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Gastrointestinal cancer is one of the leading health problems worldwide, with a high morbidity and mortality. To date, harnessing both the innate and adaptive immune system against cancer provides a selective and effective therapeutic strategy for patients. As a first line defense against cancer, natural killer (NK) cells can swiftly target and lyse tumor cells without prior activation. In addition to its pivotal role in innate immunity, NK cells also play unique roles in the adaptive immune system as it enhance anti-tumor adaptive immune responses through secretion of cytokines and retaining an immunological memory. All these characteristics make NK cell a promising anti-cancer agent for patients. In spite of scarce infiltration and impaired function of NK cells in tumors, and the fact that tumors easily develop resistant mechanisms to evade the attacks from endogenous NK cells, multiple strategies have been developed to boost anti-tumor effect of NK cells and abolish tumor resistance. Some examples include adoptive transfer of NK cells after ex vivo activation and expansion; restoration of NK cell function using immune checkpoint inhibitors, and monoclonal antibody or cytokine treatment. Preclinical data have shown encouraging results, suggesting that NK cells hold great potential in cancer therapy. In this review, we discuss NK cells’ cytotoxicity and modulation function in GI cancer and the current application in clinical therapy.

Iron plays a crucial role in many physiological processes of the human body, but iron is continuously deposited in the brain as we age. Early studies found iron overload is directly proportional to cognitive decline in Alzheimer’s disease (AD). Amyloid precursor protein (APP) and tau protein, both of which are related to the AD pathogenesis, are associated with brain iron metabolism. A variety of iron metabolism-related proteins have been found to be abnormally expressed in the brains of AD patients and mouse models, resulting in iron deposition and promoting AD progression. Amyloid β (Aβ) and hyperphosphorylated tau, two pathological hallmarks of AD, can also promote iron deposition in the brain, forming a vicious cycle of AD development-iron deposition. Iron deposition and the subsequent ferroptosis was found to be a potential mechanism underlying neuronal loss in many neurodegenerative diseases. Iron chelators, antioxidants and hepcidin were found useful for treating AD, which represents an important direction for AD treatment research and drug development in the future. The review explored the deep connection between iron dysregulation and AD pathogenesis, discussed the potential of new hypothesis related to iron dyshomeostasis and ferroptosis, and summarized the therapeutics capable of targeting iron, with the expectation to draw more attention of iron dysregulation and corresponding drug development.

Global navigation satellite system (GNSS) array antenna receivers are effective for suppressing wideband jamming. However, its anti-jamming performance decreases sharply when the number of wideband interference surpasses the number of array elements. Since a large number of jammers are often used in navigation countermeasures, it is crucial to keep array antenna receivers available in such conditions. Aiming at this issue, two main tasks were performed in this research and are presented in this paper: Firstly, the direction sensitivity of the sup-freedom anti-jamming performance is revealed and an anti-jamming method for array antenna receivers based on antenna rotation is proposed. Secondly, in order to determine the optimal rotation angle rapidly, a variable-step iteration algorithm based on gradient descent is proposed. Theoretical analysis and simulation show the effectiveness of the proposed anti-jamming method and the efficiency of the implementation algorithm. In a typical airborne scenario with a maximum azimuth difference of 90°, the anti-jamming ability of the proposed method improved by 21~26 dB and 5~10 dB for arrays adopting the PI (power inversion) and MVDR (minimum variance distortionless response) algorithms, respectively. The iterative efficiency improved by 78.35–99.63% in comparison with a traversal of 0.1° search resolution. The proposed method and algorithm are not limited to airborne scenarios and they might be influential to anti-jamming algorithms in the data domain.

Vascular dementia (VaD) is the second most common type of dementia after Alzheimer's disease (AD), characterized by progressive cognitive impairment, memory loss, and thinking or speech problems. VaD is usually caused by cerebrovascular disease, during which, cerebrovascular endothelial cells (CECs) are vulnerable. CEC dysfunction occurs before the onset of VaD and can eventually lead to dysregulation of cerebral blood flow and blood-brain barrier damage, followed by the activation of glia and inflammatory environment in the brain. White matter, neuronal axons, and synapses are compromised in this process, leading to cognitive impairment. The present review summarizes the mechanisms underlying CEC impairment during hypoperfusion and pathological role of CECs in VaD. Through the comprehensive examination and summarization, endothelial nitric oxide synthase (eNOS)/nitric oxide (NO) signaling pathway, Ras homolog gene family member A (RhoA) signaling pathway, and CEC-derived caveolin-1 (CAV-1) are proposed to serve as targets of new drugs for the treatment of VaD.

Structural health monitoring based on vibration signal analysis has been extensively employed for damage identification. Mainstream machine learning techniques, such as convolutional neural networks (CNN), often rely on single-domain inputs, which may provide limited information for accurate damage identification. To overcome this limitation, this study proposes a novel approach that combines an inner product matrix (IPM) with a parallel CNN (IPM-PCNN) to extract multidimensional features for detecting structural damage in a steel frame structure. The proposed IPM-PCNN framework consists of a one-dimensional (1D) CNN branch for processing time series data, a two-dimensional (2D) CNN branch for handling structural modal data, and several fully connected layers. This unique combination leverages the strengths of both 1D and 2D CNNs to capture temporal and modal features of the signal effectively. To validate the effectiveness and superiority of the proposed method, a five-story steel frame model is used as the research object, and five comparative methods are evaluated under the same experimental conditions. The results demonstrate that the IPM-PCNN model can automatically extract relevant features from the signals to accurately identify structural damage, achieving an accuracy of 96.60% on the test set, outperforming machine learning methods in performance. Furthermore, the internal inference processes of these methods are explored and visualized to provide insights into their decision-making mechanisms.

The Direction of Arrival (DOA) parameter is a key parameter in directional channel modeling for GNSS systems and multipath suppression. However, achieving high-precision, low-complexity DOA estimation of multiple signal sources without requiring a known source number is still a challenge. This paper introduces a satellite navigation DOA parameter estimation method based on deconvolution beamforming. By exploiting the translational invariance property of the uniform linear array pattern, the deconvolution process is applied to the de-spread array pattern of satellite navigation signals, achieving high-precision estimation of DOA parameters. This method can achieve high-precision blind DOA estimation of multiple signal sources while significantly reducing the estimation complexity. Compared with traditional methods, precise DOA estimation can be achieved even in low-signal-to-noise-ratio conditions and with a small number of elements in the array. The theoretical analysis and simulation results verify the effectiveness of the proposed algorithm.

Low Earth Orbit (LEO) satellite communication systems typically achieve identity authentication through the encryption and decryption of two-way information, which requires complex key management systems. In contrast, the integration of navigation and communication (NavCom) signals provides novel opportunities for physical observation and authentication solutions due to its measurement functions. This paper introduces a novel signal authentication scheme based on twice two-way satellite time transfer (TWSTT) for LEO satellite systems. It leverages the non-mutated nature of the clock difference to ascertain the legitimacy of the signal by measuring the clock difference of signals at different instances. Unlike traditional authentication methods, this approach directly exploits the temporal and spatial characteristics of the signal, negating the necessity for intricate authorization key systems. Additionally, it adeptly tackles the challenges posed by spoofing interference. The performance analysis indicates that this scheme can achieve a high detection probability for the repeater spoofing signal in the low carrier-to-noise ratio conditions.

Immune checkpoint inhibitors (ICIs) have limited efficacy in microsatellite stable (MSS) metastatic colorectal cancer (mCRC), and combination therapy needs to be further explored. In this single-arm, open-label, phase II trial (NCT04745130), we evaluate the efficacy and safety of the combination therapy of antiangiogenesis (regorafenib) and ICI (sintilimab) in patients with MSS mCRC. The primary endpoint is overall survival (OS). Secondary endpoints include progression free survival (PFS), objective response rate (ORR), disease control rate (DCR), duration of response (DoR) and safety. The median OS and PFS are 14.1 months (95% CI: 10.5–17.7) and 4.1 months (95% CI: 3.4–4.8), respectively. The ORR is 21.4%, DCR is 63.1%, and DoR is 13.0 months (95% CI: 2.5–23.5). Patients with RAS/RAF wild-type exhibit significantly longer median OS (23.3 months, 95% CI: 10.0–36.6) compared to those with mutations (12.1 months, 95% CI: 8.4–15.8). The combination therapy is well tolerated and has limited toxicity. Biomarker analysis, including transcriptome sequencing and multiplex immunohistochemistry staining are performed. The efficacy of this combination treatment is tied to specific gene expressions governing tumor metabolism. Moreover, the effectiveness of immunotherapy depends on the abundance of immune cells, as well as the distance between immune cells and tumor cells. The combination of targeted therapeutic agents for metastatic colorectal cancer (mCRC) salvage treatment has potential in clinics. Here this group conducts a single-arm, open-label, phase II trial assessing the combination therapy of regorafenib (tyrosine kinase inhibitor) and sintilimab (PD-1 targeting) as a safe and effective salvage-line treatment for mCRC patients who have progressed upon second-line treatment.

Background The prognosis of patients with previously treated advanced gastric or gastroesophageal junction (GEJ) cancer remains poor. Given the robust development of immunotherapy and targeted therapy during the last decades, we aimed to investigate if the combination of traditional second-line chemotherapy with sintilimab and apatinib could bring survival benefits for these patients. Methods In this single-center, single-arm, phase II trial, patients with previously treated advanced gastric or GEJ adenocarcinoma received specific dose level of intravenous paclitaxel or irinotecan (investigator’s choice), 200 mg intravenous sintilimab on day 1, and 250 mg oral apatinib once daily continuously in each cycle until disease progression, intolerable toxicity, or withdrawal of consent. The primary endpoints were objective response rate and progression-free survival. The secondary endpoints were mainly overall survival and safety. Results From May 2019 to May 2021, 30 patients were enrolled. At the data cutoff date (March 19, 2022), the median follow-up duration was 12.3 months and 53.6% (95% CI, 33.9–72.5%) patients achieved objective response. The median progression-free survival and overall survival were 8.5 months (95% CI, 5.4–11.5) and 12.5 months (95% CI, 3.7–21.3), respectively. Grade 3–4 adverse events included hematological toxicities, elevated alanine aminotransferase, elevated aspartate aminotransferase, elevated alkaline phosphatase, elevated gamma-glutamyl transpeptidase, hyperbilirubinemia and proteinuria. The most frequent grade 3–4 adverse event was neutropenia (13.3%). No serious treatment-related adverse events or treatment-related deaths occurred. Conclusion Sintilimab plus apatinib and chemotherapy demonstrates promising anti-tumor activity with manageable safety profile in patients with previously treated advanced gastric or GEJ cancer. Trial registration ClinicalTrials.gov: NCT05025033, 27/08/2021.

Low Earth Orbit (LEO) is of great benefit for the positioning performance of Global Navigation Satellite System (GNSS). To realize the system of LEO-augmented GNSS, three methods to integrate communication and navigation signal for LEO communication system with the least influence on the communication performance are analyzed. The analysis adopts the parameters of IRIDIUM signal as restrictions. This paper gives quantitative comparison of these methods considering CN0(carrier noise power spectral density rate) margin, pseudorange accuracy, Doppler accuracy, and communication loss. For method 1, a low-power navigation signal is added to the communication signal. For method 2, the navigation signal is launched in one or more frames. For method 3, the navigation signal is launched in the frequency band separated to the communication signal. The result shows that the pseudorange accuracy of method 2 is far below method 1 and method 3. However, the difference of Doppler accuracy among the three methods can be emitted. Detailed analysis shows that method 1 is practicable when the communication and navigation signal power rate is 15 dB. It achieves the balance of pseudorange accuracy and bit error rate (BER) performance under this condition. Comprehensive comparison of these methods is given in the last. The result shows that the CN0 margin of the navigation signal for method 3 can be 13.04 dB higher than method 1, based on the accuracy threshold considered in this paper. Methods 1 and 3 have the advantage of high accuracy and high CN0 margin respectively. However, method 3 causes high communication capacity loss. Considering that the main disadvantage of GNSS signals is low CN0, method 3 is a good choice for the LEO-augmented GNSS system. Methods 1 and 3 can be combined to realize both high accuracy and high CN0 margin if possible.