LiBis: an ultrasensitive alignment augmentation for low-input bisulfite sequencing.

The cell-free DNA (cfDNA) methylation profile in liquid biopsy has been utilized to diagnose early-stage disease and estimate therapy response. However, typical clinical procedures are capable of purifying only very small amounts of cfDNA. Whole-genome bisulfite sequencing (WGBS) is the gold standard for measuring DNA methylation; however, WGBS using small amounts of fragmented DNA introduces a critical challenge for data analysis, namely a low-mapping ratio. The resulting low sequencing depth and low coverage of CpG sites genome-wide is a bottleneck for the clinical application of cfDNA-based WGBS assays. We developed LiBis (Low-input Bisulfite Sequencing), a novel method for low-input WGBS data alignment. By dynamically clipping initially unmapped reads and remapping clipped fragments, we judiciously rescued those reads and uniquely aligned them to the genome. By substantially increasing the mapping ratio by up to 88%, LiBis dramatically improved the number of informative CpGs and the precision in quantifying the methylation status of individual CpG sites. LiBis significantly improved the cost efficiency of low-input WGBS experiments by dynamically removing contamination introduced by random priming. The high sensitivity and cost effectiveness afforded by LiBis for low-input samples will allow the discovery of genetic and epigenetic features suitable for downstream analysis and biomarker identification using liquid biopsy.

Social network and mental health of Chinese immigrants in affordable senior housing during the COVID-19 pandemic: a mixed-methods study.

OBJECTIVE: Chinese immigrant older adults who live in affordable housing are at high risk of experiencing social isolation during the COVID-19 pandemic, which can affect their mental health. Using a triangulation mixed-methods approach, this study describes Chinese immigrant older adults' social network, mental health status, and their associations during the pandemic. METHODS: Semi-structured in-depth interviews were conducted with 26 Chinese immigrant older adults from June to August 2021. The structure and characteristics of participants' social networks were assessed with a name-generating approach. Mental health status was self-reported with Geriatric Depression Scale and UCLA loneliness scale. RESULTS: This sample (mean age = 78.12, 69.23% female), on average, had 5.08 social ties in their network, and 58% were family ties. Participants reported decreased social contact, family and friends interaction patterns specific to immigrants, and constantly being in a low mood and bored. Having closer relationships with others and maintaining the same or higher contact frequency after COVID-19 onset was associated with fewer depressive symptoms. Resilience from religious beliefs, neighbors as role models, and wisdom learned from past experiences were reported. CONCLUSION: Knowledge built in this study can inform respondence to future crises like the COVID-19 pandemic in affordable housing settings serving older immigrant populations.

Assessment of the expression and response of PD-1, LAG-3, and TIM-3 after neoadjuvant radiotherapy in rectal cancer.

Many studies have verified the safety of combined radiotherapy and immune checkpoint blockades (ICBs) without the specific radiation dose or sequencing of combination. We aimed to evaluate the expression and response of PD-1, TIM-3, LAG-3 after neoadjuvant radiotherapy (NRT) and explore the possibility and optimal schedule of combining immunotherapy with radiotherapy in treating rectal cancer. Immunohistochemistry was performed to detect the expression of PD-1, TIM-3, LAG-3, CD8, and CD3. These molecules' expression was detected on the specimens of 76 rectal cancer patients following NRT and 13 of these patients before NRT. The expression of ICBs was assessed by the percentage of positive cells. The levels of PD-1 and immune cells (ICs) LAG-3 in rectal cancer increased after NRT (0% vs. 3%, p=0.043 and 5% vs. 45%, p=0.039, respectively). However, TIM-3 in ICs and tumor cells (TCs) were both decreased (80% vs. 50%, p=0.011, 90% vs. 0%, p=0.000, respectively). The LAG-3 expression was higher in patients treated with short-course RT than long-course RT (22.5% vs. 8.0%, p=0.0440 in ICs; 0% vs. 70%, p<0.001 in TCs). On the contrary, CD8 was higher after long-course RT (15% vs. 8%, p=0.0146). Interestingly, the level of ICs TIM-3 was low in > eight weeks after long-course RT (p=0.045). The expressions of PD-1, ICs TIM-3, ICs LAG-3, CD3, and CD8 were associated with the disease-free survival (DFS) in univariate analysis (p=0.036, 0.008, 0.018, 0.025, and 0.004, respectively). Adjusted by the relevant variables, PD-1 (HR 0.274; 95% CI 0.089-0.840; p=0.024) and ICs TIM-3 (HR 0.425; 95% CI 0.203-0.890; p=0.023) were independent prognostic factors of DFS in rectal cancer patients following NRT. In conclusion, we have identified that PD-1 and ICs LAG-3 presented a trend towards increased expression after NRT, supporting the ICBs and NRT combination as a potential treatment option for local advanced rectal cancer patients. The radiotherapeutic mode and timing of the treatment might significantly affect the expression of ICBs, which indicated that the sequencing and time window of ICBs immunotherapy utility might deserve a high value.

GsmPlot: a web server to visualize epigenome data in NCBI.

BACKGROUND: Epigenetic regulation is essential in regulating gene expression across a variety of biological processes. Many high-throughput sequencing technologies have been widely used to generate epigenetic data, such as histone modification, transcription factor binding sites, DNA modifications, chromatin accessibility, and etc. A large scale of epigenetic data is stored in NCBI Gene Expression Omnibus (GEO). However, it is a great challenge to reanalyze these large scale and complex data, especially for researchers who do not specialize in bioinformatics skills or do not have access to expensive computational infrastructure. RESULTS: GsmPlot can simply accept GSM IDs to automatically download NCBI data or can accept user's private bigwig files as input to plot the concerned data on promoters, exons or any other user-defined genome locations and generate UCSC visualization tracks. By linking public data repository and private data, GsmPlot can spark data-driven ideas and hence promote the epigenetic research. CONCLUSIONS: GsmPlot web server allows convenient visualization and efficient exploration of any NCBI epigenetic data in any genomic region without need of any bioinformatics skills or special computing resources. GsmPlot is freely available at https://gsmplot.deqiangsun.org/.

Assessment of an Elekta Versa HD linear accelerator for stereotactic radiosurgery with circular cone collimators.

BACKGROUND: Versa HD linear accelerators (linacs) are used for stereotactic radiosurgery treatment. However, the mechanical accuracy of such systems remains a concern. OBJECTIVE: The purpose of this study was to evaluate the accuracy of an Elekta Versa HD linac. METHODS: We performed measurements with a ball bearing phantom to calculate the rotational isocenter radii of the linac's gantry, collimator, and table, and determine the relative locations of those isocenters. We evaluated the accuracy of the cone-beam computed tomography (CBCT) guidance with a film-embedding head phantom and circular cone-collimated radiation beams. We also performed dosimetric simulations to study the effects of the linac mechanical uncertainties on non-coplanar cone arc delivery. RESULTS: The mechanical uncertainty of the linac gantry rotation was 0.78 mm in radius, whereas that of the collimator and the table was <0.1 mm and 0.33 mm, respectively. The axes of rotation of the collimator and the table were coinciding with and 0.13 mm away from the gantry isocenter, respectively. Experiments with test plans demonstrated the limited dosimetric consequences on the circular arc delivery given the aforementioned mechanical uncertainties. End-to-end measurements determined that the uncertainty of the CBCT guidance was≤1 mm in each direction with respect to the reference CT image. CONCLUSIONS: In arc delivery, the mechanical uncertainties associated with the gantry and the table do not require remarkable increases in geometric margins. If large enough, the residual setup errors following CBCT guidance will dominate the overall dosimetric consequence. Therefore, the Versa HD linac is a valid system for stereotactic radiosurgery using non-coplanar arc delivery.

Using weighted power mean for equivalent square estimation.

PURPOSE: Equivalent Square (ES) enables the calculation of many radiation quantities for rectangular treatment fields, based only on measurements from square fields. While it is widely applied in radiotherapy, its accuracy, especially for extremely elongated fields, still leaves room for improvement. In this study, we introduce a novel explicit ES formula based on Weighted Power Mean (WPM) function and compare its performance with the Sterling formula and Vadash/Bjärngard's formula. METHODS: The proposed WPM formula is ESWPMa,b=waα+1-wbα1/α for a rectangular photon field with sides a and b. The formula performance was evaluated by three methods: standard deviation of model fitting residual error, maximum relative model prediction error, and model's Akaike Information Criterion (AIC). Testing datasets included the ES table from British Journal of Radiology (BJR), photon output factors (Scp ) from the Varian TrueBeam Representative Beam Data (Med Phys. 2012;39:6981-7018), and published Scp data for Varian TrueBeam Edge (J Appl Clin Med Phys. 2015;16:125-148). RESULTS: For the BJR dataset, the best-fit parameter value α = -1.25 achieved a 20% reduction in standard deviation in ES estimation residual error compared with the two established formulae. For the two Varian datasets, employing WPM reduced the maximum relative error from 3.5% (Sterling) or 2% (Vadash/Bjärngard) to 0.7% for open field sizes ranging from 3 cm to 40 cm, and the reduction was even more prominent for 1 cm field sizes on Edge (J Appl Clin Med Phys. 2015;16:125-148). The AIC value of the WPM formula was consistently lower than its counterparts from the traditional formulae on photon output factors, most prominent on very elongated small fields. CONCLUSION: The WPM formula outperformed the traditional formulae on three testing datasets. With increasing utilization of very elongated, small rectangular fields in modern radiotherapy, improved photon output factor estimation is expected by adopting the WPM formula in treatment planning and secondary MU check.

Psychosocial Well-Being Differences Between the Young Old, Old-Old, and Oldest Old: A Global Comparison.

OBJECTIVES: We investigate global differences in psychosocial well-being between older adult age groups. METHODS: Using multinomial logistic regression, we analyzed 2018 data (n = 93,663) from 9 countries/regions in the Health and Retirement Study international family of studies to compare age group differences in depression, loneliness, and happiness. RESULTS: Compared to the young old, the old-old reported more depression in Southern Europe, while the oldest old had higher risk in India and Southern Europe but lower risk in the United States. The old-old reported less loneliness in the United States but more in Southern Europe, while the oldest old had greater risk in Southern Europe. The old-old reported less happiness in Korea, while the oldest old had lower reports in Korea but higher reports in the United States. DISCUSSION: The psychosocial well-being of the oldest old is exceptionally good in the United States but exceptionally poor in Southern Europe.

Nucleus Accumbens Corticotropin-Releasing Hormone Neurons Projecting to the Bed Nucleus of the Stria Terminalis Promote Wakefulness and Positive Affective State.

The nucleus accumbens (NAc) plays an important role in various emotional and motivational behaviors that rely on heightened wakefulness. However, the neural mechanisms underlying the relationship between arousal and emotion regulation in NAc remain unclear. Here, we investigated the roles of a specific subset of inhibitory corticotropin-releasing hormone neurons in the NAc (NAcCRH) in regulating arousal and emotional behaviors in mice. We found an increased activity of NAcCRH neurons during wakefulness and rewarding stimulation. Activation of NAcCRH neurons converts NREM or REM sleep to wakefulness, while inhibition of these neurons attenuates wakefulness. Remarkably, activation of NAcCRH neurons induces a place preference response (PPR) and decreased basal anxiety level, whereas their inactivation induces a place aversion response and anxious state. NAcCRH neurons are identified as the major NAc projection neurons to the bed nucleus of the stria terminalis (BNST). Furthermore, activation of the NAcCRH-BNST pathway similarly induced wakefulness and positive emotional behaviors. Taken together, we identified a basal forebrain CRH pathway that promotes the arousal associated with positive affective states.

Parasubthalamic calretinin neurons modulate wakefulness associated with exploration in male mice.

The parasubthalamic nucleus (PSTN) is considered to be involved in motivation, feeding and hunting, all of which are highly depending on wakefulness. However, the roles and underlying neural circuits of the PSTN in wakefulness remain unclear. Neurons expressing calretinin (CR) account for the majority of PSTN neurons. In this study in male mice, fiber photometry recordings showed that the activity of PSTNCR neurons increased at the transitions from non-rapid eye movement (non-REM, NREM) sleep to either wakefulness or REM sleep, as well as exploratory behavior. Chemogenetic and optogenetic experiments demonstrated that PSTNCR neurons were necessary for initiating and/or maintaining arousal associated with exploration. Photoactivation of projections of PSTNCR neurons revealed that they regulated exploration-related wakefulness by innervating the ventral tegmental area. Collectively, our findings indicate that PSTNCR circuitry is essential for the induction and maintenance of the awake state associated with exploration.

N-doped carbon-coated Cu2O nanowire arrays on copper foam for rapid and stable water disinfection.

High-speed, low-cost and long-term water disinfection method is important for us to away from waterborne diseases. Nanowires-modified electrodes can inactivate microorganisms under low energy consumption. However, small processing capacity remains a major obstacle for practical application. In this study, we coated N-doped carbon layer on Cu2O NWs to improve the conductivity and stability for electrodes. Compared with Cu2O, the work functions of Cu2O-PANI structures is 3.623 eV, indicating the electrodes can prevent the recombination of electron-hole pairs and improve the carrier transport efficiency. In addition, Mulliken charge density showed that Cu2O-PANI structure reduce the oxidation trend of Cu atom and improve the stability of electrodes. Besides, the Cu2O NWs@NC electrodes showed excellent disinfection performance for E. coli and S. aureus, which can achieve 99.9% sterilizing rate under high flux (1200 mL min-1). Under this condition, the electrodes can continuously treat 576 L wastewater, which is about 10-folds handling capacity than others. Moreover, the bactericidal mechanism is synergistic of electroporation and reactive oxygen species, and the main ROS were electrons, OH and O2-. Therefore, this electrodes has a great prospect for rapid and stable water treatment system.

Boosting Reactive Oxygen Species Generation by Regulating Excitonic Effects in Porphyrinic Covalent Organic Frameworks.

Excitonic effects play a crucial role in determining the photocatalytic performance of polymer semiconductors, which has long been ignored. Herein, metal organic frameworks (MOFs, specially NH2-MIL-125) modifying porphyrinic covalent organic frameworks (COFs, specially DhaTph) have been proven to be a suitable model to regulate excitonic effects. The photoluminescence measurements prove that DhaTph presents strong excitonic effects, which can generate 1O2 through an energy transfer process. Remarkably, the construction of the NH2-MIL-125@DhaTph heterostructure can effectively facilitate the dissociation of excitons, resulting in distinct activation of O2 to O2•- and •OH. Benefiting from the enhanced generation of reactive oxygen species, the NH2-MIL-125@DhaTph composite exhibits a superior bactericidal effect and photocatalytic degradation performance. This work provides a deeper insight into the excitonic effects based on COFs during the photocatalytic process and opens a feasible avenue for the regulation of the excitonic effects in porphyrinic COFs.

In situ synthesis of 2D/2D MXene-COF heterostructure anchored with Ag nanoparticles for enhancing Schottky photocatalytic antibacterial efficiency under visible light.

It is a major challenge to combine the advantages of two kinds of two-dimensional materials to construct a heterojunction and achieve efficient photocatalytic antifouling. In this work, we covalently connected two materials MXenes and covalent organic frameworks (COFs) through the Schiff base reaction and anchored Ag nanoparticles (NPs) to prepare a Ti3C2/TpPa-1/Ag composite material with high efficiency bactericidal properties. The covalent bonding between MXene and COF greatly improved the stability of the material. Ti3C2/TpPa-1/Ag composite showed an excellent antibacterial property against S. aureus and P. aeruginosa. The fluorescence spectra of Ti3C2/TpPa-1/Ag proved that the electron transfer channels formed between the ternary materials could greatly improve the efficiency of carrier separation and prolong the life of photogenerated carriers. Density functional theory calculations showed that the synergistic catalytic effect of Ag and Ti3C2 could greatly reduce the work function along the interface, and the built-in electric field between the layers drive carrier fast migration, which effectively improve the catalytic performance.

Effects of bromelain on the quality of smoked salted duck.

This study was aimed to assess the effects of bromelain on the eating quality of smoked salted duck. Whole ducks were marinated with different doses of bromelain (300 U/g, 600 U/g, 900 U/g, 1,200 U/g and 1,500 U/g), while the group without bromelain was considered as control (CK). After the production of smoked salted duck was completed, the pH, color, texture, electronic tongue detection, thiobarbituric acid reactive substances (TBARS), sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), and mass spectrometry analysis were determined. The results showed that, compared to CK, the pH, TBARS and hardness values in 900, 1,200 and 1,500 U/g groups were reduced. The cohesiveness and the springiness were increased while the values of b* were decreased in all bromelain treatments (p < .05). The SDS-PAGE and mass spectrometry analysis indicated that myosin and actin were further hydrolyzed into small-molecule proteins by bromelain. Electronic tongue detection showed that the umami, the saltiness and the richness of smoked salted duck were enhanced, while the bitterness was reduced at the dose of 900 U/g. Thus, bromelain improved the eating quality of smoked salted duck in particular at the level of 900 U/g.

BiOBr/MoS2 catalyst as heterogenous peroxymonosulfate activator toward organic pollutant removal: Energy band alignment and mechanism insight.

Utilization of heterogenous catalysts to trigger peroxymonosulfate (PMS) activation is considered an efficient strategy for environmental decontamination. Herein, a tightly bonded flake-like 2D/2D BiOBr/MoS2 heterojunction was successfully designed through co-precipitation process. By virtue of matched energy levels and intimate interfacial coupling, the Type-II BiOBr/MoS2 heterojunction significantly expedited charge carrier transfer and thereby promoted the catalytic performance for organic dye oxidation and Cr(VI) reduction. The specially designed BiOBr/MoS2 heterojunction is also conducive to split PMS and continuously generated highly active species (SO4-, OH and O2-) in a photo-Fenton system, achieving extraordinary catalytic capacity for various emerging organic pollutants (including phenol, bisphenol A and carbamazepine). The photoexcited electron with prolonged lifetime and exposed Mo sites with multivalence and multiphase nature can effectively activate PMS, which further promotes the oxidation efficiency of holes, as confirmed by scavenging experiments. The excellent stability and oxidative properties could justify scale up using BiOBr/MoS2 to a small pilot test, implementing the potential value in practical applications. This study would provide novel insight and cognition of PMS activation via a superior heterojunction for complex polluted wastewater treatment.

Charge transfer channels of silver @ cuprous oxide heterostructure core-shell nanoparticles strengthen high photocatalytic antibacterial activity.

Marine biological fouling has always been a hot research topic. In this study, silver @ cuprous oxide (Ag@Cu2O) core-shell nanoparticles were synthesized via in-situ synthesis method and developed an outstanding antibacterial activity. The bacteriostasis efficiency of Ag@Cu2O reached to 99% and 98% against Staphylococcus aureus and Pseudomonas aeruginosa, respectively. The minimum inhibitory concentration of Ag@Cu2O decreased from 113.6 µg/mL to 56.8 µg/mL compared with Cu2O. Ag@Cu2O had better antibacterial activity than Cu2O with lower content of Cu2O and was more environment friendly. The heterostructure formed at the interface between Ag and Cu2O promoted the separation and diffusion of photogenerated electron-hole pairs through the charge transfer channel and promoted the generation of reactive oxygen species. The outstanding antibacterial activity of Ag@Cu2O was strongly depended on the generation of the reactive oxygen species. Density functional theory and finite element method calculations demonstrated that the structure of core-shell improved photocatalytic efficiency. Additionally, synergetic effect of released Ag+ and Cu2+ also enhanced the bacteriostasis rate and the long-term antifouling performance in 60 days. Hence, the synthesized core-shell Ag@Cu2O can be applied as novel antifoulants in the marine field.

Genome-wide DNA methylation profiling of leukocytes identifies CpG methylation signatures of aggressive prostate cancer.

Most of screening-detected prostate cancer (PCa) are indolent and not lethal. Biomarkers that can predict aggressive diseases independently of clinical features are needed to improve risk stratification of localized PCa patients and reduce overtreatment. We aimed to identify leukocyte DNA methylation differences between clinically defined aggressive and non-aggressive PCa. We performed whole genome DNA methylation profiling in leukocyte DNA from 287 PCa patients with Gleason Score (GS) 6 and ≥8 using Illumina 450k methylation arrays. We observed a global hypomethylation in GS≥8 patients compared to GS=6 PCa patients; in contrast, the methylation level in core promoter and exon 1 region was significantly higher in GS≥8 patients than GS=6 PCa. We then performed 5-fold cross validated random forest model training on 1,459 differentially methylated CpG Probes (DMPs) with false discovery rate (FDR) <0.01 between GS=6 and GS≥8 groups. The power of the predictive model was further reinforced by ranking the DMPs with Decreased Gini and re-train the model with the top 97 DMPs (Testing AUC=0.920, predict accuracy =0.847). In conclusion, we identified a CpG methylation signature in leukocyte DNA that is associated with aggressive clinical features of PCa at diagnosis.

Deacetylase Plus Bromodomain Inhibition Downregulates ERCC2 and Suppresses the Growth of Metastatic Colon Cancer Cells.

There is growing evidence that DNA repair factors have clinical value for cancer treatment. Nucleotide excision repair (NER) proteins, including excision repair cross-complementation group 2 (ERCC2), play a critical role in maintaining genome integrity. Here, we examined ERCC2 expression following epigenetic combination drug treatment. Attention was drawn to ERCC2 for three reasons. First, from online databases, colorectal cancer (CRC) patients exhibited significantly reduced survival when ERCC2 was overexpressed in colon tumors. Second, ERCC2 was the most highly downregulated RNA transcript in human colon cancer cells, plus Ercc2 in rat tumors, after treatment with the histone deacetylase 3 (HDAC3) inhibitor sulforaphane (SFN) plus JQ1, which is an inhibitor of the bromodomain and extraterminal domain (BET) family. Third, as reported here, RNA-sequencing of polyposis in rat colon (Pirc) polyps following treatment of rats with JQ1 plus 6-methylsulfinylhexyl isothiocyanate (6-SFN) identified Ercc2 as the most highly downregulated gene. The current work also defined promising second-generation epigenetic drug combinations with enhanced synergy and efficacy, especially in metastasis-lineage colon cancer cells cultured as 3D spheroids and xenografts. This investigation adds to the growing interest in combination approaches that target epigenetic 'readers', 'writers', and 'erasers' that are deregulated in cancer and other pathologies, providing new avenues for precision oncology and cancer interception.

A targetable LIFR-NF-κB-LCN2 axis controls liver tumorigenesis and vulnerability to ferroptosis.

The growing knowledge of ferroptosis has suggested the role and therapeutic potential of ferroptosis in cancer, but has not been translated into effective therapy. Liver cancer, primarily hepatocellular carcinoma (HCC), is highly lethal with limited treatment options. LIFR is frequently downregulated in HCC. Here, by studying hepatocyte-specific and inducible Lifr-knockout mice, we show that loss of Lifr promotes liver tumorigenesis and confers resistance to drug-induced ferroptosis. Mechanistically, loss of LIFR activates NF-κB signaling through SHP1, leading to upregulation of the iron-sequestering cytokine LCN2, which depletes iron and renders insensitivity to ferroptosis inducers. Notably, an LCN2-neutralizing antibody enhances the ferroptosis-inducing and anticancer effects of sorafenib on HCC patient-derived xenograft tumors with low LIFR expression and high LCN2 expression. Thus, anti-LCN2 therapy is a promising way to improve liver cancer treatment by targeting ferroptosis.

Detection of hypoxia in microscopic tumors using 131I-labeled iodo-azomycin galactopyranoside (131I-IAZGP) digital autoradiography.

PURPOSE: Previous studies have shown that tumors less than 1 mm diameter derived from HT29 colorectal cancer cells are extremely hypoxic when grown intraperitoneally or intradermally in nude mice, whereas those of greater size (approximately 1-4 mm diameter) are not significantly hypoxic. The object of this study was to determine if digital autoradiography using the radiolabeled hypoxia imaging tracer iodo-azomycin galactopyranoside ((131)I-IAZGP) could detect hypoxia in this model. METHODS: Microscopic HT29 tumors were grown as disseminated peritoneal disease and intradermally in nude mice. Tumors ranged in size from a few hundred microns to several millimeters in diameter. Animals were intravenously administered (131)I-IAZGP and pimonidazole 2 h before sacrifice. Following sacrifice, the intratumoral distribution of (131)I-IAZGP was assessed by digital autoradiography and compared with immunofluorescence microscopic images of pimonidazole binding and carbonic anhydrase IX (CAIX) expression. RESULTS: The distributions of (131)I-IAZGP, pimonidazole, and CAIX expression were similar. Tumors less than 1 mm diameter displayed high (131)I-IAZGP uptake; these tumors also stained strongly for pimonidazole and CAIX. Larger tumors (approximately 1-4 mm diameter) were not significantly hypoxic and had low (131)I-IAZGP accumulation. CONCLUSION: (131)I-IAZGP can detect hypoxia in microscopic tumors. Microscopic tumors are useful models for the validation of hypoxia radiotracers, and digital autoradiography is an appropriate technique for studying the distribution of hypoxia radiotracers in microscopic tumors.

Self-assembly of graphene oxide sheets: the key step toward highly efficient desalination.

Lamellar graphene oxide (GO) membranes are new membrane materials for seawater desalination due to their selective sub-nanometer interlayer two-dimensional channels. In general, the reliable and precise desalination of GO membranes is still heavily dependent on thick membranes that usually have a low water flux. The trade-off between the water flux and ion rejection is a long-lasting problem that restricts the development of highly efficient desalination membranes. In this work, we theoretically predicted that this trade-off can be broken by the self-assembly of GO sheets during the membrane preparation. Our molecular dynamics (MD) simulations indicate that the high-water permeability of the GO membrane is due to the frictionless flow of water in the 2D nanochannels enclosed by the non-oxidized regions of neighboring GO sheets, while the oxidized regions are responsible for the high ion rejection rate. Meanwhile, the MD simulations of the self-assembly processes of GO sheets in aqueous solutions just demonstrate that the oxidized regions of neighboring GO sheets are prone to stacking with each other, while the non-oxidized regions of neighboring GO sheets are inclined to matching with each other. Therefore, more interlayer nanochannels for fast water flow and ion rejection will be formed, respectively, after the full assembly of GO sheets during membrane preparation. Finally, based on our results, a new but simple method has been proposed to prepare GO membranes with superior desalination performance via deposition rate control.