Multidimensional Electrochemistry Decodes the Operando Mechanism of Hydrogen Oxidation.

Being an efficient approach to the utilization of hydrogen energy, the hydrogen oxidation reaction (HOR) is of particular significance in the current carbon-neutrality time. Yet the mechanistic picture of the HOR is still blurred, mostly because the elemental steps of this reaction are rapid and highly entangled, especially when deviating from the thermodynamic equilibrium state. Here we report a strategy for decoding the HOR mechanism under operando conditions. In addition to the wide-potential-range I-V curves obtained using gas diffusion electrodes, we have applied the AC impedance spectroscopy to provide independent and complementary kinetic information. Combining multidimensional data sources has enabled us to fit, in mathematical rigor, the core kinetic parameter set in a 5-D data space. The reaction rate of the three elemental steps (Tafel, Heyrovsky, and Volmer reactions), as a function of the overpotential, can thus be distilled individually. Such an undocumented kinetic picture unravels, in detail, how the HOR is controlled by the elemental steps on polarization. For instance, at low polarization region, the Heyrovsky reaction is relatively slow and can be ignored; but at high polarization region, the Heyrovsky reaction will surpass the Tafel reaction. Additionally, the Volmer reaction has been the fastest within overpotentials of interest. Our findings not only offer a better understanding of the HOR mechanism, but also lay the foundation for the development of improved hydrogen energy utilization systems.

Dual-Role of Polyelectrolyte-Tethered Benzimidazolium Cation in Promoting CO2 /Pure Water Co-Electrolysis to Ethylene.

Electrochemical CO2 reduction reaction (CO2 RR), as a promising route to realize negative carbon emissions, is known to be strongly affected by electrolyte cations (i.e., cation effect). In contrast to the widely-studied alkali cations in liquid electrolytes, the effect of organic cations grafted on alkaline polyelectrolytes (APE) remains unexplored, although APE has already become an essential component of CO2 electrolyzers. Herein, by studying the organic cation effect on CO2 RR, we find that benzimidazolium cation (Beim+ ) significantly outperforms other commonly-used nitrogenous cations (R4 N+ ) in promoting C2+ (mainly C2 H4 ) production over copper electrode. Cyclic voltammetry and in situ spectroscopy studies reveal that the Beim+ can synergistically boost the CO2 to *CO conversion and reduce the proton supply at the electrocatalytic interface, thus facilitating the *CO dimerization toward C2+ formation. By utilizing the homemade APE ionomer, we further realize efficient C2 H4 production at an industrial-scale current density of 331 mA cm-2 from CO2 /pure water co-electrolysis, thanks to the dual-role of Beim+ in synergistic catalysis and ionic conduction. This study provides a new avenue to boost CO2 RR through the structural design of polyelectrolytes.

Accelerating Gas Escape in Anion Exchange Membrane Water Electrolysis by Gas Diffusion Layers with Hierarchical Grid Gradients.

At high current densities, gas bubble escape is the critical factor affecting the mass transport and performance of the electrolyzer. For tight assembly water electrolysis technologies, the gas diffusion layer (GDL) between the catalyst layer (CL) and the flow field plate plays a critical role in gas bubble removal. Herein, we demonstrate that the electrolyzer's mass transport and performance can be significantly improved by simply manipulating the structure of the GDL. Combined with 3D printing technology, ordered nickel GDLs with straight-through pores and adjustable grid sizes are systematically studied. Using an in situ high-speed camera, the gas bubble releasing size and resident time have been observed and analyzed upon the change of the GDL architecture. The results show that a suitable grid size of the GDL can significantly accelerate mass transport by reducing the gas bubble size and the bubble resident time. An adhesive force measurement has further revealed the underlying mechanism. We then proposed and fabricated a novel hierarchical GDL, reaching a current density of 2 A/cm2 at a cell voltage of 1.95 V and 80 °C, one of the highest single-cell performances in pure-water-fed anion exchange membrane water electrolysis (AEMWE).

E2EFP-MIL: End-to-end and high-generalizability weakly supervised deep convolutional network for lung cancer classification from whole slide image.

Efficient and accurate distinction of histopathological subtype of lung cancer is quite critical for the individualized treatment. So far, artificial intelligence techniques have been developed, whose performance yet remained debatable on more heterogenous data, hindering their clinical deployment. Here, we propose an end-to-end, well-generalized and data-efficient weakly supervised deep learning-based method. The method, end-to-end feature pyramid deep multi-instance learning model (E2EFP-MIL), contains an iterative sampling module, a trainable feature pyramid module and a robust feature aggregation module. E2EFP-MIL uses end-to-end learning to extract generalized morphological features automatically and identify discriminative histomorphological patterns. This method is trained with 1007 whole slide images (WSIs) of lung cancer from TCGA, with AUCs of 0.95-0.97 in test sets. We validated E2EFP-MIL in 5 real-world external heterogenous cohorts including nearly 1600 WSIs from both United States and China with AUCs of 0.94-0.97, and found that 100-200 training images are enough to achieve an AUC of >0.9. E2EFP-MIL overperforms multiple state-of-the-art MIL-based methods with high accuracy and low hardware requirements. Excellent and robust results prove generalizability and effectiveness of E2EFP-MIL in clinical practice. Our code is available at https://github.com/raycaohmu/E2EFP-MIL.

Pseudo-Pt Monolayer for Robust Hydrogen Oxidation.

Heteroepitaxial core-shell structure is conducive to combining the advantages of the epilayer and the substrate, creating a novel multifunctionality for catalysis application. Herein, we report a pseudomorphic-Pt atomic layer (PmPt) epitaxially growing on an IrPd-core matrix (PmPt@IrPd/C) as an efficient and stable catalyst for alkaline hydrogen oxidation reaction that exhibits ∼29.2 times more mass activity enhancement than that of benchmark Pt/C. The PmPt@IrPd/C catalyst also gives rise to ∼25.0 times more enhancement than Pt/C during a 50,000-cycle accelerated stability test. This robust stability originates from the resistance to carbon corrosion owing to the stronger H2O interaction instead of carbon oxide (COx) poison species, and the modulated hydroxyl (OH*) adsorption could inhibit the OH* species from shuffling the surface Pt atoms away from the substrate. Moreover, the anion-exchange membrane fuel cells assembled by PmPt@IrPd/C with an ultralow Pt loading of 0.009 mgPt cm-2 in the anode can deliver a power density of 1.27 W cm-2.

Oncolyic Virotherapy for Prostate Cancer: Lighting a Fire in Winter.

As the most common cancer of the genitourinary system, prostate cancer (PCa) is a global men's health problem whose treatments are an urgent research issue. Treatment options for PCa include active surveillance (AS), surgery, endocrine therapy, chemotherapy, radiation therapy, immunotherapy, etc. However, as the cancer progresses, the effectiveness of treatment options gradually decreases, especially in metastatic castration-resistant prostate cancer (mCRPC), for which there are fewer therapeutic options and which have a shorter survival period and worse prognosis. For this reason, oncolytic viral therapy (PV), with its exceptional properties of selective tumor killing, relatively good safety in humans, and potential for transgenic delivery, has attracted increasing attention as a new form of anti-tumor strategy for PCa. There is growing evidence that OV not only kills tumor cells directly by lysis but can also activate anticancer immunity by acting on the tumor microenvironment (TME), thereby preventing tumor growth. In fact, evidence of the efficacy of this strategy has been observed since the late 19th century. However, subsequently, interest waned. The renewed interest in this therapy was due to advances in biotechnological methods and innovations at the end of the 20th century, which was also the beginning of PCa therapy with OV. Moreover, in combination with chemotherapy, radiotherapy, gene therapy or immunotherapy, OV viruses can have a wide range of applications and can provide an effective therapeutic result in the treatment of PCa.

eQTLs play critical roles in regulating gene expression and identifying key regulators in rice.

The regulation of gene expression plays an essential role in both the phenotype and adaptation of plants. Transcriptome sequencing enables simultaneous identification of exonic variants and quantification of gene expression. Here, we sequenced the leaf transcriptomes of 287 rice accessions from around the world and obtained a total of 177 853 high-quality single nucleotide polymorphisms after filtering. Genome-wide association study identified 44 354 expression quantitative trait loci (eQTLs), which regulate the expression of 13 201 genes, as well as 17 local eQTL hotspots and 96 distant eQTL hotspots. Furthermore, a transcriptome-wide association study screened 21 candidate genes for starch content in the flag leaves at the heading stage. HS002 was identified as a significant distant eQTL hotspot with five downstream genes enriched for diterpene antitoxin synthesis. Co-expression analysis, eQTL analysis, and linkage mapping together demonstrated that bHLH026 acts as a key regulator to activate the expression of downstream genes. The transgenic assay revealed that bHLH026 is an important regulator of diterpenoid antitoxin synthesis and enhances the disease resistance of rice. These findings improve our knowledge of the regulatory mechanisms of gene expression variation and complex regulatory networks of the rice genome and will facilitate genetic improvement of cultivated rice varieties.

Prelithiation Bridges the Gap for Developing Next-Generation Lithium-Ion Batteries/Capacitors.

The ever-growing market of portable electronics and electric vehicles has spurred extensive research for advanced lithium-ion batteries (LIBs) with high energy density. High-capacity alloy- and conversion-type anodes are explored to replace the conventional graphite anode. However, one common issue plaguing these anodes is the large initial capacity loss caused by the solid electrolyte interface formation and other irreversible parasitic reactions, which decrease the total energy density and prevent further market integration. Prelithiation becomes indispensable to compensate for the initial capacity loss, enhance the full cell cycling performance, and bridge the gap between laboratory studies and the practical requirements of advanced LIBs. This review summarizes the various emerging anode and cathode prelithiation techniques, the key barriers, and the corresponding strategies for manufacturing-compatible and scalable prelithiation. Furthermore, prelithiation as the primary Li+ donor enables the safe assembly of new-configured "beyond LIBs" (e.g., Li-ion/S and Li-ion/O2 batteries) and high power-density Li-ion capacitors (LICs). The related progress is also summarized. Finally, perspectives are suggested on the future trend of prelithiation techniques to propel the commercialization of advanced LIBs/LICs.

qFC6, a major gene for crude fat content and quality in rice.

KEY MESSAGE: qFC6, a major quantitative trait locus for rice crude fat content, was fine mapped to be identical with Wx. FC6 negatively regulates crude fat content and rice quality. Starch, protein and lipids are the three major components in rice endosperm. The lipids content in rice influences both storage and quality. In this study, we identified a quantitative trait locus (QTL), qFC6, for crude fat (free lipids) content through association analysis and linkage analysis. Gene-based association analysis revealed that LOC_Os06g04200, also known as Wx, was the candidate gene for qFC6. Complementation and knockout transgenic lines revealed that Wx negatively regulates crude fat content. Lipid composition and content analysis by gas chromatography and taste evaluation analysis showed that FC6 positively influenced bound lipids content and negatively affected both free lipids content and taste. Besides, higher free lipids content rice varieties exhibit more lustrous appearance after cooking and by adding extra oil during cooking could improve rice luster and taste score, indicating that higher free lipids content may make rice more lustrous and delicious. Together, we cloned a QTL coordinating rice crude fat content and eating quality and assisted in uncovering the genetic basis of rice lipid content and in the improvement of rice eating quality.

Preanodized Cu Surface for Selective CO2 Electroreduction to C1 or C2+ Products.

The electrochemical CO2 reduction over Cu catalysts has shown great potential in producing a wide range of valuable chemicals, but it is still plagued by a poor controllability on product distribution. Herein, we demonstrate an effective regulation of CO2 reduction paths through a preanodization treatment of Cu foil electrodes in different electrolytes. The Cu electrode exhibits a superior C1 and C2+ product selectivity after being preanodized in NaClO4 (Cu-NaClO4) and Na2HPO4 electrolyte (Cu-Na2HPO4), respectively. Combined with in situ electrochemical Raman, ATR-SEIRAS, and SEM characterizations, the preferential C1 path is due to the deposition of many Cu nanocrystals with dominant Cu(111) facets on the Cu-NaClO4 electrode. In contrast, the preferential C2+ path over the Cu-Na2HPO4 is attributed to formation of a unique Cu nanodendritic morphology, which strengthens the *CO intermediate adsorption and induces an environment of low local H2O/CO2 stoichiometric ratio, thus facilitating C-C coupling for C2+ production. Our findings may shed light on the rational control of the CO2 reduction path through engineering of the Cu surface structure.

A completely precious metal-free alkaline fuel cell with enhanced performance using a carbon-coated nickel anode.

SignificanceWe present a groundbreaking advance in completely nonprecious hydrogen fuel cell technologies achieving a record power density of 200 mW/cm2 with Ni@CNx anode and Co-Mn cathode. The 2-nm CNx coating weakens the O-binding energy, which effectively mitigates the undesirable surface oxidation during hydrogen oxidation reaction (HOR) polarization, leading to a stable fuel cell operation for Ni@CNx over 100 h at 200 mA/cm2, superior to a Ni nanoparticle counterpart. Ni@CNx exhibited a dramatically enhanced tolerance to CO relative to Pt/C, enabling the use of hydrogen gas with trace amounts of CO, critical for practical applications. The complete removal of precious metals in fuel cells lowers the catalyst cost to virtually negligible levels and marks a milestone for practical alkaline fuel cells.

Intermolecular Energy Gap-Induced Formation of High-Valent Cobalt Species in CoOOH Surface Layer on Cobalt Sulfides for Efficient Water Oxidation.

Transition metal-based electrocatalysts will undergo surface reconstruction to form active oxyhydroxide-based hybrids, which are regarded as the "true-catalysts" for the oxygen evolution reaction (OER). Much effort has been devoted to understanding the surface reconstruction, but little on identifying the origin of the enhanced performance derived from the substrate effect. Herein, we report the electrochemical synthesis of amorphous CoOOH layers on the surface of various cobalt sulfides (CoSα ), and identify that the reduced intermolecular energy gap (Δinter ) between the valence band maximum (VBM) of CoOOH and the conduction band minimum (CBM) of CoSα can accelerate the formation of OER-active high-valent Co4+ species. The combination of electrochemical and in situ spectroscopic approaches, including cyclic voltammetry (CV), operando electron paramagnetic resonance (EPR) and Raman, reveals that Co species in the CoOOH/Co9 S8 are more readily oxidized to CoO2 /Co9 S8 than in CoOOH and other CoOOH/CoSα . This work provides a new design principle for transition metal-based OER electrocatalysts.

In situ surface enhanced Raman spectroscopy study of electrode-polyelectrolyte interfaces.

As polyelectrolytes play a more and more important role in electrochemical fields, further understanding of the electrode-polyelectrolyte interface is in high demand. Surface-enhanced Raman spectroscopy (SERS) is utilized widely in electrode-solution interface research due to its ultra-high sensitivity, but is still rarely in the study of the electrode-polyelectrolyte interface due to difficulties in constructing appropriate electrochemical in situ devices. Additionally, the reported electrochemical in situ Raman works on the electrode-polyelectrolyte interface have a common problem of the coexistence of electrode-solution interfaces and electrode-polyelectrolyte interfaces. Here, we used screen printing electrodes (SPE) with a compact planar three-electrode structure to carry out a new electrochemical in situ SERS test method, which was suitable for the study of the electrode-polyelectrolyte interface. Polyelectrolyte membranes can be conveniently and closely coated on the SPE's planar three electrodes to achieve isolated electrode-polyelectrolyte interfaces without electrode-solution interfaces coexisting. Strongly potential-dependent signals were obtained from the Pt-Nafion™ interface directly across the Nafion™ membrane, which verifies that this method is practical for the electrochemical in situ SERS study of the electrode-polyelectrolyte interface.

A Deep Learning-Based Approach for Glomeruli Instance Segmentation from Multistained Renal Biopsy Pathologic Images.

Glomeruli instance segmentation from pathologic images is a fundamental step in the automatic analysis of renal biopsies. Glomerular histologic manifestations vary widely among diseases and cases, and several special staining methods are necessary for pathologic diagnosis. A robust model is needed to segment and classify glomeruli with different staining methods and apply in cases with various glomerular pathologic changes. Herein, pathologic images from renal biopsy slides stained with three basic special staining methods were used to build the data sets. The snapshot group included 1970 glomeruli from 516 patients, and the whole-slide image group included 8665 glomeruli from 148 patients. Cascade Mask region-based convolutional neural net architecture was trained to detect, classify, and segment glomeruli into three categories: i) GN, structural normal; ii) global sclerosis; and iii) glomerular with other lesions. In the snapshot group, total glomeruli, GN, global sclerosis, and glomerular with other lesions achieved an F1 score of 0.914, 0.896, 0.681, and 0.756, respectively, which were comparable with those in the whole-slide image group (0.940, 0.839, 0.806, and 0.753, respectively). Among the three categories, GN achieved the best instance segmentation effect in both groups, as determined by average precision, average recall, F1 score, and Mask mean Intersection over Union. The present model segments and classifies multistained glomeruli with efficiency and robustness. It can be applied as the first step for more detailed glomerular histologic analysis.

Exploration on Gleason score variation trend of patients with prostate carcinoma from 1996 to 2019: a retrospective single center study.

BACKGROUND: Gleason score (GS) is one of the stronger prognostic factors and is integral to the management of prostate carcinoma. Subsequent modifications, recommended by the International Society of Urological Pathology in 2005 and 2014, enabled accurate prediction of prognosis. The present study investigated GS variation trend of patients with prostate carcinoma from 1996 to 2019 and offered an overview of GS changes with age, specimen type, histopathological type and serum prostate specific antigen (PSA). METHODS: One thousand three hundred and seventy-six patients, admitted to Peking University People's Hospital in 1996 to 2019, were divided into 1996 to 2006, 2007 to 2015 and 2016 to 2019 groups. Data, including demographic characteristics, GS, primary and secondary grade and percentage of primary and secondary grade of each group, were collected and analyzed. The population distribution and average of GS was evaluated, after segmented and stratified by age, type of specimen, histopathological type and PSA. RESULTS: The average of age and PSA of each cohort had no obvious change. The average of total GS fluctuated among three cohorts with statistically significant differences. The distribution of age and PSA did not differ among cohorts. The distribution of total and primary GS shifted, with more patients detected as total GS higher than 6 (86.1%), and more primary grade higher than 3 (56.7%) in 2016-2019. After segmented and stratified by age, specimen type, histological type and PSA, the population percentage of GS over 6 was significantly higher in 2016-2019 than 1996-2006 and 2007-2015 in patients aged younger than 80 years (age <60, 89.6%, age 60-69, 82.0%, age 70-79, 87.7%). Patients, aged below 80 years in 2016-2019, were detected with higher total GS. CONCLUSIONS: In the present study, GS in patients with prostate carcinoma showed a upward trend. Primary grade, age, serum PSA and specimen type were the main reasons for GS changing while secondary grade, tissue types and diagnostic criteria influenced less.

The coordination of OsbZIP72 and OsMYBS2 with reverse roles regulates the transcription of OsPsbS1 in rice.

Nonphotochemical quenching (NPQ), an intricate photoprotective process, plays fundamental roles in maintaining plant fitness. The PsbS protein is essential for the rapid induction of NPQ, and acts in a dose-dependent manner in leaves. However, little information is known on the transcriptional control of PsbS in land plants. Here we demonstrated that the expression of OsPsbS1 is directly upregulated by OsbZIP72 while repressed by OsMYBS2 in rice. We identified a new cis-element GACAGGTG in japonica OsPsbS1 promoter, to which OsbZIP72 could strongly bind and activate the expression of OsPsbS1. The new cis-element CTAATC confers specific binding for OsMYBS2 in japonica OsPsbS1 promoter. OsbZIP72 can be activated by SAPK1, and acts depending on the abscisic acid (ABA) signalling pathway. GF14A protein affects the repression activity of OsMYBS2 by regulating its nucleocytoplasmic shuttling, and Ser53 is necessary for OsMYBS2 to be retained in the cytoplasm. The inducibility of OsPsbS1 transcription under high light conditions in OsbZIP72 knockout lines was greatly impaired, while the repression of OsPsbS1 transcription under a low light environment in OsMYBS2 knockout lines was significantly alleviated. These results reveal cross-talk among NPQ processes, the ABA signalling pathway and abiotic stress signalling. The elaborate mechanisms may help enhance photoprotection and improve photosynthesis in rice.

The origin of Wxla provides new insights into the improvement of grain quality in rice.

Appearance and taste are important factors in rice (Oryza sativa) grain quality. Here, we investigated the taste scores and related eating-quality traits of 533 diverse cultivars to assess the relationships between-and genetic basis of-rice taste and eating-quality. A genome-wide association study highlighted the Wx gene as the major factor underlying variation in taste and eating quality. Notably, a novel waxy (Wx) allele, Wxla , which combined two mutations from Wxb and Wxin , exhibited a unique phenotype. Reduced GBSSI activity conferred Wxla rice with both a transparent appearance and good eating quality. Haplotype analysis revealed that Wxla was derived from intragenic recombination. In fact, the recombination rate at the Wx locus was estimated to be 3.34 kb/cM, which was about 75-fold higher than the genome-wide mean, indicating that intragenic recombination is a major force driving diversity at the Wx locus. Based on our results, we propose a new network for Wx evolution, noting that new Wx alleles could easily be generated by crossing genotypes with different Wx alleles. This study thus provides insights into the evolution of the Wx locus and facilitates molecular breeding for quality in rice.

Genetic architecture and key genes controlling the diversity of oil composition in rice grains.

Rice grain oil is a valuable nutrient source. However, the genetic basis of oil biosynthesis in rice grains remains unclear. In this study, we performed a genome-wide association study on oil composition and oil concentration in a diverse panel of 533 cultivated rice accessions. High variation for 11 oil-related traits was observed, and the oil composition of rice grains showed differentiation among the subpopulations. We identified 46 loci that are significantly associated with grain oil concentration or composition, 16 of which were detected in three recombinant inbred line populations. Twenty-six candidate genes encoding enzymes involved in oil metabolism were identified from these 46 loci, four of which (PAL6, LIN6, MYR2, and ARA6) were found to contribute to natural variation in oil composition and to show differentiation among the subpopulations. Interestingly, population genetic analyses revealed that specific haplotypes of PAL6 and LIN6 have been selected in japonica rice. Based on these results, we propose a possible oil biosynthetic pathway in rice grains. Collectively, our results provide new insights into the genetic basis of oil biosynthesis in rice grains and can facilitate marker-based breeding of rice varieties with enhanced oil and grain quality.

Genome-wide association study of flowering time reveals complex genetic heterogeneity and epistatic interactions in rice.

Since domestication, rice has cultivated in a wide range of latitudes with different day lengths. Selection of diverse natural variations in heading date and photoperiod sensitivity is critical for adaptation of rice to different geographical environments. To unravel the genetic architecture underlying natural variation of rice flowering time, we conducted a genome wide association study (GWAS) using several association analysis strategies with a diverse worldwide collection of 529 O. sativa accessions. Heading date was investigated in three environments under long-day or short-day conditions, and photosensitivity was evaluated. By dividing the whole association panel into subpopulations and performing GWAS with both linear mixed models and multi-locus mixed-models, we revealed hundreds of significant loci harboring novel candidate genes as well as most of the known flowering time genes. In total, 127 hotspots were detected in at least two GWAS. Universal genetic heterogeneity was found across subpopulations. We further detected abundant interactions between GWAS loci, especially in indica. Functional gene families were revealed from enrichment analysis of the 127 hotspots. The results demonstrated a rich of genetic interactions in rice flowering time genes and such epistatic interactions contributed to the large portions of missing heritability in GWAS. It suggests the increased complexity of genetic heterogeneity might discount the power of increasing the sample sizes in GWAS.

Genetic basis of vascular bundle variations in rice revealed by genome-wide association study.

The vascular bundles play important roles in transportation of photoassimilate, and the number, size, and capacity of vascular bundles influence the transportation efficiency. Dissecting the genetic basis may help to make better use of naturally occurring vascular bundle variations. Here, we conducted a genome-wide association study (GWAS) of the vascular bundle variations in a worldwide collection of 529 Oryza sativa accessions. A total of 42 and 93 significant association loci were identified in the neck panicle and flag leaf, respectively. The introgression lines showing extreme values of the target traits harbored at least one GWAS signal, indicating the reliability of the GWAS loci. Based on the data of near-isogenic lines and transgenic plants, Grain number, plant height, and heading date7 (Ghd7) was identified as a major locus for the natural variation of vascular bundles in the neck panicle at the heading stage. In addition, Narrow leaf1 (NAL1) was found to influence the vascular bundles in both the neck panicle and flag leaf, and the effects of the major haplotypes of NAL1 were characterized. The loci or candidate genes identified would help to improve vascular bundle system in rice breeding.