High-Throughput Two-Photon 3D Printing Enabled by Holographic Multi-Foci High-Speed Scanning.

The emerging two-photon polymerization (TPP) technique enables high-resolution printing of complex 3D structures, revolutionizing micro/nano additive manufacturing. Various fast scanning and parallel processing strategies have been proposed to promote its efficiency. However, obtaining large numbers of uniform focal spots for parallel high-speed scanning remains challenging, which hampers the realization of higher throughput. We report a TPP printing platform that combines galvanometric mirrors and liquid crystal on silicon spatial light modulator (LCoS-SLM). By setting the target light field at LCoS-SLM's diffraction center, sufficient energy is acquired to support simultaneous polymerization of over 400 foci. With fast scanning, the maximum printing speed achieves 1.49 × 108 voxels s-1, surpassing the existing scanning-based TPP methods while maintaining high printing resolution and flexibility. To demonstrate the processing capability, functional 3D microstructure arrays are rapidly fabricated and applied in micro-optics and micro-object manipulation. Our method may expand the prospects of TPP in large-scale micro/nanomanufacturing.

Acetic Acid-Catalyzed (3 + 2) Cyclization of 2-Aroyl-3-aryl-1,1-dicyanocyclopropanes with Arylhydrazines: To trans-4-Dicyanomethyl-1,3,5-triaryl-4,5-dihydropyrazoles.

Acetic acid-catalyzed (3 + 2) cyclization reaction of substituted 2-aroyl-3-aryl-1,1-dicyanocyclopropanes with arylhydrazines was investigated for the efficient synthesis of 4-dicyanomethyl-1,3,5-triaryl-4,5-dihydropyrazoles in good yields, in which 4,5-double substituents are predominantly trans selective. This approach included the consecutive condensation, ring opening, and double nucleophilic cyclization reaction.

DABCO-Promoted Cyclization of 2-Amino-4H-chromen-4-ones with 2,6-Dibenzylidenecyclohexan-1-ones for the Synthesis of Chromeno[2,3-b]tetrahydroquinoline.

DABCO-promoted cyclization reaction of substituted 2-amino-4H-chromen-4-ones with substituted 2,6-dibenzylidenecyclohexan-1-ones was investigated under mild conditions. This reaction provided a novel and efficient access to the 7,8,9,10-tetrahydro-12H-chromeno[2,3-b]quinolin-12-ones in good yields, the exocyclic double bond of which is predominantly E-selective.

DBU-Mediated Domino Annulation Reaction of 2-Amino-4H-chromen-4-ones and Aromatic Aldehydes for Synthesis of Polysubstituted 3-Hydroxy-5H-chromeno[2,3-b]pyridinones.

A pseudo-three-component annulation reaction of substituted 2-amino-4H-chromen-4-ones with aromatic aldehydes promoted by DBU was investigated to access polysubstituted 5H-chromeno[2,3-b]pyridines. This reaction included a sequential intermolecular nucleophilic addition/Michael cyclization/intramolecular epoxidation/ring opening/aromatization sequence, which possessed excellent step and atom economy in a single operation for generating 3-hydroxy-5H-chromeno[2,3-b]pyridines from readily available substrates.

Advances in epigenetic modification affecting anthocyanin synthesis.

Anthocyanins are a class of important flavonoid compounds widely present in plants, and play important roles in plant growth, metabolism and stress responses. In the process of growth and development, anthocyanin renders the flowers and fruits of plants displaying rich colors, attracts insect pollination and animal feeding, thereby facilitating seed spreading and dissemination. In metabolic stress, anthocyanin can resist low temperature, drought, fungal infection, ultraviolet damage, insect pests and other stress-resistant processes. The anthocyanin biosynthesis is co-regulated by related structural genes as well as transcription factor genes. Recent studies have showed that the anthocyanin biosynthesis-related genes in plants are epigenetically regulated, thus affecting the synthesis of anthocyanin glycosides. Epigenetics is one of the hot topics in the field of biological sciences. In this review, we summarize the advances of epigenetic modifications in anthocyanin biosynthesis and the application of genome editing in epigenetics, thereby providing new ideas for flower color breeding improvement by epigenetic regulation.

Nickel-Catalyzed Ipso/Ortho Difunctionalization of Aryl Bromides with Alkynes and Alkyl Bromides via a Vinyl-to-Aryl 1,4-Hydride Shift.

Polysubstituted arenes are ubiquitous structures in a myriad of medicinal agents and complex molecules. Herein, we report a new catalytic blueprint that merges the modularity of nickel catalysis for bond formation with the ability to enable a rather elusive 1,4-hydride shift at arene sp2 C-H sites, thus allowing access to ipso/ortho-difunctionalized arenes from readily available aryl halides under mild conditions and exquisite selectivity profile.

Comparison of sublobar resection and lobectomy for patients with small (≤2cm) second primary non-small-cell lung cancer.

BACKGROUND: This study aimed to investigate whether sublobar resection (SR) is equivalent to lobectomy for small (≤ 2 cm) second primary lung cancer (SPLC). METHODS: We identified 834 patients with T1aN0M0 SPLC from the Surveillance, Epidemiology, and End Results (SEER) database during 2000-2016. Overall survival (OS) was compared between lobectomy and SR after propensity-score matching. A total of 228 patients with SPLC were identified from three institutions in China as the validation set. RESULTS: SR was an independent risk factor for patients with 1 to 2 cm SPLC (SR vs Lob: hazard ratio [HR], 1.593; 95% confidence interval [CI], 1.186-2.141; P = .002) but not for patients with SPLC ≤ 1 cm (SR vs Lob: HR, 1.206; 95% CI, 0.790-1.841; P = .385). Subgroup analysis on the SEER data indicated that OS favored lobectomy compared with SR for contralateral SPLC ≤ 2 cm but not for ipsilateral ones (ipsilateral: P = .692; contralateral: P = .030). Our multi-institutional data also revealed that SR was equivalent to lobectomy for patients with ≤2 cm ipsilateral SPLC. CONCLUSIONS: SR is equivalent to lobectomy for SPLC ≤ 1 cm but not for SPLC > 1 to 2 cm. SR might be recommended for patients with ipsilateral small SPLC considering the difficulty in reoperations.

Nickel-Catalyzed Asymmetric Reductive 1,2-Carboamination of Unactivated Alkenes.

Starting from diverse alkene-tethered aryl iodides and O-benzoyl-hydroxylamines, the enantioselective reductive cross-electrophilic 1,2-carboamination of unactivated alkenes was achieved using a chiral pyrox/nickel complex as the catalyst. This mild, modular, and practical protocol provides rapid access to a variety of ß-chiral amines with an enantioenriched aryl-substituted quaternary carbon center in good yields and with excellent enantioselectivities. This process reveals a complementary regioselectivity when compared to Pd and Cu catalysis.

Applications of Circulating Tumor DNA in Myelodysplastic Syndromes and Acute Myeloid Leukemia: Promises and Challenges.

The term 'liquid biopsy' has become widely used by clinicians with the development of non-invasive diagnostic and monitoring techniques for malignancies. Liquid biopsy can provide genetic information for early diagnosis, risk stratification, treatment selection and postoperative follow-up. In the era of personalized medicine, liquid biopsy is an important research direction. In recent years, research on circulating tumour DNA (ctDNA) in hematological malignancies has also made great progress. This review provides an overview of the current understanding of circulating tumour DNA in myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). Additionally, recent advancements in the monitoring of minimal/measurable residual disease (MRD) through ctDNA are discussed.

Multiple Self-Powered Sensor-Integrated Mobile Manipulator for Intelligent Environment Detection.

A multiple self-powered sensor-integrated mobile manipulator (MSIMM) system was proposed to address challenges in existing exploration devices, such as the need for a constant energy supply, limited variety of sensed information, and difficult human-computer interfaces. The MSIMM system integrates triboelectric nanogenerator (TENG)-based self-powered sensors, a bionic manipulator, and wireless gesture control, enhancing sensor data usability through machine learning. Specifically, the system includes a tracked vehicle platform carrying the manipulator and electronics, including a storage battery and a microcontroller unit (MCU). An integrated sensor glove and terminal application (APP) enable intuitive manipulator control, improving human-computer interaction. The system responds to and analyzes various environmental stimuli, including the droplet and fall height, temperature, pressure, material type, angles, angular velocity direction, and acceleration amplitude and direction. The manipulator, fabricated using 3D printing technology, integrates multiple sensors that generate electrical signals through the triboelectric effect of mechanical motion. These signals are classified using convolutional neural networks for accurate environmental monitoring. Our database shows signal recognition and classification accuracy exceeding 94%, with specific accuracies of 100% for pressure sensors, 99.55% for angle sensors, and 98.66, 95.91, 96.27, and 94.13% for material, droplet, temperature, and acceleration sensors, respectively.

CXCL5 impedes CD8+ T cell immunity by upregulating PD-L1 expression in lung cancer via PXN/AKT signaling phosphorylation and neutrophil chemotaxis.

BACKGROUND: Lung cancer remains one of the most prevalent cancer types worldwide, with a high mortality rate. Upregulation of programmed cell death protein 1 (PD-1) and its ligand (PD-L1) may represent a key mechanism for evading immune surveillance. Immune checkpoint blockade (ICB) antibodies against PD-1 or PD-L1 are therefore widely used to treat patients with lung cancer. However, the mechanisms by which lung cancer and neutrophils in the microenvironment sustain PD-L1 expression and impart stronger inhibition of CD8+ T cell function remain unclear. METHODS: We investigated the role and underlying mechanism by which PD-L1+ lung cancer and PD-L1+ neutrophils impede the function of CD8+ T cells through magnetic bead cell sorting, quantitative real-time polymerase chain reaction (RT-PCR), western blotting, enzyme-linked immunosorbent assays, confocal immunofluorescence, gene silencing, flow cytometry, etc. In vivo efficacy and safety studies were conducted using (Non-obeseDiabetes/severe combined immune deficiency) SCID/NOD mice. Additionally, we collected clinical and prognostic data from 208 patients who underwent curative lung cancer resection between 2017 and 2018. RESULTS: We demonstrated that C-X-C motif chemokine ligand 5 (CXCL5) is markedly overexpressed in lung cancer cells and is positively correlated with a poor prognosis in patients with lung cancer. Mechanistically, CXCL5 activates the phosphorylation of the Paxillin/AKT signaling cascade, leading to upregulation of PD-L1 expression and the formation of a positive feedback loop. Moreover, CXCL5 attracts neutrophils, compromising CD8+ T cell-dependent antitumor immunity. These PD-L1+ neutrophils aggravate CD8+ T cell exhaustion following lung cancer domestication. Combined treatment with anti-CXCL5 and anti-PD-L1 antibodies significantly inhibits tumor growth in vivo. CONCLUSIONS: Our findings collectively demonstrate that CXCL5 promotes immune escape through PD-L1 upregulation in lung cancer and neutrophils chemotaxis through autocrine and paracrine mechanisms. CXCL5 may serve as a potential therapeutic target in synergy with ICBs in lung cancer immunotherapy.

Synthesis of a Co/Ni-MOF-74@PDI Z-scheme photocatalyst as a highly efficient photo-assisted Fenton-like catalyst for the removal of chlortetracycline hydrochloride.

In this paper, ultra-thin nanofiber PDI was obtained by self-assembly dispersion of commercial PDINH. A novel Co/Ni-MOF-74@PDI Z-scheme heterojunction photocatalyst material was constructed by a simple solvothermal method. XRD, SEM, TEM, FT-IR and other characterization techniques proved the successful preparation of the Co/Ni-MOF-74@PDI Z-scheme heterojunction photocatalyst material. By degrading chlortetracycline hydrochloride, it was found that the photocatalytic activity of Co/Ni-MOF-74@PDI was much higher than that of pure Co/Ni-MOF-74 and PDI. Subsequently, Co/Ni-MOF-74@PDI was used to activate H2O2 to further improve the degradation efficiency of chlortetracycline hydrochloride. It was found that the photocatalytic performance was greatly improved after the addition of 19.6 mM H2O2 to the system, and the degradation rate of chlortetracycline hydrochloride was 87% within 90 min. The electron transfer pathway and H2O2 activation mechanism of the Co/Ni-MOF-74@PDI composite photocatalyst were proved by free radical quenching experiments, electron paramagnetic resonance analysis and X-ray electron spectroscopy. Finally, the easy exfoliation point and degradation pathway of chlortetracycline hydrochloride were studied using density functional theory, UPLC-MS and toxicity evaluation software. It was found that the main active substances were h+, ˙O2, 1O2 and ˙OH, and the toxicity of chlortetracycline hydrochloride and its intermediates was evaluated.

Effects of high acyl gellan gum on the rheological properties, stability, and salt ion stress of sodium caseinate emulsion.

Sodium caseinate (SC) is widely used as a biological macromolecular emulsifier in oil-in-water (O/W) emulsions. However, the SC-stabilized emulsions were unstable. High-acyl gellan gum (HA) is an anionic macromolecular polysaccharide that improves emulsion stability. This study aimed to investigate the effects of HA addition on the stability and rheological properties of SC-stabilized emulsions. Study results revealed that HA concentrations >0.1 % could increase Turbiscan stability, reduce the volume average particle size, and increase the zeta-potential absolute value of the SC-stabilized emulsions. In addition, HA increased the triple-phase contact angle of SC, transformed SC-stabilized emulsions into non-Newtonian fluids, and effectively inhibited the movement of emulsion droplets. The effect of 0.125 % HA concentration was the most effective, allowing SC-stabilized emulsions to maintain good kinetic stability over a 30-d period. NaCl destabilized SC-stabilized emulsions but had no significant effect on HA-SC emulsions. In summary, HA concentration had a significant effect on the stability of SC-stabilized emulsions. HA altered the rheological properties and reduced creaming and coalescence by forming a three-dimensional network structure, increasing the electrostatic repulsion of the emulsion and the adsorption capacity of SC at the oil-water interface, and thereby improving the stability of SC-stabilized emulsions during storage and in the presence of NaCl.

Carbohydrate metabolism and cytology of S-type cytoplasmic male sterility in wheat.

Introduction: Cytoplasmic male sterility (CMS) is an important tool for hybrid heterosis utilization. However, the underlying mechanisms still need to be discovered. An adequate supply of nutrients is necessary for anther development; pollen abortion would occur if the metabolism of carbohydrates were hampered. Methods: In order to better understand the relationship between carbohydrate metabolism disorder and pollen abortion in S-CMS wheat, the submicroscopic structure of wheat anthers was observed using light microscopy and transmission electron microscopy; chloroplast proteome changes were explored by comparative proteomic analysis; sugar measuring and enzyme assays were performed; and the expression patterns of carbohydrate metabolism-related genes were studied using quantitative real-time PCR (qRT-PCR) method. Results: These results indicated that the anther and microspore in S-CMS wheat underwent serious structural damage, including premature tapetum degeneration, nutritional shortage, pollen wall defects, and pollen grain malformations. Furthermore, the number of chloroplasts in the anthers of S-CMS lines decreased significantly, causing abnormal carbohydrate metabolism, and disintegration of osmiophilic granules and thylakoids. Meanwhile, some proteins participating in the Calvin cycle and carbohydrate metabolism were abnormally expressed in the chloroplasts of the S-CMS lines, which might lead to chloroplast dysfunction. Additionally, several key enzymes and genes related to carbohydrate metabolism were significantly inhibited in S-CMS. Discussion: Based on these results, we proposed a carbohydrate metabolism pathway for anther abortion in S-type cytoplasmic male sterility, which would encourage further exploration of the pollen abortion mechanisms for CMS wheat.

Pan-mediastinal neoplasm diagnosis via nationwide federated learning: a multicentre cohort study.

BACKGROUND: Mediastinal neoplasms are typical thoracic diseases with increasing incidence in the general global population and can lead to poor prognosis. In clinical practice, the mediastinum's complex anatomic structures and intertype confusion among different mediastinal neoplasm pathologies severely hinder accurate diagnosis. To solve these difficulties, we organised a multicentre national collaboration on the basis of privacy-secured federated learning and developed CAIMEN, an efficient chest CT-based artificial intelligence (AI) mediastinal neoplasm diagnosis system. METHODS: In this multicentre cohort study, 7825 mediastinal neoplasm cases and 796 normal controls were collected from 24 centres in China to develop CAIMEN. We further enhanced CAIMEN with several novel algorithms in a multiview, knowledge-transferred, multilevel decision-making pattern. CAIMEN was tested by internal (929 cases at 15 centres), external (1216 cases at five centres and a real-world cohort of 11 162 cases), and human-AI (60 positive cases from four centres and radiologists from 15 institutions) test sets to evaluate its detection, segmentation, and classification performance. FINDINGS: In the external test experiments, the area under the receiver operating characteristic curve for detecting mediastinal neoplasms of CAIMEN was 0·973 (95% CI 0·969-0·977). In the real-world cohort, CAIMEN detected 13 false-negative cases confirmed by radiologists. The dice score for segmenting mediastinal neoplasms of CAIMEN was 0·765 (0·738-0·792). The mediastinal neoplasm classification top-1 and top-3 accuracy of CAIMEN were 0·523 (0·497-0·554) and 0·799 (0·778-0·822), respectively. In the human-AI test experiments, CAIMEN outperformed clinicians with top-1 and top-3 accuracy of 0·500 (0·383-0·633) and 0·800 (0·700-0·900), respectively. Meanwhile, with assistance from the computer aided diagnosis software based on CAIMEN, the 46 clinicians improved their average top-1 accuracy by 19·1% (0·345-0·411) and top-3 accuracy by 13·0% (0·545-0·616). INTERPRETATION: For mediastinal neoplasms, CAIMEN can produce high diagnostic accuracy and assist the diagnosis of human experts, showing its potential for clinical practice. FUNDING: National Key R&D Program of China, National Natural Science Foundation of China, and Beijing Natural Science Foundation.

Targeting sphingosine kinase 1/2 by a novel dual inhibitor SKI-349 suppresses non-small cell lung cancer cell growth.

Sphingosine kinase 1 (SphK1) and sphingosine kinase (SphK2) are both important therapeutic targets of non-small cell lung cancer (NSCLC). SKI-349 is a novel, highly efficient and small molecular SphK1/2 dual inhibitor. Here in primary human NSCLC cells and immortalized cell lines, SKI-349 potently inhibited cell proliferation, cell cycle progression, migration and viability. The dual inhibitor induced mitochondrial depolarization and apoptosis activation in NSCLC cells, but it was non-cytotoxic to human lung epithelial cells. SKI-349 inhibited SphK activity and induced ceramide accumulation in primary NSCLC cells, without affecting SphK1/2 expression. SKI-349-induced NSCLC cell death was attenuated by sphingosine-1-phosphate and by the SphK activator K6PC-5, but was potentiated by the short-chain ceramide C6. Moreover, SKI-349 induced Akt-mTOR inactivation, JNK activation, and oxidative injury in primary NSCLC cells. In addition, SKI-349 decreased bromodomain-containing protein 4 (BRD4) expression and downregulated BRD4-dependent genes (Myc, cyclin D1 and Klf4) in primary NSCLC cells. At last, SKI-349 (10 mg/kg) administration inhibited NSCLC xenograft growth in nude mice. Akt-mTOR inhibition, JNK activation, oxidative injury and BRD4 downregulation were detected in SKI-349-treated NSCLC xenograft tissues. Taken together, targeting SphK1/2 by SKI-349 potently inhibits NSCLC cell growth in vitro and in vivo.

Various Types of Negative Life Events Among Youth Predict Suicidal Ideation: A Cross-Sectional Study Based on Gender Perspective.

We sought to investigate potential gender differences in various types of negative life events and suicidal ideation among Chinese high school and university students, as well as to analyze the interrelations between different types of negative life events and suicidal ideation among these young students. Participants were 2,018 high school and university students from northwestern China, who completed a demographics questionnaire and self-report measures of negative life events and suicidal ideation. Significant gender differences emerged in the types of negative life events reported and in students' degree of suicidal ideation. Within each gender group, different types of negative life events were predictive of the intensity of suicidal ideation. The present study provides evidence of the role of negative life events in predicting adolescents' and young adults' suicidal ideation regardless of their gender. However, gender differences did emerge in the specific type of negative life events that were predictive of suicidal ideation. For males, greater reports of punishment and adaptation had a significant positive impact on the intensity of their suicidal ideation. For females, greater reports of academic stress, personal loss, interpersonal relationships, and adaptation were all significantly and positively predictive of their suicidal ideation. Parents' marital status emerged as a significant indicator of suicidal ideation across genders, while age was significant negative predictor of suicidal ideation among females only.

Nickel-catalysed migratory hydroalkynylation and enantioselective hydroalkynylation of olefins with bromoalkynes.

α-Chiral alkyne is a key structural element of many bioactive compounds, chemical probes, and functional materials, and is a valuable synthon in organic synthesis. Here we report a NiH-catalysed reductive migratory hydroalkynylation of olefins with bromoalkynes that delivers the corresponding benzylic alkynylation products in high yields with excellent regioselectivities. Catalytic enantioselective hydroalkynylation of styrenes has also been realized using a simple chiral PyrOx ligand. The obtained enantioenriched benzylic alkynes are versatile synthetic intermediates and can be readily transformed into synthetically useful chiral synthons.