Rocaglamide regulates iron homeostasis by suppressing hepcidin expression.

The anemia of inflammation (AI) is characterized by the presence of inflammation and abnormal elevation of hepcidin. Accumulating evidence has proved that Rocaglamide (RocA) was involved in inflammation regulation. Nevertheless, the role of RocA in AI, especially in iron metabolism, has not been investigated, and its underlying mechanism remains elusive. Here, we demonstrated that RocA dramatically suppressed the elevation of hepcidin and ferritin in LPS-treated mice cell line RAW264.7 and peritoneal macrophages. In vivo study showed that RocA can restrain the depletion of serum iron (SI) and transferrin (Tf) saturation caused by LPS. Further investigation showed that RocA suppressed the upregulation of hepcidin mRNA and downregulation of Fpn1 protein expression in the spleen and liver of LPS-treated mice. Mechanistically, this effect was attributed to RocA's ability to inhibit the IL-6/STAT3 pathway, resulting in the suppression of hepcidin mRNA and subsequent increase in Fpn1 and TfR1 expression in LPS-treated macrophages. Moreover, RocA inhibited the elevation of the cellular labile iron pool (LIP) and reactive oxygen species (ROS) induced by LPS in RAW264.7 cells. These findings reveal a pivotal mechanism underlying the roles of RocA in modulating iron homeostasis and also provide a candidate natural product on alleviating AI.

Cysteine-Specific Multifaceted Bioconjugation of Peptides and Proteins Using 5-Substituted 1,2,3-Triazines.

Peptide and protein postmodification have gained significant attention due to their extensive impact on biomolecule engineering and drug discovery, of which cysteine-specific modification strategies are prominent due to their inherent nucleophilicity and low abundance. Herein, the study introduces a novel approach utilizing multifunctional 5-substituted 1,2,3-triazine derivatives to achieve multifaceted bioconjugation targeting cysteine-containing peptides and proteins. On the one hand, this represents an inaugural instance of employing 1,2,3-triazine in biomolecular-specific modification within a physiological solution. On the other hand, as a powerful combination of precision modification and biorthogonality, this strategy allows for the one-pot dual-orthogonal functionalization of biomolecules utilizing the aldehyde group generated simultaneously. 1,2,3-Triazine derivatives with diverse functional groups allow conjugation to peptides or proteins, while bi-triazines enable peptide cyclization and dimerization. The examination of the stability of bi-triazines revealed their potential for reversible peptide modification. This work establishes a comprehensive platform for identifying cysteine-selective modifications, providing new avenues for peptide-based drug development, protein bioconjugation, and chemical biology research.

Predictors for new-onset conduction block in patients with pure native aortic regurgitation after transcatheter aortic valve replacement with a new-generation self-expanding valve (VitaFlow Liberty™): a retrospective cohort study.

BACKGROUND: New-generation self-expanding valves can improve the success rate of transcatheter aortic valve replacement (TAVR) for severe pure native aortic regurgitation (PNAR). However, predictors of new-onset conduction block post-TAVR using new-generation self-expanding valves in patients with PNAR remain to be established. Therefore, this study aimed to identify predictors of new-onset conduction block post-TAVR using new-generation self-expanding valves (VitaFlow Liberty™) in patients with PNAR. METHODS: In this retrospective cohort study, patients were categorized into pacemaker and non-pacemaker groups based on their need for new postoperative permanent pacemaker implantation (PPI). Based on the postoperative presence of either new-onset complete left bundle branch block (cLBBB) or high-grade atrioventricular block (AVB), patients were further classified into conduction disorder and non-conduction disorder groups. Laboratory, echocardiographic, computed tomography, preoperative and postoperative electrocardiography, and procedural and clinical data were collected immediately after TAVR and during hospitalization and compared between the groups. Multivariate logistic regression analysis was performed incorporating the significant variables from the univariate analyses. RESULTS: This study examined 68 consecutive patients with severe PNAR who underwent TAVR. In 20 patients, a permanent pacemaker was fitted postoperatively. Multivariate logistic regression analysis revealed an association between the need for postoperative PPI and preoperative complete right bundle branch block (cRBBB) or first-degree AVB, as well as a non-tubular left ventricular outflow tract (LVOT). In addition, valve implantation depth and angle of aortic root were independent predictors of new-onset cLBBB or high-grade AVB developing post-TAVR. The predictive value of valve implantation depth and angle of aortic root was further supported by receiver operating characteristic curve analysis results. CONCLUSIONS: In patients with PNAR undergoing TAVR using self-expanding valves, preoperative cRBBB or first-degree AVB and a non-tubular LVOT were indicators of a higher likelihood of PPI requirement. Moreover, deeper valve implantation depth and greater angle of aortic root may be independent risk factors for new-onset cLBBB or high-grade AVB post-TAVR. Valve implantation depth and angle of aortic root values may be used to predict the possibility of new cLBBB or high-grade AVB post-TAVR.

Neoadjuvant chemotherapy followed by concurrent chemoradiotherapy with or without nimotuzumab in the treatment of locally advanced nasopharyngeal carcinoma: a retrospective study.

PURPOSE: We aimed to investigate the efficacy and side effects of concurrent chemoradiotherapy, with or without nimotuzumab, for the treatment of locally advanced nasopharyngeal carcinoma after neoadjuvant chemotherapy. METHODS: This study retrospectively enrolled 109 patients with NPC from our hospital from July 2019 to May 2021.All patients were treated with docetaxel, cisplatin, and fluorouracil(TPF) neoadjuvant chemotherapy for 2 cycles, and concurrent chemoradiotherapy was performed 2 weeks after chemotherapy. According to whether nimotuzumab was added in concurrent chemoradiotherapy, they were divided into the nimotuzumab group and the control group, with 52 cases in the nimotuzumab group and 57 cases in the control group.The efficacy and adverse reactions of the two groups were retrospectively analyzed. RESULTS: The objective remission and complete remission rates in the nimotuzumab and control groups were 100% vs 98.2% (p = 1.000), and 92.3% vs 78.9% (p = 0.049), respectively. The 3-year distant metastasis-free survival of the nimotuzumab and control groups was 91.6% and 77.3% (p = 0.047), respectively.The 3-year progression-free survival, locoregional relapse-free survival, and overall survival of the nimotuzumab and control groups were 87.6% vs 75.5% (p = 0.110), 90.5% vs 86.9% (p = 0.566), and 94.5% vs 87.1% (p = 0.295), respectively. In the nimotuzumab group, subgroup analysis showed that patients aged < 60 years (hazard ratio [HR] = 0.350, 95% confidence interval [CI]: 0.131-0.934, p = 0.036) and those with a neutrophil-to-lymphocyte ratio (neutrophil/lymphocyte ratio) ≤ 4 (HR = 0.365, 95% CI: 0.144-0.923, p = 0.033) achieved a better result. Additionally, multivariate analysis demonstrated that neutrophil/lymphocyte ratio was an independent risk factor for disease progression (HR = 7.485, p = 0.012) and distant metastasis (HR = 17.540, p = 0.009).No grade 4 adverse reactions were observed in either group. Grade 3 oral mucosal reactions, as well as pharyngeal and esophageal reactions were slightly higher in the nimotuzumab group than in the control group, but the difference was not statistically significant. No significant differences were observed in the incidence of adverse reactions such as leukopenia, HB reduction, thrombocytopenia between the two groups (P > 0.05). CONCLUSION: The concurrent chemoradiotherapy plus nimotuzumab after neoadjuvant chemotherapy for locally advanced nasopharyngeal carcinoma achieved a higher complete remission rate and significantly improved distant metastasis-free survival compared with concurrent chemoradiotherapy alone. Additionally, an increasing trend was observed in progression-free survival, and the incidence of side effects was similar in both groups.

Introducing Spiro-locks into the Nitrogen/Carbonyl System towards Efficient Narrowband Deep-blue Multi-resonance TADF Emitters.

The current availability of multi-resonance thermally activated delayed fluorescence (MR-TADF) materials with excellent color purity and high device efficiency in the deep-blue region is appealing. To address this issue in the emerged nitrogen/carbonyl MR-TADF system, we propose a spiro-lock strategy. By incorporating spiro functionalization into a concise molecular skeleton, a series of emitters (SFQ, SOQ, SSQ, and SSeQ) can enhance molecular rigidity, blue-shift the emission peak, narrow the emission band, increase the photoluminescence quantum yield by over 92 %, and suppress intermolecular interactions in the film state. The referent CZQ without spiro structure has a more planar skeleton, and its bluer emission in the solution state redshifts over 40 nm with serious spectrum broadening and a low PLQY in the film state. As a result, SSQ achieves an external quantum efficiency of 25.5 % with a peak at 456 nm and a small full width at half maximum of 31 nm in a simple unsensitized device, significantly outperforming CZQ. This work discloses the importance of spiro-junction in modulating deep-blue MR-TADF emitters.

Design and Synthesis of Red Through-Space Charge Transfer Thermally Activated Delayed Fluorescence Emitters with Donor/Acceptor/Donor Stacking.

Red through-space charge transfer thermally activated delayed fluorescence (TSCT TADF) materials named SAF36DCPP and SAF27DCPP with sandwiched structures were synthesized. Single crystals indicated that the intramolecular C-H···π interactions play a vital role in rigidifying the sandwiched structure, which results in a fluorescence yield of 63% for SAF36DCPP compared to 40% for SAF27DCPP. Organic light-emitting diodes with SAF36DCPP as the emitter realized a maximum external quantum efficiency of 16.12%.

Relationship Between Prognostic Nutritional Index and New-Onset Atrial Fibrillation in Patients with Acute ST-Elevation Myocardial Infarction Following Percutaneous Coronary Intervention.

Multiple reports relate new-onset atrial fibrillation (NOAF) to poor clinical outcomes in patients with ST-elevation myocardial infarction (STEMI) who received percutaneous coronary intervention (PCI). The prognostic nutritional index (PNI) is a reliable indicator of immunonutritional-inflammatory status, and it is linked to clinical outcomes in cardiovascular disease patients. This research aims to explore the relationship between NOAF and PNI.Overall, 600 STEMI patients treated with PCI were recruited for this retrospective analysis. The patients were categorized into the NOAF group or sinus rhythm (SR) group. Logistic regression and receiver operating characteristic (ROC) curve analyses were conducted to assess PNI estimation. Lastly, the Kaplan-Meier curve was used to compare all-cause mortality between both groups.The combined NOAF incidence in PCI-treated STEMI patients was 7.7%. PNI was independently correlated with NOAF using multivariate regression analyses (odds ratio [OR], 0.824; 95% confidence interval [CI], 0.750-0.906; P < 0.001). In ROC curve analyses, the best PNI threshold value for predicting NOAF was 40.1, with sensitivity, and specificity of 76.09% and 71.30%, respectively area under the curve, 0.787; 95% CI, 0.752-0.819; P < 0.001). After a median of 41-month follow-up, the Kaplan-Meier curve revealed that the NOAF patients displayed an elevated all-cause death incidence compared with SR patients, with a log-rank of P = 0.005.This study demonstrated that PNI is an independent predictor of NOAF in STEMI patients during hospitalization after PCI, which is strongly correlated with a poor outcome upon discharge.

Interactions between nonfullerene acceptors lead to unstable ternary organic photovoltaic cells.

For organic photovoltaic (OPV) devices to achieve consistent performance and long operational lifetimes, organic semiconductors must be processed with precise control over their purity, composition, and structure. This is particularly important for high volume solar cell manufacturing where control of materials quality has a direct impact on yield and cost. Ternary-blend OPVs containing two acceptor-donor-acceptor (A-D-A)-type nonfullerene acceptors (NFAs) and a donor have proven to be an effective strategy to improve solar spectral coverage and reduce energy losses beyond that of binary-blend OPVs. Here, we show that the purity of such a ternary is compromised during blending to form a homogeneously mixed bulk heterojunction thin film. We find that the impurities originate from end-capping C=C/C=C exchange reactions of A-D-A-type NFAs, and that their presence influences both device reproducibility and long-term reliability. The end-capping exchange results in generation of up to four impurity constituents with strong dipolar character that interfere with the photoinduced charge transfer process, leading to reduced charge generation efficiency, morphological instabilities, and an increased vulnerability to photodegradation. As a consequence, the OPV efficiency falls to less than 65% of its initial value within 265 h when exposed to up to 10 suns intensity illumination. We propose potential molecular design strategies critical to enhancing the reproducibility as well as reliability of ternary OPVs by avoiding end-capping reactions.

Early prediction of 30- and 14-day all-cause unplanned readmissions.

BACKGROUND: An unplanned readmission is a dual metric for both the cost and quality of medical care. METHODS: We employed the random forest (RF) method to build a prediction model using a large dataset from patients' electronic health records (EHRs) from a medical center in Taiwan. The discrimination abilities between the RF and regression-based models were compared using the areas under the ROC curves (AUROC). RESULTS: When compared with standardized risk prediction tools, the RF constructed using data readily available at admission had a marginally yet significantly better ability to identify high-risk readmissions within 30 and 14 days without compromising sensitivity and specificity. The most important predictor for 30-day readmissions was directly related to the representing factors of index hospitalization, whereas for 14-day readmissions the most important predictor was associated with a higher chronic illness burden. CONCLUSIONS: Identifying dominant risk factors based on index admission and different readmission time intervals is crucial for healthcare planning.

Carbonyl-Containing Thermally Activated Delayed Fluorescence Emitters for Narrow-Band Electroluminescence.

Carbonyl-containing derivatives show enduring vitality in the field of thermally activated delayed fluorescence (TADF) materials; they can realize high device efficiency by using both singlet and triplet excitons for electroluminescence. Recently, a system based on fused ketone/amine exhibited huge potential for constructing multi-resonance TADF (MR-TADF) emitters, which exhibit higher narrow-band emission than conventional TADF emitters with twisted donor-acceptor (D-A) structure. Herein, we summarize current research progress in both traditional and MR-type ketone derivatives with TADF characteristics for introducing the molecular design strategy of maintaining high device efficiency while keeping narrow-band emission profile. We hope this review can inspire the emergence of more high-performance narrow-band materials.

Advances in cGAS-STING pathway and its inhibitors in immune and inflammatory diseases / 中国药理学通报

The cGAS-STING signaling pathway is one of the main pathways of immune defense against many types of pathogens. cGAS catalyzes the production of the second messenger cGAMP (cyclic GMP-tVMP) by recognizing plasma DNA and cGAMP subsequently binds to the interferon gene stimulating factor (STING). The pathway induces the production of type I interferon (IFN-I) and activates the innate immune system. The activation of the cGAS-STI]NG pathway could facilitate self-protection,thus STI]NG agonists for tumor immunotherapy have attracted much attention in recent years,and several drug candidates have been in clinical trials. Meanwhile,aberrant activation of cGAS-STI]NG could lead to autoimmune diseases and has attracted extensive interest in developing its inhibitors. This paper summarizes the mechanism and regulatory sites of the cGAS-STI]NG pathway,and outlines the research progress of cGAS-STING pathway-related immune and inflammatory diseases and its inhibitors.

Highly Efficient Blue Thermally Activated Delayed Fluorescence Emitters Based on Multi-Donor Modified Oxygen-Bridged Boron Acceptor.

The employment of thermally activated delayed fluorescence (TADF) emitters is one of the most promising ways to realize the external quantum efficiency (EQE) of over 25% for organic light-emitting diodes (OLEDs). In addition, the TADF emitter based on oxygen-bridged boron (BO) fragment can maintain blue emission with high color purity. Herein, we constructed two blue TADF emitters, 3TBO and 5TBO, for OLEDs application. Both emitters consist of three donors linked at the oxygen-bridged boron acceptor. OLED devices based on 3TBO and 5TBO exhibited both high excellent device efficiency and high color purity with a maximum EQE; full-width at half-maximum (FWHM); and CIE coordinates of 17.3%, 47 nm, (0.120, 0.294), and 26.2%, 57 nm, (0.125, 0.275), respectively.

Highly Efficient Sky-Blue π-Stacked Thermally Activated Delayed Fluorescence Emitter with Multi-Stimulus Response Properties.

Organic materials with multi-stimulus response (MSR) properties have demonstrated many potential and practical applications. Herein, a π-stacked thermally activated delayed fluorescence (TADF) material with multi-stimulus response (MSR) properties, named SDMAC, was designed and synthesized using distorted 9,9-dimethyl-10-phenyl-9,10-dihydroacridine as a donor. SDMAC possesses a rigid π-stacked configuration with intramolecular through-space interactions and exhibits aggregation-induced emission enhancement (AIEE), solvatochromic, piezochromic, and circularly polarized luminescence (CPL) under different external stimuli. The rigid molecular structure and efficient TADF properties of SDMAC can be used in displays and lighting. Using SDMAC as an emitter, the maximum external quantum efficiency (EQE) of the fabricated organic light-emitting diodes (OLEDs) is as high as 28.4 %, which make them the most efficient CP-TADF OLEDs based on the through-space charge transfer strategy. The CP organic light-emitting diodes (CP-OLEDs) exhibit circularly polarized electroluminescence (CPEL) signals.

Visible light-controlled living cationic polymerization of methoxystyrene.

Photo-controlled living polymerization has received great attention in recent years. However, despite the great success therein, the report on photo-controlled living cationic polymerization has been greatly limited. We demonstrate here a novel decolorable, metal-free and visible light-controlled living cationic polymerization system by using tris(2,4-dimethoxyphenyl)methylium tetrafluoroborate as the photocatalyst and phosphate as the chain transfer agent (CTA) for polymerization of 4-methoxystyrene. This polymerization reaction under green LED light irradiation shows clear living characteristics including predictable molar mass, low molar-mass dispersity (D = 1.25), and sequential polymerization capability. In addition, the photocatalytic system exits excellent "on-off" photo switchability and shows the longest "off period" of 36 h up to now for photo-controlled cationic polymerization. Furthermore, the residual photo-catalyst is easily deactivated and decolored with addition of a base after the polymerization. The present study has extended the photo-controlled living cationic polymerization systems with new organic photocatalysts, phosphate CTA and polymerizable monomer as well as the new properties of excellent photostability and in-situ decolored capacity.

Pure Hydrocarbon Materials as Highly Efficient Host for White Phosphorescent Organic Light-Emitting Diodes: A New Molecular Design Approach.

To date, all efficient host materials reported for phosphorescent OLEDs (PhOLEDs) are constructed with heteroatoms, which have a crucial role in the device performance. However, it has been shown in recent years that the heteroatoms not only increase the design complexity but can also be involved in the instability of the PhOLED, which is nowadays the most important obstacle to overcome. Herein, we design pure aromatic hydrocarbon materials (PHC) as very efficient hosts in high-performance white and blue PhOLEDs. With EQE of 27.7 %, the PHC-based white PhOLEDs display similar efficiency as the best reported with heteroatom-based hosts. Incorporated as a host in a blue PhOLED, which are still the weakest links of the technology, a very high EQE of 25.6 % is reached, surpassing, for the first time, the barrier of 25 % for a PHC and FIrpic blue emitter. This performance shows that the PHC strategy represents an effective alternative for the future development of the OLED industry.

Steric Modulation of Spiro Structure for Highly Efficient Multiple Resonance Emitters.

A multiple resonance thermally activated delayed fluorescence (MR-TADF) molecule with a fused, planar architecture tends to aggregate at high doping ratios, resulting in broad full width at half maximum (FWHM), redshifting electroluminescence peaks, and low device efficiency. Herein, we propose a mono-substituted design strategy by introducing spiro-9,9'-bifluorene (SBF) units with different substituted sites into the MR-TADF system for the first time. As a classic steric group, SBF can hinder interchromophore interactions, leading to high device efficiency (32.2-35.9 %) and narrow-band emission (≈27 nm). Particularly, the shield-like molecule, SF1BN, seldom exhibits a broadened FWHM as the doping ratio rises, which differs from the C3-substituted isomer and unhindered parent emitter. These results manifest an effective method for constructing highly efficient MR-TADF emitters through a spiro strategy and elucidate the feasibility for steric modulation of the spiro structure in π-framework.

The Chinese pine genome and methylome unveil key features of conifer evolution.

Conifers dominate the world's forest ecosystems and are the most widely planted tree species. Their giant and complex genomes present great challenges for assembling a complete reference genome for evolutionary and genomic studies. We present a 25.4-Gb chromosome-level assembly of Chinese pine (Pinus tabuliformis) and revealed that its genome size is mostly attributable to huge intergenic regions and long introns with high transposable element (TE) content. Large genes with long introns exhibited higher expressions levels. Despite a lack of recent whole-genome duplication, 91.2% of genes were duplicated through dispersed duplication, and expanded gene families are mainly related to stress responses, which may underpin conifers' adaptation, particularly in cold and/or arid conditions. The reproductive regulation network is distinct compared with angiosperms. Slow removal of TEs with high-level methylation may have contributed to genomic expansion. This study provides insights into conifer evolution and resources for advancing research on conifer adaptation and development.

Research Progress of Intramolecular π-Stacked Small Molecules for Device Applications.

Organic semiconductors can be designed and constructed in π-stacked structures instead of the conventional π-conjugated structures. Through-space interaction (TSI) occurs in π-stacked optoelectronic materials. Thus, unlike electronic coupling along the conjugated chain, the functional groups can stack closely to facilitate spatial electron communication. Using π-stacked motifs, chemists and materials scientists can find new ways for constructing materials with aggregation-induced emission (AIE), thermally activated delayed fluorescence (TADF), circularly polarized luminescence (CPL), and room-temperature phosphorescence (RTP), as well as enhanced molecular conductance. Organic optoelectronic devices based on π-stacked molecules have exhibited very promising performance, with some of them exceeding π-conjugated analogues. Recently, reports on various organic π-stacked structures have grown rapidly, prompting this review. Representative molecular scaffolds and newly developed π-stacked systems could stimulate more attention on through-space charge transfer the well-known through-bond charge transfer. Finally, the opportunities and challenges for utilizing and improving particular materials are discussed. The previous achievements and upcoming prospects may provide new insights into the theory, materials, and devices in the field of organic semiconductors.

A narrowband blue circularly polarized thermally activated delayed fluorescence emitter with a hetero-helicene structure.

A narrowband blue CP-TADF emitter with a rigid hetero-helicene structure (QAO-PhCz) was synthesized and characterized. QAO-PhCz exhibits good electroluminescence performance (EQE = 14.0%) and narrow FWHM. The enantiomers of QAO-PhCz display CPL and CPEL properties with |glum| and |gEL|values of up to 1.1 × 10-3 and 1.5 × 10-3, respectively.

Over 800 nm Emission via Harvesting of Triplet Excitons in Exciplex Organic Light-Emitting Diodes.

Triplet excitons can be utilized upon introduction of phosphors into exciplexes, and such a scenario has been studied in the development of high-performance near-infrared (NIR) organic light-emitting diodes (OLEDs). To generate exciplexes in an emitting layer (EML) in the device, commercially available phosphors bis(2-phenylpyridinato-N,C2')iridium(acetylacetonate) [Ir(ppy)2acac] and iridium(III) bis(4-phenylthieno[3,2-c]pyridinato-N,C2')acetylacetonate (PO-01) were selected as donor components; in addition, a new designed fluorescent molecule, 3-([1,1':3',1″-terphenyl]-5'-yl)acenaphtho[1,2-b]quinoxaline-9,10-dicarbonitrile (AQDC-tPh), and recently reported 3-([1,1':3',1″-terphenyl]-5'-yl)acenaphtho[1,2-b]pyrazine-8,9-dicarbonitrile (APDC-tPh) were selected as acceptor components. An OLED with PO-01:AQDC-tPh blends as the EML has realized NIR emission at 750 nm and a maximum external quantum efficiency (EQE) of >0.23%. Furthermore, an OLED containing a PO-01:APDC-tPh blend realizes a maximum EQE of 0.16% at 824 nm. The high performance of these devices underlying phosphor-based exciplexes proves the potential and feasibility of our strategy for the construction of efficient NIR OLEDs.