Verteporfin suppressed mitophagy via PINK1/parkin pathway in endometrial cancer.

Endometrial cancer (EC) is a malignancy that poses a threat to woman's health worldwide. Building upon prior work, we explored the inhibitory effect of verteporfin on EC. We showed that verteporfin can damage the mitochondria of EC cells, leading to a decrease of mitochondrial membrane potential and an increase in ROS (reactive oxygen species). In addition, verteporfin treatment was shown to inhibit the proliferation and migration of EC cells, promote apoptosis, and reduce the expression of mitophagy-related proteins PINK1/parkin and TOM20. The ROS inhibitor N-Acetyl Cysteine was able to rescue the expression of PINK1/parkin proteins. This suggests that verteporfin may inhibit mitophagy by elevating ROS levels, thereby inhibiting EC cell viability. The effect of verteporfin on mitophagy supports further investigation as a potential therapeutic option for EC.

Comparative efficacy of interventional therapies and devices for coronary in-stent restenosis: A systematic review and network meta-analysis of randomized controlled trials.

Background: In-stent restenosis (ISR) has become a significant obstacle to interventional therapy for atherosclerotic cardiovascular disease. The optimal percutaneous coronary intervention (PCI) strategy for patients with coronary ISR remains controversial. This network meta-analysis (NMA) was aimed to compare and estimate the effectiveness of different PCI strategies and commercial devices for the treatment of patients with coronary ISR. Methods: In present study, we systematically searched PubMed, Embase, Web of Science, and Cochrane Library from database inception to October 20, 2022, to identify randomized controlled trials. We included studies comparing various PCI strategies for the treatment of any type of coronary ISR. The study was registered with PROSPERO, CRD 42022364308. Results: We included 44 eligible trials including 8479 patients, 39 trials comparing the treatment effects of 10 PCIs, and 5 trials comparing the efficacy between different types of drug-eluting stent (DES) or drug-coated balloon (DCB) devices. Among the PCIs, everolimus-eluting stent was the optimal strategy considering target lesion revascularization (TLR), percent diameter stenosis (%DS), and binary restenosis (BR), and sirolimus-coated balloon was the optimal strategy considering late lumen loss (LLL). In the comparison of commercial devices, the combination strategy excimer laser coronary angioplasty plus SeQuent Please paclitaxel-coated balloon showed promising therapeutic prospects. Conclusions: DCB and DES remain the preferred treatment strategies for coronary ISR, considering both the primary clinical outcome (TLR) and the angiographic outcomes (LLL, BR, %DS). Personalized combination interventions including DCB or DES hold promise as a novel potential treatment pattern for coronary ISR.

Design of stretchable and self-powered sensing device for portable and remote trace biomarkers detection.

Timely and remote biomarker detection is highly desired in personalized medicine and health protection but presents great challenges in the devices reported so far. Here, we present a cost-effective, flexible and self-powered sensing device for H2S biomarker analysis in various application scenarios based on the structure of galvanic cells. The sensing mechanism is attributed to the change in electrode potential resulting from the chemical adsorption of gas molecules on the electrode surfaces. Intrinsically stretchable organohydrogels are used as solid-state electrolytes to enable stable and long-term operation of devices under stretching deformation or in various environments. The resulting open-circuit sensing device exhibits high sensitivity, low detection limit, and excellent selectivity for H2S. Its application in the non-invasive halitosis diagnosis and identification of meat spoilage is demonstrated, emerging great commercial value in portable medical electronics and food security. A wireless sensory system has also been developed for remote H2S monitoring with the participation of Bluetooth and cloud technologies. This work breaks through the shortcomings in the traditional chemiresistive sensors, offering a direction and theoretical foundation for designing wearable sensors catering to other stimulus detection requirements.

Investigating whether exosomal miR-205-5p derived from tongue squamous cell carcinoma cells stimulates the angiogenic activity of HUVECs by targeting AMOT.

BACKGROUND: Although exosomal microRNAs (exo-miRNAs) regulate angiogenesis, they are not sufficient for the development of anti-vascular drugs for tongue squamous cell carcinoma (TSCC). miR-205-5p is an exo-miRNA that is highly expressed in the saliva of patients with oral SCC. OBJECTIVE: We aimed to clarify the role and molecular mechanism of exosomal miR-205-5p in regulating TSCC angiogenesis. METHODS: Effect of exosomes derived from TSCC cells on human umbilical vein endothelial cell (HUVEC) function was determined using the CCK-8, Transwell, Transwell-Matrigel, and Matrigel-based tube formation assays. Protein levels were detected by western blot. The binding between miR-205-5p and the 3'UTR of AMOT was verified using a luciferase reporter assay. RESULTS: Exosomal miR-205-5p (exo-miR-205-5p) promoted the proliferation, migration, and invasion of HUVECs, increased the number of tubes formed by HUVECs, and increased the vascular endothelial growth factor receptor 2 levels in HUVECs. Exo-miR-205-5p downregulated the AMOT level in HUVECs. Results of the luciferase reporter assay showed that miR-205-5p could bind to the 3'UTR of AMOT. AMOT overexpression blocked the effect of exo-miR-205-5p on HUVEC functions. CONCLUSION: Exo-miR-205-5p derived from TSCC regulates the angiogenic activity of HUVECs by targeting AMOT and might be a new molecular target for the development of anti-vascular drugs for TSCC.

Association between distance to community health care facilities and COVID-19-related mortality across U.S. counties in the COVID-19-vaccine era.

OBJECTIVE: COVID-19 has caused tremendous damage to U.S. public health, but COVID vaccines can effectively reduce the risk of COVID-19 infections and related mortality. Our study aimed to quantify the association between proximity to a community healthcare facility and COVID-19 related mortality after COVID vaccines became publicly available and explore how this association varied across racial and ethnic groups. RESULTS: Residents living farther from a facility had higher COVID-19-related mortality across U.S. counties. This increased mortality incidence associated with longer distances was particularly pronounced in counties with higher proportions of Black and Hispanic populations.

Light availability modulates the responses of the microalgae Desmodesmus sp. to micron-sized polyvinyl chloride microplastics.

The vertical movement of large-size and high-density MPs in the water column is usually along with dynamic changes in light intensity. However, whether the change in light availability affects the bioeffects of MPs on surrounding microalgae is currently unknown. This study investigated the effects of micron-sized polyvinyl chloride (mPVC, 143.5 µm) microplastics, alone and in combination with light intensity (from 7.5 to 162.5 µmol·m-2·s-1) on the growth and physiology of Desmodesmus sp. Although mPVC did not impact microalgal growth under optimal light (40 and 93.8 µmol·m-2·s-1), it could induce a no-contact shading effect, thereby significantly affecting the physiology of Desmodesmus sp. The growth of Desmodesmus sp. exposed to mPVC was enhanced under a high light intensity of 162.5 µmol·m-2·s-1 which can induce growth inhibition but was retarded when under a light inadequacy condition (20 µmol·m-2·s-1), along with a dose-dependent effect. Significantly, the photosynthesis of Desmodesmus sp. was a highly sensitive metabolic pathway to mPVC stress and largely influenced by the plastic particles under different light conditions. Additionally, mPVC modulated the energy metabolism strategy of Desmodesmus sp., depending on exposure dose and external light availability. Our findings provided a critical basis for the risk assessment of MPs in fluctuating light conditions.

Profiling Temporal Changes of the Pineal Transcriptomes at Single Cell Level Upon Neonatal HIBD.

Neonatal hypoxic-ischemic brain damage (HIBD) often results in various neurological deficits. Among them, a common, yet often neglected, symptom is circadian rhythm disorders. Previous studies revealed that the occurrence of cysts in the pineal gland, an organ known to regulate circadian rhythm, is associated with circadian problems in children with HIBD. However, the underlying mechanisms of pineal dependent dysfunctions post HIBD remain largely elusive. Here, by performing 10x single cell RNA sequencing, we firstly molecularly identified distinct pineal cell types and explored their transcriptome changes at single cell level at 24 and 72 h post neonatal HIBD. Bioinformatic analysis of cell prioritization showed that both subtypes of pinealocytes, the predominant component of the pineal gland, were mostly affected. We then went further to investigate how distinct pineal cell types responded to neonatal HIBD. Within pinealocytes, we revealed a molecularly defined ß to α subtype conversion induced by neonatal HIBD. Within astrocytes, we discovered that all three subtypes responded to neonatal HIBD, with differential expression of reactive astrocytes markers. Two subtypes of microglia cells were both activated by HIBD, marked by up-regulation of Ccl3. Notably, microglia cells showed substantial reduction at 72 h post HIBD. Further investigation revealed that pyroptosis preferentially occurred in pineal microglia through NLRP3-Caspase-1-GSDMD signaling pathway. Taken together, our results delineated temporal changes of molecular and cellular events occurring in the pineal gland following neonatal HIBD. By revealing pyroptosis in the pineal gland, our study also provided potential therapeutic targets for preventing extravasation of pineal pathology and thus improving circadian rhythm dysfunction in neonates with HIBD.

Stretchable, Stable, and Room-Temperature Gas Sensors Based on Self-Healing and Transparent Organohydrogels.

Conductive hydrogels have emerged as promising candidate materials for fabricating wearable electronics because of their fascinating stimuli-responsive and mechanical properties. However, the inherent instability of hydrogels seriously limits their application scope. Herein, the stable, ultrastretchable (upon to 1330% strain), self-healing, and transparent organohydrogel was exploited as a novel gas-responsive material to fabricate NH3 and NO2 gas sensors for the first time with extraordinary performance. A facile solvent substitution method was employed to convert the unstable hydrogel into the organohydrogel with a remarkable moisture retention (avoid drying within a year), frost resistance (freezing point below -130 °C), and unimpaired mechanical and gas sensing properties. First-principles simulations were performed to uncover the mechanisms of antidrying and antifreezing effects of organohydrogels and the interactions between NH3/NO2 and organohydrogels, revealing the vital role of hydrogen bonds in enhancing the stability and the adsorption of NH3/NO2 on the organohydrogel. The organohydrogel gas sensor displayed high sensitivity, ultralow theoretical limit of detection (91.6 and 3.5 ppb for NH3 and NO2, respectively), reversibility, and fast recovery at room temperature. It exhibited the capabilities to work at a highly deformed state with nondegraded sensing performance and restore all the electrical, mechanical, and sensing properties after mechanical damage. The gas sensing mechanism was understood by considering the gas adsorption on functional groups, dissolution in the solvent, and the hindering effect on the transport of ions.

Simultaneous quantitation of four androgens and 17-hydroxyprogesterone in polycystic ovarian syndrome patients by LC-MS/MS.

BACKGROUND: Due to the low concentration of androgens in women and the limitation of immunoassays, it remains a challenge to accurately determine the levels of serum androgens in polycystic ovary syndrome (PCOS) patients for clinical laboratories. In this report, a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for simultaneous quantitation of testosterone (T), androstenedione (A4), dehydroepiandrosterone sulfate (DHEAS), dihydrotestosterone (DHT), and 17-hydroxyprogesterone (17-OHP) that are associated with PCOS. METHODS: The serum samples were processed by protein precipitation and solid phase extraction before analysis with the in-house developed LC-MS/MS. The chromatographic separation was achieved with a C18 column, using a linear gradient elution with two mobile phases: 0.02% formic acid in water (phase A) and 0.1% formic acid in methanol (phase B). The separated analytes were detected by positive or negative electrospray ionization mode under multiple reaction monitoring (MRM). RESULTS: The assay for all the five analytes was linear, stable, with imprecision less than 9% and recoveries within ±10%. The lower limits of quantification were 0.05, 0.05, 5, 0.025, and 0.025 ng/mL for T, A4, DHEAS, DHT, and 17-OHP, respectively. In the receiver operating characteristic curve (ROC) analyses with the PCOS (n = 63) and healthy (n = 161) subjects, the AUC of the four-androgen combined was greater than that of any single androgen tested in PCOS diagnosis. CONCLUSIONS: The LC-MS/MS method for the four androgens and 17-OHP showed good performance for clinical implementation. More importantly, simultaneous quantitation of the four androgens provided better diagnostic power for PCOS.

Green Synthesis of 3D Chemically Functionalized Graphene Hydrogel for High-Performance NH3 and NO2 Detection at Room Temperature.

To address the low gas sensitivity of pristine graphene (Gr), chemical modification of Gr has been proved as a promising route. However, the existing chemical functionalization method imposes the utilization of toxic chemicals, increasing the safety risk. Herein, vitamin C (VC)-modified reduced graphene hydrogel (V-RGOH) is synthesized via a green and facile self-assembly process with the assistance of biocompatible VC molecules for high-performance NH3 and NO2 detection. The three-dimensional (3D) structured V-RGOH is highly sensitive to low-concentration NH3 and NO2 at room temperature. In comparison with those of the unmodified RGOH, the V-RGOH gas sensors display an order of magnitude higher sensitivity and much lower limit of detection, resulting from the enhanced interaction between VC and analytes. NH3 and NO2 with extremely low concentrations of 500 and 100 ppb are detected experimentally. Notably, imbedded microheaters are exploited to explore the temperature-dependent gas sensing properties, revealing the negative and positive impacts of temperature on the sensitivity and recovery speed, respectively. Notably, the V-RGOH sensor exhibits remarkable selectivity and linearity and a wide detection range. This work reveals the remarkable effects of chemical modification with biodegradable molecules and 3D structure design on improving the gas sensing performance of the Gr material.

Ultrasensitive and Stretchable Temperature Sensors Based on Thermally Stable and Self-Healing Organohydrogels.

It is essential to impart the thermal stability, high sensitivity, self-healing, and transparent attributes to the emerging wearable and stretchable electronics. Here, a facile solvent replacement strategy is exploited to introduce ethylene glycol/glycerol (Gly) in hydrogels for enhancing their thermal sensitivity and stability synchronously. For the first time, we find that the solvent plays a key role in the thermal sensitivity of hydrogels. By adjusting the water content in hydrogels using a simple dehydration treatment, the thermal sensitivity is raised to 13.1%/°C. Thanks to the ionic transport property and water-Gly binary solvent, the organohydrogel achieves an unprecedented thermal sensitivity of 19.6%/°C, which is much higher than those of previously reported stretchable thermistors. The mechanism for the thermal response is revealed by considering the thermally activated ion mobility and dissociation. The stretchable thermistors are conformally attached on curved surfaces for the practical monitoring of minute temperature change. Notably, the uncovered Gly-organohydrogel avoids drying and freezing at 70 and -18 °C, respectively, reflecting the excellent antidrying and antifreezing attributes. In addition, the organohydrogel displays ultrahigh stretchability (1103% strain), self-healing ability, and high transparency. This work sheds light on fabricating ultrasensitive and stretchable temperature sensors with excellent thermal stability by modulating the solvent of hydrogels.

Three-Dimensional Graphene Hydrogel Decorated with SnO2 for High-Performance NO2 Sensing with Enhanced Immunity to Humidity.

A facile, one-step hydrothermal route was exploited to prepare SnO2-decorated reduced graphene oxide hydrogel (SnO2/RGOH) with three-dimensional (3D) porous structures for NO2 gas detection. Various material characterizations demonstrate the effective deoxygenation of graphene oxide and in situ growth of rutile SnO2 nanoparticles (NPs) on 3D RGOH. Compared with the pristine RGOH, the SnO2/RGOH displayed much lower limit of detection (LOD) and an order of magnitude higher sensitivity, revealing the distinct impact of SnO2 NPs in improving the NO2-sensing properties. An exceptional low theoretical LOD of 2.8 ppb was obtained at room temperature. The p-n heterojunction formed at the interface between RGOH and SnO2 facilitates the charge transfer, improving both the sensitivity in NO2 detection and the conductivity of hybrid material. Considering that existing SnO2/RGO-based NO2 sensors suffer from great vulnerability to humidity, here we employed integrated microheaters to effectively suppress the response to humidity, with nearly unimpaired response to NO2, which boosted the selectivity. Notably, a flexible NO2 sensor was constructed on a liquid crystal polymer substrate with endurance to mechanical deformation. This work indicates the feasibility of optimizing the gas-sensing performance of sensors by combining rational material hybridization, 3D structural engineering with temperature modulation.

Steady-state structural fluctuation is a predictor of the necessity of pausing-mediated co-translational folding for small proteins.

Translational pausing coordinates protein synthesis and co-translational folding. It is a common factor that facilitates the correct folding of large, multi-domain proteins. For small proteins, pausing sites rarely occurs in the gene body, and the 3'-end pausing sites are only essential for the folding of a fraction of proteins. The determinant of the necessity of the pausings remains obscure. In this study, we demonstrated that the steady-state structural fluctuation is a predictor of the necessity of pausing-mediated co-translational folding for small proteins. Validated by experiments with 5 model proteins, we found that the rigid protein structures do not, while the flexible structures do need 3'-end pausings to fold correctly. Therefore, rational optimization of translational pausing can improve soluble expression of small proteins with flexible structures, but not the rigid ones. The rigidity of the structure can be quantitatively estimated in silico using molecular dynamic simulation. Nevertheless, we also found that the translational pausing optimization increases the fitness of the expression host, and thus benefits the recombinant protein production, independent from the soluble expression. These results shed light on the structural basis of the translational pausing and provided a practical tool for industrial protein fermentation.

Expression of miR-21, miR-221, and miR-222 in exosomes of CAL27 tongue squamous cell carcinoma cells / 口腔疾病防治

Objective@# To assess the expression of miR-21, miR-221, and miR-222 in exosomes of CAL27 tongue squamous cell carcinoma cells.@*Methods @# CAL27 tongue squamous cell carcinoma cells and normal human oral keratinocytes (HOKs) were cultured, and then, the cultured supernatant was collected to separate the exosomes. Exosomes were detected by electron microscopy, and the expression levels of miR-21, miR-221, and miR-222 in the exosomes of tongue cancer cells were measured by qRT-PCR. @*Results@#Exosomes existed in the cultured supernatants of CAL27 cells and HOKs. Additionally, the expression levels of miR-21, miR-221, and miR-222 in the exosomes of CAL27 cells were significantly enhanced compared with those in the HOK exosomes (P < 0.05). @*Conclusion @#The expression levels of miR-21, miR-221, and miR-222 were markedly enhanced in the exosomes of CAL27 tongue squamous cell carcinoma cells.

Predicting Reactive Intermediate Quantum Yields from Dissolved Organic Matter Photolysis Using Optical Properties and Antioxidant Capacity.

The antioxidant capacity and formation of photochemically produced reactive intermediates (RI) was studied for water samples collected from the Florida Everglades with different spatial (marsh versus estuarine) and temporal (wet versus dry season) characteristics. Measured RI included triplet excited states of dissolved organic matter (3DOM*), singlet oxygen (1O2), and the hydroxyl radical (•OH). Single and multiple linear regression modeling were performed using a broad range of extrinsic (to predict RI formation rates, RRI) and intrinsic (to predict RI quantum yields, ΦRI) parameters. Multiple linear regression models consistently led to better predictions of RRI and ΦRI for our data set but poor prediction of ΦRI for a previously published data set,1 probably because the predictors are intercorrelated (Pearson's r > 0.5). Single linear regression models were built with data compiled from previously published studies (n ≈ 120) in which E2:E3, S, and ΦRI values were measured, which revealed a high degree of similarity between RI-optical property relationships across DOM samples of diverse sources. This study reveals that •OH formation is, in general, decoupled from 3DOM* and 1O2 formation, providing supporting evidence that 3DOM* is not a •OH precursor. Finally, ΦRI for 1O2 and 3DOM* correlated negatively with antioxidant activity (a surrogate for electron donating capacity) for the collected samples, which is consistent with intramolecular oxidation of DOM moieties by 3DOM*.

[Surgery for primary adenoid cystic carcinoma of cervical trachea].

BACKGROUND & OBJECTIVE: There were few reports about surgery for primary adenoid cystic carcinoma of cervical trachea. This study was designed to evaluate the efficacy of surgical resection of a series of 13 patients with primary adenoid cystic carcinoma of cervical trachea. METHODS: Thirteen patients who underwent surgical resection with biopsy-proven primary adenoid cystic carcinoma of cervical trachea were reviewed retrospectively. RESULTS: Of 13 patients, 6 patients showed that tracheal invasion were more than 40 mm length, 7 less than 40 mm length. Seven patients showed extratracheal invasion, 2 showed distance metastases, and 1 showed metastases in regional lymph nodes. Nine patients were treated with sleeve resection of trachea with primary anastomosis (average length of 34.8 mm resected), of which 3 underwent laryngeal release and 8 reserved laryngeal function; 2 received laryngectomy with end tracheostomy and 2 received partial tracheal resection and a patch of autologous tissue reconstruction. Of 13 patients, 4 patients were treated with complete resection and 9 with incomplete resection alone or combined by postoperative irradiation. No death occurred during operation. Two tracheal stenoses and 1 laryngeal recurrent nerve palsy after operation were observed. Seven patients died after therapy, of which 6 patients failed to local management, 1 case died of distance metastases. The total 5- and 10-year survival rates were 69.2% (9/13) and 50.0% (5/10), respectively. The 5- and 10-year survival rates were 75.0% (3/4) and 75.0% (3/4) for complete resection group, 55.0% (5/9) and 33.0% (2/6) for incomplete resection group, 83.3% (5/6) and 83.3% (5/6) for non-extratracheal invasion group, 57.1% (4/7) and 0% for extratracheal invasion group (P=0.001). CONCLUSION: Sleeve resection of trachea with primary reconstruction is the major treatment of the patients suffering from primary cervical tracheal adenoid cystic carcinoma with the long-term survival and function reservation.

Controlled Synthesis of Cross-Linked Ultrathin Polymer Films by Using Surface-Initiated Atom Transfer Radical Polymerization.

Ambient-temperature atom transfer radical polymerization of ethyleneglycol dimethacrylate from a surface yields homogeneous, cross-linked polymer films. The absence of polymerization in solution in this "living" procedure avoids physisorption and gives uniform, cross-linked films with controlled thicknesses from 3 to 300 nm.