Photoinduced HCl-Mediated Cross-Dehydrogenative Coupling of Quinolines with Alcohols and Ethers.

Via light irradiation, cross-dehydrogenative coupling of quinolines with alcohols and ethers was achieved under mild conditions. A stoichiometric amount of HCl and room temperature were necessary to promote the reaction. A green Minisci-type cross-dehydrogenative coupling reaction was performed without an oxidant or a transition-metal catalyst.

Greenhouse gas emissions and drivers of the global warming potential of vineyards under different irrigation and fertilizer management practices.

In the context of global warming and low water and fertilizer utilization efficiency in vineyards, identifying the driving factors of global warming potential (GWP) and proper irrigation and fertilization management strategies are crucial for high grape yields and emission reduction. In this experiment, drip fertigation technology was used, including three irrigation levels (W3 (100% M, where M is the irrigation quota), W2 (75% M) and W1 (50% M)) and four fertilization levels (F3 (648 kg hm-2), F2 (486 kg hm-2), F1 (324 kg hm-2) and F0 (0 kg hm-2)). Traditional furrow irrigation and fertilization (CG) and rainfed (CK) treatments were used as control treatments. The results indicated that under the drip fertigation system, fertilization significantly increased the grape leaf chlorophyll relative content (SPAD) and leaf area index (LAI) within a fertilizer application of 0-486 kg hm-2. Irrigation primarily had a direct positive effect on the water-filled pore space (WFPS) in the 0-60 cm soil layer, and the residual soil nutrient content was mainly affected by fertilization. The vital stage for reducing greenhouse gas emissions was the fruit-inflating and fruit-rendering stages. The CG treatment not only failed to ensure high grape yield but also adversely affected the soil environment and the reduction of greenhouse gas emissions in the vineyard. Fertilization had a direct positive effect on the grape SPAD, LAI, yield, and soil residual nutrient content. GWP was primarily directly driven by SPAD, WFPS, and soil residual nutrient content, while grape yield was primarily directly driven by fertilization and SPAD. In conclusion, the W2F2 treatment (25 % reduced irrigation and 486 kg hm-2 of fertilization) of drip fertigation in the vineyard was the preferred irrigation and fertilizer management strategy for maintaining good vine vigor and balancing grape yield and environmental benefits.

Construction of an immune-related gene prognostic model for obese endometrial cancer patients based on bioinformatics analysis.

Background: The tumor microenvironment (TME) affected the prognosis of tumors. However, its effect on the outcomes of obese endometrial cancer (EC) patients had not been reported. Methods: This research performed a retrospective analysis of the transcriptome profiles and medical data of 503 EC patients. Immune scores were assessed by estimation algorithms. Cox and LASSO regression analyses were utilized to pinpoint key genes linked to prognosis, and the RPS was created to forecast the outcomes of obese EC patients. The relationship among genetic mutations and RPS was examined using CNV and somatic mutation information. ssGSEA and GSVA were employed to detect immune infiltration and immune pathway enrichment associated with key genes. The TIDE algorithm and GDSC database were utilized to forecast patients' responses of patients to immunotherapy and chemotherapy, respectively. Finally, we employed the 'rms' R software package to construct the nomogram. Results: The prognosis of obese EC patients was associated with immune scores. Three key genes (EYA4, MBOAT2 and SCGB2A1) were identified. The risk prognosis score (RPS) for obese EC patients was established by risk stratification and prognostic prediction using prognostic genes. The higher the RPS, the worse the prognosis, and the more malignant the genomic alterations. The high RPS group had a significantly reduced proportion of most immune cells in comparison to the low RPS group. The high RPS group was linked to G2M, MYC and E2F related pathways such as cell proliferation, cell cycle and cell death. Cisplatin, tamoxifen and topotecan had a greater effect on the low RPS group. Notably, the nomogram had a good predictive ability. Conclusion: Our study designed a reliable RPS for obese EC patients to forecast their prognosis, immune aggressiveness, and responses to immunotherapy and drug treatments.

Bromate-induced oxidation of carbamazepine and toxicity assessment of transformation products in the freezing-sunlight process: Effects of trivalent chromium.

Bromate (BrO3-)-induced pharmaceutical and personal care products (PPCPs) oxidation is enhanced in freezing systems. Reduced forms of metals are widely present, often coexisting with various contaminants. However, their effects on the interaction of PPCPs with BrO3- in ice in cold regions may have been overlooked. Herein we investigated the effects of representative reducing metal Cr(III) on the interaction between the representative PPCP carbamazepine (CBZ) and BrO3- in the freezing system. Our findings demonstrated that the degradation rate constants of CBZ by BrO3- and Cr(III) were 29.4%-60.3% lower than those by BrO3- in ice, revealing the inhibition of Cr(III) on CBZ degradation by BrO3- in ice. In BrO3-/freezing/sunlight system, BrO3- contributed 62.8% to CBZ degradation. In BrO3-/Cr(III)/freezing/sunlight system, Cr(III) promoted the generation of hydroxyl radical (·OH), leading to 51.0% contribution of ·OH to CBZ degradation. Oxidants were consumed by Cr(III) to form Cr(VI) rather than reacting with CBZ, thereby decreasing CBZ degradation by BrO3- in ice. Due to sunlight-induced Cr(VI) reduction in ice, only 0.3% of Cr(III) was converted to Cr(VI) in BrO3-/Cr(III)/freezing/sunlight system. BrO3--induced CBZ degradation rate in ice decreased in order of Fe(II), Cr(III), and Mn(II), which was due to the different reducing capabilities. An effective reduction in comprehensive toxicity of systems followed the freezing-sunlight process, even in the presence of Cr(III). This work sheds new light on the environmental behaviors and fate of PPCPs, brominated disinfection by-products, and reducing metals during seasonal freezing.

Antiphospholipid Syndrome Nephropathy Occurs in Pregnancy: A Case Report.

OBJECTIVE: This paper presents an analysis of the pregnancy trajectory and therapeutic regimen documentation of a primigravida with APSN. It aims at communicating the therapeutic approach and preventive measures for APSN in pregnancy. CASE PRESENTATION: This paper reports the trajectory and therapeutic regimen documentation of a primigravida with APSN. The APSN was discovered in a primigravida woman aged 26 years at 11 weeks of gestation. The initial therapy regimen consists of daily administration of prednisone 10 mg, hydroxychloroquine 200 mg, dapparin 5000 IU, and aspirin 50 mg. At a gestational age of 20 + 3 weeks, the dosage of dapparin was modified to 5000 IU/other day, along with a significant rise in urinary protein level seen at 30 + 3 weeks of gestational age. The initial dosage of dapanin sodium was renewed. The patient delivered at 38 + 3 weeks of gestation without other complications. CONCLUSION: It is imperative to acknowledge that altering the dosage and administration of medication should not be done haphazardly during pregnancy.

Recent developments in immunotherapy for gastrointestinal tract cancers.

The past few decades have witnessed the rise of immunotherapy for Gastrointestinal (GI) tract cancers. The role of immune checkpoint inhibitors (ICIs), particularly programmed death protein 1 (PD-1) and PD ligand-1 antibodies, has become increasingly pivotal in the treatment of advanced and perioperative GI tract cancers. Currently, anti-PD-1 plus chemotherapy is considered as first-line regimen for unselected advanced gastric/gastroesophageal junction adenocarcinoma (G/GEJC), mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) colorectal cancer (CRC), and advanced esophageal cancer (EC). In addition, the encouraging performance of claudin18.2-redirected chimeric antigen receptor T-cell (CAR-T) therapy in later-line GI tract cancers brings new hope for cell therapy in solid tumour treatment. Nevertheless, immunotherapy for GI tumour remains yet precise, and researchers are dedicated to further maximising and optimising the efficacy. This review summarises the important research, latest progress, and future directions of immunotherapy for GI tract cancers including EC, G/GEJC, and CRC.

Catalytic Enantioselective Propargylation of Pyrazolones by Amide-Based Phase-Transfer Catalysts.

In this paper, we developed a highly enantioselective alkylation of 4-substituted pyrazolones catalyzed by phase-transfer catalysis. Cheap halohydrocarbons were employed as electrophilic alkylationg agents, and propargyl, allyl, and benzyl products with all-carbon quaternary stereocenters were afforded with excellent enantioselectivities and good yields. We found that the unique structures of the catalyst (hydrogen bond donors of the C-9 hydroxyl group and amide group, the triphenyl at the NH-position) were important for good enantioselectivity. Furthermore, chiral propargyl products could be easily connected to azide molecules by click cycloaddition, which offers unique opportunities to obtain structurally diverse chiral pyrazolones.

Predicting gastric cancer response to anti-HER2 therapy or anti-HER2 combined immunotherapy based on multi-modal data.

The sole use of single modality data often fails to capture the complex heterogeneity among patients, including the variability in resistance to anti-HER2 therapy and outcomes of combined treatment regimens, for the treatment of HER2-positive gastric cancer (GC). This modality deficit has not been fully considered in many studies. Furthermore, the application of artificial intelligence in predicting the treatment response, particularly in complex diseases such as GC, is still in its infancy. Therefore, this study aimed to use a comprehensive analytic approach to accurately predict treatment responses to anti-HER2 therapy or anti-HER2 combined immunotherapy in patients with HER2-positive GC. We collected multi-modal data, comprising radiology, pathology, and clinical information from a cohort of 429 patients: 310 treated with anti-HER2 therapy and 119 treated with a combination of anti-HER2 and anti-PD-1/PD-L1 inhibitors immunotherapy. We introduced a deep learning model, called the Multi-Modal model (MuMo), that integrates these data to make precise treatment response predictions. MuMo achieved an area under the curve score of 0.821 for anti-HER2 therapy and 0.914 for combined immunotherapy. Moreover, patients classified as low-risk by MuMo exhibited significantly prolonged progression-free survival and overall survival (log-rank test, P < 0.05). These findings not only highlight the significance of multi-modal data analysis in enhancing treatment evaluation and personalized medicine for HER2-positive gastric cancer, but also the potential and clinical value of our model.

Whole-brain inputs and outputs of Phox2b and GABAergic neurons in the nucleus tractus solitarii.

The nucleus tractus solitarii (NTS) plays a critical role in the homeostatic regulation of respiration, blood pressure, sodium consumption and metabolic processes. Despite their significance, the circuitry mechanisms facilitating these diverse physiological functions remain incompletely understood. In this study, we present a whole-brain mapping of both the afferent and efferent connections of Phox2b-expressing and GABAergic neurons within the NTS. Our findings reveal that these neuronal populations not only receive monosynaptic inputs primarily from the medulla oblongata, pons, midbrain, supra-midbrain and cortical areas, but also mutually project their axons to these same locales. Moreover, intense monosynaptic inputs are received from the central amygdala, the paraventricular nucleus of the hypothalamus, the parasubthalamic nucleus and the intermediate reticular nucleus, along with brainstem nuclei explicitly engaged in respiratory regulation. In contrast, both neuronal groups extensively innervate brainstem nuclei associated with respiratory functions, although their projections to regions above the midbrain are comparatively limited. These anatomical findings provide a foundational platform for delineating an anatomical framework essential for dissecting the specific functional mechanisms of these circuits.

Targeting hTERT Promoter G-Quadruplex DNA Structures with Small-Molecule Ligand to Downregulate hTERT Expression for Triple-Negative Breast Cancer Therapy.

Human telomerase reverse transcriptase (hTERT) may have noncanonical functions in transcriptional regulation and metabolic reprogramming in cancer cells, but it is a challenging target. We thus developed small-molecule ligands targeting hTERT promoter G-quadruplex DNA structures (hTERT G4) to downregulate hTERT expression. Ligand 5 showed high affinity toward hTERT G4 (Kd = 1.1 µM) and potent activity against triple-negative breast cancer cells (MDA-MB-231, IC50 = 1 µM). In cell-based assays, 5 not only exerts markedly inhibitory activity on classical telomere functions including decreased telomerase activity, shortened telomere length, and cellular senescence but also induces DNA damage, acute cellular senescence, and apoptosis. This study reveals that hTERT G4-targeting ligand may cause mitochondrial dysfunction, disrupt iron metabolism and activate ferroptosis in cancer cells. The in vivo antitumor efficacy of 5 was also evaluated in an MDA-MB-231 xenograft mouse model and approximately 78.7% tumor weight reduction was achieved. No observable toxicity against the major organs was observed.

Tale of two emergent games: Opinion dynamics in dynamical directed networks.

Unidirectional social interactions are ubiquitous in real social networks whereas undirected interactions are intensively studied. We establish a voter model in a dynamical directed network. We analytically obtain the degree distribution of the evolving network at any given time. Furthermore, we find that the average degree is captured by an emergent game. However, we find that the fate of opinions is captured by another emergent game. Beyond expectation, the two emergent games are typically different due to the unidirectionality of the evolving networks. The Nash equilibrium analysis of the two games facilitates us to give the criterion under which the minority opinion with few disciples initially takes over the population eventually for in-group bias. Our work fosters the understanding of opinion dynamics ranging from methodology to research content.

Ligand-Solvent Coordination Enables Comprehensive Trap Passivation for Efficient Near-Infrared Quantum Dot Light-Emitting Diodes.

Near-infrared light-emitting diodes (NIR LEDs) based on perovskite quantum dots (QDs) have produced external quantum efficiency (EQE) of ~15 %. However, these high-performance NIR-QLEDs suffer from immediate carrier quenching because of the accumulation of migratable ions at the surface of the QDs. These uncoordinated ions and carriers-if not bound to the nanocrystal surface-serve as centers for exciton quenching and device degradation. In this work, we overcome this issue and fabricate high-performance NIR QLEDs by devising a ligand anchoring strategy, which entails dissolving the strong-binding ligand (Guanidine Hydroiodide, GAI) in the mediate-polar solvent. By employing the dye-sensitized device structure (phosphorescent indicator), we demonstrate the elimination of the interface defects. The treated QDs films exhibit an exciton binding energy of 117 meV: this represents a 1.5-fold increase compared to that of the control (74 meV). We report, as a result, the NIR QLEDs with an EQE of 21 % which is a record among NIR perovskite QLEDs. These QLEDs also exhibit a 7-fold higher operational stability than that of the best previously reported NIR QLEDs. Furthermore, we demonstrate that the QDs are compatible with large-area QLEDs: we showcase 900 mm2 QLEDs with EQE approaching 20 %.

Claudin18.2-specific CAR T cells in gastrointestinal cancers: phase 1 trial final results.

Claudin18.2 (CLDN18.2) is highly expressed with the development of various malignant tumors, especially gastrointestinal cancers, and is emerging as a new target for cancer treatment. Satricabtagene autoleucel (satri-cel)/CT041 is an autologous chimeric antigen receptor (CAR) T cell targeting CLDN18.2, and the interim results of the CT041-CG4006 trial were reported in June 2022. Here we present the final results of this single-arm, open-label, phase 1 trial, which evaluated the safety and efficacy of satri-cel in patients with CLDN18.2-positive advanced gastrointestinal cancers. This trial included a dose-escalation stage (n = 15) and a dose-expansion stage in four different cohorts (total n = 83): cohort 1, satri-cel monotherapy in 61 patients with standard chemotherapy-refractory gastrointestinal cancers; cohort 2, satri-cel plus anti-PD-1 therapy in 15 patients with standard chemotherapy-refractory gastrointestinal cancers; cohort 3, satri-cel as sequential treatment after first-line therapy in five patients with gastrointestinal cancers; and cohort 4, satri-cel monotherapy in two patients with anti-CLDN18.2 monoclonal antibody-refractory gastric cancer. The primary endpoint was safety; secondary endpoints included efficacy, pharmacokinetics and immunogenicity. A total of 98 patients received satri-cel infusion, among whom 89 were dosed with 2.5 × 108, six with 3.75 × 108 and three with 5.0 × 108 CAR T cells. Median follow-up was 32.4 months (95% confidence interval (CI): 27.3, 36.5) since apheresis. No dose-limiting toxicities, treatment-related deaths or immune effector cell-associated neurotoxicity syndrome were reported. Cytokine release syndrome occurred in 96.9% of patients, all classified as grade 1-2. Gastric mucosal injuries were identified in eight (8.2%) patients. The overall response rate and disease control rate in all 98 patients were 38.8% and 91.8%, respectively, and the median progression-free survival and overall survival were 4.4 months (95% CI: 3.7, 6.6) and 8.8 months (95% CI: 7.1, 10.2), respectively. Satri-cel demonstrates therapeutic potential with a manageable safety profile in patients with CLDN18.2-positive advanced gastrointestinal cancer. ClinicalTrials.gov identifier: NCT03874897 .

Polyvinylpyrrolidone-curcumin nanoparticles with immune regulatory and metabolism regulatory effects for the treatment of experimental autoimmune uveitis.

Uveitis comprises a cluster of intraocular inflammatory disorders characterized by uncontrolled autoimmune responses and excessive oxidative stress leading to vision loss worldwide. In the present study, curcumin (CUR) was conjugated with polyvinylpyrrolidone (PVP) to form PVP-CUR nanoparticles with significantly elevated solubility and outstanding multiple radical scavenging abilities. In vitro studies revealed that PVP-CUR nanoparticles markedly mitigated oxidative stress and reduced apoptosis in a H2O2-induced human retinal pigment epithelial cell line (ARPE-19) and promoted phenotypic polarization from M1 to M2 in an LPS-induced human microglial cell line (HMC3). Further in vivo studies demonstrated the prominent therapeutic effects of PVP-CUR nanoparticles on experimental autoimmune uveitis (EAU), which relieved clinical and pathological progression, improved perfusion and tomographic manifestations of retinal vessels, and reduced blood-retinal barrier (BRB) leakage; these effects may be mediated by mitigating oxidative stress and attenuating macrophage/microglia-elicited inflammation. Notably, treatment with PVP-CUR nanoparticles was shown to regulate metabolite alterations in EAU rats, providing novel insights into the underlying mechanisms involved. Additionally, the PVP-CUR nanoparticles showed great biocompatibility in vivo. In summary, our study revealed that PVP-CUR nanoparticles may serve as effective and safe nanodrugs for treating uveitis and other oxidative stress- and inflammation-related diseases.

Banxia Xiexin decoction combined with 5-ASA protects against CPT-11-induced intestinal dysfunction in rats via inhibiting TLR4/NF-κB signaling pathway.

BACKGROUND: Banxia Xiexin decoction (BXD) can control irinotecan (CPT-11)-caused delayed diarrhea, but the corresponding mechanism remains undefined. AIMS: This paper aimed to uncover the mechanism of BXD in regulating CPT-11-caused delayed diarrhea. MATERIALS & METHODS: Sprague-Dawley (SD) rats were assigned into the control, model, BXD low-dose (BXD-L, 5 g/kg), BXD medium-dose (BXD-M, 10 g/kg), BXD high-dose (BXD-H, 15 g/kg), 5-aminosalicylic acid (5-ASA, 10 mL/kg), and BXD-M + 5-ASA groups. Rats were injected intraperitoneally with 150 mg/kg CPT-11 at Day 4 and Day 5 to induce delayed diarrhea, and later treated with various doses (low, medium, and high) of BXD and 5-ASA for 9 days, except for rats in control group. The body weight of rats was measured. The rat colon tissue injury, inflammatory cytokine levels, and the activation of toll-like receptor 4/nuclear factor-κB (TLR4/NF-κB) signaling pathway were detected. RESULTS: BXD (5, 10, or 15 g/kg) or 5-ASA (10 mL/kg) alleviated body weight loss and colon tissue injury, decreased levels of inflammatory cytokines, and inactivated TLR4/NF-κB signaling pathway in CPT-11-induced model rats. BXD at 10 g/kg (the optimal concentration) could better treat CPT-11-induced intestinal dysfunction, as evidenced by the resulting approximately 50% reduction on injury score of model rats. Moreover, BXD-M (10 g/kg) synergistic with 5-ASA (10 mL/kg) further strengthened the inhibition on rat body weight loss, colon tissue injury, inflammatory cytokine levels, and TLR4/NF-κB signaling pathway. CONCLUSION: To sum up, BXD has a protective effect against CPT-11-induced intestinal dysfunction by inhibiting inflammation through inactivation TLR4/NF-κB signaling pathway. In particular, the combined use of BXD and 5-ASA holds great promise for treating CPT-11-induced delayed diarrhea.

Long-range order enabled stability in quantum dot light-emitting diodes.

Light-emitting diodes (LEDs) based on perovskite quantum dots (QDs) have produced external quantum efficiencies (EQEs) of more than 25% with narrowband emission1,2, but these LEDs have limited operating lifetimes. We posit that poor long-range ordering in perovskite QD films-variations in dot size, surface ligand density and dot-to-dot stacking-inhibits carrier injection, resulting in inferior operating stability because of the large bias required to produce emission in these LEDs. Here we report a chemical treatment to improve the long-range order of perovskite QD films: the diffraction intensity from the repeating QD units increases three-fold compared with that of controls. We achieve this using a synergistic dual-ligand approach: an iodide-rich agent (aniline hydroiodide) for anion exchange and a chemically reactive agent (bromotrimethylsilane) that produces a strong acid that in situ dissolves smaller QDs to regulate size and more effectively removes less conductive ligands to enable compact, uniform and defect-free films. These films exhibit high conductivity (4 × 10-4 S m-1), which is 2.5-fold higher than that of the control, and represents the highest conductivity recorded so far among perovskite QDs. The high conductivity ensures efficient charge transportation, enabling red perovskite QD-LEDs that generate a luminance of 1,000 cd m-2 at a record-low voltage of 2.8 V. The EQE at this luminance is more than 20%. Furthermore, the stability of the operating device is 100 times better than previous red perovskite LEDs at EQEs of more than 20%.

Enantioselective α-Trifluoromethylthiolation of Carbonyl Compounds with AgSCF3 and Trichloroisocyanuric Acid.

We successfully developed an enantioselective trifluoromethylthiolation of structurally diverse carbonyl compounds. Trichloroisocyanuric acid and AgSCF3 were employed to generate active electrophilic trifluoromethylthio species in situ for asymmetric C-SCF3 bond formation. A broad variety of chiral SCF3-carbon nucleophiles (pyrazolones, ß-keto esters, and ß-keto amides) were obtained in excellent yields with high enantioselectivities (up to 92% ee) by Cinchona alkaloid derived squaramide catalysts. The reaction exhibits high efficiency, good enantioselectivity, and high functional group tolerance, which provided a novel and efficient way for asymmetric synthesis of trifluoromethylthiolated carbonyl compounds.

Near-Infrared Luminescent Materials Incorporating Rare Earth/Transition Metal Ions: From Materials to Applications.

The spotlight has shifted to near-infrared (NIR) luminescent materials emitting beyond 1000 nm, with growing interest due to their unique characteristics. The ability of NIR-II emission (1000-1700 nm) to penetrate deeply and transmit independently positions these NIR luminescent materials for applications in optical-communication devices, bioimaging, and photodetectors. The combination of rare earth metals/transition metals with a variety of matrix materials provides a new platform for creating new chemical and physical properties for materials science and device applications. In this review, the recent advancements in NIR emission activated by rare earth and transition metal ions are summarized and their role in applications spanning bioimaging, sensing, and optoelectronics is illustrated. It started with various synthesis techniques and explored how rare earths/transition metals can be skillfully incorporated into various matrixes, thereby endowing them with unique characteristics. The discussion to strategies of enhancing excitation absorption and emission efficiency, spotlighting innovations like dye sensitization and surface plasmon resonance effects is then extended. Subsequently, a significant focus is placed on functionalization strategies and their applications. Finally, a comprehensive analysis of the challenges and proposed strategies for rare earth/transition metal ion-doped near-infrared luminescent materials, summarizing the insights of each section is provided.

Nickel Oxide Hole Injection Layers for Balanced Charge Injection in Quantum Dot Light-Emitting Diodes.

Quantum dot (QD) light-emitting diodes (QLEDs) are promising for next-generation displays, but suffer from carrier imbalance arising from lower hole injection compared to electron injection. A defect engineering strategy is reported to tackle transport limitations in nickel oxide-based inorganic hole-injection layers (HILs) and find that hole injection is able to enhance in high-performance InP QLEDs using the newly designed material. Through optoelectronic simulations, how the electronic properties of NiOx affect hole injection efficiency into an InP QD layer, finding that efficient hole injection depends on lowering the hole injection barrier and enhancing the acceptor density of NiOx is explored. Li doping and oxygen enriching are identified as effective strategies to control intrinsic and extrinsic defects in NiOx, thereby increasing acceptor density, as evidenced by density functional theory calculations and experimental validation. With fine-tuned inorganic HIL, InP QLEDs exhibit a luminance of 45 200 cd m-2 and an external quantum efficiency of 19.9%, surpassing previous inorganic HIL-based QLEDs. This study provides a path to designing inorganic materials for more efficient and sustainable lighting and display technologies.