A spike in coronavirus disease 2019 (COVID-19) has occurred in Southern California since October 2020. Analysis of the severe acute respiratory syndrome coronavirus (SARS-CoV-2) in Southern California prior to October indicated most isolates originated from clade 20C that likely emerged from New York via Europe early in the pandemic. 1 Since then, novel variants of SARS-CoV-2 including those seen in the UK (20I/ 501Y.V1/B.1.1.7), South Africa (20H/501Y.V2/B.1.351), and Brazil (P.1/20J/501Y.V3/B.1.1.248) have emerged with the concern of increased infectivity and virulence. 2,3 Thus, we analyzed variants of SARS-CoV-2 in Southern California to establish whether one of these known strains or a novel variant had emerged. Methods | Regulatory review with waiver of consent was completed by Cedars-Sinai Medical Center (CSMC). From all samples from symptomatic inpatients and ambulatory care (urgent care, primary care, and employee health) that tested positive for SARS-CoV-2 collected from November 22, 2020, to December 28, 2020, at CSMC with cycle threshold values less than 30, a random sample from selected runs and dates within the collection period was sequenced and analyzed (Supplement). In addition, phylogenetic analysis was conducted with CSMC samples and globally representative genomes on January 11, 2021, by utilizing Nextstrain, a collection of open-source tools for visualizing the genetics behind the spread of viral outbreaks. 4 The representative global samples were randomly chosen using a computer algorithm from more than 400 000 available genomes on GISAID (Global Initiative on Sharing All Influenza Data), an open-access global collection of viral genomic data, 5 collected between December 21, 2019, and January 11, 2021 (Supplement). The proportional prevalence of each clade over time in samples from California as a whole and Southern California specifically and presence of any novel lineages discovered worldwide was calculated using publicly available sequences from GISAID (including samples from CSMC), collected between

Peptide–nanoparticle conjugates (PNCs) have recently emerged as a versatile tool for biomedical applications. Synergism between the two promising classes of materials allows enhanced control over their biological behaviors, overcoming intrinsic limitations of the individual materials. Over the past decades, a myriad of PNCs has been developed for various applications, such as drug delivery, inhibition of pathogenic biomolecular interactions, molecular imaging, and liquid biopsy. This paper provides a comprehensive overview of existing technologies that have been recently developed in the broad field of PNCs, offering a guideline especially for investigators who are new to this field.

Neoadjuvant chemotherapy (NAC) prior to surgery and immune checkpoint therapy (ICT) have revolutionized bladder cancer management. However, stratification of patients that would benefit most from these modalities remains a major clinical challenge. Here, we combine single nuclei RNA sequencing with spatial transcriptomics and single-cell resolution spatial proteomic analysis of human bladder cancer to identify an epithelial subpopulation with therapeutic response prediction ability. These cells express Cadherin 12 (CDH12, N-Cadherin 2), catenins, and other epithelial markers. CDH12-enriched tumors define patients with poor outcome following surgery with or without NAC. In contrast, CDH12-enriched tumors exhibit superior response to ICT. In all settings, patient stratification by tumor CDH12 enrichment offers better prediction of outcome than currently established bladder cancer subtypes. Molecularly, the CDH12 population resembles an undifferentiated state with inherently aggressive biology including chemoresistance, likely mediated through progenitor-like gene expression and fibroblast activation. CDH12-enriched cells express PD-L1 and PD-L2 and co-localize with exhausted T-cells, possibly mediated through CD49a (ITGA1), providing one explanation for ICT efficacy in these tumors. Altogether, this study describes a cancer cell population with an intriguing diametric response to major bladder cancer therapeutics. Importantly, it also provides a compelling framework for designing biomarker-guided clinical trials.

This study investigates the long-term effects of deoxynivalenol (DON) consumption on avian growth performance, on the proliferation, apoptosis, and DNA damage of spleen cells, and on intestinal integrity. Two hundred and eight 5-day-old black-feathered Taiwan country chickens were fed diets containing 0, 2, 5, and 10 mg/kg of DON for 16 weeks. Body weight gain of male birds in the 2 mg/kg group was significantly lower than that in the 5 mg/kg group. At the end of trial, feeding DON-contaminated diets of 5 mg/kg resulted in heavier spleens. Moreover, the increase in DON induced cellular proliferation, apoptosis, and DNA damage signals in the spleen, the exception being female birds fed 10 mg/kg of DON showing reduced proliferation. Expression of claudin-5 was increased in jejunum of female birds fed 2 and 5 mg/kg of DON, whereas decreased expression levels were found in male birds. In conclusion, our results verified that DON may cause a disturbance to the immune system and alter the intestinal barrier in Taiwan country chickens, and may also lead to discrepancies in growth performances in a dose- and sex-dependent manner.

Since October 2020, novel strains of SARS-CoV-2 including B.1.1.7, have been identified to be of global significance from an infection and surveillance perspective. While this strain (B.1.1.7) may play an important role in increased COVID rates in the UK, there are still no reported strains to account for the spike of cases in Los Angeles (LA) and California as a whole, which currently has some of the highest absolute and per-capita COVID transmission rates in the country. From the early days of the pandemic when LA only had a single viral genome uploaded onto GISAID we have been at the forefront of generating and analyzing the SARS-CoV-2 sequencing data from the LA region. We report a novel strain emerging in Southern California. Most current cases in the catchment population in LA fall into two distinct subclades: 1) 20G (24% of total) is the predominant subclade currently in the United States 2) a relatively novel strain in clade 20C, CAL.20C strain (∼36% of total) is defined by five concurrent mutations. After an analysis of all of the publicly available data and a comparison to our recent sequences, we see a dramatic growth in the relative percentage of the CAL.20C strain beginning in November of 2020. The predominance of this strain coincides with the increased positivity rate seen in this region. Unlike 20G, this novel strain CAL.20C is defined by multiple mutations in the S protein, a characteristic it shares with both the UK and South African strains, both of which are of significant clinical and scientific interest