Artificial intelligence velocimetry reveals in vivo flow rates, pressure gradients, and shear stresses in murine perivascular flows.

Quantifying the flow of cerebrospinal fluid (CSF) is crucial for understanding brain waste clearance and nutrient delivery, as well as edema in pathological conditions such as stroke. However, existing in vivo techniques are limited to sparse velocity measurements in pial perivascular spaces (PVSs) or low-resolution measurements from brain-wide imaging. Additionally, volume flow rate, pressure, and shear stress variation in PVSs are essentially impossible to measure in vivo. Here, we show that artificial intelligence velocimetry (AIV) can integrate sparse velocity measurements with physics-informed neural networks to quantify CSF flow in PVSs. With AIV, we infer three-dimensional (3D), high-resolution velocity, pressure, and shear stress. Validation comes from training with 70% of PTV measurements and demonstrating close agreement with the remaining 30%. A sensitivity analysis on the AIV inputs shows that the uncertainty in AIV inferred quantities due to uncertainties in the PVS boundary locations inherent to in vivo imaging is less than 30%, and the uncertainty from the neural net initialization is less than 1%. In PVSs of N = 4 wild-type mice we find mean flow speed 16.33 ± 11.09 µm/s, volume flow rate 2.22 ± 1.983 × 103 µm3/s, axial pressure gradient ( - 2.75 ± 2.01)×10-4 Pa/µm (-2.07 ± 1.51 mmHg/m), and wall shear stress (3.00 ± 1.45)×10-3 Pa (all mean ± SE). Pressure gradients, flow rates, and resistances agree with prior predictions. AIV infers in vivo PVS flows in remarkable detail, which will improve fluid dynamic models and potentially clarify how CSF flow changes with aging, Alzheimer's disease, and small vessel disease.

Male-pronuclei-specific granulin facilitates somatic cells reprogramming via mitigating excessive cell proliferation and enhancing lysosomal function.

Critical reprogramming factors resided predominantly in the oocyte or male pronucleus can enhance the efficiency or the quality of induced pluripotent stem cells (iPSCs) induction. However, few reprogramming factors exist in the male pronucleus had been verified. Here, we demonstrated that granulin (Grn), a factor enriched specifically in male pronucleus, can significantly improve the generation of iPSCs from mouse fibroblasts. Grn is highly expressed on Day 1, Day 3, Day 14 of reprogramming induced by four Yamanaka factors and functions at the initial stage of reprogramming. Transcriptome analysis indicates that Grn can promote the expression of lysosome-related genes, while inhibit the expression of genes involved in DNA replication and cell cycle at the early reprogramming stage. Further verification determined that Grn suppressed cell proliferation due to the arrest of cell cycle at G2/M phase. Moreover, ectopic Grn can enhance the lysosomes abundance and rescue the efficiency reduction of reprogramming resulted from lysosomal protease inhibition. Taken together, we conclude that Grn serves as an activator for somatic cell reprogramming through mitigating cell hyperproliferation and promoting the function of lysosomes.

WD repeat domain 82 (Wdr82) facilitates mouse iPSCs generation by interfering mitochondrial oxidative phosphorylation and glycolysis.

BACKGROUND: Abundantly expressed factors in the oocyte cytoplasm can remarkably reprogram terminally differentiated germ cells or somatic cells into totipotent state within a short time. However, the mechanism of the different factors underlying the reprogramming process remains uncertain. METHODS: On the basis of Yamanaka factors OSKM induction method, MEF cells were induced and reprogrammed into iPSCs under conditions of the oocyte-derived factor Wdr82 overexpression and/or knockdown, so as to assess the reprogramming efficiency. Meanwhile, the cellular metabolism was monitored and evaluated during the reprogramming process. The plurpotency of the generated iPSCs was confirmed via pluripotent gene expression detection, embryoid body differentiation and chimeric mouse experiment. RESULTS: Here, we show that the oocyte-derived factor Wdr82 promotes the efficiency of MEF reprogramming into iPSCs to a greater degree than the Yamanaka factors OSKM. The Wdr82-expressing iPSC line showed pluripotency to differentiate and transmit genetic material to chimeric offsprings. In contrast, the knocking down of Wdr82 can significantly reduce the efficiency of somatic cell reprogramming. We further demonstrate that the significant suppression of oxidative phosphorylation in mitochondria underlies the molecular mechanism by which Wdr82 promotes the efficiency of somatic cell reprogramming. Our study suggests a link between mitochondrial energy metabolism remodeling and cell fate transition or stem cell function maintenance, which might shed light on the embryonic development and stem cell biology.

Resveratrol alleviates imidacloprid-induced mitochondrial apoptosis, necroptosis, and immune dysfunction in chicken lymphocyte lines by inhibiting the ROS/MAPK signaling pathway.

Imidacloprid (IMI) is a neonicotinoid insecticide with the highest global market share, and IMI exposure in the environment can negatively affect many nontarget organisms (a general term for organisms affected by drugs other than target organisms). Resveratrol (RSV), a non-flavonoid polyphenolic organic compound derived from peanuts, grapes, and other plants, has anti-inflammatory and antioxidant effects. It is currently unclear how RSV protects against cell damage caused by IMI. Therefore, we established an experimental model of chicken lymphocyte lines exposed to 110 µg/mL IMI and/or 0.5 µM RSV for 24 h. According to the experimental results, IMI markedly raised intracellular reactive oxygen species levels and diminished the activity of the cellular antioxidant enzymes (CAT, SOD, and GPx), leading to MDA accumulation and decreased T-AOC. JNK, ERK, and P38, the essential components of the mitogen-activated protein kinase (MAPK) signaling pathway, were also expressed more when IMI was present. Additionally, IMI resulted in upregulation of mitochondrial apoptosis (Caspase 3, Caspase 9, Bax, and Cyt-c) and necroptosis (Caspase 8, RIPK1, RIPK3, and MLKL) related factors expression, downregulation of Bcl-2 expression, induction of upregulation of cytokine IL-6 and TNF-α expression, and downregulation of IFN-γ expression. The combined treatment of RSV and IMI significantly reduced cellular oxidative stress levels, inhibited the MAPK signaling pathway, and alleviated IMI-induced mitochondrial apoptosis, necroptosis, and immune dysfunction. To summarize, RSV antagonized IMI-induced mitochondrial apoptosis, necroptosis, and immune dysfunction in chicken lymphocyte lines by inhibiting the ROS/MAPK signaling pathway.

Dimerization of PtrMYB074 and PtrWRKY19 mediates transcriptional activation of PtrbHLH186 for secondary xylem development in Populus trichocarpa.

Wood formation is controlled by transcriptional regulatory networks (TRNs) involving regulatory homeostasis determined by combinations of transcription factor (TF)-DNA and TF-TF interactions. Functions of TF-TF interactions in wood formation are still in the early stages of identification. PtrMYB074 is a woody dicot-specific TF in a TRN for wood formation in Populus trichocarpa. Here, using yeast two-hybrid and bimolecular fluorescence complementation, we conducted a genome-wide screening for PtrMYB074 interactors and identified 54 PtrMYB074-TF pairs. Of these pairs, 53 are novel. We focused on the PtrMYB074-PtrWRKY19 pair, the most highly expressed and xylem-specific interactor, and its direct transregulatory target, PtrbHLH186, the xylem-specific one of the pair's only two direct TF target genes. Using transient and CRISPR-mediated transgenesis in P. trichocarpa coupled with chromatin immunoprecipitation and electrophoretic mobility shift assays, we demonstrated that PtrMYB074 is recruited by PtrWRKY19 and that the PtrMYB074-PtrWRKY19 dimers are required to transactive PtrbHLH186. Overexpressing PtrbHLH186 in P. trichocarpa resulted in retarded plant growth, increased guaiacyl lignin, a higher proportion of smaller stem vessels and strong drought-tolerant phenotypes. Knowledge of the PtrMYB074-PtrWRKY19-PtrbHLH186 regulation may help design genetic controls of optimal growth and wood formation to maximize beneficial wood properties while minimizing negative effects on growth.

Gastrointestinal digestion and absorption characterization in vitro of zinc-chelating hydrolysate from scallop adductor (Patinopecten yessoensis).

BACKGROUD: Zinc (Zn) is an essential catalytic element in the human health system but its absorption in the intestinal system can be strongly affected by gastrointestinal (GI) digestion. In this study, the food-derived potential Zn carrier, scallop adductor hydrolysates (SAHs), was produced and characterized. RESULTS: During temporary storage at 4 °C, SAH decreased in Zn-chelating capacity in the aqueous phase, whereas the SAH-Zn complex exhibited high stability. Moreover, the secondary structure of SAH had no significant alteration. Zn morphologically altered the surface structures of SAH, which was involving in carboxyl group of SAH. Results of in vitro GI digestion suggested that the SAH-Zn maintained good stability in GI system and only proportion of high molecular weight cleaved. In addition, SAH could successfully carry and transport Zn while the fluorescence staining revealed free Zn accumulation inside the tissue. Finally, three representative absorbed peptides (around 600 Da) were identified and synthesized. Three synthetic peptides exhibit higher Zn-chelating capacity than SAH and could also successfully transported through the intestine. CONCLUSION: This study provided a theoretical basis for the investigation of digestion and absorption of marine animal-derived peptides as Zn carriers. © 2021 Society of Chemical Industry.

Characterization of a synthetic zinc-chelating peptide from sea cucumber (Stichopus japonicus) and its gastrointestinal digestion and absorption in vitro.

BACKGROUND: Zinc absorption in intestinal system could be strongly affected by the gastrointestinal digestion and absorption of zinc-chelating peptides serving as zinc carriers. In this study, a novel zinc-chelating sea cucumber synthetic peptide (SCSP) was synthesized to estimate its gastrointestinal digestion and promotive effect of zinc absorption in vitro. RESULTS: Analysis of isothermal titration calorimetry suggested that the binding of SCSP and zinc (N ≈ 1) was exothermic, with relatively weak binding affinity (K = 1.0 × 10-3  mol L-1 ). The formation of SCSP-Zn complexes brought morphological changes to the peptides confirmed by scanning electron microscopy (SEM), which also indicated 6.88% of the existence of zinc element. In addition, the SCSP-Zn complexes remained stable under simulated human gastrointestinal digestion. In an in vitro study, the SCSP-Zn complex could successfully transport through the intestinal membrane in the model of everted rat gut sacs (nearly 7.5 µM cm-2 ) as well as Caco-2 cells where the zinc transport reached 0.0014 mg mL-1 carried by SCSP. Fluorescence staining experiments revealed free zinc accumulation inside the tissues and cells treated with the SCSP-Zn complex. CONCLUSIONS: The chelation SCSP-Zn had the promotion ability of zinc absorption in vitro and ex vivo experiments, which suggested a theoretical basis for the design and production of effective zinc chelating peptides as zinc carriers to improve zinc bioavailability. © 2022 Society of Chemical Industry.

Five-channel fiber-based laser Doppler vibrometer for underwater acoustic field measurement.

In this paper, a 1550 nm five-channel all-fiber homodyne laser Doppler vibrometer with high sensitivity and good signal probing probability is presented. Under the anechoic tank, standing on an airborne platform above the water surface 3 m away, the calibration experiments of the designed system are conducted. The minimum detectable sound pressure level is up to 101.73 dB re 1 µPa at 10 kHz under the hydrostatic water surface condition, and the time distribution of the final outputs are consistent with that of the underwater sound transducer. For the hydrodynamic detection capability, with the help of a 1064 nm high-pulse-energy laser whose pulse energy is 6J, pulse duration is about 8 ns, and repetition rate is 1 Hz, the system performance is tested in Qiandao Lake. And the signal probing probability of the whole sensing system is up to 59.77%.

Polarization-independent nematic liquid crystal phase modulator based on optical compensation with sub-millisecond response.

In this paper, we propose a design utilizing two identically parallel-aligned nematic liquid crystal (LC) plates for fast-response and polarization-independent phase modulator. Driven by synchronized voltage signals, such a polarizer-free variable phase modulator shows a wide tunable range from zero to more than 3π, back and forth at 532nm. Due to the optical compensation of the two plates, the rise and fall time of the phase retardation corresponds to the switching-on time of the two plates. Several advantages are illustrated based on the optical compensation of two identical parallel-aligned plates. First, zero phase retardation is obtained, which overcomes the residual phase due to surfaced anchored liquid crystal molecules. The second advantage is sub-millisecond response of rise and fall of retardation since simultaneous relaxation of the two plates remains optically hidden during the synchronized voltages fall. This fast-response and polarization-independent phase modulator has great potential for practical use, including optical communications and light field imaging systems.

Omicron wave during December 2022 - January 2023: access to pharmaceuticals and healthcare resources and impacts on health outcomes in Shenzhen, China.

Purpose: This study described pharmaceutical and medical resource accessibility of COVID-19 treatment in Shenzhen, China during the peak of COVID-19 infection from December 2022 to January 2023, and examined its influence on clinical outcomes. Methods: We surveyed Shenzhen residents on COVID-19-related topics using electronic questionnaires. We conducted descriptive statistical analyses and multiple regressions including logistic and Tobit models to explore the impacts of resource constraints on patient outcomes. Resource utilisation and attempts to seek medical care were also described for severity-stratified subgroups. Results: 76.8% of respondents reported experiencing COVID-19 symptoms between December 7, 2022 and January 29, 2023. Of those who attempted to purchase medication, 72.8% reported drug shortage. 49% of those seeking medical treatment experienced difficulties. Compared with those who did not experience drug shortages, those who did had an odds ratio of 1.959 (95% CI: 1.159 ∼3.313) of presenting with moderate to severe symptoms. Compared with those without difficulties in seeking medical treatment, those who did had an average of 0.39 (95% CI: 0.110 ∼0.670) more days absent from work. Conclusion: Shenzhen residents with COVID-19 symptoms from December 2022 to January 2023 experienced a certain degree of pharmaceutical and medical resource constraints, which might have compromised their prognosis.

Impacts of COVID-19 vaccine boosters on clinical outcomes associated with the Omicron variant in China: A cross-sectional survey.

Objective: To investigate the real-world effectiveness of COVID-19 vaccine boosters during China's Omicron wave. Methods: In January 2023, we surveyed Shenzhen, China residents via online questionnaires to investigate their COVID-19 symptoms and vaccination history. The outcomes of interest included fever, other COVID-19-related symptoms, severity of symptoms, whether early onset (before December 23, 2022) and duration. Respondents were categorized as no booster, one booster 6mo ago, one booster within 6mo, or two boosters based on dose count and vaccination timing. We used multivariable logistic regressions and Tobit models to assess COVID-19 vaccine booster impacts. Results: Compared to the no booster group, two booster recipients had a lower fever risk (OR = 0.35, 95 %CI = 0.16-0.76) but not lower risks of COVID-19-related symptoms (OR = 0.74, 95 %CI = 0.26-2.06) and self-reported severe symptoms (OR = 0.47, 95 %CI = 0.19-1.15). Nor did the two booster recipients had a shorter illness duration (marginal effect = -0.79 days, 95 %CI = -1.65-0.07) and a lower risk of symptom onset delay (OR = 0.48, 95 %CI = 0.19-1.23). Compared to the no booster group, both one booster within six months (OR = 2.17, 95 %CI = 1.34-3.52) and one booster six months ago (OR = 1.30, 95 %CI = 0.92-1.82) did not reduce the risks of fever and symptoms (one booster within six months: OR = 1.57, 95 %CI = 0.84-2.90; one booster six months ago: OR = 1.23, 95 %CI = 0.79-1.93). Regardless of timing, one booster did not reduce illness duration (within six months: marginal effect = 0.25 days, 95 %CI = -0.20-0.70; six months ago: marginal effect = 0.27 days, 95 %CI = -0.08-0.62). However, receiving one booster within six months delayed symptom onset (OR = 0.54, 95 %CI = 0.34-0.86), while one booster six months ago did not (OR = 1.03, 95 %CI = 0.74-1.44). Conclusions: Receiving two booster doses reduced the onset of fever during the Omicron outbreak in mainland China.

Evaluating the Public Health and Health Economic Impacts of Baloxavir Marboxil and Oseltamivir for Influenza Pandemic Control in China: A Cost-Effectiveness Analysis Using a Linked Dynamic Transmission-Economic Evaluation Model.

BACKGROUND: Pandemic influenza poses a recurring threat to public health. Antiviral drugs are vital in combating influenza pandemics. Baloxavir marboxil (BXM) is a novel agent that provides clinical and public health benefits in influenza treatment. METHODS: We constructed a linked dynamic transmission-economic evaluation model combining a modified susceptible-exposed-infected-recovered (SEIR) model and a decision tree model to evaluate the cost-effectiveness of adding BXM to oseltamivir in China's influenza pandemic scenario. The cost-effectiveness was evaluated for the general population from the Chinese healthcare system perspective, although the users of BXM and oseltamivir were influenza-infected persons. The SEIR model simulated the transmission dynamics, dividing the population into four compartments: susceptible, exposed, infected, and recovered, while the decision tree model assessed disease severity and costs. We utilized data from clinical trials and observational studies in the literature to parameterize the models. Costs were based on 2021 CN¥ and not discounted due to a short time-frame of one year in the model. One-way, two-way, and probabilistic sensitivity analyses were also conducted. RESULTS: The integrated model demonstrated that adding BXM to treatment choices reduced the cumulative incidence of infection from 49.49% to 43.26% and increased quality-adjusted life years (QALYs) by 0.00021 per person compared with oseltamivir alone in the base-case scenario. The intervention also amounted to a positive net monetary benefit of CN¥77.85 per person at the willingness to pay of CN¥80,976 per QALY. Sensitivity analysis confirmed the robustness of these findings, with consistent results across varied key parameters and assumptions. CONCLUSIONS: Adding BXM to treatment choices instead of only treating with oseltamivir for influenza pandemic control in China appears to be cost-effective compared with oseltamivir alone. The dual-agent strategy not only enhances population health outcomes and conserves resources, but also mitigates influenza transmission and alleviates healthcare burden.

Quercetin antagonizes apoptosis, autophagy and immune dysfunction induced by di(2-ethylhexyl) phthalate via ROS/ASK1/JNK pathway.

Di(2-ethylhexyl) phthalate (DEHP) is a plasticizer that can damage various organizations and physiques through oxidative stress. Quercetin (Que) is a rich polyphenol flavonoid with good anti-inflammatory and antioxidant effects. However, the protection mechanism of Que against DEHP exposure-induced IPEC-J2 cell injury and the implication of autophagy, apoptosis and immunity are still unclear. In this experiment, we looked into the toxicity regime of DEHP exposure on IPEC-J2 cells and the antagonistic function of Que on DEHP. In the experiment, 135 µM DEHP and/or 80 µM Que were used to treat the IPEC-J2 cells for 24 h. Experiments indicated that DEHP exposure can cause increased reactive oxygen species (ROS) levels leading to oxidative stress, decreased CAT, T-AOC and GSH-Px activities, increased MDA and H2O2 accumulation, activated the ASK1/JNK signalling pathway, and further increases in the levels of apoptosis markers Bax, Caspase3, Caspase9, and Cyt-c, while reduced the Bcl-2 expression. DEHP also increased the expression of genes linked to autophagy (ATG5, Beclin1, LC3), while decreasing the expression of P62. Additionally, DEHP exposure led to elevated levels of IL1-ß, IL-6, MCP-1, and TNF expression. When exposed to Que alone, there were no significant changes in cellular oxidative stress level, ASK1/JNK signalling pathway expression level, apoptosis, autophagy and cellular immune function. The combination of DEHP and Que treatment remarkably decreased the proportion of autophagy and apoptosis, and recovered cellular immunity. In summary, Que can attenuate DEHP-induced apoptosis and autophagy in IPEC-J2 cells by regulating the ROS/ASK1/JNK signalling pathway and improving the immune dysfunction of IPEC-J2 cells.

Effects of atrazine and curcumin exposure on TCMK-1 cells: Oxidative damage, pyroptosis and cell cycle arrest.

Atrazine (ATR), a commonly used herbicide, is highly bioaccumulative and toxic, posing a threat to a wide range of organisms. Curcumin has strong antioxidant properties. However, it is unclear whether curcumin counteracts cellular pyroptosis as well as cell cycle arrest induced by ATR exposure. Therefore, we conducted a study using TCMK-1 cells and established cell models by adding 139 µmol/L ATR and 20 µmol/L curcumin. The results showed that ATR exposure produced excessive reactive oxygen species (ROS), reduced activities of enzymes such as GSH-PX, SOD and Total Antioxidant Capacity, markedly increased the content of H2O2, disrupted the antioxidant system, activated Caspase-1, and the expression levels of the pyroptosis-related genes NLRP3, GSDMD, ASC, Caspase-1, IL-1ß and IL-18 were increased. The simultaneous excess of ROS led to DNA damage, activation of P53 led to elevated expression levels of P53 and P21, as a consequence, the expression levels of cyclinE, CDK2 and CDK4 were reduced. These results suggest that Cur can modulate ATR exposure-induced pyroptosis as well as cell cycle arrest in TCMK-1 cells by governing oxidative stress.

Hydraulic resistance of three-dimensional pial perivascular spaces in the brain.

BACKGROUND: Perivascular spaces (PVSs) carry cerebrospinal fluid (CSF) around the brain, facilitating healthy waste clearance. Measuring those flows in vivo is difficult, and often impossible, because PVSs are small, so accurate modeling is essential for understanding brain clearance. The most important parameter for modeling flow in a PVS is its hydraulic resistance, defined as the ratio of pressure drop to volume flow rate, which depends on its size and shape. In particular, the local resistance per unit length varies along a PVS and depends on variations in the local cross section. METHODS: Using segmented, three-dimensional images of pial PVSs in mice, we performed fluid dynamical simulations to calculate the resistance per unit length. We applied extended lubrication theory to elucidate the difference between the calculated resistance and the expected resistance assuming a uniform flow. We tested four different approximation methods, and a novel correction factor to determine how to accurately estimate resistance per unit length with low computational cost. To assess the impact of assuming unidirectional flow, we also considered a circular duct whose cross-sectional area varied sinusoidally along its length. RESULTS: We found that modeling a PVS as a series of short ducts with uniform flow, and numerically solving for the flow in each, yields good resistance estimates at low cost. If the second derivative of area with respect to axial location is less than 2, error is typically less than 15%, and can be reduced further with our correction factor. To make estimates with even lower cost, we found that instead of solving for the resistance numerically, the well-known resistance of a circular duct could be scaled by a shape factor. As long as the aspect ratio of the cross section was less than 0.7, the additional error was less than 10%. CONCLUSIONS: Neglecting off-axis velocity components underestimates the average resistance, but the error can be reduced with a simple correction factor. These results could increase the accuracy of future models of brain-wide and local CSF flow, enabling better prediction of clearance, for example, as it varies with age, brain state, and pathological conditions.

RNA m6A modification regulates cell fate transition between pluripotent stem cells and 2-cell-like cells.

N6-methyladenosine (m6A) exerts essential roles in early embryos, especially in the maternal-to-zygotic transition stage. However, the landscape and roles of RNA m6A modification during the transition between pluripotent stem cells and 2-cell-like (2C-like) cells remain elusive. Here, we utilised ultralow-input RNA m6A immunoprecipitation to depict the dynamic picture of transcriptome-wide m6A modifications during 2C-like transitions. We found that RNA m6A modification was preferentially enriched in zygotic genome activation (ZGA) transcripts and MERVL with high expression levels in 2C-like cells. During the exit of the 2C-like state, m6A facilitated the silencing of ZGA genes and MERVL. Notably, inhibition of m6A methyltransferase METTL3 and m6A reader protein IGF2BP2 is capable of significantly delaying 2C-like state exit and expanding 2C-like cells population. Together, our study reveals the critical roles of RNA m6A modification in the transition between 2C-like and pluripotent states, facilitating the study of totipotency and cell fate decision in the future.

Hydraulic resistance of three-dimensional pial perivascular spaces in the brain.

Background: Perivascular spaces (PVSs) carry cerebrospinal fluid (CSF) around the brain, facilitating healthy waste clearance. Measuring those flows in vivo is difficult, and often impossible, because PVSs are small, so accurate modeling is essential for understanding brain clearance. The most important parameter for modeling flow in a PVS is its hydraulic resistance, defined as the ratio of pressure drop to volume flow rate, which depends on its size and shape. In particular, the local resistance per unit length varies along a PVS and depends on variations in the local cross section. Methods: Using segmented, three-dimensional images of pial PVSs in mice, we performed fluid dynamical simulations to calculate the resistance per unit length. We applied extended lubrication theory to elucidate the difference between the calculated resistance and the expected resistance assuming a uniform flow. We tested four different approximation methods, and a novel correction factor to determine how to accurately estimate resistance per unit length with low computational cost. To assess the impact of assuming unidirectional flow, we also considered a circular duct whose cross-sectional area varied sinusoidally along its length. Results: We found that modeling a PVS as a series of short ducts with uniform flow, and numerically solving for the flow in each, yields good resistance estimates at low cost. If the second derivative of area with respect to axial location is less than 2, error is typically less than 15%, and can be reduced further with our correction factor. To make estimates with even lower cost, we found that instead of solving for the resistance numerically, the well-known resistance of a circular duct could be scaled by a shape factor. As long as the aspect ratio of the cross section was less than 0.7, the additional error was less than 10%. Conclusions: Neglecting off-axis velocity components underestimates the average resistance, but the error can be reduced with a simple correction factor. These results could increase the accuracy of future models of brain-wide and local CSF flow, enabling better prediction of clearance, for example, as it varies with age, brain state, and pathological conditions.

Dispersion and Tunable Alignment of Colloidal Silver Nanowires in a Nematic Liquid Crystal for Applications in Electric-Optic Devices.

The dispersion and tunable alignment of colloidal nanomaterials is desirable for practical applications in electric-optic (E-O) devices; however, it remains challenging for large one-dimensional nanomaterials with a large aspect ratio. Here, we demonstrate a large-scale, simple, multi-microdomain, and noncontact photoalignment technology to align colloidal silver nanowires (AgNWs, length ∼4.5 µm, diameter ∼70.6 nm) in a liquid crystal (LC) with a high two-dimensional order parameter (about 0.9). The AgNWs are precisely self-assembled via photomasks with twisted nematic and planar alignment models in microdomain regions. The AgNW orientation is tuned with an electric field, through the rotation of an LC director n, which allows three-dimensional (3D) tunable orientation combined with photoalignment. The colloidal dispersions of AgNWs in the LC cell influenced the ion transfer, elastic constant, dielectric anisotropy, and near LC alignment, changing the E-O properties of the LC devices. The 3D tunable orientation of an AgNW by photoalignment and an electric field could provide a new way to assemble large colloidal nanomaterials and fabricate functional E-O devices.

Remodeling of H3K9me3 during the pluripotent to totipotent-like state transition.

Multiple chromatin modifiers associated with H3K9me3 play important roles in the transition from embryonic stem cells to 2-cell (2C)-like cells. However, it remains elusive how H3K9me3 is remodeled and its association with totipotency. Here, we integrated transcriptome and H3K9me3 profiles to conduct a detailed comparison of 2C embryos and 2C-like cells. Globally, H3K9me3 is highly preserved and H3K9me3 dynamics within the gene locus is not associated with gene expression change during 2C-like transition. Promoter-deposited H3K9me3 plays non-repressive roles in the activation of genes during 2C-like transition. In contrast, transposable elements, residing in the nearby regions of up-regulated genes, undergo extensive elimination of H3K9me3 and are tended to be induced in 2C-like transitions. Furthermore, a large fraction of trophoblast stem cell-specific enhancers undergo loss of H3K9me3 exclusively in MERVL+/Zscan4+ cells. Our study therefore reveals the unique H3K9me3 profiles of 2C-like cells, facilitating the further exploration of totipotency.

Liquid crystal gratings based on alternate TN and PA photoalignment.

A diffraction grating is proposed by periodically defining the liquid-crystal director distribution to form alternate parallel aligned and twist nematic regions in a cell placed between two crossed polarizers. Based on the combined phase and amplitude modulation, both 1D and 2D tunable gratings are demonstrated. Low voltage ON/OFF switching of 1st order diffracted light with extinction ratio over 80 is achieved within a small voltage interval of 0.15 Vrms. Unique four-state feature of the cell is obtained and their applications in optical logic devices are discussed.