High harmonic generation driven by femtosecond lasers makes it possible to capture the fastest dynamics in molecules and materials. However, to date the shortest subfemtosecond (attosecond, 10 ⁻¹⁸ s) ...pulses have been produced only in the extreme UV region of the spectrum below 100 eV, which limits the range of materials and molecular systems that can be explored. Here we experimentally demonstrate a remarkable convergence of physics: when midinfrared lasers are used to drive high harmonic generation, the conditions for optimal bright, soft X-ray generation naturally coincide with the generation of isolated attosecond pulses. The temporal window over which phase matching occurs shrinks rapidly with increasing driving laser wavelength, to the extent that bright isolated attosecond pulses are the norm for 2-µm driving lasers. Harnessing this realization, we experimentally demonstrate the generation of isolated soft X-ray attosecond pulses at photon energies up to 180 eV for the first time, to our knowledge, with a transform limit of 35 attoseconds (as), and a predicted linear chirp of 300 as . Most surprisingly, advanced theory shows that in contrast with as pulse generation in the extreme UV, long-duration, 10-cycle, driving laser pulses are required to generate isolated soft X-ray bursts efficiently, to mitigate group velocity walk-off between the laser and the X-ray fields that otherwise limit the conversion efficiency. Our work demonstrates a clear and straightforward approach for robustly generating bright isolated attosecond pulses of electromagnetic radiation throughout the soft X-ray region of the spectrum.
We analyzed the number of circulating tumor cells (CTCs) and Epstein–Barr virus DNA (EBV DNA) for diagnosis, monitoring and prognosis of patients with metastatic nasopharyngeal carcinoma (mNPC). The ...levels of CTCs and EBV DNA were measured at baseline and after first‐line chemotherapy in 148 mNPC patients prospectively enrolled between December 2014 and August 2016. We also collected 122 non‐mNPC cases within the same time frame for examining CTCs and EBV DNA at baseline. In 270 NPC patients, we observed improved specificity (86.0% vs. 41.0%) and inferior sensitivity (42.3% vs. 81.3%) of CTCs as compared to EBV DNA for diagnosis of distant metastasis. mNPC patients were stratified into unfavorable and favorable prognostic groups, respectively, based on CTC of 12 at baseline and 1 after first‐line chemotherapy and EBV DNA of 10,000 at baseline and 4,000 after first‐line chemotherapy. Conversion of baseline unfavorable CTCs and EBV DNA to favorable after first‐line chemotherapy was associated with significantly longer progression‐free survival (PFS) and overall survival (OS) compared to patients with unfavorable CTCs and EBV DNA at both time points. Among patients with a complete/partial response as per imaging evaluation, favorable CTCs and EBV DNA levels after first‐line chemotherapy were associated with significantly longer PFS and OS. In conclusion, our data demonstrated the number of CTCs and EBV DNA before, after and during first‐line chemotherapy were strong predictive markers for mNPC patients. When utilized in conjunction with imaging studies, CTCs and EBV DNA could provide additional prognostic information.
What's new?
Endemic nasopharyngeal carcinoma (NPC) is associated with latent infection of the oncogenic Epstein‐Barr virus (EBV) and frequently metastasizes to distant lymph nodes and organs. Metastatic NPC is treated by serial administration of cytotoxic or targeted therapies and treatment response is generally assessed with serial imaging, which often fails to detect changes in tumor burden. Here, the authors show that the number of circulating tumor cells (CTCs) and EBV DNA levels before, after, and during first‐line chemotherapy are strong predictive markers for mNPC patients. When utilized in conjunction with imaging studies, CTCs and EBV DNA could provide additional prognostic information.
Architectural and civil engineering (ACE) education is inextricably connected to real-world practice. The application of augmented reality (AR) technology can help to establish a link between virtual ...and real-world information for students. Studies of applying AR in ACE education have increased annually, and numerous research have indicated that AR possesses immense application potential. To address and analyze pertinent research issues, published studies in the Scopus database were explored, and revealed that problems persist and are worthy of attention, such as the selection of system types and devices, the application of research methods, and appropriate learning strategies and teaching methods. Courses with objective grading standards should be given priority in AR experimental courses for a meticulous investigation of AR influence on students’ learning outcomes and ultimately improvement of classroom quality. Suitable types of AR systems should be selected based on course content, prior to the design and development of the system. It is recommended to develop markerless systems for a larger application range to benefit students with additional convenience. Systems can also be accompanied by functions, such as instant online assessments, synchronized assessments, and exchange capabilities to assist learning what has been taught and develop critical thinking abilities. The combination of AR and building information modeling (BIM) in architectural and civil practice, which has immense application potential, has become an emerging research trend. Collaboration between academics and practice should be enhanced with roles and knowledge of instructors, engineers, designers, and computer experts integrated for an optimal connection between general pedagogy and domain-specific learning. Teaching methods that emphasize “locations”, as well as “roles”, can be adopted in order to create a superior reality learning environment with diversified learning methods. The trends and research have become an integration and collaboration issue that should be performed interactively with pedagogical findings, and resources integrated across roles, fields, and university departments.
In most species, homologous chromosomes must recombine in order to segregate accurately during meiosis
. Because small chromosomes would be at risk of missegregation if recombination were randomly ...distributed, the double-strand breaks (DSBs) that initiate recombination are not located arbitrarily
. How the nonrandomness of DSB distributions is controlled is not understood, although several pathways are known to regulate the timing, location and number of DSBs. Meiotic DSBs are generated by Spo11 and accessory DSB proteins, including Rec114 and Mer2, which assemble on chromosomes
and are nearly universal in eukaryotes
. Here we demonstrate how Saccharomyces cerevisiae integrates multiple temporally distinct pathways to regulate the binding of Rec114 and Mer2 to chromosomes, thereby controlling the duration of a DSB-competent state. The engagement of homologous chromosomes with each other regulates the dissociation of Rec114 and Mer2 later in prophase I, whereas the timing of replication and the proximity to centromeres or telomeres influence the accumulation of Rec114 and Mer2 early in prophase I. Another early mechanism enhances the binding of Rec114 and Mer2 specifically on the shortest chromosomes, and is subject to selection pressure to maintain the hyperrecombinogenic properties of these chromosomes. Thus, the karyotype of an organism and its risk of meiotic missegregation influence the shape and evolution of its recombination landscape. Our results provide a cohesive view of a multifaceted and evolutionarily constrained system that allocates DSBs to all pairs of homologous chromosomes.
•Two novel zinc complexes were synthesized with the same dicarboxylate and different bis-imidazole as co-ligand.•SNUT-7 exhibits 2D→2D twofold interpenetrating framework.•SNUT-8 exhibits a ...2D + 2D → 3D framework structure.•Their photoluminescence properties and photocatalytic performance were also investigated.
Two novel Zn(II) coordination polymers, { Zn(µ-HBCPT)(µ-1,3-BIP)·2H2O·DMF}n (SNUT-7) and { Zn2(µ3-BCPT)(HCOO)(µ-1,3-BMIP)2n (SNUT-8), where 1,3-BIP is a 1,3-bis(1H-imidazol-1-yl)propane, 1,3-BMIP is 1,3-bis(2-methyl-1H-imidazol-1-yl)propane, H3BCPT is 3,5-bis(4′-carboxy-phenyl)-1,2,4-triazole and formate (HCOO−) ligands, were prepared under solvothermal conditions and characterized by single-crystal and powder X-ray diffraction, IR spectra, thermogravimetric analysis and elemental analysis. SNUT-7 exhibits a 2D → 2D interspersed with each other, which can be further expanded into 3D supramolecule through hydrogen bonds. SNUT-8 exhibits a rare 2D + 2D → 3D framework structure. SNUT-7 and SNUT-8 are efficient and universal photocatalysts for the degradation of organic dye rhodamine B (Rh B) under visible light irradiation. The degradation of SNUT-7 and SNUT-8 are near ∼82.79% and ∼68%. SNUT-7 and SNUT-8 also show stronger blue light emission than the H3BCPT ligand. At room temperature, SNUT-7 and SNUT-8 have the highest emission peaks at 371 and 363 nm upon excitation at 360 and 290 nm.
The poor efficiency and low immunogenicity of photodynamic therapy (PDT), and the immunosuppressive tumor microenvironment (ITM) lead to tumor recurrence and metastasis. In this work, TCPP‐TER‐Zn@RSV ...nanosheets (TZR NSs) that co‐assembled from the endoplasmic reticulum (ER)‐targeting photosensitizer TCPP‐TER‐Zn nanosheets (TZ NSs for short) and the autophagy promoting and indoleamine‐(2, 3)‐dioxygenase (IDO) inhibitor‐like resveratrol (RSV) are fabricated to enhance antitumor PDT. TZR NSs exhibit improved therapeutic efficiency and amplified immunogenic cancer cell death (ICD) by ER targeting PDT and ER autophagy promotion. TZR NSs reversed the ITM with an increase of CD8+ T cells and reduce of immunosuppressive Foxp3 regulatory T cells, which effectively burst antitumor immunity thus clearing residual tumor cells. The ER‐targeting TZR NSs developed in this paper presents a simple but valuable reference for high‐efficiency tumor photodynamic immunotherapy.
TCPP‐TER‐Zn@RSV nanosheets (TZR NSs) exhibit excellent tumor‐killing effect by precisely targeting the endoplasmic reticulum (ER) and generating reactive oxygen species (ROS) in situ, promoting oxidative stress to induce lethal ER‐phagy and induce strong immunogenic cancer cell death (ICD) effects, which promotes the maturation of dendritic cells (DCs) in vitro and in vivo. TZR NSs regulate abundance of T cells in the tumor microenvironment (TME) and evoked T cells‐mediated immune responses, thereby significantly enhancing antitumor efficacy.
A concise asymmetric total synthesis of (−)‐quinocarcin has been accomplished with high step economy from commercially available starting materials. A catalytic enantioselective reductive 1,3‐dipolar ...cycloaddition reaction of N‐heteroaryl secondary amides with reactive dipolarophiles using iridium/copper relay catalysis was developed to prepare the key chiral pyrrolidine intermediate with three stereocenters. This protocol features excellent regio‐, exo‐ and enantioselectivities, broad substrate scope, and good functional group tolerance. The high efficiency was also ensured by a RhIII‐catalyzed C−H activation/cyclization and a tandem diastereoselective hydrogenation/cyclization to construct the tetrahydroisoquinoline‐pyrrolidine tetracyclic core unit of quinocarcin.
A concise asymmetric total synthesis of (−)‐quinocarcin has been accomplished with high step economy. A catalytic enantioselective reductive 1,3‐dipolar cycloaddition reaction of secondary amides using iridium/copper relay catalysis was developed to prepare the key chiral pyrrolidine intermediate with three stereocenters. This protocol features excellent enantioselectivity, broad substrate scope, and good functional group tolerance.
The immunosuppressive microenvironment that is shaped by hepatic metastatic pancreatic ductal adenocarcinoma (PDAC) is essential for tumor cell evasion of immune destruction. Neutrophils are ...important components of the metastatic tumor microenvironment and exhibit heterogeneity. However, the specific phenotypes, functions and regulatory mechanisms of neutrophils in PDAC liver metastases remain unknown. Here, we show that a subset of P2RX1-negative neutrophils accumulate in clinical and murine PDAC liver metastases. RNA sequencing of murine PDAC liver metastasis-infiltrated neutrophils show that P2RX1-deficient neutrophils express increased levels of immunosuppressive molecules, including PD-L1, and have enhanced mitochondrial metabolism. Mechanistically, the transcription factor Nrf2 is upregulated in P2RX1-deficient neutrophils and associated with PD-L1 expression and metabolic reprogramming. An anti-PD-1 neutralizing antibody is sufficient to compromise the immunosuppressive effects of P2RX1-deficient neutrophils on OVA-activated OT1 CD8+ T cells. Therefore, our study uncovers a mechanism by which metastatic PDAC tumors evade antitumor immunity by accumulating a subset of immunosuppressive P2RX1-negative neutrophils.
Ni-rich cathode materials always suffer from surface lithium residues mainly caused by the reduction of Ni3+ to Ni2+ when exposing to moisture, and severe side reactions between organic electrolyte ...and highly active Ni4+ when fully charged. An appropriate amount of NH4H2PO4 is firstly coated on the hydroxide precursor Ni0.815Co0.15Al0.035(OH)2 before mixing with Li2CO3. The NH4H2PO4 can react with the lithium residues and form a uniform Li3PO4 coating layer. X-ray diffraction, scanning electron microscopy, field emission transmission electron microscopy and element mapping are employed to investigate the Li3PO4 coating layer. Electrochemical measurements results show that the cycle stability of the synthesized LiNi0.815Co0.15Al0.035O2 both at room temperature and 55 °C has been significantly improved. Its thermal stability has also been greatly enhanced.
•NH4H2PO4 can remove lithium residues and form a uniform Li3PO4 coating layer.•Porous Li3PO4 coating layer suppresses side reactions.•The thermal stability of Ni-rich cathode materials can be significantly enhanced.
The imino‐Nazarov cyclization of the polysubstituted pentan‐1,4‐diene‐3‐imines was realized. To this aim, a one‐pot procedure involving reductive alkenyliminylation of α,β‐unsaturated secondary ...amides with potassium organotrifluoroborates, followed by acid‐catalyzed imino‐Nazarov cyclization of the polysubstituted pentan‐1,4‐diene‐3‐imine intermediates, was studied systematically. This mild, operationally simple, flexible, and high‐yielding protocol efficiently affords polysubstituted pentan‐1,4‐diene‐3‐imines, cyclopentenimines, and α‐amino cyclopentenones, which are useful scaffolds in organic synthesis. The substituent effect at the C2 position of the polysubstituted pentan‐1,4‐diene‐3‐imines was studied by means of density‐functional theory calculations. Results suggested that the electron‐donating group facilitates the imino‐Nazarov cyclization process.
An imino‐Nazarov cyclization of polysubstituted pentan‐1,4‐diene‐3‐imines (3) to prepare polysubstituted cyclopentenimines (4) was studied, and features a one‐pot procedure of reductive alkenyliminylation of α,β‐unsaturated secondary amides (1) with potassium organotrifluoroborates, and acid‐catalyzed 4π electrocyclization of 3.
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