Myricetin inhibits 4 T1 breast tumor growth in mice via induction of Nrf-2/GPX4 pathway-mediated Ferroptosis.

Ferroptosis is a recently identified form of programmed cell death that is iron-dependent and closely involved in the pathogenesis of breast cancer. Past studies have identified myricetin as being able to inhibit breast cancer growth through its targeting of apoptotic mechanisms, but the precise mechanisms whereby it exerts its antitumoral effects in breast cancer remain to be characterized in detail. Here, the effects of myricetin on the induction of ferroptosis in breast cancer cells were investigated. It was found that myricetin was able to significantly inhibit 4 T1 tumor cell viability and colony forming activity, increasing the level of MDA, Fe2+, and ROS within these cells. From a mechanistic perspective, myricetin was found to induce ferroptotic 4 T1 cell death via downregulating Nrf-2 and GPX4. In vivo experimentation demonstrated that myricetin treatment was sufficient to reduce the growth of subcutaneous breast tumors in female mice as evidenced by decreases in tumor weight and volume, while significantly inhibiting Nrf-2 and GPX4 expression within the tumors of treated mice. Myricetin is capable of readily suppressing breast tumor growth in mice via the induction of ferroptotic activity through the Nrf-2/GPX4 pathway. Myricetin may thus offer utility as a therapeutic agent for the management of breast cancer in clinical settings.

High-Performance Ir1/CeO2 Single-Atom Catalyst for the Oxidation of Toluene.

The elimination of toluene is an obligatory target with increasing VOC emission in recent years. This study successfully prepared a single-atom Ir catalyst (Ir1/CeO2) by a simple incipient wetness impregnation method, confirmed by in situ CO DRIFTS and AC-HAADF-STEM. Compared to the cluster Ir catalyst (Ir/CeO2-C), Ir1/CeO2 exhibited excellent catalytic performance, stability, and water resistance for the oxidation of toluene. By Raman, H2-TPR, O2-TPD, and XPS experiments, abundant oxygen defects and a unique Ir3+-Ov-Ce3+ structure were formed for the Ir1/CeO2 sample because it had a lower oxygen vacancy formation energy. Furthermore, the DFT results revealed that the Ir1/CeO2 sample had a lower ring-opening energy barrier and adsorption energy of the ring-opening products, which was the rate-determining step for the oxidation of toluene. This work provides instructive insights into the construction of Ir/CeO2 catalysts for the highly efficient removal of VOCs.

Detection of Arsenic(V) by Fluorescence Sensing Based on Chlorin e6-Copper Ion.

The high toxicity of arsenic (As) can cause irreversible harm to the environment and human health. In this study, the chlorin e6 (Ce6), which emits fluorescence in the infrared region, was introduced as the luminescence center, and the addition of copper ion (Cu2+) and As(V) provoked a regular change in fluorescence at 652 nm, whereas that of As(III) was 665 nm, which was used to optionally detect Cu2+, arsenic (As(III), and As(V)). The limit of detection (LOD) values were 0.212 µM, 0.089 ppm, and 1.375 ppb for Cu2+, As(III), and As(V), respectively. The developed method can be used to determine Cu2+ and arsenic in water and soil with good sensitivity and selectivity. The 1:1 stoichiometry of Ce6 with Cu2+ was obtained from the Job plot that was developed from UV-visible spectra. The binding constants for Cu2+ and As(V) were established to be 1.248 × 105 M-1 and 2.35 × 1012 M-2, respectively, using B-H (Benesi-Hildebrand) plots. Fluorescence lifetimes, B-H plots, FT-IR, and 1H-NMR were used to postulate the mechanism of Cu2+ fluorescence quenching and As(V) fluorescence restoration and the interactions of the two ions with the Ce6 molecule.

Molecular Engineering of Perylene Diimide Polymers with a Robust Built-in Electric Field for Enhanced Solar-Driven Water Splitting.

The built-in electric field of the polymer semiconductors could be regulated by the dipole moment of its building blocks, thereby promoting the separation of photogenerated carriers and achieving efficient solar-driven water splitting. Herein, three perylene diimide (PDI) polymers, namely oPDI, mPDI and pPDI, are synthesized with different phenylenediamine linkers. Notably, the energy level structure, light-harvesting efficiency, and photogenerated carrier separation and migration of polymers are regulated by the orientation of PDI unit. Among them, oPDI enables a large dipole moment and robust built-in electric field, resulting in enhanced solar-driven water splitting performance. Under simulated sunlight irradiation, oPDI exhibits the highest photocurrent of 115.1 µA cm-2 for photoelectrochemical oxygen evolution, which is 11.5 times that of mPDI, 26.8 times that of pPDI and 104.6 times that of its counterparts PDI monomer at the same conditions. This work provides a strategy for designing polymers by regulating the orientation of structural units to construct efficient solar energy conversion systems.

α-Synuclein induces prodromal symptoms of Parkinson's disease via activating TLR2/MyD88/NF-κB pathway in Schwann cells of vagus nerve in a rat model.

BACKGROUND: Increasing evidence suggests that patients with Parkinson's disease (PD) present with peripheral autonomic dysfunction (AutD) that even precedes motor deficits, through which α-synuclein can spread to the central nervous system. However, the pathological mechanisms underlying AutD in prodromal PD remain unclear. Here, we investigated the role of α-synuclein and its interplay with the activation of Schwann cells (SCs) of the vagus nerve in AutD. METHODS: Rats were subjected to injection with adeno-associated viruses containing the human mutated A53T gene (AAV-A53T) or an empty vector into the left cervical vagus nerve and evaluated for gastrointestinal symptoms, locomotor functions, intestinal blood flow, and nerve electrophysiology. Further, we examined the impact of α-synucleinopathy on vagus nerves, SCs, and central nervous system neurons using electron microscopy, immunofluorescence, immunohistochemistry, and western blot. Finally, the role of Toll-like receptor 2 (TLR2) in regulating the neuroinflammation in the vagus nerve via MyD88 and NF-κB pathway was determined using genetic knockdown. RESULTS: We found that rats injected with AAV-A53T in the vagus nerve exhibited prominent signs of AutD, preceding the onset of motor deficits and central dopaminergic abnormalities by at least 3 months, which could serve as a model for prodromal PD. In addition, reduced intestinal blood flow and decreased nerve conduction velocity were identified in AAV-A53T-injected rats, accompanied by disrupted myelin sheaths and swollen SCs in the vagus nerve. Furthermore, our data demonstrated that p-α-synuclein was deposited in SCs but not in axons, activating the TLR2/MyD88/NF-κB signaling pathway and leading to neuroinflammatory responses. In contrast, silencing the TLR2 gene not only reduced inflammatory cytokine expression but also ameliorated vagal demyelination and secondary axonal loss, consequently improving autonomic function in rats. CONCLUSIONS: These observations suggest that overexpression of α-synuclein in the vagus nerve can induce symptoms of AutD in prodromal PD, and provide support for a deeper understanding of the pathological mechanisms underlying AutD and the emergence of effective therapeutic strategies for PD.

Efficacy of immune checkpoint inhibitor monotherapy or combined with other small molecule-targeted agents in ovarian cancer.

Ovarian cancer is the most lethal female reproductive system tumour. Despite the great advances in surgery and systemic chemotherapy over the past two decades, almost all patients in stages III and IV relapse and develop resistance to chemotherapy after first-line treatment. Ovarian cancer has an extraordinarily complex immunosuppressive tumour microenvironment in which immune checkpoints negatively regulate T cells activation and weaken antitumour immune responses by delivering immunosuppressive signals. Therefore, inhibition of immune checkpoints can break down the state of immunosuppression. Indeed, Immune checkpoint inhibitors (ICIs) have revolutionised the therapeutic landscape of many solid tumours. However, ICIs have yielded modest benefits in ovarian cancer. Therefore, a more comprehensive understanding of the mechanistic basis of the immune checkpoints is needed to improve the efficacy of ICIs in ovarian cancer. In this review, we systematically introduce the mechanisms and expression of immune checkpoints in ovarian cancer. Moreover, this review summarises recent updates regarding ICI monotherapy or combined with other small-molecule-targeted agents in ovarian cancer.

Evaluation of the clinical efficacy of vaginal treatment options for persistent high-risk human papillomavirus infection after excisional treatment of cervical high-grade squamous intraepithelial lesions: a systematic review and Bayesian network meta-analysis.

BACKGROUND: To evaluate the clinical efficacy of different vaginal administration on cervical persistent high-risk human papillomavirus (HR-HPV) infection after excisional treatment for high-grade squamous intraepithelial lesions (HSIL). METHODS: Six databases (PubMed, EmBase, Cochrane Central, China Knowledge Network database, China Biomedical Literature Service, and WanFang database) were searched to collect randomized controlled trials (RCTs) of various types of vaginal administration compared to no treatment on persistent HR-HPV infection after HSIL excisional treatment, and comprehensive analysis of the clearance of different drugs on HR-HPV was performed using Bayesian reticulation meta-analysis. RESULTS: The study analyzed the efficacy of eight interventions, including Interferon, Baofukang, Paiteling, Bletilla striata Sanhuang Powder, Lactobacilli vaginal capsules, Fuanning + Interferon, Interferon + Lactobacilli vaginal capsules, and Interferon + Baofukang, on the clearance of HR-HPV after excisional treatment through pooling and analyzing data from 52 RCTs. The results of the study demonstrated that Interferon + Lactobacilli vaginal capsules [OR 16.0 (95% CIs 8.1-32.0)], Interferon + Fuanning [OR 16.0 (95% CIs 1.1-52.0)], and Interferon + Baofukang [OR 14.0 (95% CIs 6.8-28.0)] were all found to significantly improve postoperative HR-HPV clearance rates when compared to no treatment. Furthermore, when studies with high-risk bias were excluded, Interferon + Lactobacilli vaginal capsules [OR 8.6 (95% CIs 4.7-19.0)] and Interferon + Baofukang [OR 22.0 (95% CIs 8.7-59.0)] were still found to be positively associated with increased postoperative HR-HPV clearance rate. Additionally, the study´s results also indicate that Interferon + Baofukang was effective in enhancing the postoperative HR-HPV clearance rates, mainly when the studies were restricted to a follow-up period of at least 12 months [OR 9.6 (95% CIs 2.9-34.0)]. However, it is important to note that the majority of the trials (29 out of 52, 51.6%) were rated as moderate to high risk of bias, and the certainty of the evidence was moderate to very low. CONCLUSION: The application of various forms of vaginal administration, except for individual use of Lactobacilli vaginal capsules, is more efficacious than no treatment in patients with cervical persistent HR-HPV infection after excisional treatment. However, all of the estimates of the effect size for change in the efficiency of HR-HPV clearance are uncertain. Our confidence in effect estimates and ranking of treatments is low, which needs larger, more rigorous, and longer follow-up RCTs to resolve.

Size Effect of Platinum Nanoparticles over Platinum-Manganese Oxide on the Low-Temperature Oxidation of Toluene.

The effect of size of Pt nanoparticles has an important influence on the performance of supported Pt-based catalysts for the elimination of toluene. Herein, uniform Pt nanoparticles with average sizes of 1.5, 2.0, 2.5, 2.9, and 3.6 nm were obtained and supported on manganese oxide octahedral molecular sieves (OMS-2), and their catalytic performances for toluene oxidation were evaluated. Benefiting from the moderate interfacial interaction between nanoparticles and manganese oxide support, Pt/OMS-2-3 with the Pt particle size of 3.0 nm showed the best catalytic performance owing to the highest content of Pt2+ species. It also facilitates the formation of more abundant Mnδ+ (Mn2+ and Mn3+) and oxygen vacancies than that of the other sizes of the OMS-2-supported Pt nanoparticles, which can be filled by a large amount of adsorbed oxygen and converted into reactive oxygen species. We further showed that the resulting surface synergetic oxygen vacancies (Pt2+-Ov-Mnδ+) play a decisive part in catalyzing the complete oxidation of toluene. The result will provide new insights for designing efficient Pt-based catalysts for deep purification of toluene.

Facile H2O-Contributed O2 Activation Strategy over Mn-Based SCR Catalysts to Counteract SO2 Poisoning.

Mn-based catalysts preferred in low-temperature selective catalytic reduction (SCR) are susceptible to SO2 poisoning. The stubborn sulfates make insufficient O2 activation and result in deficient reactive oxygen species (ROS) for activating reaction molecules. H2O has long been regarded as an accomplice to SO2, hastening catalyst deactivation. However, such a negative impression of the SCR reaction was reversed by our recent research. Here, we reported a H2O contribution over Mn-based SCR catalysts to counteract SO2 poisoning through accessible O2 activation, in which O2 was synergistically activated with H2O to generate ROS for less deactivation and more expected regeneration. The resulting ROS benefited from the energetically favorable route supported by water-induced Ea reduction and was actively involved in the NH3 activation and NO oxidation process. Besides, ROS maintained high stability over the SO2 + H2O-deactivated γ-MnO2 catalyst throughout the mild thermal treatment, achieving complete regeneration of its own NO disposal ability. This strategy was proven to be universally applicable to other Mn-based catalysts.

Global analysis of RNA-binding proteins identifies a positive feedback loop between LARP1 and MYC that promotes tumorigenesis.

In addition to genomic alterations, aberrant changes in post-transcriptional regulation can modify gene function and drive cancer development. RNA-binding proteins (RBPs) are a large class of post-transcriptional regulators that have been increasingly implicated in carcinogenesis. By integrating multi-omics data, we identify LARP1 as one of the most upregulated RBPs in colorectal cancer (CRC) and demonstrate its oncogenic properties. We perform LARP1:RNA interactome profiling and unveil a previously unexplored role for LARP1 in targeting the 3'UTR of oncogenes in CRC. Notably, we identify the proto-oncogenic transcription factor MYC as a key LARP1-regulated target. Our data show that LARP1 positively modulates MYC expression by associating with its 3'UTR. In addition, antisense oligonucleotide-mediated blocking of the interaction between LARP1 and the MYC 3'UTR reduces MYC expression and in vitro CRC growth. Furthermore, a systematic analysis of LARP1:protein interactions reveals IGF2BP3 and YBX1 as LARP1-interacting proteins that also regulate MYC expression and CRC development. Finally, we demonstrate that MYC reciprocally modulates LARP1 expression by targeting its enhancer. In summary, our data reveal a critical, previously uncharacterized role of LARP1 in promoting CRC tumorigenesis, validate its direct regulation of the proto-oncogene MYC and delineate a model of the positive feedback loop between MYC and LARP1 that promotes CRC growth and development.

Tris-Copper Nanozyme as a Novel Laccase Mimic for the Detection and Degradation of Phenolic Compounds.

Phenolic compounds are one of the main organic pollutants in the environment that can seriously affect ecosystems, even at very low concentrations. Due to the resistance of phenolic compounds to microorganisms, conventional biological treatment methods face challenges in effectively addressing this pollution problem. In this study, a novel laccase mimic (Tris-Cu nanozyme) is prepared using a simple and rapid synthesis strategy based on the coordination of copper ions and amino groups in Tris(hydroxymethyl)aminomethane (Tris). It is found that the Tris-Cu nanozyme exhibits good catalytic activity against a variety of phenolic compounds, the Km, Vmax and Kcat are determined to be 0.18 mM, 15.62 µM·min-1 and 1.57 × 107 min-1 using 2,4-dichlorophenol (2,4-DP) as the substrate, respectively. Then, based on the laccase-like activity of the Tris-Cu nanozyme, a novel colorimetric method for 2,4-DP (the limit of detection (LOD) = 2.4 µM, S/N = 3) detection in the range of 10-400 µM was established, and its accuracy was verified by analyzing tap and lake water samples. In addition, the Tris-Cu nanozyme shows excellent removal abilities for six phenolic compounds in experiments. The removal percentages for 2,4-DP, 2-chlorophenol (2-CP), phenol, resorcinol, 2,6-dimethoxyphenol (2,6-DOP), and bisphenol A (BPA) are 100%, 100%, 100%, 100%, 87%, and 81% at 1 h, respectively. In the simulated effluent, the Tris-Cu nanozyme maintains its efficient catalytic activity towards 2,4-DP, with a degradation percentage of 76.36% at 7 min and a reaction rate constant (k0) of 0.2304 min-1. Therefore, this metal-organic complex shows promise for applications in the monitoring and degrading of environmental pollutants.

Ultra-High Adsorption Capacity of Core-Shell-Derived Magnetic Zeolite Imidazolate Framework-67 as Adsorbent for Selective Extraction of Theophylline.

A core-shell-derived structural magnetic zeolite imidazolate framework-67 (Fe3O4-COOH@ZIF-67) nanocomposite was fabricated through a single-step coating of zeolite imidazolate framework-67 on glutaric anhydride-functionalized Fe3O4 nanosphere for the magnetic solid-phase extraction (MSPE) of theophylline (TP). The Fe3O4-COOH@ZIF-67 nanocomposite was characterized through scanning electron microscopy, transmission electron microscopy, energy dispersive X-ray spectrometry, Fourier transform infrared spectroscopy, Zeta potential analysis, X-ray diffraction, Brunauer-Emmett-Teller, and vibrating sample magnetometer. The material has a high specific surface area and good magnetism, which maintains the regular dodecahedron structure of ZIF-67 without being destroyed by the addition of Fe3O4-COOH nanospheres. The Fe3O4-COOH@ZIF-67 can rapidly adsorb TP mainly through the strong coordination interaction between undercoordinated Co2+ on ZIF-67 and -NH from imidazole of TP. The adsorption and desorption conditions, such as the amount of adsorbent, adsorption time, pH value, and elution solvent, were optimized. The kinetics of TP adsorption on Fe3O4-COOH@ZIF-67 was found to follow pseudo-second-order kinetics. The Langmuir model fits the adsorption data well and the maximum adsorption capacity is 1764 mg/g. Finally, the developed MSPE-HPLC method was applied in the enrichment and analysis of TP in four tea samples and rabbit plasma. TP was not detected in oolong tea and rabbit plasma, and its contents in jasmine tea, black tea, and green tea are 5.80, 4.31, and 1.53 µg/g, respectively. The recoveries of spiked samples are between 74.41% and 86.07% with RSD in the range of 0.81-3.83%. The adsorption performance of Fe3O4-COOH@ZIF-67 nanocomposite was nearly unchanged after being stored at room temperature for at least 80 days and two consecutive adsorption-desorption cycles. The results demonstrate that Fe3O4-COOH@ZIF-67 nanocomposite is a promising magnetic adsorbent for the preconcentration of TP in complex samples.

Metal-Free Photocatalytic CO2 Reduction to CH4 and H2 O2 under Non-sacrificial Ambient Conditions.

Photocatalytic CO2 reduction to CH4 requires photosensitizers and sacrificial agents to provide sufficient electrons and protons through metal-based photocatalysts, and the separation of CH4 from by-product O2 has poor applications. Herein, we successfully synthesize a metal-free photocatalyst of a novel electron-acceptor 4,5,9,10-pyrenetetrone (PT), to our best knowledge, this is the first time that metal-free catalyst achieves non-sacrificial photocatalytic CO2 to CH4 and easily separable H2 O2 . This photocatalyst offers CH4 product of 10.6 µmol ⋅ g-1 ⋅ h-1 under non-sacrificial ambient conditions (room temperature, and only water), which is two orders of magnitude higher than that of the reported metal-free photocatalysts. Comprehensive in situ characterizations and calculations reveal a multi-step reaction mechanism, in which the long-lived oxygen-centered radical in the excited PT provides as a site for CO2 activation, resulting in a stabilized cyclic carbonate intermediate with a lower formation energy. This key intermediate is thermodynamically crucial for the subsequent reduction to CH4 product with the electronic selectivity of up to 90 %. The work provides fresh insights on the economic viability of photocatalytic CO2 reduction to easily separable CH4 in non-sacrificial and metal-free conditions.

PD-1/PD-L1 Inhibitors Monotherapy for the Treatment of Endometrial Cancer: Meta-Analysis and Systematic Review.

PURPOSE: The efficacy of programmed cell death protein 1(PD-1)/Programmed cell death 1 ligand 1 (PD-L1) inhibitors for endometrial cancer remain controversial, and guidelines are inconsistent on which are preferred therapies for advanced disease, or who develop metastases and recurrence. Therefore, we aimed to estimate the efficacy and safety of PD-1/PD-L1 inhibitors in endometrial cancer on a more complete database by adding multiple randomized trials. METHODS: A systematic and comprehensive search was carried out in PD-1/PD-L1 inhibitors monotherapy. RESULTS: The ORR of PD-1/PDL-1 inhibitors was 29%, and subgroup analysis showed that the pooled ORR of the proficient mismatch repair (pMMR) group was 4% and which was 45% of the deficient mismatch repair (dMMR) group. The DCR of PD-1/PD-L1 inhibitors was 48%, through subgroup analysis, we found that the DCR of the pMMR group was 21% and which was 58% of the dMMR group. The proportion of patients occurring overall adverse events was 65% and grade three or higher adverse events was 14%. The proficient mismatch repair (pMMR) group and the deficient mismatch repair (dMMR) group showed different results. CONCLUSION: PD-1/PD-L1 inhibitors had shown little success in the pMMR population and better efficacy in the dMMR population.

TRIM36 inhibits tumorigenesis through the Wnt/ß-catenin pathway and promotes caspase-dependent apoptosis in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer and has an extremely poor prognosis. We aimed to determine the latent relationships between TRIM36 regulation of apoptosis and the Wnt/ß-catenin pathway in HCC. METHODS: Immunohistochemistry and western blotting were used to characterize the aberrant expression of TRIM36 in HCC and adjacent tissues. Clinical information was analyzed using Kaplan-Meier and Cox methods. RNA-seq of potential targets was conducted to detect the regulation of TRIM36. Apoptosis assays and cellular proliferation, invasion and migration were conducted in a loss- and gain-of-function manner in cultured cells to determine the biological functions of TRIM36. A rescue experiment was conducted to confirm the role of Wnt/ß-catenin signaling in TRIM36 regulation. Finally, in vivo experiments were conducted using cell line-derived xenografts in nude mice to validate the central role of TRIM36 in HCC. RESULTS: TRIM36 expression was significantly downregulated in HCC tissues compared to adjacent non-tumor tissues. TRIM36 repressed the proliferation, migration, and invasion of Huh7 and HCCLM3 cells, whereas it stimulated apoptosis. Wnt/ß-catenin signaling was inhibited by TRIM36, and rescue experiments highlighted its importance in HCC proliferation, migration, and invasion. In vivo experiments further confirmed the effects of sh-TRIM36 on HCC tumorigenesis, inhibition of apoptosis, and promotion of Wnt/ß-catenin signaling. CONCLUSION: Our study is the first to indicate that TRIM36 acts as a tumor suppressor in HCC. TRIM36 activates apoptosis and inhibits cellular proliferation, invasion, and migration via the Wnt/ß-catenin pathway, which may serve as an important biomarker and promising therapeutic target for HCC.

Enhanced Photoelectrochemical Water Splitting of Black Silicon Photoanode with pH-Dependent Copper-Bipyridine Catalysts.

Since the water oxidation half-reaction requires the transfer of multi-electrons and the formation of O-O bond, it's crucial to investigate the catalytic behaviours of semiconductor photoanodes. In this work, a bio-inspired copper-bipyridine catalyst of Cu(dcbpy) is decorated on the nanoporous Si photoanode (black Si, b-Si). Under AM1.5G illumination, the b-Si/Cu(dcbpy) photoanode exhibits a high photocurrent density of 6.31 mA cm-2 at 1.5 VRHE at pH 11.0, which is dramatically improved from the b-Si photoanode (1.03 mA cm-2 ) and f-Si photoanode (0.0087 mA cm-2 ). Mechanism studies demonstrate that b-Si/Cu(dcbpy) has improved light-harvesting, interfacial charge-transfer, and surface area for water splitting. More interestingly, b-Si/Cu(dcbpy) exhibits a pH-dependent water oxidation behaviour with a minimum Tafel slope of 241 mV/dec and the lowest overpotential of 0.19 V at pH 11.0, which is due to the monomer/dimer equilibrium of copper catalyst. At pH ∼11, the formation of dimeric hydroxyl-complex could form O-O bond through a redox isomerization (RI) mechanism, which decreases the required potential for water oxidation. This in-depth understanding of pH-dependent water oxidation catalyst brings insights into the design of dimer water oxidation catalysts and efficient photoanodes for solar energy conversion.

Rapid visual detection of porcine reproductive and respiratory syndrome virus via recombinase polymerase amplification combined with a lateral flow dipstick.

Porcine reproductive and respiratory syndrome (PRRS) is one of the most economically devastating infectious diseases in the global swine industry. A rapid and sensitive on-site detection method for PRRS virus (PRRSV) is critically important for diagnosing PRRS. In this study, we established a method that combines reverse transcription recombinase polymerase amplification (RT-RPA) with a lateral flow dipstick (LFD) for detecting North American PRRSV (PRRSV-2). The primers and probe were designed based on the conserved region of all complete PRRSV-2 genomic sequences available in China (n = 512) from 1996 to 2020. The detection limit of the assay was 5.6 × 10-1 median tissue culture infection dose (TCID50) per reaction within 30 min at 42 °C, which was more sensitive than that of reverse transcription polymerase chain reaction (RT-PCR) (5.6 TCID50 per reaction). The assay was highly specific for the epidemic lineages of PRRSV-2 in China and did not cross-react with pseudorabies virus, porcine circovirus 2, classical swine fever virus, or porcine epidemic diarrhea virus. The assay performance was evaluated by testing 179 samples and comparing the results with those of quantitative RT-PCR (RT-qPCR). The results showed that the detection coincidence rate of RT-RPA and RT-qPCR was 100% when the cycle threshold values of RT-qPCR were < 32. The assay provides a new alternative for simple and reliable detection of PRRSV-2 and has great potential for application in the field.

Recent Advances in Visible-Light Photoredox Catalysis for the Thiol-Ene/Yne Reactions.

Visible-light photoredox catalysis has been established as a popular and powerful tool for organic transformations owing to its inherent characterization of environmental friendliness and sustainability in the past decades. The thiol-ene/yne reactions, the direct hydrothiolation of alkenes/alkynes with thiols, represents one of the most efficient and atom-economic approaches for the carbon-sulfur bonds construction. In traditional methodologies, harsh conditions such as stoichiometric reagents or a specialized UV photo-apparatus were necessary suffering from various disadvantages. In particular, visible-light photoredox catalysis has also been demonstrated to be a greener and milder protocol for the thiol-ene/yne reactions in recent years. Additionally, unprecedented advancements have been achieved in this area during the past decade. In this review, we will summarize the recent advances in visible-light photoredox catalyzed thiol-ene/yne reactions from 2015 to 2021. Synthetic strategies, substrate scope, and proposed reaction pathways are mainly discussed.

Iron-Catalyzed Regiodivergent Hydrostannation of Alkynes: Intermediacy of Fe(IV)-H versus Fe(II)-Vinylidene.

We report an iron system, Cp*Fe(1,2-R2PC6H4X), which controls the Markovnikov and anti-Markovnikov hydrostannation of alkynes by tuning the ionic metal-heteroatom bonds (Fe-X) reactivity. The sequential addition of nBu3SnH to the iron-amido catalyst (1, X = HN-, R = Ph) affords a distannyl Fe(IV)-H species responsible for syn-addition of the Sn-H bond across the C≡C bond to produce branched α-vinylstannanes. Activation of the C(sp)-H bond of alkynes by an iron-aryloxide catalyst (2, X = O-, R = Cy) affords an iron(II) vinylidene intermediate, allowing for gem-addition of the Sn-H to the terminal-carbon producing ß-vinylstannanes. These catalytic reactions exhibit excellent regioselectivity and broad functional group compatibility and enable the large-scale synthesis of diverse vinylstannanes. Many new reactions have been established based on such a synthetic Fe-X platform to demonstrate that the initial step of the catalysis is conveniently controlled by the activation of either the tin hydride or the alkyne substrate.

Inhibition of the transient receptor potential vanilloid 3 channel attenuates carbon tetrachloride-induced hepatic fibrosis.

Transient receptor potential vanilloid 3 (TRPV3) is a member of the TRP superfamily. Previous studies have demonstrated that TRPV3 is associated with myocardial fibrosis. However, the role of TRPV3 in hepatic fibrosis and its underlying mechanisms are still unclear. This study aimed to elucidate the underlying effects of TRPV3 on hepatic fibrosis at multiple biological levels. First, immunohistochemical staining was performed to examine TRPV3 expression in human hepatic cirrhosis tissues. Then, we established a CCl4-induced hepatic fibrosis mouse model. The TRPV3 selective agonist drofenine and its inhibitor, forsythoside B, were intraperitoneally injected to investigate the relationship between TRPV3 and liver fibrosis progression. Finally, in vitro studies were performed using hepatic stellate cells (HSCs) to discover the potential molecular biological mechanisms. Immunohistochemistry revealed TRPV3 overexpression in liver cirrhosis. In the liver fibrosis groups, TRPV3 inhibitor treatment significantly reduced liver fibrosis, while TRPV3 agonist exacerbated its progression. In HSCs, knocking down TRPV3 with siRNA impaired DNA synthesis and cell proliferation and increased cell apoptosis. Furthermore, we found that knockdown of TRPV3 could reduce the lectin like oxidized lowdensity lipoprotein receptor-1 (LOX-1) protein levels. Our research suggests that lower expression or functional levels of TRPV3 can ameliorate the inflammatory response and fibrotic tissue proliferation.