Genome-wide CRISPR screen identifies ESPL1 limits the response of gastric cancer cells to apatinib.

Apatinib was the first anti-angiogenic agent approved for treatment of metastatic gastric cancer (GC). However, the emergence of resistance was inevitable. Thus investigating new and valuable off-target effect of apatinib directly against cancer cells is of great significance. Here, we identified extra spindle pole bodies-like 1 (ESPL1) was responsible for apatinib resistance in GC cells through CRISPR genome-wide gain-of-function screening. Loss of function studies further showed that ESPL1 inhibition suppressed cell proliferation, migration and promoted apoptosis in vitro, and accordingly ESPL1 knockdown sensitized GC cells to apatinib. In addition, we found ESPL1 interacted with mouse double minute 2 (MDM2), a E3 ubiquitin protein ligase, and the combination of MDM2 siRNA with apatinib synergistically ameliorated the resistance induced by ESPL1 overexpression. In summary, our study indicated that ESPL1 played a critical role in apatinib resistance in GC cells. Inhibition of MDM2 could rescue the sensitivity of GC cells to apatinib and reverse ESPL1-mediated resistance.

Reversible Acid-Base Long Persistent Luminescence Switch Based on Amino-Functionalized Metal-Organic Frameworks.

Metal-organic frameworks (MOFs) with long persistent luminescence (LPL) have attracted extensive research attention from researchers due to their potential applications in information encryption, anticounterfeiting technology, and security logic. In contrast to short-lived fluorescent materials, LPL materials offer a visible response that can be easily distinguished by the naked eye, thereby facilitating a much clearer visualization. However, there are few reports on functional LPL MOF materials as probes. In this article, two amino-functional LPL MOFs (VB4-2D and VB4-1D) were synthesized. They both exhibited adjustable fluorescence and phosphorescence from blue to green and from cyan to green, respectively. Notably, the MOFs emitted bright and adjustable LPL upon the removal of the different radiation sources. The basic amino functional groups in the MOFs exhibited acid and ammonia sensitivity, and fluorescence and phosphorescence emission intensities can be burst and restored in two atmospheres, respectively, which can be cycled multiple times. Furthermore, LPL intensity undergoes switching between two different conditions as well, which can be visually discerned by the naked eye, enabling visual sensing of volatiles by LPL. This combination of photoluminescence and the visual LPL switching behavior of acids and bases in functional MOFs may provide an effective avenue for stimulus response, anticounterfeiting, and encryption applications.

Organic-Inorganic Hybrid Crystal-Assisted Etching of Nickel Foam for the Collectively Exhaustive Electrochemical Performance of Oxygen Evolution Reaction.

In this work, an organic-inorganic hybrid crystal, violet-crystal (VC), was used to etch the nickel foam (NF) to fabricate a self-standing electrode for the water oxidation reaction. The efficacy of VC-assisted etching manifests the promising electrochemical performance towards the oxygen evolution reaction (OER), requiring only ~356 and ~376 mV overpotentials to reach 50 and 100 mA cm-2 , respectively. The OER activity improvement is attributed to the collectively exhaustive effects arising from the incorporation of various elements in the NF, and the enhancement of active site density. Furthermore, the self-standing electrode is robust, exhibiting a stable OER activity after 4,000 cyclic voltammetry cycles, and ~50 h. The anodic transfer coefficients (αa ) show that the first electron transfer step is the rate-determining step on the surface of NF-VCs-1.0 (NF etched by 1 g of VCs) electrode, while the chemical step involving dissociation following the first electron transfer step is identified as the rate-limiting step in other electrodes. The lowest Tafel slope value observed in the NF-VCs-1.0 electrode indicates the high surface coverage of oxygen intermediates and more favorable OER reaction kinetics, as confirmed by high interfacial chemical capacitance and low charge transport/interfacial resistance. This work demonstrates the importance of VCs-assisted etching of NF to activate the OER, and the ability to predict reaction kinetics and rate-limiting step based on αa values, which will open new avenues to identify advanced electrocatalysts for the water oxidation reaction.

Mass Spectrometry-Guided Discovery of Multi-N-Methylated Cyclodecapeptides Auyuittuqamides E-H from Sesquicillium sp. QL0466.

Mass spectrometry-based dereplication and prioritization led to the discovery of four multi-N-methylated cyclodecapeptides, auyuittuqamides E-H (1-4), from a soil-derived Sesquicillium sp. The planar structures of these compounds were elucidated based on analysis of HRESIMS and NMR data. Absolute configurations of the chiral amino acid residues were assigned by a combination of the advanced Marfey's method, chiral-phase LC-MS analysis, and J-based configuration analysis, revealing that 1-4 contain both d- and l-isomers of N-methylleucine (MeLeu). Differentiation of d- and l-MeLeu in the sequence was achieved by advanced Marfey's analysis of the diagnostic peptide fragments generated from partial hydrolysis of 1. Bioinformatic analysis identified a putative biosynthetic gene cluster (auy) for auyuittuqamides E-H, and a plausible biosynthetic pathway was proposed. These newly identified fungal cyclodecapeptides (1-4) displayed in vitro growth inhibitory activity against vancomycin-resistant Enterococcus faecium with MIC values of 8 µg/mL.

Polycrystalline SnSe with a thermoelectric figure of merit greater than the single crystal.

Thermoelectric materials generate electric energy from waste heat, with conversion efficiency governed by the dimensionless figure of merit, ZT. Single-crystal tin selenide (SnSe) was discovered to exhibit a high ZT of roughly 2.2-2.6 at 913 K, but more practical and deployable polycrystal versions of the same compound suffer from much poorer overall ZT, thereby thwarting prospects for cost-effective lead-free thermoelectrics. The poor polycrystal bulk performance is attributed to traces of tin oxides covering the surface of SnSe powders, which increases thermal conductivity, reduces electrical conductivity and thereby reduces ZT. Here, we report that hole-doped SnSe polycrystalline samples with reagents carefully purified and tin oxides removed exhibit an ZT of roughly 3.1 at 783 K. Its lattice thermal conductivity is ultralow at roughly 0.07 W m-1 K-1 at 783 K, lower than the single crystals. The path to ultrahigh thermoelectric performance in polycrystalline samples is the proper removal of the deleterious thermally conductive oxides from the surface of SnSe grains. These results could open an era of high-performance practical thermoelectrics from this high-performance material.

A Bidirectional Nanomodification Approach for Synthesizing Hierarchically Architected Mixed Oxide Electrodes for Oxygen Evolution.

Several transition-metal oxides and hydroxides based on earth-abundant elements, such as Fe, Ni, and Co, have emerged as a new generation of oxygen evolution reaction (OER) catalysts due to their low cost, favorable activity, and multifunctional behavior. However, the relatively complicated surface structuring methods, high Tafel slope, and low stability hinder their practical applications to replace the conventional Ir- and Ru-based catalysts. Herein, a strategy to construct hierarchically architected mixed oxides on conductive substrates (e.g., ITO and Ni foam) via a nanosheet (NS) deposition and subsequent bidirectional nanomodification approach, with metal salts in an aprotic polar solvent (e.g., acetone) as the primary modifying reactants is reported. This strategy is used to prepare NiO-based NSs with nanopores, nanobranches, or a combination of both, containing up to four transition metal elements. Record-low Tafel slope (22.3 mV·dec-1 , ≈lowest possible by computational predictions) and week-long continuous operation durability are achieved by FeMnNi-O NSs supported on Ni foams. Taken together, properly designed hierarchical mixed oxide electrodes may provide a cost-effective route to generating high, reliable, and stable OER catalytic activities, paving the way for both new electrocatalyst design and practical water-splitting devices.

Planococcus maritimus ML1206 Isolated from Wild Oysters Enhances the Survival of Caenorhabditis elegans against Vibrio anguillarum.

With the widespread occurrence of aquaculture diseases and the broad application of antibiotics, drug-resistant pathogens have increasingly affected aquatic animals' health. Marine probiotics, which live under high pressure in a saltwater environment, show high potential as a substitute for antibiotics in the field of aquatic disease control. In this study, twenty strains of non-hemolytic bacteria were isolated from the intestine of wild oysters and perch, and a model of Caenorhabditis elegans infected by Vibrio anguillarum was established. Based on the model, ML1206, which showed a 99% similarity of 16S rRNA sequence to Planococcus maritimus, was selected as a potential marine probiotic, with strong antibacterial capabilities and great acid and bile salt tolerance, to protect Caenorhabditis elegans from being damaged by Vibrio anguillarum. Combined with plate counting and transmission electron microscopy, it was found that strain ML1206 could significantly inhibit Vibrio anguillarum colonization in the intestinal tract of Caenorhabditis elegans. Acute oral toxicity tests in mice showed that ML1206 was safe and non-toxic. The real-time qPCR results showed a higher expression level of genes related to the antibacterial peptide (ilys-3) and detoxification (ugt-22, cyp-35A3, and cyp-14A3) in the group of Caenorhabditis elegans protected by ML1206 compared to the control group. It is speculated that ML1206, as a potential probiotic, may inhibit the infection caused by Vibrio anguillarum through stimulating Caenorhabditis elegans to secrete antibacterial effectors and detoxification proteins. This paper provides a new direction for screening marine probiotics and an experimental basis to support the potential application of ML1206 as a marine probiotic in aquaculture.

Multiscale architectures boosting thermoelectric performance of copper sulfide compound.

Owing to their high performance and earth abundance, copper sulfides (Cu2-x S) have attracted wide attention as a promising medium-temperature thermoelectric material. Nanostructure and grain-boundary engineering are explored to tune the electrical transport and phonon scattering of Cu2-x S based on the liquid-like copper ion. Here multiscale architecture-engineered Cu2-x S are fabricated by a room-temperature wet chemical synthesis combining mechanical mixing and spark plasma sintering. The observed electrical conductivity in the multiscale architecture-engineered Cu2-x S is four times as much as that of the Cu2-x S sample at 800 K, which is attributed to the potential energy filtering effect at the new grain boundaries. Moreover, the multiscale architecture in the sintered Cu2-x S increases phonon scattering and results in a reduced lattice thermal conductivity of 0.2 W·m-1·K-1 and figure of merit (zT) of 1.0 at 800 K. Such a zT value is one of the record values in copper sulfide produced by chemical synthesis. These results suggest that the introduction of nanostructure and formation of new interface are effective strategies for the enhancement of thermoelectric material properties. SUPPLEMENTARY INFORMATION: The online version of this article (10.1007/s12598-020-01698-6) contains supplementary material, which is available to authorized users.

Establishment of variation source and age-related reference interval models for 22 common biochemical analytes in older people using real-world big data mining.

BACKGROUND: the ageing population has increased in many countries, including China. However, reference intervals (RIs) for older people are rarely established because of difficulties in selecting reference individuals. Here, we aimed to analyse the factors affecting biochemical analytes and establish RI and age-related RI models for biochemical analytes through mining real-world big data. METHODS: data for 97,220 individuals downloaded from electronic health records were included. Three derived databases were established. The first database included 97,220 individuals and was used to build age-related RI models after identifying outliers by the Tukey method. The second database consisted of older people and was used to establish variation source models and RIs for biochemical analytes. Differences between older and younger people were compared using the third database. RESULTS: sex was the main source of variation of biochemical analytes for older people in the variation source models. The distributions of creatinine and uric acid were significantly different in the RIs of biochemical analytes for older people established according to sex. Age-related RI models for biochemical analytes that were most affected by age were built and visualized, revealing various patterns of changes from the younger to older people. CONCLUSION: the study analysed the factors affecting biochemical analytes in older people. Moreover, RI and age-related RI models of biochemical analytes for older people were established to provide important insight into biological processes and to assist clinical use of various biochemical analytes to monitor the status of various diseases for older people.

Structural analysis of the initial lithiation of NiO thin film electrodes.

Observations of the initial lithiation of NiO electrodes demonstrate how to seed conversion reactions using interfaces in a thin film Ni/NiO bilayer architecture. Operando X-ray reflectivity (XRR) reveals that structural changes in a NiO film begin at potentials near the theoretical reduction potential (1.8-2.0 V) with detectable lithiation of both the buried Ni/NiO interface and the outer NiO surface that occur prior to the reaction of the NiO film. This initial conversion reaction is most pronounced in ultrathin NiO films (∼20 Å) with only small changes to the NiO film surface for thicker films (∼67 Å). The limited reactivity of thicker NiO films probed using operando grazing incidence small-angle X-ray scattering (GISAXS) shows the growth of nanoparticles at the electrode/electrolyte interface during initial lithium ion insertion, with a 16-20 Å average radius. Ex situ X-ray photoelectron spectroscopy (XPS), time-of-flight secondary ion mass spectrometry (ToF-SIMS), and scanning transmission electron microscopy/electron energy loss spectroscopy (STEM/EELS) confirm our conclusions about the morphological changes accompanying initial stage of lithiation in these conversion reaction electrodes. The present study reveals the interconnected challenges of solid-solid transitions, overpotentials, interfacial nucleation and kinetics, and transition metal dissolution in conversion-type electrodes that are critical for their use as electrodes in lithium-ion batteries.

Exploring the Potential of Natural Products From Mangrove Rhizosphere Bacteria as Biopesticides Against Plant Diseases.

With increasing concerns of the environmental problems associated with current fungicide application, investigation of alternative, environmentally compatible biopesticides for plant disease management is needed. A total of 113 strains associated with Acanthus ilicifolius Linn in the Maipo Reserve, Hong Kong, were isolated and identified. In vitro assay with crude extracts of bacterial fermentation cultures identified ∼26% of the isolates producing antimicrobial compounds against a variety of agriculturally important phytopathogens. Selected crude extracts with inhibition to Colletotrichum fructicola and Magnaporthe oryzae growth significantly suppressed anthracnose and rice blast development in pear fruits and rice plants, respectively, when applied at 50 µg ml-1. Furthermore, 10 of 14 selected crude extracts with good antimicrobial activities had no significant differences in toxicity to the genus Chlorella compared with the control when used at 25 µg ml-1, whereas Amistar Top and Mancozeb completely killed the alga under the same concentration. These data illustrate the potential of natural products from mangrove rhizosphere bacteria in future agricultural application.

Morphological Engineering of Winged Au@MoS2 Heterostructures for Electrocatalytic Hydrogen Evolution.

Molybdenum disulfide (MoS2) has been recognized as a promising cost-effective catalyst for water-splitting hydrogen production. However, the desired performance of MoS2 is often limited by insufficient edge-terminated active sites, poor electrical conductivity, and inefficient contact to the supporting substrate. To address these limitations, we developed a unique nanoarchitecture (namely, winged Au@MoS2 heterostructures enabled by our discovery of the "seeding effect" of Au nanoparticles for the chemical vapor deposition synthesis of vertically aligned few-layer MoS2 wings). The winged Au@MoS2 heterostructures provide an abundance of edge-terminated active sites and are found to exhibit dramatically improved electrocatalytic activity for the hydrogen evolution reaction. Theoretical simulations conducted for this unique heterostructure reveal that the hydrogen evolution is dominated by the proton adsorption step, which can be significantly promoted by introducing sufficient edge active sites. Our study introduces a new morphological engineering strategy to make the pristine MoS2 layered structures highly competitive earth-abundant catalysts for efficient hydrogen production.

Porous-Carbon-Confined Formation of Monodisperse Iron Nanoparticle Yolks toward Versatile Nanoreactors for Metal Extraction.

All-in-one architectures in which uniform nanoscale zero-valent iron nanoparticles are wrapped in hollow porous carbon shells are highly desirable for environmental applications such as wastewater treatment and for use as catalysts, but their preparation remains a significant challenge. Herein, a spatially confined strategy for the in situ preparation of uniform Fe0 @mC (mC=micro/mesoporous carbon) yolk-shell nanospheres, in which the iron nanoparticles are encapsulated in thin, porous carbon shells, is reported. The elaborately designed Fe0 @mC yolk-shell nanospheres were obtained by utilizing silica- and phenolic-resin-coated magnetite nanoparticle core-shell structures as templates by means of selective etching and in situ thermal reduction. The highly dispersed iron nanoparticles with superior reduction capability can effectively remove metal pollutants (e.g., AuIII , AgI , and CuII ), the carbon shell acts as protective cover and prevents aggregation of iron nanoparticles, and the void space in the capsules serves as a reactor for reduction and catalytic reactions.

Designing 3D interconnected continuous nanoporous Co/CoO core-shell nanostructure electrodes for a high-performance pseudocapacitor.

A high-performance supercapacitor electrode is designed and fabricated with the 3D interconnected continuous nanoporous Co/CoO core-shell hybrid nanostructure grown on nickel foam. The Co/CoO core-shell hybrid nanostructures are obtained via a hydrothermal method, followed by high-temperature annealing in hydrogen atmosphere, and finally placed in air at 50 °C for 1 h. The Co/CoO core-shell nanostructure assembled by a conductive metal-core and a CoO shell, brings low resistance, high specific capacitance of 5.632 F cm-2 and good capability stability (81.5% capacitance retention after 6000 cycles). An asymmetric supercapacitor device built by the Co/CoO (positive electrode) and activated carbon (negative electrode) can deliver a working voltage of 1.7 V and display a high energy density of 0.002 67 Wh cm-2 at a power density of 0.001 62 W cm-2, which is far superior to that of a supercapacitor at a similar power density.

Au@MoS2 Core-Shell Heterostructures with Strong Light-Matter Interactions.

There are emerging opportunities to harness diverse and complex geometric architectures based on nominal two-dimensional atomically layered structures. Herein we report synthesis and properties of a new core-shell heterostructure, termed Au@MoS2, where the Au nanoparticle is snugly and contiguously encapsulated by few shells of MoS2 atomic layers. The heterostructures were synthesized by direct growth of multilayer fullerene-like MoS2 shell on Au nanoparticle cores. The Au@MoS2 heterostructures exhibit interesting light-matter interactions due to the structural curvature of MoS2 shell and the plasmonic effect from the underlying Au nanoparticle core. We observed significantly enhanced Raman scattering and photoluminescence emission on these heterostructures. We attribute these enhancements to the surface plasmon-induced electric field, which simulations show to mainly localize within the MoS2 shell. We also found potential evidence for the charge transfer-induced doping effect on the MoS2 shell. The DFT calculations further reveal that the structural curvature of MoS2 shell results in a modification of its electronic structure, which may facilitate the charge transfer from MoS2 to Au. Such Au@MoS2 core-shell heterostructures have the potential for future optoelectronic devices, optical imaging, and other energy-environmental applications.

Depressive symptoms were associated with an elevated prevalence of gallstones among adults in the United States: A cross-sectional analysis of NHANES 2017-2020.

Background:  Gallstone disease is one of the most common gastrointestinal disorders. Despite extensive research exploring the risk factors associated with gallstones, the association between depressive symptoms and gallstones remains inadequately understood. This study aimed to assess the association between depressive symptoms and the prevalence of gallstones among adults in the United States. Methods: In this study, a cross-sectional design utilized data from the National Health and Nutrition Examination Survey (NHANES) spanning the years 2017 to 2020. The assessment of depressive symptoms was conducted through the utilization of the Patient Health Questionnaire-9 (PHQ-9), which assigns total scores ranging from 0 to 27. Participants with PHQ-9 scores equal to or exceeding 10 were categorized as having clinically relevant depressive symptoms. Multivariable adjusted logistic regression and subgroup analysis were used to assess the association between depressive symptoms and gallstone prevalence. Results: A total of 7,797 participants aged 20 years or older were enrolled in this study, of whom 835 had a self-reported history of gallstones. After multiple adjustments, each one-point increase in PHQ-9 scores was associated with a 5 % increase in the risk of gallstones (odds ratio [OR], 1.05; 95 % confidence interval [CI], 1.03, 1.07, P < 0.001). Compared to individuals with PHQ-9 scores < 10, participants with PHQ-9 total scores ≥ 10 exhibited a 79 % higher risk of gallstones (OR = 1.79, 95 % CI: 1.43, 2.23, P < 0.001). Conclusion: Depressive symptoms were associated with an elevated prevalence of gallstones. However, it is important to note that further validation through prospective cohort studies is warranted to confirm this finding.

C-reactive protein/lymphocyte ratio as a prognostic biomarker in acute pancreatitis: a cross-sectional study assessing disease severity.

BACKGROUND: The C-reactive protein/lymphocyte ratio (CLR) is a prognostic biomarker of various diseases. However, its significance in acute pancreatitis (AP) remains unknown. The main aim of this study was to investigate the association between the CLR and disease severity in patients with AP. METHODS: This cross-sectional study included 476 AP patients [mild acute pancreatitis (MAP), n =176; moderately severe acute pancreatitis (MSAP) and severe acute pancreatitis (SAP), n =300]. The primary exposure of interest was the baseline CLR. The primary outcome was the incidence of moderate to severe AP. Multivariate logistic regression and restricted cubic spline analyses were performed to evaluate the association between the CLR and the incidence of moderate to severe AP. Receiver operating characteristic (ROC) analysis was conducted to assess the predictive efficacy, sensitivity, and specificity of CLR in predicting the incidence of moderate to severe AP. RESULTS: The mean age of the patients was 44±13.2 years, and 76.5% were male. The distribution of CLR was 31.6 (interquartile range, 4.5, 101.7). Moderate to severe AP occurred in 300 cases (63.0%). After multiple adjustments, CLR was independently associated with the incidence of moderate to severe AP (odds ratio, 1.04; 95% CI: 1.03-1.05; P < 0.001). A nonlinear relationship was found between CLR and the incidence of moderate to severe AP, with a threshold of approximately 45. The effect size and CI below and above the threshold value were 1.061 (1.033-1.089) and 1.014 (0.997-1.031), respectively. The area under the curve (AUC) for CLR was 87.577% (95% CI: 84.443- 90.710%) with an optimal cut-off value of 30.835, resulting in a sensitivity of 73.7% and a specificity of 88.6%. CONCLUSIONS: There was a nonlinear relationship with a saturation effect between the CLR and the incidence of moderate to severe AP. The CLR measured within 24 h of admission may serve as a promising biomarker for predicting the emergence of moderate to severe AP, thereby providing a more scientifically grounded basis for preventing such cases. Nonetheless, further research is warranted to validate and strengthen these findings.

Wind-driven post-bloom dispersion of Microcystis in a large shallow eutrophic lake: A case study in Lake Taihu.

To clarify the wind-driven post-bloom dispersion range of Microcystis, which originally clustered on the water surface, an Individual-Based Model (IBM) of Microcystis movement considering the combined effects of wind and light was developed based on actual hydrodynamic data and Microcystis biomass. After calibrating the effects of hydrodynamics and light, 66 cases of short-term (within a week) post-bloom with satellite images from 2011 to 2017 were simulated. The results showed that there were three short-term post-bloom types: vertical reduction (VR), horizontal reduction (HR) and mixed reduction (MR). For VR type, the cyanobacterial bloom reduction rate was rapid (>160 km2/day), but the dispersion range of Microcystis was limited (<2 km/day), and a larger bloom area was likely to form in the original location when wind speed decreased. For HR type, the cyanobacterial bloom reduction rate was slow (<10 km2/day), but Microcystis exhibited a broad dispersion range (>4 km/day), often leading to smaller, thicker, and longer-lasting cyanobacterial blooms downwind, albeit with a lower probability of occurrence. The characteristics of MR lay between the two aforementioned types.

Ball milling synthesis of Fe3O4 nanoparticles-functionalized porous boron nitride with enhanced cationic dye removal performance.

Enhancement of the adsorption performance and recyclability of adsorbents is a crucial aspect of water treatment. Herein, we used one-dimensional porous boron nitride (PBN) as a carrier to load Fe3O4 nanoparticles for the preparation of Fe3O4 nanoparticles-functionalized porous boron nitride (Fe3O4/PBN) via a ball milling method. The high-energy ball milling promoted the creation of a negatively charged PBN surface and facilitated the uniform distribution of Fe3O4 nanoparticles on the surface of PBN. The adsorption performance of Fe3O4/PBN toward cationic dyes could be significantly improved while no enhancement was observed for anionic dyes. The great adsorption performance of Fe3O4/PBN is due to its surface functional groups and surface defects formed in the ball milling process. Moreover, the strong interaction force between Fe3O4/PBN and cationic dyes promotes rapid initial adsorption due to their negatively charged surface. Magnetic measurements demonstrated that Fe3O4/PBN is superparamagnetic. The composites with low loadings of Fe3O4 nanoparticles could be quickly separated from the aqueous solution under a low applied magnetic field, improving their recyclability. This work highlights the role of ball milling in improving the adsorption performance of Fe3O4/PBN and greatly promotes the practical application of Fe3O4/PBN in the field of environmental purification.

Ultrathin silicon nitride microchip for in situ/operando microscopy with high spatial resolution and spectral visibility.

Utilization of in situ/operando methods with broad beams and localized probes has accelerated our understanding of fluid-surface interactions in recent decades. The closed-cell microchips based on silicon nitride (SiNx) are widely used as "nanoscale reactors" inside the high-vacuum electron microscopes. However, the field has been stalled by the high background scattering from encapsulation (typically ~100 nanometers) that severely limits the figures of merit for in situ performance. This adverse effect is particularly notorious for gas cell as the sealing membranes dominate the overall scattering, thereby blurring any meaningful signals and limiting the resolution. Herein, we show that by adopting the back-supporting strategy, encapsulating membrane can be reduced substantially, down to ~10 nanometers while maintaining structural resiliency. The systematic gas cell work demonstrates advantages in figures of merit for hitherto the highest spatial resolution and spectral visibility. Furthermore, this strategy can be broadly adopted into other types of microchips, thus having broader impact beyond the in situ/operando fields.