5-methylcytosine modification by Plasmodium NSUN2 stabilizes mRNA and mediates the development of gametocytes.

5-methylcytosine (m5C) is an important epitranscriptomic modification involved in messenger RNA (mRNA) stability and translation efficiency in various biological processes. However, it remains unclear if m5C modification contributes to the dynamic regulation of the transcriptome during the developmental cycles of Plasmodium parasites. Here, we characterize the landscape of m5C mRNA modifications at single nucleotide resolution in the asexual replication stages and gametocyte sexual stages of rodent (Plasmodium yoelii) and human (Plasmodium falciparum) malaria parasites. While different representations of m5C-modified mRNAs are associated with the different stages, the abundance of the m5C marker is strikingly enhanced in the transcriptomes of gametocytes. Our results show that m5C modifications confer stability to the Plasmodium transcripts and that a Plasmodium ortholog of NSUN2 is a major mRNA m5C methyltransferase in malaria parasites. Upon knockout of P. yoelii nsun2 (pynsun2), marked reductions of m5C modification were observed in a panel of gametocytogenesis-associated transcripts. These reductions correlated with impaired gametocyte production in the knockout rodent malaria parasites. Restoration of the nsun2 gene in the knockout parasites rescued the gametocyte production phenotype as well as m5C modification of the gametocytogenesis-associated transcripts. Together with the mRNA m5C profiles for two species of Plasmodium, our findings demonstrate a major role for NSUN2-mediated m5C modifications in mRNA transcript stability and sexual differentiation in malaria parasites.

Terahertz metalens for generating multi-polarized focal points and images with uniform intensity distributions.

Metasurfaces have provided a flexible platform for designing ultracompact metalenses with unusual functionalities. However, traditional multi-foci metalenses are limited to generating circularly polarized (CP) or linearly polarized (LP) focal points, and the intensity distributions are always inhomogeneous/chaotical between the multiple focal points. Here, an inverse design approach is proposed to optimize the in-plane orientation of each meta-atom in a terahertz (THz) multi-foci metalens that can generate multi-polarized focal points with nearly uniform intensity distributions. As a proof-of-principle example, we numerically and experimentally demonstrate an inversely designed metalens for simultaneously generating multiple CP- and LP-based focal points with homogeneous intensity distributions, leading to a multi-polarized image (rather than the holography). Furthermore, the multi-channel and multi-polarized images consisting of multiple focal points with homogeneous intensity distributions are also numerically demonstrated. The unique approach for inversely designing multi-foci metalens that can generate multi-polarized focal points and images with uniform intensity distributions will enable potential applications in imaging and sensing.

SP1 induced long non-coding RNA AGAP2-AS1 promotes cholangiocarcinoma proliferation via silencing of CDKN1A.

BACKGROUND: LncRNA can regulate gene at various levels such as apparent genetics, alternative splicing, and regulation of mRNA degradation. However, the molecular mechanism of LncRNA in cholangiocarcinoma is still unclear. This deserves further exploration. METHODS: We investigated the expression of AGAP2-AS1 in 32 CCA tissues and two CCA cell lines. We found a LncRNA AGAP2-AS1 which induced by SP1 has not been reported in CCA, and Knockdown and overexpression were used to investigate the biological role of AGAP2-AS1 in vitro. CHIP and RIP were performed to verify the putative targets of AGAP2-AS1. RESULTS: AGAP2-AS1 was significantly upregulated in CCA tumor tissues. SP1 induced AGAP2-AS1 plays an important role in tumorigenesis. AGAP2-AS1 knockdown significantly inhibited proliferation and caused apoptosis in CCA cells. In addition, we demonstrated that AGAP2-AS1 promotes the proliferation of CCA. CONCLUSIONS: We conclude that the long non-coding RNA AGAP2-AS1 plays a role in promoting the proliferation of cholangiocarcinoma.

Integrative Analysis of NSCLC Identifies LINC01234 as an Oncogenic lncRNA that Interacts with HNRNPA2B1 and Regulates miR-106b Biogenesis.

The discovery of long noncoding RNAs (lncRNAs) has increased our understanding of the development and progression of many cancers, but their contributions to non-small cell lung cancer (NSCLC) remain poorly understood. Here, we profiled lncRNA expression in NSCLC and investigated in detail the molecular function of one upregulated lncRNA, LINC01234. LINC01234 was overexpressed in NSCLC compared with normal lung tissue and correlated positively with poor prognosis. Downregulation of LINC01234 impaired cell proliferation in vitro and tumor growth in vivo. RNA pull-down/mass spectrometry experiments showed that LINC01234 interacted with the RNA-binding protein heterogeneous nuclear ribonucleoprotein A2/B1 (HNRNPA2B1), which, in turn, led to the recruitment of DiGeorge syndrome critical region gene 8 (DGCR8), a subunit of the microRNA (miRNA) microprocessor complex. Accordingly, depletion of either LINC01234 or HNRNPA2B1 reduced the processing of several miRNA precursors, including primary microRNA (pri-miR)-106b. miR-106b-5p enhanced NSCLC cell growth by downregulating cryptochrome 2 (CRY2), thereby increasing c-Myc expression. Finally, we found that activated c-Myc binds to the LINC01234 promoter to increase its transcription, creating a c-Myc-LINC01234-HNRNPA2B1-miR-106b-5p-CRY2-c-Myc positive-feedback loop. We identified numerous lncRNAs with dysregulated expression in NSCLC and demonstrated a novel oncogenic axis involving LINC01234, HNRNPA2B1, miR-106b-5p, CRY2, and c-Myc. Components of this axis may be potential novel targets for NSCLC.

Direct Analysis of Carbonyl Compounds by Mass Spectrometry with Double-Region Atmospheric Pressure Chemical Ionization.

Direct analysis of highly reactive volatile species such as the aliphatic aldehydes as vital biomarkers remains a great challenge due to difficulties in the sample pretreatment. To address such a challenge, we herein report the development of a novel double-region atmospheric pressure chemical ionization mass spectrometry (DRAPCI-MS) method. The DRAPCI source implements a separated structural design that uses a focus electrode to divide the discharge and ionization region to reduce sample fragmentation in the ionization process. Counterflow introduction (CFI) configuration was adopted in the DRAPCI source to reduce background noise, while ion transmission efficiency was optimized through simulating the voltage of the focus electrode and the ion trajectory of the ion source. The limits of detection (LODs) of four carbonyl compounds cyclohexanone, hexanal, heptanal, and octanal by DRAPCI-MS were between 0.1 and 3 µg·m-3, approximately two to eight times lower than those by atmospheric pressure chemical ionization mass spectrometry. Additionally, the DRAPCI-MS method carried out effective in situ analyses of the volatile components in expired milk and the exhaled breath of smokers, demonstrating the DRAPCI-MS as a practical tool to analyze complex mixtures. The DRAPCI-MS method provides a rapid, sensitive, and high-throughput technique in the real-time analysis of gaseous small-molecule compounds.

Nicotine Pharmacokinetics in Rat Brain and Blood by Simultaneous Microdialysis, Stable-Isotope Labeling, and UHPLC-HRMS: Determination of Nicotine Metabolites.

The disposition and metabolism of nicotine in the brain is an important determinant of its exposure. We have developed a novel method for the dynamic determination of nicotine and its metabolites in rat brain and blood by simultaneous microdialysis sampling, stable-isotope labeling, and ultra high-performance liquid chromatography-high-resolution mass spectrometry (UHPLC-HRMS) assaying. Microdialysis probes were inserted into both the right striatum and jugular vein of Sprague-Dawley rats. The collections of dialystes after nicotine intraperitoneal injection were analyzed by the optimized UHPLC-HRMS. Nicotine-pyridyl- d4 was used as a metabolic tracer, and several stably labeled isotopes were applied to calibrate the in vivo recoveries of retrodialysis. The quadrupole-Orbitrap HRMS provided reliable characterization of the nicotine derivatives with less than 3.5 ppm mass measurement accuracy. Good precision and accuracy were obtained for different analytes within the predefined limits of acceptability and the range of the standard curve. Nicotine and its 11 metabolites were identified in most microdialysis samples from the blood and brain tissue samples. Besides cotinine as the main metabolic product of nicotine, trans-3'-hydroxy-cotinine, nicotine- N-oxide, and norcotinine were proven to be the second most abundant metabolites. The other seven nicotine products, including 4-oxo-4-(3-pyridyl)-butanoic acid, 4-hydroxy-4-(3-pyridyl)-butanoic acid, cotinine- N-oxide, nicotine- N-glucuronide, cotinine- N-glucuronide, and trans-3'- hydroxy-cotinine- O-glucuronide, which have not been determined previously in animal brain, were present in minor amounts. The pharmacokinetic profile of nicotine metabolites indicated that the metabolic characteristic of nicotine in the brain was relatively different from that in the blood. The present work would provide comprehensive evidence for clarifying the differences between nicotine metabolism in the brain and peripheral system.

Altererythrobacter amylolyticus sp. nov., isolated from lake sediment.

An aerobic, motile, Gram-stain-negative bacterium, designated strain NS1T, was isolated from interfacial sediment from Taihu Lake, China. The strain formed yellow colonies on R2A medium. Cells were ovoid to rod-shaped and non-spore-forming. Growth occurred at 15-40 °C (optimum, 28 °C), at pH 5.0-10.5 (optimum, 6.5-7.5) and in the presence of 0-1 % (w/v) NaCl (optimum, 0 %). Phylogenetic trees based on 16S rRNA gene sequences showed that strain NS1T represented a member of the genus Altererythrobacter and had the highest sequence similarity to Altererythrobacter troitsensis CCTCC AB 2015180T (97.1 %). The average nucleotide identity value between strain NS1T and the closest related strain based on their genomes was 78.6 %. The predominant ubiquinone was Q-10. The major fatty acids were summed feature 8 (C18 : 1ω7c and/or C18 : 1ω6c), summed feature 3 (C16 : 1ω7c and/or C16 : 1ω6c) and C16 : 0. The polar lipids comprised diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, phosphatidylcholine, an unidentified phospholipid, an unidentified glycolipid and six unidentified lipids. The genomic DNA G+C content was 66.6 mol%. On the basis of phenotypic and genotypic characteristics, strain NS1T represents a novel species of the genus Altererythrobacter, for which the name Altererythrobacter amylolyticus sp. nov. is proposed. The type strain is NS1T (=CGMCC 1.13679T=NBRC 113553T).

Magnetic mesoporous polyimide composite for efficient extraction of Rhodamine B in food samples.

A core-shell structured magnetic polyimide composite has been synthesized by the covalent coating of a mesoporous polyimide polymer onto the surface of magnetite nanoparticles. The nanocomposite was characterized by scanning electron microscopy, transmission electron microscopy, N2 adsorption-desorption isotherms, X-ray diffraction, infrared spectroscopy, and vibrating sample magnetometry. The results showed that the prepared composite had a large surface area (306.45 m²/g), a unique pore size (2.15 nm), and strong magnetic properties (45.7 emµ/g), rendering it a promising sorbent material for magnetic solid-phase extraction. The parameters that affect the extraction efficiency of rhodamine B were optimized with the assistance of response surface methodology. Under the optimal conditions, the developed method has been successfully applied to determine the rhodamine B in food samples. The linearities and limits of detection of rhodamine B in hot pepper, red wine, and chili powder samples were measured. Satisfactory recoveries in the range of 94.8-103.3% with relative standard deviations <5.5% were obtained. Investigation of the adsorption mechanism of magnetic polyimide composite indicated that multiple interactions, including hydrophobic, π-π, and hydrogen bonding interactions, were involved in the adsorption process.

Inhibitory effect of Par-4 combined with cisplatin on human Wilms' tumor cells.

Wilms' tumor is associated with a high treatment success rate, but there is still a risk of recurrence. Cisplatin, which is one of the chemotherapeutic agents used for its treatment, is associated with a very high rate of resistance. Par-4 (prostate apoptosis response 4) is a tumor suppressor, which is capable of sensitizing tumor cells to chemotherapy. Therefore, the aim of this study was to determine whether combined treatment with Par-4 and cisplatin is effective for inhibiting growth of Wilms' tumor. Wilms' tumor and control cell samples were collected and analyzed by immunofluorescence assay and immunohistochemistry. Total proteins extracted from cultured cells were analyzed using western blotting and flow cytometry. In addition, a mouse xenograft model was established. We discovered significantly low expression of Par-4 in the tumor tissue, which was positively correlated with high expression of GRP78 (glucose-regulated protein 78). In addition, we found that ectopic Par-4 co-localized with cell surface GRP78 and induced high expression of the endoplasmic reticulum proteins ATF4 and BAX, which activated the endoplasmic reticulum apoptosis pathway. Moreover, treatment with ectopic Par-4 and cisplatin suppressed xenograft growth in nude mice. In conclusion, our results showed that Par-4 overexpression and cisplatin had a synergistic effect on SK-NEP-1 cells, as a result of which cell growth was inhibited and cellular apoptosis was induced. Thus, in vitro and in vivo upregulation of Par-4 expression is indispensable for the trafficking of GRP78 to the cell membrane and subsequent apoptosis of cancer cells.

Simultaneous determination of nicotine and its nine metabolites in rat blood utilizing microdialysis coupled with UPLC-tandem mass spectrometry for pharmacokinetic application.

To develop a simple and rapid method for the simultaneous determination of nicotine and its nine metabolites in rat blood, an in vivo microdialysis sampling technique coupled with ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was established for quantitation and characterization of the pharmacokinetics of nicotine and its metabolites. Microdialysis probes were inserted into the jugular vein of Sprague Dawley rats, and dialysates were collected after nicotine (0.5 mg/kg, i.p.) administration. Target analytes and corresponding deuterated internal standards were separated on a hydrophilic interaction liquid chromatography column (HILIC BEH 2.1. × 150 mm, 1.7 µm) and detected by UPLC-MS/MS under multiple reaction monitoring mode. The limits of quantification for nicotine and its nine metabolites ranged from 0.039 to 0.46 ng/mL. Intra- and inter-day precision and accuracy were well within the predefined limits of acceptability (<11 %). Pharmacokinetic results showed that the mean half-lives of nicotine, cotinine, nornicotine, norcotinine, nicotine-N'-oxide, cotinine-N'-oxide, trans-3'-hydroxy-cotinine, nicotine-N-glucuronide, cotinine-N-glucuronide, and trans-3'-hydroxy-cotinine-O-glucuronide in rat plasma were 63, 291, 175, 440, 251, 451, 322, 341, 488, and 516 min, respectively. The blood concentration-time profiles of nicotine and its nine metabolites indicate that nicotine is rapidly consumed after the administration and subsequently cotinine is generated as the main metabolite; meanwhile, cotinine and other eight minor metabolites exhibit longer retention times in rat body.

MicroRNA-409-3p functions as a tumor suppressor in human lung adenocarcinoma by targeting c-Met.

BACKGROUND/AIMS: Dysregulation of microRNAs is correlated with tumor development. The aim of this study is to investigate the clinicopathologic and prognostic significance of microRNA (miR)-409-3p and its tumor suppressor roles in lung adenocarcinoma (LAD). METHODS: Quantitative real-time PCR (qRT-PCR) was performed to detect miR-409-3p expression in LAD tissues and corresponding noncancerous tissues. Additionally, the correlations of miR-409-3p expression with clinicopathologic factors and prognosis of patients were statistically analyzed. Next, we investigated whether miR-409-3p could function as a tumor suppressor in LAD cells via regulation of Akt signaling by targeting receptor tyrosine kinase (c-Met). RESULTS: MiR-409-3p was significantly downregulated in LAD tissues compared with corresponding noncancerous tissues. Low miR-409-3p expression was observed to be significantly correlated with poorer tumor differentiation, advanced pTNM stage and higher incidence of lymph node metastasis. Multivariate Cox regression analyses showed that miR-409-3p expression was an independent prognostic factor for LAD patients. Functional analyses indicated that miR-409-3p could inhibit growth, induce apoptosis, reduce migration and invasion in LAD cells via inactivation of Akt signaling by targeting c-Met. CONCLUSIONS: MiR-409-3p was an independent prognostic factor and functioned as a tumor suppressor in LAD via regulation of Akt signaling by targeting c-Met.

Analysis of sustainable water resource management and driving mechanism in arid region: a case study of Xinjiang, China, from 2005 to 2020.

The long-term dynamic comprehensive evaluation of the water resource carrying capacity (WRCC) and the analysis of its potential driving mechanism in arid areas are contemporary research issues and technical means of mitigating and coordinating the conflict between severe resource shortages and human needs. The purpose of this study was to explore the distribution of the WRCC and the spatiotemporal heterogeneity of drivers in arid areas based on an improved two-dimensional spatiotemporal dynamic evaluation model. The results show that (1) the spatial distribution of the WRCC in Xinjiang, China, is high in the north, low in the south, high in the west, and low in the east. (2) From 2005 to 2020, the centers of gravity of the WRCC in northern and southern Xinjiang moved to the southeast and west, respectively, and the spatial distribution exhibited slight diffusion. (3) The factors influencing the WRCC exhibit more obvious spatial and temporal heterogeneity. The domestic waste disposal rate and ecological water use rate were the main factors influencing the WRCC in the early stage, while the GDP per capita gradually played a dominant role in the later stage. (4) In the next 30 years, the WRCC in Xinjiang will increase. The results provide a theoretical reference for the sustainable development of water resources in arid areas.

Clinical significance of peripheral T-cell receptor repertoire profiling and individualized nomograms in patients with gastrointestinal cancer treated with anti-programmed death 1 antibody.

Background: Immune checkpoint inhibitors (ICIs) have significant clinical benefit for a subset of patients with gastrointestinal cancers (GICs) including esophageal cancer, gastric cancer and colorectal cancer. However, it is difficult to predict which patients will respond favorably to immune checkpoint blockade therapy. Thus, this study was initiated to determine if peripheral T-cell receptor (TCR) repertoire profiling could predict the clinical efficacy of anti-programmed death 1 (PD-1) treatment. Methods: Blood samples from 31 patients with GICs were collected before anti-PD-1 antibody treatment initiation. The clinical significance of the combinatorial diversity evenness of the TCR repertoire [the diversity evenness 50 (DE50), with high values corresponding to less clonality and higher TCR diversity] from peripheral blood mononuclear cells (PBMCs) was evaluated in all the enrolled patients. A highly predictive nomogram was set up based on peripheral TCR repertoire profiling. The performance of the nomogram was assessed by receiver operating characteristic (ROC) curve, concordance index (C-index), and calibration curves, and decision curve analysis (DCA) was used to assess its clinical applicability. Results: Compared to non-responders [progression disease (PD)], the DE50 scores were significantly higher in responders [stable disease (SD) and partial response (PR)] (P=0.018). Patients with a high DE50 score showed better progression-free survival (PFS) than those with a low DE50 score (P=0.0022). The multivariable Cox regression demonstrated that high DE50 and low platelet-lymphocyte ratio (PLR) were significant independent predictors for better PFS when treated with anti-PD-1 antibody. Furthermore, a highly predictive nomogram was set up based on peripheral TCR repertoire profiling. The area under the curves (AUCs) of this system at 3-, 6- and 12-month PFS reached 0.825, 0.802, and 0.954, respectively. The nomogram had a C-index of 0.768 [95% confidence interval (CI): 0.658-0.879]. Meanwhile, the calibration curves also demonstrated the reliability and stability of the model. Conclusions: High DE50 scores were predictive of a favorable response and longer PFS to anti-PD-1 treatment in GIC patients. The nomogram based on TCR repertoire profiling was a reliable and practical tool, which could provide risk assessment and clinical decision-making for individualized treatment of patients.

Integrated multi-omics profiling to dissect the spatiotemporal evolution of metastatic hepatocellular carcinoma.

Comprehensive molecular analyses of metastatic hepatocellular carcinoma (HCC) are lacking. Here, we generate multi-omic profiling of 257 primary and 176 metastatic regions from 182 HCC patients. Primary tumors rich in hypoxia signatures facilitated polyclonal dissemination. Genomic divergence between primary and metastatic HCC is high, and early dissemination is prevalent. The remarkable neoantigen intratumor heterogeneity observed in metastases is associated with decreased T cell reactivity, resulting from disruptions to neoantigen presentation. We identify somatic copy number alterations as highly selected events driving metastasis. Subclones without Wnt mutations show a stronger selective advantage for metastasis than those with Wnt mutations and are characterized by a microenvironment rich in activated fibroblasts favoring a pro-metastatic phenotype. Finally, metastases without Wnt mutations exhibit higher enrichment of immunosuppressive B cells that mediate terminal exhaustion of CD8+ T cells via HLA-E:CD94-NKG2A checkpoint axis. Collectively, our results provide a multi-dimensional dissection of the complex evolutionary process of metastasis.

miR-206 is down-regulated in breast cancer and inhibits cell proliferation through the up-regulation of cyclinD2.

MicroRNAs act as important gene regulators in human genomes, and their aberrant expression is linked to many malignancies. Aberrant expression of miR-206 has been frequently reported in cancer studies; however, the role and mechanism of its function in breast cancer remains unclear. Quantitative real-time PCR was performed to detect the relative expression levels of miR-206 in breast cancer and normal breast tissues. Lower expression of miR-206 in breast cancer tissues was associated with larger tumour size and a more advanced clinical stage. Further in vitro observations showed that the enforced expression of miR-206 in MCF-7 breast cancer cells inhibited cell growth by blocking the G1/S transition and suppressed cell proliferation and colony formation, implying that miR-206 functions as a tumour suppressor in the progression of breast cancer. Interestingly, Luciferase assays first revealed that miR-206 inhibited cyclinD2 expression by targeting two binding sites in the 3'-untranslated region of cyclinD2 mRNA. qRT-PCR and Western blot assays verified that miR-206 reduced cyclinD2 expression at both the mRNA and protein levels. A reverse correlation between miR-206 and cyclinD2 expression was noted in breast cancer tissues. Altogether, our results identify a crucial tumour suppressive role of miR-206 in the progression of breast cancer, at least partly via up-regulation of the expression of cyclinD2, and suggest that miR-206 might be a candidate prognostic predictor or an anticancer therapeutic target for breast cancer patients.

Time-feature attention-based convolutional auto-encoder for flight feature extraction.

Quick Access Recorders (QARs) provide an important data source for Flight Operation Quality Assurance (FOQA) and flight safety. It is generally characterized by large volume, high-dimensionality and high frequency, and these features result in extreme complexities and uncertainties in its usage and comprehension. In this study, we proposed a Time-Feature Attention (TFA)-based Convolutional Auto-Encoder (TFA-CAE) network model to extract essential flight features from QAR data. As a case study, we used the QAR data landing at the Kunming Changshui International Airport and Lhasa Gonggar International Airport as the experimental data. The results show that (1) the TFA-CAE model performs the best in extracting representative flight features in comparison to some traditional or similar approaches, such as Principal Component Analysis (PCA), Convolutional Auto-Encoder (CAE), Self-Attention-based CAE (SA-CAE), Gate Recurrent Unit based Auto-Encoder (GRU-AE) and TFA-GRU-AE models; (2) flight patterns corresponding to different runways can be recognized; and (3) anomalous flights can effectively deviate from many observations. Overall, the TFA-CAE model provides a well-established technique for further usage of QAR data, such as flight risk detection or FOQA.

Important role of precipitation in controlling a more uniform spring phenology in the Qinba Mountains, China.

Under global warming, the gradual pattern of spring phenology along elevation gradients (EG) has significantly changed. However, current knowledge on the phenomenon of a more uniform spring phenology is mainly focused on the effect of temperature and neglected precipitation. This study aimed to determine whether a more uniform spring phenology occurs along EG in the Qinba Mountains (QB) and explore the effect of precipitation on this pattern. We used Savitzky-Golay (S-G) filtering to extract the start of season (SOS) of the forest from the MODIS Enhanced Vegetation Index (EVI) during 2001-2018 and determined the main drivers of the SOS patterns along EG by partial correlation analyses. The SOS showed a more uniform trend along EG in the QB with a rate of 0.26 ± 0.01 days 100 m-1 per decade during 2001-2018, but there were differences around 2011. A delayed SOS at low elevations was possibly due to the reduced spring precipitation (SP) and spring temperature (ST) between 2001 and 2011. Additionally, an advanced SOS at high elevations may have been caused by the increased SP and reduced winter temperature (WT). These divergent trends contributed to a significant uniform trend of SOS with a rate of 0.85 ± 0.02 days 100 m-1 per decade. Since 2011, significantly higher SP (especially at low elevations) and rising ST advanced the SOS, and the SOS at lower altitudes was more advanced than at higher altitudes, resulting in greater SOS differences along EG (0.54 ± 0.02 days 100 m-1 per decade). The SP determined the direction of the uniform trend in SOS by controlling the SOS patterns at low elevations. A more uniform SOS may have important effects on local ecosystem stability. Our findings could provide a theoretical basis for establishing ecological restoration measures in areas experiencing similar trends.

A novel target state detection method for accurate cardiopulmonary signal extraction based on FMCW radar signals.

Frequency-modulated continuous wave radar is capable of constant, real-time detection of human presence and monitoring of cardiopulmonary signals such as respiration and heartbeat. In highly cluttered environments or when the human body moves randomly, noise signals may be relatively large in some range bins, making it crucial to accurately select the range bin containing the target cardiopulmonary signal. In this paper, we propose a target range bin selection algorithm based on a mixed-modal information threshold. We introduce a confidence value in the frequency domain to determine the state of the human target and employ the range bin variance in the time domain to determine the range bin change status of the target. The proposed method accurately detects the state of the target and effectively selects the range bin containing the cardiopulmonary signal with a high signal-to-noise ratio. Experimental results demonstrate that the proposed method achieves better accuracy in cardiopulmonary signal rate estimation. Moreover, the proposed algorithm is lightweight in data processing and has good real-time performance.

Low-dose metronomic chemotherapy triggers oxidized mtDNA sensing inside tumor cells to potentiate CD8+T anti-tumor immunity.

Low-dose metronomic (LDM) chemotherapy, the frequent and continuous use of low doses of conventional chemotherapeutics, is emerging as a promising form of chemotherapy utilization. LDM chemotherapy exerts immunomodulatory effects. However, the underlying mechanism is not fully understood. Here we found that suppressing tumor growth by LDM chemotherapy was dependent on the activation of CD8+T cells. LDM chemotherapy potentiated the cytotoxic function of CD8+T cells by stimulating cancer-cell autonomous type I interferon (IFN) induction. Mechanistically, LDM chemotherapy evoked mitochondrial dysfunction and increased reactive oxygen species (ROS) production. ROS triggered the oxidation of cytosolic mtDNA, which was sensed by cGAS-STING, consequently inducing type I IFN production in the cancer cells. Moreover, the cGAS-STING-IFN axis increased PD-L1 expression and predicted favorable clinical responses to chemoimmunotherapy. Antioxidant N-acetylcysteine inhibited oxidized mtDNA-induced type I IFN production and attenuated the efficacy of combination therapy with LDM chemotherapy and PD-L1 blockade. This study elucidates the critical role of intratumoral oxidized mtDNA sensing in LDM chemotherapy-mediated activation of CD8+T cell immune response. These findings may provide new insights for designing combinatorial immunotherapy for cancer patients.

Usnic acid inhibits breast tumor angiogenesis and growth by suppressing VEGFR2-mediated AKT and ERK1/2 signaling pathways.

Tumor growth depends on angiogenesis and inducing angiogenesis is one of the most important hallmarks in the cancer development. Treatment with small molecules that inhibit angiogenesis has been an effective strategy for anti-cancer therapy. Some anti-angiogenic factors are derived from traditional Chinese herbs. Usnic acid (UA), an active compound mainly found in lichens, has shown some biological and physiological activities. However, the role and mechanism of UA in tumor angiogenesis are still unknown. The aim of this study was to assess the effects of UA on tumor angiogenesis. In this study, we demonstrated that UA strongly inhibited in vivo angiogenesis in a chick embryo chorioallantoic membrane assay and vascular endothelial growth factor-induced mouse corneal angiogenesis model. In a mouse xenograft tumor model, UA suppressed Bcap-37 breast tumor growth and angiogenesis without affecting mice body weight. In an in vitro assay, UA not only significantly inhibited endothelial cell proliferation, migration and tube formation, but also induced morphological changes and apoptosis in endothelial cells. In addition, UA inhibited Bcap-37 tumor cell proliferation. Moreover, western blot analysis of cell signaling molecules indicated that UA blocked vascular endothelial growth factor receptor (VEGFR) 2 mediated Extracellular signal-regulated protein kinases 1 and 2(ERK1/2) and AKT/P70S6K signaling pathways in endothelial cells. These results provided the first evidence of the biological function and molecular mechanism of UA in tumor angiogenesis.