Copper-nickel-MOF/nickel foam catalysts grown in situ for efficient electrochemical nitrate reduction to ammonia.

Reducing nitrate (NO3-) in an aqueous solution to ammonia under ambient conditions can provide a green and sustainable NH3-synthesis technology and mitigate global energy and pollution issues. In this work, a CuNi0.75-1,3,5-benzenetricarboxylic acid/nickel foam (CuNi0.75-MOF/NF) catalyst grown in situ was prepared via a one-pot method as an efficient cathode material for electrocatalytic nitrate reduction reaction (NO3RR). The CuNi0.75-MOF/NF catalyst exhibited excellent electrocatalytic NO3RR performance at -1.0 V versus a reversible hydrogen electrode, achieving an outstanding faradaic efficiency of 95.88 % and an NH3 yield of 51.78 mg h-1 cm-2. The 15N isotope labeling experiments confirmed that the sole source of N in the electrocatalytic NO3RR was the NO3- in the electrolyte. The reaction pathway for the electrocatalytic NO3RR was derived by in situ Fourier transform infrared spectroscopy and in situ differential electrochemical mass spectrometry. Density functional theory calculations revealed that the Ni element in the CuNi0.75-MOF/NF catalyst had excellent O-H activation ability and strong *H adsorption capacity. These *H species were transferred from the Ni sites to the *NO adsorption intermediates located on the Cu sites, providing a continuous supply of *H to Cu, thereby promoting the formation of *NOH intermediates and enhancing the hydrogenation process of the electrocatalytic NO3RR.

Modification d x 2 - y 2 ${{d}_{{{x}2} - {{y}2}}}$ Orbital Electronic States in Nickel-Based Hydroxides Via Cobalt/Iron Co-Doping for High-Efficiency Methanol Electrooxidation.

The nickel hydroxide-based (Ni(OH)2) methanol-to-formate electrooxidation reaction (MOR) performance is greatly related to the d x 2 - y 2 ${{d}_{{{x}^2} - {{y}^2}}}$ orbital electronic states. Hence, optimizing the d x 2 - y 2 ${{d}_{{{x}^2} - {{y}^2}}}$ orbital electronic states to achieve enhanced MOR activities are highly desired. Here, cobalt (Co) and iron (Fe) doping are used to modify the d x 2 - y 2 ${{d}_{{{x}^2} - {{y}^2}}}$ orbital electronic states. Although both dopants can broaden the d x 2 - y 2 ${{d}_{{{x}^2} - {{y}^2}}}$ orbital; however, Co doping leads to an elevation in the energy level of d x 2 - y 2 ${{d}_{{{x}^2} - {{y}^2}}}$ highest occupied crystal orbital (HOCO), whereas Fe doping results in its reduction. Such a discrepancy in the regulation of d x 2 - y 2 ${{d}_{{{x}^2} - {{y}^2}}}$ orbital electronic states stems from the disparate partial electron transfer mechanisms amongst these transition metal ions, which possess distinct energy level and occupancy of d orbitals. Motivated by this finding, the NiCoFe hydroxide is prepared and exhibited an excellent MOR performance. The results showed that the Co dopants effectively suppress the partial electron transfer from Ni to Fe, combined with the d x 2 - y 2 ${{d}_{{{x}^2} - {{y}^2}}}$ orbital broadening induced by NiO6 octahedra distortion, endowing NiCoFe hydroxide with high d x 2 - y 2 ${{d}_{{{x}^2} - {{y}^2}}}$ HOCO and broad d x 2 - y 2 ${{d}_{{{x}^2} - {{y}^2}}}$ orbital. It is believed that the work gives an in-depth understanding on d x 2 - y 2 ${{d}_{{{x}^2} - {{y}^2}}}$ orbital electronic states regulation in Ni(OH)2, which is beneficial for designing Ni(OH)2-based catalysts with high MOR performance.

Enhancing laboratory biosafety management: a comprehensive strategy from theory to practice.

Objective: This study examines biosafety management practices in a psychiatric hospital's laboratory in China, focusing on how outdated information technology impacts the hospital's ability to respond to public health emergencies. The goal is to enhance the hospital's emergency response capabilities by updating risk assessments, biosafety manuals, and implementing a comprehensive quality management system alongside a specialized infection control system for significant respiratory diseases. Methods: We utilized an integrated research approach, expanding the scope of risk assessments, updating the biosafety manual according to the latest international standards, and implementing a quality management system. A specialized infection control system for significant respiratory diseases was introduced to improve emergency response capabilities. Results: Updated risk assessments and a new biosafety manual have significantly improved the identification and management of biosafety threats. Implementing new quality management and infection control systems has enhanced response efficiency and operational standardization. Conclusion: The measures taken have strengthened the biosafety management and emergency response capabilities of the laboratory department, highlighting the importance of information technology in biosafety management and recommending similar strategies for other institutions.

Application of MALDI-TOF mass spectrometry for identification of Nocardia species.

BACKGROUND: Nocardiosis, despite its rarity and underreporting, is significant due to its severe impact, characterized by high morbidity and mortality rates. The development of a precise, reliable, rapid, and straightforward technique for identifying the pathogenic agent in clinical specimens is crucial to reduce fatality rates and facilitate timely antimicrobial treatment. In this study, we aimed to identify Nocardia spp. in clinical isolates, using MALDI-TOF MS as the primary method, with molecular methods as the gold standard. Clinical Nocardia isolates were identified using 16S rRNA/hsp65/gyrB/secA1/rpoB gene sequencing. Identification performance of the Bruker MALDI Biotyper 3.1 (V09.0.0.0_8468) and MBT Compass 4.1 (V11.0.0.0_10833) for Nocardia identification was evaluated. RESULTS: Seventy-six Nocardia isolates were classified into 12 species through gene sequencing. The MALDI Biotyper 3.1 (V09.0.0.0_8468) achieved 100% genus-level accuracy and 84.2% species accuracy (64/76). The MBT Compass 4.1 with the BDAL Database (V11.0.0.0_10833) improved species identification to 98.7% (75/76). The updated database enhanced species level identification with scores > 1.7, increasing from 77.6% (59/76) to 94.7% (72/76), a significant improvement (P = 0.001). The new and simplified extraction increased the proportion of strains identified to the species level with scores > 1.7 from 62.0% (18/29) to 86.2% (25/29) (P = 0.016). An in-house library construction ensured accurate species identification for all isolates. CONCLUSIONS: The Bruker mass spectrometer can accurately identify Nocardia species, albeit with some variations observed between different database versions. The MALDI Biotyper 3.1 (V09.0.0.0_8468) has limitations in identifying Nocardia brasiliensis, with some strains only identifiable to the genus level. MBT Compass 4.1 (V11.0.0.0_10833) effectively addresses this shortfall, improving species identification accuracy to 98.7%, and offering quick and reliable identification of Nocardia. Both database versions incorrectly identified the clinically less common Nocardia sputorum as Nocardia araoensis. For laboratories that have not upgraded their databases and are unable to achieve satisfactory identification results for Nocardia, employing the new and simplified extraction method can provide a degree of improvement in identification outcomes.

Enhancing diabetic foot ulcer healing: Impact of the regulation of the FUS and ILF2 RNA­binding proteins through negative pressure wound therapy.

Diabetic foot ulcer (DFU) is a destructive complication of diabetes. Negative pressure wound therapy (NPWT) promotes DFU wound healing through an undetermined mechanism. In the present study, RNA sequencing was performed on wound granulation tissue from 3 patients with DFU before and after 1 week of NPWT. The fused in sarcoma (FUS) and interleukin enhancer binding factor 2 (ILF2) encoding RNA­binding proteins (RBPs) were screened from the sequencing data, and wound tissue samples from 24 patients with DFU were validated and analyzed before and after receiving NPWT by reverse transcription­quantitative PCR, western blotting and immunohistochemistry. In addition, in vitro and in vivo experiments were conducted to determine the effect of the expression of FUS and ILF2 on the function of human epidermal keratinocyte cells (HaCaT cells) and the healing of diabetic skin wounds. The results indicated that NPWT induced the upregulation of 101 genes and the downregulation of 98 genes in DFU wound granulation tissue. After NPWT, the expression of FUS and ILF2 was significantly upregulated (P<0.05). Pearson's correlation coefficient showed that the changes in FUS and ILF2 before and after NPWT were negatively correlated with changes in white blood cells, the neutrophil percentage, C­reactive protein, tumor necrosis factor­α, reactive oxygen species, lipid peroxides, matrix metalloproteinase (MMP) 2 and MMP9 (P<0.05), but positively correlated with the anti­inflammatory factor, IL­4 (P<0.01). There was also a positive correlation (P<0.05) with the 4­week ulcer healing rate. Additionally, the knockdown of FUS and ILF2 expression inhibited the proliferation and migration of HaCaT cells, while increasing cell apoptosis. In vivo, the knockdown of FUS and ILF2 significantly reduced the rate of skin wound healing in diabetic mice. The results of the present study therefore provide new insights into the mechanism by which NPWT promotes DFU wound healing. In conclusion, the RBPs, FUS and ILF2, promoted DFU wound healing by regulating the function of keratinocytes and reducing the inflammatory response and oxidative stress.

Cyclo-farnesyl Diphosphate-Dependent Prenylation in Fungi.

A conserved two-gene cassette in fungi was discovered by genome mining, which encodes a UbiA family intramembrane prenyltansferase (VviA) and a haloacid dehalogenase-like hydrolase family terpene cyclase (VviB), respectively. A series of in vivo and in vitro investigations revealed that VviA exclusively uses VviB-synthesized drim-8-ene diphosphate (cyclo-farnesyl diphosphate) as the native prenyl donor to catalyze prenylation on d-mannitol, showcasing a previously unidentified function of UbiA-type prenyltransferases and a new prenylation manner in fungi.

Bone targeted nano-drug and nano-delivery.

There are currently no targeted delivery systems to satisfactorily treat bone-related disorders. Many clinical drugs consisting of small organic molecules have a short circulation half-life and do not effectively reach the diseased tissue site. This coupled with repeatedly high dose usage that leads to severe side effects. With the advance in nanotechnology, drugs contained within a nano-delivery device or drugs aggregated into nanoparticles (nano-drugs) have shown promises in targeted drug delivery. The ability to design nanoparticles to target bone has attracted many researchers to develop new systems for treating bone related diseases and even repurposing current drug therapies. In this review, we shall summarise the latest progress in this area and present a perspective for future development in the field. We will focus on calcium-based nanoparticle systems that modulate calcium metabolism and consequently, the bone microenvironment to inhibit disease progression (including cancer). We shall also review the bone affinity drug family, bisphosphonates, as both a nano-drug and nano-delivery system for bone targeted therapy. The ability to target and release the drug in a controlled manner at the disease site represents a promising safe therapy to treat bone diseases in the future.

Safety, effectiveness, and complications of the first-in-human minimally invasive transthoracic ventricular septal defect closure using a bioabsorbable occluder: a cohort study with 12-month follow-up.

Background: Ventricular septal defect (VSD) is one of the most common congenital heart diseases. This study aims to evaluate the clinical value and benefit of transesophageal echocardiography (TEE) in transthoracic minimally invasive closure of VSDs using a completely biodegradable occluders, summarize the main points of surgical procedures, and analyze the follow-up results of short-term and medium-term treatment. Methods: We conducted a retrospective analysis of 24 pediatric cases of VSD, successfully treated with TEE-guided minimally invasive closure using fully biodegradable occluders between June 2019 and June 2022. The preoperative TEE meticulously examined the defect's location, size, and surrounding anatomical relationships, aiding in the selection of appropriate occluders and guiding the entire closure process. All patients were followed up for 1 year. Results: In our cohort, 13 cases were perimembranous inlet VSDs, and 11 involved VSDs with membranous aneurysm formation. The effective shunt size of VSD measured by TEE preoperatively ranged from 2.8 to 4.9 mm, with the defect located 2-6 mm from the aortic valve. Occluders used were 6-8 mm in diameter. All 24 procedures were successful. TEE confirmed that the occluders were tightly fitted at the edges of the VSDs. Twenty-three cases had no residual shunt post-surgery, while one case exhibited a small left-to-right shunt (<1.5 mm) at the occluder's edge. Follow-up was conducted on postoperative day 3, and in months 1, 3, 6, and 12, showing that the occluder's position remained normal in all patients. Except for one child who had a 1.2 mm left-to-right shunt at the edge of the occluder, no residual shunts were observed in the others. The occluder started to degrade from month 6, and the sizes of the left and right occluder discs were significantly smaller compared to those on postoperative day 3 (P=0.003). Conclusions: TEE-guided minimally invasive VSD occlusion using fully biodegradable occluders has the advantages of minimal trauma, high safety, and few complications, with satisfactory recent efficacy, and good prospects for clinical safety applications.

Efficacy and safety of telitacicept in IgA nephropathy: A retrospective, multicenter study.

Introduction The efficacy of Telitacicept treatment in reducing proteinuria in patients with IgA nephropathy (IgAN) was indicated in a phase II clinical trial with small sample size. In this study, we conducted a large multicenter retrospective study to explore the efficacy and safety of Telitacicept in patients with IgAN. Methods This study recruited patients with IgAN from 19 sites from China who were treated with Telitacicept and had been followed up at least once or with side effect reported, since April 1, 2021 to April 1, 2023. The primary outcomes of the study were the changing in proteinuria and eGFR over time. Results A cohort of 97 patients with IgAN who were treated with Telitacicept were recruited, with a median follow-up duration of 3 months. The median baseline proteinuria was 2.3 [1.3, 3.9] g/day and eGFR was 45.0 [26.8, 73.7] ml/min/1.73m2. There was a significant reduction of proteinuria at 2,4,6 months when compared with baseline (2.3 [1.5, 4.1] vs. 1.5 [0.8, 2.3] g/day; 2.3 [1.1, 3.7] vs. 1.1 [0.6, 1.9] g/day; 2.1 [1.0, 2.7] vs. 0.9 [0.5,1.7] g/day, all P values < 0.01). The level of eGFR were comparable between at the baseline and 2, 4, 6 months of follow-up time (41.5 [29.7, 72.0] vs. 42.5 [28.8, 73.3] ml/min/1.73m2; 41.0 [26.8, 67.7] vs. 44.7 [31.0, 67.8] ml/min/1.73m2; 33.7 [24.0, 58.5] vs. 32.6 [27.8, 57.5] ml/min/1.73m2, all P values > 0.26). Telitacicept was well tolerated in the patients. Conclusions This study indicates that Telitacicept alone or on top of steroids therapy can significantly and safely reduce proteinuria in patients with IgAN. The long-term kidney protection still need to be confirmed in large Phase III trial.

Monocyte to high-density lipoprotein ratio based prognostic nomogram for patients following allogeneic vascular replacement pancreaticoduodenectomy.

Background: Preoperative immune-inflammatory condition influencing the metabolism of malignancies. We sought to investigate the prognostic value of a novel immune-inflammatory metabolic marker, the monocyte-to-high-density lipoprotein ratio (MHR), in patients with locally advanced pancreatic cancer. Methods: A retrospective analysis was conducted on the clinical data of 118 patients with locally advanced pancreatic cancer and obstructive jaundice who underwent allogeneic vascular replacement pancreaticoduodenectomy in our hospital from Apr. 2011 to Dec. 2023. To assess the predictive capacity of immune-inflammatory metabolic marker, we utilized the area under the receiver operating characteristic curve (AUC-ROC) and assessed the predictive potential of MHR in forecasting outcomes through both univariate and multivariate Cox proportional hazard analyses. Results: The area under AUC for MHR in predicting 1-year postoperative survival was 0.714, with an optimal cutoff value of 1.184, yielding a sensitivity of 78.9% and specificity of 66.2%. Based on this cutoff value, patients were divided into a low MHR group (MHR ≤1.184, n = 61) and a high MHR group (MHR >1.184, n = 57). The median survival times for the low and high MHR groups were 27.0 months and 12.0 months, respectively (χ2 = 30.575, p < 0.001), and the median DFS were 18.0 months and 8.0 months, respectively (χ2 = 26.330, p < 0.001). Univariate and multivariate analyses indicated that preoperative MHR, preoperative creatinine, operation duration, and TNM stage were independent predictors of postoperative mortality, while preoperative MHR, preoperative creatinine, and TNM stage were independent predictors of postoperative recurrence risk. Conclusion: MHR, as an independent immune-inflammatory metabolic predictor of OS and DFS in patients with advanced PC after pancreaticoduodenectomy. Early monitoring and reduction of MHR may be of great significance in improving prognosis.

Tailoring near-infrared amyloid-ß probes with high-affinity and low background based on CN and amphipathic regulatory strategies and in vivo imaging of AD mice.

Amyloid-ß (Aß) species (Aß fibrils and Aß plaques), as one of the typical pathological markers of Alzheimer's disease (AD), plays a crucial role in AD diagnosis. Currently, some near-infrared I (NIR I) Aß probes have been reported in AD diagnosis. However, they still face challenges such as strong background interference and the lack of effective probe design. In this study, we propose molecular design strategy that incorporates CN group and amphiphilic modulation to synthesize a series of amphiphilic NIR I Aß probes, surpassing the commercial probe ThT and ThS. Theoretical calculations indicate that these probes exhibit stronger interaction with amino acid residues in the cavities of Aß. Notably, the probes containing CN group display the ability of binding two distinct sites of Aß, which dramatically enhanced the affinity to Aß species. Furthermore, these probes exhibit minimal fluorescence in aqueous solution and offer ultra-high signal-to-noise ratio (SNR) for in vitro labeling, even in wash-free samples. Finally, the optimal probe DM-V2CN-PYC3 was utilized for in vivo imaging of AD mice, demonstrating its rapid penetration through the blood-brain barrier and labelling to Aß species. Moreover, it enabled long-term monitoring for a duration of 120 min. These results highlight the enhanced affinity and superior performance of the designed NIR I Aß probe for AD diagnosis. The molecular design strategy of CN and amphiphilic modulation presents a promising avenue for the development Aß probes with low background in vivo/in vitro imaging for Aß species.

Immune-metabolic marker of albumin-to-fibrinogen ratio based prognostic nomogram for patients following peritoneal dialysis.

Background: The nutritional status and coagulation function of peritoneal dialysis (PD) patients are closely associated with their prognosis. This study aims to investigate the prognostic value of the albumin-to-fibrinogen ratio (AFR) on mortality in PD patients and to establish a prognostic prediction model based on AFR. Methods: We retrospectively collected data from 148 PD patients treated at our hospital between Oct. 2011 and Dec. 2021. Using the "survminer" package in R, we determined the optimal cutoff value for AFR and divided the patients into low-AFR and high-AFR groups. The primary endpoint of this study was overall survival (OS). Univariate and multivariate Cox analyses were used to assess the impact of AFR and other factors on prognosis, and a corresponding prognostic prediction model was constructed using a nomogram, which was evaluated through ROC curves, the c-index, and calibration plots. Results: The optimal cutoff value for AFR was 9.06. In the entire cohort, 30 patients (20.2%) were classified into the low-AFR group. Compared to the high-AFR group, patients in the low-AFR group were older, had lower total urine output over 24 h, higher blood urea nitrogen, higher total protein and urinary microalbumin levels, and longer remission times (p < 0.05). They also had a poorer OS (HR: 1.824, 95%CI: 1.282-2.594, p < 0.05). Multivariate Cox analysis indicated that AFR was an independent prognostic factor for OS (HR: 1.824, 95% CI: 1.282-2.594, p < 0.05). A prognostic prediction model based on AFR, age, and cause of ESRD was successfully validated for predicting OS in PD patients. Conclusion: AFR represents a potential prognostic biomarker for PD patients. The prognostic prediction model based on AFR can provide accurate OS predictions for PD patients, aiding clinicians in making better-informed decisions.

Fabrication of multifunctional hybrid pigment for color cosmetics based on chitosan-modified palygorskite and sappanwood extract.

Consumer perception and market demand have driven the replacement of synthetic colorants with naturally derived alternatives in the cosmetic industry. This study describes a facile way to prepare durable inorganic-organic hybrid pigment with advanced biocompatibility, antibacterial and hydrophobic properties tailored for color cosmetics by initial modification of palygorskite with chitosan to anchor sappanwood dye extract and subsequently coating with amino-modified silicone oil (ASO). The hybrid pigments were characterized by transmittance electron microscopy, X-ray diffraction, Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy and the Brunauer-Emmett-Teller method. The results indicated that the sappanwood dye was loaded on chitosan-modified palygorskite via hydrogen bonding and electrostatic interaction. Furthermore, the chitosan-palygorskite/sappanwood hybrid pigment exhibited enhanced biocompatibility and color stability on exposure to different heating temperatures and UVA radiation after subsequent hydrophobic modification with amino-modified silicone oil. Moreover, facial foundation cosmetics based on the chitosan-palygorskite/sappanwood@ASO composites exhibited excellent brightening and skin color corrective effect on human volunteers without any adverse response. And no significant difference was observed in 12 out of 14 sensory evaluation indexes in the comparison of this hybrid pigment-based makeup with two commercially available products. This study provides a new route to stabilize natural botanical colorant for cosmetic use by chitosan-modified clay minerals.

COVID-19 mRNA vaccines induce robust levels of IgG but limited amounts of IgA within the oronasopharynx of young children.

BACKGROUND: Understanding antibody responses to SARS-CoV-2 vaccination is crucial for refining COVID-19 immunization strategies. Generation of mucosal immune responses, including mucosal IgA, could be of potential benefit to vaccine efficacy, yet limited evidence exists regarding the production of mucosal antibodies following the administration of current mRNA vaccines to young children. METHODS: We measured the levels of antibodies against SARS-CoV-2 from a cohort of children under 5 years of age (N=24) undergoing SARS-CoV-2 mRNA vaccination (serially collected, matched serum and saliva samples) or in a convenience sample of children under 5 years of age presenting to pediatric emergency department (nasal swabs, N=103). Further, we assessed salivary and nasal samples for the ability to induce SARS-CoV-2 spike-mediated neutrophil extracellular traps (NET) formation. RESULTS: Longitudinal analysis of post-vaccine responses in saliva revealed the induction of SARS-CoV-2 specific IgG but not IgA. Similarly, SARS-CoV-2 specific IgA was only observed in nasal samples obtained from previously infected children with or without vaccination, but not in vaccinated children without a history of infection. In addition, oronasopharyngeal samples obtained from children with prior infection were able to trigger enhanced spike-mediated NET formation, and IgA played a key role in driving this process. CONCLUSIONS: Despite the induction of specific IgG in the oronasal mucosa, current intramuscular vaccines have limited ability to generate mucosal IgA in young children. These results confirm the independence of mucosal IgA responses from systemic humoral responses following mRNA vaccination and suggest potential future vaccination strategies for enhancing mucosal protection in this young age group.

Interfacial Dipole Engineering for Energy Level Alignment in NiOx-Based Quantum Dot Light-Emitting Diodes.

The solution-derived non-stoichiometric nickel oxide (NiOx) is a promising hole-injecting material for stable quantum dot light-emitting diodes (QLEDs). However, the carrier imbalance due to the misalignment of energy levels between the NiOx and polymeric hole-transporting layers (HTLs) curtails the device efficiency. In this study, the modification of the NiOx surface is investigated using either 3-cyanobenzoic acid (3-CN-BA) or 4-cyanobenzoic acid (4-CN-BA) in the QLED fabrication. Morphological and electrical analyses revealed that both 4-CN-BA and 3-CN-BA can enhance the work function of NiOx, reduce the oxygen vacancies on the NiOx surface, and facilitate a uniform morphology for subsequent HTL layers. Moreover, it is found that the binding configurations of dipole molecules as a function of the substitution position of the tail group significantly impact the work function of underlying layers. When integrated in QLEDs, the modification layers resulted in a significant improvement in the electroluminescent efficiency due to the enhancement of energy level alignment and charge balance within the devices. Specifically, QLEDs incorporating 4-CN-BA achieved a champion external quantum efficiency (EQE) of 20.34%, which is a 1.8X improvement in comparison with that of the devices utilizing unmodified NiOx (7.28%). Moreover, QLEDs with 4-CN-BA and 3-CN-BA modifications exhibited prolonged operational lifetimes, indicating potential for practical applications.

Investigation of the furcation morphology of permanent mandibular first molars by using micro-computed tomography.

BACKGROUND: To investigate the anatomic features of the root furcation of permanent mandibular first molars. METHODS: A total of 50 extracted mandibular first molars (25 two-rooted and 25 three-rooted) were collected and scanned using micro-computed tomography. The digital models of teeth and root canal systems were reconstructed three-dimensionally. The tooth models were displayed in parallel projection mode from buccal and distal views. Screenshots were captured and subsequently analyzed using Image-Pro Plus 6.0 software after calibration. The furcation angle, root trunk length, maximum depth and level of distal root concaves of mesial roots, and length of enamel projections were measured, and the furcation types (classified into type V, type U and type W) were detected. Statistical analysis was performed using the Shapiro-Wilk's test, one-way analysis of variance, Student's t-test and Chi-square test. RESULTS: The mean furcation angle between the distobuccal (DB) and distolingual (DL) roots (in distal view) was the greatest (59.2°), whereas the furcation angle between the mesial and DL roots (in buccal view) was the smallest (25.4°) among the four furcation angles (all p < 0.05). Regarding the furcation types, bucco-lingual root trunk length, maximum depth and site of the distal root concavities, and enamel projection length, no significant differences were detected between the three- and two-rooted molar groups (all p > 0.05). The frequency of type V was the highest (54.0%), followed by type U (26.0%), and type W had the lowest occurrence rate (20.0%). The mean length of distal root trunk in the three-rooted mandibular molars was significantly greater than that of the buccal/lingual one (3.7 mm vs. 3.0 mm, p < 0.01). The maximum depth of the distal concavities of the mesial roots was on average 0.66 ± 0.19 mm, and the site was located at an average of 2.8 ± 1.3 mm below furcation. The mean length of buccal enamel projections was significantly longer than that of lingual ones (3.1 mm vs. 0.7 mm, p < 0.01). CONCLUSIONS: The furcation anatomy of the mandibular first molar is complex, and the presence of the DL root may further complicate its topography. A thorough understanding of these anatomic features is essential for successful periodontal treatment.

Highly Stretchable, Transparent, Solvent-Resistant Multifunctional Ionogel with Underwater Self-Healing and Adhesion for Wearable Strain Sensors and Barrier-Free Information Transfer.

Ionogels with excellent deformability, high ionic conductivity, and a sensitive stimulus response have been widely used and rapidly developed in flexible wearable systems. However, previously reported ionogels are mainly limited to atmospheric environments applications and have difficulty meeting the requirements of solvent-resistant, self-healing, and adhesion properties in underwater environments. Herein, a multifunctional ionogel capable of underwater applications is prepared by one-step photoinitiated polymerization of a fluorine-containing monomer (2,2,3,4,4,4-hexafluorobutyl acrylate, HFBA) and acrylic acid (AA) in a hydrophobic ionic liquid ([EMIM][TFSI]). The dynamic physical interactions of hydrogen bonds and ionic dipoles endow the ionogel with remarkable transparency, tunable mechanical properties, and underwater self-healing properties. Moreover, the fluoropolymer matrix offers high resistance to water and various solvents and exhibits strong underwater adhesion on different substrates. Thus, the sensor based on the ionogel exhibits excellent sensing properties, including high sensitivity, fast response, and superior durability. In particular, the ionogel can be used as a wearable underwater sensor to perform barrier-free information transfer. This study provides a design idea for the development of underwater flexible strain sensors.

Post-transcriptional regulation of IFI16 promotes inflammatory endothelial pathophenotypes observed in pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is a progressive disease driven by endothelial cell inflammation and dysfunction, resulting in the pathological remodeling of the pulmonary vasculature. Innate immune activation has been linked to PAH development; however, the regulation, propagation, and reversibility of the induction of inflammation in PAH is poorly understood. Here, we demonstrate a role for interferon inducible protein 16 (IFI16), an innate immune sensor, as a modulator of endothelial inflammation in pulmonary hypertension, utilizing human pulmonary artery endothelial cells (PAECs). Inflammatory stimulus of PAECs with IL-1ß up-regulates IFI16 expression, inducing proinflammatory cytokine up-regulation and cellular apoptosis. IFI16 mRNA stability is regulated by post-transcriptional m6A modification, mediated by Wilms' tumor 1-associated protein (WTAP), a structural stabilizer of the methyltransferase complex, via regulation of m6A methylation of IFI16. Additionally, m6A levels are increased in the peripheral blood mononuclear cells of PAH patients compared to control, indicating that quantifying this epigenetic change in patients may hold potential as a biomarker for disease identification. In summary, our study demonstrates IFI16 mediates inflammatory endothelial pathophenotypes seen in pulmonary arterial hypertension.

BBOX1 mediates metabolic reprogramming driven by hypoxia and participates in the malignant progress of high-grade serous ovarian cancer.

High-grade serous ovarian cancer (HGSOC) is the most aggressive type of ovarian cancer that causes great threats to women's health. Therefore, we performed RNA-sequencing technology in clinical samples to explore the molecular mechanisms underlying the progression of HGSOC. We then noticed BBOX1, a kind of 2-oxoglutarate-dependent enzyme that is highly expressed in HGSOC tumor tissues. Functional studies showed that BBOX1 promotes cell survival and growth of HGSOC cells in vitro and in vivo. Overexpression of the wild-type BBOX1 promoted cell proliferation, but the Asn191 and Asn292 mutation (key amino acid for the enzymatic activity of BBOX1) counteracted this effect (P < 0.05), which indicated that the promotion effect of BBOX1 on HGSOC cell proliferation was related to its catalytic activity. Downregulation of BBOX1 reduced the activity of the mTORC1 pathway, and decreased protein expression of IP3R3 and phosphorylation level of S6KThr389. Metabolomics analysis revealed that BBOX1 is implicated in the glucose metabolism, amino acid metabolism, and nucleotide metabolism of HGSOC cells. In addition, inhibition of BBOX1 suppressed HGSOC cell glycolysis and decreased glucose consumption, lactate production, and the expression of key factors in glycolysis. Finally, we found hypoxia induced the expression of BBOX1 in HGSOC cells and confirmed that BBOX1 could be transcriptionally activated by hypoxia-inducible factor-1α, which could directly bind to the BBOX1 promoter. In summary, BBOX1 mediated the metabolic reprogramming driven by hypoxia, and affected cell metabolism through the mTORC1 pathway, thus acting as an oncogene during HGSOC development.