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Pumped storage technology is well-developed, cost-effective, and offers promising future growth. It is crucial to the development of energy storage technology. The work discussed in this paper is concentrated on advancements in pumped hydro storage. The development of pumped storage is demonstrated in three ways in this essay including development history, current situation and future prospects. The use of pumped hydro storage dates back more than a century. Over the past 100 years, it has been split into four distinct periods of development. To get pumped hydro storage to its maximum, several optimization approaches have been made made at each stage. Regarding the state of development, the size of the world's pumped storage has continued to increase. In order to create a new sort of system, pumped storage technology can be combined with other technologies. That is, form a new type of power system, so there is a lot of room for development. Generally speaking, the future development of pumped storage, has great development and good prospects.

STUDY QUESTION Are there differences in Mediator Complex Subunit 12 mutations (MED12) mutation, transcriptomics, and protein expression in uterine myometrium and leiomyomas of Black and White women? SUMMARY ANSWER RNA sequencing, tissue microarray, and immunohistochemistry data revealed that Black and White women have significant differences in their myometrium and leiomyoma profiles. WHAT IS KNOWN ALREADY Black women develop uterine leiomyoma earlier than White women, and are more likely to be anemic, have multiple tumors, undergo hysterectomy at an earlier age, have a higher uterine weight, and report very severe pelvic pain. STUDY DESIGN, SIZE, DURATION Uterine tissues were collected from premenopausal women undergoing hysterectomy or myomectomy at Northwestern University Prentice Women’s Hospital (Chicago, IL) from 2010 to 2021. Tissues were collected from a total of 309 women, including from 136 Black women, 135 White women, and 38 women from other racial groups. A total of 529 uterine leiomyomas (290 from Black women, 184 from White women, and 55 from women of other racial groups) were subjected to molecular analysis. Leiomyoma and matched myometrium from a total of 118 cases including 60 Black women and 58 White women, were used for tissue microarrays, along with 34 samples of myometrium without leiomyoma from White women. PARTICIPANTS/MATERIALS, SETTING, METHODS Tissues from the above patient cohorts were analyzed by tissue microarray, immunohistochemistry, RNA sequencing, and mutation analysis. MAIN RESULTS AND THE ROLE OF CHANCE The results indicated that leiomyoma from Black women have a higher rate of MED12 mutations (79.0%) than those from White women (68.5%) (*P ≤ 0.05). RNA-sequencing analysis in myometrium revealed differentially expressed genes (270 upregulated, 374 downregulated) dependent on race, wherein reactive oxygen species, hypoxia, and oxidative phosphorylation pathways were positively correlated with samples derived from Black patients. The levels of proteins associated with oxidative DNA damage and repair, 8-hydroxyguanosine (8-OHdG), 8-oxoguanine glycosylase (OGG1), heme oxygenase-1 (HO-1), and kelch-like ECH-associated protein 1 (KEAP1), were higher in leiomyoma and matched myometrium, particularly those from Black patients, compared to the control myometrium (with leiomyoma) (***P ≤ 0.001). LARGE SCALE DATA The datasets are available in the NCBI (The BioProject number: PRJNA859428). LIMITATIONS, REASONS FOR CAUTION Myometrium without leiomyoma derived from White patients was used as a control in the tissue microarray analysis, as myometrium without leiomyoma from Black patients was not accessible in large numbers. The RNA sequencing was performed on myometrium tissue with leiomyoma present from 10 White and 10 Black women. However, one sample from a Black woman yielded low-quality RNA-sequencing data and was excluded from further analysis. WIDER IMPLICATIONS OF THE FINDINGS Women with symptomatic leiomyomas have a considerable loss in their quality of life. This study provides information on underlying genetic and molecular defects that may be necessary for future therapeutics targeted at leiomyomas. STUDY FUNDING/COMPETING INTEREST(S) This work was supported by grants from NCI (R01CA254367) and NICHD (P01HD057877). The authors declare no conflict of interest.

The iBNCT project aims to develop “iBNCT001,” a demonstration device of the linac-based neutron irradiation facility for boron neutron capture therapy (BNCT) application. iBNCT001 generates an epithermal neutron beam by irradiating 8 MeV protons accelerated by a linac onto a beryllium target. Currently, the linac can drive an average proton current of 2.1 mA. Several experiments were performed using a water phantom to confirm the main physical characteristics of the neutron beam produced at the irradiation position. The measurement results demonstrated that the maximum thermal neutron flux achievable in the phantom volume was approximately 1.36 × 10 9 cm − 2 s − 1 when a normal beam collimator with a 120 mm diameter was used. This neutron beam intensity was sufficient to complete the irradiation within 30 min using the BNCT approach. In addition to normal beam collimators, extended collimators that protrude 100 mm from the wall were developed. By using an extended collimator, it is possible to prevent interference of the patient’s body with the wall when irradiating head and neck cancers. The measurement results for the extended collimator demonstrated that irradiation with the collimator could be completed within 1 h when the neutron beam is generated with an average proton current of 2.1 mA.

Cervical cancer ranks as the fourth leading cause of cancer-related deaths among women, with low response rates to immune-checkpoint blockade (ICB). Here we conducted a multidimensional analysis encompassing single-cell RNA-seq (scRNA-seq), spatial transcriptomics, and spatial proteomics, combined with genetic and pharmacological perturbations to systematically develop a high-resolution and spatially-resolved map of intra-tumoral expression heterogeneity in cervical squamous cell carcinoma (CSCC). Three context-specific tumor states (Epithelial-cytokeratin (Epi-Krt), epithelial-immune (Epi-imm) and epithelial senescence (Epi-Sen)) that recapitulate squamous differentiation substantially alter the tumor immune microenvironment (TIME). Bidirectional interactions between Epi-Krt malignant epithelial cells and MMP11+ CAF form an immune exclusionary microenvironment through TGFβ pathway signaling mediated by FABP5. Epi-Imm malignant epithelial cells and NK/T cells interact bidirectionally through interferon signaling. Notably, preliminary analysis of the NACI clinical trial (NCT04516616) demonstrated neoadjuvant chemotherapy (NACT) induce a state transition to Epi-Imm with the extent of this transition being associated with pathological complete remission (pCR) to subsequent ICB treatment. These findings provide a comprehensive and nuanced understanding of cellular state diversity and have significant implications for developing novel therapeutic strategies in CSCC and potentially other squamous cancers.

Trimethylamine-N-oxide (TMAO), an intestinal flora metabolite of choline, may aggravate atherosclerosis by inducing a chronic inflammatory response and thereby promoting the occurrence of cerebrovascular diseases. Knowledge about the influence of TMAO-related inflammatory response on the pathological process of acute stroke is limited. This study was designed to explore the effects of TMAO on neuroinflammation, brain injury severity, and long-term neurologic function in mice with acute intracerebral hemorrhage (ICH). We fed mice with either a regular chow diet or a chow diet supplemented with 1.2% choline pre- and post-ICH. In this study, we measured serum levels of TMAO with ultrahigh-performance liquid chromatography-tandem mass spectrometry at 24 h and 72 h post-ICH. The expression level of P38-mitogen-protein kinase (P38-MAPK), myeloid differentiation factor 88 (MyD88), high-mobility group box1 protein (HMGB1), and interleukin-1β (IL-1β) around hematoma was examined by western blotting at 24 h. Microglial and astrocyte activation and neutrophil infiltration were examined at 72 h. The lesion was examined on days 3 and 28. Neurologic deficits were examined for 28 days. A long-term choline diet significantly increased serum levels of TMAO compared with a regular diet at 24 h and 72 h after sham operation or ICH. Choline diet-induced high serum levels of TMAO did not enhance the expression of P38-MAPK, MyD88, HMGB1, or IL-1β at 24 h. However, it did increase the number of activated microglia and astrocytes around the hematoma at 72 h. Contrary to our expectations, it did not aggravate acute or long-term histologic damage or neurologic deficits after ICH. In summary, choline diet-induced high serum levels of TMAO increased the cellular inflammatory response probably by activating microglia and astrocytes. However, it did not aggravate brain injury or worsen long-term neurologic deficits. Although TMAO might be a potential risk factor for cerebrovascular diseases, this exploratory study did not support that TMAO is a promising target for ICH therapy.

A novel multifunctional poly(ionic liquid)s with Brønsted–Lewis dibasic sites, well-defined mesoporous channels, and hydrophobicity show excellent catalytic performance with 21.99 wt% yield of lignin-based monocyclic aromatic compounds.

A high gain low-frequency bow-tie antenna with artificial magnetic conductor and metamaterial lens for ground penetrating radar (GPR) is proposed. Firstly, a bow-tie antenna working in 348-772 MHz frequency band is designed. The substrate is a square with side length of 420 mm. A periodic artificial magnetic conductor reflector is designed. The in-phase reflection region of the unit is 481 MHz-1.44 GHz. The results show that the gain of antenna loaded with reflector is increased by 5 dB. A metamaterial lens based on the zero-index metamaterial element is also proposed to improve the gain. The zero refractive index frequency point is 810 MHz, the unit size of the metamaterial is 60 mm, and the lens size is consistent with the antenna substrate size. The gain of the antenna loaded with artificial magnetic conductor (AMC) reflector and the metamaterial lens is increased by 6.5 dB and the front-to-back ratio is 23 dB. The directivity of the antenna is further optimized. The measured results are in good agreement with the simulations.

Excess electrons play a crucial role in surface reactions on transition metal oxides. However, the role of excess electrons in the selectivity of bond cleavage in photocatalytic reactions is rarely...

Chemotherapy is a widely used and effective adjuvant treatment for cancer, and it has unavoidable damage to female fertility, with statistics showing 38% of women who have received chemotherapy are infertile. How to reduce fertility toxicity while enhancing the oncologic chemotherapy is a clinical challenge. Herein, we developed the co-delivery micelles (BML@PMP), which are composed of a reduction-sensitive paclitaxel prodrug (PMP) for chemotherapy and a CHEK2 inhibitor (BML277) for both fertility protection and chemotherapy enhancement. BML@PMP achieves fertility protection through three actions. (1) Due to the enhanced permeability and retention (EPR) effect, BML@PMP is more enriched in the tumor, while very little in the ovary (about 1/10th of the tumor). (2) Glutathione (GSH) triggers the release of PTX, and with low levels of GSH in the ovary, the amount of PTX released in the ovary is correspondingly reduced. (3) BML277 inhibits oocyte apoptosis by inhibiting the CHEK2-TAp63α pathway. Because of the different downstream targets of CHEK2 in tumor cells and oocytes, BML277 also enhances chemotherapeutic efficacy by reducing DNA damage repair which is activated through the CHEK2 pathway. This bidirectional effect of CHEK2 inhibitor-based co-delivery system represents a promising strategy for improving oncology treatment indices and preventing chemotherapy-associated fertility damage. This article is protected by copyright. All rights reserved.

Background Epigenetic modifications established in mammalian gametes are largely reprogrammed during early development, however, are partly inherited by the embryo to support its development. In this study, we examine CpG island (CGI) sequences to predict whether a mouse blastocyst CGI inherits oocyte-derived DNA methylation from the maternal genome. Recurrent neural networks (RNNs), including that based on gated recurrent units (GRUs), have recently been employed for variable-length inputs in classification and regression analyses. One advantage of this strategy is the ability of RNNs to automatically learn latent features embedded in inputs by learning their model parameters. However, the available CGI dataset applied for the prediction of oocyte-derived DNA methylation inheritance are not large enough to train the neural networks. Results We propose a GRU-based model called CMIC (CGI Methylation Inheritance Classifier) to augment CGI sequence by converting it into variable-length k-mers, where the length k is randomly selected from the range $$k_{\min }$$ k min to $$k_{\max }$$ k max , N times, which were then used as neural network input. N was set to 1000 in the default setting. In addition, we proposed a new embedding vector generator for k-mers called splitDNA2vec. The randomness of this procedure was higher than the previous work, dna2vec. Conclusions We found that CMIC can predict the inheritance of oocyte-derived DNA methylation at CGIs in the maternal genome of blastocysts with a high F-measure (0.93). We also show that the F-measure can be improved by increasing the parameter N, that is, the number of sequences of variable-length k-mers derived from a single CGI sequence. This implies the effectiveness of augmenting input data by converting a DNA sequence to N sequences of variable-length k-mers. This approach can be applied to different DNA sequence classification and regression analyses, particularly those involving a small amount of data.

Particle trajectories around an aircraft will change during a flight; therefore, analyzing particle distribution around the aircraft is necessary to accurately sample aerosols. Both computational fluid dynamics (CFD) simulations and wind tunnel experiments are employed to optimize the sampling zones around an aircraft. The wind tunnel model is the Harbin Y-12, similar to the Twin Otter and King Air. The aircraft head is taken as the coordinate original point. The coordinate X is parallel to the wings, the coordinate Y is parallel to the fuselage, and the coordinate Z is perpendicular to the fuselage. The results show that the closer the distance to the central line for the X direction is, the greater the velocity error is. A suitable position for sampling is under the fuselage because of low turbulence, convenient connection pipelines, and safety considerations. The shadow and enhancement zone area thicknesses gradually increase with increasing particle size. The shadow zone thickness under the fuselage is approximately 20, 70, 110, and 350 mm for particle sizes of 1, 10, 20, and 50 μm, respectively. The greater the distance from the aircraft head for the Y direction is, the smaller the velocity error is. The attack angle has no obvious effect on the flow speed at different positions. The CFD simulation results are in basic agreement with the wind tunnel experiment results. The optimal sampling zone is approximately 2300–6500 mm for the Y direction for the aircraft head, 250–500 mm for the X direction for the aircraft head, and 490–600 mm for the Z direction under the fuselage of aircraft.

Uterine leiomyosarcoma (LMS) is a rare but deadly disease. Due to poor understanding of the molecular and genetic causes of the disease, the diagnosis of LMS has been based primarily on histology. Nuclear atypia is one of hallmarks in LMS, however, it also occurs in 2 clinically benign variants, including smooth muscle tumors with fumarate hydratase alteration (SMT‐FH) and leiomyoma with bizarre nuclei (LM‐BN). In addition to nuclear atypia, many well recognized biomarkers used for LMS are also frequently overexpressed in LM‐BN, and the histogenesis and molecular natures for LM‐BN and LMS remain largely unknown. To characterize the molecular profiling of LMS, SMT‐FH, and LM‐BN, we performed integrated comprehensive genomic profiling including whole‐genome sequencing (WGS) and RNA sequencing and genomic microarray analyses to assess genome‐wide copy number alterations (CNAs) and immunohistochemistry (IHC) in all 3 tumor types. We found that both LM‐BN and LMS showed genomic instability and harbored extensive CNAs throughout the whole genome. By contrast, the SMT‐FH presented its characteristic 1q43‐44 deletions in all cases tested, with minimal CNAs in the rest of genomic regions. Further analyses revealed that LMS and LM‐BN groups showed similar patterns of CNAs that are tended to cluster together and separated from the SMT‐FH group. The integrated molecular profiling enabled the detection of novel and traditional biomarkers and showed excellent discrimination between LM‐BN and LMS. Our study suggests that LM‐BN, despite having similar nuclear atypia to SMT‐FH, showed similar genomic instability but distinct genomic alterations with its malignant counterpart of LMS. The integrated molecular profiling is of clinical importance in characterizing these rare uterine smooth muscle tumors., Leiomyosarcoma and 2 benign mimics (leiomyoma with FH alteration [SMT‐FH] and leiomyoma with bizarre nuclei [LM‐BN]) have characteristic nuclear atypia and often cause diagnostic challenge. LM‐BN and LMS are highly genomically unstable and harbor extensive CNAs in the genome, whereas SMT‐FH shows simple 1q43‐44 deletions. Integrated molecular profiling enabled the detection of novel and traditional biomarkers and showed excellent discrimination between LM‐BN and LMS.

To examine the applicability of Chinese Cumberland Ankle Instability Tool (CAIT-C) and Foot and Ankle Ability Measure (FAAM-C) as inclusion criteria recommended by the International Ankle Consortium (IAC) for study of chronic ankle instability in the Chinese individuals.Cross-sectional comparative design with known groups.Research laboratory.145 participants with chronic ankle instability (CAI) and 66 participants without injury.CAIT-C and FAAM-C Activities of Daily Living (FAAM-C-ADL) and FAAM-C Sports (FAAM-C-Sports).The CAIT-C scores (18.2 ± 5.6), FAAM-C-ADL scores (97.0 ± 4.3) and FAAM-C-Sports scores (92.2 ± 10.3) of the CAI group were all lower than the CAIT-C scores (27.4 ± 3.1), FAAM-ADL scores (99.0 ± 2.1) and FAAM-Sports scores (98.4 ± 3.1) (P 0.01) of the uninjured group. The recommended cutoff score of CAIT-C24 by the IAC for identifying CAI had a sensitivity of 80.7% and a specificity of 84.9%. If the recommended cutoff scores of FAAM-ADL90，FAAM-Sports80 by the IAC as inclusion criteria for the study of CAI were applied, 97% of participants with CAI in this sample would be excluded.The results support the recommended cutoff score of CAIT-C24 by the IAC to identify Chinese individuals with CAI for study. However, the recommended cutoff scores of FAAM-ADL90 and FAAM-Sports80 will exclude most Chinese individuals with CAI having only mild functional impairments.

A high-throughput and selective fluorimetric platform has been constructed for the analysis of ammonia in blood by using a polymer-stabilized metal-organic framework (MOF) of porous NH2-MIL-125, which was coated onto a wettable microwells array constructed on an indium tin oxide (ITO) substrate. It was found that the nitrogen plasma treatment for the ITO substrate could create a super-hydrophilic interface that combined with the hydrophobic pattern yielded a wettable microwells array, enabling the condensation-based enrichment of targets from the sample droplets. Moreover, the NH2-MIL-125 MOF encapsulated using polymers could be firmly coated onto the microwells to act as fluorescent probes for sensing NH3 with enhanced responses. In addition, the use of the polymer polyvinyl pyrrolidone could protect and stabilize the crystals of NH2-MIL-125 probe in aqueous media, revealing the improved hydrophilicity and significantly depressed signal background. The as-developed fluorimetric platform, containing a MOF-coated microwells array, can enable the detection of ammonia in blood, with concentrations ranging linearly from 0.10 to 300 μM. More importantly, this plasma treatment-based fabrication route may hold promise for designing different wettable microwells arrays for the high-throughput detection of multiple targets in the fields of biomedical analysis and environmental monitoring.

Objective To study the role of HMGA2 in promoting angiogenesis in uterine leiomyoma (LM). Design This study involved evaluation of vessel density and angiogenic factors in leiomyomas with HMGA2 overexpression; examining angiogenic factor expression and AKT signaling in myometrial (MM) and leiomyoma cells by introducing HMGA2 overexpression in vitro; and exploring vessel formation induced by HMGA2 overexpression both in vitro and in vivo. Setting University research laboratory. Patients None. Interventions None. Main Outcome Measures The main outcome measures include vessel density in leiomyomas with HMGA2 (HMGA2-LM) or MED12 (MED12-LM) alteration; angiogenic factor expression in primary leiomyoma and in vitro cell line model; and vessel formation in leiomyoma cells with HMGA2 overexpression in vitro and in vivo. Results Angiogenic factors and receptors were significantly upregulated at mRNA and protein levels in HMGA2-LM. Specifically, HMGA2-LM exhibited increased expression of VEGFA, EGF, bFGF, TGFα, VEGFR1, and VEGFR2 compared to MED12-LM and myometrium. Overexpression of HMGA2 in MM and LM cell lines resulted in increased secretion of angiogenesis-associated factors. Secreted factors promoted human umbilical vein endothelial cell (HUVEC) migration, tube formation, and wound healing. HMGA2 overexpression upregulated IGF2BP2 and pAKT, and silencing the IGF2BP2 gene reduced pAKT levels and reduced HUVEC migration. Myometrial cells with stable HMGA2 overexpression exhibited increased colony formation and cell growth in vitro and formed xenografts with increased blood vessels. Conclusions HMGA2-LM have a high vasculature density, which likely contributes to tumor growth and disease burden of this leiomyoma subtype. HMGA2 plays an important role in angiogenesis and the involvement of IGF2BP2-mediated pAKT activity in angiogenesis, which provides a potential novel target for therapy for this subtype of LM.

Background More than 70% of leiomyomas (LM) harbor MED12 mutations, primarily in exon 2 at c.130-131(GG). The cause of MED12 mutations in myometrial cells remains largely unknown. We hypothesized that increased ROS promotes MED12 mutations in myometrial cells through the oxidation of guanine nucleotides followed by misrepair. Methods Genomic oxidative burden (8-OHdG) was evaluated in vitro and in vivo by immunohistochemistry. MED12 mutations were examined by Sanger sequencing and deep sequencing. Transcriptome examined by RNA-seq was performed in myometrium with and without LM, in primary myometrial cells treated with ROS. 8-OHdG mediated misrepair was analyzed by CRISPR/Cas9. Results Uteri with high LM burden had a significantly higher rate of MED12 mutations than uteri with low LM burden. Compelling data suggest that the uterus normally produces reactive oxidative species (ROS) in response to stress, and ROS levels in LM are elevated due to metabolic defects. We demonstrated that genomic oxidized guanine (8-OHdG) was found at a significantly higher level in the myometrium of uteri that had multiple LM compared to myometrium without LM. Transcriptome and pathway analyses detected ROS stress in myometrium with LM. Targeted replacement of guanine with 8-OHdG at MED12 c.130 by CRISPR/Cas9 significantly increased the misrepair of G>T. Exposure of primary myometrial cells to oxidative stress in vitro increased misrepair/mutations as detected by duplex sequencing. Conclusions Together, our data identified a clear connection between increased myometrial oxidative stress and a high rate of MED12 mutations that may underlie the risk of LM development and severity in women of reproductive age. Graphical Abstract

Background More than 70% of leiomyomas (LM) harbor MED12 mutations, primarily in exon 2 at c.130–131(GG). The cause of MED12 mutations in myometrial cells remains largely unknown. We hypothesized that increased ROS promotes MED12 mutations in myometrial cells through the oxidation of guanine nucleotides followed by misrepair. Methods Genomic oxidative burden (8-OHdG) was evaluated in vitro and in vivo by immunohistochemistry. MED12 mutations were examined by Sanger sequencing and deep sequencing. Transcriptome examined by RNA-seq was performed in myometrium with and without LM, in primary myometrial cells treated with ROS. 8-OHdG mediated misrepair was analyzed by CRISPR/Cas9. Results Uteri with high LM burden had a significantly higher rate of MED12 mutations than uteri with low LM burden. Compelling data suggest that the uterus normally produces reactive oxidative species (ROS) in response to stress, and ROS levels in LM are elevated due to metabolic defects. We demonstrated that genomic oxidized guanine (8-OHdG) was found at a significantly higher level in the myometrium of uteri that had multiple LM compared to myometrium without LM. Transcriptome and pathway analyses detected ROS stress in myometrium with LM. Targeted replacement of guanine with 8-OHdG at MED12 c.130 by CRISPR/Cas9 significantly increased the misrepair of G > T. Exposure of primary myometrial cells to oxidative stress in vitro increased misrepair/mutations as detected by duplex sequencing. Conclusions Together, our data identified a clear connection between increased myometrial oxidative stress and a high rate of MED12 mutations that may underlie the risk of LM development and severity in women of reproductive age.

Cervical cancer remains a leading cause of cancer death in women, seriously threatening their physical and mental health. It is an easily preventable cancer with early screening and diagnosis. Although technical advancements have significantly improved the early diagnosis of cervical cancer, accurate diagnosis remains difficult owing to various factors. In recent years, artificial intelligence (AI)-based medical diagnostic applications have been on the rise and have excellent applicability in the screening and diagnosis of cervical cancer. Their benefits include reduced time consumption, reduced need for professional and technical personnel, and no bias owing to subjective factors. We, thus, aimed to discuss how AI can be used in cervical cancer screening and diagnosis, particularly to improve the accuracy of early diagnosis. The application and challenges of using AI in the diagnosis and treatment of cervical cancer are also discussed.

Endometrial cancer (EC) is increasingly undermining female health worldwide, with poor survival rates for advanced or recurrent/metastatic diseases. The application of immune checkpoint inhibitors (ICIs) has opened a window of opportunity for patients with first-line therapy failure. However, there is a subset of patients with endometrial cancer who remain insensitive to immunotherapy alone. Therefore, it is necessary to develop new therapeutic agents and further explore reliable combinational strategies to optimize the efficacy of immunotherapy. DNA damage repair (DDR) inhibitors as novel targeted drugs are able to generate genomic toxicity and induce cell death in solid tumors, including EC. Recently, growing evidence has demonstrated the DDR pathway modulates innate and adaptive immunity in tumors. In this review, we concentrate on the exploration of the intrinsic correlation between DDR pathways, especially the ATM-CHK2-P53 pathway and the ATR-CHK1-WEE1 pathway, and oncologic immune response, as well as the feasibility of adding DDR inhibitors to ICIs for the treatment of patients with advanced or recurrent/metastatic EC. We hope that this review will offer some beneficial references to the investigation of immunotherapy and provide a reasonable basis for “double-checkpoint inhibition” in EC.

Wavefront distortion induced by scattering media seriously affects optical focusing. Wavefront shaping based on a transmission matrix (TM) is useful in controlling light propagation in highly scattering media. Traditional TM generally studies amplitude and phase, but the stochastic nature of the light propagation in the scattering medium also affects its polarization. Based on the binary polarization modulation, we propose a single polarization transmission matrix (SPTM) and achieve single-spot focusing through scattering media. We anticipate that the SPTM will be widely used in wavefront shaping.

Ovarian aging occurs approximately 10 years prior to the natural age-associated functional decline of other organ systems. With the increase of life expectancy worldwide, ovarian aging has gradually become a key health problem among women. Therefore, understanding the causes and molecular mechanisms of ovarian aging is very essential for the inhibition of age-related diseases and the promotion of health and longevity in women. Recently, studies have revealed an association between adipose tissue (AT) and ovarian aging. Alterations in the function and quantity of AT have profound consequences on ovarian function because AT is central for follicular development, lipid metabolism, and hormonal regulation. Moreover, the interplay between AT and the ovary is bidirectional, with ovary-derived signals directly affecting AT biology. In this review, we summarize the current knowledge of the complex molecular mechanisms controlling the crosstalk between the AT and ovarian aging, and further discuss how therapeutic targeting of the AT can delay ovarian aging.

Older age is a major risk factor for colorectal cancer. Macrophage is one of the most abundant immune cell types infiltrated in colorectal cancer, but the contribution of macrophages in elder tumor microenvironment is far from clear. In this study, we first detected the expression of CD206, CD68 in colorectal cancer tissues by multiplex fluorescence immunohistochemical staining. The infiltration of CD68+/CD206+ cells in tumor tissues from old patients was higher than those from young patients. When mixed with CT26 cells, both young and aged TAMs enhanced tumor growth of CT26 cells, but CT26 mixed with aged TAMs form larger tumors compared with young TAMs. CT26 formed more and larger tumors in the abdominal cavity of aged mice compared with young. Total macrophage infiltration and the CD206+ macrophages infiltration were both higher in aged mice compared with young mice. The expression signatures of tumor-associated macrophages altered with ageing and p-NF-κB translocation to nucleus was more significant in TAMs from aged mice compared with young. Our results showed that infiltration of macrophages in colorectal cancer tissues increased with ageing. Macrophages from aged host were more likely to polarize to pro-tumor phenotype, and more powerful in promoting tumor cell proliferation.

This study aims to propose a new treatment model for glioblastoma (GBM). The combination of chemotherapy, molecular targeted therapy and radiotherapy has been achieved in a highly simultaneous manner through the application of a safe, non-toxic, locally sustained drug-releasing composite Nanofiber mesh (NFM). The NFM consisted of biodegradable poly(ε-caprolactone) with temozolomide (TMZ) and 17-allylamino-17-demethoxygeldanamycin (17AAG), which was used in radiation treatment. TMZ and 17AAG combination showed a synergistic cytotoxicity effect in the T98G cell model. TMZ and 17AAG induced a radiation-sensitization effect, respectively. The NFM containing 17AAG or TMZ, known as 17AAG-NFM and TMZ-NFM, enabled cumulative drug release of 34.1% and 39.7% within 35 days. Moreover, 17AAG+TMZ-NFM containing both drugs revealed a synergistic effect in relation to the NFM of a single agent. When combined with radiation, 17AAG+TMZ-NFM induced in an extremely powerful cytotoxic effect. These results confirmed the application of NFM can simultaneously allow multiple treatments to T98G cells. Each modality achieved a significant synergistic effect with the other, leading to a cascading amplification of the therapeutic effect. Due to the superior advantage of sustained drug release over a long period of time, NFM has the promise of clinically addressing the challenge of high recurrence of GBM post-operatively.

An ultra-thin transmitarray (TA) working at 10 GHz with bandwidth of 1.15 GHz is proposed. The TA is designed by arranging two types of phase-shifting cells, with a thickness of only 2.8 mm (0.09 λ 0). The proposed focus TA has an obvious convergence effect for plane wave. It enhances the electric field intensity by 11.85 dB at the focus and can also transform the incident spherical wave into the plane wave. When a substrate cylinder antenna is loaded with the proposed TA, it reaches a peak gain of 17.8 dBi (increased by 8.8 dB) and its half-power beamwidth is reduced from 84° to 11°. The TA is fabricated and measured. The measured results are highly consistent with the simulated results, which validates the good performance of the TA.

Rad50 is a component of MRN (Mre11‐Rad50‐Nbs1), which participates in DNA double‐strand break repair and DNA‐damage checkpoint activation. Here, we sought to investigate the clinical and functional significance of Rad50 in high‐grade serous ovarian cancer (HGSOC). We found that Rad50 was frequently upregulated in HGSOCs and enhanced Rad50 expression inversely correlated with patient survival. In addition, ectopic expression of Rad50 promoted proliferation/invasion and induced EMT of ovarian cancer cells, whereas knockdown of Rad50 led to decreased aggressive behaviors. Mechanistic investigations revealed that Rad50 induced aggressiveness in HGSOC via activation of NF‐κB signaling pathway. Moreover, we identified CARD9 as an interacting protein of Rad50 in ovarian cancer cells and the activation of NF‐κB pathway by Rad50 is CARD9 dependent. Our findings provide evidence that Rad50 exhibits oncogenic property via NF‐κB activation in HGSOC.