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Abstract Background This study aimed to investigate the effects of immune checkpoint inhibitors (ICIs) versus chemotherapy on the prognosis of real‐world diffuse pleural mesothelioma patients in China. Methods Clinical data of 90 patients with diffuse pleural mesothelioma from 2019 to 2022 were collected from Harbin Medical University Cancer Hospital. Patients were divided into two groups: the ICIs‐treated group (n = 46) and the chemotherapy‐only group (n = 44). The efficacy and safety of immunotherapy relative to chemotherapy at different treatment stages were explored. Results The median progression‐free survival (PFS) was 10.0 and 7.0 months, and the median overall survival (OS) was 24.7 and 15.8 months in the ICIs‐treated group and the chemotherapy group, respectively. The ICIs‐treated group showed an 11% increase in objective response rate (ORR) (52.2% vs. 41.0%) and an 8.0% increase in disease control rate (DCR) (78.3% vs. 70.0%) compared to the chemotherapy group. The Kaplan–Meier curves demonstrated significant PFS (HR: 0.61; 95% CI: 0.38–0.98; p = 0.038) and OS (HR: 0.47; 95% CI: 0.26–0.86; p = 0.011) benefits of receiving immunotherapy over chemotherapy alone. Subgroup analysis according to treatment timing showed the same trend. Conclusion In patients with nonsurgical diffuse pleural mesothelioma, immunotherapy achieved better survival benefits compared to chemotherapy in both first‐ and second‐/third‐line treatments. The early addition of immunotherapy improved survival in patients with nonsurgical diffuse pleural mesothelioma.

Abstract Natural killer (NK) cells play a crucial role in both innate immunity and the activation of adaptive immunity. The activating effect of Mn2+ on cyclic GMP‐AMP(cGAS)–stimulator of interferon genes (STING signaling has been well known, but its effect on NK cells remains elusive. In this study, we identified the vital role of manganese (Mn2+) in NK cell activation. Mn2+ directly boosts cytotoxicity of NK cells and promotes the cytokine secretion by NK cells, thereby activating CD8+ T cells and enhancing their antitumor activity. Furthermore, Mn2+ can simultaneously activate NK‐cell intrinsic cGAS and STING and consequently augment the expression of ubiquitously transcribed tetratricopeptide repeat on chromosome X (UTX to promote the responsiveness of NK cells. Our results contribute to a broader comprehension of how cGAS–STING regulates NK cells. As a potent agonist of cGAS–STING, Mn2+ provides a promising option for NK cell‐based immunotherapy of cancers.

Abstract Immune checkpoint inhibitor (ICI) rechallenge in non‐small cell lung cancer (NSCLC) is a promising therapeutic strategy. The situation for ICI rechallenge can be divided into three categories: adverse events (AEs); resistance to ICIs, and rechallenge becomes compulsive because of tumor relapse while the patients had completed a 2 year course of immunotherapy. However, these categories are still controversial and should be explored further. Through voting at the 6th Straits Summit Forum on Lung Cancer, in this study we summarize the consensus of 147 experts in ICI rechallenges. A total of 97.74% experts agreed to rechallenge; 48.87% experts rechallenge with the original drug, and the others rechallenge with a different drug; 40.3% agreed to rechallenge directly after progression; 88.06% experts agreed to ICI rechallenge with a combination regimen; and factors such as previous performance status score, PD‐1 expression, and age should also be considered. Understanding the the clinical studies in ICI rechallenge could bring us one step closer to understanding the consensus. In patients with advanced NSCLC who have suffered recurrent or distant metastasis after immunotherapy, the option of rechallenge with ICIs is a promising treatment option.

Abstract Immune checkpoint inhibitors (PD‐1/PD‐L1 and CTLA‐4 blockade) have revolutionized the treatment landscape in non‐small cell lung cancer (NSCLC). Secondary resistance to immunotherapy (IO), which poses a substantial challenge in clinical settings, occurs in several initial responders. Currently, new treatment approaches have been extensively evaluated in investigational studies for these patients to tackle this difficult problem; however, the lack of consistency in clinical definition, uniform criteria for enrollment in clinical trials, and interpretation of results remain significant hurdles to progress. Thus, our expert panel comprehensively synthesized data from current studies to propose a practical clinical definition of secondary resistance to immunotherapy in NSCLC in metastatic and neoadjuvant settings. In addition to patients who received IO alone (including IO‐IO combinations), we also generated a definition for patients treated with chemotherapy plus IO. This consensus aimed to provide guidance for clinical trial design and facilitate future discussions with investigators. It should be noted that additional updates in this consensus are required when new data is available.

Objective To describe the health care resource use (HCRU) and costs of patients with systemic sclerosis (SSc) prior to and after diagnosis. Methods This retrospective study used a claims data set (Merative MarketScan; 2015‐2019). Eligible patients with SSc were identified by diagnosis codes and required at least 24 months of enrollment without an SSc diagnosis before their first SSc claim and at least 12 months of enrollment thereafter. Total HCRU and costs were reported for three intervals: 2 years and 1 year before and 1 year after index diagnosis. A general population cohort without SSc was matched 1:1 to the SSC cohort on age and sex for comparison. Results Eligibility criteria identified 902 patients with SSc (mean age: 54 years old; 85% female). Mean per‐member per year costs increased each year from $22,383 to $29,708 to $47,095, 2 years before, 1 year before, and 1 year after index diagnosis versus $10,232 to $9656 to $9714 in the general population cohort. Outpatient settings represented the largest proportion of cost 1 year after SSc diagnosis ($16,392), followed by prescription drugs ($10,692), physician office ($10,523), and inpatient ($9448) settings. Conclusion Patients with SSC accrued greater costs and required more services than a general population cohort. These elevated expenditures and HCRU were observed at least 2 years before an SSc diagnosis and increased over time, reflecting both the progressive, multisystem nature of SSc and potential challenges in diagnosis. These findings suggest that SSc poses a substantial burden on the US health care system and highlights the need for early diagnosis and effective therapies.

Abstract Background Multiple system atrophy (MSA) is a neurodegenerative disease that progresses rapidly and has a poor prognosis. This study aimed to assess the value of video oculomotor evaluation (VOE) in the differential diagnosis of MSA and Parkinson's disease (PD). Methods In total, 28 patients with MSA, 31 patients with PD, and 30 age‐ and sex‐matched healthy controls (HC) were screened and included in this study. The evaluation consisted of a gaze‐holding test, smooth pursuit eye movement (SPEM), random saccade, and optokinetic nystagmus (OKN). Results The MSA and PD groups had more abnormalities and decreased SPEM gain than the HC group (64.29%, 35.48%, 10%, p

Abstract Asthenozoospermia (AZS) is a prevalent contributor to male infertility, characterized by a substantial decline in sperm motility. In recent years, large‐scale studies have explored the interplay between the male reproductive system's microecology and its implications for reproductive health. Nevertheless, the direct association between seminal microecology and male infertility pathogenesis remains inconclusive. This study used 16S rDNA sequencing and multi‐omics analysis to conduct a comprehensive investigation of the seminal microbial community and metabolites in AZS patients. Patients were categorized into four distinct groups: Normal, mild AZS (AZS‐I), moderate AZS (AZS‐II), and severe AZS (AZS‐III). Microbiome differential abundance analysis revealed significant differences in microbial composition and metabolite profiles within the seminal plasma of these groups. Subsequently, patients were classified into a control group (Normal and AZS‐I) and an AZS group (AZS‐II and AZS‐III). Correlation and cross‐reference analyses identified distinct microbial genera and metabolites. Notably, the AZS group exhibited a reduced abundance of bacterial genera such as Pseudomonas, Serratia, and Methylobacterium‐Methylorubrum in seminal plasma, positively correlating with core differential metabolite (hexadecanamide). Conversely, the AZS group displayed an increased abundance of bacterial genera such as Uruburuella, Vibrio, and Pseudoalteromonas, with a negative correlation with core differential metabolite (hexadecanamide). In vitro and in vivo experiments validated that hexadecanamide significantly enhanced sperm motility. Using predictive metabolite‐targeting gene analysis and single‐cell transcriptome sequencing, we profiled the gene expression of candidate target genes PAOX and CA2. Protein immunoblotting techniques validated the upregulation protein levels of PAOX and CA2 in sperm samples after hexadecanamide treatment, enhancing sperm motility. In conclusion, this study uncovered a significant correlation between six microbial genera in seminal plasma and the content of the metabolite hexadecanamide, which is related to AZS. Hexadecanamide notably enhances sperm motility, suggesting its potential integration into clinical strategies for managing AZS, providing a foundational framework for diagnostic and therapeutic advancements.

Abstract Treatment response and prognosis estimation in advanced pulmonary adenocarcinoma are challenged by the significant heterogeneity of the disease. The current Response Evaluation Criteria in Solid Tumors (RECIST) criteria, despite providing a basis for solid tumor response evaluation, do not fully encompass this heterogeneity. To better represent these nuances, we introduce the intertumoral heterogeneity response score (THRscore), a measure built upon and expanding the RECIST criteria. This retrospective study included patients with 3–10 measurable advanced lung adenocarcinoma lesions who underwent first‐line chemotherapy or targeted therapy. The THRscore, derived from the coefficient of variation in size for each measurable tumor before and 4–6 weeks posttreatment, unveiled a correlation with patient outcomes. Specifically, a high THRscore was associated with shorter progression‐free survival, lower tumor response rate, and a higher tumor mutation burden. These associations were further validated in an external cohort, confirming THRscore's effectiveness in stratifying patients based on progression risk and treatment response, and enhancing the utility of RECIST in capturing complex tumor behaviors in lung adenocarcinoma. These findings affirm the promise of THRscore as an enhanced tool for tumor response assessment in advanced lung adenocarcinoma, extending the RECIST criteria's utility.

Abstract With the increasing number of flexible distributed energy resources, it is difficult for the distribution network to control various devices directly. Therefore, managing and dispatching the resources in a cluster way is required. This article proposes an equivalent model‐based asynchronous dispatch framework, which is composed of three layers, the distribution network, clusters, and distributed energy resources. With this framework, economic dispatch is carried out with the equivalent models of clusters, simplifying the dispatch problem of the distribution network. The numerical test results show that the proposed method can significantly reduce the calculation time and maintain high accuracy in the economic dispatch problem.

Abstract Chromosomal instability (CIN) is closely associated to the early detection of several clinical tumours. In this study, the authors first established a novel prognostic model of melanoma using the hub genes of CIN, based on the datasets of The cancer genome atlas‐skin cutaneous melanoma (TCGA‐SKCM) and GSE65904 cohorts. Based on the risk scores of our model, the disease‐specific survival (DSS) prognosis was worse in the high‐risk group. Combining risk score, stage, age, ulceration, and clark factors, a Nomogram was generated to predict 1, 3, 5‐year survival rates, which indicated a good clinical validity. Our finding also showed a correlation between high/low risk and tumour infiltration levels of ‘activated CD8 T cells’ and ‘effector memory CD8 T cells’. Moreover, the authors first performed a CIN‐based tumour clustering analysis using TCGA‐SKCM cases, and identified two melanoma clusters, which exhibit the distinct DSS prognosis and the tumour‐infiltrating levels of CD8 T cells. Taken together, a promising CIN‐related prognostic signature and clustering for melanoma cases were first established in our study.

Abstract Background Genetic disorders ascribe to half of cases of congenital hearing loss. Hearing screening is significant in detecting hearing loss (HL) but weak at diagnosis, which can be complemented by genetic screening. Methods To find a feasible method to accomplish genetic screening and evaluate its advantage when combined with hearing screening, between 1 January 2022, and 10 December 2023, we performed an observational cohort study based on 2488 neonates from the Han population at three hospitals in Jiangsu province. Genetic screening for 20 variants in four common HL‐associated genes by multicolor melting curve analysis (MMCA) and hearing screening were offered concurrently to all participants. Results In total, 170 (6.8%) of 2488 eligible neonates were detected at least one variant and among them, the proportion of referral was higher (p

Abstract Due to its ability to adapt to a variety of electromagnetic (EM) environments, the sensing‐enabled metasurface has garnered significant attention. However, large‐scale EM‐field sensing to obtain more information is still very challenging. Here, an adaptive information metasurface is proposed to enable intelligent sensing and wave manipulating simultaneously or more specifically, to realize intelligent target localization and beam tracking adaptively. The metasurface is composed of an array of meta‐atoms, and each is loaded with two PIN diodes and a sensing‐channel structure, for polarization‐insensitive and programmable beamforming and sensing. By controlling the state of the PIN diode, the proposed meta‐atom has 1‐bit phase response in the designed frequency band, while the sensing loss keeps higher than ‐10 dB for both “ON” and “OFF” states. Hence there is nearly no interaction between the beamforming and sensing modes. Experiments are conducted to show multiple functions of the metasurface, including intelligent target sensing and self‐adaptive beamforming, and the measured results are in good agreement with the numerical simulations and theoretical calculations.

Background The association of age at coronary heart disease (CHD) onset with incident dementia remains unexplored. This study aimed to examine whether younger onset age of CHD is associated with a higher risk of incident dementia. Methods and Results Data were obtained from the UK Biobank. Information on the diagnosis of CHD and dementia was collected at baseline and follow‐ups. Propensity score matching method and Cox proportional hazards models were used to evaluate the association between different ages at CHD onset and incident dementia. A total of 432 667 adults (mean±SD age, 56.9±8.1 years) were included, of whom 11.7% had CHD. Compared with participants without CHD, participants with CHD exhibited higher risks of developing all‐cause dementia, Alzheimer's disease, and vascular dementia. More importantly, younger age at CHD onset (per 10‐year decrease) was significantly associated with elevated risks of all‐cause dementia (hazard ratio [HR], 1.25 [95% CI, 1.20–1.30]; P

Abstract Globally, land alkalinization affecting agricultural development. Considering the increasingly serious effects of alkaline stress on agriculture and environment, phytoremediation may be an efficient way to addressed land alkalinization. Broomcorn millet (Panicum miliaceum L.) is a saline‐alkaline‐tolerant crop and bioenergy crop. However, the molecular mechanism of alkaline response on broomcorn millet remains large gap. To explore the alkaline stress on broomcorn millet and the mitigation of 24‐epicastasterone (BR), the effects of CK (nutrient solution only), CB (nutrient solution + 0.5 mg L−1 BR), AS (alkaline stress), and AB (alkaline stress + 0.5 mg L−1 BR) on TA289 (alkaline‐tolerant) and SA223 (alkaline‐sensitive) were investigated. Alkaline stress enhanced reactive oxygen species and membrane lipid peroxidation. BR boosted antioxidant enzyme activities to reduce oxidative stress. Simultaneously, BR attenuated Na+ toxicity and maintained ion homeostasis. Additionally, BR significantly maintained the physiological structure and photosynthetic properties. Transcriptomic and metabolomic analyses were applied to further evaluate the effect of BR on photosynthetic and antioxidant defense. The results showed that BR significantly reduced the transcriptional responses of photosynthesis and antioxidant defense and promoted the accumulation of effective metabolites such as biliverdin, l‐glutamate, and phosphoric acid. Taken together, BR application can significantly alleviate the damage of alkaline stress to broomcorn millet by altering transcriptional expression and metabolite accumulation and is a simple and effective strategy to alleviate alkaline stress. This study reveals the molecular mechanism of BR to enhance photosynthetic capacity and antioxidant defense of broomcorn millet under alkaline stress, which provides theoretical support for the cultivation of bioenergy crops on alkaline lands and the breeding of alkaline‐tolerant bioenergy varieties.

Abstract Preeclampsia (PE) is a multisystemic and placental inflammatory disease that causes maternal and infant health issues. As one of the active components in peony root extract, paeonol (Pae) exerts anti‐apoptosis and anti‐inflammatory effects. Nonetheless, the protective role of Pae in PE has not yet been characterized. A mouse model of PE was constructed through tail vein injection of 1 mg/d phosphatidylserine/dioleoyl‐phosphatidycholine suspension. The levels of inflammatory cytokines in the placenta were examined via enzyme‐linked immunosorbent assay (ELISA). The mRNA levels of inflammatory cytokines (TNF‐α, IL‐6, IFN‐γ, and IL‐4) and apoptosis markers (Bax, Bcl‐2, and caspase‐3) were tested using quantitative reverse transcription‐polymerase chain reaction (qRT–PCR). Western blot analysis was performed to detect the protein levels of apoptosis markers and Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway‐related molecules. Here, Pae repressed the inflammatory response in the placenta of PE‐like mouse models, as demonstrated by the decreased concentrations and mRNA levels of TNF‐α, IL‐6, and IFN‐γ and the increased concentrations and mRNA levels of IL‐4. Apoptosis in the placentas of PE‐like mouse models was attenuated by Pae, as manifested by the downregulated mRNA and protein levels of Bax and cleaved‐caspase‐3 and the upregulated Bcl‐2. Administration of Pae inhibited the phosphorylation of JAK2 and STAT3 in the placental tissues of PE mice. The JAK2/STAT3 pathway agonist (SC‐39100) reversed Pae treatment‐mediated suppression of placental inflammation and apoptosis in PE mice. Overall, Pae inhibits the JAK2/STAT3 signaling pathway to attenuate placental inflammation and apoptosis in PE mice.

Introduction Mesenteric lymph nodes (MLNs) are central in immune anatomy. MLNs are associated with the composition of gut microbiota, affecting the central system and immune system. Gut microbiota was found to differ among individuals of different social hierarchies. Nowadays, excision of MLNs is more frequently involved in gastrointestinal surgery; however, the potential side effects of excision of MLNs on social dominance are still unknown. Methods MLNs were removed from male mice (7–8 weeks old). Four weeks after MLN removal, social dominance test was performed to investigate social dominance; hippocampal and serum interleukin (IL)‐1β, IL‐10, and tumor necrosis factor‐alpha (TNF‐α) were investigated; and histopathology was used to evaluate local inflammation of the ileum. The composition of the gut microbiota was then examined to understand the possible mechanism, and finally intraperitoneal injection of IL‐10 was used to validate the effect of IL‐10 on social dominance. Results There was a decrease in social dominance in the operation group compared to the control group, as well as a decrease in serum and hippocampal IL‐10 levels, but no difference in serum and hippocampal IL‐1β and TNF‐α levels, and no local inflammation of the ileum after MLN removal. 16S rRNA sequencing analysis showed that the relative abundance of the class Clostridia was decreased in the operation group. This decrease was positively associated with serum IL‐10 levels. Furthermore, intraperitoneal injection of IL‐10 in a subset of mice increased social dominance. Conclusions Our findings suggested that MLNs contributed to maintaining social dominance, which might be associated with reduced IL‐10 and the imbalance of specific flora in gut microbiota.

Abstract Fluorescent probes for detection of CN− still have many limitations, such as small Stokes shift, irreversible, and background interference, which hamper their applications for on‐site detection and bioimaging of CN−. In this work, we design a new CN−‐activatable fluorescent probe (named AHMM) containing an ESIPT (excited‐state intramolecular proton transfer) and hydrogen bond features, which show a large Stokes shift (225 nm) and molecular structural reversible detection. The probe AHMM exhibits an excellent selectivity for CN− without any interference from other anions in aqueous DMSO system. Furthermore, the mechanism of the interaction of AHMM with CN− is concluded by various experiments. The limit of detection of AHMM for CN− is calculated as low as 4.47 × 10−8 M, lower than the concentration of CN− deemed acceptable by WHO (World Health Organization). AHMM can recognize CN− in tap water quantitatively and on‐site by a smartphone APP. Moreover, food samples such as almond and cassava including CN− are visualized by fluorescence imaging. In addition, the probe shows practical applications of CN− imaging in cells and mice. This concept can be applied for designing multifunctional fluorescent probes with ESIPT and reversible characteristics for detection of CN−.

Abstract With the overconsumption of disposable plastics, there is a considerable emphasis on the recycling of waste plastics to relieve the environmental, economic, and health‐related consequences. Here, a sulfur‐assisted pyrolysis strategy is demonstrated for versatile upcycling of plastics into high‐value carbons with an ultrahigh carbon‐atom recovery (up to 85%). During the pyrolysis process, the inexpensive elemental sulfur molecules are covalently bonded with polymer chains, and then thermally stable intermediates are produced via dehydrogenation and crosslinking, thereby inhibiting the decomposition of plastics into volatile small hydrocarbons. In this manner, the carbon products obtained from real‐world waste plastics exhibit sulfur‐rich skeletons with an enlarged interlayer distance, and demonstrate superior sodium storage performance. It is believed that the present results offer a new solution to alleviate plastic pollution and reduce the carbon footprint of plastic industry.

Abstract Aiming at the occluded real‐world face images across illumination, pose, expression, and resolution variations, a robust face recognition for occluded real‐world images using constrained probabilistic sparse network is presented. A constrained probabilistic sparse representation network is constructed to obtain the features of all the training images from a global perspective, and the new network nodes are generated through the random combination of the training images. In the probabilistic sparse representation network, the probabilities of each class of the sparse subspace that the occluded test images individually belong to are defined and calculated. The final classifications of the test images are determined by the joint maximum probability of the network nodes. Meanwhile the second‐order gradient constraint is the first introduced in the probabilistic sparse representation network. It is found that the constraint uses the adjacent pixels of the face images to obtain the local texture similarity, and further use the local texture similarity to distinguish the occlusion and non‐occlusion parts. Thus the constraint can reduce the influence of the occlusion part on face recognition. Extensive experiments with the 12 existing methods on the five face databases demonstrate that the recognition rate of the proposed method is the best than the non‐deep learning methods compared, and the proposed method can obtain nearly the same recognition rate with an advantage of a very less time consumption compared to the state‐of‐the‐art deep learning methods.

Abstract Proso millet (Panicum miliaceum L.) has potential applications as a new source of bioenergy owing to its high‐yielding C4 attribute. Besides, it has a short life cycle, high harvest index, low planting costs, and strong adaptability and resistance. This study comprehensively reveals the sodium ion (Na+) toxicity resistance strategies from germination to the seedling stage, root to leaf, outside to inside, macro to micro, and the phenotype to the mechanism. Comparative phenotypic and physiological analysis suggested that salt‐tolerant proso millet (ST 47) had better salt tolerance, biomass accumulation, and osmo‐protection than salt‐sensitive proso millet (SS 212). Microstructural analysis indicated that ST 47 could maintain better internal surfaces and intact structures to resist Na+ toxicity and maintain optimal growth. Further, digital RNA sequence analysis indicated that ST 47 could maintain better Na+ and K+ homeostasis by coordinated regulation of transporter genes; the abundance of transcripts involved in chlorophyll metabolism and photosynthesis pathways was higher in ST 47 than SS 212, which contributed to the biomass accumulation. These results suggest that ST 47 resists Na+ toxicity via coordinated physiological, morphological, and molecular mechanisms. Therefore, this crop can serve as an emerging salt‐tolerant bioenergy crop for sustainable saline agriculture and simultaneous phytoremediation.

Abstract Background Kidney cancer is one of the most common solid tumors. The advancement of human kidney cancer research and treatment has been hindered by a lack of research models that faithfully recapitulate the diversity of the disease. Methods We established an effective three‐dimensional culture system for generating kidney cancer organoids from clinical renal cell carcinoma samples. Renal cell carcinoma (RCC) organoids were characterized by H&E staining, immunofluorescence, whole‐exome sequencing, RNA sequencing and single‐cell RNA sequencing. The use of RCC organoids in personalized cancer therapy was assessed by testing their responses to treatment drugs and chimeric antigen receptor T cells. Results Using this organoid culture system, 33 kidney cancer organoid lines from common kidney cancer subtypes, including clear cell renal cell carcinoma (ccRCC), papillary renal cell carcinoma (pRCC), and chromophobe renal cell carcinoma (chRCC), were generated. RCC organoids preserved the histological architectures, mutational landscapes, and transcriptional profile of the parental tumor tissues. Single‐cell RNA‐sequencing revealed inter‐ and intra‐tumoral heterogeneity in RCC organoids. RCC organoids allowed for in vitro drug screening and provided a tool for assessing the efficacy of chimeric antigen receptor T cells. Conclusions Patient‐derived RCC organoids are valuable pre‐clinical models for academic research and personalized medicine.

Abstract Human–robot collaboration is playing more and more important roles in current deployments of robotic systems in our lives. Haptic perception and intelligent control are essential to ensure safety and efficiency of human–robot interaction. However, existing robotic sensory and control systems are deficient in terms of performance issues, complexity, and cost. Here, the authors report a multifunctional electronic skin (e‐skin) incorporating multiple perceptions with intelligent robotic control, by which robots can safely and dexterously interact with humans. The e‐skin with a simple and cost‐effective sensory structure has multimodal perceptions of proximity, temperature, contact force, and contact position with broad measuring range, high sensitivity, and fast response. The e‐skin is applied onto robots to accomplish obstacle avoidance, safe and dexterous human–robot interaction, smart teaching, and playing Tai‐Chi, which demonstrate a broad range of applications for intelligent robots equipped with e‐skins.

Abstract Conventional antiplatelet agents indiscriminately inhibit both thrombosis and hemostasis, and the increased bleeding risk thus hampers their use at more aggressive dosages to achieve adequate effect. Blocking integrin αIIbβ3 outside‐in signaling by separating the β3/Src interaction, yet to be proven in vivo, may nonetheless resolve this dilemma. Identification of a specific druggable target for this strategy remains a fundamental challenge as Src SH3 is known to be responsible for binding to not only integrin β3 but also the proteins containing the PXXP motif. In vitro and in vivo mutational analyses show that the residues, especially E97, in the RT loop of Src SH3 are critical for interacting with β3. DCDBS84, a small molecule resulting from structure‐based virtual screening, is structurally validated to be directed toward the projected target. It specifically disrupts β3/Src interaction without affecting canonical PXXP binding and thus inhibits the outside‐in signaling‐regulated platelet functions. Treatment of mice with DCDBS84 causes a profound inhibition of thrombosis, equivalent to that induced by extremely high doses of αIIbβ3 antagonist, but does not compromise primary hemostasis. Specific targets are revealed for a preferential inhibition of thrombosis that may lead to new classes of potent antithrombotics without hemorrhagic side effects.

Abstract Background Ovarian cancer (OC) is the deadliest gynecological cancer. The absence of biomarkers in early detection and chemotherapy resistance is a principal cause of treatment failure in OC. Methods In this study, next generation sequencing (NGS) was used to sequence the mRNA of 44 OC patients including 14 chemotherapy insensitive and 18 sensitive patients. Differentially expressed genes (DEGs) from OC patients (compared with healthy controls) and chemotherapy sensitive patients (compared with chemotherapy insensitive patients) were identified by edgeR v3.12.0 in R v3.2.2, which were enriched using Gene Ontology (GO) database and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG). The common DEGs in cancer occurring and chemotherapy sensitivity were further screened. Among them, genes participating in chemotherapy sensitivity associated pathways were regarded as chemotherapy sensitivity‐related key genes. Quantitative real‐time PCR (qPCR) and immunohistochemistry (IHC) were used to verify the expression of the key genes. Results We found 1588 DEGs between OC patients and healthy controls (HCs), which were mainly enriched in cell cycle pathway. Meanwhile, 249 DEGs were identified between chemotherapy sensitive and insensitive OC patients, which were mainly enriched in MAPK signaling pathway, ERBB signaling pathway, TNF signaling pathway, and IL‐17 signaling pathway. Thirty‐five DEGs were shared in chemotherapy sensitivity group and cancer occurring group. Among them, there are five genes (JUND, JUNB, MUC5B, NRG1, and NR4A1) participating in the above four chemotherapy sensitivity‐related pathways. It is remarkable that JUND is in the upstream of MUC5B in IL‐17 signaling pathway and their expressions were verified by qPCR and IHC. Conclusions The expression levels of the key genes related to chemotherapy sensitivity might be used as biomarkers to predict the treatment outcome and as a target to improve prognosis.

Background TP73 antisense RNA 1 (TP73‐AS1) is a long noncoding RNA which has been shown to be involved in the progression of multiple malignant tumors. Previous studies have demonstrated the oncogenic role of TP73‐AS1 in breast cancer. However, its molecular mechanism remains largely unknown in breast tumorigenesis. Methods Expression of TP63‐AS1, miRNA‐125a‐3p (miR‐125a) and metadherin (MTDH) was detected by real‐time quantitative PCR and western blotting. The malignancy was evaluated by cell counting kit 8 (CCK‐8), transwell assays, flow cytometry and western blotting. The target binding was confirmed by dual luciferase reporter assay. Xenograft tumor model was performed to detect tumor growth in vivo. Results Expression of TP73‐AS1 was higher in breast cancer tissues and cell lines. Biologically, its knockdown could promote cell apoptosis rate, and inhibit proliferative capacity, migration and invasion ability in HCC‐70 and MB231 cells, accompanied with higher cleaved caspase 3 level and lower Ki67, N‐cadherin and Vimentin level. Moreover, TP73‐AS1 downregulation restrained the tumor growth of HCC‐70 cells in vivo. Mechanically, TP73‐AS1 functioned as a molecular “sponge” for miR‐125a to modulate MTDH, a downstream target of miR‐125a. Intriguingly, both miR‐125a overexpression and MTDH silencing exerted a tumor‐suppressive effect in the malignant progression of HCC‐70 and MB231 cells, which was counteracted by TP73‐AS1 upregulation and miR‐125a downregulation, respectively. Conclusion Knockdown of TP73‐AS1 inhibited cell proliferation, migration and invasion, but facilitated apoptosis in breast cancer cells in vitro through targeting miR‐125a and upregulating MTDH, suggesting a novel TP73‐AS1/miR‐125a/MTDH pathway in the malignant progression of breast cancer.

Abstract Introduction Several studies have investigated the efficacy of human urinary kallidinogenase (HUK) combined with edaravone (Eda) in acute ischemic stroke (AIS) patients. Our aim was to provide the best available evidence for clinical practice and further research programs for stroke treatment. Methods We searched the online database for paper published between January 2015 and April 2021. We calculated weighted mean difference (WMD) or odds risk (OR) and their corresponding 95% confidence interval (95% CI) of reported outcomes between HUK plus Eda and Eda groups for each study. The random‐effect models or fixed‐effect models were used to pool the analysis. Results Thirteen studies with 1242 patients were included. In the pooled analysis, the scores of NIHSS in the HUK plus Eda group were significantly lower than that in patients receiving Eda (WMD = –3.92, 95% CI (–4.82, –3.02), p

Abstract Next‐generation inter‐chip communication requires ultrafast ultra‐compact interconnects. Designer plasmonics offers a possible route towards this goal. Further development of the plasmonic technique to circuit applications requires the direct amplification of plasmonic signals on a compact platform. However, significant signal distortions and limited operational speeds prevent the application of traditional MOS‐based amplifiers to plasmonics. Up to day, the amplification of surface plasmons without phase distortion has remained a scientific challenge. In this work, the concept of parametric amplification (PA) is transplanted to the plasmonics and is realized experimentally an ultrathin reconfigurable PA using a spoof surface plasmon polariton (SSPP) waveguide integrated with tunable and nonlinear varactors. The measured parametric gain in the experiment can reach up to 9.14 dB within a short nonlinear propagation length, for example, six SSPP wavelengths, in excellent agreement with the theoretical prediction. By tuning the bias voltage of varactors, the phase‐matching condition can be precisely controlled over a broad frequency band, enabling the authors to realize the multi‐frequency PA of plasmonic signals. Measured phase responses confirm that the plasmonic parametric amplifier can significantly suppress the signal distortions as compared with the traditional MOS‐based amplifier, which is a property highly desired for ultrafast wireless communication systems and integrated circuits.

Abstract Recently, programmable metamaterials or metasurfaces have been developed to dynamically edit electromagnetic waves for realizing different functions in the same platform. However, the proposed programmable metasurfaces can only control reflected or transmitted wavefronts in half‐space. Here, a “Janus” digital coding metasurface with the capabilities to program various electromagnetic functions in the reflected (with R‐codes) and transmitted (with T‐codes) waves simultaneously is presented. Three PIN diodes are employed to design the metaparticle, and the state of the PIN diodes can be switched to change the reflected and transmitted phases independently. Three schemes achieved by the proposed programmable metasurface are provided as illustrative examples, including anomalous deflections, beam focusing, and scattering reduction in the full space. As a proof‐of‐concept, a prototype composed of 10 × 20 metaparticles is fabricated and the measured results are in good agreement with the designs and numerical results, validating the full‐space modulations enabled by the programmable metasurface. It is expected that the new programmable metasurface can broaden the applications in stealth technologies, imaging systems, and the next generation of wireless communications.

Recently, programmable metasurfaces have aroused great attention for various applications such as beam manipulation, wireless communication, and holograms by modulating the spatial phase or amplitude. However, programmable amplitude‐coding modulations have rarely been investigated due to the difficulty in realizing dynamic control of amplitude. Herein, a real‐time programmable amplitude‐coding metasurface with multifrequency modulation is proposed by integrating PIN diodes and chip attenuators to the metaelement. The element is encoded as “11,” “10,” and “00,” corresponding to the ON/OFF states of two diodes. By switching the two states of the PIN diode, the metaelement exhibits distinctly reflected amplitude responses in three frequencies (2.98, 4.11, and 5.73 GHz). For the whole metasurface, the magnitude of the reflected beam can be modulated with some specific coding patterns. To verify the performance, six coding patterns with 10 × 10 metaelements are designed, and four of them are measured. Experimental results are fundamentally consistent with theoretical designs and simulations. Further a wireless communication demonstration is designed and implemented to perform direct modulation of digital signals without using mixers required in the conventional wireless communication systems. It is envisioned that this work will find applications in new architecture encrypted communication and imaging systems.