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Objective: To deepen the imaging-pathological mechanism of primary central nervous system lymphoma (PCNSL) and provide a theoretical basis for clinical diagnosis and treatment, the functional magnetic resonance imaging (fMRI) characteristics of PCNSL were analyzed, and the relationship between the fMRI characteristics and vasculogenic mimicry (VM) and reticular fiber in PCNSL was discussed. Methods: Ninety-six patients with PCNSL treated in our hospital were divided into three groups according to the pathological examination results, including strong positive group of VM (n = 40), weak positive group of VM (n = 56), strong positive group of reticular fiber (n = 45) and weak positive group of reticular fiber (n = 51). The levels of augmentation index and apparent diffusion coefficient (ADC) were compared among the groups. receiver operator characteristic (ROC) curve analysis was used to analyze the clinical value of ADC value in differential diagnosis of PCNSL. Results: The levels of augmentation index in the strong positive group of VM were significantly higher than that in the weak positive group of VM, and the ADC value in the strong positive group of VM was significantly lower than that in the weak positive group of VM (P

Sustained myocardial injury due to hypertension and diabetes mellitus leads to production of endogenous reactive oxygen species (ROS) and insufficient myocardial antioxidant capacity, increasing the risk of cardiomyocyte ferroptosis. Ferroptosis is a nonapoptotic form of cell death driven by unrestricted lipid peroxidation. Dysfunction of the glutathione peroxidase 4 (GPX4) antioxidant system also plays an important role in ferroptosis. Cardiomyocyte ferroptosis ultimately leads to myocardial deterioration, such as inflammation, fibrosis, and cardiac remodeling, resulting in structural and functional changes. Pterostilbene (PTS), a demethylated derivative of resveratrol, exhibits strong anti-inflammatory and antioxidative activities. In this study, we used in vitro experiments to explore ferroptosis induced by angiotensin II (Ang II) of primary cardiac myocytes (CMs) and in vivo experiments to prepare a transverse aortic constriction (TAC)-induced cardiac dysfunction mouse model. PTS can significantly ameliorate Ang II-induced cardiomyocyte ferroptosis in vitro and reduce cardiac remodeling, while improving cardiac function in mice after TAC in vivo. Further mechanistic investigations revealed that PTS exerts its protective effect through the SIRT1/GSK-3β/GPX4 pathway. After siRNA-mediated knockdown of SIRT1 or GPX4 in CMs, the protective effects of PTS on cardiomyocytes were abolished. This study provides important theoretical support for the potential of PTS to attenuate pathological cardiac remodeling and heart failure and provides a preliminary exploration of the molecular pathways involved in its protective mechanism.

Tumor-specific antigens (TSAs) are crucial for tumor-specific immune response that reduces tumor burden and thus serve as important targets for immunotherapy. Identification of novel TSAs can provide new strategies for immunotherapies. In this study, we demonstrated that the upstream open reading frame (uORF) of RNF10 encodes an antigenic peptide (RNF10 uPeptide), capable of eliciting a T cell-mediated anti-tumor immune response. We initially demonstrated the immunogenicity of the RNF10 uPeptide in a CT26 tumor mouse model, by showing that its epitope was specifically recognized by CD8+ T cells. Vaccination of mice with the long form of the RNF10 uPeptide conferred strong anti-tumor activity. Next, we proved that the human RNF10 uORF could be translated. In addition, we predicted the binding of an RNF10 uPeptide epitope to HLA-A∗02:01 (HLA-A2). This HLA-A2-restricted epitope of the RNF10 uPeptide induced a potent specific human T cell response. Finally, we showed that an HLA-A2-restricted cytotoxic T cell (CTL) clone, derived from a pancreatic cancer patient, recognized the RNF10 uPeptide epitope (RLFGQQQRA) and lysed HLA-A2+ pancreatic carcinoma cells expressing the RNF10 uPeptide. These results indicate that the RNF10 uPeptide could be a promising target for pancreatic carcinoma immunotherapy.

The construction of the reservoir has changed the nitrogen migration and transformation processes in the river, and a large amount of sediment deposition in the reservoir may also lead to the spatial differentiation of complete ammonia oxidation (comammox) bacteria. The study investigated the abundance and diversity of comammox bacteria in the sediments of three cascade reservoirs, namely, Xiaowan, Manwan, and Nuozhadu on the Lancang River in China. In these reservoirs, the average amoA gene abundance of clade A and clade B of comammox bacteria, ammonia-oxidizing archaea (AOA), and ammonia-oxidizing bacteria (AOB) was 4.16 ± 0.85 × 105, 1.15 ± 0.33 × 105, 7.39 ± 2.31 × 104, and 3.28 ± 0.99 × 105 copies g−1, respectively. The abundance of clade A was higher than that of other ammonia oxidizing microorganisms. The spatial variation of comammox bacteria abundance differed among different reservoirs, but the spatial variation trends of the two clades of comammox bacteria in the same reservoir were similar. At each sampling point, clade A1, clade A2, and clade B coexisted, and clade A2 was usually the dominant species. The connection between comammox bacteria in the pre-dam sediments was looser than that in non-pre-dam sediments, and comammox bacteria in pre-dam sediments exhibited a simpler network structure. The main factor affecting comammox bacteria abundance was NH4+-N, while altitude, temperature, and conductivity of overlying water were the main factors affecting comammox bacteria diversity. Environmental changes caused by differences in the spatial distribution of these cascade reservoirs may be the main driver of the changes of community composition and abundance of comammox bacteria. This study confirms that the construction of cascade reservoirs results in niche spatial differentiation of comammox bacteria.

In this paper, we carry out the non-Hermitian stimulated Raman shortcut-to-adiabatic passage (NH-STIRSAP) to create ultracold deeply-bound molecules. The open three-level molecular system is supposed to have irreversible decays out of all levels. Under the assumption of large single-photon detuning and/or strong loss rate of the excited level, the NH three-level system can be theoretically reduced to an effective two-level system. By continuously using the counter-diabatic driving of the shortcut-to-adiabaticity, an auxiliary field is produced to couple the Feshbach level with the ground level. In the numerical calculations, we firstly consider the case of decaying only from the excited level, which is the main loss of the system. Under the NH-STIRSAP, the calculations reveal that complete population transfer from the Feshbach to the ground level can occur even if the adiabatic condition is not fulfilled. Therefore, the creation efficiency of ultracold deeply-bound molecules is greatly improved. The results hold equally for counter-intuitive and intuitive time sequence of the Stokes and pump pulse. If the decays from the Feshbach and ground level are also included, the NH-STIRSAP can still restore most of that efficiency, which performs much better than typical stimulated Raman adiabatic passage. Finally, we point out that the robustness and fast transfer speed of the NH-STIRSAP facilitate the creation and detection of ultracold deeply-bound molecules.

Drug repurposing or repositioning has been well-known to refer to the therapeutic applications of a drug for another indication other than it was originally approved for. Repurposing non-oncology small-molecule drugs has been increasingly becoming an attractive approach to improve cancer therapy, with potentially lower overall costs and shorter timelines. Several non-oncology drugs approved by FDA have been recently reported to treat different types of human cancers, with the aid of some new emerging technologies, such as omics sequencing and artificial intelligence to overcome the bottleneck of drug repurposing. Therefore, in this review, we focus on summarizing the therapeutic potential of non-oncology drugs, including cardiovascular drugs, microbiological drugs, small-molecule antibiotics, anti-viral drugs, anti-inflammatory drugs, anti-neurodegenerative drugs, antipsychotic drugs, antidepressants, and other drugs in human cancers. We also discuss their novel potential targets and relevant signaling pathways of these old non-oncology drugs in cancer therapies. Taken together, these inspiring findings will shed new light on repurposing more non-oncology small-molecule drugs with their intricate molecular mechanisms for future cancer drug discovery.

Adipose derived stem cell (ASC) spheroids show enhanced cellular viability and paracrine function to promote tissue regeneration and cell therapy effect. However, efficient preparation of numerous ASC spheroids, as well as convenient application on skin wound remains a challenge. The present study explored a new function of frequently-used polymer, Poly (N-isopropylacrylamide) (PNIPAM), developing a simple but efficient method based on PNIPAM to produce numerous ASC spheroids and apply them towards wound healing. PNIPAM-based porous hydrogel that crosslinked with disulfide bonds was fabricated, showing pore size of 300 μm at 37 °C. ASCs seeded into porous hydrogel spontaneously aggregated inside the inner pores to form a large number of spheroids. Higher cell seeding density could produce larger size of spheroids, which showed up-regulated paracrine secretion. After spheroids production, the porous hydrogel became a solution within 25 min after the addition of glutathione at 15 °C. The PNIPAM-based polymer solution carrying the produced ASC spheroids gelled again within 80 s at 33 °C and could tightly attach on skin. The in vivo wound healing evaluation illustrated that ASC spheroids promoted M2 polarization of macrophages, and effectively inhibited the local inflammatory response of wounds, thus accelerating wound healing. Thus, for one thing, this method was expected to realize the industrialized manufacturing of a large number of stem cell spheroids. For another, the spheroids produced by the present method could be easily collected and applied for biomedical engineering.

Background: We investigated the effect of the mammalian target of rapamycin (mTOR) pathway on CD8+ T cell immunity through Eomesodermin (Eomes) in intensive care unit (ICU) patients with invasive candidiasis (IC) and in a mouse model. Methods: We evaluated quantitative changes in parameters of the mTOR/phosphorylated ribosomal S6 kinase (pS6K) pathway and immune system at the onset of infection in ICU patients. The study was registered on 28 February 2017 at chictr.org.cn (ChiCTR-ROC-17010750). We also used a mouse model of Candida infection and constructed T-cell-specific mTOR and T-cell-specific tuberous sclerosis complex (TSC) 1 conditional knockout mice to elucidate the molecular mechanisms. Results: We enrolled 88 patients, including 8 with IC. The IC group had lower CD8+ T cell counts, higher serum levels of mTOR, pS6K, Eomes and interleukin (IL)-6. The mouse model with IC showed results consistent in the clinical study. The CD8+ T cell immune response to IC seemed to be weakened in TSC1 knockout mice compared with wild-type IC mice, demonstrating that mTOR activation resulted in the impaired CD8+ T cell immunity in IC. Conclusions: In IC, the mTOR activation may play a vital role in impaired CD8+ T cell immunity through enhancing expression of Eomes.The study was registered on 28 February 2017 at chictr.org.cn (identifier ChiCTR-ROC-17010750).

The effects of the symmetrical tilt Σ5 (310) ⟨001⟩ grain boundary (GB) on the evolution of radiation-induced point defects in pure δ-plutonium (Pu) were studied by Molecular dynamics (MD) simulations. The evolution of radiation-induced point defects was obtained when primary knock-on atom (PKA) was respectively set as −15 Å and 15 Å far from the GB and the number of residual defects was obtained as the distance from PKA to GB was changed. According to the results, compared with vacancies, interstitial atoms were more easily absorbed by GB. In addition, the formation energy of point defects was also calculated. The results showed that there was almost no difference for the formation energy of vacancies in the all matrix. However, the formation energy of interstitial atoms close to the GB was lower than that in the other bulk regions.

Molecular dynamics (MD) simulations were performed to investigate the evolution of radiation-induced point defects affected by the symmetrical tilt Σ5 (310) 〈001〉 grain boundary (GB) in Ga stabilised δ-Pu. From the perspective of formation energy, the formation energy of vacancies had no prominent change in the whole region, but it was lower than the formation energy of interstitial atoms. The formation energy of interstitial atoms near GB was lower than that in the bulk. On the other hand, the average formation energy of interstitial Pu atoms was greater than that of interstitial Ga atoms. Furthermore, by comparing the evolution of radiation-induced point defects when primary knock-on atom (PKA) was located at −25 Å and 25 Å far from the GB, respectively, and analyzing the tendency of the number of remaining defects with the distance between PKA and GB changing, it could be found that interstitial atoms were more easily trapped in Σ5 (310) 〈001〉 GB than vacancies for Pu-Ga alloy. Simultaneously, the influence of temperature on the number of point defects near GB was taken into consideration, and the results displayed that the number of residual point defects in Pu-Ga alloy with Σ5 (310) 〈001〉 GB showed a decreasing trend with temperature increasing because temperature had an effect on the diffusion of point defects. Remaining interstitial atoms rather than remaining vacancies, moreover, are more severely affected by temperature, for interstitial atoms were more easily absorbed by GB.

Objectives: This study investigated the use of lymphocyte subset counts as diagnostic and prognostic markers for carbapenem-resistant Enterobacteriaceae (CRE) infection. Methods: We assessed the lymphocyte subset populations and other clinical parameters of septic patients upon intensive care unit (ICU) admission, and evaluated their potential impact on CRE infection diagnosis and outcome. Results: Among 373 septic patients, 51 were diagnosed with CRE infection. The 28-day mortality was significantly higher in CRE than non-CRE patients (35.3% vs 14.9%). The T lymphocyte count and CD4+CD28+ T cell count were both independent risk factors for CRE infection, with the latter had the best diagnostic ability (AUC: 0.908; p < 0.0001). Lower CD4+CD28+ T cell counts were associated with higher likelihoods of CRE infection. The CRE incidence and 28-day mortality of CRE-infected patients could be predicted using cutoff values of 242 (sensitivity: 83.9%; specificity: 87.5%) and 58.5 (sensitivity: 100%; specificity: 61.1%) CD4+CD28+ T cells/μl at ICU admission, respectively. Conclusions: Septic patients with CRE infection had higher 28-day mortality. Given that the CD4+CD28+ T cell count was significantly lower in CRE than non-CRE septic patients and a lower cell count was significantly associated with higher 28-day mortality, CD4+CD28+ T cell counts may be useful markers for early diagnosis of CRE infection and outcome prediction.

Molecular dynamics (MD) simulations were conducted to investigate the temperature effects on the primary damage in gallium nitride (GaN) material. Five temperatures ranging from 300 K to 900 K were studied for 10 keV Ga primary knock-on atom (PKA) with inject direction of [0001]. The results of MD simulations showed that threshold displacement energy (Ed) was affected by temperatures and at higher temperature, it was larger. The evolutions of defects under various temperatures were similar. However, the higher temperature was found to increase the peak number, peak time, final time and recombination efficiency while decreasing the final number. With regard to clusters, isolated point defects and little clusters were common clusters and the fraction of point defects increased with temperature for vacancy clusters, whereas it did not appear in the interstitial clusters. Finally, at each temperature, the number of Ga interstitial atoms was larger than that of N and besides that, there were other different results of specific types of split interstitial atoms.

Leaf is essential for plant growth and development; however, the relative importance of environmental filtering and phylogeny in determining leaf size across different spatial scales in grassland ecosystems remains poorly explored. We used transect methodology to explore the spatial variation in leaf size and its underlying mechanisms in grasslands along three topographically and floristically distinctive plateaus in northern China. We measured leaf size of a total of 1192 grassland species in the Tibetan Plateau (TP, temperature limited), Loess Plateau (LP, soil-nutrient limited), and Mongolia Plateau (MP, precipitation limited) along three transects encompassing meadow, typical, and desert steppes. Leaf size ranged from 0.01 to 258.16 cm2, with an average of 5.54 cm2. The smallest leaves were measured in the TP. At the vegetation association level, the largest leaves were present in the meadow steppe, followed by those in typical and desert steppes, irrespective of the plateau. Unexpectedly, phylogeny had a negligible effect on the spatial variation in leaf size in the grasslands. Leaf size was positively correlated with growing-season temperature and precipitation but negatively correlated with ultraviolet (UV) radiation, suggesting that environmental filtering plays a more important role in affecting leaf size than phylogeny. Furthermore, leaf size in the TP and MP was mainly affected by precipitation and UV radiation, respectively, whereas that in the LP was affected by temperature, precipitation, soil nutrients and UV light. Specifically, our results underscored the importance of environmental filtering rather than phylogeny in determining plant leaf size and shed light on the unexpected role of UV radiation in contributing to leaf size variations in these plateaus. Our study provides novel insights into the response of plants to global change, especially in plateaus, alpine zone, and high-latitude areas.

Objectives: This study aimed to investigate the distinguishing ability of lymphocyte subtyping for Invasive candidiasis (IC) diagnosis and prognosis in non-neutropenic critically ill patients. Methods: We assessed the quantitative changes in key parameters of lymphocyte subtyping at the onset of clinical signs of infection in non-neutropenic critically ill patients and their potential influence on diagnosis and outcome of IC. The primary outcome was 28-day mortality. Results: Among the 182 consecutive critically ill patients, 22 (12.1%) were in the IC group. The CD28+CD8+ T-cell counts (AUC 0.863, 95%CI 0.804–0.909, P

Objective: The purpose of this study was to investigate whether the large-scale structural rich club organization was abnormal in patients with Leber's hereditary optic neuropathy (LHON) using diffusion tensor imaging (DTI), and the associations among disrupted brain structural connectivity, disease duration, and neuro-ophthalmological impairment. Methods: Nineteen acute, 34 chronic LHON patients, and 36 healthy controls (HC) underwent DTI and neuro-ophthalmological measurements. The brain structural network and rich club organization were constructed based on deterministic fiber tracking at the individual level. Then intergroup differences among the acute, chronic LHON patients and healthy controls (HC) in three types of structural connections, including rich club, feeder, and local ones, were compared. Network-based Statistics (NBS) was also used to test the intergroup connectivity differences for each fiber. Several linear and nonlinear curve fit models were applied to explore the associations among large-scale brain structural connectivity, disease duration, and neuro-ophthalmological metrics. Results: Compared to the HC, both the acute and chronic LHON patients had consistently significantly lower fractional anisotropy (FA) and higher radial diffusion (RD) for feeder connections (p 0.05, FDR correction). NBS also identified reduced FA of three feeder connections and five local ones linking visual, auditory, and basal ganglia areas in LHON patients (p 0.05, FDR correction). A significant negative correlation was shown between the retinal nerve fiber layer (RNFL) thickness and disease duration (p