[A new nor-neolignan compound identified from Itea yunnanensis].

Various separation methods in combination with spectral data analysis, X-ray single crystal diffraction analysis, and litera-ture data comparison were employed to clarify the chemical constituents of Itea yunnanensis. Seven compounds were obtained from I. yunnanensis, which were identified as(S)-3-[1-(4-hydroxyphenyl)propane-2-yl]-4-methoxybenzoate methyl ester(1), iteafuranal B(2), syringaresinol(3), dihydrokaempferol(4), trimethoxybenzene(5), eicosane(6), and nonacosane(7), respectively. Among them, compound 1 was a new nor-neolignan compound named iteanorneoligan A, and the rest of the compounds were identified from I. yunnanensis for the first time. The anti-hepatocellular carcinoma effect of the compound was evaluated based on Sk-hep-1 cells model via MTT assay, and compound 2 showed a significant inhibitory effect on the proliferation of Sk-hep-1 cells with an IC_(50) of 9.4 µmol·L~(-1). The antioxidant capacity was determined via DPPH, ABTS~(·+), and O■ radical scavenging ability, and compound 1 exhibited a significant ABTS~(·+) radical scavenging effect with an IC_(50) of 0.178 mg·mL~(-1).

Docosahexaenoic Acid Supplementation for Neonatal Hyperbilirubinemia: A Double-Blind, Randomized Clinical Trial.

Docosahexaenoic acid (DHA) is an essential component for brain development during fetal and early postnatal life. Hyperbilirubinemia is characterized by abnormally high levels of bilirubin in the bloodstream, frequently leading to jaundice in newborns. In severe instances, this condition can progress to neurological damage or kernicterus, a form of brain damage. Initial cell-based experiments conducted by our research team revealed that DHA significantly enhances the survival rate of nerve cells treated with bilirubin and diminishes the oxidative stress indicated by reduced peroxide activity caused by unconjugated bilirubin (UCB). Further investigations through animal studies demonstrated that DHA effectively mitigates bilirubin-induced brain injury in neonatal rats. However, the potential of DHA to decrease the incidence of bilirubin-induced brain damage in clinical settings has not been previously explored or reported. Infants with neonatal hyperbilirubinemia (n = 30 per group) participated in a double-blind, randomized, placebo-controlled parallel study. They received either 100 mg/d DHA or placebo syrup immediately when they were diagnosed. The study found that the bilirubin level at 48 hours of treatment, serum neuron-specific enolase (NSE) levels, mean phototherapy duration, and abnormal rate of cranial magnetic resonance imaging (MRI) were lower in the DHA group than those in the control group (P < .05). These results suggested that DHA is effective as an adjuvant treatment for hyperbilirubinemia in children. It can reduce the incidence of neonatal hyperbilirubinemia brain injury and plays a certain protective role. Clinical study on protective effect of DHA on neonatal bilirubin injury is registered at Chinese Clinical Trial Registry as ChiCTR2300070250.

N6-methyladenosine reader protein IGF2BP1 suppresses CD8 + T cells-mediated tumor cytotoxicity and apoptosis in colon cancer.

Tumor immune escape is an important manner for colon cancer to escape effective killing by immune system. Currently, the immune checkpoint PD-1/PD-L1-targeted immunotherapy has emerged as a promising therapeutic strategy in colon cancer. Here, present work aims to investigate the biological function of N6-methyladenosine (m6A) reader insulin-like growth factor 2 mRNA binding protein 1 (IGF2BP1) in regulating colon cancer's immune escape and CD8 + T cells-mediated tumor cytotoxicity and apoptosis. Results illustrated that IGF2BP1 was closely correlated to the colon cancer patients' poor clinical outcome. Functionally, upregulation of IGF2BP1 suppressed the CD8+ T-cells mediated antitumor immunity through reducing their tumor cytotoxicity. Mechanistically, MeRIP-Seq revealed that programmed death ligand 1 (PD-L1) mRNA had a remarkable m6A modified site on 3'-UTR genomic. Moreover, PD-L1 acted as the target of IGF2BP1, which enhanced the stability of PD-L1 mRNA. Overall, these results indicated that IGF2BP1 targeted PD-L1 to accelerate the immune escape in colon cancer by reducing CD8 + T cells-mediated tumor cytotoxicity in m6A-dependent manner. The findings demonstrate the potential of m6A-targeted immune checkpoint blockade in colon cancer, providing a novel insight for colon cancer immune escape and antitumor immunity in further precise treatment.

Effect of high-frequency oscillation on reduction of atelectasis in perioperative patients: a prospective randomized controlled study.

BACKGROUND: Atelectasis affects approximately 90% of anaesthetized patients, with laparoscopic surgery and pneumoperitoneum reported to exacerbate this condition. High-frequency oscillation therapy applies continuous positive pressure pulses to oscillate the airway, creating a pressure difference in small airways obstructed by secretions. This process helps reduce peak airway pressure, open small airways, and decrease atelectasis incidence, while also facilitating respiratory tract clearance. This study examines the efficacy of high-frequency oscillation on reduction of atelectasis in laparoscopic cholecystectomy (LC) patients under general anaesthesia, evaluated using lung ultrasound. METHODS: Sixty-four patients undergoing laparoscopic cholecystectomy were randomly divided into a control group and a high-frequency oscillation (HFO) group. Both groups underwent total intravenous anaesthesia under invasive arterial monitoring. The HFO group received a 10-minute continuous high-frequency oscillation therapy during surgery, while the control group received no intervention. Lung ultrasound evaluations were performed three times: five minutes post-intubation (T1), at the end of the surgery (T2), and before leaving the Post-Anaesthesia Care Unit (PACU; T3). Blood gas analysis was performed twice: prior to induction with no oxygen supply and before PACU discharge (oxygen supply off). RESULTS: The HFO group displayed a significantly lower incidence of atelectasis at T3 (57.5% vs. 90.3%, OR 6.88, 95%CI (1.74 to 27.24)) compared to the control group. Moreover, the HFO group's PaO2 levels remained consistent with baseline levels before PACU discharge, unlike the control group. Although there was no significant difference in LUS scores between the groups at T1 (8.56 ± 0.15 vs. 8.19 ± 0.18, p = 0.1090), the HFO group had considerably lower scores at T2 (13.41 ± 0.17 vs.7.59 ± 0.17, p < 0.01) and T3 (13.72 ± 0.14 vs.7.25 ± 0.21, p < 0.01). CONCLUSION: Our study indicates that high-frequency oscillation effectively reduces atelectasis in patients undergoing laparoscopic cholecystectomy. Additionally, it can mitigate the decline in oxygen partial pressure associated with atelectasis.

The Role of NCS1 in Immunotherapy and Prognosis of Human Cancer.

The Neural Calcium Sensor1 (NCS1) is a crucial protein that binds to Ca2+ and is believed to play a role in regulating tumor invasion and cell proliferation. However, the role of NCS1 in immune infiltration and cancer prognosis is still unknown. Our study aimed to explore the expression profile, immune infiltration pattern, prognostic value, biological function, and potential compounds targeting NCS1 using public databases. High expression of NCS1 was detected by immune histochemical staining in LIHC (Liver hepatocellular carcinoma), BRCA (Breast invasive carcinoma), KIRC (Kidney renal clear cell carcinoma), and SKCM (Skin Cutaneous Melanoma). The expression of NCS1 in cancer was determined by TCGA (The Cancer Genome Atlas Program), GTEx (The Genotype-Tissue Expression), the Kaplan-Meier plotter, GEO (Gene Expression Omnibus), GEPIA2.0 (Gene Expression Profiling Interactive Analysis 2.0), HPA (The Human Protein Atlas), UALCAN, TIMER2.0, TISIDB, Metascape, Drugbank, chEMBL, and ICSDB databases. NCS1 has genomic mutations as well as aberrant DNA methylation in multiple cancers compared to normal tissues. Also, NCS1 was significantly different in the immune microenvironment, tumor mutational burden (TMB), microsatellite instability (MSI), and immune infiltrate-associated cells in different cancers, which could be used for the typing of immune and molecular subtypes of cancer and the presence of immune checkpoint resistance in several cancers. Univariate regression analysis, multivariate regression analysis, and gene enrichment analysis to construct prognostic models revealed that NCS1 is involved in immune regulation and can be used as a prognostic biomarker for SKCM, LIHC, BRCA, COAD, and KIRC. These results provide clues from a bioinformatic perspective and highlight the importance of NCS1 in a variety of cancers.

Construction of Indole-Fused Seven- and Eight-Membered Azaheterocycles via a Tandem Pd/NBE-Catalyzed Decarbonylation and Dual C-H Activation Sequence.

Herein, we report the transformation of aromatic acids to indole-fused seven- and eight-membered azaheterocycles. Two C-C bonds are formed via the cleavage of one C-C bond and two C-H bonds. The incorporation of indole moieties into bioactive pharmaceuticals and natural products to construct a medium-sized polyfused heterocycle demonstrates the synthetic utility of the protocol.

Hydrogen sulfide functions as a micro-modulator bound at the copper active site of Cu/Zn-SOD to regulate the catalytic activity of the enzyme.

The present study examines whether there is a mechanism beyond the current concept of post-translational modifications to regulate the function of a protein. A small gas molecule, hydrogen sulfide (H2S), was found to bind at active-site copper of Cu/Zn-SOD using a series of methods including radiolabeled binding assay, X-ray absorption near-edge structure (XANES), and crystallography. Such an H2S binding enhanced the electrostatic forces to guide the negatively charged substrate superoxide radicals to the catalytic copper ion, changed the geometry and energy of the frontier molecular orbitals of the active site, and subsequently facilitated the transfer of an electron from the superoxide radical to the catalytic copper ion and the breakage of the copper-His61 bridge. The physiological relevance of such an H2S effect was also examined in both in vitro and in vivo models where the cardioprotective effects of H2S were dependent on Cu/Zn-SOD.

Oxidative Three-Component Selenofunctionalization of Alkenes: Convenient Access to Vicinally Functionalized Selenides.

Three-component selenofunctionalization processes of olefins, diselenides and sulfonamides, water, alcohols, or acids utilizing 1-fluoropyridinium triflate (FP-OTf) as a reaction promoter are reported. Under the optimal conditions, a broad range of vicinally functionalized selenide derivatives was accessible with high yields and excellent functional group compatibilities. Mechanistic studies revealed that the FP-OTf played a key role in this selenofunctionalization process.

Study on 2-arylbenzo[b]furans from Itea omeiensis and their fragmentation patterns with Q-Orbitrap mass spectrometry.

One new 2-arylbenzo[b]furan named iteafuranal F (1) as well as two known analogues (2-3) were isolated from the 95% EtOH extract of aerial parts of Itea omeiensis. Their chemical structures were constructed based on extensive analyses of UV, IR, 1D/2D NMR and HRMS spectra. Antioxidant assays revealed significant superoxide anion radical scavenging capacity of 1 with IC50 value of 0.66 mg/mL, which was comparable to the efficiency of positive control of luteolin. In addition, the preliminary MS fragmentation patterns in negative ion mode were established to distinguish 2-arylbenzo[b]furans with C-10 in different oxidation states: the characteristic loss of CO molecule [M-H-28]- was observed for 3-formyl-2-arylbenzo[b]furans, and the loss of CH2O fragment [M-H-30]- for 3-hydroxymethyl-2-arylbenzo[b]furans, and the loss of CO2 fragment [M-H-44]- for 2-arylbenzo[b]furan-3-carboxylic acids.

Recent Breakthroughs in Supercapacitors Boosted by Macrocycles.

Supercapacitors are essential for electrochemical energy storage because of their high-power density, good cycle stability, fast charging and discharging rates, and low maintenance cost. Macrocycles, including cucurbiturils, calixarene, and cyclodextrins, are cage-like organic compounds (with a nanocavity that contains O and N heteroatoms) with unique potential in supercapacitors. Here, we review the applications of macrocycles in supercapacitor systems, and we illustrate the merits of organic macrocycles in electrodes and electrolytes for improving the electrochemical double-layer capacitors and pseudocapacitance via supramolecular strategies. Then, the observed relationships between electrochemical performance and macrocyclic structures are introduced. This comprehensive review describes recent progress on macrocycle-block supercapacitors for researchers.

An integrated approach of high-performance liquid chromatography-mass spectrometry-based chemical profiling, network pharmacology, and molecular docking to reveal the potential mechanisms of Qishen Gubiao granules for treating coronavirus disease 2019.

Qishen Gubiao granules, a traditional Chinese medicine preparation composed of nine herbs, have been widely used to prevent and treat coronavirus disease 2019 with good clinical efficacy. In the present study, an integrated strategy based on chemical profiling followed by network pharmacology and molecular docking was employed, to explore the active components and potential molecular mechanisms of Qishen Gubiao granules in the therapy of coronavirus disease 2019. Using the ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry technique, a total of 186 ingredients corresponding to eight structure types in Qishen Gubiao preparation were identified or structurally annotated with the elucidation of the fragmentation pathways in the typical compounds. The network pharmacology analysis screened 28 key compounds including quercetin, apigenin, scutellarein, luteolin and naringenin acting on 31 key targets, which possibly modulated signal pathways associated with immune and inflammatory responses in the treatment of coronavirus disease 2019. The molecular docking results observed that the top 5 core compounds had a high affinity for angiotensin-converting enzyme 2 and 3-chymotrypsin-like protease. This study proposed a reliable and feasible approach for elucidating the multi-components, multi-targets, and multi-pathways intervention mechanism of Qishen Gubiao granules against coronavirus disease 2019, providing a scientific basis for its further quality evaluation and clinical application.

Photocatalytic Aerobic Cyclization of N-Propargylamides Enabled by Selenium-π-Acid Catalysis.

A dual catalytic approach combining photocatalyst and selenium-π-acid synergy has been used to cyclized of N-propargylamides. This method offers readily access to oxazole aldehydes under chemical oxidant-free conditions with low catalyst loadings, where air acts as a terminal and gratuitous oxidant. The reaction is demonstrated with a range of substrates, including aryl and alkyl propargyl amides, and in the late-stage functionalization of several amide-containing drug molecules. Mechanistic studies suggest that the acridinium catalyst is able to oxidize diselenide and generate singlet oxygen (1 O2 ), which is responsible for this transformation.

Statins and risk of venous thromboembolic diseases: A two-sample mendelian randomization study.

BACKGROUND AND AIMS: In observational studies, statins have been suggested to have protective effects on venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE). To this aim, we performed a two-sample mendelian randomization (MR) analysis to determine whether these associations were causal. METHODS AND RESULTS: Data on the single nucleotide polymorphisms (SNPs) related to statin medication were obtained from the FinnGen study, and data for VTE, PE and DVT of lower extremities (LEDVT) were from the UK Biobank study, respectively. Inverse variance weighted (IVW) method was used as the principal analysis of MR, and sensitivity analysis was performed to detect horizontal pleiotropy and heterogeneity. MR estimates showed an inverse causal association between statin medication and the risk of VTE (odds ratio [OR]: 0.999, 95% CI: 0.998-1.000, P = 0.004), PE (OR: 0.999, 95% CI: 0.999-1.000, P = 0.011) and LEDVT (OR: 0.999, 95% CI: 0.999-1.000, P = 0.008). CONCLUSION: Our findings provide direct evidence that statins might decrease the risk of VTE, PE and LEDVT in agreement with observational studies. The specific mechanism of statin therapy for venous thromboembolism needs to be further studied.

The priming effects of plant leachates on dissolved organic matter degradation in water depend on leachate type and water stability.

The modification of dissolved organic matter (DOM) degradation by plant carbon inputs represents a critical biogeochemical process that controls carbon dynamics. However, the priming effects (PEs) different plant tissues induce on the degradation of DOM pools with different stabilities remain unknown. In this study, PEs, induced by different tissue leachates of Phragmites australis, were evaluated via changes in DOM components and properties of both fresh and tidal water (with different stabilities). The results showed that DOM derived from different plant tissue leachates differed in composition and bioavailability. Inputs of tissue leachates induced PEs with different intensities and directions (negative or positive) on DOM degradation of fresh and tidal water. In fresh water, the PEs of leaf and root leachates were significantly higher than those of stem and rhizome leachates. The PE direction changed for DOM degradation between fresh and tidal water. The addition of leaf and root leachates tended to induce positive PEs on DOM degradation of fresh water, while resulting in negative PEs on DOM degradation of tidal water. Negative PEs for tidal water DOM may be due to preferential utilization of microbes, high salinity, and/or the promotion of exogenous DOM production from plant tissues. The results indicate that intensity and direction of PEs induced by plant leachates depend on both leachate type and water stability. The findings highlight the necessity to examine the nature of exogenous and native DOM when interpreting the interactive processes that regulate DOM degradation.

Treatment of radiation-induced brain injury with bisdemethoxycurcumin.

Radiation therapy is considered the most effective non-surgical treatment for brain tumors. However, there are no available treatments for radiation-induced brain injury. Bisdemethoxycurcumin (BDMC) is a demethoxy derivative of curcumin that has anti-proliferative, anti-inflammatory, and anti-oxidant properties. To determine whether BDMC has the potential to treat radiation-induced brain injury, in this study, we established a rat model of radiation-induced brain injury by administering a single 30-Gy vertical dose of irradiation to the whole brain, followed by intraperitoneal injection of 500 µL of a 100 mg/kg BDMC solution every day for 5 successive weeks. Our results showed that BDMC increased the body weight of rats with radiation-induced brain injury, improved learning and memory, attenuated brain edema, inhibited astrocyte activation, and reduced oxidative stress. These findings suggest that BDMC protects against radiation-induced brain injury.

A Study on the Dynamic Tunning Range of CVD Graphene at Microwave Frequency: Determination, Prediction and Application.

In recent years, graphene has shown great application prospects in tunable microwave devices due to its tunable conductivity. However, the electromagnetic (EM) properties of graphene, especially the dynamic tunning characteristics, are largely dependent on experimental results, and thus are unable to be effectively predicted according to growth parameters, which causes great difficulties in the design of graphene-based tunable microwave devices. In this work, we systematically explored the impact of chemical vapor deposition (CVD) parameters on the dynamic tunning range of graphene. Firstly, through improving the existing waveguide method, the dynamic tunning range of graphene can be measured more accurately. Secondly, a direct mathematical model between growth parameters and the tunning range of graphene is established. Through this, one can easily obtain needed growth parameters for the desired tunning range of graphene. As a verification, a frequency tunable absorber prototype is designed and tested. The good agreement between simulation and experimental results shows the reliability of our mathematic model in the rapid design of graphene-based tunable microwave devices.

Graphitic carbon nitride (g-C3N4)-based photocatalytic materials for hydrogen evolution.

The semiconductors, such as TiO2, CdS, ZnO, BiVO4, graphene, produce good applications in photocatalytic water splitting for hydrogen production, and great progress have been made in the synthesis and modification of the materials. As a two-dimensional layered structure material, graphitic carbon nitride (g-C3N4), with the unique properties of high thermostability and chemical inertness, excellent semiconductive ability, affords good potential in photocatalytic hydrogen evolution. However, the related low efficiency of g-C3N4 with fast recombination rate of photogenerated charge carriers, limited visible-light absorption, and low surface area of prepared bulk g-C3N4, has called out the challenge issues to synthesize and modify novel g-C3N4-block photocatalyst. In this review, we have summarized several strategies to improve the photocatalytic performance of pristine g-C3N4 such as pH, morphology control, doping with metal or non-metal elements, metal deposition, constructing a heterojunction or homojunction, dye-sensitization, and so forth. The performances for photocatalytic hydrogen evolution and possible development of g-C3N4 materials are shared with the researchers interested in the relevant fields hereinto.

Case report: Vaccine-induced immune thrombotic thrombocytopenia complicated by acute cerebral venous thrombosis and hemorrhage after AstraZeneca vaccines followed by Moderna COVID-19 vaccine booster and surgery.

Vaccine-induced thrombotic thrombocytopenia (VITT) is a well-known complication of adenoviral vector COVID-19 vaccines including ChAdOx1 nCoV-19 (AstraZeneca) and Ad26. COV2.S (Janssen, Johnson & Johnson). To date, only a few cases of mRNA COVID-19 vaccine such as mRNA-1273 (Moderna) or BNT162b2 (Pfizer-BioNTech)-induced VITT have been reported. We report a case of VITT with acute cerebral venous thrombosis and hemorrhage after a booster of mRNA-1273 (Moderna) vaccine in a patient previously vaccinated with two doses of the AstraZeneca vaccine. A 42-year-old woman presented with sudden onset of weakness of the right upper limb with focal seizure. She had received two doses of AstraZeneca vaccines and a booster with Moderna vaccine 32 days before presentation. She had also undergone a laparoscopic myomectomy 12 days previously. Laboratory examinations revealed anemia (9.5 g/dl), thrombocytopenia (31 × 103/µl), and markedly elevated d-dimer (>20.0 mg/L; reference value < 0.5 mg/L). The initial brain computed tomography (CT) was normal, but a repeated scan 10 h later revealed hemorrhage at the left cerebrum. Before the results of the blood smear were received, on suspicion of thrombotic microangiopathy with thrombocytopenia and thrombosis, plasmapheresis and pulse steroid therapy were initiated, followed by intravenous immunoglobulin (1 g/kg/day for two consecutive days) due to refractory thrombocytopenia. VITT was confirmed by positive anti-PF4 antibody and both heparin-induced and PF4-induced platelet activation testing. Clinicians should be aware that mRNA-1273 Moderna, an mRNA-based vaccine, may be associated with VITT with catastrophic complications. Additionally, prior exposure to the AstraZeneca vaccine and surgical procedure could also have precipitated or aggravated autoimmune heparin-induced thrombocytopenia/VITT-like presentation.

Sirtuin5 protects colorectal cancer from DNA damage by keeping nucleotide availability.

In our previous study, we reported that sirtuin5 (SIRT5), a member of the NAD+-dependent class III histone deacetylase family, is highly expressed in colorectal cancer (CRC). Herein we show that SIRT5 knockdown impairs the production of ribose-5-phosphate, which is essential for nucleotide synthesis, resulting in continuous and irreparable DNA damage and consequently leading to cell cycle arrest and enhanced apoptosis in CRC cells. These SIRT5 silencing-induced effects can be reversed by nucleoside supplementation. Mechanistically, SIRT5 activates transketolase (TKT), a key enzyme in the non-oxidative pentose phosphate pathway, in a demalonylation-dependent manner. Furthermore, TKT is essential for SIRT5-induced malignant phenotypes of CRC both in vivo and in vitro. Altogether, SIRT5 silencing induces DNA damage in CRC via post-translational modifications and inhibits tumor growth, suggesting that SIRT5 can serve as a promising target for CRC treatment.