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Bone is the most common metastatic site of advanced breast cancer. Bone related events caused by bone metastasis seriously affect the quality of life and survival time of patients. Therefore, in order to improve the quality of life and prolong the survival time of breast cancer patients with bone metastases, it is of great clinical value to investigate the occurrence and development mechanism of bone metastases, explore early diagnosis methods, and pursue abundant and effective treatment methods and drugs for bone metastases. This article mainly reviews the new research progress of bone metastasis of breast cancer from the aspects of molecular mechanism, imaging and biological diagnosis methods, systematic treatment, in order to provide more reference for clinical diagnosis and treatment.

The accuracy of traditional milling force prediction model is low, and it is difficult to provide effective support for the reasonable selection of process parameters in practical production, by synthetically considering the equivalent turning force model of working angle, cutting edge arc and radius of tool tip arc, in this model, the actual turning tool is equivalent to the ideal turning tool model to identify the material constant, the chip flow angle and the average friction angle in the material constitutive equation, according to the oblique cutting model, the shear stress on the main shear plane and the F0 vector of the unit cutting force at different cutting speeds are calculated, thus the instantaneous cutting force on the front face of the end mill can be calculated, the three-dimensional cutting force of end mill in X-Y-Z coordinate system is obtained by coordinate transformation. The prediction of the cutting force model is verified by simulation and experiment.

This study investigates the AD574, a 12-bit analog/digital converter (ADC) produced by American Analog Devices, Inc. (ADI) using bipolar/I2L technology. The test samples are subjected to a total ionizing dose (TID) of 400 Gy(Si) under 60Co γ irradiation. The samples with and without the TID are then subjected to a single-event upset (SEU) test, and the upset times of the output codes under the input signal conditions of 0 V, 1 V, and 2.5 V are obtained. The test results indicate that, after accumulating a total dose of 400 Gy(Si), the upset of the AD574 output code shifts toward the right of the center code value, resulting in a change in the upset times. Furthermore, the mechanism of the TID-SEU synergistic effect for the AD574 is preliminarily analyzed; it is believed that this phenomenon is related to the sensitivity of the ADC internal comparator single-event transient (SET). The amplitude and width of the SET pulse of the comparator with the TID increase significantly; this causes a change in the AD574 output code value upset distribution and the number of upset times. This study on the TID-SEU synergistic effect serves as a useful reference for aerospace components with radiation hardness.

BackgroundBipolar devices used in space radiation environment for a long time are simultaneously threatened by the total ionization dose (TID) effect and single event transient (SET), and there is a synergistic effect between TID and SET. The enhanced low dose rate sensitivity (ELDRS) effect unique to bipolar devices may affect the synergistic effect.PurposeThis study aims to investigate the physical mechanism of TID's impact on the SET in bipolar operational amplifier LM158.MethodsFirst of all, the LM158 samples were irradiated by 60Co γ-ray of a high dose rate of 0.1 Gy·s-1(Si) and a low dose rate of 1×10-4 Gy·s-1(Si). Then, the heavy ion (Tantalum) irradiation test was performed after the total dose was accumulated to 1 000 Gy(Si). The output single event transients of irradiated LM158 were observed by oscilloscope, and all the collected SETs were saved in computer and processed by MATLAB programming.ResultsThe experimental results show that the TID of bipolar operational amplifier LM158 causes the SET pulse amplitude to decrease and pulse width to expand. At the same time, compared with the high dose rate irradiation condition, the SET pulse width of LM158 is expanded by 50% under the low dose rate irradiation condition.ConclusionsThe study indicates that the interface trap charge accumulated in the bipolar transistor is the fundamental reason for the synergistic effect of TID and SET.

In the treatment of central nervous system (CNS) diseases such as glioma, Alzheimer's disease (AD) and Parkinson's disease (PD), drugs are expected to reach specific areas of the brain to achieve the desired effect. Although a growing number of therapeutic targets have been identified in preclinical studies, the ones that can ultimately be used in the clinic are limited. Therefore, the research process and clinical application of drugs for treating CNS diseases are still large challenges. Physiological barriers such as the blood–brain barrier (BBB) act as selective permeable membranes, allowing only certain molecules to enter the brain; this barrier is the major obstacle restricting the arrival of most drugs to brain lesions. Recently, nanoparticles, including lipid-based, cell-derived biomimetic, polymeric and inorganic nanoparticles, have gained increasing attention because of their ability to cross physiological barriers, and could play an important role as delivery carriers and immunomodulators. Additionally, clinical applications of nanoparticles in CNS diseases are underway. This review focuses on the progress of current research on the use of nanoparticles for the treatment of CNS diseases to provide additional insight into the treatment of CNS diseases. [ABSTRACT FROM AUTHOR]

Peptides with suitable aggregation behavior and electrical properties are potential siRNA delivery vectors. However, identifying suitable peptides with ideal delivery and safety features is difficult owing to the variations in amino acid sequences. Here, a holistic program based on computer modeling and single‐cell RNA sequencing (scRNA‐seq) is used to identify ideal siRNA delivery peptides. Stage one of this program consists of a sequential screening process for candidates with ideal assembly and delivery ability; stage two is a cell subtype‐level analysis program that screens for high in vivo tissue safety. The leading candidate peptide selected from a library containing 12 amino acids showed strong lung‐targeted siRNA delivery capacity after hydrophobic modification. Systemic administration of these compounds caused the least damage to liver and lung tissues and has little impact on macrophage and neutrophil numbers. By loading STAT3 siRNA, strong anticancer effects are achieved in multiple models, including patient‐derived xenografts (PDX). This screening procedure may facilitate the development of peptide‐based RNA interference (RNAi) therapeutics. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusion Primary stage IV breast cancer is associated with a poor prognosis. At present, the value of local surgical treatment for patients with stage IV breast cancer remains uncertain; therefore, treatment principles remain controversial. Because of the high heterogeneity of these patients, it is often difficult to evaluate their prognoses. As a result, this study aimed to establish a prognostic nomogram to evaluate the prognosis of patients with breast cancer experiencing primary bone metastasis.The clinical characteristics and follow‐up data of patients with primary breast cancer and bone metastasis from 2010 to 2018 were collected from the Surveillance, Epidemiology, and End Results database and from 2013 to 2021 at the Peking Union Medical College Hospital. Patients were divided into training and validation groups. Multivariate Cox regression analysis was used to identify the independent prognostic variables for predicting cancer‐specific survival (CSS). On the basis of these independent risk factors, a nomogram was developed and used calibration curves to evaluate its accuracy. Patients were divided into three risk groups according to their scores and surgery‐related survival curves plotted using the log‐rank test.Overall, 6372 patients were included, with 6319 from the Surveillance, Epidemiology, and End Results database and 53 from the Peking Union Medical College Hospital Breast Surgery Department. Multivariate analysis showed that age, race, marital status, grade, tumor stage, estrogen receptor status, progesterone receptor status, human epidermal growth factor receptor 2 status, and burden of other metastatic lesions were all associated with CSS. Based on these results, a nomogram that predicted the 1‐, 3‐, and 5‐year CSS rates in patients with primary breast cancer and bone metastasis (concordance index > 0.69) was developed. After dividing patients into low‐risk, high‐risk, or super‐high‐risk groups based on nomogram scoring criteria, survival analysis revealed that patients in the low‐ and high‐risk groups had significant survival benefits from primary focal surgery.Independent risk factors for primary breast cancer in patients with bone metastasis were analyzed and a nomogram established to predict CSS. The prognostic tool derived in this study can assist clinicians in predicting the survival and surgical benefits of these patients through scoring, thereby providing further guidance for treatment strategies. [ABSTRACT FROM AUTHOR]

The injectable progestin depot-medroxyprogesterone acetate (DMPA) is a popular contraceptive choice in sub-Saharan Africa although mouse models indicate it weakens genital epithelial integrity and barrier function and increases susceptibility to genital infection. The intravaginal ring NuvaRing® is another contraceptive option that like DMPA suppresses hypothalamic pituitary ovarian (HPO) axis function with local release of progestin (etonogestrel) and estrogen (ethinyl estradiol). As we previously reported that treating mice with DMPA and estrogen averts the loss of genital epithelial integrity and barrier function induced by DMPA alone, in the current investigation we compared genital levels of the cell-cell adhesion molecule desmoglein-1 (DSG1) and genital epithelial permeability in rhesus macaques (RM) treated with DMPA or a NuvaRing®re-sized for RM (N-IVR). While these studies demonstrated comparable inhibition of the HPO axis with DMPA or N-IVR, DMPA induced significantly lower genital DSG1 levels and greater tissue permeability to intravaginally administered low molecular mass molecules. By identifying greater compromise of genital epithelial integrity and barrier function in RM administered DMPA vs. N-IVR, our results add to the growing body of evidence that indicate DMPA weakens a fundamental mechanism of anti-pathogen host defense in the female genital tract. [ABSTRACT FROM AUTHOR]

The FY-4B satellite is one of the second generation of China's geosynchronous meteorological satellites aiming at numerical weather forecasts. The space environment monitoring package (SEMP) onboard the FY-4B is a comprehensive instrument package for plasma, high-energy particle, and energetic neutral particle measurements. The low-energy particle analyzer (LEPA) is one of the instruments of the SEMP and consists of two top hat electrostatic analyzers designed for plasma detection. The electron and ion sensors are back-to-back assembled and are integrated to a shared electronic box. It measures the three-dimensional velocity distribution of low-energy electrons and ions on the geosynchronous orbit. In this paper, we present the ground calibration and in-flight performance of the instrument. With the electrostatic deflectors and the cylindrically symmetric structure, the instrument provides high-cadence measurements of electron and ion velocity distributions with a wide field of view (FOV) of 180° by 100°, an angular resolution of 16.7° × 20°, and a broad energy range for both the electrons and ions from tens of eV to above 30 keV, with a 1 s time resolution. The geometric factors of the electron and ion analyzers are 1.1 × 10−3 cm2·sr·eV/eV and 1.4 × 10−3 cm2·sr·eV/eV, respectively, which fulfills the requirements of the low-energy plasma measurement. The LEPA monitored typical space environment disturbance such as geomagnetic storms and successfully recorded the responses of plasma energy fluxes. Satellite surface charging events were measured, with the highest potentials of −2000 V in the shadow period and −500 V in the nonshadow period. [ABSTRACT FROM AUTHOR]

Oocyte maturation arrest, fertilization failure, and early embryonic arrest are important causes of female infertility, whereas the genetic events that contribute to these processes are largely unknown. Loss‐of‐function of PABPC1L in mice has been suggested to cause female infertility involved in the absence of mature oocytes or embryos in vivo or in vitro. However, the role of PABPC1L in human female reproduction remains largely elusive. In this study, we identified a homozygous missense mutation (c.536G>A, p.R179Q) and a compound heterozygous mutation (c.793C>T, p.R265W; c.1201C>T, p.Q401*) in PABPC1L in two unrelated infertile females characterized by recurrent oocyte maturation abnormalities and early embryonic arrest. These variants resulted in nonfunctional PABPC1L protein and were associated with impaired chromatin configuration and transcriptional silencing in GV oocytes. Moreover, the binding capacity of mutant PABPC1L to mRNAs related to oocyte maturation and early embryonic development was decreased significantly. Our findings revealed novel PABPC1L mutations causing oocyte maturation abnormalities and early embryonic arrest, confirming the essential role of PABPC1L in human female fertility. [ABSTRACT FROM AUTHOR]

The Multiband Ultraviolet Spectrum Imager (MUSI) is an optical remote sensing instrument scheduled to launch on the Fengyun‐4C meteorological satellite in 2024. MUSI is designed to measure the airglow emissions between ∼120 and 160 nm above the East Asia and Pacific region from a geostationary orbit to infer ionospheric parameters. Here we develop a lookup‐table algorithm for retrieving the peak electron density (nmF2) and the Total Electron Content (TEC) from nighttime observations of the OI 135.6 nm emission. The algorithm takes into account the north‐south asymmetry of the equatorial ionization anomaly and the atmospheric variations with solar activity and local time. Analysis of synthetic observations shows that the assumptions made in the algorithm only lead to ∼2%–4% uncertainties in the retrievals under the modeled ionospheric conditions. The algorithm is verified by retrieving nmF2 and TEC from the Global‐Scale Observations of the Limb and Disk (GOLD) mission and comparing with coincided radio measurements. The comparison indicates almost negligible systematic differences (typically less than ∼3%) between the GOLD and the ionosonde nmF2, which are within the error limit of the GOLD retrievals. The accuracy of the GOLD TEC retrievals is shown to be comparable to (or in some sense even better than) that of the measurements from the Global Navigation Satellite System. Several simplified yet robust retrieval methods are also developed, which can be readily implemented for both existing and upcoming missions. Our results promote far ultraviolet (FUV) remote sensing to be a key technology for accurate determination of the ionospheric state. Key Points: We develop a lookup‐table algorithm for ionosphere retrieval with the FUV spectral imager on the Fengyun‐4C geostationary satelliteAssumptions made in the algorithm lead to only ∼2%–4% uncertainties in the nmF2 and Total Electron Content (TEC) retrievals under the modeled ionospheric conditionsThe algorithm is verified by retrieving nmF2 and TEC from the Global‐Scale Observations of the Limb and Disk observations and comparing with external radio measurements [ABSTRACT FROM AUTHOR]

In situ vaccination is a desirable strategy for cancer immunotherapy due to its convenience and capacity to target tumor antigens. Here, an in situ nanovaccine based on a cationic peptide with cholesterol‐modified, DP7‐C, for cancer immunotherapy is rationally designed, and developed a cancer nanovaccine that is easy to preparate. The nanovaccine includes cocktail small interfering RNAs (siRNAs) and immunologic adjuvant CpG ODNs, has synergistic effect in the cancer treatment. This nanovaccine can induce tumor cell death, promote antigen presentation and relieve immune suppression in the tumor microenvironment (TME). Moreover, this nanovaccine is administered to CT26 (hot) and B16F10 (cold) tumor model mice, in which it targeted the primary tumors and induced systemic antitumor immunity to inhibit metastasis. It is validated that the nanovaccine can convert cold tumors into hot tumors. Furthermore, the nanovaccine increased the immune response to anti‐PD‐1 therapy by modulating the TME in both CT26‐ and B16F10‐tumor‐bearing mice. The siRNA cocktail/CpG ODN/self‐assembling peptide nanovaccine is a simple and universal tool that can effectively generate specific tumor cell antigens and can be combined with immuno‐oncology agents to enhance antitumor immune activity. The versatile methodology provides an alternative approach for developing cancer nanovaccines. [ABSTRACT FROM AUTHOR]

Simple Summary: Chimeric antigen receptor (CAR)-T cell therapy has been highly successful in treating hematological malignancies like leukemia and lymphoma, leading to advancements in immunotherapy. The approval of anti-CD19 CAR-T cells by the FDA in 2017 has paved the way for CAR-T therapies to be extended to various cancers, autoimmune disorders, viral infections, and fibrosis. However, the therapy faces challenges, including severe side effects like cytokine release syndrome and graft-versus-host disease. Additionally, CAR-T therapy has limited efficacy against solid tumors and antigen escape, poor persistence, and difficulties in industrialization. Overall, this review provides a comprehensive understanding of the challenges and opportunities associated with CAR-T cell therapy, highlighting the need for further advancements in CAR-T cell construction and production. By facilitating future research and development, CAR-T therapy has the potential to become a powerful tool in the fight against cancer and other diseases. Chimeric antigen receptor (CAR)-T cell therapy is a promising form of immunotherapy that has seen significant advancements in the past few decades. It involves genetically modifying T cells to target cancer cells expressing specific antigens, providing a novel approach to treating various types of cancer. However, the initial success of first-generation CAR-T cells was limited due to inadequate proliferation and undesirable outcomes. Nonetheless, significant progress has been made in CAR-T cell engineering, leading to the development of the latest fifth-generation CAR-T cells that can target multiple antigens and overcome individual limitations. Despite these advancements, some shortcomings prevent the widespread use of CAR-T therapy, including life-threatening toxicities, T-cell exhaustion, and inadequate infiltration for solid tumors. Researchers have made considerable efforts to address these issues by developing new strategies for improving CAR-T cell function and reducing toxicities. This review provides an overview of the path of CAR-T cell development and highlights some of the prominent advances in its structure and manufacturing process, which include the strategies to improve antigen recognition, enhance T-cell activation and persistence, and overcome immune escape. Finally, the review briefly covers other immune cells for cancer therapy and ends with the discussion on the broad prospects of CAR-T in the treatment of various diseases, not just hematological tumors, and the challenges that need to be addressed for the widespread clinical application of CAR-T cell therapies. [ABSTRACT FROM AUTHOR]

Background: Multiple morphological abnormalities of the sperm flagella (MMAF), which is characterized as asthenoteratospermia involving absent, short, bent, coiled, and/or irregular‐caliber flagella, is a rare recessive inherited disorder associated with male infertility. To date, genetic causes of MMAF cases are not fully explored. Methods: Whole‐exome sequencing was conducted to identify pathogenic variants in a patient with MMAF. The functional effect of the identified mutations was investigated by immunofluorescence staining and western blotting. Intracytoplasmic sperm injection was used to assist fertilization for the patient with MMAF. Results: We identified novel biallelic mutations, a splicing variant NC_000004.12:g.146937593C>T (c.254+1G>A), and a nonsense mutation NM_001300761.4:c.1185C>G (NP_001287690.1:p.Tyr395*), in TTC29 from an infertile patient. In addition to the typical MMAF phenotype, the patient also presented aberrant morphology of sperm heads. Further functional experiments confirmed the absence of TTC29 expression in the spermatozoa. We also explored the specific expression pattern of TTC29 in human and mouse spermatogenesis. The outcome of intracytoplasmic sperm injection in the patient was unsuccessful, while additional female risk factors should not be excluded. Conclusions: Our study revealed the novel biallelic mutations in TTC29 in a MMAF patient, which findings expand the mutational spectrum of TTC29 and further contribute to the diagnosis, genetic counseling, and prognosis of male infertility. [ABSTRACT FROM AUTHOR]

Background: Ultrasound is more widely used than mammography for early diagnosis of breast cancer in China as most Chinese women have small and dense mammary glands. This study compared the diagnostic performance of ultrasound and mammography for breast cancer among Chinese women with suspected breast lesions. Methods: From November 2019 to November 2021, we compared the results of ultrasound and mammography for breast lesion diagnosis in 2737 consecutive participants with suspected breast lesions; all patients underwent biopsies. We measured the sensitivity, specificity, and diagnostic accuracy separately. Results: Among the 2737 participants, 2844 breast lesions were detected, including 1935 (68.0%) breast cancers and 909 (32.0%) benign lesions. Of the breast cancers, ultrasound detected 1851 (95.7%), whereas mammography detected 1527 (78.9%). The sensitivity of ultrasound for breast cancer diagnosis was significantly higher than that of mammography (95.7% vs. 78.9%, p < 0.001), whereas the specificity was significantly lower than that of mammography (42.9% vs. 62.3%, p < 0.001). The receiver operating characteristic curves revealed that ultrasound was more accurate in detecting breast cancer than mammography (76.8% vs. 71.3%, p < 0.001). Age, body mass index, and breast density did not influence ultrasound sensitivity and accuracy. Conclusions: Ultrasound is more sensitive and accurate than mammography and detects more breast cancers with a lower specificity. [ABSTRACT FROM AUTHOR]