TFE3-SLC36A1 axis promotes resistance to glucose starvation in kidney cancer cells.

Higher demand for nutrients including glucose is characteristic of cancer. "Starving cancer" has been pursued to curb tumor progression. An intriguing regime is to inhibit glucose transporter GLUT1 in cancer cells. In addition, during cancer progression, cancer cells may suffer from insufficient glucose supply. Yet, cancer cells can somehow tolerate glucose starvation. Uncovering the underlying mechanisms shall shed insight into cancer progression and benefit cancer therapy. TFE3 is a transcription factor known to activate autophagic genes. Physiological TFE3 activity is regulated by phosphorylation-triggered translocation responsive to nutrient status. We recently reported TFE3 constitutively localizes to the cell nucleus and promotes cell proliferation in kidney cancer even under nutrient replete condition. It remains unclear whether and how TFE3 responds to glucose starvation. In this study, we show TFE3 promotes kidney cancer cell resistance to glucose starvation by exposing cells to physiologically relevant glucose concentration. We find glucose starvation triggers TFE3 protein stabilization through increasing its O-GlcNAcylation. Furthermore, through an unbiased functional genomic study, we identify SLC36A1, a lysosomal amino acid transporter, as a TFE3 target gene sensitive to TFE3 protein level. We find SLC36A1 is overexpressed in kidney cancer, which promotes mTOR activity and kidney cancer cell proliferation. Importantly, SLC36A1 level is induced by glucose starvation through TFE3, which enhances cellular resistance to glucose starvation. Suppressing TFE3 or SLC36A1 significantly increases cellular sensitivity to GLUT1 inhibitor in kidney cancer cells. Collectively, we uncover a functional TFE3-SLC36A1 axis that responds to glucose starvation and enhances starvation tolerance in kidney cancer.

The P53-P21-RB1 pathway promotes BRD4 degradation in liver cancer through USP1.

Liver cancer is notoriously refractory to conventional therapeutics. Tumor progression is governed by the interplay between tumor-promoting genes and tumor-suppressor genes. BRD4, an acetyl lysine-binding protein, is overexpressed in many cancer types, which promotes activation of a pro-tumor gene network. But the underlying mechanism for BRD4 overexpression remains incompletely understood. In addition, understanding the regulatory mechanism of BRD4 protein level will shed insight into BRD4-targeting therapeutics. In this study, we investigated the potential relation between BRD4 protein level and P53, the most frequently dysregulated tumor suppressor. By analyzing the TCGA datasets, we first identify a strong negative correlation between protein levels of P53 and BRD4 in liver cancer. Further investigation shows that P53 promotes BRD4 protein degradation. Mechanistically, P53 indirectly represses the transcription of USP1, a deubiquitinase, through the P21-RB1 axis. USP1 itself is also overexpressed in liver cancer and we show USP1 deubiquitinates BRD4 in vivo and in vitro, which increases BRD4 stability. With cell proliferation assays and xenograft model, we show the pro-tumor role of USP1 is partially mediated by BRD4. With functional transcriptomic analysis, we find the USP1-BRD4 axis upholds expression of a group of cancer-related genes. In summary, we identify a functional P53-P21-RB1-USP1-BRD4 axis in liver cancer.

Optical Encryption Using Attention-Inserted Physics-Driven Single-Pixel Imaging.

Optical encryption based on single-pixel imaging (SPI) has made great advances with the introduction of deep learning. However, the use of deep neural networks usually requires a long training time, and the networks need to be retrained once the target scene changes. With this in mind, we propose an SPI encryption scheme based on an attention-inserted physics-driven neural network. Here, an attention module is used to encrypt the single-pixel measurement value sequences of two images, together with a sequence of cryptographic keys, into a one-dimensional ciphertext signal to complete image encryption. Then, the encrypted signal is fed into a physics-driven neural network for high-fidelity decoding (i.e., decryption). This scheme eliminates the need for pre-training the network and gives more freedom to spatial modulation. Both simulation and experimental results have demonstrated the feasibility and eavesdropping resistance of this scheme. Thus, it will lead SPI-based optical encryption closer to intelligent deep encryption.

Cystathionine gamma-lyase (Cth) induces efferocytosis in macrophages via ERK1/2 to modulate intestinal barrier repair.

BACKGROUND: The inflammatory response induced by intestinal ischaemia‒reperfusion injury (I/R) is closely associated with infectious complications and mortality in critically ill patients, and the timely and effective clearance of apoptotic cells is an important part of reducing the inflammatory response. Studies have shown that the efferocytosis by phagocytes plays an important role. Recently, studies using small intestine organoid models showed that macrophage efferocytosis could promote the repair capacity of the intestinal epithelium. However, no studies have reported efferocytosis in the repair of I/R in animal models. RESULTS: We used an in vivo efferocytosis assay and discovered that macrophage efferocytosis played an indispensable role in repairing and maintaining intestinal barrier function after I/R. In addition, the specific molecular mechanism that induced macrophage efferocytosis was Cth-ERK1/2 dependent. We found that Cth drove macrophage efferocytosis in vivo and in vitro. Overexpression/silencing Cth promoted/inhibited the ERK1/2 pathway, respectively, which in turn affected efferocytosis and mediated intestinal barrier recovery. In addition, we found that the levels of Cth and macrophage efferocytosis were positively correlated with the recovery of intestinal function in clinical patients. CONCLUSION: Cth can activate the ERK1/2 signalling pathway, induce macrophage efferocytosis, and thus promote intestinal barrier repair. Video Abstract.

STK25: a viable therapeutic target for cancer treatments?

Serine/threonine protein kinase 25 (STK25) is a critical regulator of ectopic lipid storage, glucose and insulin homeostasis, fibrosis, and meta-inflammation. More and more studies have revealed a strong correlation between STK25 and human diseases. On the one hand, STK25 can affect glucose and fatty acid metabolism in normal cells or tumors. On the other hand, STK25 participates in autophagy, cell polarity, cell apoptosis, and cell migration by activating various signaling pathways. This article reviews the composition and function of STK25, the energy metabolism and potential drugs that may target STK25, and the research progress of STK25 in the occurrence and development of tumors, to provide a reference for the clinical treatment of tumors.

Development and application of a multi-centre cloud platform architecture for water environment management.

To promote the intelligent and accurate management of river basins, especially large basins which involve many catchments, it is highly required to develop a useful platform to effectively coordinate arithmetic resources and data, and simultaneously help to make decisions based on the real-time calculation. In this study, a multi-centre cloud platform architecture called 3L4C was constructed, which includes a Cloud-edge-terminal Layer (3L), data centre, model centre, control centre, and customer-service centre (4C). Data fusion technology and an air-land-water coupled model were constructed. Based on HTML5, JavaScript, and Java, an integrated water environment management platform was created and applied to the Three Gorges Reservoir Basin, China. The platform was tested and successfully used for automatic water quality prediction, water environment pollution analysis and control, early warning of abnormal water quality, and emergency water pollution incident evaluation. This platform quickly and accurately forecasts and perfectly displays past, present and future state of the water environment, and offers beneficial support for management decisions in various water environment departments.

Determination of Dicofol in Tea Using Surface-Enhanced Raman Spectroscopy Coupled Chemometrics.

Dicofol is a highly toxic residual pesticide in tea, which seriously endangers human health. A method for detecting dicofol in tea by combining stoichiometry with surface-enhanced Raman spectroscopy (SERS) technology was proposed in this study. AuNPs were prepared, and silver shells were grown on the surface of AuNPs to obtain core-shell Au@AgNPs. Then, the core-shell Au@AgNPs were attached to the surface of a PDMS membrane by physical deposition to obtain a Au@AgNPs/PDMS substrate. The limit of detection (LOD) of this substrate for 4-ATP is as low as 0.28 × 10-11 mol/L, and the LOD of dicofol in tea is 0.32 ng/kg, showing high sensitivity. By comparing the modeling effects of preprocessing and variable selection algorithms, it is concluded that the modeling effect of Savitzky-Golay combined with competitive adaptive reweighted sampling-partial least squares regression is the best (Rp = 0.9964, RPD = 10.6145). SERS technology combined with stoichiometry is expected to rapidly detect dicofol in tea without labels.

Efficient representations of tumor diversity with paired DNA-RNA aberrations.

Cancer cells display massive dysregulation of key regulatory pathways due to now well-catalogued mutations and other DNA-related aberrations. Moreover, enormous heterogeneity has been commonly observed in the identity, frequency and location of these aberrations across individuals with the same cancer type or subtype, and this variation naturally propagates to the transcriptome, resulting in myriad types of dysregulated gene expression programs. Many have argued that a more integrative and quantitative analysis of heterogeneity of DNA and RNA molecular profiles may be necessary for designing more systematic explorations of alternative therapies and improving predictive accuracy. We introduce a representation of multi-omics profiles which is sufficiently rich to account for observed heterogeneity and support the construction of quantitative, integrated, metrics of variation. Starting from the network of interactions existing in Reactome, we build a library of "paired DNA-RNA aberrations" that represent prototypical and recurrent patterns of dysregulation in cancer; each two-gene "Source-Target Pair" (STP) consists of a "source" regulatory gene and a "target" gene whose expression is plausibly "controlled" by the source gene. The STP is then "aberrant" in a joint DNA-RNA profile if the source gene is DNA-aberrant (e.g., mutated, deleted, or duplicated), and the downstream target gene is "RNA-aberrant", meaning its expression level is outside the normal, baseline range. With M STPs, each sample profile has exactly one of the 2M possible configurations. We concentrate on subsets of STPs, and the corresponding reduced configurations, by selecting tissue-dependent minimal coverings, defined as the smallest family of STPs with the property that every sample in the considered population displays at least one aberrant STP within that family. These minimal coverings can be computed with integer programming. Given such a covering, a natural measure of cross-sample diversity is the extent to which the particular aberrant STPs composing a covering vary from sample to sample; this variability is captured by the entropy of the distribution over configurations. We apply this program to data from TCGA for six distinct tumor types (breast, prostate, lung, colon, liver, and kidney cancer). This enables an efficient simplification of the complex landscape observed in cancer populations, resulting in the identification of novel signatures of molecular alterations which are not detected with frequency-based criteria. Estimates of cancer heterogeneity across tumor phenotypes reveals a stable pattern: entropy increases with disease severity. This framework is then well-suited to accommodate the expanding complexity of cancer genomes and epigenomes emerging from large consortia projects.

Chronic atrophic gastritis and Helicobacter pylori infection status in liver transplant recipients.

AIM: To investigate the abnormalities of the upper gastrointestinal tract in liver transplant (LT) recipients, especially the prevalence of Helicobacter pylori infection and the incidence of chronic atrophic gastritis (CAG), and to explore the efficacy and safety of H pylori eradication treatment. METHODS: Endoscopic screening was performed prospectively on LT recipients who received regular follow-up in our center. A group of healthy subjects with same age and sex was selected as a control group at a ratio of 1:3 with propensity score matching. All H pylori-positive recipients received Bismuth-containing quadruple therapy (esomeprazole 20 mg + clarithromycin 500 mg + amoxicillin 1 g + bismuth 220 mg, all of the medicines were applied twice daily, for 14 days). RESULT: The prevalence of H pylori infection was significantly lower in LT group than control group [12/102 (11.8%) vs 98/306 (32.0%), P < .001], whereas the prevalence of CAG was similar between the two groups [48/102 (47.1%) vs 138/306 (45.1%), P = .731]. Meanwhile, the incidence of reflux esophagitis [18/102 (17.6%) vs 31/306 (10.1%), P = .043] and bile regurgitation [19/102 (18.6%) vs 30/306 (9.8%), P = .018] were higher in LT group. No correlation between the incidence of upper gastroduodenal abnormalities and postoperative time after liver transplantation was found. The success rate of H pylori eradication therapy was 100% (10/10). The blood concentration of immunosuppressants was 1.7-3.6 times above baseline values during H pylori eradication therapy; however, no severe adverse effects were observed during the proceed with dose adjustments of the immunosuppressants. CONCLUSION: Although the prevalence of H pylori infection was lower in LT recipients than in control subjects, the prevalence of CAG was like that of the general population. H pylori eradication therapy was safe and effective after liver transplantation in our preliminary study.

Digitizing omics profiles by divergence from a baseline.

Data collected from omics technologies have revealed pervasive heterogeneity and stochasticity of molecular states within and between phenotypes. A prominent example of such heterogeneity occurs between genome-wide mRNA, microRNA, and methylation profiles from one individual tumor to another, even within a cancer subtype. However, current methods in bioinformatics, such as detecting differentially expressed genes or CpG sites, are population-based and therefore do not effectively model intersample diversity. Here we introduce a unified theory to quantify sample-level heterogeneity that is applicable to a single omics profile. Specifically, we simplify an omics profile to a digital representation based on the omics profiles from a set of samples from a reference or baseline population (e.g., normal tissues). The state of any subprofile (e.g., expression vector for a subset of genes) is said to be "divergent" if it lies outside the estimated support of the baseline distribution and is consequently interpreted as "dysregulated" relative to that baseline. We focus on two cases: single features (e.g., individual genes) and distinguished subsets (e.g., regulatory pathways). Notably, since the divergence analysis is at the individual sample level, dysregulation can be analyzed probabilistically; for example, one can estimate the probability that a gene or pathway is divergent in some population. Finally, the reduction in complexity facilitates a more "personalized" and biologically interpretable analysis of variation, as illustrated by experiments involving tissue characterization, disease detection and progression, and disease-pathway associations.

Dual active sites of the Co2N and single-atom Co-N4 embedded in nitrogen-rich nanocarbons: a robust electrocatalyst for oxygen reduction reactions.

The development of low-cost, highly efficient and durable non-precious-metal (NPM) electrocatalysts for the oxygen reduction reaction (ORR) is of great significance. Herein, we report an ingenious two-step strategy for the fabrication of NPM electrocatalysts containing multifarious cobalt species embedded in nitrogen-rich nanocarbons (Co-N-C). Firstly, Co ions were fixed by coordination with 1H-Imidazo[4,5-f][1,10]phenanthroline (Hip), and secondly the Co-Hip precursor with abundant Co, C and N sources was subjected to calcination at various temperatures (700-900 °C). The obtained Co-N-C catalysts exhibited excellent activity in terms of the ORR in alkaline conditions, with a half-wave potential of 0.82 eV versus the reversible hydrogen electrode, which is close to that of commercial Pt/C. Moreover, the Co-N-C exhibited an unexpected catalytic activity with long-term stability and immunity to methanol which is better than commercial Pt/C catalyst, suggesting that Co-N-C with dual active sites of the single-atom Co sites (Co-N4) and Co2N can be a promising alternative to replace Pt-based electrocatalysts in fuel cells. This work can provide a new route to designing promising catalysts with dual active sites for ORR.

Evaluation of global and regional left ventricular myocardial work by echocardiography in patients with chronic kidney disease.

OBJECTIVE: This study aimed to quantitatively evaluate the left ventricular myocardial work of patients with chronic kidney disease (CKD) by echocardiographic pressure-strain loop (PSL) analysis. METHODS: Ninety-three patients with CKD and forty-two age- and sex-matched controls were included in the study. CKD patients were divided into group 1 (stages 2-4) and group 2 (stage 5). Left ventricular blood pressure was estimated noninvasively according to echocardiographic valvular events and brachial artery systolic pressure. Left ventricular myocardial work parameters were acquired by echocardiographic PSL analysis. RESULTS: The CKD groups had a significantly lower global work index (WI), global work efficiency (GWE), global constructive strain (GCW) and global longitudinal strain (GLS) and higher global waste work (GWW) than the control group. Segmental analysis showed that the myocardial WI, work efficiency (WE), and constructive work (CW) were lower in group 2 than the control group (P < .05), while the regional myocardial waste work (WW) was higher (P < .05). A Pearson correlation analysis revealed that GWE and GWW have good correlations with the LVEF and GLS. A multiple regression analysis showed that the systolic blood pressure (SBP), estimated glomerular filtration rate (eGFR), end-diastolic volume (EDV), and GLS were associated with global work index (GWI) (b' = 0.476, 0.252, -0.407, and -0.355, P < .05). CONCLUSIONS: Left ventricular PSL analysis can be applied to assess global and regional myocardial work in CKD patients. This approach may serve as a noninvasive method for the detection of left ventricular systolic dysfunction at an early stage.

A hydroxyl-functionalized homochiral porous organic cage for gas chromatographic separations.

A hydroxyl-functionalized homochiral porous organic cage (POC) was synthesized and characterized by FTIR, NMR, thermogravimetric analysis (TGA), MALDI-TOF-MS, and elemental analysis. The synthesized homochiral POC was used as stationary phase to prepare a capillary gas chromatography (GC) column by a static coating method. The fabricated column shows excellent selectivity not only for the separation of positional isomers but also for the resolution of various racemates. Thirty-nine racemates have been resolved on the column, including alcohols, diols, halohydrocarbons, epoxides, esters, lactones, ketones, ethers, and organic acids. Compared to the commercial ß-DEX 120 column and previously reported chiral POCs (CC3-R, CC9, and CC10)-coated columns, there are 11, 10, 24, and 15 tested racemates that cannot be resolved on ß-DEX 120 column, CC3-R column, CC9 column, and CC10 column, respectively. This reveals that the fabricated column has prominent complementarity or superior separation performance to these columns in enantioseparation. Besides, the fabricated column can achieve some enantioseparations which are not possible using all previously reported chiral POC-based columns. Some positional isomers (xylenes, dichlorobenzenes, dibromobenzenes, nitrochlorobenzenes, and nitrobromobenzenes) were also separated with high-resolution values. The column exhibits good repeatability, reproducibility, and stability. The relative standard deviation (RSD) values of retention times were 0.03-0.18%, 0.11-0.92%, and 2.1-6.6% for run-to-run (n = 5), day-to-day (n = 5), and column-to-column (n = 3), respectively. The experimental results demonstrate the great potential of POCs for practical application in GC. Graphical Abstract A hydroxyl-functionalized homochiral porous organic cage was used as stationary phase for gas chromatography separation of racemates and positional isomers. The resolution of racemates mainly depended on hydrogen bonding, π-interaction, host-guest inclusion, steric fit, etc., while separation of positional isomers by shape-selective guest binding.

Assessment on China's urbanization after the implementation of main functional areas planning.

China has implemented main functional areas planning (MFAP) since 2010, which is essential for improving the efficiency of land space utilization and achieving sustainable urban development. Quantitative assessments of the urban development levels (UDLs) at the county level across China after the implementation of MFAP have not been well-documented. In this study, a unified indicator system was developed, and the UDLs of 2850 counties in China after MFAP implementation were evaluated. The results showed that MFAP played a positive role in urban development in China. The UDLs in China generally increased but showed obvious spatial differences. The higher UDLs were mostly found in the counties in the five urban belts, which reflects the overall urban layout of China. The UDLs were generally low in the western counties in comparison with those in the eastern part of China. The differences in the UDLs from east to west were greater than those from north to south. Moreover, the differences in the UDLs presented a spatial agglomeration effect. This study could offer insight into the refinement of MFAP in China and sustainable urban development in developing countries.

Sustainable biodegradation of phenol by immobilized Bacillus sp. SAS19 with porous carbonaceous gels as carriers.

In this study, high-efficient phenol-degrading bacterium Bacillus sp. SAS19 which was isolated from activated sludge by resuscitation-promoting factor (Rpf) addition, were immobilized on porous carbonaceous gels (CGs) for phenol degradation. The phenol-degrading capabilities of free and immobilized Bacillus sp. SAS19 were evaluated under various initial phenol concentrations. The obtained results showed that phenol could be removed effectively by both free and immobilized Bacillus sp. SAS19. Furthermore, for degradation of phenol at high concentrations, long-term utilization and recycling were more readily achieved for immobilized bacteria as compared to free bacteria. Immobilized bacteria exhibited significant increase in phenol-degrading capabilities in the third cycle of recycling and reuse, which demonstrated 87.2% and 100% of phenol (1600 mg/L) degradation efficiency at 12 and 24 h, respectively. The present study revealed that immobilized Bacillus sp. SAS19 can be potentially used for enhanced treatment of synthetic phenol-laden wastewater.

Generation of fully pluripotent female murine-induced pluripotent stem cells.

The high quality of induced pluripotent stem cells (iPSCs) has been determined to be high-grade chimeras that are competent for germline transmission, and viable mice can be generated through tetraploid complementation. Most of the high-quality iPSCs described to date have been male. Female iPSCs, especially fully pluripotent female iPSCs, are also essential for clinical applications and scientific research. Here, we show, for the first time, that a gender-mixed induction strategy could lead to a skewed sex ratio of iPSCs. After reprogramming, 50%, 70%, and 90% female initiating mouse embryonic fibroblasts at different male ratios resulted in 14.1 ± 6.8% (P < 0.05), 31.8 ± 5.4% (P < 0.05), and 80.1 ± 2.8% (P < 0.05) female iPSCs, respectively. Furthermore, these female iPSCs had pluripotent properties typical of embryonic stem cells. Importantly, these fully pluripotent female iPSCs could generate viable mice by tetraploid complementation. These findings indicate that high-quality female iPSCs could be derived effectively, and suggest that clinical application of female iPSCs is feasible.

[Optimization of sperm alkaline single-cell gel electrophoresis].

OBJECTIVE: To investigate the main factors that influence the results of sperm alkaline single-cell gel electrophoresis (SCGE), optimize the conditions, and standardize its procedures. METHODS: Using alkaline SCGE, we detected the DNA fragments of sperm treated with different concentrations of H2O2 and determined the influences of the number of agarose gel layers, pH during DNA unwinding and electrophoresis, the time of DNA unwinding and electrophoresis, and cumulative sperm number on the results of sperm alkaline SCGE. Then we optimized the procedures, analyzed the repeatability of the optimized method, and examined 40 semen samples using the method. RESULTS: Three agarose gel layers could reduce the background. The optimal pH during DNA unwinding and electrophoresis was 10, and the best times for DNA unwinding and electrophoresis were 40 min and 30 min, respectively. Fifty sperm were adequate to ensure the reliability of the results. Based on the percentage of tail DNA, the intra- and inter-assay repeatabilities of the optimized sperm alkaline SCGE were 3.12% and 7.13%, and by the DNA damage score, they were 2.38% and 6.09%, respectively. Sperm DNA fragments were significantly increased in the infertile patients with oligoasthenoteratozoospermia as compared with healthy fertile males (P <0.05). CONCLUSION: The optimized sperm alkaline SCGE, highly repeatable and easy to be standardized, can be applied to the clinical detection of sperm DNA fragmentation in infertile men.

Circulating microRNA-21 (MIR-21) and phosphatase and tensin homolog (PTEN) are promising novel biomarkers for detection of oral squamous cell carcinoma.

The purpose of this study was to investigate the potential of the blood levels of MIR-21 and PTEN as novel biomarkers for oral squamous cell carcinoma (OSCC). We initially detected MIR-21 and PTEN using real-time RT-PCR from 90 blood samples and then compared their results with expression in cancer tissues from 10 OSCC patients. Finally, we examined the relationship between these markers and clinical parameters. Blood MIR-21 and PTEN had significant diagnostic value for OSCC and, to an extent, correlated with the expression level of tumour MIR-21 and PTEN. In addition, they were associated with differentiation and nodal status. Thus circulating MIR-21 and PTEN might represent new complementary tumour markers for OSCC.

Decompression as a treatment for odontogenic cystic lesions of the jaw.

PURPOSE: To evaluate the effectiveness of decompression as the primary treatment of odontogenic cystic lesions of the jaw involving factors that affect relative shrinking speed and bone regeneration. PATIENTS AND METHODS: A total of 32 patients with odontogenic cystic lesions of the jaw underwent decompression with customized thermoplastic resin stents. Clinical examinations and pre- and postdecompression panoramic radiographs were analyzed. RESULTS: The mean relative speed of shrinkage of radicular cysts (RCs; 3.37 cm(2)/month) was faster than those of keratocystic odontogenic tumors (KCOTs; 2.87 cm(2)/month) and unicystic ameloblastomas (UABs; 2.71 cm(2)/month). The relative shrinking size increased linearly in a time-dependent manner for KCOTs (r = 0.849, P < .001), RCs (r = 0.681, P = .319), and UABs (r = 0.146, P = .730); a similar relation was detected between the primary radiolucent area of cystic lesions before decompression and relative shrinking speed after decompression in KCOTs (r = 0.481, P = .032), RCs (r = 0.260, P = .673), and UABs (r = 0.370, P = .366), but patient age did not affect the relative speed of shrinkage (P > .05). Furthermore, the increase in bone density was more significant in RCs than in KCOTs (P = .026) and UABs (P = .012) after decompression. CONCLUSION: Decompression was effective in reducing odontogenic cystic lesions of the jaw and increasing bone density. For aggressive lesions, secondary definitive surgery was necessary.