Personalized neoantigen cancer vaccines: current progression, challenges and a bright future.

Tumor neoantigens possess specific immunogenicity and personalized therapeutic vaccines based on neoantigens which have shown promising results in some clinical trials, with broad application prospects. However, the field is developing rapidly and there are currently few relevant review articles. Summarizing and analyzing the status of global personalized neoantigen vaccine clinical trials will provide important data for all stakeholders in drug development.

BRD4 phosphorylation regulates the structure of chromatin nanodomains.

The interplay between chromatin structure and phase-separating proteins is an emerging topic in cell biology with implications for understanding disease states. Here, we investigate the functional relationship between bromodomain protein 4 (BRD4) and chromatin architecture. By combining molecular dynamics simulations with live-cell imaging, we demonstrate that BRD4, when mutated at specific N-terminus sites, significantly impacts nucleosome nanodomain (NN) organization and dynamics.

Prevalence and molecular characterization of multi-resistant isolates from clinical bovine mastitis in China.

Different antibiotics are used to treat mastitis in dairy cows that is caused by Antimicrobial resistance in food-producing animals in China has been monitored since 2000. Surveillance data have shown that the prevalence of multiresistant in animals has increased significantly. This study aimed to investigate the occurrence and molecular characteristics of resistance determinants in strains ( = 105) obtained from lactating cows with clinical bovine mastitis (CBM) in China.

Suppression of osteosarcoma progression by engineered lymphocyte-derived proteomes.

Cancer cells tend to develop resistance to chemotherapy and enhance aggressiveness. A counterintuitive approach is to tame aggressiveness by an agent that acts opposite to chemotherapeutic agents. Based on this strategy, induced tumor-suppressing cells (iTSCs) have been generated from tumor cells and mesenchymal stem cells.

Proteomes from AMPK-inhibited peripheral blood mononuclear cells suppress the progression of breast cancer and bone metastasis.

During a developmental process, embryos employ varying tactics to remove unwanted cells. Using a procedure analogous to some of the embryonic cells, we generated a tumor-eliminating conditioned medium (CM) from AMPK-inhibited lymphocytes and monocytes in peripheral blood mononuclear cells (PBMCs). AMPK signaling was inhibited by the application of a pharmacological agent, Dorsomorphin, and the therapeutic effects of their conditioned medium (CM) were evaluated using cell cultures, breast cancer tissues, and a mouse model of mammary tumors and tumor-induced osteolysis.

Estrogen valerate pretreatment with the antagonist protocol does not increase oocyte retrieval in patients with low ovarian response: a randomized controlled trial.

Study Question: Does luteal phase estrogen valerate pretreatment improve oocyte yield and clinical outcomes in patients with low ovarian response during ovarian stimulation with the antagonist protocol?

Summary Answer: Pretreatment with oral estrogen valerate from Day 7 after ovulation to Day 2 of the next menstrual cycle did not increase oocyte yield in patients with a low ovarian response compared to no pretreatment.

What Is Known Already: Previous studies showed that patients with a normal ovarian response can obtain better clinical outcomes after pretreatment with estrogen in the antagonist protocol. For patients with advanced age and low ovarian response, it remains unclear if estrogen valerate pretreatment with the antagonist protocol yields more oocytes and improves pregnancy outcomes.

Curriculum-Based Deep Reinforcement Learning for Quantum Control.

Deep reinforcement learning (DRL) has been recognized as an efficient technique to design optimal strategies for different complex systems without prior knowledge of the control landscape. To achieve a fast and precise control for quantum systems, we propose a novel DRL approach by constructing a curriculum consisting of a set of intermediate tasks defined by fidelity thresholds, where the tasks among a curriculum can be statically determined before the learning process or dynamically generated during the learning process. By transferring knowledge between two successive tasks and sequencing tasks according to their difficulties, the proposed curriculum-based DRL (CDRL) method enables the agent to focus on easy tasks in the early stage, then move onto difficult tasks, and eventually approaches the final task.

Bradykinin-mediated estrogen-dependent depressor response by direct activation of female-specific distribution of myelinated Ah-type baroreceptor neurons in rats.

Aim: To understand the direct impact of bradykinin in autonomic control of circulation through baroreflex afferent pathway.

Methods: The mean arterial pressure (MAP) was monitored while bradykinin and its agonists were applied via nodose (NG) microinjection, the expression of bradykinin receptors (BRs) in the NG (1 -order) and nucleus tractus solitarius (NTS, 2 -order) were tested in adult male, age-matched female, and ovariectomized rats under physiological and hypertensive conditions. Additionally, bradykinin-induced depolarization was also tested in identified baroreceptor and baroreceptive neurons using whole-cell patch-clamp technique.

Live Birth with or without Preimplantation Genetic Testing for Aneuploidy.

Background: Embryo selection with preimplantation genetic testing for aneuploidy (PGT-A) may improve pregnancy outcomes after initial embryo transfer. However, it remains uncertain whether PGT-A improves the cumulative live-birth rate as compared with conventional in vitro fertilization (IVF).

Methods: In this multicenter, randomized, controlled trial, we randomly assigned subfertile women with three or more good-quality blastocysts to undergo either PGT-A or conventional IVF; all the women were between 20 and 37 years of age.

Estrogen-dependent KCa1.1 modulation is essential for retaining neuroexcitation of female-specific subpopulation of myelinated Ah-type baroreceptor neurons in rats.

Female-specific subpopulation of myelinated Ah-type baroreceptor neurons (BRNs) in nodose ganglia is the neuroanatomical base of sexual-dimorphic autonomic control of blood pressure regulation, and KCa1.1 is a key player in modulating the neuroexcitation in nodose ganglia. In this study we investigated the exact mechanisms underlying KCa1.

Deep Reinforcement Learning With Quantum-Inspired Experience Replay.

In this article, a novel training paradigm inspired by quantum computation is proposed for deep reinforcement learning (DRL) with experience replay. In contrast to the traditional experience replay mechanism in DRL, the proposed DRL with quantum-inspired experience replay (DRL-QER) adaptively chooses experiences from the replay buffer according to the complexity and the replayed times of each experience (also called transition), to achieve a balance between exploration and exploitation. In DRL-QER, transitions are first formulated in quantum representations and then the preparation operation and depreciation operation are performed on the transitions.

Intrauterine transplantation of autologous menstrual blood stem cells increases endometrial thickness and pregnancy potential in patients with refractory intrauterine adhesion.

Aim: This study was designed to evaluate the effects of intrauterine transplantation of menstrual blood stem cells (MenSCs) on endometrial thickness and pregnancy outcomes in patients with refractory intrauterine adhesion (IUA).

Methods: This study included a group of infertile women (n = 12, age 22-40 years), with refractory IUA. Autologous MenSCs isolated from the women's menstrual blood were expanded in vitro and transplanted into their uteruses, followed by hormone replacement therapy.

Learning-Based Quantum Robust Control: Algorithm, Applications, and Experiments.

Robust control design for quantum systems has been recognized as a key task in quantum information technology, molecular chemistry, and atomic physics. In this paper, an improved differential evolution algorithm, referred to as multiple-samples and mixed-strategy DE (msMS_DE), is proposed to search robust fields for various quantum control problems. In msMS_DE, multiple samples are used for fitness evaluation and a mixed strategy is employed for the mutation operation.

Inhibition of Endometrial Tiam1/Rac1 Signals Induced by miR-22 Up-Regulation Leads to the Failure of Embryo Implantation During the Implantation Window in Pregnant Mice.

This study assessed first the impact of endometrial Tiam1/Rac1 signals and microRNA-22 (miR-22) on embryo implantation in mice, and then the expression of the above three genes in the endometrium during the embryo implantation window in the natural menstrual cycle in women with repeated implantation failure (RIF) after in vitro fertilization treatment. Four hundred fifty-two Kun-ming female mice and 200 women (70 infertility patients with RIF, 130 women as controls) were entered into this study. Endometrial Tiam1/Rac1 signals and miR-22 expression were studied in clinical and mouse samples and serum estrogen (E2) and progesterone (P) were analyzed in clinical subjects.

Expression of transcriptional repressor Slug gene in mouse endometrium and its effect during embryo implantation.

Slug, a member of the Snail family of zinc-finger transcription factors, is involved in regulating embryonic development and tumorigenesis. The aim of this study was to investigate the expression of Slug in mouse endometrium during early pregnancy and its possible role during embryo implantation. Fluorescence quantitative polymerase chain reaction and immunohistochemistry were applied to detect Slug mRNA and Slug protein expression in endometrium of nonpregnant and early pregnant mice, respectively.

The role of T-lymphoma invasion and metastasis inducing protein 1 in early pregnancy in mice.

T-lymphoma invasion and metastasis inducing protein 1 (Tiam1) is involved in tumorigenesis processes, including cell migration, adhesion and invasion, proteolysis, cytoskeleton reorganization, cell morphological transformation and intracellular signaling. These processes are also critical for embryo implantation, although the role of Tiam1 during embryo implantation remains poorly understood. The aim of this study was to investigate the spatio-temporal expression of Tiam1 in endometria of mice comparing early pregnancy and non-pregnancy.

Expression of phosphatase and tensin homolog deleted on chromosome ten in mouse endometrium and its effect during blastocyst implantation.

The present study was aimed to investigate the expression of tumor suppressor gene PTEN (phosphatase and tensin homolog deleted on chromosome ten) in mouse endometrium during early pregnancy and its possible role during blastocyst implantation. Real-time fluorescent quantitative PCR (FQ-PCR) and immunohistochemical techniques were applied to detect PTEN mRNA and protein expressions in endometrium in un-pregnant and pregnant mice on days 1, 3, 4, 5, 7 of pregnancy, respectively. In addition, PTEN antisense oligonucleotide was injected into the horns of uterus in pregnant mice on day 3 of pregnancy and its effects on blastocyst implantation was detected in vivo.