy unveiled the presence of sulfate groups in the polysaccharides and oligosaccharides derived from Sargassum sp. The antioxidant capabilities were assessed through various assays (DPPH, ABTS, Fe-ion chelation, and reducing power), revealing that SAR-OSC exhibited superior antioxidant activity than others. This was attributed to its higher phenolic content (24.6 µg/mg), FRAP value (36 µM Vitamin C/g of extract), and relatively low molecular weight (5.17 kDa). The study also investigated the protective effects of these polysaccharides and oligosaccharides against oxidative stress-induced damage in Hep G2 cells by measuring ROS production and intracellular antioxidant enzyme expressions (SOD, GPx, and CAT). Remarkably, SAR-OSC demonstrated the highest efficacy in protecting Hep G2 cells reducing ROS production and downregulating SOD, GPx, and CAT expressions. Current findings have confirmed that the oligosaccharides extracted by the chemical method show higher antioxidant activity, particularly SAR-OSC, and robust protective abilities in the Hep G2 cells.

The multifaceted perspectives on the regulation of lncRNAs in hepatocellular carcinoma ferroptosis: from bench-to-bedside.

Despite being characterized by high malignancy, high morbidity, and low survival rates, the underlying mechanism of hepatocellular carcinoma (HCC) has not been fully elucidated. Ferroptosis, a non-apoptotic form of regulated cell death, possesses distinct morphological, biochemical, and genetic characteristics compared to other types of cell death. Dysregulated actions within the molecular network that regulates ferroptosis have been identified as significant contributors to the progression of HCC. Long non-coding RNAs (lncRNAs) have emerged as influential contributors to diverse cellular processes, regulating gene function and expression through multiple mechanistic pathways. An increasing body of evidence indicates that deregulated lncRNAs are implicated in regulating malignant events such as cell proliferation, growth, invasion, and metabolism by influencing ferroptosis in HCC. Therefore, elucidating the inherent role of ferroptosis and the modulatory functions of lncRNAs on ferroptosis in HCC might promote the development of novel therapeutic interventions for this disease. This review provides a succinct overview of the roles of ferroptosis and ferroptosis-related lncRNAs in HCC progression and treatment, aiming to drive the development of promising therapeutic targets and biomarkers for HCC patients.

Detection of GSH with a dual-mode biosensor based on carbon quantum dots prepared from dragon fruit peel and the T-Hg(II)-T mismatch.

Glutathione (GSH) is commonly used as a diagnostic biomarker for many diseases. In this study, based on carbon quantum dots prepared from dragon fruit peel (D-CQDs) and the T-Hg(II)-T mismatch, a dual-mode biosensor was developed for the detection of GSH. This system consists of two single-stranded DNA (ssDNA). DNA1 was the T-rich sequence; DNA2 was attached to streptavidin-coated magnetic beads and consisted of T-rich and G-rich fragments. Due to the presence of Hg(II), the T-Hg(II)-T mismatch was formed between T-rich fragments of two ssDNA. In the presence of GSH, Hg(II) detached from dsDNA and bound with GSH to form a new complex. The G-rich fragment assembled with the hemin shed from D-CQDs to form the G-quadruplex/hemin complex. At this time, in fluorescence mode, the fluorescence of D-CQDs quenched by hemin could be restored. In colorimetric mode, after the magnetic beads separate, a visual signal could be produced by catalyzing the oxidation of ABTS using the peroxide-like activity of the G-quadruplex/hemin complex. This biosensor in both fluorescence mode and colorimetric mode had excellent selectivity and sensitivity, and the limit of detection was 0.089 µM and 0.26 µM for GSH, respectively. Moreover, the proposed dual-mode biosensor had good application prospects for detection of GSH.

Design and radiosynthesis of class-IIa HDAC inhibitor with high molar activity via repositioning the 18F-radiolabel.

The design and radiosynthesis of [18F]NT376, a high potency inhibitor of class-IIa histone deacetylases (HDAC) is reported. We utilized a three-step radiochemical approach that led to the radiosynthesis of [18F]NT376 in a good radiochemical yield, (17.0 ± 3%, decay corrected), high radiochemical purity (> 97%) and relatively high molar activity of 185.0 GBq/µmol (> 5.0 Ci/µmol). The repositioning of the 18F-radiolabel into a phenyl ring (18F-Fluoro-aryl) of the class-IIa HDAC inhibitor avoided the shortcomings of the direct radiolabeling of the 5-trifluoromethyl-1,2,4-oxadiazole moiety that was reported by us previously and was associated with low molar activity (0.74-1.51 GBq/µmol, 20-41 mCi/µmol). This radiochemical approach could find a wider application for radiolabeling similar molecules with good radiochemical yield and high molar activity.

RNF149 Destabilizes IFNGR1 in Macrophages to Favor Post-Infarction Cardiac Repair.

BACKGROUND: Macrophage-driven inflammation critically involves in cardiac injury and repair following myocardial infarction (MI). However, the intrinsic mechanisms that halt the immune response of macrophages, which is critical to preserve homeostasis and effective infarct repair, remain to be fully defined. Here, we aimed to determine the ubiquitination-mediated regulatory effects on averting exaggerated inflammatory responses in cardiac macrophages. METHODS: We used transcriptome analysis of mouse cardiac macrophages and bone marrow-derived macrophages to identify the E3 ubiquitin ligase RNF149 (RING finger protein 149) as a modulator of macrophage response to MI. Employing loss-of-function methodologies, bone marrow transplantation approaches, and adenovirus-mediated RNF149 overexpression in macrophages, we elucidated the functional role of RNF149 in MI. We explored the underlying mechanisms through flow cytometry, transcriptome analysis, immunoprecipitation/mass spectrometry analysis, and functional experiments. RNF149 expression was measured in the cardiac tissues of patients with acute MI and healthy controls. RESULTS: RNF149 was highly expressed in murine and human cardiac macrophages at the early phase of MI. Knockout of RNF149, transplantation of Rnf149-/- bone marrow, and bone marrow macrophage-specific RNF149-knockdown markedly exacerbated cardiac dysfunction in murine MI models. Conversely, overexpression of RNF149 in macrophages attenuated the ischemia-induced decline in cardiac contractile function. RNF149 deletion increased infiltration of proinflammatory monocytes/macrophages, accompanied by a hastened decline in reparative subsets, leading to aggravation of myocardial apoptosis and impairment of infarct healing. Our data revealed that RNF149 in infiltrated macrophages restricted inflammation by promoting ubiquitylation-dependent proteasomal degradation of IFNGR1 (interferon gamma receptor 1). Loss of IFNGR1 rescued deleterious effects of RNF149 deficiency on MI. We further demonstrated that STAT1 activation induced Rnf149 transcription, which, in turn, destabilized the IFNGR1 protein to counteract type-II IFN (interferon) signaling, creating a feedback control mechanism to fine-tune macrophage-driven inflammation. CONCLUSIONS: These findings highlight the significance of RNF149 as a molecular brake on macrophage response to MI and uncover a macrophage-intrinsic posttranslational mechanism essential for maintaining immune homeostasis and facilitating cardiac repair following MI.

Hong Guo Ginseng Guo (HGGG) protects against kidney injury in diabetic nephropathy by inhibiting NLRP3 inflammasome and regulating intestinal flora.

BACKGROUND: Diabetic nephropathy (DN) is one of the most serious complications of diabetes which leads to end-stage renal failure and approximately one-third of patients need dialysis. There is still a lack of effective and specific treatment for DN. Searching new drugs from natural foods is an alternative approach to treat diabetes and its complications. Hong Guo Ginseng Guo (HGGG), a berry with palatability and nutritional benefits, has exhibited medicinal properties to mitigate the progression of DN. PURPOSE: This study investigates the effects of HGGG on streptozotocin (STZ)-induced diabetic nephropathy (DN) in rats and elucidates the mechanisms underlying its reno-protective and diabetes management benefits. METHODS: The LC-MS spectra method identified the primary ingredients in HGGG. To induce DN, male Sprague-Dawley (SD) rats received a single intraperitoneal injection of 75 mg/kg STZ. Over an eight-week treatment period, we assessed biochemical parameters including blood glucose, urine albumin-to-creatinine ratio (UACR), blood urea nitrogen (BUN), and urine N-acetyl-beta-d-glucosaminidase (NAG). Tissue pathology was examined using Masson's trichrome, Periodic Acid-Schiff (PAS), and Hematoxylin-Eosin (H&E) stains. We analyzed pro-inflammatory mediators and tissue fibrosis extent using Western blotting and immunohistochemistry. Gut microbiota composition was characterized via 16S rDNA sequencing. RESULTS: Seventeen chemical compounds were identified, with lobetyolin, luteolin, and rutin highlighted as the primary active elements. HGGG extract appeared to confer renal protection, demonstrated by improvements in UACR, BUN, and urine NAG levels. The reno protective effects in HGGG-treated DN rats were linked to reduced renal fibrosis and inhibition of the NLRP3 inflammasome. Additionally, HGGG administration improved gut barrier integrity and altered the gut microbiota in DN rats, increasing the relative abundance of beneficial bacteria known for regulating polyamines and producing short-chain fatty acids (SCFAs), including Ruminococcus, Barnesiella_sp, Anaerovoracaceae, and Prevotellaceae_NK3B31. Meanwhile, treatment with HGGG decreasing the presence of Oscillospira, potential pathogens responsible for producing lipopolysaccharide (LPS). CONCLUSION: HGGG has potential as a beneficial fruit for managing diabetes and its associated complications through modulation of the gut microbiota.

Risk of chronic kidney disease in patients with a hyperglycemic crisis as the initial presentation of type 2 diabetes.

Limited data exist on long-term renal outcomes in patients with hyperglycemic crisis (HC) as initial type 2 diabetes presentation. We evaluated the risk of chronic kidney disease (CKD) development in those with concurrent HC at diagnosis. Utilizing Taiwan's insurance claims from adults newly diagnosed with type 2 diabetes during 2006-2015, we created HC and matched non-HC cohorts. We assessed incident CKD/diabetic kidney disease (DKD) by 2018's end, calculating the hazard ratio (HR) with the Cox model. Each cohort comprised 13,242 patients. The combined CKD and DKD incidence was two-fold higher in the HC cohort than in the non-HC cohort (56.47 versus 28.49 per 1000 person-years) with an adjusted HR (aHR) of 2.00 (95% confidence interval [CI] 1.91-2.10]). Risk increased from diabetic ketoacidosis (DKA) (aHR:1.69 [95% CI 1.59-1.79]) to hyperglycemic hyperosmolar state (HHS) (aHR:2.47 [95% CI 2.33-2.63]) and further to combined DKA-HHS (aHR:2.60 [95% CI 2.29-2.95]). Subgroup analysis in individuals aged ≥ 40 years revealed a similar trend with slightly reduced incidences and HRs. Patients with HC as their initial type 2 diabetes presentation face a higher CKD risk than do those without HC. Enhanced medical attention and customized interventions are crucial to reduce this risk.

Disulfiram inhibits coronaviral main protease by conjugating to its substrate entry site.

Coronaviruses (CoV) are highly pathogenic single-strand RNA viruses. CoV infections cause fatal respiratory symptoms and lung injuries in humans and significant economic losses in livestock. Since the SARS-2 outbreak in 2019, the highly conserved main protease (Mpro), also termed 3-chymotrypsin-like protease (3CLpro), has been considered an attractive drug target for treating CoV infections. Mpro mediates the proteolytic cleavage of eleven sites in viral polypeptides necessary for virus replication. Here, we report that disulfiram, an FDA-approved drug for alcoholic treatment, exhibits a broad-spectrum inhibitory effect on CoV Mpros. Analytical ultracentrifugation and circular dichroism analyses indicated that disulfiram treatment blocks the dimeric formation of SARS and PEDV Mpros and decreases the thermostability of SARS, SARS-2, and PEDV Mpros, whereas it facilitates the dimerization and stability of MERS Mpro. Furthermore, mass spectrometry and structural alignment revealed that disulfiram targets the Cys44 residue of Mpros, which is located at the substrate entrance and close to the catalytic His41. In addition, molecular docking analysis suggests that disulfiram conjugation interferes with substrate entry to the catalytic center. In agreement, mutation of Cys44 modulates the disulfiram sensitivity of CoV Mpros. Our study suggests a broad-spectrum inhibitory function of disulfiram against CoV Mpros.

End-tidal Carbon Dioxide Trajectory-based Prognostication of Out-of-hospital Cardiac Arrest.

Background: During cardiopulmonary resuscitation (CPR), end-tidal carbon dioxide (EtCO2) is primarily determined by pulmonary blood flow, thereby reflecting the blood flow generated by CPR. We aimed to develop an EtCO2 trajectory-based prediction model for prognostication at specific time points during CPR in patients with out-of-hospital cardiac arrest (OHCA). Methods: We screened patients receiving CPR between 2015-2021 from a prospectively collected database of a tertiary-care medical center. The primary outcome was survival to hospital discharge. We used group-based trajectory modeling to identify the EtCO2 trajectories. Multivariable logistic regression analysis was used for model development and internally validated using bootstrapping. We assessed performance of the model using the area under the receiver operating characteristic curve (AUC). Results: The primary analysis included 542 patients with a median age of 68.0 years. Three distinct EtCO2 trajectories were identified in patients resuscitated for 20 minutes (min): low (average EtCO2 10.0 millimeters of mercury [mm Hg]; intermediate (average EtCO2 26.5 mm Hg); and high (average EtCO2: 51.5 mm Hg). Twenty-min EtCO2 trajectory was fitted as an ordinal variable (low, intermediate, and high) and positively associated with survival (odds ratio 2.25, 95% confidence interval [CI] 1.07-4.74). When the 20-min EtCO2 trajectory was combined with other variables, including arrest location and arrest rhythms, the AUC of the 20-min prediction model for survival was 0.89 (95% CI 0.86-0.92). All predictors in the 20-min model remained statistically significant after bootstrapping. Conclusion: Time-specific EtCO2 trajectory was a significant predictor of OHCA outcomes, which could be combined with other baseline variables for intra-arrest prognostication. For this purpose, the 20-min survival model achieved excellent discriminative performance in predicting survival to hospital discharge.

Development of a Radiolabeled Cyclin-Dependent Kinases 4 and 6 (CDK4/6) Inhibitor for Brain and Cancer PET Imaging.

The synthesis, biochemical evaluation and radiosynthesis of a cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitor and radioligand was performed. NT431, a newly synthesized 4-fluorobenzyl-abemaciclib, exhibited high potency to CDK4/6 and against four cancer cell lines with IC50 similar to that of the parent abemaciclib. We performed a two-step one-pot radiosynthesis to produce [18F]NT431 with good radiochemical yield (9.6 ± 3%, n = 3, decay uncorrected), high radiochemical purity (>95%), and high molar activity (>370 GBq/µmol (>10.0 Ci/µmol). In vitro autoradiography confirmed the specific binding of [18F]NT431 to CDK4/6 in brain tissues. Dynamic PET imaging supports that both [18F]NT431 and the parent abemaciclib crossed the BBB albeit with modest brain uptake. Therefore, we conclude that it is unlikely that NT431 or abemaciclib (FDA approved drug) can accumulate in the brain in sufficient concentrations to be potentially effective against breast cancer brain metastases or brain cancers. However, despite the modest BBB penetration, [18F]NT431 represents an important step towards the development and evaluation of a new generation of CDK4/6 inhibitors with superior BBB penetration for the treatment and visualization of CDK4/6 positive tumors in the CNS. Also, [18F]NT431 may have potential application in peripheral tumors such as breast cancer and other CDK4/6 positive tumors.

Formation of Zwitterionic and Self-Healable Hydrogels via Amino-yne Click Chemistry for Development of Cellular Scaffold and Tumor Spheroid Phantom for MRI.

In situ-forming biocompatible hydrogels have great potential in various medical applications. Here, we introduce a pH-responsive, self-healable, and biocompatible hydrogel for cell scaffolds and the development of a tumor spheroid phantom for magnetic resonance imaging. The hydrogel (pMAD) was synthesized via amino-yne click chemistry between poly(2-methacryloyloxyethyl phosphorylcholine-co-2-aminoethylmethacrylamide) and dialkyne polyethylene glycol. Rheology analysis, compressive mechanical testing, and gravimetric analysis were employed to investigate the gelation time, mechanical properties, equilibrium swelling, and degradability of pMAD hydrogels. The reversible enamine and imine bond mechanisms leading to the sol-to-gel transition in acidic conditions (pH ≤ 5) were observed. The pMAD hydrogel demonstrated potential as a cellular scaffold, exhibiting high viability and NIH-3T3 fibroblast cell encapsulation under mild conditions (37 °C, pH 7.4). Additionally, the pMAD hydrogel also demonstrated the capability for in vitro magnetic resonance imaging of glioblastoma tumor spheroids based on the chemical exchange saturation transfer effect. Given its advantages, the pMAD hydrogel emerges as a promising material for diverse biomedical applications, including cell carriers, bioimaging, and therapeutic agent delivery.

Benmelstobart, anlotinib and chemotherapy in extensive-stage small-cell lung cancer: a randomized phase 3 trial.

Immunochemotherapy is the first-line standard for extensive-stage small-cell lung cancer (ES-SCLC). Combining the regimen with anti-angiogenesis may improve efficacy. ETER701 was a multicenter, double-blind, randomized, placebo-controlled phase 3 trial that investigated the efficacy and safety of benmelstobart (a novel programmed death-ligand 1 (PD-L1) inhibitor) with anlotinib (a multi-target anti-angiogenic small molecule) and standard chemotherapy in treatment-naive ES-SCLC. The ETER701 trial assessed two primary endpoints: Independent Review Committee-assessed progression-free survival per RECIST 1.1 and overall survival (OS). Here the prespecified final progression-free survival and interim OS analysis is reported. Patients randomly received benmelstobart and anlotinib plus etoposide/carboplatin (EC; n = 246), placebo and anlotinib plus EC (n = 245) or double placebo plus EC ('EC alone'; n = 247), followed by matching maintenance therapy. Compared with EC alone, median OS was prolonged with benmelstobart and anlotinib plus EC (19.3 versus 11.9 months; hazard ratio 0.61; P = 0.0002), while improvement of OS was not statistically significant with anlotinib plus EC (13.3 versus 11.9 months; hazard ratio 0.86; P = 0.1723). The incidence of grade 3 or higher treatment-related adverse events was 93.1%, 94.3% and 87.0% in the benmelstobart and anlotinib plus EC, anlotinib plus EC, and EC alone groups, respectively. This study of immunochemotherapy plus multi-target anti-angiogenesis as first-line treatment achieved a median OS greater than recorded in prior randomized studies in patients with ES-SCLC. The safety profile was assessed as tolerable and manageable. Our findings suggest that the addition of anti-angiogenesis therapy to immunochemotherapy may represent an efficacious and safe approach to the management of ES-SCLC. ClinicalTrials.gov identifier: NCT04234607 .

Application of psychological intervention in intensive care unit nursing for patients with severe acute pancreatitis.

BACKGROUND: Severe acute pancreatitis (SAP) is a familiar critical disease in the intensive care unit (ICU) patients. Nursing staff are important spiritual pillars during the treatment of patients, and in addition to routine nursing, more attention needs be paid to the patient's psychological changes. AIM: To investigate the effects of psychological intervention in ICU patients with SAP. METHODS: One hundred ICU patients with SAP were hospitalized in the authors' hospital between 2020 and 2023 were selected, and divided into observation and control groups per the hospitalization order. The control and observation groups received routine nursing and psychological interventions, respectively. Two groups are being compared, using the Self-rating Anxiety Scale (SAS), Self-Determination Scale (SDS), Acute Physiology and Chronic Health Evaluation (APACHE) II, and 36-item Short Form Health Survey (SF-36) scores; nursing satisfaction of patients; ICU care duration; length of stay; hospitalization expenses; and the incidence of complications. RESULTS: After nursing, the SDS, SAS, and APACHE II scores in the experimental group were significantly lower than in the control group (P < 0.05). The SF-36 scores in the observation group were significantly higher than those in the control group (P < 0.05). The nursing satisfaction of patients in the experimental group was 94.5%, considerably higher than that of 75.6% in the control group (P < 0.05). The ICU care duration, length of stay, and hospitalization expenses in the observation group were significantly lower than those in the control group, and the incidence of complications was lower (P < 0.05). CONCLUSION: For patients with SAP, the implementation of standardized psychological intervention measures can effectively alleviate adverse psychological conditions.

The effect of low-level laser therapy on osteoclast differentiation: Clinical implications for tooth movement and bone density.

Background/purpose: Osteoclast differentiation is crucial for orchestrating both tooth movement and the maintenance of bone density. Therefore, the current study sought to explore the impact of low-level laser therapy (LLLT) on osteoclast differentiation, functional gene expression, molecular signaling pathways, and orthodontic tooth movement in clinical settings. Materials and methods: The RAW 264.7 cell line served as the precursor for osteoclasts, and these cells underwent irradiation using a 808-nm LLLT. Osteoclast differentiation was assessed through tartrate-resistant acid phosphatase (TRAP) staining. Functional gene expression levels were evaluated using real-time quantitative polymerase chain reaction (RT-qPCR) while signaling molecules were examined through Western blot analysis. In the clinical study, 12 participants were enrolled. Their tooth movement was monitored using a TRIOS desktop scanner. Bone density measurements were conducted using Mimics software, which processed cone-beam computed tomography (CBCT) images exported in Digital Imaging and Communications in Medicine (DICOM) format. Results: We found that LLLT effectively promoted receptor activator of nuclear factor-κB ligand (RANKL)-dependent osteoclast differentiation and the expression of osteoclast functional genes, including matrix metallopeptidase 9 (MMP9), nuclear factor of activated T-cells cytoplasmic 1(NFATc1), tartrate-resistant acid phosphatase (TRAP) and cathepsin K (CTSK) in RAW264.7 cells. Clinically, the cumulative tooth movement over 90 days was significantly higher in the laser group than in the control group. Conclusion: Our research demonstrates that LLLT not only significantly promotes osteoclast differentiation but is also a valuable adjunct in orthodontic therapy.

exo-6b2-Methyl-Substituted Pentabenzocorannulene: Synthesis, Structural Analysis, and Properties.

exo-6b2-Methyl-substituted pentabenzocorannulene (exoPBC-Me) was synthesized by the palladium-catalyzed cyclization of 1,2,3-triaryl-1H-cyclopenta[l]phenanthrene. Its bowl-shaped geometry with an sp3 carbon atom in the backbone and a methyl group located at the convex (exo) face was verified by X-ray crystallography. According to DFT calculations, the observed conformer is energetically more favorable than the endo one by 39.9 kcal/mol. Compared to the nitrogen-doped analogs with intact π-conjugated backbones (see the main text), exo-PBC-Me displayed a deeper bowl depth (avg. 1.93 Å), redshifted and broader absorption (250-620 nm) and emission (from 585 to more than 850 nm) bands and a smaller optical HOMO-LUMO gap (2.01 eV). exo-PBC-Me formed polar crystals where all bowl-in-bowl stacking with close π···π contacts is arranged unidirectionally, providing the potential for applications as organic semiconductors and pyroelectric materials. This unusual structural feature, molecular packing, and properties are most likely associated with the assistance of the methyl group and the sp3 carbon atom in the backbone.

[Expression and Clinical Significance of LINC00475 in Multiple Myeloma].

OBJECTIVE: To investigate the relative expression level and clinical significance of LINC00475 in serum of patients with multiple myeloma (MM). METHODS: The expression of LINC00475 in serum of 108 MM patients and five MM cell lines including RPMI 8226, NCI-H929, U266, OPM2 and CAG were detected by real-time fluorescence quantitative PCR. The diagnostic value of LINC00475 in MM was evaluated by receiver operating characteristic (ROC) curve analysis. The correlation of LINC00475 with patients' characteristics was analyzed. RESULTS: Compared with control groups, the expression of LINC00475 was up-regulated in serum of MM patients and MM cell lines (all P < 0.05). ROC curve analysis showed that the optimal cut-off value of LINC00475 was 262.4, the area under curve (AUC) was 0.924(95%CI : 0.884-0.964), and sensitivity and specificity was 83.3% and 91.7%, respectively, which indicated that LINC00475 had good evaluation value in MM patients. Compared with low-LINC00475 expression group, patients in high-LINC00475 expression group had higher levels of ß2microglobulin (ß2-MG) and Cystatin C (Cys-C) but lower albumin (ALB) (all P < 0.05). Compared with MM patients with International Staging System (ISS) stage I, the expression level of LINC00475 was significantly higher in patients with stage II and III (both P < 0.05). CONCLUSION: LINC00475 is helpful to distinguish MM patients from healthy adults, which is correlated with the prognostic indicators such as ß2-MG, ALB, and ISS stage.

Rationale Design for Anchoring Pendant Groups of Zwitterionic Polymeric Medical Coatings.

A biocompatible and antifouling polymeric medical coating was developed through rational design for anchoring pendant groups for the modification of stainless steel. Zwitterionic 2-methacryloyloxyethyl phosphorylcholine (MPC) was copolymerized individually with three anchoring monomers of carboxyl acrylamides with different alkyl spacers, including acryloylglycine (2-AE), 6-acrylamidohexanoic acid (6-AH), and 11-acrylamidoundecanoic acid (11-AU). The carboxylic acid groups are responsible for the stable grafting of copolymers onto stainless steel via a coordinative interaction with metal oxides. Due to hydrophobic interaction and hydrogen bonding, the anchoring monomers enable the formation of self-assembling structures in solution and at a metallic interface, which can play an important role in the thin film formation and functionality of the coatings. Therefore, surface characterizations of anchoring monomers on stainless steel were conducted to analyze the packing density and strength of the intermolecular hydrogen bonds. The corresponding copolymers were synthesized, and their aggregate structures were assessed, showing micelle aggregation for copolymers with higher hydrophobic compositions. The synergistic effects of inter/intramolecular interactions and hydrophobicity of the anchoring monomers result in the diversity of the thickness, surface coverage, wettability, and friction of the polymeric coatings on stainless steel. More importantly, the antifouling properties of the coatings against bacteria and proteins were strongly correlated to thin film formation. Ultimately, the key lies in deciphering the molecular structure of the anchoring pendants in thin film formation and assessing the effectiveness of the coatings, which led to the development of medical coatings through the graft-onto approach.