3D reconstruction of a gastrulating human embryo.

Progress in understanding early human development has been impeded by the scarcity of reference datasets from natural embryos, particularly those with spatial information during crucial stages like gastrulation. We conducted high-resolution spatial transcriptomics profiling on 38,562 spots from 62 transverse sections of an intact Carnegie stage (CS) 8 human embryo. From this spatial transcriptomic dataset, we constructed a 3D model of the CS8 embryo, in which a range of cell subtypes are identified, based on gene expression patterns and positional register, along the anterior-posterior, medial-lateral, and dorsal-ventral axis in the embryo. We further characterized the lineage trajectories of embryonic and extra-embryonic tissues and associated regulons and the regionalization of signaling centers and signaling activities that underpin lineage progression and tissue patterning during gastrulation. Collectively, the findings of this study provide insights into gastrulation and post-gastrulation development of the human embryo.

A multi-tissue metabolome atlas of primate pregnancy.

Pregnancy induces dramatic metabolic changes in females; yet, the intricacies of this metabolic reprogramming remain poorly understood, especially in primates. Using cynomolgus monkeys, we constructed a comprehensive multi-tissue metabolome atlas, analyzing 273 samples from 23 maternal tissues during pregnancy. We discovered a decline in metabolic coupling between tissues as pregnancy progressed. Core metabolic pathways that were rewired during primate pregnancy included steroidogenesis, fatty acid metabolism, and arachidonic acid metabolism. Our atlas revealed 91 pregnancy-adaptive metabolites changing consistently across 23 tissues, whose roles we verified in human cell models and patient samples. Corticosterone and palmitoyl-carnitine regulated placental maturation and maternal tissue progenitors, respectively, with implications for maternal preeclampsia, diabetes, cardiac hypertrophy, and muscle and liver regeneration. Moreover, we found that corticosterone deficiency induced preeclampsia-like inflammation, indicating the atlas's potential clinical value. Overall, our multi-tissue metabolome atlas serves as a framework for elucidating the role of metabolic regulation in female health during pregnancy.

Primate gastrulation and early organogenesis at single-cell resolution.

Our understanding of human early development is severely hampered by limited access to embryonic tissues. Due to their close evolutionary relationship with humans, nonhuman primates are often used as surrogates to understand human development but currently suffer from a lack of in vivo datasets, especially from gastrulation to early organogenesis during which the major embryonic cell types are dynamically specified. To fill this gap, we collected six Carnegie stage 8-11 cynomolgus monkey (Macaca fascicularis) embryos and performed in-depth transcriptomic analyses of 56,636 single cells. Our analyses show transcriptomic features of major perigastrulation cell types, which help shed light on morphogenetic events including primitive streak development, somitogenesis, gut tube formation, neural tube patterning and neural crest differentiation in primates. In addition, comparative analyses with mouse embryos and human embryoids uncovered conserved and divergent features of perigastrulation development across species-for example, species-specific dependency on Hippo signalling during presomitic mesoderm differentiation-and provide an initial assessment of relevant stem cell models of human early organogenesis. This comprehensive single-cell transcriptome atlas not only fills the knowledge gap in the nonhuman primate research field but also serves as an invaluable resource for understanding human embryogenesis and developmental disorders.

Role of transient receptor potential ankyrin 1 in idiopathic pulmonary fibrosis: modulation of M2 macrophage polarization.

Idiopathic pulmonary fibrosis (IPF) poses significant challenges due to limited treatment options despite its complex pathogenesis involving cellular and molecular mechanisms. This study investigated the role of transient receptor potential ankyrin 1 (TRPA1) channels in regulating M2 macrophage polarization in IPF progression, potentially offering novel therapeutic targets. Using a bleomycin-induced pulmonary fibrosis model in C57BL/6J mice, we assessed the therapeutic potential of the TRPA1 inhibitor HC-030031. TRPA1 upregulation was observed in fibrotic lungs, correlating with worsened lung function and reduced survival. TRPA1 inhibition mitigated fibrosis severity, evidenced by decreased collagen deposition and restored lung tissue stiffness. Furthermore, TRPA1 blockade reversed aberrant M2 macrophage polarization induced by bleomycin, associated with reduced Smad2 phosphorylation in the TGF-ß1-Smad2 pathway. In vitro studies with THP-1 cells treated with bleomycin and HC-030031 corroborated these findings, highlighting TRPA1's involvement in fibrotic modulation and macrophage polarization control. Overall, targeting TRPA1 channels presents promising therapeutic potential in managing pulmonary fibrosis by reducing pro-fibrotic marker expression, inhibiting M2 macrophage polarization, and diminishing collagen deposition. This study sheds light on a novel avenue for therapeutic intervention in IPF, addressing a critical need in the management of this challenging disease.

Sulfur-Induced Electronic Optimization of N-Doped Carbon with CoP/Co2P Heterostructure by Precursor Design for Rechargeable Zinc-Air Batteries.

Heteroatom doping and heterostructure construction are the key methods to improve the performance of electrocatalysts. However, developing such catalysts remains a challenging task. Herein, we designed two comparable polymers, phytic acid/thiourea polymer (PATP) and phytic acid/urea polymer (PAUP), as precursors, which contain C, N, S/O, and P by microwave heating. To pinpoint how the introduction of sulfur would affect the electronic structure and catalytic activity, these two polymers were physically blended with CoCo-Prussian blue analogue (CoCo-PBA) and further calcination, respectively. The highly dispersed CoP/Co2P-rich interfacial catalysts anchored on the N,S-codoped or N-doped carbon support were successfully prepared (CoP/Co2P@CNS and CoP/Co2P@CN). The prepared CoP/Co2P@CNS catalyst showed good ORR properties (E1/2 = 0.856 V vs RHE) and OER properties (Ej10 = 1.54 V vs RHE), which were superior to the commercial Pt/C and RuO2 catalysts. The reversible oxygen electrode index (ΔE = Ej10 - E1/2) can reach ∼0.684 V. Meanwhile, the rechargeable zinc-air battery assembled with a CoP/Co2P@CNS catalyst as the air cathode also showed excellent performance, with a charge-discharge cycle stability of up to 900 h. DFT calculations further confirm that the introduction of S atoms can affect the electronic structure and enhance the catalytic activity of C and N atoms on carbon support.

Synthesis and evaluation of antisense oligonucleotides prodrug with G-quadruplex assembly and lysosome escape capabilities for oncotherapy.

The applications of antisense oligonucleotides (ASOs) in rare or common diseases treatment have garnered great attention in recent years. Nevertheless, challenges associated with stability and bioavailability still persist, hampering the efficiency of ASOs. This work presents an ASO prodrug with parallel G-quadruplex assembly and lysosome escape capabilities for oncotherapy. Our findings revealed that the end-assembled quadruplex structure effectively shielded the ASO from enzymatic degradation. Meanwhile, the conjugation of maleimide within the quadruplex enhanced cellular uptake, potentially offering an alternative cell entry mechanism that circumvents lysosome involvement. Notably, an optimized molecule, Mal2-G4-ASO, exhibited remarkable therapeutic effects both in vitro and in vivo. This work presents a promising avenue for enhancing the activity of nucleic acid drugs in oncotherapy and potentially other disease contexts.

SNR Enhancement for Comparator-Based Ultra-Low-Sampling Φ-OTDR System Using Compressed Sensing.

The large amount of sampled data in coherent phase-sensitive optical time-domain reflectometry (Φ-OTDR) brings heavy data transmission, processing, and storage burdens. By using the comparator combined with undersampling, we achieve simultaneous reduction of sampling rate and sampling resolution in hardware, thus greatly decreasing the sampled data volume. But this way will inevitably cause the deterioration of detection signal-to-noise ratio (SNR) due to the quantization noise's dramatic increase. To address this problem, denoising the demodulated phase signals using compressed sensing, which exploits the sparsity of spectrally sparse vibration, is proposed, thereby effectively enhancing the detection SNR. In experiments, the comparator with a sampling parameter of 62.5 MS/s and 1 bit successfully captures the 80 MHz beat signal, where the sampled data volume per second is only 7.45 MB. Then, when the piezoelectric transducer's driving voltage is 1 Vpp, 300 mVpp, and 100 mVpp respectively, the SNRs of the reconstructed 200 Hz sinusoidal signals are respectively enhanced by 23.7 dB, 26.1 dB, and 28.7 dB by using compressed sensing. Moreover, multi-frequency vibrations can also be accurately reconstructed with a high SNR. Therefore, the proposed technique can effectively enhance the system's performance while greatly reducing its hardware burden.

Anatomical sectionectomy based on Takasaki's segmentation for solitary intrahepatic cholangiocarcinoma: a propensity-matched analysis.

BACKGROUND: Anatomical sectionectomy based on Takasaki's segmentation has shown advantages in hepatocellular carcinoma. However, whether this approach improves the survival of intrahepatic cholangiocarcinoma (ICC) remains unknown. METHODS: A series of 248 consecutive patients with solitary ICCs who underwent hepatectomy were studied retrospectively. The patients were classified into the groups of anatomical sectionectomy based on Takasaki's segmentation (TS group) and non-Takasaki's hepatectomy (NTH group). The bias between the two groups was minimized using propensity score matching (PSM). Recurrence-free survival (RFS) and overall survival (OS) were evaluated with Kaplan-Meier analysis. The Cox proportional hazards model was performed to determine the adverse risk factors associated with survival. RESULTS: After PSM, 67 pairs of patients were compared. Both the RFS and OS rates in the TS group were significantly better than those in the NTH group (23.2 % vs. 16.5 %, and 40.4 % vs. 27.3 %, P = 0.035 and 0.032, respectively). Multivariate analysis showed that NTH was independently associated with worse RFS and OS than TS. The stratified analysis demonstrated that the RFS and OS rates in the TS group with tumor stage I and tumor size ≥3 cm were significantly better than those in the NTH group, while the survival rates for ICC with stage I and tumor size <3 cm or stage II-III showed no significant difference. CONCLUSION: TS was associated with improved RFS and OS in patients with solitary ICC even after PSM. TS may be preferred particularly in patients with tumor stage I and tumor size ≥3 cm.

Anisotropic Topological Anderson Transitions in Chiral Symmetry Classes.

We study quantum phase transitions of three-dimensional disordered systems in the chiral classes (AIII and BDI) with and without weak topological indices. We show that the systems with a nontrivial weak topological index universally exhibit an emergent thermodynamic phase where wave functions are delocalized along one spatial direction but exponentially localized in the other two spatial directions, which we call the quasilocalized phase. Our extensive numerical study clarifies that the critical exponent of the Anderson transition between the metallic and quasilocalized phases, as well as that between the quasilocalized and localized phases, are different from that with no weak topological index, signaling the new universality classes induced by topology. The quasilocalized phase and concomitant topological Anderson transition manifest themselves in the anisotropic transport phenomena of disordered weak topological insulators and nodal-line semimetals, which exhibit the metallic behavior in one direction but the insulating behavior in the other directions.

Efficacy and safety of the C5 inhibitor crovalimab in complement inhibitor-naive patients with PNH (COMMODORE 3): A multicenter, Phase 3, single-arm study.

The Phase 3 single-arm COMMODORE 3 study (ClinicalTrials.gov, NCT04654468) evaluated efficacy and safety of crovalimab (novel C5 inhibitor) in complement inhibitor-naive patients with paroxysmal nocturnal hemoglobinuria (PNH). COMMODORE 3 enrolled patients from five China centers. Eligible complement inhibitor-naive patients with PNH were ≥12 years old, had lactate dehydrogenase (LDH) ≥2 × upper limit of normal (ULN), and had ≥4 transfusions of packed red blood cells within the prior 12 months. Patients received crovalimab loading doses (one intravenous, four subcutaneous) and subsequent every-4-weeks subcutaneous maintenance doses per weight-based tiered-dosing schedule. Co-primary efficacy endpoints were mean proportion of patients with hemolysis control (LDH ≤1.5 × ULN) from Week (W)5 through W25 and difference in proportion of patients with transfusion avoidance from baseline through W25 versus within 24 weeks of prescreening in patients who had ≥1 crovalimab dose and ≥1 central LDH assessment after first dose. Between March 17 and August 24, 2021, 51 patients (15-58 years old) were enrolled; all received treatment. At primary analysis, both co-primary efficacy endpoints were met. Estimated mean proportion of patients with hemolysis control was 78.7% (95% CI: 67.8-86.6). Difference between proportion of patients with transfusion avoidance from baseline through W25 (51.0%; n = 26) versus within 24 weeks of prescreening (0%) was statistically significant (p < .0001). No adverse events led to treatment discontinuation. One treatment-unrelated death (subdural hematoma following a fall) occurred. In conclusion, crovalimab, with every-4-weeks subcutaneous dosing is efficacious and well tolerated in complement inhibitor-naive patients with PNH.

Ultrafast Microwave Synthesis of Ru-Doped MoP with Abundant P Vacancies as the Electrocatalyst for Hydrogen Generation in a Wide pH Range.

Molybdenum phosphide (MoP) has received increasing attention for the hydrogen evolution reaction (HER) due to its Pt-like electronic structure and high electrical conductivity. In this work, a flake-like Ru-doped MoP with phosphorus vacancy (Ru-MoP-PV) electrocatalyst is synthesized for the first time by a simple and rapid room-temperature microwave approach within 30 s. The created abundant phosphorus vacancies provide rich active sites and favor rapid electron transfer. The introduced Ru also enhances the catalytic activity of the synthesized electrocatalyst efficiently. Then, the designed Ru-MoP-PV possesses low overpotentials for HER with 79, 100, and 161 mV in 1.0 M KOH, 0.5 M H2SO4, and 1.0 M phosphate-buffered saline to obtain 10 mA cm-2. The Ru-MoP-PV and NiFe-layered double hydroxide are used as the cathode and the anode, respectively, to drive water splitting and just need a low cell voltage of 1.6 V to achieve 10 mA cm-2. This work provides a feasible way for the rapid production of metal phosphides for energy conversion and storage applications.

CoNiFe alloy nanoparticles encapsulated into nitrogen-doped carbon nanotubes toward superior electrocatalytic overall water splitting in alkaline freshwater/seawater under large-current density.

Developing bifunctional catalysts for overall water splitting with high activity and durability at high current density remains a challenge. In an attempt to overcome this bottleneck, in this work, unique CoNiFe-layered double hydroxide nanoflowers are in situ grown on nickel-iron (NiFe) foam through a corrosive approach and following a chemical vapor deposition process to generate nitrogen-doped carbon nanotubes at the presence of melamine (CoNiFe@NCNTs). The coupling effects between various metal species act a key role in accelerating the reaction kinetics. Moreover, the in situ formed NCNTs also favor promoting electrocatalytic activity and stability. For oxygen evolution reaction it requires low overpotentials of 330 and 341 mV in 1M KOH and 1M KOH + seawater to drive 500 mA cm-2. Moreover, water electrolysis can be operated with CoNiFe@NCNTs as both anode and cathode with small voltages of 1.95 and 1.93 V to achieve 500 mA cm-2 in 1M KOH and 1M KOH + seawater, respectively.

A Phase-Sensitive Optical Time Domain Reflectometry with Non-Uniform Frequency Multiplexed NLFM Pulse.

In the domain of optical fiber distributed acoustic sensing, the persistent challenge of extending sensing distances while concurrently improving spatial resolution and frequency response range has been a complex endeavor. The amalgamation of pulse compression and frequency division multiplexing methodologies has provided certain advantages. Nevertheless, this approach is accompanied by the drawback of significant bandwidth utilization and amplified hardware investments. This study introduces an innovative distributed optical fiber acoustic sensing system aimed at optimizing the efficient utilization of spectral resources by combining compressed pulses and frequency division multiplexing. The system continuously injects non-linear frequency modulation detection pulses spanning various frequency ranges. The incorporation of non-uniform frequency division multiplexing augments the vibration frequency response spectrum. Additionally, nonlinear frequency modulation adeptly reduces crosstalk and enhances sidelobe suppression, all while maintaining a favorable signal-to-noise ratio. Consequently, this methodology substantially advances the spatial resolution of the sensing system. Experimental validation encompassed the multiplexing of eight frequencies within a 120 MHz bandwidth. The results illustrate a spatial resolution of approximately 5 m and an expanded frequency response range extending from 1 to 20 kHz across a 16.3 km optical fiber. This achievement not only enhances spectral resource utilization but also reduces hardware costs, making the system even more suitable for practical engineering applications.

Integrative analysis of CRISPR screening data uncovers new opportunities for optimizing cancer immunotherapy.

BACKGROUND: In recent years, the application of functional genetic immuno-oncology screens has showcased the striking ability to identify potential regulators engaged in tumor-immune interactions. Although these screens have yielded substantial data, few studies have attempted to systematically aggregate and analyze them. METHODS: In this study, a comprehensive data collection of tumor immunity-associated functional screens was performed. Large-scale genomic data sets were exploited to conduct integrative analyses. RESULTS: We identified 105 regulator genes that could mediate resistance or sensitivity to immune cell-induced tumor elimination. Further analysis identified MON2 as a novel immune-oncology target with considerable therapeutic potential. In addition, based on the 105 genes, a signature named CTIS (CRISPR screening-based tumor-intrinsic immune score) for predicting response to immune checkpoint blockade (ICB) and several immunomodulatory agents with the potential to augment the efficacy of ICB were also determined. CONCLUSION: Overall, our findings provide insights into immune oncology and open up novel opportunities for improving the efficacy of current immunotherapy agents.

"HOT" Alkaline Hydrolysis of Amorphous MOF Microspheres to Produce Ultrastable Bimetal Hydroxide Electrode with Boosted Cycling Stability.

Nickel/cobalt hydroxide is a promising battery-type electrode material for supercapacitors. However, its low cycle stability hinders further applications. Herein, Ni0.7 Co0.3 (OH)2 core-shell microspheres exhibiting extreme-prolonged cycling life are successfully synthesized, employing Ni-Co-metal-organic framework (MOF) as the precursor/template and a specific hydrolysis strategy. The Ni-Co-MOF and KOH aqueous solution are separated and heated to 120 °C before mixing, rather than mixing before heating. Through this hydrolysis strategy, no MOF residual exists in the product, contributing to close stacking of the hydroxide nanoflakes to generate Ni0.7 Co0.3 (OH)2 microspheres with a robust core-shell structure. The electrode material exhibits high specific capacity (945 C g-1 at 0.5 A g-1 ) and unprecedented cycling performance (100% after 10 000 cycles). The fabricated asymmetric supercapacitor delivers an energy density of 40.14 Wh kg-1 at a power density of 400.56 W kg-1 and excellent cycling stability (100% after 20 000 cycles). As far as is known, it is the best cycling performance for pure Ni/Co(OH)2 .

An Amino-Functionalized Metal-Organic Framework, Based on a Rare Ba12 (COO)18 (NO3 )2 Cluster, for Efficient C3 /C2 /C1 Separation and Preferential Catalytic Performance.

A barium(II) metal-organic framework (MOF) based on a predesigned amino-functionalized ligand, namely [Ba2 (L)(DMF)(H2 O)(NO3 )1/3 ]⋅DMF⋅EtOH⋅2 H2 O (UPC-33) [H3 L=4,4'-((2-amino-5-carboxy-1,3-phenylene)bis(ethyne-2,1-diyl))dibenzoic acid] has been synthesized. UPC-33 is a 3-dimensional 3,18-connected network with fcu topology with a rare twelve-nuclear Ba12 (COO)18 (NO3 )2 cluster. UPC-33 shows permanent porosity and a high adsorption heat of CO2 (49.92 kJ mol-1 ), which can be used as a platform for selective adsorption of CO2 /CH4 (8.09). In addition, UPC-33 exhibits high separation selectivity for C3 light hydrocarbons with respect to CH4 (228.34, 151.40 for C3 H6 /CH4 , C3 H8 /CH4 at 273k and 1 bar), as shown by single component gas sorption and selectivity calculations. Due to the existence of -NH2 groups in the channels, UPC-33 can effectively catalyze Knoevenagel condensation reactions with high yield, and substrate size and electron dependency.

Bimetallic-MOF Derived Accordion-like Ternary Composite for High-Performance Supercapacitors.

Supercapacitors are regarded to be highly probable candidates for next-generation energy storage devices. Herein, a bimetallic Co/Ni MOF is used as a sacrificial template through an alkaline hydrolysis and selective oxidation process to prepare an accordion-like ternary NiCo2O4/ß-Ni xCo1- x(OH)2/α-Ni xCo1- x(OH)2 composite, which is composed of Co/Ni(OH)2 nanosheets with large specific surface as the frame and NiCo2O4 nanoparticles with high conductivity as the insertion, for supercapacitor application. This material exhibits both high specific capacitance (1315 F·g-1 at 5 A·g-1) and excellent cycle performance (retained 90.7% after 10 000 cycles). This hydrolysis-oxidation process, alkali hydrolysis followed by oxidation with H2O2, offers a novel approach to fabricate the Ni/Co-based electrode materials with enhanced supercapacitor performance.

Additive-Enhanced Crystallization of Solution Process for Planar Perovskite Solar Cells with Efficiency Exceeding 19 .

To reduce intrinsic defect density in perovskite films, various additives are often added into the precursor solution. In this paper, a novel solution, in which isopropanol (IPA) was added into the precursor solution, was developed for the preparation of normal planar perovskite solar cells (PSCs). A champion power conversion efficiency (PCE) of 19.70 % was achieved with this approach. By adding IPA into the precursor solution, CH3 NH3 PbI3 perovskite showed better crystallization and stability, indicating improved film quality. Because of the improved morphology of perovskite crystal, the PCE of PSCs increased. In addition, the unencapsulated PSCs retained high output for up to 40 days in air at room temperature, indicating the stability of PSCs. These results may provide a new avenue for manufacturing high efficiency and high stability PSCs.

A Stable Amino-Functionalized Interpenetrated Metal-Organic Framework Exhibiting Gas Selectivity and Pore-Size-Dependent Catalytic Performance.

An amino-functionalized doubly interpenetrated microporous zinc metal-organic framework (UPC-30) has been solvothermally synthesized. UPC-30 can be stable at 190 °C and confirmed by powder X-ray diffraction. Gas adsorption measurements indicate that UPC-30 exhibits high H2 adsorption heat and CO2/CH4 separation efficiency. After the exchange of Me2NH2+ by Li+ in the channels, the H2 adsorption heat increased by 19.7%. Because of the existence of -NH2 groups in the channels, UPC-30 can effectively catalyze Knoevenagel condensation reactions with high yield and pore-size-dependent selectivity.

Monitoring thermally induced structural deformation and framework decomposition of ZIF-8 through in situ temperature dependent measurements.

ZIF-8 is an easily synthesized porous material which is widely applied in gas storage/separation, catalysis, and nanoarchitecture fabrication. Thermally induced atomic displacements and the resultant framework deformation/collapse significantly influence the application of ZIF-8, and therefore, in situ temperature dependent FTIR spectroscopy was utilized to study the framework changes during heating in the oxidative environment. The results suggest that ZIF-8 undergoes three transition stages, which are the lattice expansion stage below 200 °C, the "reversible" structural deformation stage from 200 to 350 °C, and the decomposition/collapse stage over 350 °C. Our research indicates that the Zn-N bond breaks at a temperature of 350 °C in the oxidant environment, leading to a drastic deformation of the ZIF-8 structure.