Cascaded orbital-oriented hybridization of intermetallic Pd3Pb boosts electrocatalysis of Li-O2 battery.

Catalysts with a refined electronic structure are highly desirable for promoting the oxygen evolution reaction (OER) kinetics and reduce the charge overpotentials for lithium-oxygen (Li-O2) batteries. However, bridging the orbital interactions inside the catalyst with external orbital coupling between catalysts and intermediates for reinforcing OER catalytic activities remains a grand challenge. Herein, we report a cascaded orbital-oriented hybridization, namely alloying hybridization in intermetallic Pd3Pb followed by intermolecular orbital hybridization between low-energy Pd atom and reaction intermediates, for greatly enhancing the OER electrocatalytic activity in Li-O2 battery. The oriented orbital hybridization in two axes between Pb and Pd first lowers the d band energy level of Pd atoms in the intermetallic Pd3Pb; during the charging process, the low-lying 4dxz/yz and 4dz2 orbital of the Pd further hybridizes with 2π* and 5σ orbitals of lithium superoxide (LiO2) (key reaction intermediate), eventually leading to lower energy levels of antibonding and, thus, weakened orbital interaction toward LiO2. As a consequence, the cascaded orbital-oriented hybridization in intermetallic Pd3Pb considerably decreases the activation energy and accelerates the OER kinetics. The Pd3Pb-based Li-O2 batteries exhibit a low OER overpotential of 0.45 V and superior cycle stability of 175 cycles at a fixed capacity of 1,000 mAh g-1, which is among the best in the reported catalysts. The present work opens up a way for designing sophisticated Li-O2 batteries at the orbital level.

mitoSplitter: A mitochondrial variants-based method for efficient demultiplexing of pooled single-cell RNA-seq.

Single-cell RNA-seq (scRNA-seq) analysis of multiple samples separately can be costly and lead to batch effects. Exogenous barcodes or genome-wide RNA mutations can be used to demultiplex pooled scRNA-seq data, but they are experimentally or computationally challenging and limited in scope. Mitochondrial genomes are small but diverse, providing concise genotype information. We developed "mitoSplitter," an algorithm that demultiplexes samples using mitochondrial RNA (mtRNA) variants, and demonstrated that mtRNA variants can be used to demultiplex large-scale scRNA-seq data. Using affordable computational resources, mitoSplitter can accurately analyze 10 samples and 60,000 cells in 6 h. To avoid the batch effects from separated experiments, we applied mitoSplitter to analyze the responses of five non-small cell lung cancer cell lines to BET (Bromodomain and extraterminal) chemical degradation in a multiplexed fashion. We found the synthetic lethality of TOP2A inhibition and BET chemical degradation in BET inhibitor-resistant cells. The result indicates that mitoSplitter can accelerate the application of scRNA-seq assays in biomedical research.

Electron Localization in Rationally Designed Pt1Pd Single-Atom Alloy Catalyst Enables High-Performance Li-O2 Batteries.

Li-O2 batteries (LOBs) are considered as one of the most promising energy storage devices due to their ultrahigh theoretical energy density, yet they face the critical issues of sluggish cathode redox kinetics during the discharge and charge processes. Here we report a direct synthetic strategy to fabricate a single-atom alloy catalyst in which single-atom Pt is precisely dispersed in ultrathin Pd hexagonal nanoplates (Pt1Pd). The LOB with the Pt1Pd cathode demonstrates an ultralow overpotential of 0.69 V at 0.5 A g-1 and negligible activity loss over 600 h. Density functional theory calculations show that Pt1Pd can promote the activation of the O2/Li2O2 redox couple due to the electron localization caused by the single Pt atom, thereby lowering the energy barriers for the oxygen reduction and oxygen evolution reactions. Our strategy for designing single-atom alloy cathodic catalysts can address the sluggish oxygen redox kinetics in LOBs and other energy storage/conversion devices.

Enhanced Two-Step LAMP-CRISPR Assay with an Engineered Zst Polymerase for Contamination-Free and Ultrasensitive DNA Detection.

Current loop-mediated isothermal amplification (LAMP)-coupled clustered regularly interspaced short palindromic repeats (LAMP-CRISPR) biosensing in two-step or one-step formats has been applied to next-generation accurate molecular diagnosis. However, two-step LAMP-CRISPR assays intrinsically confront aerosol contamination, while one-step assays possess a compromised detection performance. To this end, we propose an enhanced two-step LAMP-CRISPR assay (ETL-CRISPR) with an engineered Zst polymerase to mediate ultrasensitive DNA detection and thoroughly eliminate aerosol contamination. Instead of supplementing any dTTP, the newly engineered Zst polymerase can efficiently polymerize four oligonucleotides (dATP, dCTP, dGTP, and dUTP), thereby enabling contamination-free and ultrasensitive ETL-CRISPR assay. By targeting the L1 gene of human papillomaviruses (HPV) 16 and the E7 gene of HPV18, our ETL-CRISPR assay achieves high specificity and single-copy level sensitivity within 1 h. Furthermore, we validated the assay by using 85 HPV clinical swab samples with an accuracy of 98.8%, which is comparable to the real-time quantitative polymerase chain reaction. Therefore, ETL-CRISPR provides a straightforward strategy for the contamination-free and ultrasensitive point-of-care diagnosis of clinical pathogens.

Well-Paired-Seq2: High-Throughput and High-Sensitivity Strategy for Characterizing Low RNA-Content Cell/Nucleus Transcriptomes.

Single-cell RNA sequencing (scRNA-seq) is a transformative technology that unravels the intricate cellular state heterogeneity. However, the Poisson-dependent cell capture and low sensitivity in scRNA-seq methods pose challenges for throughput and samples with a low RNA-content. Herein, to address these challenges, we present Well-Paired-Seq2 (WPS2), harnessing size-exclusion and quasi-static hydrodynamics for efficient cell capture. WPS2 exploits molecular crowding effect, tailing activity enhancement in reverse transcription, and homogeneous enzymatic reaction in the initial bead-based amplification to achieve 3116 genes and 8447 transcripts with an average of ∼20000 reads per cell. WPS2 detected 1420 more genes and 4864 more transcripts than our previous Well-Paired-Seq. It sensitively characterizes transcriptomes of low RNA-content single cells and nuclei, overcoming the Poisson limit for cell and barcoded bead capture. WPS2 also profiles transcriptomes from frozen clinical samples, revealing heterogeneous tumor copy number variations and intercellular crosstalk in clear cell renal cell carcinomas. Additionally, we provide the first single-cell-level characterization of rare metanephric adenoma (MA) and uncover potential specific markers. With the advantages of high sensitivity and high throughput, WPS2 holds promise for diverse basic and clinical research.

Proteomics analysis of Toxoplasma gondii merozoites reveals regulatory proteins involved in sexual reproduction.

Sexual reproduction plays a crucial role in the transmission and life cycle of toxoplasmosis. The merozoites are the only developmental stage capable of differentiation into male and female gametes, thereby initiating sexual reproduction to form oocysts that are excreted into the environment. Hence, our study aimed to perform proteomic analyses of T. gondii Pru strain merozoites, a pre-sexual developmental stage in cat IECs, and tachyzoites, an asexual developmental stage, using the tandem mass tag (TMT) method in order to identify the differentially expressed proteins (DEPs) of merozoites. Proteins functions were subjected to cluster analysis, and DEPs were validated through the qPCR method. The results showed that a total of 106 proteins were identified, out of which 85 proteins had quantitative data. Among these, 15 proteins were differentially expressed within merozoites, with four exhibiting up-regulation and being closely associated with the material and energy metabolism as well as the cell division of T. gondii. Two novel DEPs, namely S8GHL5 and A0A125YP41, were identified, and their homologous family members have been demonstrated to play regulatory roles in oocyte maturation and spermatogenesis in other species. Therefore, they may potentially exhibit regulatory functions during the differentiation of micro- and macro-gametophytes at the initiation stage of sexual reproduction in T. gondii. In conclusion, our results showed that the metabolic and divisional activities in the merozoites surpass those in the tachyzoites, thereby providing structural, material, and energetic support for gametophytes development. The discovery of two novel DEPs associated with sexual reproduction represents a significant advancement in understanding Toxoplasma sexual reproduction initiation and oocyst formation.

Alterations in gut microbiota contribute to cognitive deficits induced by chronic infection of Toxoplasma gondii.

Chronic infection with Toxoplasma gondii (T. gondii) emerges as a risk factor for neurodegenerative diseases in animals and humans. However, the underlying mechanisms are largely unknown. We aimed to investigate whether gut microbiota and its metabolites play a role in T. gondii-induced cognitive deficits. We found that T. gondii infection induced cognitive deficits in mice, which was characterized by synaptic ultrastructure impairment and neuroinflammation in the hippocampus. Moreover, the infection led to gut microbiota dysbiosis, barrier integrity impairment, and inflammation in the colon. Interestingly, broad-spectrum antibiotic ablation of gut microbiota attenuated the adverse effects of the parasitic infection on the cognitive function in mice; cognitive deficits and hippocampal pathological changes were transferred from the infected mice to control mice by fecal microbiota transplantation. In addition, the abundance of butyrate-producing bacteria and the production of serum butyrate were decreased in infected mice. Interestingly, dietary supplementation of butyrate ameliorated T. gondii-induced cognitive impairment in mice. Notably, compared to the healthy controls, decreased butyrate production was observed in the serum of human subjects with high levels of anti-T. gondii IgG. Overall, this study demonstrates that gut microbiota is a key regulator of T. gondii-induced cognitive impairment.

Phytic Acid-Functional Cellulose Nanocrystals and Their Application in Self-Healing Nanocomposite Hydrogels.

Cellulose nanocrystals (CNCs) have garnered significant attention as a modifiable substrate because of their exceptional performances, including remarkable degradability, high tensile strength, high elastic modulus, and biocompatibility. In this article, the successful adsorption of phytic acid (PA) onto the surface of cellulose nanocrystals @polydopamine (CNC@PDA) was achieved. Taking inspiration from mussels, a dopamine self-polymerization reaction was employed to coat the surface of CNCs with PDA. Utilizing Pickering emulsion, the CNC@PDA-PA nanomaterial was obtained by grafting PA onto CNC@PDA. An environmentally friendly hydrogel was prepared through various reversible interactions using poly(acrylic acid) (PAA) and Fe3+ as raw materials with the assistance of CNC@PDA-PA. By multiple hydrogen bonding and metal-ligand coordination, nanocomposite hydrogels exhibit remarkable mechanical properties (the tensile strength and strain were 1.82 MPa and 442.1%, respectively) in addition to spectacular healing abilities (96.6% after 5 h). The study aimed to develop an innovative approach for fabricating nanocomposite hydrogels with exceptional self-healing capabilities.

Electrochemically Enable N-Sulfenylation/Phosphinylation of Sulfoximines via Oxidative Dehydrocoupling Reaction.

An electrochemical oxidative cross-coupling strategy for the synthesis of N-sulfenylsulfoximines from sulfoximines and thiols was accomplished, giving diverse N-sulfenylsulfoximines in moderate to good yields. Moreover, this strategy can be extended to construct the N-P bond of N-phosphinylated sulfoximines. With electrons as reagents, the oxidative dehydrogenation cross-coupling reaction proceeds smoothly in the absence of traditional redox reagents.

Amplification-free CRISPR/Cas detection technology: challenges, strategies, and perspectives.

Rapid and accurate molecular diagnosis is a prerequisite for precision medicine, food safety, and environmental monitoring. The clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas)-based detection, as a cutting-edged technique, has become an immensely effective tool for molecular diagnosis because of its outstanding advantages including attomolar level sensitivity, sequence-targeted single-base specificity, and rapid turnover time. However, the CRISPR/Cas-based detection methods typically require a pre-amplification step to elevate the concentration of the analyte, which may produce non-specific amplicons, prolong the detection time, and raise the risk of carryover contamination. Hence, various strategies for target amplification-free CRISPR/Cas-based detection have been developed, aiming to minimize the sensitivity loss due to lack of pre-amplification, enable detection for non-nucleic acid targets, and facilitate integration in portable devices. In this review, the current status and challenges of target amplification-free CRISPR/Cas-based detection are first summarized, followed by highlighting the four main strategies to promote the performance of target amplification-free CRISPR/Cas-based technology. Furthermore, we discuss future perspectives that will contribute to developing more efficient amplification-free CRISPR/Cas detection systems.

Sparse 2-D optical phased array with large grating-lobe-free steering range based on an aperiodic grid.

Two-dimensional (2-D) optical phased arrays (OPAs) usually suffer from limited scan ranges and small aperture sizes. To overcome these bottlenecks, we utilize an aperiodic 32 × 32 grid to increase the beam scanning range and furthermore distribute 128 grating antennas sparsely among 1024 grid points so as to reduce the array element number. The genetic algorithm is used to optimize the uneven grid spacings and the sparse distribution of grating antennas. With these measures, a 128-channel 2-D OPA operating at 1550 nm realizes a grating-lobe-free steering range of 53° × 16°, a field of view of 24° × 16°, a beam divergence of 0.31° × 0.49°, and a sidelobe suppression ratio of 9 dB.

CRISPR-based Biosensors for Human Health: A Novel Strategy to Detect Emerging Infectious Diseases.

Infectious diseases (such as sepsis, influenza, and malaria), caused by various pathogenic bacteria and viruses, are widespread across the world. Early and rapid detection of disease-related pathogens is necessary to reduce their spread in the world and prevent their potential global pandemics. The clustered regularly interspaced short palindromic repeats (CRISPR) technology, as the next-generation molecular diagnosis technique, holds immense promise in the detection of infectious diseases because of its remarkable advantages, including supreme flexibility, sensitivity, and specificity. While numerous CRISPR-based biosensors have been developed for application in environmental monitoring, food safety, and point-of-care diagnosis, there remains a critical need to summarize and explore their potential in human health. This review aims to address this gap by focusing on the latest advancements in CRISPR-based biosensors for infectious disease detection. We provide an overview of the current status, pre-amplification methods, the unique feature of each CRISPR system, and the design of CRISPR-based biosensing strategies to detect disease-associated nucleic acids. Last but not least, the review analyzes the current challenges and provides future perspectives, which will contribute to developing more effective CRISPR-based biosensors for human health.

Anxiety, depression, and coping styles among patients with chronic pancreatitis in East China.

BACKGROUND: Anxiety and depression are common psychological comorbidities in patients with chronic pancreatitis (CP). There is still a lack of epidemiological studies on anxiety and depression in Chinese CP patients. This study aimed to identify the incidence and related factor of anxiety and depression among East Chinese CP patients and explore the relationship between anxiety, depression, and coping styles. METHODS: This prospective observational study was conducted from June 1, 2019 to March 31, 2021 in Shanghai, China. Patient diagnosed with CP were interviewed using the sociodemographic and clinical characteristics questionnaire, Self-rating Anxiety Scale (SAS), Self-rating Depression Scale (SDS), and Coping Style Questionnaire (CSQ). Multivariate logistic regression analysis was conducted to identify the related factors of anxiety and depression. Correlation test was preformed to analyze the correlation between anxiety, depression, and coping styles. RESULTS: The incidence of anxiety and depression in East Chinese CP patients was 22.64% and 38.61%, respectively. Patients' previous health status, level of disease coping, frequency of abdominal pain episodes, and pain severity were significantly associated with anxiety and depression. Mature coping styles (Problem solving, Seeking for help) had a positive impact on anxiety and depression, while immature coping styles (Self-blame, Fantasy, Repression, Rationalization) had negative effects on anxiety and depression. CONCLUSION: Anxiety and depression were common in patients with CP in China. The factors identified in this study may provide references for the management of anxiety and depression in CP patients.

Molecular detection and species identification of Plasmodium spp. infection among imported cases in Eastern China, 2012-2018.

Due to the increasing number of returnees from malaria endemic areas, imported malaria has become a public health challenge in China. To better understand the characteristics of imported Plasmodium species and adjust appropriate strategies for malaria prevention and control in Eastern China, we conducted molecular detection and species identification on 1282 imported malaria cases in Shandong Province between 2012 and 2018. The findings showed that P. falciparum was predominant, particularly in cases imported from Africa. P. vivax was the dominant species imported from Asian countries. Additionally, imported P. ovale and P. malariae emerged in the province. Further surveillance and control of imported malaria among returnees from Africa and Southeast Asia is needed to be strengthened in Eastern China.

Multiple anthropogenic stressors influence the taxonomic and functional homogenization of macroinvertebrate communities on the mainstream of an urban-agricultural river in China.

Biodiversity loss is caused by intensive human activities and threatens human well-being. However, less is known about how the combined effects of multiple stressors on the diversity of internal (alpha diversity) and multidimensional (beta diversity) communities. Here, we conducted a long-term experiment to quantify the contribution of environmental stressors (including water quality, land use, climate factors, and hydrological regimes) to macroinvertebrate communities alpha and beta diversity in the mainstream of the Songhua River, the third largest river in China, from 2012 to 2019. Our results demonstrated that the alpha and beta diversity indices showed a decline during the study period, with the dissimilarity in community composition between sites decreasing significantly, especially in the impacted river sections (upper and midstream). Despite overall improvement in water quality after management intervention, multiple human-caused stressors still have led to biotic homogenization of macroinvertebrate communities in terms of both taxonomic and functional diversities in the past decade. Our study revealed the increased human land use explained an important portion of the variation of diversities, further indirectly promoting biotic homogenization by changing the physical and chemical factors of water quality, ultimately altering assemblage ecological processes. Furthermore, the facets of diversity have distinct response mechanisms to stressors, providing complementary information from the perspective of taxonomy and function to better reflect the ecological changes of communities. Environmental filtering determined taxonomic beta diversity, and functional beta diversity was driven by the joint efforts of stressors and spatial processes. Finally, we proposed that traditional water quality monitoring alone cannot fully reveal the status of river ecological environment protection, and more importantly, we should explore the continuous changes in biodiversity over the long term. Meanwhile, our results also highlight timely control of nutrient input and unreasonable expansion of land use can better curb the ecological degradation of rivers and promote the healthy and sustainable development of floodplain ecosystems.

High genetic diversity in Plasmodium falciparum isolates among Chinese migrant workers returnee from Africa.

Malaria is one of the most important parasitic diseases that causes a serious public health problem. The genetic diversity of malaria parasites may affect malaria transmission and malaria control strategies. In China, imported malaria was significantly increased in recent years, among which numerous migrant workers were infected with Plasmodium falciparum from Africa. However, little was known about genetic diversity of these populations in China. In this study, we evaluated genetic polymorphism and allele frequencies of msp1, msp2, and glurp genes in P. falciparum among Chinese migrant workers returnee from Africa between 2013 and 2017. Of the 381 P. falciparum isolates, 89.0% for msp1 gene, 71.7% for msp2 gene, and 78.0% for glurp gene were successfully genotyped. In msp1, 29 different alleles were observed, among which the K1 allelic family (71.7%) was predominant. In msp2, 21 different alleles were detected, of which the 3D7 allelic family (91.2%) was more frequent than FC27 allelic family (72.5%). For glurp, 12 individual alleles were detected in the samples. Taken together, the findings showed a high genetic diversity of these isolates, which provided the baseline data for African P. falciparum population imported to China.

Exploring the influence mechanism of dissolved organic matter on the bioavailability and thyroid hormone disrupting effect of zinc: A case study of effluents from galvanizing plants.

The effect of dissolved organic matter (DOM) on metal bioavailability and toxicity is a complex process. Effluents from galvanizing plants containing large amounts of DOM and Zn were selected to investigate the potential influence and mechanism of DOM on Zn bioavailability and its role in inducing thyroid hormone disrupting effects. Thyroid hormone disrupting effects were evaluated using a recombinant thyroid hormone receptor ß gene yeast assay. The results suggest that Zn could be the main metal contributor to the toxic effects. Then, Zn-binding characteristics with different fluorescent components of DOM were analyzed using three-dimensional excitation emission matrix fluorescence spectroscopy (3DEEM) and revealed that Zn was more susceptible to interactions with fulvic-like materials. Furthermore, DOM altered the cellular biouptake and compartmentalization processes of Zn by downregulating Zn transmembrane transport-related genes (ZRT1, ZRT2 and ZAP1) and upregulating detoxification-related genes (COT1 and ZRC1), thus altering thyroid toxicity. These results provide comprehensive insights into the influence and mechanism of DOM on bioavailability and thyroid toxicity of Zn and suggest that the influence is associated with complex physical, chemical and biological processes, indicating that more refined medium constraints along with subtle biological reactions should be considered when predicting the bioavailability and toxicity of Zn in environmental water samples.

Cesium Lead Bromide Perovskite-Based Lithium-Oxygen Batteries.

The main challenge for lithium-oxygen (Li-O2) batteries is their sluggish oxygen evolution reaction (OER) kinetics and high charge overpotentials caused by the poorly conductive discharge products of lithium peroxide (Li2O2). In this contribution, the cesium lead bromide perovskite (CsPbBr3) nanocrystals were first employed as a high-performance cathode for Li-O2 batteries. The battery with a CsPbBr3 cathode can exhibit the lowest charge overpotential of 0.5 V and the best cycling performance of 400 cycles among all the reported perovskite-based Li-O2 cells, which represents a new benchmark. Most importantly, the density functional theory (DFT) calculations further prove that the rate limitation step during OER processes is the decomposition of LiO2 to form O2 and Li+, and the weak adsorption strength between CsPbBr3 surfaces and LiO2 results in a low charge overpotential for the CsPbBr3-based Li-O2 battery. This work first demonstrates the good potential of CsPbBr3 for application in metal-air batteries.

Development of Toxoplasma gondii Chinese I genotype Wh6 Strain in Cat Intestinal Epithelial Cells.

Felids are the unique definitive host of Toxoplasma gondii. The intestine of felid is the only site for initiating Toxoplasma gondii sexual reproduction. T. gondii excretes millions of infectious oocysts from the intestine, which are the primary source of infection. There are many difficulties in developing vaccines and drugs to control oocyst excretion due to the lack of an appropriate experimental model. Here, we established an in vitro feline intestinal epithelial cell (IEC) infection system and an efficient animal model of T. gondii Chinese 1 genotype, Wh6 strain (TgCtwh6). The Kunming mice brain tissues containing TgCtwh6 cysts were harvested 42-day post-infection. The bradyzoites were co-cultured with cat IECs in vitro at a ratio of 1:10. Five 3-month-old domestic cats were orally inoculated with 600 cysts each. The oocysts were detected by daily observation of cat feces by microscopy and polymerase chain reaction. We found that the parasite adhered and invaded cat IECs in vitro, transformed into tachyzoites, and then divided to form rose-like structures. These parasites eventually destroyed host cells, escaped, and finished the asexual reproduction process. Schizonts associated with sexual reproduction have not been observed during development in vitro cultured cells. However, schizonts were detected in all infected cat intestinal epithelial cells, and oocysts were presented in all cat feces. Our study provides a feasible cell model and an efficient infection system for the following studies of T. gondii sexual reproduction, and also lays a foundation to develop drugs and vaccines for blocking excretion and transmission of oocysts.

Research Progress on Sport-Related Sudden Cardiac Death.

Physical exercise can reduce the overall risk of cardiovascular disease, prolong lifespan and improve the quality of life, but some studies have shown that there is a certain correlation between vigorous physical exercise and sudden cardiac death. A number of retrospective or prospective studies on sports-related sudden cardiac death (SrSCD) have been conducted at home and abroad. This article reviews the related studies on the definition, epidemiological characteristics, common causes of SrSCD and effects of excercise on cardiovascular function, pre-exercise screening and evaluation of SrSCD, in order to understand the latest research progress on SrSCD and provide clues and references for SrSCD research.