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Abstract Fluid sensing has been an important but missing part of the massive Internet-of-Things sensor networks due to challenges including excessive manufacturing time/cost, finite wireless interrogation range, limited immunity to ambient clutter, and excessive required power for autonomous microfluidics operability. Here, we proposed an additive manufacturing flexible system as a solution to those challenges while enabling fluid analysis from controlled labs to virtually everywhere. Energy harvesting provides all required power for the actuation of the micro-pump enabling battery-less liquid sample acquisition. Energy sources including ultra-high-frequency radio frequency identification and hand-held devices like two-way talk radio are harvested simultaneously to support energy requirements for periodic monitoring every 6.6 min and on-demand monitoring within 4.63 s. Backscattering topologies are used to significantly extend the reading range while increasing the immunity to interferences and reducing the cost to the reader. A new additive manufacturing process is proposed to reduce fabrication time and cost while enabling massive scalability of flexible microfluidics. The good flexibility makes the system suitable for working toward future wearable applications. Prototypes of a sweat sensing system are demonstrated and successfully interrogated at 3 m with more than 15 dB signal-to-noise ratio using only a 14 dBm transmitter equivalent isotropic radiated power.

Activating mutations in RAS genes, notably KRASG12C, are pervasive in numerous cancers, presenting formidable challenges to therapy due to their elusive druggability. The landmark discovery of KRASG12C allosteric inhibitors marked a transformative milestone in cancer treatment, resulting in the approval of sotorasib and adagrasib. However, limitations in the depth and duration of response prompted the quest for alternative strategies. Recently, Holderfield et al., Wasko et al., and Jiang et al. reported on tri-complex inhibitors, namely RMC-7977 and RMC-6236, targeting activated RAS variants, demonstrating promising preclinical efficacy surpassing adagrasib. These advancments signify a paradigm shift in RAS oncology, promising enduring therapeutic benefits and warranting further clinical exploration.

Abstract Formaldehyde (HCHO) is a serious hazardous air pollutant and crucial precursor of PM2.5 and ozone compound pollution. There has been a dearth of HCHO research in Tibet where pressing need to protect the unique ecosystem. Therefore, this study aims to investigate the spatial-temporal distribution of HCHO from 2013 to 2021 and identify its influencing factors using satellite observations. Our findings reveal a noteworthy annual growth rate of 2.25% yr−1 in HCHO vertical column density (VCD) in Tibet. This rate is comparable to that in India and even surpasses levels observed in many other regions worldwide, including eastern China. Furthermore, unlike other areas, the eastern region of Tibet exhibits no discernible seasonal pattern in HCHO VCD. The anomalous variation in HCHO concentrations in Tibet can primarily be attributed to long-distance transnational transport originating from incomplete combustion in India Assam. Our research underscores the urgent need for enhanced atmospheric environmental management in Tibet.

Abstract Spacer acquisition step in CRISPR-Cas system involves the recognition and subsequent integration of protospacer by the Cas1-Cas2 complex in CRISPR-Cas systems. Here we report an anti-CRISPR protein, AcrVA5, and reveal the mechanisms by which it strongly inhibits protospacer integration. Our biochemical data shows that the integration by Cas1-Cas2 was abrogated in the presence of AcrVA5. AcrVA5 exhibits low binding affinity towards Cas2 and acetylates Cas2 at Lys55 on the binding interface of the Cas2 and AcrVA5 N-terminal peptide complex to inhibit the Cas2-mediated endonuclease activity. Moreover, a detailed structural comparison between our crystal structure and homolog structure shows that binding of AcrVA5 to Cas2 causes steric hindrance to the neighboring protospacer resulting in the partial disassembly of the Cas1-Cas2 and protospacer complex, as demonstrated by electrophoretic mobility shift assay. Our study focuses on this mechanism of spacer acquisition inhibition and provides insights into the biology of CRISPR-Cas systems.

BackgroundThe correlation between oxidative stress and female infertility pathogenesis was established, and the oxidative balance score (OBS) can serve as a measure of overall oxidative stress burden within an individual. Prior reports have not addressed the relationship between OBS and female infertility. This study endeavors to investigate the association between infertility risk in female and OBS.MethodsThe analysis focused on data from the National Health and Nutrition Examination Survey 2013-2018. OBS was determined from 16 dietary components and 4 lifestyle components. Multivariate logistic regression was employed to investigate the relationship between OBS and female infertility. Further stratified analysis was conducted to examine the associations across various subgroups. To elucidate the dose-response relationship between infertility risk in female and OBS, a restricted cubic spline function was employed.ResultsThe study included a total of 1410 participants. Through weighted multivariable logistic regression analysis, we observed a consistent inverse correlation between OBS and the risk of female infertility [OR (95% CI) = 0.97 (0.95, 0.99), p = 0.047]. When participants were segregated into quartiles based on OBS, those in the highest quartile had a 61% [OR (95% CI) = 0.39 (0.2, 0.79), p = 0.01] reduced risk of infertility compared to those in the lowest quartile of OBS. A trend test assessing OBS by quartile also revealed the relationship between OBS and female infertility. This correlation remained constant across both dietary and lifestyle OBS. Additionally, lifestyle OBS and female infertility exhibited a nonlinear association. A sensitivity analysis verified the consistency of our findings.ConclusionThe study found that a higher OBS is associated with a lower prevalence of female infertility. These results emphasized the potential role of oxidative homeostasis in the pathogenesis of infertility and highlighted the importance of follow-up studies and prevention strategies.

Understanding the vertical distribution of ozone is crucial when assessing both its horizontal and vertical transport, as well as when analyzing the physical and chemical properties of the atmosphere. One of the most effective ways to obtain high spatial resolution ozone profiles is through satellite observations. The Environmental Trace Gases Monitoring Instrument (EMI) deployed on the Gaofen-5 satellite is the first Chinese ultraviolet–visible hyperspectral spectrometer. However, retrieving ozone profiles using backscattered radiance values measured by the EMI is challenging due to unavailable measurement errors and a low signal-to-noise ratio. The algorithm developed for the Tropospheric Monitoring Instrument did not allow us to retrieve 87% of the EMI pixels. Therefore, we developed an algorithm specific to the characteristics of the EMI. The fitting residuals are smaller than 0.3% in most regions. The retrieved ozone profiles were in good agreement with ozonesonde data, with maximum mean biases of 20% at five latitude bands. By applying EMI averaging kernels to the ozonesonde profiles, the integrated stratospheric column ozone and tropospheric column ozone also showed excellent agreement with ozonesonde data. The lower layers (0–7.5 km) of the EMI ozone profiles reflected the seasonal variation in surface ozone derived from the China National Environmental Monitoring Center (CNEMC). However, the upper layers (9.7–16.7 km) of the ozone profiles show different trends, with the ozone peak occurring at an altitude of 9.7–16.7 km in March, 2019. A stratospheric intrusion event in central China from August 11 to 15, 2019, is captured using the EMI ozone profiles, potential vorticity data, and relative humidity data. The increase in the CNEMC ozone concentration showed that downward transport enhanced surface ozone pollution.

Ecological source areas play a pivotal role in nature preservation and soil conservation. These areas are critical in optimizing land-use patterns and fostering the establishment facilitating the establishment of protected ecological source areas. In this study, two types of state layers of ecological source area change were extracted based on land cover data and integrated with an intelligent algorithm to analyze the role of ecological factors contributing to land change. Recommendations are proposed to enhance the optimization of the ecological spatial pattern within the Yellow River Basin. The results indicate key findings: (1) The ecological source areas in the Daxia River Basin experienced Fluctuations between 1990 and 2020 due to the interconversion of grassland and unused land. The change was relatively smooth during 1990–2000, with the ecological source areas increasing slightly by 16.016 km2. From 2000 to 2010, the proportion of unutilized land transferred to grassland was 6.3%, which is significantly higher than the annual transfer average of 1.6%. This is mainly due to the ecological protection measures in the cities of Linxia and Hezuo. Between 2010 and 2020, economic construction resulted in the loss of grassland, and the percentage of grassland turned out was 7.3%, which was significantly higher than the annual average of 1.8%. (2) In the Daxia River Basin, rainfall, sunlight intensity, temperature, and elevation had a greater impact on land change during the period from 1990 to 2020, with contributions of −0.4, 0.09, 0.08, and −0.26, respectively.

The Ili River Basin (IRB) is located in the northwest of China. With its large-scale zone and abundant resources, it is believed to be a “wet island” and a biotic resource storehouse in the dry regions of Eurasia. The IRB has stable ecological conditions and abundant water resources, providing natural conditions for agricultural production and human settlements. With the population increasing and economic development advancing, the competition for land resources is becoming fierce, leading to some ecological problems in this region. Therefore, understanding the spatiotemporal changes and driving mechanisms of the “three-zone space” (TZS) in the IRB is of significant practical importance for promoting sustainable development and optimizing the territorial spatial pattern. This study first analyzes the characteristics and intensity of the TZS changes from 2000 to 2020. Then, it utilizes the optimized parameter Geodetector (OPGD) to analyze the driving mechanisms behind these changes. The results show the following. Firstly, the agricultural space (AS) increased by a total of 837.5 km2, the urban space (US) increased by 519.64 km2, and other ecological space (OES) increased by 1518.83 km2. Green ecological space (GES) decreased by 2875.97 km2. Secondly, intensity analysis indicated that the total TZS change in IRB was 11.07%. At the spatial-type level, the increased intensities of OES, US, and AS were active. In spatial transformation intensity, US and OES tended to transform into AS; AS tended to transform into US; and OES and GES had a mutual transformation tendency. Thirdly, AS converted into US around emerging cities like Khorgas and Cocodala. The conversion towards GES was scattered. The mutual conversion between OES and GES showed spatial distribution consistency, mainly occurring in the Borohoro ranges and the Halik ranges. Lastly, regarding the driving mechanisms, the evolution of US in the IRB was driven by social and economic factors. Location and climate factors accelerated agricultural development, facilitating the transformation of GES and OES into AS. Climate and economic factors played a crucial role in the scale of conversions between OES and GES. The findings can provide a basis for the governance and protection of the IRB, help to form a rational territorial spatial pattern, and offer scientific guidance for sustainable land management.

Abstract Background Microcystic urothelial carcinoma (MUC) is a rare variant of urothelial carcinoma with histological appearances similar to begin lesions. Thus far, approximately 50 cases have been reported. Here, we investigated the clinicopathological features of MUC. Methods Clinical data and paraffin-embedded tissue blocks were collected. Immunohistochemical staining and polymerase chain reaction–Sanger sequencing were performed to detect the phenotype and TERT mutation status of MUC, respectively. Results The mean patient age was 58.8 ± 14.5 years, with a male predominance (8:2). The pathological stage was T1 in one case, T2 in three cases, T3 in four cases, and T4 in two cases. Tumor metastases or death occurred in all five patients who were followed up within 1–3 years. Histological analyses revealed microcystic, tubular, cribriform, and occasionally cord-like structures, which generally lacked interstitial reactions. The lumens were empty, contained eosinophilic secretion, or were filled with mucin. The microcysts/tubules/cribriform patterns were lined by flat, cuboid, signet ring, or columnar types of epithelia. The cuboid, signet ring, and columnar types represented “glandular metaplasia” or glandular differentiation of urothelial carcinoma. Immunohistochemistry analyses revealed distinct co-expression patterns involving the luminal markers FOXA1 and GATA3, as well as the basal markers CK5/6 and CD44. All 10 cases exhibited a luminal phenotype according to the GATA3+/CK14- criterion, whereas nine cases exhibited a luminal phenotype according to the FOXA1+/CK14- criterion. The telomerase reverse transcriptase-C228T mutation was detected in seven cases. Conclusions MUC is a rare variant with a deceptively benign form of urothelial carcinoma, which is generally identified as a late-stage tumor with a poor prognosis. It exhibits distinct co-expression of luminal and basal markers, along with the TERT-C228T mutation.

Recently, the vascular protective effect of anti-diabetic agents has been receiving much attention. Sodium glucose cotransporter 2 (SGLT2) inhibitors had demonstrated reductions in cardiovascular (CV) events. However, the therapeutic effect of dapagliflozin on angiogenesis in peripheral arterial disease was unclear. This study aimed to explore the effect and mechanism of dapagliflozin on angiogenesis after hindlimb ischemia. We first evaluated the effect of dapagliflozin on post-ischemic angiogenesis in the hindlimbs of rats. Laser doppler imaging was used to detect the hindlimb blood perfusion. In addition, we used immunohistochemistry to detect the density of new capillaries after ischemia. The relevant signaling pathways of dapagliflozin affecting post-ischemic angiogenesis were screened through phosphoproteomic detection, and then the mechanism of dapagliflozin affecting post-ischemic angiogenesis was verified at the level of human umbilical vein endothelial cells (HUVECs). After subjection to excision of the left femoral artery, all rats were randomly distributed into two groups: the dapagliflozin group (left femoral artery resection, receiving intragastric feeding with dapagliflozin (1 mg/kg/d), for 21 consecutive days) and the model group, that is, the positive control group (left femoral artery resection, receiving intragastric feeding with citric acid–sodium citrate buffer solution (1 mg/kg/d), for 21 consecutive days). In addition, the control group, that is the negative control group (without left femoral artery resection, receiving intragastric feeding with citric acid–sodium citrate buffer solution (1 mg/kg/d), for 21 consecutive days) was added. At day 21 post-surgery, the dapagliflozin-treatment group had the greatest blood perfusion, accompanied by elevated capillary density. The results showed that dapagliflozin could promote angiogenesis after hindlimb ischemia. Then, the ischemic hindlimb adductor-muscle tissue samples from three rats of model group and dapagliflozin group were taken for phosphoproteomic testing. The results showed that the PI3K-Akt-eNOS signaling pathway was closely related to the effect of dapagliflozin on post-ischemic angiogenesis. Our study intended to verify this mechanism from the perspective of endothelial cells. In vitro, dapagliflozin enhanced the tube formation, migration, and proliferation of HUVECs under ischemic and hypoxic conditions. Additionally, the dapagliflozin administration upregulated the expression of angiogenic factors phosphorylated Akt (p-Akt) and phosphorylated endothelial nitric oxide synthase (p-eNOS), as well as vascular endothelial growth factor A (VEGFA), both in vivo and in vitro. These benefits could be blocked by either phosphoinositide 3-kinase (PI3K) or eNOS inhibitor. dapagliflozin could promote angiogenesis after ischemia. This effect might be achieved by promoting the activation of the PI3K-Akt-eNOS signaling pathway. This study provided a new perspective, new ideas, and a theoretical basis for the treatment of peripheral arterial disease.

Habitat quality is an indicator of the ecological evolution of a region, and evaluating habitat quality utilizing Machine Learning approaches can reflect the ecological status of a region more objectively. Gridded statistical ecological factors in the study region were utilized to build the Ecological Information State Layer (EISL) in the grid space. Calculate the Environmental Quality Index (EQI) of the sampled grid to evaluate the performance index of the models on the sampled grid. The model with the optimal performance index is selected for the task of habitat quality classification in the research region, and then especially decision-making advice is offered by inverting the degree of influence of ecological elements on habitat quality. The results show that: (1) The Semi-supervised Ensemble Learning model (Tri-training) Accuracy, Kappa coefficient, and F1-score are 0.93, 0.89, and 0.92, respectively, as the optimal model for the habitat quality classification task. (2) Based on the results of the ecological categories calculation, the current ecosystem quality of the southwestern section of the Daxia River Basin is maintained as a positive indicator. the ecosystem quality inside the living space centered on the cities of Linxia and Hezuo shows negative indicator changes. (3) The calculation results of the inverse importance of ecological factors show that vegetation index and human population density are the key factors impacting the habitat quality of the Daxia River Basin. In the ecological management of Daxia River Basin, the degree of spatial aggregation of people's settlements should be reduced while preserving and expanding vegetation cover. Using Tri-training's comprehensive analysis of multiple ecological factors, regional habitat quality can be accurately assessed.

Cross-body link refers to the wireless connection between two wearable devices when they are both worn or near the body, such as that of a virtual reality (VR) headset and its controllers. It is one of the most challenging wireless scenarios in terms of link budget, due to severe shadowing effects when controllers are placed at the back side of the body. This is especially true when the users are in an outdoor environment where there is less reflection from the surrounding. This paper investigates the wireless propagation mechanism, including line-of-sight, ground reflection, and creeping waves. Based on that, through simulation and measurement experiments, this work analyzes the impact of different antenna designs on the cross-body link of VR/AR devices, including one novel compact low-profile antenna named Distributed Monopole (DM), and two conventional antennas. Due to the polarization advantages, both the novel DM antenna and the patch antenna shows significantly better performance than the dipole antenna. The DM antenna also shows a 2–4 dB advantage over the patch antenna due to its omni-directional field pattern. Time-domain analysis and statistical approaches are suggested to fully characterize the cross-body link of VR/AR antennas and body propagation.

Abstract Polycystic ovary syndrome (PCOS), a common reproductive endocrine disease, has clinically heterogeneous characteristics. Recently, cuproptosis causes several diseases by killing cells. Hence, we aimed to explore cuproptosis-related molecular clusters in PCOS and construct a prediction model. Based on the GSE5090, GSE43264, GSE98421, and GSE124226 datasets, an analysis of cuproptosis regulators and immune features in PCOS was conducted. In 25 cases of PCOS, the molecular clusters of cuproptosis-related genes and the immune cell infiltration associated with PCOS were investigated. Weighted gene co-expression network analysis was used to identify differentially expressed genes within clusters. Next, we compared the performance of the random forest model, support vector machine model, generalized linear model, and eXtreme Gradient Boosting for deciding the optimum machine model. Validation of the predictive effectiveness was accomplished through nomogram, calibration curve, decision curve analysis, and using other two datasets. PCOS and non-PCOS controls differed in the dysregulation of cuproptosis-related genes and the activation of immunoreaction. Two cuproptosis-related molecular clusters associated with PCOS were identified. Significant heterogeneity was noted in immunity between the two clusters based on the analysis of immune infiltration. The immune-related pathways related to cluster-specific differentially expressed genes in Cluster1 were revealed by functional analysis. With a relatively low residual error and root mean square error and a higher area under the curve (1.000), the support vector machine model demonstrated optimal discriminative performance. An ultimate 5-gene-based support vector machine model was noted to perform satisfactorily in the other two validation datasets (area under the curve = 1.000 for both). Moreover, the nomogram, calibration curve, and decision curve analysis showed that PCOS subtypes can be accurately predicted. Our study results helped demonstrate a comprehensive understanding of the complex relationship between cuproptosis and PCOS and establish a promising prediction model for assessing the risk of cuproptosis in patients with PCOS.

The effect of Tremella fuciformis polysaccharide (TFP) on the retrogradation property and aroma profile changes of tteok during storage was investigated. Results indicated that addition of TFP significantly increased the stability to thermal and mechanical shearing of starch, decreased short-term retrogradation, the hardness and the retrogradation enthalpy (ΔH) of tteok during storage, but had no significant effect on the amylopectin chain length of tteok. The possible mechanism for the retarding staling effect of TFP is related to the interaction between TFP and starch chains that interferes with the alignment of starch chains. Electronic nose and gas chromatography-mass spectrum (GC-MS) analysis results showed that the difference in the concentrations of volatile compounds and fatty acids of tteoks at different storage time gradually increased with the advancement of storage period. The addition of TFP to tteok inhibited the development of unpleasant volatile compounds, probably by delaying the oxidation and decomposition of lipids and preserving the antioxidant phenolic compounds in tteok, thus slowing down the flavor deterioration of tteok and contributing to flavor maintainace. Overall, this study could help food manufacturers to choose a high-effective and natural polysaccharide to control the retrogradation rate and flavor loss of tteok.

Abstract Background Phyllodes tumors belong to a spectrum of biphasic fibroepithelial lesions and are most commonly found in the breast. They are extremely rare in the urinary tract and only one case of bladder phyllodes tumor has been reported. Case presentation We present a 69-year-old man with gross hematuria without an apparent cause. Computed tomography-urography and cystoscopic examination revealed a 5 × 4 cm lesion in the right ureteral orifice. He underwent a laparoscopic nephroureterectomy and partial cystectomy. Postoperative pathology confirmed a leaf-like structure consisting of myxoid stroma and peripheral urothelium. Stromal cells were spindle-shaped and stellate in appearance with no conspicuous cytological atypia or mitosis. The outlining urothelium had varying degrees of dysplasia, while in areas with moderate-to-severe dysplasia, active mitotic activity, abnormal giant cells, and focal early infiltration were observed. Overall, this case had the morphological features of benign phyllodes tumors and concomitant invasive urothelial carcinoma inside. The patient remained disease-free at 7 months after surgery. Conclusion We report the first ureteral tumor with the morphological characteristics of a phyllodes tumor and concomitant invasive urothelial carcinoma inside. Considering the potential for local recurrence of phyllodes tumors and invasive urothelial carcinoma, long-term clinical and radiological follow-up of such lesions are advisable.

Ibuprofen (IBU) was a widely used NSAID (a type of nonsteroidal anti-inflammatory drug) worldwide, and many drug deliveries had been reported to enhance bioavailability. However, higher bioavailability would increase the danger of renal injury caused by oxidative stress. This study prepared IBU-Polygonatum sibiricum polysaccharide (IBU-PSP) drug delivery system via mechanochemical method. Due to drug delivery and renal protection effect of Polygonatum sibiricum polysaccharide (PSP), the solubility of IBU-PSP was increased 8.22 times, and the bioavailability was increased 2.52 times compared with IBU, carrageenin-induced rat paw edema test also increased. Meanwhile, short-term and long-term renal injuries induced by IBU were notable decreases. In conclusion, IBU-PSP was a multifunctional drug delivery system with superior anti-inflammatory and renal protection effects. It will benefit from developing high-efficiency NADIs preparations with safer clinical applications while providing an efficient and energy-saving technology for polysaccharide drug delivery.

Abstract 7-methylguanosine (m7G) modification is recently found to conservatively exist in RNA internal position besides mRNA caps and mediates the various RNA metabolisms. As the core confirmed transmethylase of m7G modification, METTL1 has been reported in certain human cancers. However, the role of internal m7G at miRNAs and its core writer METTL1 in bladder cancer (BCa) remains to be elucidated. Here, we demonstrated that METTL1 was indispensable for BCa proliferation and metastasis in vitro and in vivo. By combining miRNA sequencing, m7G methylated RNA immunoprecipitation (MeRIP) and RIP, we identified METTL1 promoted the processing of miR-760 in an m7G-dependent manner. Transcription sequencing suggested that METTL1 indirectly degrades tumor suppressor ATF3 mRNA mediated by miR-760. Together, we concluded a regulatory axis composed of METTL1/m7G/miR-760/ATF3 in regulating BCa progression and provided potential therapeutic targets for BCa.

BackgroundDysregulation of cell death and defective clearance of dying cells are closely related to the pathogenesis of lupus nephritis (LN). However, the contribution of a recently discovered form of programmed cell death (PCD) called ferroptosis to LN has not been explored in detail. The purpose of this study was to investigate the role of ferroptosis and its associated metabolic pathways in the pathogenesis of LN.MethodsThe composite gene expression scores were calculated by averaging the z-scored transformed log2 expressed genes within each form of PCD and pathway. Immunohistochemistry and immunofluorescence assays were used to verify the bioinformatics results.ResultsWe determined that ferroptosis is prominently and specifically elevated in the glomerular compartment of LN patients compared to other forms of PCD and kidney disease. This finding was then verified by immunohistochemical staining of 4-HNE (a key indicator for ferroptosis) expression in our own cohort (P < 0.0001). Intercorrelation networks were observed between 4-HNE and blood urea nitrogen, SLE disease activity index, serum creatinine, and complement 4, and negatively correlated with glomerular filtration rate in our own LN cohort (P < 0.05). Furthermore, enhanced iron metabolism and reduced fatty acid synthesis may be the most important factors for ferroptosis within the glomerulus. Through analysis of a single cell sequencing dataset and verification of immunohistochemical and immunofluorescence staining, aberrantly activated lipid peroxidation in CD163+ macrophages and CD10+ PC+ (pyruvate carboxylase) epithelial cells indicated that they may be undergoing ferroptosis in the glomerular compartment.ConclusionsTwo dysregulated genes, CD163 and PC, were identified and verified that were significantly associated with lipid peroxidation. Targeting ferroptosis in CD163+ macrophages and CD10+ PC+ epithelial cells may provide novel therapeutic approaches in LN.

Abstract Background Circular RNA (circRNA) is a novel class noncoding RNA (ncRNA) that plays a critical role in various cancers, including prostate cancer (PCa). However, the clinical significance, biological function, and molecular mechanisms of circRNAs in prostate cancer remain to be elucidated. Methods A circRNA array was performed to identified the differentially expressed circRNAs. circPDE5A was identified as a novel circRNA which downregulated in clinical samples. Functionally, the in vitro and in vivo assays were applied to explore the role of circPDE5A in PCa metastasis. Mechanistically, the interaction between circPDE5A and WTAP was verified using RNA pulldown followed by mass spectrometry, RNA Immunoprecipitation (RIP) assays. m6A methylated RNA immunoprecipitation sequencing (MeRIP-seq) was then used to identified the downstream target of circPDE5A. Chromatin immunoprecipitation assay (ChIP) and dual-luciferase reporter assay were used to identified transcriptional factor which regulated circPDE5A expression. Results circPDE5A was identified downregulated in PCa tissues compared to adjacent normal tissue and was negatively correlated with gleason score of PCa patients. circPDE5A inhibits PCa cells migration and invasion both in vitro and in vivo. circPDE5A blocks the WTAP-dependent N6-methyladenisine (m6A) methylation of eukaryotic translation initiation factor 3c (EIF3C) mRNA by forming the circPDE5A-WTAP complex, and finally disrupts the translation of EIF3C. Moreover, the circPDE5A-dependent decrease in EIF3C expression inactivates the MAPK pathway and then restrains PCa progression. Conclusions Our findings demonstrate that FOXO4-mediated upregulation of circPDE5A controls PCa metastasis via the circPDE5A-WTAP-EIF3C-MAPK signaling pathway and could serve as a potential therapeutic targer for PCa.

The changes of global gaseous pollutants during the COVID-19 pandemic in early 2020 were retrieved from Chinese ultraviolet–visible hyperspectral satellite instrument through a series of remote sensing algorithm optimizations.

We experimentally investigate trap-loss spectra of the cesium 6S1/2(F = 4) → 71P3/2 Rydberg transition by combining the cesium atomic magneto-optical trap with the narrow-linewidth, continuously tunable 318.6 nm ultraviolet laser. Specifically, the atoms in the magneto-optical trap are excited to the Rydberg state due to the ultraviolet laser single-step Rydberg excitation, which leads to the reduction of atomic fluorescence. Based on the trap-loss spectroscopy technology, the Autler–Townes (AT) splitting due to a strong cooling laser is observed, and the parameter dependence of the AT splitting interval of trap-loss spectroscopy is investigated. The effective temperature of cold atoms is measured by using simplified time-of-flight fluorescence imaging. In addition, closed-loop feedback power stabilization of 318.6 nm ultraviolet laser is carried out. This lays the foundation for further experimental research related to the Rydberg atoms using ultraviolet lasers, which is of great significance for the development of quantum computing and quantum information.

Formaldehyde (HCHO) is a toxic and hazardous air pollutant that widely exists in atmosphere. Insufficient spatial and temporal coverage of surface HCHO measurements is limiting studies on surface HCHO-related air quality management and health risk assessment. This study develops a method to derive global ground-level HCHO concentrations from satellite-based tropospheric HCHO columns using TM5-simulated surface-to-column conversion factor with coarse spatial resolution. The method improves the factor more representative in finer grids by constraining TM5-simulated vertical profile shapes with satellite HCHO columns. The surface HCHO concentrations derived by the Ozone Mapping and Profiler Suite (OMPS) show good correlation with in situ HCHO measurements (R = 0.59) from the U.S. Environmental Protection Agency surface network. We investigated how surface HCHO relates to urbanization and population aggregation over seven regions with high HCHO pollution. The results show urban HCHO increases as a power function with population size in China, India, and West Asia. HCHO concentrations in rural aeras also present strong log–log relationship with population aggregation in China, India, the United States, and Europe. Moreover, OMPS-derived ground-level HCHO concentrations were used to estimate global cancer burden caused by long-term outdoor HCHO exposure. The results show that up to 418188 more people worldwide will develop this cancer during the human life cycle. The global cancer burden is mainly from the South-East Asia region (33.11 %) and the Western Pacific region (22.95 %). This cancer occurrence in India and China is ranked 1st and 2nd in the world due to the large population size and serious HCHO pollution. Besides, global surface HCHO concentrations and cancer burden derived from the Environmental Trace Gases Monitoring Instrument which is China’s first hyperspectral space-based spectrometer are found similar patterns with that from OMPS. Our results provide new insight into the impact of population urbanization on HCHO pollution and global outdoor HCHO-caused health risks.

This paper proposes a novel miniaturized wearable antenna (mosaic antenna) for cross-body communication featuring a superior performance compared to five commonly utilized wearable antenna topologies. The proposed mosaic antenna optimally excites the surface waves to enable cross-body communication yet still with a low profile and a miniaturized size. As a proof-of-concept of the unique capabilities of this antenna, an inkjet-printed flexible wearable prototype on Polytetrafluoroethylene (PTFE, also known as Teflon) has been fabricated in a highly customizable, scalable and low-cost process and has been used as an enabler for human activities recognition coupled with machine learning techniques powered by Google TensorFlow. By utilizing proof-of-concept on-body networks consisting of mosaic antennas, human activity can be detected with an accuracy 91.9% for RF signal-based recognition techniques, despite the variability among different users and environments.

This paper explores antenna's polarization for Radio-Frequency Identification (RFID) based non-contact human activity detection. For the first time, a cross circular polarization configuration between reader antenna and tag antenna is proposed to increase the sensing range and spatial sensitivity. Compared to conventional RFID configurations - linearly polarized (LP) tag and circularly polarized (CP) reader, a cross CP configuration can improve the signal-to-noise ratio (SNR) which leads to 230% increase in the detection area over traditional approach in our experiment. As the result of the improvement of spatial sensitivity, the proposed approach can detect subtle and small body movements at almost 4.5m from the reader, such as head movements or even respiration, which enables a low-cost, easy-to-use, non-contact and non-intrusive monitoring of the elderly and disabled peoples in places like hospitals and assisted living homes.

Background Unruptured intracerebral aneurysm wall enhancement (AWE) on vessel wall magnetic resonance imaging scans may be a promising predictor for rupture‐prone intracerebral aneurysms. However, the pathophysiology of AWE remains unclear. To this end, the association between AWE and histopathological changes was assessed in this study. Methods and Results A total of 35 patients with 41 unruptured intracerebral aneurysms who underwent surgical clipping were prospectively enrolled. A total of 27 aneurysms were available for histological evaluation. The macroscopic and microscopic features of unruptured intracerebral aneurysms with and without enhancement were assessed. The microscopic features studied included inflammatory cell invasion and vasa vasorum, which were assessed using immunohistochemical staining with CD68, CD3, CD20, and myeloperoxidase for the former and CD34 for the latter. A total of 21 (51.2%) aneurysms showed AWE (partial AWE, n=7; circumferential AWE, n=14). Atherosclerotic and translucent aneurysms were identified in 17 and 14 aneurysms, respectively. Aneurysm size, irregularity, and atherosclerotic and translucent aneurysms were associated with AWE on univariate analysis (P

Analyzing vertical distribution characters of air pollutants is conducive to study the mechanisms under polluted atmospheric conditions. Nitrous acid (HONO) is a kind of crucial species in photochemical cycles. Exploring the influence and sources of HONO in air pollution at different altitudes offers some insights into the research of tropospheric oxidation chemistry processes. Ground-based multi-axis differential optical absorption spectroscopy (MAX-DOAS) measurements were conducted in Shanghai, China, from December 2017 to March 2018 to investigate vertical distributions and diurnal variations of trace gases (NO2, HONO, HCHO, SO2, and water vapor) and aerosol extinction coefficient in the boundary layer. Aerosol and NO2 showed decreasing profile exponentially, SO2 and HCHO concentrations were observed relatively high values in the middle layer. SO2 was caused by industrial emissions, while HCHO was from secondary sources. As for HONO, below 0.82 km, the heterogeneous reactions of NO2 impacted on forming HONO, while in the upper layers, vertical diffusion might be the dominant source. The contribution of OH production from HONO photolysis at different altitudes was mainly controlled by the concentration of HONO. MAX-DOAS measurements characterize the vertical structure of air pollutants in Shanghai and provide further understanding for HONO formation, which can help deploy advanced measurement platforms of regional air pollution over eastern China.

Context: Curcumin (CUR) is a promising drug candidate based on its broad bioactivities and good antitumor effect, but the application of CUR is potentially restricted because of its poor solubility and bioavailability. Objective: This study aims at developing a simple and effective drug delivery system for CUR to enhance its solubility and bioavailability thus to improve its antitumor efficacy. Materials and methods: Curcumin nanosuspensions (CUR-NSps) were prepared by precipitation-ultrasonication method using mPEG2000-DSPE and soybean lecithin as a combined stabilizer. Results: CUR-NSps with a high drug payload of 67.07% were successfully prepared. The resultant CUR-NSps had a mean particle size of 186.33 ± 2.73 nm with a zeta potential of −19.00 ± 1.31 mV. In vitro cytotoxicity assay showed that CUR-NSps exhibited enhanced cytotoxicity compared to CUR solution. The pharmacokinetics results demonstrated that CUR-NSps exhibited a significantly greater AUC0–24 and prolonged MRT compared to CUR injections after intravenous administration. In the biodistribution study, CUR-NSps demonstrated enhanced biodistribution compared with CUR injections in liver, spleen, kidney, brain, and tumor. The CUR-NSps also showed improved antitumor therapeutic efficacy over the injections (70.34% versus 40.03%, p

While genomic sequencing routinely identifies oncogenic alterations for the majority of cancers, many tumors harbor no discernable driver lesion. Here, we describe the exceptional molecular phenotype of a genomically quiet kidney tumor, clear cell papillary renal cell carcinoma (CCPAP). In spite of a largely wild-type nuclear genome, CCPAP tumors exhibit severe depletion of mitochondrial DNA (mtDNA) and RNA and high levels of oxidative stress, reflecting a shift away from respiratory metabolism. Moreover, CCPAP tumors exhibit a distinct metabolic phenotype uniquely characterized by accumulation of the sugar alcohol sorbitol. Immunohistochemical staining of primary CCPAP tumor specimens recapitulates both the depletion of mtDNA-encoded proteins and a lipid-depleted metabolic phenotype, suggesting that the cytoplasmic clarity in CCPAP is primarily related to the presence of glycogen. These results argue for non-genetic profiling as a tool for the study of cancers of unknown driver.

Recently, the occurrence of fog and haze over China has increased. The retrieval of trace gases from the multi-axis differential optical absorption spectroscopy (MAX-DOAS) is challenging under these conditions. In this study, various reported retrieval settings for formaldehyde (HCHO) and sulfur dioxide (SO2) are compared to evaluate the performance of these settings under different meteorological conditions (clear day, haze, and fog). The dataset from 1st December 2019 to 31st March 2020 over Nanjing, China, is used in this study. The results indicated that for HCHO, the optimal settings were in the 324.5–359 nm wavelength window with a polynomial order of five. At these settings, the fitting and root mean squared (RMS) errors for column density were considerably improved for haze and fog conditions, and the differential slant column densities (DSCDs) showed more accurate values compared to the DSCDs between 336.5 and 359 nm. For SO2, the optimal settings for retrieval were found to be at 307–328 nm with a polynomial order of five. Here, root mean square (RMS) and fitting errors were significantly lower under all conditions. The observed HCHO and SO2 vertical column densities were significantly lower on fog days compared to clear days, reflecting a decreased chemical production of HCHO and aqueous phase oxidation of SO2 in fog droplets.

Air quality is strongly influenced by both local emissions and regional transport. Atmospheric chemical transport models can distinguish between emissions and regional transport sources in air pollutant concentrations. However, quantifying model inventories is challenging due to emission changes caused by the recent strict control measures taken by the Chinese government. In this study, we use NO2 column observations from the Tropospheric Monitoring Instrument to retrieve top-down nitrogen oxide (NOX) emissions and quantify the contributions of local emissions and regional transport to NOx in Beijing (BJ), from 1 November 2018 to 28 February 2019 (W_2018) and 1 November 2019 to 29 February 2020 (W_2019). In W_2018 and W_2019, the BJ bottom-up NOX emissions from the multi-resolution emission inventory for China in 2017 were overestimated by 11.8% and 40.5%, respectively, and the input of NOX from other cities to BJ was overestimated by 10.9% and 51.6%, respectively. The simulation using our adjusted inventory exhibited a much higher spatial agreement (slope = 1.0, R2 = 0.79) and reduced a mean relative error by 45% compared to those of bottom-up NOX emissions. The top-down inventory indicated that (1) city boundary transport contributes approximately 40% of the NOX concentration in BJ; (2) in W_2019, NOX emissions and transport in BJ decreased by 20.4% and 17.2%, respectively, compared to those of W_2018; (3) in W_2019, NOX influx substantially decreased (−699 g/s) in BJ compared to that of W_2018 despite negative meteorological conditions that should have increased NOx influx by +503 g/s. Overall, the contribution of intercity input to NOx in BJ has declined with decreasing emissions in the surrounding cities due to regional cooperative control measures, and the role of local emissions in BJ NOx levels was more prominent. Our findings indicate that local emissions may play vital roles in regional center city air quality.

Restrictions on human activities remarkably reduced emissions of air pollutants in China during the COVID-19 lockdown periods. However, distinct responses of O3 concentrations were observed across China. In the Beijing–Tianjin–Hebei (BTH) and Yangtze River Delta (YRD) regions, O3 concentrations were enhanced by 90.21 and 71.79% from pre-lockdown to lockdown periods in 2020, significantly greater than the equivalent concentrations for the same periods over 2015–2019 (69.99 and 43.62%, p < 0.001). In contrast, a decline was detected (−1.1%) in the Pearl River Delta (PRD) region. To better understand the underlying causes for these inconsistent responses across China, we adopted the least absolute shrinkage and selection operator (Lasso) and ordinary linear squares (OLS) methods in this study. Statistical analysis indicated that a sharp decline in nitrogen dioxide (NO2) was the major driver of enhanced O3 in the BTH region as it is a NOx-saturated region. In the YRD region, season-shift induced changes in the temperature/shortwave radiative flux, while lockdown induced declines in NO2, attributable to the rise in O3. In the PRD region, the slight drop in O3 is attributed to the decreased intensity of radiation. The distinct regimes of the O3 response to the COVID-19 lockdown in China offer important insights into different O3 control strategies across China.

In this paper, we present the Hefei EMI Cloud Retrieval Algorithm (HECORA), which uses information from the O2-O2 absorption band around 477 nm to retrieve effective cloud fraction and effective cloud pressure from satellite observations. The retrieved cloud information intends to improve the atmospheric trace gas products based on the Environment Monitoring Instrument (EMI) spectrometer. The HECORA method builds on OMCLDO2 and presents some evolutions. The Vector Linearized Discrete Ordinate Radiative Transfer (VLIDORT) model has been used to produce the Top of the Atmosphere (TOA) reflectance Look-up Tables (LUT) as a function of the cloud fraction and cloud pressure. Applying the Differential Optical Absorption Spectroscopy (DOAS) technique to the synthetic reflectance LUT, the reflectance spectra can be associated with O2-O2 geometrical vertical column densities (VCDgeo) and continuum reflectance. This is the core of the retrieval method, since there is a one-to-one relationship between O2-O2 VCDgeo and continuum reflectance, on the one hand, and effective cloud fraction and effective cloud pressure, on the other hand, for a given illumination and observing geometry and given surface height and surface albedo. We first used the VLIDORT synthetic spectra to verify the HECORA algorithm and obtained good results in both the Lambertian cloud model and the scattering cloud model. Secondly, HECORA is applied to OMI and TROPOMI and compared with OMCLDO2, FRESCO+, and OCRA/ROCINN cloud products. Later, the cloud pressure results from TROPOMI observations obtained using HECORA and FRESCO+ are compared with the CALIOP Cloud Layer product. HECORA is closer to the CALIOP results under low cloud conditions, while FRESCO+ is closer to high clouds due to the higher sensitivity of the O2 A-band to cloud vertical information. Finally, HECORA is applied to the TROPOMI NO2 retrieval. Validation of the tropospheric NO2 VCD with ground-based MAX-DOAS measurements shows that choosing HECORA cloud products to correct for photon path variations on the TROPOMI tropospheric NO2 VCD retrievals has better performance than using FRESCO+ under low cloud conditions. In conclusion, this paper shows that the HECORA cloud products are in good agreement with the well-established cloud products and that they are suitable for correcting the effect of cloud in trace gas retrievals. Therefore, HECORA has the potential to be applied to EMI.

BACKGROUND:HIV-related opportunistic infections (OIs) and malignancies continued to cause morbidity and mortality in Chinese HIV-infected individuals. The objective for this study is to elucidate the prevalence and spectrums of OIs and malignancies in HIV-infected patients in the Beijing Ditan Hospital. METHODS:The evaluation of the prevalence and spectrums of OIs and malignancies was conducted by using the clinical data of 834 HIV-infected patients admitted in the Beijing Ditan hospital from January 1, 2009, to November 30, 2012. RESULTS:The prevalence and spectrums of OIs and malignancies varied contingent on geographic region, transmission routes, and CD4 levels. We found that tuberculosis was most common OI and prevalence was 32.5%, followed by candidiasis(29.3%), Pneumocystis pneumonia(PCP)(22.4%), cytomegalovirus(CMV) infection(21.7%), other fungal infections(16.2%), mycobacterium avium complex(MAC)(11.3%), cryptococcosis(8.0%), progressive multifocal leukoencephalopathy(PML)(4.4%), Cerebral Toxoplasmosis(3.5%) and Penicillium marneffei infection(1.4%); while Lymphoma(2.9%), Kaposi's sarcoma(0.8%) and cervix carcinoma(0.3%) were emerged as common AIDS-defining malignancies. Pulmonary OI infections were the most prevalent morbidity and mortality in patients in the AIDS stage including pulmonary tuberculosis (26.6%) and PCP (22.4%). CMV infection(21.7%) was most common viral infection; Fungal OIs were one of most prevalent morbidity in patients in the AIDS stage, including oral candidiasis (29.3%), other fungal infection (16.2%), Cryptococcosis (8.0%) and Penicillium marneffei infection (1.4%). We found the low prevalence of AIDS-defining illnesses in central neural system in this study, including progressive multifocal leukoencephalopathy (4.4%), cerebral toxoplasmosis (3.5%), tuberculosis meningitis (3.2%), cryptococcal meningitis (2.4%) and CMV encephalitis (1.1%). In-hospital mortality rate was 4.3 per 100 person-years due to severe OIs, malignancies, and medical cost constraints. CONCLUSIONS:The prevalence and spectrums of OIs, malignancies and co-infections were discussed in this study. It would help increase the awareness for physicians to make a diagnosis and empirical treatment sooner and plan good management strategies, especially in resource limited regions.