Acetylcytidine modification of Amotl1 by N-acetyltransferase 10 contributes to cardiac fibrotic expansion in mice after myocardial infarction.

Cardiac fibrosis is a pathological scarring process that impairs cardiac function. N-acetyltransferase 10 (Nat10) is recently identified as the key enzyme for the N4-acetylcytidine (ac4C) modification of mRNAs. In this study, we investigated the role of Nat10 in cardiac fibrosis following myocardial infarction (MI) and the related mechanisms. MI was induced in mice by ligation of the left anterior descending coronary artery; cardiac function was assessed with echocardiography. We showed that both the mRNA and protein expression levels of Nat10 were significantly increased in the infarct zone and border zone 4 weeks post-MI, and the expression of Nat10 in cardiac fibroblasts was significantly higher compared with that in cardiomyocytes after MI. Fibroblast-specific overexpression of Nat10 promoted collagen deposition and induced cardiac systolic dysfunction post-MI in mice. Conversely, fibroblast-specific knockout of Nat10 markedly relieved cardiac function impairment and extracellular matrix remodeling following MI. We then conducted ac4C-RNA binding protein immunoprecipitation-sequencing (RIP-seq) in cardiac fibroblasts transfected with Nat10 siRNA, and revealed that angiomotin-like 1 (Amotl1), an upstream regulator of the Hippo signaling pathway, was the target gene of Nat10. We demonstrated that Nat10-mediated ac4C modification of Amotl1 increased its mRNA stability and translation in neonatal cardiac fibroblasts, thereby increasing the interaction of Amotl1 with yes-associated protein 1 (Yap) and facilitating Yap translocation into the nucleus. Intriguingly, silencing of Amotl1 or Yap, as well as treatment with verteporfin, a selective and potent Yap inhibitor, attenuated the Nat10 overexpression-induced proliferation of cardiac fibroblasts and prevented their differentiation into myofibroblasts in vitro. In conclusion, this study highlights Nat10 as a crucial regulator of myocardial fibrosis following MI injury through ac4C modification of upstream activators within the Hippo/Yap signaling pathway.

Fluoride impairs vascular smooth muscle A7R5 cell lines via disrupting amino acids metabolism.

Given the insidious and high-fatality nature of cardiovascular diseases (CVDs), the emergence of fluoride as a newly identified risk factor demands serious consideration alongside traditional risk factors. While vascular smooth muscle cells (VSMCs) play a pivotal role in the progression of CVDs, the toxicological impact of fluoride on VSMCs remains largely uncharted. In this study, we constructed fluorosis model in SD rats and A7R5 aortic smooth muscle cell lines to confirm fluoride impaired VSMCs. Fluoride aggravated the pathological damage of rat aorta in vivo. Then A7R5 were exposed to fluoride with concentration ranging from 0 to 1200 µmol/L over a 24-h period, revealing a dose-dependent inhibition of cell proliferation and migration. The further metabolomic analysis showed alterations in metabolite profiles induced by fluoride exposure, notably decreasing organic acids and lipid molecules level. Additionally, gene network analysis underscored the frequency of fluoride's interference with amino acids metabolism, potentially impacting the tricarboxylic acid (TCA) cycle. Our results also highlighted the ATP-binding cassette (ABC) transporters pathway as a central element in VSMC impairment. Moreover, we observed a dose-dependent increase in osteopontin (OPN) and α-smooth muscle actin (α-SMA) mRNA level and a dose-dependent decrease in ABC subfamily C member 1 (ABCC1) and bestrophin 1 (BEST1) mRNA level. These findings advance our understanding of fluoride as a CVD risk factor and its influence on VSMCs and metabolic pathways, warranting further investigation into this emerging risk factor.

Hereditary hemorrhagic telangiectasia involving portal venous system: A case report and review of the literature.

BACKGROUND: Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant genetic disorder with an incidence of approximately 1 in 5000 in the general population. It is characterized by vasodilation, which affects specific organs, such as the skin, mucous membranes, brain, lungs, gastrointestinal tract, liver, and others. However, HHT rarely involves the portal venous system to cause serious clinical complications. CASE SUMMARY: A 68-year-old woman was admitted to the emergency department due to four consecutive days of abdominal pain and bloody stool and was subsequently diagnosed with HHT. Computed tomography angiography confirmed the presence of an arteriovenous fistula (AVFs). Considering this specific manifestation, whole exome sequencing was performed. After a comprehensive evaluation, a selective superior mesenteric artery embolization was prioritized to avoid intestinal ischemia. The postoperative symptoms of the patient were quickly relieved. Unfortunately, two months post-procedure the patient died from intestinal necrosis and abdominal infection related to remaining AVFs. CONCLUSION: For patients with diffuse superior mesenteric AVFs, selective mesenteric arterial embolization may lead to positive short-term outcomes.

Exosomes derived from mesenchymal stromal cells exert a therapeutic effect on hypoxia-induced pulmonary hypertension by modulating the YAP1/SPP1 signaling pathway.

OBJECTIVE: Hypoxic pulmonary hypertension (HPH) is a progressive and life-threatening disease characterized by perivascular inflammation, pulmonary vascular remodeling, and occlusion. Mesenchymal stromal cell-derived exosomes (MSC-exo) have emerged as potential therapeutic agents due to their role in cell communication and the transportation of bioactive molecules. In this study, we aimed to investigate the therapeutic effects of MSC-exo against HPH and elucidate the underlying molecular mechanism. METHODS: Exosomes were isolated from conditioned media of human bone mesenchymal stromal cells using ultracentrifugation and characterized through western blotting, transmission electron microscopy (TEM), and nanoparticle tracking analysis (NTA). An HPH animal model was established in male SD rats, and MSC-exo or phosphate-buffered saline (PBS) were administered via the tail vein for three weeks. Subsequently, right ventricular systolic pressure (RVSP), right ventricular hypertrophy index (RVHI), and pulmonary vascular remodeling were evaluated. Lung tissues from HPH rats and normal rats underwent high-throughput sequencing and transcriptomic analysis. Gene Ontology (GO) analysis was employed to identify upregulated differentially expressed genes. Additionally, rat pulmonary artery smooth muscle cells (PASMC) exposed to platelet-derived growth factor-BB (PDGF-BB) were used to simulate HPH-related pathological behavior. In vitro cellular models were established to examine the molecular mechanism of MSC-exo in HPH. RESULTS: MSC-exo administration protected rats from hypoxia-induced increases in RVSP, RVHI, and pulmonary vascular remodeling. Additionally, MSC-exo alleviated PDGF-BB-induced proliferation and migration of PASMC. Transcriptomic analysis revealed 267 upregulated genes in lung tissues of HPH rats compared to control rats. Gene Ontology analysis indicated significant differences in pathways associated with Yes Associated Protein 1 (YAP1), a key regulator of cell proliferation and organ size. RT-qPCR and western blot analysis confirmed significantly increased expression of YAP1 in HPH lung tissues and PASMC, which was inhibited by MSC-exo treatment. Furthermore, analysis of datasets demonstrated that Secreted Phosphoprotein 1 (SPP1), also known as Osteopontin (OPN), is a downstream binding protein of YAP1 and can be upregulated by PDGF-BB. MSC-exo treatment reduced the expression of both YAP1 and SPP1. Lentivirus-mediated knockdown of YAP1 inhibited PDGF-BB-induced PASMC proliferation, migration, and SPP1 protein levels. CONCLUSION: Our findings demonstrate that MSC-exo exert a therapeutic effect against hypoxia-induced pulmonary hypertension by modulating the YAP1/SPP1 signaling pathway. The inhibition of YAP1 and downstream SPP1 expression by MSC-exo may contribute to the attenuation of pulmonary vascular remodeling and PASMC proliferation and migration. These results suggest that MSC-exo could serve as a potential therapeutic strategy for the treatment of HPH. Further investigations are warranted to explore the clinical applicability of MSC-exo-based therapies in HPH patients.

Suppressing gas swelling in self-assembled Li4Ti5O12 (400) for high-performance rechargeable batteries.

Lithium titanate is a promising anode material for lithium-ion batteries due to its high-rate capability and long-cycle duration. However, gas swelling during electrochemical reactions has hindered its industrial application. Here, we synthesize self-assembled (400)-orientation lithium titanate (SA-LTONF) with ultrafine nanoparticles using a feasible thermal method. The SA-LTONF with an organic carbon coating exhibited superior electrochemical performance. To understand such high-rate capability, we perform density functional theory (DFT) calculations which elucidate the orientation-dependent electrochemical mechanism of hydrogen evolution and the atomically dynamic mechanism of lithium-ion migration in Li4Ti5O12 and Li7Ti5O12. Our findings provide a unique insight into the gas generation and ultrafast lithium-ion transportation in lithium titanate and offer guidance for nanoarchitecture construction and materials design of lithium titanate for commercial applications.

Magnetic ε-Phosphorene for Sensing Greenhouse Gas Molecules.

It is critical for gas sensors that sense greenhouse gas molecules to have both good sensitivity and selectivity for water molecules in the ambient environment. Here, we study the charge transfer, IV curves, and electric field tuning of vanadium-doped monolayer ϵ-phosphorene as a sensor for NO, NO2, and H2O gas molecules via first-principle and transport calculations. We find that the paramagnetic toxic molecules of NO and NO2 have a high adsorption energy on V-ϵ-phosphorene, which originates from a large amount of charge transfer driven by the hybridisation of the localised spin states of the host with the molecular frontier orbital. Using the non-equilibrium Green's function, we investigate the IV responses with respect to the adsorption of different molecules to study the performance of gas molecule sensors. Our IV curves show a larger amount of changes in resistance of the paramagnetic NO and NO2 than nonmagnetic H2O gas molecules, suggesting both sensitivity and selectivity. Moreover, our calculations show that an applied external electric field (gate voltage) can effectively tune the amount of charge transfer. More charge transfer makes the sensor more sensitive to the molecule, while less charge transfer can reduce the adsorption energy and remove the adsorbed molecules, allowing for the repeated use of the sensor.

Enhancing the Electrical Conductivity and Strength of PET by Single-Wall Carbon Nanotube Film Coating.

Single-wall carbon nanotubes (SWCNTs) with excellent physicochemical properties are considered a promising candidate for the electrical and mechanical reinforcements of polymers. However, the poor dispersion of SWCNTs in plastics seriously limits their application and their achieved performance enhancement. Here, we coat a freestanding, highly conductive SWCNT film onto the surface of a polyethylene terephthalate (PET) film by a hot-pressing method. Due to the uniform SWCNT network structure and strong interfacial interaction, the SWCNT/PET hybrid film showed notably enhanced electrical and mechanical properties even though with a very low SWCNT weight fraction of 0.066%. The surface square resistance of the SWCNT/PET film decreased to 120-140 Ω/□ from 1016 Ω. In addition, Young's modulus and tensile strength of the SWCNT/PET film reached 4.6 GPa and 148 MPa, which are 31.3 and 24.4%, respectively, higher than the pure PET film. The SWCNT/PET film shows excellent mechanical durability and thermal stability, demonstrating its potential use as an antistatic material.

Effects of ultrasonic-assisted pH shift treatment on physicochemical properties of electrospinning nanofibers made from rapeseed protein isolates.

Electrospinning nanofibers (NFs) made from natural proteins have drawn increasing attention recently. Rapeseed meal is a by-product that rich in protein but not fully utilized due to poor properties. Therefore, modification of rapeseed protein isolates (RPI) is necessary to expand applications. In this study, pH shift alone or ultrasonic-assisted pH shift treatment was adopted, the solubility of RPI, along with the conductivity and viscosity of the electrospinning solution were detected. Moreover, the microstructure and functional characteristics of the electrospinning NFs, as well as the antibacterial activity of clove essential oil loaded-NFs were investigated. The tested parameters were remarkably improved after different treatments compared with the control, and synergistic effects were observed, especially under alkaline conditions. Hence, pH12.5 + US showed the maximum value of solubility, conductivity, and viscosity, which was more than 7-fold, 3-fold, and almost 1-fold higher than the control respectively. Additionally, SEM and AFM images showed a finer and smoother surface of NFs after treatments, and the finest diameter of 216.7 nm was obtained after pH12.5 + US treatment in comparison with 450.0 nm in control. FTIR spectroscopy of NFs demonstrated spatial structure changes of RPI, and improved thermal stability and mechanical strength of NFs were achieved after different treatments. Furthermore, an inhibition zone with a diameter of 22.8 mm was observed from the composite NFs. This study indicated the effectiveness of ultrasonic-assisted pH shift treatment on the physicochemical properties improvement and functional enhancement of NFs made from RPI, as well as the potential antibacterial application of the composite NFs in the future.

Interfacial Chemical Bridging Constructed by Multifunctional Lewis Acid for Carbon Nanotube/Silicon Heterojunction Solar Cells with an Efficiency Approaching 17.7.

Single-wall carbon nanotube/silicon (SWCNT/Si) heterojunction shows appealing potential for use in photovoltaic devices. However, the relatively low conductivity of SWCNT network and interfacial recombination of carriers have limited their photovoltaic performance. Herein, a multifunctional Lewis acid (p-toluenesulfonic acid, TsOH) is used to significantly reduce the energy loss in SWCNT/Si solar cells. Owing to the charge transfer doping effect of TsOH, the conductivity and work function of SWCNT films are optimized and tuned. More importantly, a chemical bridge is constructed at the interface of SWCNT/Si heterojunction. Experimental studies indicate that the phenyl group of TsOH can interact with SWCNTs through π-π interaction, meanwhile, the oxygen in the sulfonic functional group of the TsOH molecule can graft on the dangling bonds of the Si surface. The chemical bridge structure effectively suppresses the recombination of photogenerated carriers. The TsOH coating also works as an antireflection layer, leading to a 19% increment of the photocurrent. As a result, a champion power conversion efficiency of 17.7% is achieved for the TsOH-SWCNT/Si device, and it also exhibits an excellent stability, retaining more than 96% of the initial efficiency in the ambient air after 1 month.

Intravitreal slow-release dexamethasone alleviates traumatic proliferative vitreoretinopathy by inhibiting persistent inflammation and Müller cell gliosis in rabbits.

AIM: To evaluate the effects of intravitreal slow-release dexamethasone on traumatic proliferative vitreoretinopathy (PVR) and Müller cell gliosis and preliminarily explored the possible inflammatory mechanism in a rabbit model induced by penetrating ocular trauma. METHODS: Traumatic PVR was induced in the right eyes of pigmented rabbits by performing an 8-mm circumferential scleral incision placed 2.5 mm behind the limbus, followed by treatment with a slow-release dexamethasone implant (Ozurdex) or sham injection. Left eyes were used as normal controls. The intraocular pressure (IOP) was monitored using an iCare tonometer. PVR severity was evaluated via anatomical and histopathological examinations every week for 6wk; specific inflammatory cytokine and proliferative marker levels were measured by quantitative real-time polymerase chain reaction, Western blot, protein chip analysis, or immunofluorescence staining. RESULTS: During the observation period, PVR severity gradually increased. Intense Müller cell gliosis was observed in the peripheral retina near the wound and in the whole retina of PVR group. Ozurdex significantly alleviated PVR development and Müller cell gliosis. Post-traumatic inflammation fluctuated and was persistent. The interleukin-1ß (IL-1ß) mRNA level was significantly upregulated, peaking on day 3 and increasing again on day 21 after injury. The expression of nod-like receptor family pyrin domain containing 3 (NLRP3) showed a similar trend that began earlier than that of IL-1ß expression. Ozurdex suppressed the expression of IL-1ß, NLRP3, and phosphorylated nuclear factor-kappa B (NF-κB). The average IOP after treatment was within normal limits. CONCLUSION: The present study demonstrates chronic and fluctuating inflammation in a traumatic PVR rabbit model over 6wk. Ozurdex treatment significantly inhibites inflammatory cytokines expression and Müller cell gliosis, and thus alleviates PVR severity. This study highlights the important role of IL-1ß, and Ozurdex inhibites inflammation presumably via the NF-κB/NLRP3/IL-1ß inflammatory axis. In summary, Ozurdex provides a potential therapeutic option for traumatic PVR.

Intentional Watch and Wait or Organ Preservation Surgery Following Neoadjuvant Chemoradiotherapy Plus Consolidation CAPEOX for MRI-defined Low-risk Rectal Cancer: Findings From a Prospective Phase 2 Trial (PKUCH-R01 Trial, NCT02860234).

OBJECTIVE: To assess the efficacy and safety of intentional watch and wait (W&W) and organ preservation surgery following neoadjuvant chemoradiotherapy plus consolidation CAPEOX in magnetic resonance imaging (MRI)-defined low-risk rectal cancer. BACKGROUND: Clinical T2/early T3 rectal cancers can achieve high yield pathological complete response (ypCR) rates after chemoradiotherapy; thus, an intentional W&W or organ preservation strategy for good clinical responders in these subgroups can be further tested. METHODS: This prospective, single-arm, phase 2 trial enrolled patients with low-risk MRI prestaged rectal cancers, who concurrently received chemoradiation, followed by four 3-weekly cycles of CAPEOX regimen. Following reassessment, clinical complete response (cCR) or near-cCR patients underwent W&W/organ preservation surgery; the primary endpoint was a 3-year organ preservation rate. RESULTS: Of the 64 participants, 58 completed treatment, with 6.4% and 33.9% grade 3 to 4 toxicities in the radiotherapy and consolidation CAPEOX phases, respectively, during a median 39.5-month follow-up. Initial cCR, and non-cCR occurred in 33, 13, and 18 patients, respectively. Of the 31 cCR and 7 near-cCR cases managed by W&W, local regrowth occurred in 7; of these, 6 received salvage surgery. The estimated 2-year local regrowth rates were 12.9% [95% confidence interval (CI): 1.1%-24.7%] in cCR and 42.9% (95% CI: 6.2%-79.6%) in near-cCR cases, respectively. Eight patients received local excision, including 2 with regrowth salvage. Lung metastases occurred in 3 patients and multiple metastasis occurred in 1 patient; no local recurrence occurred. The estimated 3-year organ preservation rate was 67.2% (95% CI: 55.6%-78.8%). The estimated 3-year cancer-specific survival, non-regrowth disease-free survival, and stoma-free survival were 96.6% (95% CI: 92.1%-100%), 92.2% (95% CI: 85.5%-98.9%), and 82.7% (95% CI: 73.5%-91.9%), respectively. CONCLUSIONS: Chemoradiotherapy plus consolidation CAPEOX for MRI-defined low-risk rectal cancer can lead to high rates of organ preservation through intentional W&W or local excision. The oncologic safety of this strategy should be further tested.

Ultrasonic washing as an abiotic elicitor to increase the phenolic content in fruits and vegetables: A review.

Ultrasonic washing has been widely applied to the postharvest storage of fruits and vegetables as a residue-free physical washing technology, which plays an important role in improving shelf-life, safety, and nutritional value. Phenolics are a large group of phytochemicals widespread in fruits and vegetables, and they have been considered potential protective factors against some diseases because of potent antioxidative properties. Previous studies have shown that ultrasonic washing can increase the phenolic content of fruits and vegetables immediately or during storage through the induction of plant stress responses, which is of great significance for improving the functional and nutritional value of fruits and vegetables. However, the mechanisms of ultrasound as an elicitor to improve the phenolic content remain controversial. Therefore, this review summarizes the applications of ultrasonic washing to increase the phenolic content in fruits and vegetables. Meanwhile, the corresponding physiological stress response mechanisms of the phenolic accumulation in terms of immediate stress responses (i.e., higher extractability of phenolics) and late stress responses (i.e., metabolism of phenolics) are expounded. Moreover, a hypothetical model is proposed to explain phenolic biosynthesis triggered by signaling molecules produced under ultrasound stress, including primary signal (i.e., extracellular adenosine triphosphate) and secondary signals (e.g., reactive oxygen species, Ca2+ , NO, jasmonates, and ethylene). Additionally, the techno-economic feasibility of ultrasonic washing technology is also discussed. Further, challenges and trends for further development of ultrasonic washing as an abiotic elicitor applied to the postharvest storage of fruits and vegetables are presented.

Corrigendum: Ultrasonic washing as an abiotic elicitor to induce the accumulation of phenolics of fresh-cut red cabbages: Effects on storage quality and microbial safety.

[This corrects the article DOI: 10.3389/fnut.2022.1006440.].

Anti-hyperlipidemia on rats in vivo and new compounds from the seeds of Psoralea corylifolia.

In this study, it was confirmed at first time that the crude extracts of Psoralea corylifolia seeds (PCE34) can reduce serum lipids (AST, ALT, TG, TC, LDL, ALP, ACP and LDH), body weight and serum sugar, increase HDL and serum insulin in hyperlipidemic wistar rat induced by high-fat diet in vivo. Furthermore, eight new chalcones 1-8, one new flavanone 12, one new coumarin 14, three new meroterpenes 15-17 and one new bakuchiol 20 together with seven known compounds (9-11, 13, 18-19 and 21) were isolated from the PCE34. Their structures were elucidated based on analyses of their spectroscopic (UV, CD, NMR and HREIMS) data. All the isolates were evaluated for in vitro inhibitory activity against DGAT1/2, PTP1B and α-Glucosidase. Among them, compounds 1-3, 8-11, 14-17, 19 and 20 were found to exhibit selective inhibitory activity on DGAT1 with IC50 values ranging from 66.7 ± 1.2 to 87.2 ± 1.3 µM; 1, 8-12, 14 and 20 has the best inhibit active on PTP1B with IC50 values ranging from 13.8 ± 1.1 to 19.1 ± 1.6 µM; 1-12 and 14 displayed the significant inhibitory activities on α-Glucosidase with IC50 values ranging from 29.1 ± 1.2 to 79.4 ± 1.2 µM.

Ultrasonic washing as an abiotic elicitor to induce the accumulation of phenolics of fresh-cut red cabbages: Effects on storage quality and microbial safety.

Ultrasonic washing has been proved to be an abiotic elicitor to induce the accumulation of phenolics in some fruit and vegetables. However, the feasibility of ultrasonic washing on the accumulation of phenolics in fresh-cut red cabbages has not yet been reported. Therefore, the effects of ultrasonic washing on the phenolics and related phenolic metabolism enzymes of fresh-cut red cabbages, as well as quality and microbial safety during cold storage, were investigated. Firstly, the single-factor tests were used to optimize the ultrasonic processing parameters, including frequency mode, frequency amplitude, power density, frequency cycle time, and ultrasonic washing. Then the activities of the enzymes related to phenolic metabolisms after optimal ultrasound treatment were investigated, including phenylalanine ammonia-lyase (PAL), polyphenol oxidase (PPO), and peroxidase (POD). Additionally, the quality and microbial safety of fresh-cut red cabbages stored at 4°C under the optimal ultrasound treatment were evaluated. The results showed that the content of soluble phenolics (SPs) in fresh-cut red cabbages increased significantly during storage under the optimal conditions (28 ± 2 kHz, 60 W/L, 400 ms, and 20 min) compared with the control (P < 0.05). The PAL activity was activated and the PPO and POD activities were inhibited after ultrasonic washing, which contributed to the increase in the content of SPs. Meanwhile, the storage quality and microbial safety of fresh-cut red cabbages were improved. Ultrasonic washing reduced the weight loss and respiration rate and improved the color and texture characteristics. Additionally, the fresh-cut red cabbages after ultrasonic washing showed more retention of ascorbic acid (AA), total soluble proteins (TSPs), total soluble sugars (TSSs), and total soluble solids (SSs) compared with the control. Finally, ultrasonic washing effectively inhibited the growth of bacteria, molds and yeasts, which is beneficial to the extension of the shelf-life of fresh-cut red cabbages. Therefore, ultrasonic washing can be used as a tool to increase the content of SPs in fresh-cut red cabbages while retaining quality attributes and microbial safety.

Streptomyces: The biofactory of secondary metabolites.

Natural products derived from microorganisms serve as a vital resource of valuable pharmaceuticals and therapeutic agents. Streptomyces is the most ubiquitous bacterial genus in the environments with prolific capability to produce diverse and valuable natural products with significant biological activities in medicine, environments, food industries, and agronomy sectors. However, many natural products remain unexplored among Streptomyces. It is exigent to develop novel antibiotics, agrochemicals, anticancer medicines, etc., due to the fast growth in resistance to antibiotics, cancer chemotherapeutics, and pesticides. This review article focused the natural products secreted by Streptomyces and their function and importance in curing diseases and agriculture. Moreover, it discussed genomic-driven drug discovery strategies and also gave a future perspective for drug development from the Streptomyces.

A Flexible NO2 Gas Sensor Based on Single-Wall Carbon Nanotube Films Doped with a High Level of Nitrogen.

Carbon nanotubes (CNTs) are considered a promising candidate for the detection of toxic gases because of their high specific surface area and excellent electrical and mechanical properties. However, the detecting performance of CNT-based detectors needs to be improved because covalently bonded CNTs are usually chemically inert. We prepared a nitrogen-doped single-wall CNT (SWCNT) film by means of gas-phase fluorination followed by thermal annealing in NH3. The doped nitrogen content could be changed in the range of 2.9-9.9 at%. The N-doped SWCNT films were directly used to construct flexible and transparent gas sensors, which can work at a low voltage of 0.01 V. It was found that their NO2 detection performance was closely related to their nitrogen content. With an optimum nitrogen content of 9.8 at%, a flexible sensor had a detection limit of 500 ppb at room temperature with good cycling ability and stability during bending.

Clinical outcomes of hepatic arterial infusion chemotherapy combined with tyrosine kinase inhibitors and anti-PD-1 immunotherapy for unresectable intrahepatic cholangiocarcinoma.

OBJECTIVE: To compare the treatment efficacy and safety of tyrosine kinase inhibitors (TKIs) and anti-programmed cell death 1 (PD-1) immunotherapy combined with transarterial chemoembolization (TACE) or hepatic arterial infusion chemotherapy (HAIC) for patients with unresectable intrahepatic cholangiocarcinoma (ICC). METHODS: Patients with unresectable ICC received TKIs and anti-PD-1 immunotherapy combined with HAIC (HTP group) or TACE (TTP group) were included. The clinicopathological characteristics, treatment efficacy, and adverse events (AEs) were compared between the two groups. The factors associated with response rate to the treatments were evaluated. RESULTS: A total of 58 patients were enrolled, with 39 in the HTP group and 19 in the TTP group. Patients in the HTP group exhibited a better objective response rate (ORR; Response Evaluation Criteria in Solid Tumors [RECIST] 48.7% vs 15.8%, P = 0.02; modified RECIST [mRECIST] 61.5% vs 21.1%, P = 0.004) and disease control rate (DCR; 82.1% vs 36.8%, P = 0.001) compared to the TTP group. The median progression-free survival (PFS) rate was not reached and the 1-year PFS rate was 61.9% in the HTP group, whereas the median PFS was 11.0 months and the 1-year PFS rate was 31.6% in the TTP group. The type of treatment and tumor size were significant factors for the response rate. More patients in the HTP group presented rash, abdominal pain and hand-foot syndrome, but all AEs were relieved after symptomatic treatment, and no treatment-related death occurred. CONCLUSIONS: For unresectable ICC, treatment with a combination of HAIC with TKIs and anti-PD-1 immunotherapy was effective and safe. Tumor size might serve as a significant factor for the response rate following treatment for unresectable ICC.

Effects of dual-frequency slit ultrasound on the enzymolysis of high-concentration hydrolyzed feather meal: Biological activities and structural characteristics of hydrolysates.

Ultrasound-assisted enzymolysis has been applied to improve conventional enzymolysis, while there are rare reports on the application of ultrasound to high-concentration feather protein enzymolysis. Therefore, the feasibility of dual-frequency slit ultrasound (DFSU) for enzymolysis of high-concentration hydrolyzed feather meal (HFM), as well as the biological activities and structural characteristics of hydrolysates were investigated. The single-factor test was used to optimize the ultrasonic processing parameters: substrate concentration, frequency mode, intermittent ratio, power density, and time. The results showed that protein recovery rate and conversion rate increased by 6.08% and 18.63% under the optimal conditions (200 g/L, 28/80 kHz, 5:2 s/s, 600 W/L, and 3 h) compared with conventional enzymolysis, respectively. The macromolecular proteins in hydrolysates were converted into micromolecular peptides (< 500 Da) when treated by DFSU, and antioxidant activity and angiotensin-I-converting enzyme (ACE) inhibitory activity of hydrolysates were increased. Scanning electron microscopy (SEM) and atomic force microscopy (AFM) images illustrated the microstructure changes of feather protein particles in the ultrasound-assisted enzymatic hydrolysates of HFM (UEH), including more porous, smaller, and more uniform. Additionally, the conformation of protein molecules was significantly affected (P < 0.05), including the increase in free sulfhydryl (SH), the decrease in disulfide bond (SS) and surface hydrophobicity (H0). Fourier transform infrared (FTIR) spectra analysis further showed that the secondary structure of feather proteins was modified with a reduction in α-helix, ß-turn, and ß-sheet, while an increase in random coil content was observed. These results indicated that DFSU could be a promising method to enhance high-concentration HFM for preparing peptide-rich hydrolysates with high antioxidant activity and ACE inhibitory activity.

Cu-Catalyzed Diarylthiolation of Ynones with Aryl Iodides and Elemental Sulfur: An Access to Tetrasubstituted (Z)-1,2-Bis(arylthio)alkenes and Benzo[b][1,4]dithiines.

A copper-catalyzed three-component reaction of ynones, aryl iodides, and elemental sulfur via a syn-addition process is established. The reaction features operational practicality, broad substrate scope, and readily accessible scale-up synthesis by affording a series of (Z)-1,2-bis(arylthio)alkenes in good to excellent yield. Moreover, benzo[b][1,4]dithiines can be also constructed efficiently by using 1,2-diiodobenzene as the coupling partner.