Immunotherapy, represented by immune checkpoint inhibitors (ICIs), has greatly improved the clinical efficacy of malignant tumor therapy. ICI-mediated antitumor responses depend on the infiltration ...of T cells capable of recognizing and killing tumor cells. ICIs are not effective in "cold tumors", which are characterized by the lack of T-cell infiltration. To realize the full potential of immunotherapy and solve this obstacle, it is essential to understand the drivers of T-cell infiltration into tumors. We present a critical review of our understanding of the mechanisms underlying "cold tumors", including impaired T-cell priming and deficient T-cell homing to tumor beds. "Hot tumors" with significant T-cell infiltration are associated with better ICI efficacy. In this review, we summarize multiple strategies that promote the transformation of "cold tumors" into "hot tumors" and discuss the mechanisms by which these strategies lead to increased T-cell infiltration. Finally, we discuss the application of nanomaterials to tumor immunotherapy and provide an outlook on the future of this emerging field. The combination of nanomedicines and immunotherapy enhances cross-presentation of tumor antigens and promotes T-cell priming and infiltration. A deeper understanding of these mechanisms opens new possibilities for the development of multiple T cell-based combination therapies to improve ICI effectiveness.
Artificial intelligence (AI) is a new technical discipline that uses computer technology to research and develop the theory, method, technique, and application system for the simulation, extension, ...and expansion of human intelligence. With the assistance of new AI technology, the traditional medical environment has changed a lot. For example, a patient’s diagnosis based on radiological, pathological, endoscopic, ultrasonographic, and biochemical examinations has been effectively promoted with a higher accuracy and a lower human workload. The medical treatments during the perioperative period, including the preoperative preparation, surgical period, and postoperative recovery period, have been significantly enhanced with better surgical effects. In addition, AI technology has also played a crucial role in medical drug production, medical management, and medical education, taking them into a new direction. The purpose of this review is to introduce the application of AI in medicine and to provide an outlook of future trends.
Most ABC transporters are engaged in transport of various compounds, but its subfamily F lacks transmembrane domain essential for chemical transportation. Thus the function of subfamily F remains ...further elusive.
Here, we identified General Control Non-Repressible 20 (GCN20), a member of subfamily F, as new factor for DNA damage repair in root growth. While gcn20-1 mutant had a short primary root with reduced meristem size and cell number, similar primary root lengths were assayed in both wild-type and GCN20::GCN20 gcn20-1 plants, indicating the involvement of GCN20 in root elongation. Further experiments with EdU incorporation and comet assay demonstrated that gcn20-1 displays increased cell cycle arrest at G2/M checkpoint and accumulates more damaged DNA. This is possible due to impaired ability of DNA repair in gcn20-1 since gcn20-1 seedlings are hypersensitive to DNA damage inducers MMC and MMS compared with the wild type plants. This note was further supported by the observation that gcn20-1 is more sensitive than the wild type when subjected to UV treatment in term of changes of both fresh weight and survival rate.
Our study indicates that GCN20 functions in primary root growth by modulating DNA damage repair in Arabidopsis. Our study will be useful to understand the functions of non-transporter ABC proteins in plant growth.
ABSTRACT
Ammonium-oxidizing archaea (AOA) and bacteria (AOB) play crucial roles in ammonium oxidation in freshwater lake sediment. However, previous reports on the predominance of AOA and AOB in the ...surface sediment of Lake Taihu have been based on DNA levels, detecting the total abundance of microbiota (including inactive cells), and have resulted in numerous contradictory conclusions. Existing RNA-level studies detecting active transcription are very limited. The current study, using RNA-based real-time quantification and clone library analysis, demonstrated that the amoA gene abundance of active AOB was higher than that of active AOA, despite conflicting results at the DNA level. Further exploration revealed a significant positive correlation between the potential nitrification rate (PNR) and the abundance of AOA and AOB at the RNA level, with irregular or contradictory correlation found at the DNA level. Ultimately, using quantitative analysis of RNA levels, we show AOB to be the active dominant contributor to ammonium oxidation. Our investigations also indicated that AOB were more diverse in high-ammonium lake regions, with Nitrosomonas being the active and dominating cluster, but that AOA had an advantage in the low-ammonium lake regions.
The quantification study of amoA gene based on the RNA level was performed on the surface sediment of Lake Taihu, and suggests that active ammonium-oxidizing bacteria are the dominant ammonia oxidizer.
Herein, we highlight redox‐inert Zn2+ in spinel‐type oxide (ZnXNi1−XCo2O4) to synergistically optimize physical pore structure and increase the formation of active species on the catalyst surface. ...The presence of Zn2+ segregation has been identified experimentally and theoretically under oxygen‐evolving condition, the newly formed VZn−O−Co allows more suitable binding interaction between the active center Co and the oxygenated species, resulting in superior ORR performance. Moreover, a liquid flow Zn–air battery is constituted employing the structurally optimized Zn0.4Ni0.6Co2O4 nanoparticles supported on N‐doped carbon nanotube (ZNCO/NCNTs) as an efficient air cathode, which presents remarkable power density (109.1 mW cm−2), high open circuit potential (1.48 V vs. Zn), excellent durability, and high‐rate performance. This finding could elucidate the experimentally observed enhancement in the ORR activity of ZnXNi1−XCo2O4 oxides after the OER test.
The outstanding electrocatalytic performance of Zn0.4Ni0.6Co2O4/NCNTs towards ORR/OER is validated, presenting remarkable rate capability and durability in liquid‐flow Zn–air batteries. A dual‐reinforcement mechanism in the Zn–Ni–Co ternary spinel is also proposed. Zn0.4Ni0.6Co2O4/NCNTs exhibits extreme durability and electrochemically enhanced properties, enabling its application in practical rechargeable zinc–air batteries.
DNA methylation is a crucial regulator of gene transcription in the etiology and pathogenesis of hepatocellular carcinoma (HCC). Thus, it is reasonable to identify DNA methylation‐related prognostic ...markers. Currently, we aimed to make an integrative epigenetic analysis of HCC to identify the effectiveness of epigenetic drivers in predicting prognosis for HCC patients. By the software pipeline TCGA‐Assembler 2, RNA‐seq, and methylation data were downloaded and processed from The Cancer Genome Atlas. A bioconductor package MethylMix was utilized to incorporate gene expression and methylation data on all 363 samples and identify 589 epigenetic drivers with transcriptionally predictive. By univariate survival analysis, 72 epigenetic drivers correlated with overall survival (OS) were selected for further analysis in our training cohort. By the robust likelihood‐based survival model, six epi‐drivers (doublecortin domain containing 2, flavin containing monooxygenase 3, G protein‐coupled receptor 171, Lck interacting transmembrane adaptor 1, S100 calcium binding protein P, small nucleolar RNA host gene 6) serving as prognostic markers was identified and then a DNA methylation signature for HCC (MSH) predicting OS was identified to stratify patients into low‐risk and high‐risk groups in the training cohort (p < 0.001). The capability of MSH was also assessed in the validation cohort (p = 0.002). Furthermore, a receiver operating characteristic curve confirmed MSH as an effective prognostic model for predicting OS in HCC patients in training area under curve (AUC = 0.802) and validation (AUC = 0.691) cohorts. Finally, a nomogram comprising MSH and pathologic stage was generated to predict OS in the training cohort, and it also operated effectively in the validation cohort (concordance index: 0.674). In conclusion, MSH, a six epi‐drivers based signature, is a potential model to predict prognosis for HCC patients.
In this study, we identified a DNA methylation signature for hepatocellular carcinoma (HCC), a six epi‐drivers based signature, could act as a potential model to predict prognosis for HCC patients.
Leeches are classic annelids that have a huge diversity and are closely related to people, especially medicinal leeches. Medicinal leeches have been widely utilized in medicine based on the ...pharmacological activities of their bioactive ingredients. Comparative genomic study of these leeches enables us to understand the difference among medicinal leeches and other leeches and facilitates the discovery of bioactive ingredients.
In this study, we reported the genome of Whitmania pigra and compared it with Hirudo medicinalis and Helobdella robusta. The assembled genome size of W. pigra is 177 Mbp, close to the estimated genome size. Approximately about 23% of the genome was repetitive. A total of 26,743 protein-coding genes were subsequently predicted. W. pigra have 12346 (46%) and 10295 (38%) orthologous genes with H. medicinalis and H. robusta, respectively. About 20 and 24% genes in W. pigra showed syntenic arrangement with H. medicinalis and H. robusta, respectively, revealed by gene synteny analysis. Furthermore, W. pigra, H. medicinalis and H. robusta expanded different gene families enriched in different biological processes. By inspecting genome distribution and gene structure of hirudin, we identified a new hirudin gene g17108 (hirudin_2) with different cysteine patterns. Finally, we systematically explored and compared the active substances in the genomes of three leech species. The results showed that W. pigra and H. medicinalis exceed H. robusta in both kinds and gene number of active molecules.
This study reported the genome of W. pigra and compared it with other two leeches, which provides an important genome resource and new insight into the exploration and development of bioactive molecules of medicinal leeches.
The development of drug-resistance in the opportunistic pathogen
has become a global public health concern. Due to the share of similar flora between pets and their owners, the detection of ...pet-origin antibiotic-resistant
is necessary. This study aimed to detect the prevalence of feline-origin ESBL
in China and to explore the resistance elimination effect of garlic oil to cefquinome on ESBL
. Cat fecal samples were collected from animal hospitals. The
isolates were separated and purified by indicator media and polymerase chain reaction (PCR). ESBL genes were detected by PCR and Sanger sequencing. The MICs were determined. The synergistic effect of garlic oil and cefquinome against ESBL
was investigated by checkerboard assays, time-kill and growth curves, drug-resistance curves, PI and NPN staining, and a scanning electronic microscope. A total of 80
strains were isolated from 101 fecal samples. The rate of ESBL
was 52.5% (42/80). The prevailing ESBL genotypes in China were
,
, and
. In ESBL
, garlic oil increased the susceptibility to cefquinome with FICIs from 0.2 to 0.7 and enhanced the killing effect of cefquinome with membrane destruction. Resistance to cefquinome decreased with treatment of garlic oil after 15 generations. Our study indicates that ESBL
has been detected in cats kept as pets. The sensitivity of ESBL
to cefquinome was enhanced by garlic oil, indicating that garlic oil may be a potential antibiotic enhancer.
Transition‐metal oxides as electrocatalysts for the oxygen evolution reaction (OER) provide a promising route to face the energy and environmental crisis issues. Although palmeirite oxide A2Mo3O8 as ...OER catalyst has been explored, the correlation between its active sites (tetrahedral or octahedral) and OER performance has been elusive. Now, magnetic Co2Mo3O8@NC‐800 composed of highly crystallized Co2Mo3O8 nanosheets and ultrathin N‐rich carbon layer is shown to be an efficient OER catalyst. The catalyst exhibits favorable performance with an overpotential of 331 mV@10 mA cm−2 and 422 mV@40 mA cm−2, and a full water‐splitting electrolyzer with it as anode catalyst shows a cell voltage of 1.67 V@10 mA cm−2 in alkaline. Combined HAADFSTEM, magnetic, and computational results show that factors influencing the OER performance can be attributed to the tetrahedral Co sites (high spin, t23e4), which improve the OER kinetics of rate‐determining step to form *OOH.
Magnetic Co2Mo3O8@NC‐800 composed of single‐crystal Co2Mo3O8 and ultrathin nitrogen‐rich carbon was synthesized to uncover its OER active sites (Td Co2+ or Oh Co2+). Electrochemical data, magnetism data, and computations suggest that the Td Co2+ atoms (high spin, t23e4) in Co2Mo3O8 act as active sites facilitating the rate‐determining step, forming *OOH to promote the reaction kinetics for OER.
In recent years, interest in sulfoximine chemistry has been greatly increased. For example, at least three sulfoximine containing drugs BAY 1143572, BAY 1251152 and AZD6738 have entered the clinic. ...Despite the increasing interest in sulfoximines and their chemistry, the routine application of this structure in drug discovery is still hampered due to limited experience in physicochemical and in vitro parameters of sulfoximines. Therefore, we reviewed all relevant articles from 2013 to the present in terms of potency and pharmacokinetic properties in order to support the addition of the sulfoximine component to the toolbox of medicinal chemists.
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•Isosteres of a variety of functional groups.•Show favorable characteristics.•Are synthetically accessible.•Treat multiple diseases potential intellectual property advantages.
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