Search

Tumor immune microenvironment has been the focus of tumor research in recent years, and its role in tumor regulation has become prominent and has received increasing attention. The imbalance of the tumor immune microenvironment plays an important role in promoting tumor progression, and the adjustment of its instability plays an important role in controlling tumor progression. The theoretical idea of Traditional Chinese Medicine's "Yipingweiqi" is basically the same as that of modern medicine of controlling tumors by maintaining the balance of the immune microenvironment. This study discusses the aspects of tumor immune microenvironment, its destabilization, relationship to tumor progression, importance in Traditional Chinese Medicine, and regulation by Traditional Chinese Medicine with different treatments. In particular, this work focuses on the role of Traditional Chinese Medicine in maintaining the balance of the tumor immune microenvironment and its potential mechanism by using qi benefit, yang warming, dampness eliminating, and heat clearing under the guidance of the principle of "Yipingweiqi". Results will provide reference for the application of Traditional Chinese Medicine in the diagnosis and treatment of tumors.

Objective To investigate the inhibitory effect of cryptotanshinone (CPT) on human breast cancer cell MCF7 and its mechanism. Methods The survival rate of MCF7 cells was measured by MTT assay. Cell apoptosis was detected by Annexin V/PI assay and Hoechst 33258 fluorescence staining assay. Cell cycle and reactive oxygen species were detected by flow cytometry. Cell migration and invasion were detected by cell scratch test and Transwell chamber test. The surface molecules CD44 and CD24 were detected by flow cytometry and microsphere culture. The expression of cell-associated proteins was detected by Western blot. Results CPT inhibited the proliferation of MCF7 cells in a dose-dependent manner, and the 24 h IC50 value was 19.24 μmol/L. Compared with the untreated group, the CPT-treated group showed cell cycle arrested in the S phase, and apoptosis was induced. The results of the cell scratch and Transwell chamber tests showed that CPT significantly inhibited the migration and invasion of MCF7 cells. Furthermore, CPT reduced the CD24-/LowCD44+ cell population in MCF7 cell-derived microspheres. Western blot results showed that CPT could up-regulate the expression of Bax protein, down-regulate the expression of BCL-2, PI3K-p85, Akt, N-cadherin, Twist1, Sox2, Oct4, and Nanog protein, effectively inhibit the phosphorylation of ER-α, and decrease the expression of ABCG2. Conclusion CPT can inhibit the proliferation of MCF7 cells by inhibiting the migration and invasion of MCF7 cells, decreasing the number of CD24-/lowCD44+ cells and affecting the expression of tumor stem cell-related proteins.

STUDY QUESTION Can novel genetic factors contributing to early embryonic arrest in infertile patients be identified, along with the underlying mechanisms of the pathogenic variant? SUMMARY ANSWER We identified a heterozygous variant in the SPRY4 (sprouty RTK signaling antagonist 4) in infertile patients and conducted in vitro and in vivo studies to investigate the effects of the variant/deletion, highlighting its critical role in female reproductive health. WHAT IS KNOWN ALREADY SPRY4 acts as a negative regulator of receptor tyrosine kinases (RTKs) and functions as a tumor suppressor. Its abnormal expression can lead to recurrent miscarriage by affecting trophoblast function. In mice, Spry4 knockout (KO) leads to craniofacial anomalies and growth defects. A human study links the SPRY4 variant to a male patient with isolated hypogonadotropic hypogonadism (IHH), hypothetically impacting gonadotropin-releasing hormone (GnRH) neurons, and causing reproductive dysfunctions. SPRY4 is thus potentially integral in regulating endocrine homeostasis and reproductive function. To date, no study has reported SPRY4 variants associated with female fertility, and a causal relationship has not been established with functional evidence. STUDY DESIGN, SIZE, DURATION Whole-exome sequencing (WES) was performed in 392 infertile women who suffered from primary infertility of unknown reason, and the heterozygous SPRY4 variant were identified in one independent family. The infertile patients presenting were recruited from July 2017 to November 2023. PARTICIPANTS/MATERIALS, SETTING, METHODS Women diagnosed with primary infertility were recruited from the Reproduction Center of Zhongshan Hospital, Fudan University. Genomic DNA was extracted from peripheral blood for WES analysis. The SPRY4 variant were identified through WES, in silico analysis, and variant screening. All variants were confirmed by Sanger sequencing. The effects of the variants were investigated in human embryonic kidney (HEK) 293T (HEK293T) cells via western blotting, and in mouse oocytes and embryos through complementary RNA (cRNA) injection, RNA sequencing, fluorescence, absorbance, and RT-qPCR assays. Gene function was further examined in Spry4 KO mice via histology, western blotting, ELISA, and RT-qPCR assays. MAIN RESULTS AND THE ROLE OF CHANCE We identified a missense heterozygous pathogenic variant in SPRY4 (GRCh38, GenBank: NM_030964.5 , c.157C>T p.(Arg53Trp), rs200531302) that reduces SPRY4 protein levels in HEK293T cells and disrupts the redox system and mitochondrial function in mouse oocyte, and perturbs developmental potential in mouse embryos. These phenotypes could be partially reversed by the exogenous addition of Nrf1 cRNA. Additionally, Spry4−/ − mice exhibit ovarian oxidative stress and decreased ovarian function. LIMITATIONS, REASONS FOR CAUTION Due to the limited WES data and population, we identified only one family with a SPRY4 mutation. The deeper mechanism and therapeutic strategy should be further investigated through mutant mice and recovery experiment. WIDER IMPLICATIONS OF THE FINDINGS Our study has identified a pathogenic variant in SPRY4 associated with early embryonic arrest in humans. These findings enhance our understanding of the role of SPRY4 in early embryonic development and present a new genetic marker for female infertility. STUDY FUNDING/COMPETING INTEREST(S) This work was supported by the National Natural Science Foundation of China (82071643 and 82171655) and Natural Science Foundation of Shanghai (22ZR1456200). None of the authors have any competing interests. TRIAL REGISTRATION NUMBER N/A [ABSTRACT FROM AUTHOR]

It is well-known that(see e.g. Proposition 1.3.17 in [10]) the normalized principal eigenfunction $ \phi_1 $ of single elliptic eigenvalue problem$ -d\Delta \phi -c(x)\phi = \lambda\phi $with Robin boundary condition converges to $ 0 $ as $ d\rightarrow 0^+ $ locally uniformly in $ \{x\in\bar\Omega|\; c(x)<\max_{\bar{\Omega}} c(x)\} $. The method used in [10] is designed for single equation and seems difficult to be applied to the elliptic systems directly. In this paper, we extend the conclusion above to elliptic system by introducing a different approach. [ABSTRACT FROM AUTHOR]

Fanconi anemia (FA) is generally classified as a DNA repair disorder, conferring a genetic predisposition to cancer and prominent bone marrow failure (BMF) in early childhood. Corroborative human and murine studies point to a fetal origin of hematopoietic stem cell (HSC) attrition under replicative stress. Along with intriguing recent insights into non‐canonical roles and domain‐specific functions of FA proteins, these studies have raised the possibility of a DNA repair‐independent BMF etiology. However, deeper mechanistic insight is critical as current curative options of allogeneic stem cell transplantation and emerging gene therapy have limited eligibility, carry significant side effects, and involve complex procedures restricted to resource‐rich environments. To develop rational and broadly accessible therapies for FA patients, the field will need more faithful disease models that overcome the scarcity of patient samples, leverage technological advances, and adopt investigational clinical trial designs tailored for rare diseases. [ABSTRACT FROM AUTHOR]

During the occurrence, development and treatment of gynecological tumors, mainly including cervical cancer, endometrial cancer and ovarian cancer, patients are prone to sleep disorders which seriously affect the quality of life. At present, there are few relevant studies on gynecological tumors associated with sleep disorders, and there is a lack of research on TCM syndromes, so there is no targeted treatment plan. This article mainly introduces the present situation of diagnosis and treatment of sleep disorders caused by gynecological tumors in Chinese and western medicine, to provide reference for further study.

BackgroundBacterial biofilm is a structure formed by bacteria communities living in a self-produced matrix of extracellular polymeric substances (EPS) composed of polysaccharides, proteins, nucleic acids, and so on. In the field of synthetic biology, bacterial biofilms can be transformed into variable active functional materials by regulating the expression of specific bacterial proteins with different gene circuits. However, the weak mechanical properties of bacterial biofilms limit the application of these materials in wearable devices, coatings and building materials. [Propose] This study aims to investigate the effect of expression of fusion protein to the mechanical property of bacterial biofilm, and the non-opportunistic pathogen Bacillus subtilis was selected as model strain.MethodsThe engineering bacterial biofilm was prepared as a block gel by traditional calcium carbonate mineralization method. After characterization with synchrotron radiation X-ray transmission microscope, scanning electron microscope (SEM) and transmission electron microscope (TEM), the mechanical property of the original biofilm and biofilm gel was studied by rheological analysis.ResultsResults of rheological test show that slight increase of the storage modulus is discovered, indicating the enhancement of the mechanical property of biofilm block gel, and the bacterial structure inside the biofilm is complete and remains active.ConclusionsThis study provides a new idea for the biomimetic mineralization of bacterial biofilms and the design and preparation of active functional materials.

This paper deals with the Cauchy problem to the Keller–Segel model coupled with the incompressible 3-D Navier–Stokes equations. Based on so-called Gevrey regularity estimates, which are motivated by the works of Foias and Temam [20], we prove that the solutions are analytic for a small interval of time with values in a Gevrey class of functions. As a consequence of Gevrey estimates, we particularly imply higher-order derivatives of solutions in Besov and Lebesgue spaces. Moreover, we prove that the existence of a positive constant C~{\tilde{C}} such that the initial data (u0,n0,c0):=(u0h,u03,n0,c0){(u_{0},n_{0},c_{0}):=(u_{0}^{h},u_{0}^{3},n_{0},c_{0})} satisfy