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•Physioxia improves the selectivity of PVA-based mouse HSC cultures.•Selective HSC cultures deplete GvHD-causing T cells.

Cell and gene therapies using haematopoietic stem cells (HSCs) epitomize the transformative potential of regenerative medicine. Recent clinical successes for gene therapies involving autologous HSC transplantation (HSCT) demonstrate the potential of genetic engineering in this stem cell type for curing disease. With recent advances in CRISPR gene-editing technologies, methodologies for the ex vivo expansion of HSCs and non-genotoxic conditioning protocols, the range of clinical indications for HSC-based gene therapies is expected to significantly expand. However, substantial immunological challenges need to be overcome. These include pre-existing immunity to gene-therapy reagents, immune responses to neoantigens introduced into HSCs by genetic engineering, and unique challenges associated with next-generation and off-the-shelf HSC products. By synthesizing these factors in this Review, we hope to encourage more research to address the immunological issues associated with current and next-generation HSC-based gene therapies to help realize the full potential of this field.

The epidemiology of psychiatric symptoms among patients with coronavirus disease 2019 is poorly characterized.

AbstractSeeds, the reproductive organs of plants, are common as trace evidence from crime scenes. Seed evidence could be grouped into several categories based on the types of crimes they are associated with, including child abuse, homicides and drugs. Most commonly, seeds are examined microscopically and identified to the plant species level to show a linkage between persons and places. More recently, forensic researchers have evaluated the potential for extracting and typing DNA from seeds to further individualize the samples. As a model system, tomato seeds were examined microscopically after different cooking treatments and assessed for the potential to DNA type seeds for variety identification. A sufficient quantity and quality of DNA were recovered from uncooked, digested and undigested tomato seeds for amplified fragment length polymorphism (AFLP) analysis; however, any form of cooking destroyed the seed DNA. A simple microscopic analysis was able to distinguish between a cooked tomato seed versus an uncooked seed. This article is intended to provide an overview of case examples and current techniques for the forensic examination of seeds as plant-derived evidence.

The epidemiology of psychiatric symptoms among patients with coronavirus disease 2019 is poorly characterized.

The presence of a quaternary centre—a carbon with four other carbons bonded to it—in any given molecule can have a substantial chemical and biological impact. In many cases, it can enable otherwise challenging chemistry. For example, quaternary centres induce large rate enhancements in cyclization reactions—known as the Thorpe–Ingold effect—which has application in drug delivery for molecules with modest bioavailability1. Similarly, the addition of quaternary centres to a drug candidate can enhance both its activity and its metabolic stability2. When present in chiral ligands3, catalysts4and auxiliaries5, quaternary centres can guide reactions toward both improved and unique regio-, stereo- and/or enantioselectivity. However, owing to their distinct steric congestion and conformational restriction, the formation of quaternary centres can be achieved reliably by only a few chemical transformations6,7. For particularly challenging cases—for example, the vicinal all-carbon8, oxa- and aza-quaternary centres9in molecules such as azadirachtin10,11, scopadulcic acid A12,13and acutumine14—the development of target-specific approaches as well as multiple functional-group and redox manipulations is often necessary. It is therefore desirable to establish alternative ways in which quaternary centres can positively affect and guide synthetic planning. Here we show that if a synthesis is designed such that each quaternary centre is deliberately leveraged to simplify the construction of the next—either through rate acceleration or blocking effects—then highly efficient, scalable and modular syntheses can result. This approach is illustrated using the conidiogenone family of terpenes as a representative case; however, this framework provides a distinct planning logic that is applicable to other targets of similar synthetic complexity that contain multiple quaternary centres.

Pimarane diterpenes are produced by a diverse array of plants, fungi, and bacteria. Many members of this family possess antimicrobial and antiproliferative activities. The pimarane diterpenes are characterized by a tricyclic carbon scaffold comprising three fused six-membered rings and at least three quaternary centers. Here, we describe two convergent, fragment-based strategies toward the synthesis of diaporthein B (3), one of the most highly oxidized pimarane diterpenes. The first approach provided access to the tricyclic carbon scaffold of the target and featured a highly diastereoselective fragment coupling, a novel carbonylative Stille cross-coupling to directly access an α-hydroxyketone from a vinyl iodide, and a tandem aldol cyclization–deprotection cascade. The second route utilized a diastereoselective 1,4-addition of a silyloxyfuran to an unsaturated ketone, followed by an epoxidation–ring opening sequence, to access a highly oxidized intermediate containing two elaborated cyclohexane rings. The chemistry developed herein may ultimately be useful in an eventual synthesis of this class of natural products.

Cordyceps sinensis(CS), a Chinese tonifying herb, has been widely used for centuries in Asian countries as a medicine and a health supplement. Although ample evidence indicates that CS can modulate immune responses, the functional effect of CS on dendritic cells (DCs) is still unclear. This study examines how CS affects human monocyte‐derived DCs in two physiological states: naïve and LPS‐induced inflammatory. Our experimental results demonstrate that CS acts as an activator and maturation inducer of immature DCs by stimulating the expression of costimulatory molecules and proinflammatory cytokines by DCs, enhancing the DC‐induced, allogeneic T cell proliferation, and reducing the endocytic ability of DCs. In contrast, CS suppresses the LPS‐induced, inflammatory response by decreasing the LPS‐induced expression of costimulatory molecules and proinflammatory cytokines by DCs. CS also suppresses the LPS‐induced, DC‐elicited, allogeneic T cell proliferation and shifts the LPS‐activated, DC‐driven Th1 response toward a Th2 response. These results demonstrate that CS differentially regulates the DC activities according to the presence or absence of the inflammatory signs. Restated, with the lack of an ongoing inflammatory environment, CS primes DCs toward a Th1‐type immunity, whereas in a potential inflammatory reaction, CS balances the over‐reactivity of elicited Th1 immunity. This investigation illustrates the Yin‐Yang balancing effects of CS as a medicine and a health supplement.

Convergent syntheses are characterized by the coupling of two or more synthetic intermediates of similar complexity, often late in a pathway. At its limit, a fully convergent synthesis is achieved when commercial or otherwise readily available intermediates are coupled to form the final target in a single step. Of course, in all but exceptional circumstances this level of convergence is purely hypothetical; in practice, additional steps are typically required to progress from fragment coupling to the target. Additionally, the length of the sequence required to access each target is a primary consideration in synthetic design.

To investigate the relative beam lifetime contributions from the Touschek effect and the gas scattering effects, the two unequal bunches method is conventionally used. However, in a multibunch operation, the lifetimes can significantly differ from that measured by the few bunches mode. In this study, we present a method, that we fill every bucket and then measure the beam lifetimes before and after enlarging the transverse beam sizes. This measurement allows us to estimate the Touschek lifetime and the gas scattering lifetime, including the ion effects. According to the measurement results, the Touschek lifetime is longer by 8% when measured by the multibunch method than when estimated by the two unequal bunches method. Also, there is a 54% discrepancy of the gas scattering lifetime. The possible error sources for the two methods are also discussed, and it is obtained that the multibunch method is the superior one.