Our results imply that tumor-reactive effector T cells were present even in pathologically non-metastatic lymph nodes and could be expanded in vitro in the presence of autologous tumor cells and possibly be applied for ACT.

Our results imply that tumor-reactive effector T cells were present even in pathologically non-metastatic lymph nodes and could be expanded in vitro in the presence of autologous tumor cells and possibly be applied for ACT.

Concomitant double valve pathology in the presence of severe MAC poses significant technical challenges when planning surgical intervention. With continued evolution of valve prosthesis, innovative techniques can be considered with the potential for additional therapeutic benefit.

We present a novel technique of using a rapid deployment surgical aortic valve in combination with open surgical transcatheter mitral valve implantation (TMVI) for severe Mitral Annular Calcification (MAC). The Intuity Elite rapid deployment prosthesis (Edwards Lifesciences, Irvine, CA) was used concomitantly with the Sapien 3 (Edwards Lifesciences, Irvine, CA) transcatheter prosthesis trans-atrially on cardiopulmonary bypass in a patient with critical aortic stenosis and moderate-severe mixed mitral valve disease in the setting of severe MAC (off-label use).

We demonstrate how both technologies can, not only be accommodated, but indeed complement each other achieving an excellent outcome in a high-risk patient.

We demonstrate how both technologies can, not only be accommodated, but indeed complement each other achieving an excellent outcome in a high-risk patient.

Traditional markets are important trading places for medicinal plants, and researchers performing market surveys often engage in ethnobotanical research to record the herbal plants used locally and any related traditional knowledge. However, information on market-traded medicinal plants from traditional markets in the Lijiang area of Yunnan is not well documented. This research is an ethnobotanical survey focusing on medicinal plants traded in the traditional markets of the Lijiang area and contributes to the understanding of medicinal plants and related information used by the Naxi people.

Ethnobotanical surveys were performed for two years (2019-2020). Three traditional markets in the Lijiang area were investigated. The methods we used included literature research, participatory surveys and group discussions. The collected voucher specimens were identified using the botanical taxonomy method and were deposited in the herbarium. The data were analysed through the informant consensus factor and use frequeeloped.

Thermoinducible bioswitches are unique in that the all-or-none switch response is triggered by temperature, which is a global factor that impacts all biochemical reaction processes. To date, temperature-inducible bioswitches rely exclusively on special thermal sensing biomolecules of DNA, RNA, proteins and lipids whose conformations are critically temperature dependent.

This paper extends the traditional thermal switch by utilizing purposely designed network topologies of biomolecular interactions to achieve the switching function. By assuming the general Arrhenius law for biochemical reactions, we explore the full space of all three-node genetic interaction networks to screen topologies capable of thermal bioswitches. Three target bioswitches, i.e., thermal-inducible Off-On, cold-inducible On-Off, and hybrid Off-On-Off double switches, are considered separately.

We identify the minimal and core network skeletons that are basic and essential for building robust high-performance bioswitches three Off-On motifs, three On-Off motifs, and an incoherent feedforward motif for an Off-On-Off double switch. Functional topologies are implicitly preferential in choosing parameter values to achieve the target functions. The scenario of the topology-based bioswitch we propose here is an extension of molecule-based bioswitches and would be valuable in aiding the rational design and synthesis of efficient high-performance thermal bioswitches.

We identify the minimal and core network skeletons that are basic and essential for building robust high-performance bioswitches three Off-On motifs, three On-Off motifs, and an incoherent feedforward motif for an Off-On-Off double switch. Functional topologies are implicitly preferential in choosing parameter values to achieve the target functions. The scenario of the topology-based bioswitch we propose here is an extension of molecule-based bioswitches and would be valuable in aiding the rational design and synthesis of efficient high-performance thermal bioswitches.

Despite continuous developments and advances in the perioperative management of patients suffering from acute aortic dissection type A (AADA), the associated postoperative morbidity and mortality remain high and strongly depend on the preoperative clinical status. The associated postoperative mortality is still hard to predict prior to the surgical procedure. The so-called German Registry of Acute Aortic Dissection Type A (GERAADA) score uses very basic and easily retrievable parameters and was specifically designed for predicting the 30-day mortality rate in patients undergoing surgery for AADA. This study evaluated impact of the GERAADA score in the authors’ institutional results.

Among 101 acute type A aortic dissection patients treated at our hospital during August 2015-March 2021, the GERAADA was calculated individually and retrospectively. Predicted and actual mortalities were assessed, and independent predicted factors were searched. The primary endpoint was defined as comparison of GERAADA scores r further accuracy.

Although the actual mortality was lower than predicted, GERAADA score may impact on the postoperative course. In addition, it would be desirable to add parameters such as the time from onset to arrival, family background, and hemodialysis for further accuracy.

Hypospadias is a congenital anomaly of the male urogenital system. Genetics factors play an important role in its pathogenesis. To search for potential causal genes/variants for hypospadias, we performed exome sequencing in a pedigree with three patients across two generations and a cohort of 49 sporadic patients with hypospadias.

A novel BRAF variant (NM_004333.6 c.362C > A) was found to co-segregate with the hypospadias phenotype in the disease pedigree. In cells overexpressing the BRAF mutant, the phosphorylation level of p38 MAPK was significantly increased as compared with the cells overexpressing the wild-type BRAF or RASopathy-related BRAF mutant. This variant further led to a reduced transcription level of the SRY gene, which is essential for the normal development of the male reproductive system. In the cohortof sporadic patients, we identified two additional variants in p38 MAPK signaling-related genes (TRIM67 and DAB2IP) potentially associated with hypospadias.

Our study expands the phenotypic spectrum of variants affecting p38 MAPK signaling toward the involvement of hypospadias.

Our study expands the phenotypic spectrum of variants affecting p38 MAPK signaling toward the involvement of hypospadias.

Highly contagious respiratory diseases caused by viral infections are a constantly emerging threat, particularly the elderly with the higher risk of developing serious complications. Vaccines are the best strategy for protection against influenza-related diseases. However, the elderly has lower vaccine efficacy than young populationand the age-driven decline of the influenza vaccine efficacy remains unresolved.

This study investigates the effect of an adjuvant, poly-γ-glutamic acid and alum (PGA/Alum) on vaccine efficacy in aged mice (18-months) and its mechanism is investigated using ovalbumin as a model antigen and a commercial pandemic H1N1 (pH1N1)flu vaccine. Antigen trafficking, dendritic cell (DC) activation, and the DC-mediated T cell activation were analyzed via in vivo imaging and flow cytometry. Antigen-specific humoral and cellular immune responses were evaluated in sera and splenocytes from the vaccinated mice. Also, we analyzed gene expression profiles of splenocytes from the vaccinated mice vaccine-immunized aged mice showed a significant increase in vaccine efficacy compared to aged mice administered with vaccine only. The enhanced vaccine efficacy by PGA/Alum is associated with significant increases ofactivation of DCs and effector CD8

T cells and a decrease in age-associated CD8

T cell proportion of splenocytes. Collectively, PGA/Alum adjuvanted flu vaccine may be a promising vaccine candidate for the elderly.

PGA/Alum adjuvanted pH1N1 vaccine-immunized aged mice showed a significant increase in vaccine efficacy compared to aged mice administered with vaccine only. The enhanced vaccine efficacy by PGA/Alum is associated with significant increases of activation of DCs and effector CD8+ T cells and a decrease in age-associated CD8+ T cell proportion of splenocytes. Collectively, PGA/Alum adjuvanted flu vaccine may be a promising vaccine candidate for the elderly.As a promising alternative platform for cellular immunotherapy, natural killer cells (NK) have recently gained attention as an important type of innate immune regulatory cell. NK cells can rapidly kill multiple adjacent cancer cells through non-MHC-restrictive effects. Although tumors may develop multiple resistance mechanisms to endogenous NK cell attack, in vitro activation, expansion, and genetic modification of NK cells can greatly enhance their anti-tumor activity and give them the ability to overcome drug resistance. Some of these approaches have been translated into clinical applications, and clinical trials of NK cell infusion in patients with hematological malignancies and solid tumors have thus far yielded many encouraging clinical results. CAR-T cells have exhibited great success in treating hematological malignancies, but their drawbacks include high manufacturing costs and potentially fatal toxicity, such as cytokine release syndrome. To overcome these issues, CAR-NK cells were generated through genetic engineering and demonstrated significant clinical responses and lower adverse effects compared with CAR-T cell therapy. In this review, we summarize recent advances in NK cell immunotherapy, focusing on NK cell biology and function, the types of NK cell therapy, and clinical trials and future perspectives on NK cell therapy.Genetic and neuropathological evidence strongly implicates aberrant forms of α-synuclein in neurodegeneration. Antibodies specific for α-synuclein phosphorylated at serine 129 (pS129) are selective for the pathological protein aggregates that are characteristic of Parkinson’s disease (PD) and other synucleinopathies, such as dementia with Lewy bodies (DLB) and multiple system atrophy (MSA). Although the etiology of most synucleinopathies remains uncertain, a large body of evidence points to mitochondrial dysfunction. The recent development of animal models based on intracranial injection of α-synuclein pre-formed fibrils (PFFs) has provided a valuable experimental system in which to study the spread and neurotoxicity of α-synuclein aggregates, yet the effects of PFF-induced protein aggregates on mitochondrial function and dynamics have not been rigorously examined in vivo. To help fill this knowledge gap, we injected the striatum of mice unilaterally with well-characterized small length ( less then  30 nm) PFFs or monomeric α-synuclein control and measured the distribution and extent of pS129 α-synuclein-immunoreactive aggregates, the loss of tyrosine hydroxylase-immunoreactive neurons in the substantia nigra, the abundance of mitochondrial proteins, and the activity of mitochondrial respiratory chain components at 3 months and 6 months post injection.