MB38(M=Be and Zn): A Quasi-Planar Structure Rather Than A Core-Shell Octahedral Borospherene Structure.

In a recent paper (ChemPhysChem, 2023, 24, e202200947), based on the results computed using DFT method, the perfect core-shell octahedral configuration Be@B38 and Zn@B38 was reported to be the global minima of the MB38(M=Be and Zn) clusters. However, this paper presents the lower energy structures of MB38(M=Be and Zn) clusters as a quasi-planar configuration, the Be atom is found to reside on the convex surface of the quasi-planar B38 isomer, while the Zn atom tends to be attached to the top three B atoms of the quasi-planar B38 isomer. Our results show that quasi-planar MB38(M=Be and Zn) at DFT method have lower energy than core-shell octahedral configuration M@B38(M=Be and Zn). Natural atomic charges, valence electron density, electron localization function (ELF) analyses identify the MB38(M=Be and Zn) to be charge transfer complexes (Be2+B382-and Be1+B381-) and suggest primarily the electrostatic interactions between doped atom and B38 fragment. The photoelectron spectra of the corresponding anionic structures were simulated, providing theoretical basis for future structural identification.

In Vivo Activation of T-Cell Proliferation by Regulating Cell Surface Receptor Clustering Using a pH-Driven Interlocked DNA Nano-Spring.

Activation of T-cell proliferation specifically in a tumor is crucial for reducing the autoimmune side effects of antitumor immunotherapy. Herein, we developed a pH-driven interlocked DNA nano-spring (iDNS) to stimulate T-cell activation in vivo in response to the low pH value in a tumor microenvironment. The interlocked structure of iDNS provide a more rigid scaffold in comparison to double-stranded DNA for ligand assembly, which can help to control the spatial distribution of ligands with more accuracy. We have demonstrated that the pH-driven reversible reconfiguration of iDNS provides a powerful way to regulate the nanoscale distribution of T-cell receptors (CD3) on the cell surface. The relatively low pH value (pH 6.5) in a solid tumor was able to drive the springlike shrinking of iDNS and induce significant T-cell proliferation, leading to an enhanced antitumor effect, thus providing a tool for specifically inducing an immune response in a tumor for immunotherapy.

Supramolecular Assembly of Single-Tail ssDNA-Amphiphiles through π-π Interactions.

In this work, we demonstrate the formation of supramolecular architectures from the assembly of single-tail single stranded DNA (ssDNA)-amphiphiles. Short ssDNA sequences of 10 nucleotides that were either unstructured or formed G-quadruplex secondary structures were conjugated to a single 4-(hexadecyloxy)benzamide tail, either directly or through a polycarbon (C12) spacer. Conjugation of the ssDNA to the tail did not interfere with the G-quadruplex secondary structure of the ssDNA sequence. The ssDNA-amphiphiles self-assembled into ellipsoidal micelles, vesicles, nanotapes, and nanotubes. These nanotubes appeared to be formed by the rolling up of nanotapes. The increase of the hydrophobic block of the ssDNA-amphiphiles through the addition of a C12 spacer led to an increase in wall thickness and nanotube diameter. The presence of π-π interactions, through the benzoic group, was verified via X-ray diffraction (XRD) and played a critical role in the formation of the different nanostructures. In contrast, ssDNA-amphiphiles with a single heptadecanoic acid tail self-assembled only into ellipsoidal micelles.

Photoactivated Self-Disassembly of Multifunctional DNA Nanoflower Enables Amplified Autophagy Suppression for Low-Dose Photodynamic Therapy.

Low-dose photodynamic therapy (PDT) holds great promise for reducing undesired patient photosensitivity in cancer treatment. Yet, its therapeutic effect is significantly affected by intracellular cytoprotective processes, such as autophagy. Here, an efficient autophagy suppressor is developed, which is a multifunctional DNA nanoflower (DNF) consisted of tumor-targeting aptamers and DNAzymes for silencing autophagy-related genes, with surface modification of low-dose photosensitizer (Ce6). It is found that the multifunctional DNF can specifically target tumor cells and generate reactive oxygen species (ROS) under light irradiation to trigger self-disassembly of DNF, enhancing the bioavailability of encoded DNAzymes, leading to amplified autophagy suppression. As a facile spatiotemporally programmable photogene therapy platform, the designed DNF is able to suppress tumor growth in vivo with a very low injection dose of Ce6 (18 µg kg-1 , around 100 times lower than the generally applied dose), representing a promising strategy for cancer therapy with safely low-dose PDT.

Nanoenabled Intracellular Calcium Bursting for Safe and Efficient Reversal of Drug Resistance in Tumor Cells.

Multidrug resistance (MDR) of a tumor is the main cause of failure of clinical chemotherapy. Herein, we report a simple, yet versatile, tumor-targeting "calcium ion nanogenerator" (TCaNG) to reverse drug resistance by inducing intracellular Ca2+ bursting. Consequently, the TCaNG could induce Ca2+ bursting in acidic lysosomes of tumor cells and then reverse drug resistance according to the following mechanisms: (i) Ca2+ specifically accumulates in mitochondria, suppressing cellular respiration and relieving tumor hypoxia, thus inhibiting P-glycoprotein biosynthesis by downregulating HIF-1α expression. (ii) Ca2+-bursting-induced respiratory depression blocks intracellular ATP production, which further leads to the P-gp incompetence. As a result, the TCaNG could decrease the IC50 of DOX to MCF-7/ADR cells by approximately 30 times and reduce the proliferation of drug-resistant tumors by approximately 13 times without obvious side effects. This simple, safe, and effective "Ca2+ bursting" strategy holds the potential for clinical application in tumor treatment.

Janus Graft Block Copolymers: Design of a Polymer Architecture for Independently Tuned Nanostructures and Polymer Properties.

The graft-through synthesis of Janus graft block copolymers (GBCPs) from branched macromonomers composed of various combinations of homopolymers is presented. Self-assembly of GBCPs resulted in ordered nanostructures with ultra-small domain sizes down to 2.8 nm (half-pitch). The grafted architecture introduces an additional parameter, the backbone length, which enables control over the thermomechanical properties and processability of the GBCPs independently of their self-assembled nanostructures. The simple synthetic route to GBCPs and the possibility of using a variety of polymer combinations contribute to the universality of this technique.

Skeleton extraction and phase interpolation for single ESPI fringe pattern based on the partial differential equations.

A novel phase extraction method for single electronic speckle pattern interferometry (ESPI) fringes is proposed. The partial differential equations (PDEs) are used to extract the skeletons of the gray-scale fringe and to interpolate the whole-field phase values based on skeleton map. Firstly, the gradient vector field (GVF) of the initial fringe is adjusted by an anisotropic PDE. Secondly, the skeletons of the fringe are extracted combining the divergence property of the adjusted GVF. After assigning skeleton orders, the whole-field phase information is interpolated by the heat conduction equation. The validity of the proposed method is verified by computer-simulated and experimentally obtained poor-quality ESPI fringe patterns.

Rodent disturbance reduces ecosystem stability through regulating plant and soil functions in Hulun Buir steppe.

Brandt's vole (Lasiopodomys brandtii), a typical rodent in the eastern Eurasian Steppe, has unclear impacts on ecosystem stability. In our field study in the Hulun Buir steppe, a multifunctional grazing ecosystem in this region, we used burrow entrance area and burrow density as alternative disturbance indices to derive a Disturbance Index (DI) for quantifying disturbance levels from rodents, and employed generalized linear mixed-effects model and the N-dimensional hypervolume framework to assess the influence of Brandt's vole disturbance on plant and soil functions, and then on the ecosystem functional stability. Our findings unequivocally illustrate that various plant functions including vegetation cover (Cover), aboveground biomass (ABG) and shoot carbon (ShootC) significantly declined with increasing disturbance, while shoot nitrogen (ShootN) and root nitrogen (RootN) show significantly positive responses. Soil functions such as soil nitrogen (SoilN), soil phosphorus (SoilP) and soil organic carbon (SoilC) showed significantly negative responses. Notably, the burrow entrance area exerts a more pronounced impact on both plant and soil functions in comparison to burrow density. Additionally, both disturbance indicators have a more significant influence on plant functions than on soil functions. Overall, the ecosystem functional stability progressively decreases with intensified disturbance, with varying response patterns for plant and soil functions, the former exhibited heightened stability as disturbance intensified, while the latter proved more stable at moderate disturbance levels. Our findings suggest that plant functions were more susceptible to disturbance by Brandt's vole compared to soils. Additionally, an ecosystem destabilization was synchronized with increasing Brandt's vole disturbance, although alterations in the functional stability of plants and soil show a different pattern.

Effects of plant diversity and community structure on ecosystem multifunctionality under different grazing potentials in the eastern Eurasian steppe.

Grazing potential represents the potential carrying capacity of steppe livestock production. Understanding the impact of changes in plant diversity and community structure on ecosystem multifunctionality (EMF) at different grazing potentials is crucial for the sustainable management of steppe ecosystems. We examined the associations between plant diversity, community structure, above-ground ecosystem multifunctionality (AEMF), and below-ground ecosystem multifunctionality (BEMF) at various grazing potentials. Our assessment employed generalized linear mixed-effects models and structural equation models to determine the impact of these factors on ecosystem multifunctionality. Our study results indicated that ecosystem multifunctionality differed depending on the level of grazing potential and decreased as grazing potential declined. The impact of plant diversity and community structure on above- and below-ground ecosystem multifunctionality varied. Plant diversity and community structure correlated more with AEMF than BEMF. Plant diversity had the most significant effect on EMF under high grazing potential, while community structure had the greatest effect on EMF under moderate and low grazing potential. These improve our understanding of the correlation between steppe plant diversity, community structure, and above- and below-ground ecosystem multifunctionality. This understanding is necessary to develop strategies to increase plant diversity or regulate community structure and the sustainability of steppes.

Rapid response in relapsed follicular lymphoma to novel anti-CD19 CAR-T therapy with pseudo-progression and cytomegalovirus infection: A case report.

CD19-directed chimeric antigen receptor (CAR) T cell therapy has been shown to achieve a considerably durable response in patients with refractory or relapsed B cell non-Hodgkin lymphomas. Most of these CARs were generated by lentivirus. With the exception of Yescarta and Tecartus, few patients with relapsed-/refractory- lymphoma have been treated clinically with a CARs using retroviral vector (RV). Here, we reported a relapsed/refractory grade 2 follicular lymphoma patient with multiple chemotherapy failures, and was treated with a novel CD19 CAR-T cell manufactured from a RV. After tumor burden was reduced with Obinutuzumab and Duvelisib, the patient was infused novel CD19 CAR-T cells at a dose of 3 × 106 cells/ kg. Then he experienced a rapid response and achieved almost complete remission by day 26. Only grade 2 CRS, bilateral submaxillary lymph node enlargement and cytomegalovirus (CMV) infection occurred without neurotoxicity, and the patient's condition improved after a series of symptomatic treatments. In addition, CAR copy number peaked at 532,350 copies/µg on day 15 and continued to expand for 5 months. This may be the first case report of RV preparation of novel CD19 CAR-T cells for direct treatment of recurrent follicular lymphoma. We will observe its long-term efficacy and conduct trials in more patients in the future.

Comparison of the Efficacy Among Nilotinib, Dasatinib, Flumatinib and Imatinib in Newly Diagnosed Chronic-Phase Chronic Myeloid Leukemia Patients: A Real-World Multi-Center Retrospective Study.

BACKGROUND: There are limited data comprehensively comparing therapy responses and outcomes among nilotinib, dasatinib, flumatinib and imatinib for newly diagnosed chronic-phase chronic myeloid leukemia in a real-world setting. PATIENTS AND METHODS: Data from patients with chronic-phase CML receiving initial a second-generation tyrosine-kinase inhibitor (2G-TKI, nilotinib, dasatinib or flumatinib) or imatinib therapy from 77 Chinese centers were retrospectively interrogated. Propensity-score matching (PSM) analyses were performed to to compare therapy responses and outcomes among these 4 TKIs. RESULTS: 2,496 patients receiving initial nilotinib (n = 512), dasatinib (n = 134), flumatinib (n = 411) or imatinib (n = 1,439) therapy were retrospectively interrogated in this study. PSM analyses indicated that patients receiving initial nilotinib, dasatinib or flumatinib therapy had comparable cytogenetic and molecular responses (p = .28-.91) and survival outcomes including failure-free survival (FFS, p = .28-.43), progression-free survival (PFS, p = .19-.93) and overall survival (OS) (p values = .76-.78) but had significantly higher cumulative incidences of cytogenetic and molecular responses (all p values < .001) and higher probabilities of FFS (p < .001-.01) than those receiving imatinib therapy, despite comparable PFS (p = .18-.89) and OS (p = .23-.30). CONCLUSION: Nilotinib, dasatinib and flumatinib had comparable efficacy, and significantly higher therapy responses and higher FFS rates than imatinib in newly diagnosed CML patients. However, there were no significant differences in PFS and OS among these 4 TKIs. These real-world data may provide additional evidence for routine clinical assessments to identify more appropriate therapies.

Sand Burial, Rather than Salinity or Drought, Is the Main Stress That Limits the Germination Ability of Sophora alopecuroides L. Seed in the Desert Steppe of Yanchi, Ningxia, China.

Global change and environmental pollution have reawakened ecologists to the great threat of multi-stress interactions to different growth stages of plants. Sophora alopecuroides L., a dune plant, has been widely studied for its medicinal components and strong salinity tolerance. S. alopecuroides seeds, obtained from the desert steppe of Yanchi, Ningxia, China, were used to analyze the effects of sand burial, salinity, drought, and their interactions on seed germination (germination percentage, germination energy, and germination index). The results showed that sand burial and salinity stress had significant effects on the seed germination ability of S. alopecuroides, and drought stress had no significant effect, but the interaction of the three stresses had a significant effect. Under different drought-stress treatments, the interaction of no sand burial and a certain degree of salinity stress significantly improved the germination ability of S. alopecuroides, and the overall intensity of the effects of the three stresses showed that sand burial > salinity > drought. Considering the germination percentage, germination energy, and germination index of S. alopecuroides under various stress interactions, the treatment of no sand burial × 1% soil saline-alkali content × 18-20% soil water content was adopted to maximize the germination ability of S. alopecuroides. In the desert steppe area of Yanchi, Ningxia, sand burial stress was still the most limiting factor for seed germination of S. alopecuroides, and soil saline-alkali content should be increased moderately, and soil moisture should be ensured to obtain the best germination ability.

Stimuli-Responsive Self-Degradable DNA Hydrogels: Design, Synthesis, and Applications.

DNA hydrogels play an increasingly important role in biomedicine and bioanalysis applications. Due to their high programmability, multifunctionality and biocompatibility, they are often used as effective carriers for packing drugs, cells, or other bioactive cargoes in vitro and in vivo. However, the stability of the DNA hydrogels prevents their in-demand rapid release of cargoes to achieve a full therapeutic effect in time. For bioanalysis, the generation of signals sometimes needs the DNA hydrogel to be rapidly degraded when sensing target molecules. To meet these requirements, stimulus-responsive DNA hydrogels are designed. By responding to different stimuli, self-degradable DNA hydrogels can switch from gel to solution for quantitative bioanalysis and precision cargo delivery. This review summarizes the recently developed innovative methods for designing stimuli-responsive self-degradable DNA hydrogels and showed their applications in the bioanalysis and biomedicines fields. Challenges, as well as prospects, are also discussed.

Photoactivated DNA Nanodrugs Damage Mitochondria to Improve Gene Therapy for Reversing Chemoresistance.

Multidrug resistance (MDR) is a major cause of chemotherapy failure in oncology, and gene therapy is an excellent measure to reverse MDR. However, conventional gene therapy only modulates the expression of MDR-associated proteins but hardly affects their existing function, thus limiting the efficiency of tumor treatment. Herein, we designed a photoactivated DNA nanodrug (MCD@TMPyP4@DOX) to improve tumor chemosensitivity through the downregulation of MDR-related genes and mitochondria-targeted photodynamic therapy (PDT). The self-assembled DNA nanodrug encodes the mucin 1 (MUC1) aptamer and the cytochrome C (CytC) aptamer to facilitate its selective targeting to the mitochondria in tumor cells; the encoded P-gp DNAzyme can specifically cleave the substrate and silence MDR1 mRNA with the help of Mg2+ cofactors. Under near-infrared (NIR) light irradiation, PDT generates reactive oxygen species (ROS) that precisely damage the mitochondria of tumor cells and break single-stranded DNA (ssDNA) to activate MCD@TMPyP4@DOX self-disassembly for release of DOX and DNAzyme. We have demonstrated that this multifunctional DNA nanodrug has high drug delivery capacity and biosafety. It enables downregulation of P-gp expression while reducing the ATP on which P-gp pumps out drugs, improving the latency of gene therapy and synergistically reducing DOX efflux to sensitize tumor chemotherapy. We envision that this gene-modulating DNA nanodrug based on damaging mitochondria is expected to provide an important perspective for sensitizing tumor chemotherapy.

Enrichment and sensing tumor cells by embedded immunomodulatory DNA hydrogel to inhibit postoperative tumor recurrence.

Postoperative tumor recurrence and metastases often lead to cancer treatment failure. Here, we develop a local embedded photodynamic immunomodulatory DNA hydrogel for early warning and inhibition of postoperative tumor recurrence. The DNA hydrogel contains PDL1 aptamers that capture and enrich in situ relapsed tumor cells, increasing local ATP concentration to provide a timely warning signal. When a positive signal is detected, local laser irradiation is performed to trigger photodynamic therapy to kill captured tumor cells and release tumor-associated antigens (TAA). In addition, reactive oxygen species break DNA strands in the hydrogel to release encoded PDL1 aptamer and CpG, which together with TAA promote sufficient systemic antitumor immunotherapy. In a murine model where tumor cells are injected at the surgical site to mimic tumor recurrence, we find that the hydrogel system enables timely detection of tumor recurrence by enriching relapsed tumor cells to increase local ATP concentrations. As a result, a significant inhibitory effect of approximately 88.1% on recurrent tumors and effectively suppressing metastasis, offering a promising avenue for timely and effective treatment of postoperative tumor recurrence.

Chinese expert consensus on the management of patients with hematologic malignancies infected with SARS-CoV-2.

In December 2022, the Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) became dominant in China due to its high infectivity and lower mortality rate. The risk of critical illness and mortality among patients with hematologic malignancies who contracted SARS-CoV-2 was particularly high. The aim of this study was to draft a consensus to facilitate effective treatments for these patients based on the type and severity of the disease. Following the outbreak of the novel coronavirus in China, a steering committee consisting of experienced hematologists was formed by the Specialized Committee of Oncology and Microecology of the Chinese Anti-Cancer Association. The expert group drafted a consensus on the management and intervention measures for different types of hematologic malignancies based on the clinical characteristics of the Omicron variant of the SARS-CoV-2 infection, along with relevant guidelines and literature. The expert group drafted independent recommendations on several important aspects based on the epidemiology of the Omicron variant in China and the unique vulnerability of patients with hematologic malignancies. These included prophylactic vaccinations for those with hematologic malignancies, the use of plasma from blood donors who recovered from the novel coronavirus infection, the establishment of negative pressure wards, the use of steady-state mobilization of peripheral blood hematopoietic stem cells, the provision of psychological support for patients and medical staff, and a focus on maintaining a healthy intestinal microecology.

Global assessment of the distribution and conservation status of a key medicinal plant (Artemisia annua L.): The roles of climate and anthropogenic activities.

As a medicinal plant, Artemisia annua L. is the main source of artemisinin in malaria drugs, but the lack of understanding of its distribution, environmental conditions and protection status limits the mass acquisition of artemisinin. Therefore, we used the ensemble forecast method to model the current and future global distribution areas of A. annua, evaluated the changes in suitable distribution areas on each continent under impacts of human activities and climate change, and its protection status on each continent in the corresponding period. The results showed that the main distribution areas of A. annua were concentrated in mid-latitudes in western and central Europe, southeastern Asia, southeastern North America and southeastern South America. Under the current climate scenario, human modifications have greatly reduced the suitable distribution area of A. annua, which was projected to expand inland with climate change and human socioeconomic impacts of CMIP6 in the future, but the effects of increasing temperature were different in different periods. Among all continents, the suitable distribution area in Europe was the most affected. However, at present and in the future, A. annua needs high priority protection on all continents. Asia and Europe have slightly better protection status scores than other continents, but the protection status scores of all continents are still very low. Our findings can be useful to guide development of protective measures for medicinal plants such as A. annua to further support drug production and disease treatment.

A Localized Enantioselective Catalytic Site on Short DNA Sequences and Their Amphiphiles.

A DNA-based artificial metalloenzyme (ArM) consisting of a copper(II) complex of 4,4'-dimethyl-2,2'-bipyridine (dmbipy-Cu) bound to double-stranded DNA (dsDNA) as short as 8 base pairs with only 2 contiguous central pairs (G for guanine and C for cytosine) catalyzes the highly enantioselective Diels-Alder reaction, Michael addition, and Friedel-Crafts alkylation in water. Molecular simulations indicate that these minimal sequences provide a single site where dmbipy-Cu is groove-bound and able to function as an enantioselective catalyst. Enantioselective preference inverts when d-DNA is replaced with l-DNA. When the DNA is conjugated to a hydrophobic tail, the obtained ArMs exhibit enantioselective performance in a methanol-water mixture superior to that of non-amphiphilic dsDNA, and dsDNA-amphiphiles with more complex G•C-rich sequences.

Photocontrolled Spatiotemporal Delivery of DNA Immunomodulators for Enhancing Membrane-Targeted Tumor Photodynamic Immunotherapy.

Immunotherapy is emerging as a paradigm-shifting modality for treatment cancer. However, systemic administration of immunomodulators is usually accompanied by extra-tumor toxicity and adverse immune effects. Precise delivery of immunomodulators with a highly controllable system may provide a solution for this issue. Here, we developed a photocontrolled DNA nanomedicine for localized delivery of DNA immunomodulators to enhance membrane-targeted photodynamic immunotherapy. Specifically, the DNA nanomedicine is composed of long tandemly repeated functional DNA sequences (PDL1 aptamers and CpG) with a photosensitizer (TMPyP4) inserted into the DNA structure, providing high drug-loading capacity. By blocking the surface PDL1 aptamer with a pHLIP-modified cDNA, the DNA nanomedicine does not induce any obvious immune response and can be specifically delivered and anchored to the tumor membrane. Under localized irradiation, photodynamically generated reactive oxygen species (ROS) causes breakage of DNA sequences, which triggers the collapse of the nanostructure and release of internal DNA immunomodulators. Under localized illumination, photodynamically generated ROS can cause DNA sequence breaks, triggering the collapse of nanostructures and the release of internal DNA immunomodulators thus enhancing membrane-targeted photodynamic immunotherapy. We have demonstrated that the developed DNA nanomedicine can drive efficient immune responses in tumor tissue without perceptibly interfering off-tumor immunity, resulting in efficient antitumor treatment while mitigating systemic toxicity.