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Revealing fine-scale cellular heterogeneity among spatial context and the functional and structural foundations of tissue architecture is fundamental within biological research and pharmacology. Unlike traditional approaches involving single molecules or bulk omics, cutting-edge, spatially resolved transcriptomics techniques offer near-single-cell or even subcellular resolution within tissues. Massive information across higher dimensions along with position-coordinating labels can better map the whole 3D transcriptional landscape of tissues. In this review, we focus on developments and strategies in spatially resolved transcriptomics, compare the cell and gene throughput and spatial resolution in detail for existing methods, and highlight the enormous potential in biomedical research. To accurately reflect organ architecture, spatially resolved transcriptomics aims to provide spatial and expression information at the single cellular level for higher-order reconstruction.In silico methods combine single-cell RNA sequencing (scRNA-seq), in situ hybridization, and prior knowledge to reconstruct spatial transcriptomes of tissues but cannot match coordinates and tend to simplify.Laser capture microdissection (LCM)-based approaches allow full gene single-cell profiling plus position information, but assay only a few cells.RNA imaging provides the expression landscape for millions of cells in situ but detects only targeted transcripts.In situ sequencing provides spatial whole genome-wide expression at the micron level by combining barcoding with NGS but fails to describe individual cells.

Nanoparticle drug delivery systems have proved anti-tumor effects; however, they are not widely used in tumor therapy due to insufficient ability to target specific sites, multidrug resistance to anti-tumor drugs, and the high toxicity of the drugs. With the development of RNAi technology, nucleic acids have been delivered to target sites to replace or correct defective genes or knock down specific genes. Also, synergistic therapeutic effects can be achieved for combined drug delivery, which is more effective for overcoming multidrug resistance of cancer cells. These combination therapies achieve better therapeutic effects than delivering nucleic acids or chemotherapeutic drugs alone, so the scope of combined drug delivery has also been expanded to three aspects: drug-drug, drug-gene, and gene-gene. This review summarizes the recent advances of nanocarriers to co-delivery agents, including i) the characterization and preparation of nanocarriers, such as lipid-based nanocarriers, polymer nanocarriers, and inorganic delivery carriers; ii) the advantages and disadvantages of synergistic delivery approaches; iii) the effectual delivery cases that are applied in the synergistic delivery systems; and iv) future perspectives in the design of nanoparticle drug delivery systems to co-deliver therapeutic agents.

The present study assessed the link between the frailty index and deaths from all causes or specific causes in patients with chronic kidney disease (CKD). The study data were derived from the National Health and Nutrition Examination Survey (NHANES) (1999-2018) involving 3262 CKD patients. We used 53 multifaceted assessment instruments to measure frailty degree. Multivariable Cox regression analysis was performed, and hazard ratio (HR) and 95% confidence interval (CI) were calculated. The median frailty index was 0.166 (interquartile range [IQR]: 0.01 to 0.665). During the median follow-up period of 9.4 years, a total of 1102 deaths from all causes were recorded, which included 196 cancer-related deaths and 402 heart disease-related deaths. Patients in the highest frailty index tertile showed more risk of dying from cardiovascular illness (adjusted HR 2.00, 95% CI 1.52-2.64), all causes (adjusted HR 1.81, 95% CI 1.54-2.13), and cancer (adjusted HR 1.59, 95% CI 1.09-2.33). The increase in cardiovascular-related deaths, all-cause-related deaths, and cancer-related deaths was 112% (P < 0.001), 85% (P < 0.001), and 72% (P < 0.001), respectively, for every logarithmic unit increase in the frailty index. These associations remained robust in stratified tests by sex, body mass index, age, race, diabetes history, hypertension status, and CKD stages. Our findings suggest that among patients with CKD, the frailty index is linked to both cause-specific and all-cause deaths. A key element of managing CKD should be frailty intervention as the frailty index may indicate prognosis in these patients.

This study empirically examines whether firms' environmental capital expenditures impact institutional investors' investment decisions in the Chinese market. We particularly examine the impact of ownership type on the relationship of environmental capital expenditures and the behavior of different types of institutional investors by classifying institutional investors into two categories, short-term and long-term investors. In addition, this study further investigates whether environmental capital expenditures related to ownership type increase firm value. We find that long-term institutional investors tend to invest in stateowned firms (SOEs) making environmental capital expenditures. Results also indicate that, with governmental backing and encouragement, the market value of SOEs making more environmental capital expenditures is likely to increase. However, no similar results are found for non-SOEs.

Due to the rapid economic development, many listed companies blindly pursue diversification, resulting in the company into the main business diversification, loss of core competitiveness, performance decline and other difficulties, therefore, the means of asset stripping came into being. Taking Humanwell Healthcare as an example, this paper not only analysizes the motivation of enterprise asset stripping, but also measures the economic consequences of enterprise asset stripping from two aspects of market reaction and financial performance. In terms of market reaction, it makes a comprehensive evaluation through the event study method. In the aspect of financial performance, the financial indicators are used to analysize the performance changes of enterprises before and after asset stripping. Through the research of Humanwell Healthcare asset stripping, it can provide reference for other enterprises planning to carry out strategic contraction.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was identified as the etiologic agent associated with coronavirus disease, which emerged in late 2019. In response, we developed a diagnostic panel consisting of 3 real-time reverse transcription PCR assays targeting the nucleocapsid gene and evaluated use of these assays for detecting SARS-CoV-2 infection. All assays demonstrated a linear dynamic range of 8 orders of magnitude and an analytical limit of detection of 5 copies/reaction of quantified RNA transcripts and 1 x 10 50% tissue culture infectious dose/mL of cell-cultured SARS-CoV-2. All assays performed comparably with nasopharyngeal and oropharyngeal secretions, serum, and fecal specimens spiked with cultured virus. We obtained no false-positive amplifications with other human coronaviruses or common respiratory pathogens. Results from all 3 assays were highly correlated during clinical specimen testing. On February 4, 2020, the Food and Drug Administration issued an Emergency Use Authorization to enable emergency use of this panel.

Aryl- and heteroaryl units are present in a wide variety of natural products, pharmaceuticals, and functional materials. The method for reduction of aryl halides with ubiquitous distribution is highly sought after for late-stage construction of various aromatic compounds. The visible-light-driven reduction of aryl halides to aryl radicals by electron transfer provides an efficient, simple, and environmentally friendly method for the construction of aromatic compounds. This review summarizes the recent progress in the generation of aryl radicals by visible-light-driven reduction of aryl halides with metal complexes, organic compounds, semiconductors as catalysts, and alkali-assisted reaction system. The ability and mechanism of reduction of aromatic halides in various visible light induced systems are summarized, intending to illustrate a comprehensive introduction of this research topic to the readers.

A healthy 35 year-old man who had visited Wuhan, China, presented with cough and fever that progressed to pneumonia. This report describes the diagnosis, clinical course, and management of the condition. The case highlights the importance of close coordination between clinicians and public health authorities at the local, state, and federal levels.

Spatially resolved transcriptomics provides genetic information in space toward elucidation of the spatial architecture in intact organs and the spatially resolved cell-cell communications mediating tissue homeostasis, development, and disease. To facilitate inference of spatially resolved cell-cell communications, we here present SpaTalk, which relies on a graph network and knowledge graph to model and score the ligand-receptor-target signaling network between spatially proximal cells by dissecting cell-type composition through a non-negative linear model and spatial mapping between single-cell transcriptomic and spatially resolved transcriptomic data. The benchmarked performance of SpaTalk on public single-cell spatial transcriptomic datasets is superior to that of existing inference methods. Then we apply SpaTalk to STARmap, Slide-seq, and 10X Visium data, revealing the in-depth communicative mechanisms underlying normal and disease tissues with spatial structure. SpaTalk can uncover spatially resolved cell-cell communications for single-cell and spot-based spatially resolved transcriptomic data universally, providing valuable insights into spatial inter-cellular tissue dynamics. Cell-cell communication is a vital feature involving numerous biological processes. Here, the authors develop SpaTalk, a cell-cell communication inference method using knowledge graph for spatially resolved transcriptomic data, providing valuable insights into spatial intercellular tissue dynamics.

Ferroelastic switching in ferroelectric/multiferroic oxides plays a crucial role in determining their dielectric, piezoelectric, and magnetoelectric properties. In thin films of these materials, however, substrate clamping is generally thought to limit the electric-field- or mechanical-force-driven responses to the local scale. Here, we report mechanical-force-induced large-area, non-local, collective ferroelastic domain switching in PbTiO 3 epitaxial thin films by tuning the misfit-strain to be near a phase boundary wherein c/a and a 1 / a 2 nanodomains coexist. Phenomenological models suggest that the collective, c - a - c - a ferroelastic switching arises from the small potential barrier between the degenerate domain structures, and the large anisotropy of a and c domains, which collectively generates much larger response and large-area domain propagation. Large-area, non-local response under small stimuli, unlike traditional local response to external field, provides an opportunity of unique response to local stimuli, which has potential for use in high-sensitivity pressure sensors and switches. Clamping effects in ferroelestastic thin films limits their usefulness for applications such as sensitive mechanical sensors. Here, the authors report on non-local mechanical force induced switching in PbTiO 3 thin films by tuning the material to a state of nearly energetically degenerate co-existing domains.