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The Taiwan orogeny, an example of arc-continental collision, exhibits complex geological structures and rapid exhumation. Many models have tried and failed to fully capture the dynamics of these processes. We developed a comprehensive thermomechanical model that considers the transition from brittle to ductile behavior with depth, lithology-dependent erosion and observed decollement and backstop geometries. This model successfully reproduces the intricate structures observed within the Taiwan orogeny, aligns with structural complexities, metamorphic temperature profiles, thermochronological records, strain distributions, and the rates of exhumation and cooling and elucidates the roles of ductile deformation and ramp structures in forming the Hsuehshan Range and the Western fold and thrust belt. The insights from this model offer potential applicability to other orogenic wedges worldwide.

Background: Vaccine clinical trials should strive to recruit a racially, socioeconomically, and ethnically diverse range of participants to ensure appropriate representation that matches population characteristics. Yet, full inclusion in research is often limited., Methods: A single-center retrospective study was conducted of adults enrolled at Brigham and Women's Hospital (Boston, MA) between July 2020 and December 2021. Demographic characteristics, including age, race, ethnicity, ZIP code, and sex assigned at birth, were analyzed from both HIV and COVID-19 vaccine trials during the study period, acknowledging the limitations to representation under these parameters. We compared the educational attainment of vaccine trial participants to residents of the Massachusetts metropolitan area, geocoded participants' addresses to their census block group, and linked them to reported median household income levels from publicly available data for 2020. Frequency and quartile analyses were carried out, and spatial analyses were performed using ArcGIS Online web-based mapping software (Esri)., Results: A total of 1030 participants from four COVID-19 vaccine trials ( n  = 916 participants) and six HIV vaccine trials ( n  = 114 participants) were included in the analysis. The median age was 49 years (IQR 33-63) and 28 years (IQR 24-34) for the COVID-19 and HIV vaccine trials, respectively. Participants identifying as White were the majority group represented for both the COVID-19 ( n  = 598, 65.3%) and HIV vaccine trials ( n  = 83, 72.8%). Fewer than 25% of participants identified as Hispanic or Latin. Based on ZIP code of residence, the median household income for COVID-19 vaccine clinical trial participants ( n  = 846) was 102,088 USD (IQR = 81,442-126,094). For HIV vaccine clinical trial participants ( n  = 109), the median household income was 101,266 USD (IQR 75,052-108,832)., Conclusion: We described the characteristics of participants enrolled for HIV and COVID-19 vaccine trials at a single center and found similitude in geographical distribution, median incomes, and proportion of underrepresented individuals between the two types of vaccine candidate trials. Further outreach efforts are needed to ensure the inclusion of individuals from lower educational and socioeconomic brackets. In addition, continued and sustained efforts are necessary to ensure inclusion of individuals from diverse racial and ethnic backgrounds., Competing Interests: LB, SW, and AS are involved in HIV, COVID, and other vaccine clinical trials conducted in collaboration with the NIH, HIV Vaccine Trials Network, COVID Vaccine Prevention Network, International AIDS Vaccine Initiative, Crucell/Janssen, Moderna, Military HIV Research Program, the Bill & Melinda Gates Foundation, and the Ragon Institute. SW has received grant and research support from Johnson & Johnson, Moderna, Pfizer, Sanofi Pasteur, VIR, and Worcester HIV Vaccine. AS has received grant and research support from Merck. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Lezo Ramirez, Koleske, Ometoruwa, Park Chang, Kanwal, Morreale, Avila Paz, Tong, Baden, Sherman and Walsh.)

Objective: To develop a highly sensitive and rapid nucleic acid detection method for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)., Methods: We designed, developed, and manufactured an integrated disposable device for SARS-CoV-2 nucleic acid extraction and detection. The precision of the liquid transfer and temperature control was tested. A comparison between our device and a commercial kit for SARS-Cov-2 nucleic acid extraction was performed using real-time fluorescence reverse transcription polymerase chain reaction (RT-PCR). The entire process, from SARS-CoV-2 nucleic acid extraction to amplification, was evaluated., Results: The precision of the syringe transfer volume was 19.2 ± 1.9 μL (set value was 20), 32.2 ± 1.6 (set value was 30), and 57.2 ± 3.5 (set value was 60). Temperature control in the amplification tube was measured at 60.0 ± 0.0 °C (set value was 60) and 95.1 ± 0.2 °C (set value was 95) respectively. SARS-Cov-2 nucleic acid extraction yield through the device was 7.10 × 10 6 copies/mL, while a commercial kit yielded 2.98 × 10 6 copies/mL. The mean time to complete the entire assay, from SARS-CoV-2 nucleic acid extraction to amplification detection, was 36 min and 45 s. The detection limit for SARS-CoV-2 nucleic acid was 250 copies/mL., Conclusion: The integrated disposable devices may be used for SARS-CoV-2 Point-of-Care test (POCT)., (Copyright © 2024 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.)

Phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P 2 ] is implicated in various processes, including hormone-induced signal transduction, endocytosis, and exocytosis in the plasma membrane. However, how H 2 O 2 accumulation regulates the levels of PtdIns(4,5)P 2 in the plasma membrane in cells stimulated with epidermal growth factors (EGFs) is not known. We show that a plasma membrane PtdIns(4,5)P 2 -degrading enzyme, synaptojanin (Synj) phosphatase, is inactivated through oxidation by H 2 O 2 . Intriguingly, H 2 O 2 inhibits the 4-phosphatase activity of Synj but not the 5-phosphatase activity. In EGF-activated cells, the oxidation of Synj dual phosphatase is required for the transient increase in the plasma membrane levels of phosphatidylinositol 4-phosphate [PtdIns(4)P], which can control EGF receptor-mediated endocytosis. These results indicate that intracellular H 2 O 2 molecules act as signaling mediators to fine-tune endocytosis by controlling the stability of plasma membrane PtdIns(4)P, an intermediate product of Synj phosphoinositide dual phosphatase., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Toll-like receptor (TLR) 7, a transmembrane signal transduction receptor expressed on the surface of endosomes, has become an attractive target for antiviral and cancer immunotherapies. TLR7 can induce signal transduction by recognizing single-stranded RNA or its analogs, leading to the release of cytokines such as IL-6, IL-12, TNF-α and type-I IFN. Activation of TLR7 helps to enhance immunogenicity and immune memory by stimulating immune cells. Herein, we identified a novel selective TLR7 agonist, GY101, and determined its ability to activate TLR7. In summary, in vitro, compound GY101 significantly induced the secretion of IL-6, IL-12, TNF-α and IFN-γ in mouse splenic lymphocytes; in vivo, peritumoral injection of GY101 significantly suppressed colon cancer CT26, as well as poorly immunogenic B16-F10 and 4T1 cancer cell-derived tumor growth by activating the infiltration of lymphocytes and polarization of M2-like macrophages into M1-like macrophages. These results demonstrate that GY101, as a potent TLR7 agonist, holds great potential for cancer immunotherapy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

InP/ZnSe/ZnS quantum dots (QDs) stand as promising candidates for advancing QD-organic light-emitting diodes (QLED), but low emission efficiency due to their susceptibility to oxidation impedes applications. Structural defects play important roles in the emission efficiency degradation of QDs, but the formation mechanism of defects in oxidized QDs has been less investigated. Here, we investigated the impact of diverse structural defects formation on individual QDs and propagation during UV-facilitated oxidation using high-resolution (scanning) transmission electron microscopy. UV-facilitated oxidation of the QDs alters shell morphology by the formation of surface oxides, leaving ZnSe surfaces poorly passivated. Further oxidation leads to the formation of structural defects, such as dislocations, and induces strain at the oxide-QD interfaces, facilitating In diffusion from the QD core. These changes in the QD structures result in emission quenching. This study provides insight into the formation of structural defects through photo-oxidation, and their effects on emission properties of QDs., (© 2024. The Author(s).)

Macroscopic assembly offers immense potential for constructing complex systems due to the high design flexibility of the building blocks. In such assembly systems, hydrogels are promising candidates for building blocks due to their versatile chemical compositions and ease of property tuning. However, two major challenges must be addressed to facilitate application in a broader context: the precision of assembly and the quantity of orthogonally matching pairs must both be increased. Although previous studies have attempted to address these challenges, none have successfully dealt with both simultaneously. Here, we propose topology-based design criteria for the selective assembly of hydrogel building blocks. By introducing the dual lock-and-key structures, we demonstrate highly precise assembly exclusively between the matching pairs. We establish principles for selecting multiple orthogonally matching pairs and achieve selective assembly involving simple one-to-one matching and complex assemblies with multiple orthogonal matching points. Moreover, by harnessing hydrogel tunability and the abundance of matching pairs, we synthesize complementary single-stranded structures for programmable assembly and successfully assemble them in the correct order. Finally, we demonstrate a hydrogel-based self-assembled logic gate system, including a YES gate, an OR gate, and an AND gate. The output is generated only when the corresponding inputs are provided according to each logic.

Introduction: Red blood cell (RBC) storage solution is used for suspending and preserving RBCs for later use in in vitro immunohematology testing. Proper RBC preservation is crucial for obtaining accurate results in RBC phenotyping and pretransfusion antibody screening tests. Haemolysis or RBC antigen degradation during storage can result in inaccurate RBC phenotyping, thereby decreasing the sensitivity of pretransfusion antibody screening and identification assays. The conventional RBC storage solutions usually contain adenosine, adenine, and antibiotics. We designed an RBC storage solution and determined whether it could preserve RBC integrity for 70 days., Materials and Methods: The new storage solution has a different formula from that of the conventional solution-in particular, it is strengthened with polyethylene glycol (PEG). The extent of haemolysis and hemagglutination reactivity of the RBC antigen systems, Rh, Duffy, Kidd, Lewis, MNS, P1, and the rare antigen Mi a (which has a low prevalence antigen in most parts of the world but a higher prevalence in Taiwan), in the new RBC storage solution was compared with that of the conventionally preserved RBC storage solution., Results: The RBCs preserved in the new solution for 70 days retained a similar haemolysis grade as those preserved in the control solution for 28 days. Although both solutions largely preserved RBC antigenicity, the decline in RBC hemagglutination scores in new solution often occurred later than that in the control solution in most antigen phenotyping assays, especially labile antigens such as D, P1, and M., Conclusion: The new solution reduces haemolysis more effectively and preserves antigenicity throughout the 70-day storage period. Moreover, Mi a antigen is more stable in the experimental group.

Biological systems are composed of hierarchical structures made of a large number of proteins. These structures are highly sophisticated and challenging to replicate using artificial synthesis methods. To exploit these structures in materials science, biotemplating is used to achieve biocomposites that accurately mimic biological structures and impart functionality of inorganic materials, including electrical conductivity. However, the biological scaffolds used in previous studies are limited to stereotypical and simple morphologies with little synthetic diversity because of a lack of control over their morphologies. This study proposes that the specific protein assemblies within the cell-derived extracellular matrix (ECM), whose morphological features are widely tailorable, can be employed as versatile biotemplates. In a typical procedure, a fibrillar assembly of fibronectin-a constituent protein of the ECM-is metalized through an antibody-guided biotemplating approach. Specifically, the antibody-bearing nanogold is attached to the fibronectin through antibody-antigen interactions, and then metals are grown on the nanogold acting as a seed. The biomimetic structure can be adapted for hydrogen production and sensing after improving its electrical conductivity through thermal sintering or additional metal growth. This study demonstrates that cell-derived ECM can be an attractive option for addressing the diversity limitation of a conventional biotemplate., (© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Here we report SUPPORT (statistically unbiased prediction utilizing spatiotemporal information in imaging data), a self-supervised learning method for removing Poisson-Gaussian noise in voltage imaging data. SUPPORT is based on the insight that a pixel value in voltage imaging data is highly dependent on its spatiotemporal neighboring pixels, even when its temporally adjacent frames alone do not provide useful information for statistical prediction. Such dependency is captured and used by a convolutional neural network with a spatiotemporal blind spot to accurately denoise voltage imaging data in which the existence of the action potential in a time frame cannot be inferred by the information in other frames. Through simulations and experiments, we show that SUPPORT enables precise denoising of voltage imaging data and other types of microscopy image while preserving the underlying dynamics within the scene., (© 2023. The Author(s).)

This paper introduces a transformer encoding linker network (TELNet) for automatically identifying scene boundaries in videos without prior knowledge of their structure. Videos consist of sequences of semantically related shots or chapters, and recognizing scene boundaries is crucial for various video processing tasks, including video summarization. TELNet utilizes a rolling window to scan through video shots, encoding their features extracted from a fine-tuned 3D CNN model (transformer encoder). By establishing links between video shots based on these encoded features (linker), TELNet efficiently identifies scene boundaries where consecutive shots lack links. TELNet was trained on multiple video scene detection datasets and demonstrated results comparable to other state-of-the-art models in standard settings. Notably, in cross-dataset evaluations, TELNet demonstrated significantly improved results (F-score). Furthermore, TELNet's computational complexity grows linearly with the number of shots, making it highly efficient in processing long videos.

Hydrogels have been utilized extensively as a material for retaining position information in tissue imaging procedures, such as tissue clearing and super-resolution imaging. Immunostaining thick biological tissues, however, poses a bottleneck that restricts sample size. The recently developed technique known as entangled link-augmented stretchable tissue-hydrogel (ELAST) accelerates the immunostaining process by embedding specimens in long-chain polymers and stretching them. A more advanced version of ELAST, magnifiable entangled link-augmented stretchable tissue-hydrogel (mELAST), achieves rapid immunostaining and tissue expansion by embedding specimens in long-chain neutral polymers and subsequently hydrolyzing them. Building on these techniques, we introduce a variant of mELAST called ExELAST. This approach uses charged monomers to stretch and expand tissue slices. Using ExELAST, we first tested two hydrogel compositions that could permit uniform expansion of biological specimens. Then, we apply the tailored hydrogel to the 500-μm-thick mouse brain slices and demonstrated that they can be stained within two days and imaged with a resolution below the diffraction limit of light., (© 2023. The Author(s).)

Background: Although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination reduces the risk and severity of coronavirus disease 2019 (COVID-19), several variables may impact the humoral response among patients undergoing hematopoietic stem cell transplantation (HSCT)., Methods: A retrospective chart review was conducted among SARS-CoV-2-vaccinated HSCT recipients between 2020 and 2022 at a single center in Boston, Massachusetts. Patients age ≥18 years who received doses of Pfizer, Moderna, or J&J vaccines were included. Anti-spike (S) immunoglobulin G (IgG) titer levels were measured using the Roche assay. Responders (≥0.8 U/mL) and nonresponders (<0.8 U/mL) were categorized and analyzed. Multivariable linear and logistic regression were used to estimate the correlation coefficient and odds ratio of response magnitude and status., Results: Of 152 HSCT recipients, 141 (92.8%) were responders, with a median (interquartile range [IQR]) anti-S IgG titer of 2500 (107.9-2500) U/mL at a median (IQR) of 80.5 (36-153.5) days from last dose, regardless of the number of doses received. Higher quantitative titers were associated with receipt of more vaccine doses (coeff, 205.79; 95% CI, 30.10 to 381.47; P = .022), being female (coeff, 343.5; 95% CI, -682.6 to -4.4; P = .047), being younger (<65 years; coeff, 365.2; 95% CI, -711.3 to 19.1; P = .039), and not being on anti-CD20 therapy (coeff, -1163.7; 95% CI, -1717.7 to -609.7; P = .001). Being male (odds ratio [OR], 0.11; 95% CI, 0.01 to 0.93; P = .04) and being on anti-CD20 therapy (OR, 0.16; 95% CI, 0.03 to 0.70; P = .016) were associated with nonresponse., Conclusions: Overall, most HSCT recipients had high SARS-CoV-2 antibody responses. More vaccine doses improved the magnitude of immune responses. Anti-S IgG monitoring may be useful for identifying attenuated vaccine-induced responses., Competing Interests: Potential conflicts of interest. S.R.W. has received institutional funding from the National Institute of Allergy and Infectious Diseases/National Institutes of Health and institutional grants or contracts from Sanofi Pasteur, Janssen Vaccines/Johnson & Johnson, Moderna Tx, Pfizer, Vir Biotechnology, and Worcester HIV Vaccine; has participated in data safety monitoring or advisory boards for Janssen Vaccines/Johnson & Johnson; and his spouse holds stock/stock options in Regeneron Pharmaceuticals. A.C.S. is involved in HIV, coronavirus (COVID), and other vaccine clinical trials conducted in collaboration with the NIH, HIV Vaccine Trials Network, and COVID Vaccine Prevention Network. The views expressed are those of the authors and not necessarily of any funding agency., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Records of secondary hydrocephalus patients undergoing shunt surgery in the Department of Neurosurgery of Peking Union Medical College Hospital from September 2012 to April 2022 and their clinical characteristics and outcomes were retrospectively reviewed and analyzed. Among 121 patients who received first time shunt placement, the most common causes of secondary hydrocephalus were brain hemorrhage (55, 45.5%) and trauma (35, 28.9%). Cognition decline (106, 87.6%), abnormal gait (50, 41.3%) and incontinence (40, 33.1%) were the most prevalent manifestations. Postoperative central nervous system infection (4, 3.3%), shunt obstruction (3, 2.5%) and subdural hematoma/effusion (4, 3.3%) were the most frequent neurological complications. Overall incidence of postoperative complications was 9% (11 cases) in the current cohort. And 50.5% (54/107) of the patients receiving shunting achieved a Glasgow outcome scale (GOS) score of at least 4. Shunt surgery is preferred for secondary hydrocephalus, especially for secondary normal pressure hydrocephalus. Moreover, it is recommended to complete cranioplasty in staged operation or one-stage operation for the patients with decompressive craniectomy.

Human hands are highly versatile. Even though they are primarily made of materials with high water content, they exhibit a high load capacity. However, existing hydrogel grippers do not possess a high load capacity due to their innate softness and mechanical strength. This work demonstrates a human hand-inspired all-hydrogel gripper that can bear more than 47.6 times its own weight. This gripper is made of two hydrogels: poly(methacrylamide- co -methacrylic acid) (P(MAAm- co -MAAc)) and poly( N -isopropylacrylamide) (PNIPAM). P(MAAm- co -MAAc) is extremely stiff but becomes soft above its transition temperature. By taking advantage of the difference in the kinetics of the stiff-soft transition of P(MAAm- co -MAAc) hydrogels and the swelling-shrinking transition of PNIPAM hydrogels, this gripper can be switched between its stiff-bent and stiff-stretched states by simply changing the temperature. The assembly of these two hydrogels into a gripper necessitated the development of a new hydrogel adhesion method, as existing topological adhesion methods are not applicable to such stiff hydrogels. A new hydrogel adhesion method, termed split-brushing adhesion, has been demonstrated to satisfy this need. When applied to P(MAAm- co -MAAc) hydrogels, this method achieves an adhesion energy of 1221.6 J m -2 , which is 67.5 times higher than that achieved with other topological adhesion methods.

Collagen is a prominent target of nonenzymatic glycation, which is a hallmark of aging and causes functional alteration of the matrix. Here, we uncover glycation-mediated structural and functional changes in the collagen-enriched meningeal membrane of the human and mouse brain. Using an in vitro culture platform mimicking the meningeal membrane composed of fibrillar collagen, we showed that the accumulation of advanced glycation end products (AGEs) in the collagen membrane is responsible for glycation-mediated matrix remodeling. These changes influence fibroblast-matrix interactions, inducing cell-mediated ECM remodeling. The adherence of meningeal fibroblasts to the glycated collagen membrane was mediated by the discoidin domain-containing receptor 2 (DDR2), whereas integrin-mediated adhesion was inhibited. A-kinase anchoring protein 12 (AKAP12)-positive meningeal fibroblasts in the meningeal membrane of aged mice exhibited substantially increased expression of DDR2 and depletion of integrin beta-1 (ITGB1). In the glycated collagen membrane, meningeal fibroblasts increased the expression of matrix metalloproteinase 14 (MMP14) and less tissue inhibitor of metalloproteinase-1 (TIMP1). In contrast, the cells exhibited decreased expression of type I collagen (COL1A1). These results suggest that glycation modification by meningeal fibroblasts is intimately linked to aging-related structural and functional alterations in the meningeal membrane., (© 2023 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.)

Achieving strong adhesion between hydrogels and diverse materials is greatly significant for emerging technologies yet remains challenging. Existing methods using non-covalent bonds have limited pH and ion stability, while those using covalent bonds typically lack on-demand detachment capability, limiting their applications. In this study, a general strategy of covalent bond-based and detachable adhesion by incorporating amine-rich proteins in various hydrogels and inducing the interfacial crosslinking of the hydrogels using a protein-crosslinking agent is demonstrated. The protein crosslink offers topological adhesion and can reach a strong adhesion energy of ≈750 J m -2 . The chemistry of the adhesion is characterized and that the inclusion of proteins inside the hydrogels does not alter the hydrogels' properties is shown. The adhesion remains intact after treating the adhered hydrogels with various pH solutions and ions, even at an elevated temperature. The detachment is triggered by treating proteinase solution at the bonding front, causing the digestion of proteins, thus breaking up the interfacial crosslink network. In addition, that this approach can be used to adhere hydrogels to diverse dry surfaces, including glass, elastomers and plastics, is shown. The stable chemistry of protein crosslinks opens the door for various applications in a wide range of chemical environments., (© 2023 Wiley-VCH GmbH.)

In biological studies and diagnoses, brightfield (BF), fluorescence, and electron microscopy (EM) are used to image biomolecules inside cells. When compared, their relative advantages and disadvantages are obvious. BF microscopy is the most accessible of the three, but its resolution is limited to a few microns. EM provides a nanoscale resolution, but sample preparation is time-consuming. In this study, we present a new imaging technique, which we termed decoration microscopy (DecoM), and quantitative investigations to address the aforementioned issues in EM and BF microscopy. For molecular-specific EM imaging, DecoM labels proteins inside cells using antibodies bearing 1.4 nm gold nanoparticles (AuNPs) and grows silver layers on the AuNPs' surfaces. The cells are then dried without buffer exchange and imaged using scanning electron microscopy (SEM). Structures labeled with silver-grown AuNPs are clearly visible on SEM, even they are covered with lipid membranes. Using stochastic optical reconstruction microscopy, we show that the drying process causes negligible distortion of structures and that less structural deformation could be achieved through simple buffer exchange to hexamethyldisilazane. Using DecoM, we visualize the nanoscale alterations in microtubules by microtubule-severing proteins that cannot be observed with diffraction-limited fluorescence microscopy. We then combine DecoM with expansion microscopy to enable sub-micron resolution BF microscopy imaging. We first show that silver-grown AuNPs strongly absorb white light, and the structures labeled with them are clearly visible on BF microscopy. We then show that the application of AuNPs and silver development must follow expansion to visualize the labeled proteins clearly with sub-micron resolution., Competing Interests: The authors declare no competing financial interest., (This journal is © The Royal Society of Chemistry.)

Photochemical instability and reactivity of organic ultraviolet (UV) filters not only degrade the performance of sunscreen formulations but also generate toxic photodegradation products and reactive oxygen species (ROS). Although the encapsulation of organic UV filters into synthetic polymer particles has been widely investigated, synthetic plastics were recently banned for personal care and cosmetic products due to marine and coastal pollution issues. Here we present a plastic-free, photochemically stable and inactive UV filter platform based on chitosan-coated mesoporous silica microparticles, denoted 'mSOCPs', incorporating octyl methoxycinnamate (OMC) as a sunscreen agent. Sunlight induced the degradation of ∼80% free OMC in artificial sweat in 1 h at room temperature, while only 20% of OMC degraded for 3 h when encapsulated within mSOCPs. Moreover, mSOCPs efficiently suppressed the photochemical generation of ROS by about 99% through the combined effects of the mesoporous silica structure and chitosan coating. Accordingly, mSOCPs substantially increased the cell viability of fibroblasts exposed to UV irradiation. This work demonstrates that the biopolymer coatings of mesoporous inorganic particles can be a promising approach to the plastic-free encapsulation of organic UV filters for suppressing their photochemical reactivity and degradation., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Biological systems consist of hierarchical protein structures, each of which has unique 3D geometries optimized for specific functions. In the past decades, the growth of inorganic materials on specific proteins has attracted considerable attention. However, the use of specific proteins as templates has only been demonstrated in relatively simple organisms, such as viruses, limiting the range of structures that can be used as scaffolds. This study proposes a method for synthesizing metallic structures that resemble the 3D assemblies of specific proteins in mammalian cells and animal tissues. Using 1.4 nm nanogold-conjugated antibodies, specific proteins within cells and ex vivo tissues are labeled, and then the nanogold acts as nucleation sites for growth of metal particles. As proof of concept, various metal particles are grown using microtubules in cells as templates. The metal-containing cells are applied as catalysts and show catalytic stability in liquid-phase reactions due to the rigid support provided by the microtubules. Finally, this method is used to produce metal structures that replicate the specific protein assemblies of neurons in the mouse brain or the extracellular matrices in the mouse kidney and heart. This new biotemplating approach can facilitate the conversion of specific protein structures into metallic forms in ex vivo multicellular organisms., (© 2022 Wiley-VCH GmbH.)

Curved hydrogel surfaces bearing chemical patterns are highly desirable in various applications, including artificial blood vessels, wearable electronics, and soft robotics. However, previous studies on the fabrication of chemical patterns on hydrogels employed two-photon lithography, which is still not widely accessible to most laboratories. This work demonstrates a new patterning technique for fabricating curved hydrogels with chemical patterns on their surfaces without two-photon microscopy. In this work, we show that exposing hydrogels in fluorophore solutions to single photons via confocal microscopy enables the patterning of fluorophores on hydrogels. By applying this technique to highly stretchable hydrogels, we demonstrate three applications: (1) improving pattern resolution by fabricating patterns on stretched hydrogels and then returning the hydrogels to their initial, unstretched length; (2) modifying the local stretchability of hydrogels at a microscale resolution; and (3) fabricating perfusable microchannels with chemical patterns by winding chemically patterned hydrogels around a template, embedding the hydrogels in a second hydrogel, and then removing the template. The patterning method demonstrated in this work may facilitate a better mimicking of the physicochemical properties of organs in tissue engineering and may be used to make hydrogel robots with specific chemical functionalities.

Amplification of immunofluorescence (IF) signals is becoming increasingly critical in cancer research and neuroscience. Recently, we put forward a new signal amplification technique, which we termed fluorescent signal amplification via cyclic staining of target molecules (FRACTAL). FRACTAL amplifies IF signals by repeatedly labeling target proteins with a pair of secondary antibodies that bind to each other. However, simultaneous amplification of multiple IF signals via FRACTAL has not yet been demonstrated because of cross-reactivity between the secondary antibodies. In this study, we show that mutual cross-adsorption between antibodies can eliminate all forms of cross-reactions between them, enabling simultaneous amplification of multiple IF signals. First, we show that a typical cross-adsorption process-in which an antibody binds to proteins with potential cross-reactivity with the antibody-cannot eliminate cross-reactions between antibodies in FRACTAL. Next, we show that all secondary antibodies used in FRACTAL need to be mutually cross-adsorbed to eliminate all forms of cross-reactivity, and then we demonstrate simultaneous amplification of multiple IF signals using these antibodies. Finally, we show that multiplexed FRACTAL can be applied to expansion microscopy to achieve higher fluorescence intensities after expansion. Multiplexed FRACTAL is a highly versatile tool for standard laboratories, as it amplifies multiple IF signals without the need for custom antibodies., (© 2022. The Author(s).)

Ultra-multiplexed fluorescence imaging requires the use of spectrally overlapping fluorophores to label proteins and then to unmix the images of the fluorophores. However, doing this remains a challenge, especially in highly heterogeneous specimens, such as the brain, owing to the high degree of variation in the emission spectra of fluorophores in such specimens. Here, we propose PICASSO, which enables more than 15-color imaging of spatially overlapping proteins in a single imaging round without using any reference emission spectra. PICASSO requires an equal number of images and fluorophores, which enables such advanced multiplexed imaging, even with bandpass filter-based microscopy. We show that PICASSO can be used to achieve strong multiplexing capability in diverse applications. By combining PICASSO with cyclic immunofluorescence staining, we achieve 45-color imaging of the mouse brain in three cycles. PICASSO provides a tool for multiplexed imaging with high accessibility and accuracy for a broad range of researchers., (© 2022. The Author(s).)

Simultaneous nanoscale imaging of mRNAs and proteins of the same specimen can provide better information on the translational regulation, molecular trafficking, and molecular interaction of both normal and diseased biological systems. Expansion microscopy (ExM) is an attractive option to achieve such imaging; however, simultaneous ExM imaging of proteins and mRNAs has not been demonstrated. Here, a technique for simultaneous ExM imaging of proteins and mRNAs in cultured cells and tissue slices, which we termed dual-expansion microscopy (dual-ExM), is demonstrated. First, we verified a protocol for the simultaneous labeling of proteins and mRNAs. Second, we combined the simultaneous labeling protocol with ExM to enable the simultaneous ExM imaging of proteins and mRNAs in cultured cells and mouse brain slices and quantitatively study the degree of signal retention after expansion. After expansion, both proteins and mRNAs can be visualized with a resolution beyond the diffraction limit of light in three dimensions. Dual-ExM is a versatile tool to study complex biological systems, such as the brain or tumor microenvironments, at a nanoscale resolution., (© 2022. The Author(s).)

MicroRNAs (miRNAs), as key negative regulators of gene expression, are closely related to tumor occurrence and progression. miR-194-5p (miR-194-1) has been shown to play a regulatory role in various cancers however, its biological function and mechanism of action in breast cancer have not yet been well explored. In this study, we use the UALCAN and LinkedOmics databases to analyze transcription expression in The Cancer Genome Atlas Breast Invasive Carcinoma (TCGA-BRCA). The epithelial-mesenchymal transition status of breast cancer cells was evaluated by wound-healing assay, trans-well assays, and gelatin zymography, while protein expression was assessed by Western blotting. miR-194-5p expression was found to be up-regulated in breast cancer clinical specimens but down-regulated in the triple-negative breast cancer (TNBC) cell line MDA-MB-231 and breast cancer clinical specimens in The Cancer Genome Atlas (TCGA). miR-194-5p significantly inhibited the expression of the epithelial marker ZO-1 and increased the expression of mesenchymal markers, including ZEB-1 and vimentin, in MDA-MB-231 cells. miR-194-5p significantly reduced the gelatin-degrading activity of matrix metalloproteinase-2 (MMP-2) and MMP-9 in zymography assays. In MDA-MB-231 cells and TCGA patient samples, ZEB-1 expression was significantly inversely correlated with miR-194-5p expression. High levels of miR-194-5p were associated with good overall survival. miR-194-5p regulates epithelial-mesenchymal transition (EMT) in TNBC. Our findings suggest that miR-194-5p functions as a tumor biomarker in breast cancer, providing new insights for the study of breast cancer development and metastasis.

Azvudine (FNC) is a nucleoside analog that inhibits HIV-1 RNA-dependent RNA polymerase (RdRp). Recently, we discovered FNC an agent against SARS-CoV-2, and have taken it into Phase III trial for COVID-19 patients. FNC monophosphate analog inhibited SARS-CoV-2 and HCoV-OC43 coronavirus with an EC 50 between 1.2 and 4.3 μM, depending on viruses or cells, and selective index (SI) in 15-83 range. Oral administration of FNC in rats revealed a substantial thymus-homing feature, with FNC triphosphate (the active form) concentrated in the thymus and peripheral blood mononuclear cells (PBMC). Treating SARS-CoV-2 infected rhesus macaques with FNC (0.07 mg/kg, qd, orally) reduced viral load, recuperated the thymus, improved lymphocyte profiles, alleviated inflammation and organ damage, and lessened ground-glass opacities in chest X-ray. Single-cell sequencing suggested the promotion of thymus function by FNC. A randomized, single-arm clinical trial of FNC on compassionate use (n = 31) showed that oral FNC (5 mg, qd) cured all COVID-19 patients, with 100% viral ribonucleic acid negative conversion in 3.29 ± 2.22 days (range: 1-9 days) and 100% hospital discharge rate in 9.00 ± 4.93 days (range: 2-25 days). The side-effect of FNC is minor and transient dizziness and nausea in 16.12% (5/31) patients. Thus, FNC might cure COVID-19 through its anti-SARS-CoV-2 activity concentrated in the thymus, followed by promoted immunity., (© 2021. The Author(s).)

Environmental DNA(eDNA), a new tool for monitoring the biodiversity of aquatic ecosystems, is able to analyze characteristics of biodiversity from a microscopic perspective. Based on eDNA data collected from the Weihe River, diversity indexes, non-metric multidimensional scaling, cluster analysis, and correlation network analysis were employed to explore the diversity and community structure of zooplankton focusing on the niche differentiation of keystone species and environmental adaptability. The eDNA approach identified three types of zooplankton including Rotifera, Cladocera, and Copepoda, among which the dominant species was Brachionus calyciflorus . The zooplankton community shows significant differences in species composition, abundance, diversity and spatial distribution characteristics( P <0.01). The average values of the Chao1 index, ACE index, Shannon index, and Simpson index were 22.25, 22.38, 2.32, and 0.68, respectively. The downstream biodiversity is significantly higher than in the upstream area. Non-metric multidimensional scale analysis and hierarchical cluster analysis further showed that the zooplankton community structure shows distinct regional differences. The keystone species in the community have a high degree of connection with other species, with a high node degree, centrality, and modularity. The niche breadth( B i ) of the operational taxonomic units(OTUs) of the keystone species varied from 0.38 to 0.80. The medium niche species accounted for 63% of all keystone species. The average niche overlap index( Q ik ) was 0.72, and the degree of overlap was generally high. RDA analysis further identified that water environmental variables were closely related to changes in the zooplankton community structure and niche differentiation. For example, total nitrogen and water temperature were the main limiting factors, which play important roles in shaping the zooplankton community structure.