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Abstract Immune checkpoint blockade (ICB) immunotherapy remains hampered by insufficient immunogenicity and a high‐lactate immunosuppressive tumor microenvironment (TME). Herein, a nanobody‐engineered NIR‐II nanoadjuvant with targeting metabolic reprogramming capability is constructed for potentiating NIR‐II photothermal‐ferroptosis immunotherapy. Specifically, the nanoadjuvant (2DG@FS‐Nb) is prepared by metallic iron ion‐mediated coordination self‐assembly of D‐A‐D type NIR‐II molecules and loading of glycolysis inhibitor, 2‐deoxy‐D‐glucose (2DG), followed by modification with aPD‐L1 nanobody (Nb), which can effectively target the immunosuppressive TME and trigger in situ immune checkpoint blockade. The nanoadjuvants responsively release therapeutic components in the acidic TME, enabling the precise tumor location by NIR‐II fluorescence/photoacoustic imaging while initiating NIR‐II photothermal‐ferroptosis therapy. The remarkable NIR‐II photothermal efficiency and elevated glutathione (GSH) depletion further sensitize ferroptosis to induce severe lipid peroxidation, provoking robust immunogenic cell death (ICD) to trigger anti‐tumor immune response. Importantly, the released 2DG markedly inhibits lactate generation through glycolysis obstruction. Decreased lactate efflux remodels the immunosuppressive TME by suppressing M2 macrophage proliferation and downregulating regulatory T cell levels. This work provides a new paradigm for the integration of NIR‐II phototheranostics and lactate metabolism regulation into a single nanoplatform for amplified anti‐tumor immunotherapy combined with ICB therapy.

Abstract Cone‐beam computed tomography (CBCT) system can provide real‐time 3D images and fluoroscopy images of the region of interest during the operation. Some systems can even offer augmented fluoroscopy and puncture guidance. The use of CBCT for interventional pulmonary procedures has grown significantly in recent years, and numerous clinical studies have confirmed the technology's efficacy and safety in the diagnosis, localization, and treatment of pulmonary nodules. In order to optimize and standardize the technical specifications of CBCT and guide its application in clinical practice, the consensus statement has been organized and written in a collaborative effort by the Professional Committee on Interventional Pulmonology of China Association for Promotion of Health Science and Technology.

Background This study seeks to characterize cardiovascular health (CVH) from early childhood to late adolescence and identify sociodemographic correlates of high CVH that serve as levers for optimizing CVH across early life. Methods and Results Among 1530 youth aged 3 to 20 years from 2 cohorts in the ECHO (Environmental Influences on Child Health Outcomes) consortium, we first derived CVH scores on the basis of the Life's Essential 8 construct comprising 4 behavioral (nicotine use/exposure, physical activity, sleep, and diet) and 4 health factors (body mass index, blood pressure, non–high‐density lipoprotein cholesterol, and fasting glucose) during early childhood (mean age, 3.5 years), middle childhood (8.0 years), early adolescence (13.3 years), and late adolescence (17.8 years). Next, we used generalized regression to estimate the probability of high (versus not high) CVH with respect to sociodemographic characteristics. Overall CVH score was stable across life stages: 81.2±7.6, 83.3±8.0, and 81.7±8.9 of 100 possible points in early childhood, middle childhood, and early adolescence, respectively. Accordingly, during these life stages, most children (63.3%–71.5%) had high CVH (80 to $70 000. These associations were driven by behavioral factors. Conclusions Although most youth maintained high CVH across childhood, the decline by late adolescence indicates that cardiovascular disease prevention should occur before the early teen years. Disparities in high CVH over time with respect to sociodemographic characteristics were explained by behavioral factors, pointing toward prevention targets.

Abstract Background To investigate the sex‐based heterogeneity of immune microenvironmental feature and its impact on the response to first‐line PD‐1 blockade plus chemotherapy in patients with driver‐negative advanced or metastatic non‐small‐cell lung cancer (NSCLC). Patients and Methods A total of 439 patients with advanced NSCLC treated with first‐line PD‐1 blockade plus chemotherapy or chemotherapy were identified. Differences in clinical outcomes between female and male patients were determined using Kaplan–Meier curves. Neoantigen burden and five immune microenvironmental markers expression including PD‐L1, CD4, CD8, FOXP3, and CD68 were compared between two groups. Results Of 175 eligible patients, 89 received PD‐1 blockade plus chemotherapy and 86 received first‐line chemotherapy. Forty five were women (25.7%) and 130 were men (74.3%). Female patients received first‐line PD‐1 blockade in combination with chemotherapy had dramatically better ORR (85.2% vs. 53.2%; p = 0.009), PFS (23.7 vs. 7.3 months; p = 0.013), and OS (46.2 vs. 20.0 months; p = 0.004) than males. Treatment outcomes were similar between females and males in chemotherapy group. Multivariate analyses showed that sex was the independent prognostic factor for patients received PD‐1 blockade combined with chemotherapy. Although female patients had significantly lower tumor mutational and neoantigen burden than males, pretreatment tumor tissues of female patients had markedly higher CD4, CD4/FOXP3, and CD4/FOXP3/PD‐L1 expression level than male patients. Conclusions Female patients with untreated advanced or metastatic NSCLC would derive a larger benefit from PD‐1 blockade in combination with chemotherapy than males. The biological significances of heterogeneity of tumor immune microenvironmental features between them need further investigation.

Abstract Background Circulating tumor DNA (ctDNA) is a promising biomarker for predicting relapse in multiple solid cancers. However, the predictive value of ctDNA for disease recurrence remains indefinite in locoregional gastric cancer (GC). Here, we aimed to evaluate the predictive value of ctDNA in this context. Methods From 2016 to 2019, 100 patients with stage II/III resectable GC were recruited in this prospective cohort study (NCT02887612). Primary tumors were collected during surgical resection, and plasma samples were collected perioperatively and within 3 months after adjuvant chemotherapy (ACT). Somatic variants were captured via a targeted sequencing panel of 425 cancer‐related genes. The plasma was defined as ctDNA‐positive only if one or more variants detected in the plasma were presented in at least 2% of the primary tumors. Results Compared with ctDNA‐negative patients, patients with positive postoperative ctDNA had moderately higher risk of recurrence [hazard ratio (HR) = 2.74, 95% confidence interval (CI) = 1.37–5.48; P = 0.003], while patients with positive post‐ACT ctDNA showed remarkably higher risk (HR = 14.99, 95% CI = 3.08‐72.96; P < 0.001). Multivariate analyses indicated that both postoperative and post‐ACT ctDNA positivity were independent predictors of recurrence‐free survival (RFS). Moreover, post‐ACT ctDNA achieved better predictive performance (sensitivity, 77.8%; specificity, 90.6%) than both postoperative ctDNA and serial cancer antigen. A comprehensive model incorporating ctDNA for recurrence risk prediction showed a higher C‐index (0.78; 95% CI = 0.71–0.84) than the model without ctDNA (0.71; 95% CI = 0.64–0.79; P = 0.009). Conclusions Residual ctDNA after ACT effectively predicts high recurrence risk in stage II/III GC, and the combination of tissue‐based and circulating tumor features could achieve better risk prediction.

Abstract PtII based organometallic photosensitizers (PSs) have emerged as novel potent photodynamic inactivation (PDI) reagents through their enhanced intersystem crossing (ISC) processes. Currently, few PtII PSs have been investigated as antibacterial materials, with relatively poor performances reported and with structure‐activity relationships not well described. Herein, a pair of configurational isomers are reported of Bis‐BODIPY (4,4‐difluoro‐boradizaindacene) embedded PtII PSs. The cis‐isomer (cis‐BBP) displayed enhanced 1O2 generation and better bacterial membrane anchoring capability as compared to the trans‐isomer (trans‐BBP). The effective PDI concentrations (efficiency > 99.9%) for cis‐BBP in Acinetobacter baumannii (multi‐drug resistant (MDR)) and Staphylococcus aureus are 400 nM (12 J cm−2) and 100 nM (18 J cm−2), respectively; corresponding concentrations and light doses for trans‐BBP in the two bacteria are 2.50 µM (30 J cm−2) and 1.50 µM (18 J cm−2), respectively. The 50% and 90% minimum inhibitory concentration (MIC50 and MIC90) ratio of trans‐BBP to cis‐BBP is 22.22 and 24.02 in A. baumannii (MDR); 21.29 and 22.36 in methicillin resistant S. aureus (MRSA), respectively. Furthermore, cis‐BBP displays superior in vivo antibacterial performance, with acceptable dark and photoinduced cytotoxicity. These results demonstrate cis‐BBP is a robust light‐assisted antibacterial reagent at sub‐micromolecular concentrations. More importantly, configuration of PtII PSs should be an important issue to be considered in further PDI reagents design.

Abstract Objective Radiation‐induced skin injury (RISI) remains a serious concern during radiotherapy. IL‐10 is considered as an immune suppressive cytokine by inhibiting the secretion of the proinflammatory cytokines in cells. The aim of this study was to evaluate the protective role of Erb (IL10) 2 against ionizing radiation. Methods We fused Interleukin 10 (IL‐10) dimer onto an anti‐epidermal growth factor receptor antibody Cetuximab (Erbitux) to form a new bispecific protein Erb‐(IL10)2. The protective effect and biological activity of Erb‐(IL10)2 was measured in model of RISI. Results Under the condition of 20 Gy irradiation, surviving cells in the IR group decreased significantly compared with the non‐IR group (p = 0.0021). The survival rates of HaCaT (p = 0.0038) and WS1 (p = 0.0003) cells were significantly increased after IL‐10 treatment. The apoptosis rates of HaCaT (p = 0.0048) and WS1 (p = 0.0074) cells in the IL‐10 group were significantly lower compared to the NC group. Under 20 Gy irradiation conditions, IL‐10 fusion protein reduced the level of reactive oxygen in HaCaT (p = 0.0046) and WS1 (p

Abstract Hypoxic environments like those present at high altitudes may negatively affect brain function. Varying levels of hypoxia, whether acute or chronic, are previously shown to impair cognitive function in humans. Assessment and prevention of such cognitive impairment require detection of cognitive changes and impairment using specific cognitive function assessment tools. This paper summarizes the findings of previous research, outlines the methods for cognitive function assessment used at a high altitude, elaborates the need to develop standardized and systematic cognitive function assessment tools for high‐altitude hypoxia environments.

Abstract All solid‐state batteries (ASSBs) are the holy grails of rechargeable batteries, where extensive searches are ongoing in the pursuit of ideal solid‐state electrolytes. Nevertheless, there is still a long way off to the satisfactorily high (enough) ionic conductivity, long‐term stability and especially being able to form compatible interfaces with the solid electrodes. Herein, we have explored ionic transport behavior and high mobility in the sub‐nano pore networks in the framework structures. Macroscopically, the frameworked electrolyte behaves as a solid, and however in the (sub)‐nano scales, the very limited number of solvent molecules in confinement makes them completely different from that in liquid electrolyte. Differentiated from a liquid‐electrolyte counterpart, the interactions between the mobile ions and surrounding molecules are subject to dramatic changes, leading to a high ionic conductivity at room temperature with a low activation energy. Li+ ions in the sub‐nano cages of the network structure are highly mobile and diffuse rather independently, where the rate‐limiting step of ions crossing cages is driven by the local concentration gradient and the electrostatic interactions between Li+ ions. This new class of frameworked electrolytes (FEs) with both high ionic conductivity and desirable interface with solid electrodes are demonstrated to work with Li‐ion batteries, where the ASSB with LiFePO4 shows a highly stable electrochemical performance of over 450 cycles at 2°C at room temperature, with an almost negligible capacity fade of 0.03‰ each cycle. In addition, the FE shows outstanding flexibility and anti‐flammability, which are among the key requirements of large‐scale applications.

Abstract Ceramic membranes are taking center stage for separation technologies in water treatment. Among them, ceramic nanofiltration membranes are at the forefront of membrane technologies. The desalination of seawater using ceramic nanofiltration membranes is a potential application toward increasing the global water supply and tackling water scarcity. However, while the high fabrication cost poses a challenge to their large‐scale applications, high‐value separation applications can help to offset the overall cost. In this regard, ceramic nanofiltration membranes can also be explored as a viable option for high‐value lithium extraction from the waste seawater brine. In order to determine the potential of nanofiltration ceramic membranes for desalination and lithium recovery from seawater, the current efficiency of salt rejection across various operation parameters must be thoroughly evaluated. Specifically, the interactions between the Donnan exclusion, steric exclusion, zeta potential, and salt concentration play an important role in determining the salt rejection efficiency. Several strategies are then proposed to guide ceramic nanofiltration membranes toward potentially practical applications regarding desalination and lithium recovery.

Abstract Background Immune cells are crucial components in the tumor microenvironment and have a significant impact on the outcomes of patients. Aims Here, we aimed to establish a prognostic score based on different types of tumor‐infiltrating immune cells for Endometrial Carcinoma (EC). Methods and Results We enrolled and analyzed 516 EC patients from The Cancer Genome Atlas. The relative abundance of 22 immune cells were estimated by using the CIBERSORTx algorithm. Cox regression was performed to identify potential prognostic immune cells, which were used to develop a Tumor‐infiltrating Immune Cell Score (TICS). The prognostic and incremental value of TICS for overall survival were compared with traditional prognostic factors using the C‐index and decision curves. Clustering analysis using all immune cells identified three immune landscape subtypes, which had weak correlation with survival. A TICS was constructed using CD8T cells, resting memory CD4 T cells, activated NK and activated DCs, and classified patients as low‐, moderate‐ and high‐risk subgroups. The low‐risk subgroup had higher tumor mutation burden and activation of IL2/STAT5, IL2/STAT3 and IFN‐gamma response pathways. Conversely, the high‐risk subgroup was associated with DNA copy number variation, hypoxia and EMT process. The TICS subgroups significantly predicted overall survival, which was independent of patient age, tumor stage, grade and molecular classification. Moreover, we developed a nomogram incorporating TICS and clinicopathologic factors, which significantly improved the predictive accuracy compared to the clinicopathologic model alone. Conclusion The TICS is an effective and independent prognostic predictor for EC patients and may serve as a useful supplement to clinicopathological factors and molecular subtyping.

Abstract Systemic lupus erythematosus (SLE) is a complex autoimmune disease with abnormal activation of the immune system. Recent attention is increasing about how aberrant lipid and cholesterol metabolism is linked together with type I interferon (IFN‐I) signaling in the regulation of the pathogenesis of SLE. Here, a metabonomic analysis is performed and increased plasma concentrations of oxysterols, especially 7α, 25‐dihydroxycholesterol (7α, 25‐OHC), are identified in SLE patients. The authors find that 7α, 25‐OHC binding to its receptor Epstein–Barr virus‐induced gene 2 (EBI2) in macrophages can suppress STAT activation and the production of IFN‐β, chemokines, and cytokines. Importantly, monocytes/macrophages from SLE patients and mice show significantly reduced EBI2 expression, which can be triggered by IFN‐γ produced in activated T cells. Previous findings suggest that EBI2 enhances immune cell migration. Opposite to this effect, the authors demonstrate that EBI2‐deficient macrophages produce higher levels of chemokines and cytokines, which recruits and activates myeloid cells,T and B lymphocytes to exacerbate tetramethylpentadecane‐induced SLE. Together, via sensing the oxysterol 7α, 25‐OHC, EBI2 in macrophages can modulate innate and adaptive immune responses, which may be used as a potential diagnostic marker and therapeutic target for SLE.

Abstract Background Perineural invasion (PNI) is a typical pathological characteristic of salivary adenoid cystic carcinoma (SACC) and other neurotrophic cancers. The mechanism of the neural microenvironment controlling tumor progression during the PNI process is unclear. In the present study, we investigated the role and molecular mechanisms of nerve‐derived neuropeptide galanin (GAL) and its receptor (GALR2) in the regulation of PNI in SACC. Methods Immunohistochemistry staining and clinical association studies were performed to analyze the expression of GAL and GALR2 in SACC tissues and their clinical value. Dorsal root ganglion or SH‐SY5Y cells were co‐cultured with SACC cells in vitro to simulate the interactions between the neural microenvironment and tumor cells, and a series of assays including transcriptome sequencing, Western blot, and Transwell were performed to investigate the role and molecular mechanism of GAL and GALR2 in the regulation of SACC cells. Moreover, both the in vitro and in vivo PNI models were established to assess the potential PNI‐specific therapeutic effects by blocking the GAL/GALR2 axis. Results GAL and GALR2 were highly expressed in SACC tissues, and were associated with PNI and poor prognosis in SACC patients (p

Abstract The Mesozoic subduction history of the Paleo‐Pacific plate below the East Asian margin remains contentious, in part because the southern part is poorly understood. To address this, we conducted a sediment provenance study to constrain Mesozoic subduction history below West Sarawak, Borneo. A combination of detrital zircon U‐Pb geochronology, heavy minerals, trace element, and bulk rock Nd isotope data were used to identify the tectonic events. The overall maturity of mineral assemblages, dominantly felsic sources, abundant Precambrian‐aged zircons, and low εNd(0) values (average −13.07) seen in Late Triassic sedimentary rocks suggest a period of inactive subduction near Borneo. Slab shallowing subduction occurred between 200 and 170 Ma based on subdued magmatism and tectonic compression across West Sarawak. From c. 170 to 70 Ma there was widespread magmatism and we interpret the Paleo‐Pacific slab steepened. Collectively, we show the Paleo‐Pacific plate subduction had variable slab dip histories in Borneo.

Abstract Blindness caused by corneal damage affects millions of people worldwide, and this number continues to rise. However, rapid epithelization and a stable epithelium process are the two biggest challenges for traditional corneal materials. These processes are related to corneal curvature, which is an important factor in determination of the corneal healing process and epithelial behavior during corneal damage. In this study, smooth 3D‐printed convex corneal implants based on gelatin methacrylate and collagen are generated. As epithelium distribution and adhesion vary in different regions of the natural cornea, this work separates the surfaces into four regions and studies how cells sense topological cues on curvature. It is found that rabbit corneal epithelial cells (RCECs) seeded on steeper slope gradient surfaces on convex structures result in more aligned cell organization and tighter cell‐substrate adhesion, which can also be verified through finite element simulation and signaling pathway analysis. In vivo transplantation of convex implants result in a better fit with adjacent tissue and stronger cell adhesion than flat implants, thereby accelerating corneal epithelialization and promoting collagen fibers and neural regeneration within 180 days. Taken together, printed convex corneal implants that facilitate corneal regeneration may offer a translational strategy for the treatment of corneal damage.

Abstract The urgent need for power transmission is the reason for leading research on the safer operation of high‐voltage cables. These high‐voltage cables are emerging as an efficient technology for underground power transmission. However, the electrochemical corrosion of aluminium (Al) metal sheaths in these cables is a common and challenging degradation process. Herein, the corrosion mechanisms and electrochemical analysis are investigated by using scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), electrochemical impedance spectroscopy (EIS) and laboratory‐designed electrochemical characterisation techniques. In the corrosion experiments, the authors evaluated the corrosion rate by measuring the release rate of hydrogen gas and explored the different roles of sodium polyacrylate (NaPA) during the corrosion process. It is found that the complexation reactions between NaPA and Al inhibited corrosion while increased the resistance of the buffer layer. The proposed mechanisms of corrosion in this study can improve the lifespan and sustainability of high‐voltage power transmission.

Abstract Objective Although radiotherapy (RT) has been widely used in cancer treatment, it provides limited benefits in patients with metastatic cancers due to rare abscopal antitumor effects. Recent progress in cancer immunotherapy provides a potential new strategy to boost the abscopal antitumor effects of RT. Methods We fused interleukin 10 (IL10) dimer onto the anti‐epidermal growth factor receptor antibody cetuximab (Erbitux) to form a new bispecific protein Erb‐(IL10)2. The antitumor effect and biological activity of Erb‐(IL10)2 were measured in the B16‐EGFR‐OVA tumor model. In vivo cell depletion and flow cytometry analyses were used to assess the mechanism of antitumor effects. Results Erb‐(IL10)2 treatment alone showed modest tumor growth inhibition, while local single dose RT (10 Gy) retarded irradiated tumor growth without affecting the growth of nonirradiated tumors. Notably, the combination therapy of RT and Erb‐(IL10)2 not only additively inhibited irradiated tumor growth but also induced abscopal antitumor responses. In vivo depletion of CD8+ T cells abrogated the combinational antitumor effects, while blocking lymphocyte trafficking through FTY720 treatment abolished the abscopal antitumor responses without affecting the antitumor effects on the irradiated tumor sites. Conclusion This study provides evidence for the radiosensitive role of Erb‐(IL10)2 in the B16‐EGFR‐OVA tumor model. Our findings suggest a novel strategy to elicit the abscopal antitumor effects of RT by combining tumor‐targeted therapy with IL10.

Abstract In China, traditional Chinese medicine (TCM) has been widely used for coronavirus infectious disease 2019 (COVID‐19) prevention, treatment, and recovery and has played a part in the battle against the disease. A variety of TCM treatments have been recommended for different stages of COVID‐19. But, to the best of our knowledge, a comprehensive database for storing and organizing anti‐COVID TCM treatments is still lacking. Herein, we developed TCM2COVID, a manually curated resource of anti‐COVID TCM formulas, natural products (NPs), and herbs. The current version of TCM2COVID (1) documents over 280 TCM formulas (including over 300 herbs) with detailed clinical evidence and therapeutic mechanism information; (2) records over 80 NPs with detailed potential therapeutic mechanisms; and (3) launches a useful web server for querying, analyzing and visualizing documented formulas similar to those supplied by the user (formula similarity analysis). In summary, TCM2COVD provides a user‐friendly and practical platform for documenting, querying, and browsing anti‐COVID TCM treatments, and will help in the development and elucidation of the mechanisms of action of new anti‐COVID TCM therapies to support the fight against the COVID‐19 epidemic. TCM2COVID is freely available at http://zhangy-lab.cn/tcm2covid/.

Abstract Accurate prognosis prediction is the key to achieving precision treatment and guiding the selection of adjuvant chemotherapy in high‐risk stage II/III colorectal cancer (CRC) patients. Here we developed a novel machine learning method, the random non‐negative matrix factorization (RNMF) algorithm, which outperformed traditional non‐negative matrix factorization in terms of computational speed, accuracy, and robustness in simulated data sets. Moreover, based on multidimensional data from CRC patients from The Cancer Genome Atlas database and DNA methylation data from those from Sun Yat‐sen University cancer center, we further demonstrated the excellent performance of a novel prognostic computational framework based on the RNMF (PCF_RNMF), which is capable of integrating multidimensional training while allowing survival prediction when single dimensional data for validation is provided. This novel algorithm has great potential to mitigate the challenge of integrating various types of data in public databases with clinically available single‐dimensional data to allow cost‐effective survival prediction for CRC patients in clinical practice.

Abstract Face recognition has become ubiquitous for authentication or security purposes. Meanwhile, there are increasing concerns about the privacy of face images, which are sensitive biometric data and should be protected. Software‐based cryptosystems are widely adopted to encrypt face images, but the security level is limited by insufficient digital secret key length or computing power. Hardware‐based optical cryptosystems can generate enormously longer secret keys and enable encryption at light speed, but most reported optical methods, such as double random phase encryption, are less compatible with other systems due to system complexity. In this study, a plain yet highly efficient speckle‐based optical cryptosystem is proposed and implemented. A scattering ground glass is exploited to generate physical secret keys of 17.2 gigabit length and encrypt face images via seemingly random optical speckles at light speed. Face images can then be decrypted from random speckles by a well‐trained decryption neural network, such that face recognition can be realized with up to 98% accuracy. Furthermore, attack analyses are carried out to show the cryptosystem's security. Due to its high security, fast speed, and low cost, the speckle‐based optical cryptosystem is suitable for practical applications and can inspire other high‐security cryptosystems.

Abstract Biogas industry in China is developing rapidly. This is particularly the case for livestock farm biogas plants, which are built to treat manure and wastewater. Managing the liquid digestate (LD) generated by anaerobic digestion of livestock wastes is becoming a bottleneck, restricting the sustainable development of the biogas industry in China. The separation of livestock breeding and arable farming, caused by rapid intensive animal husbandry development, is the main reason for the LD problem. Researchers, government representatives, and biogas plant operators in China have invested significant research efforts to maximize biogas‐linked agro‐ecosystem balance, which is considered as an important solution to the LD problem. This article reviewed these studies and proposed several solutions from the following four aspects: breeding mode, waste treatment mode, LD transportation mode, and LD utilization mode. One proposal is to reduce the scale of newly built livestock farms and disperse them in farmland, by promoting the “company + agent” livestock breeding mode. In this approach, farm scale would be based on the size of available farmland, and would allow for the use of LD in the near farmland. The second approach involves the intense separation of the livestock slurry and further transportation of the LD produced by the thick slurry. The third one is to expand the possible distances for transferring LD, using a pipe network or vehicle supervised by a professional third party. Finally, the development of high value‐added products and bringing them to market is the ultimate solution for the future.

Abstract The molecules of programmed cell death protein‐1 (PD‐1) and ligand‐1 (PD‐L1) become new therapeutic targets for cancer therapy. Although tumor‐expressed PD‐L1 molecule is frequently dispensable for checkpoint blockade in some cancer patients, recent studies suggest that T cell‐expressed PD‐L1 molecule might play a crucial role in antitumor immunity. Here, to investigate CD22 chimeric antigen receptor (CAR)‐T cell therapy, we have generated the different CD22 CAR‐T constructs. We noticed that tumor cells induced PD‐L1 expression on the surface of CD22 CAR‐T cells. The induced PD‐L1 might limit immunogenic responses of CAR‐T cells. T cell‐expressed PD‐L1 leads to a suppressive signal by PD‐1/PD‐L1 engagement of CD22 CAR‐T cells. Meanwhile, PD‐L1 suppresses CD22 CAR‐T cell differentiation into memory T cells and negatively affected secretions of several essential cytokines, such as interleukin‐2 (IL‐2) and tumor necrosis factor (TNF)‐α. We further observed that anti‐PD‐L1 monoclonal antibodies rescued cytokine secretion of CD22 CAR‐T cells rather than anti‐PD‐1 monoclonal antibodies. Our current studies provide a potential mechanism to understand the functions and roles of T cell‐expressed PD‐L1 in tumor microenvironment. These results will encourage the physicians to re‐recognize the important roles of PD‐L1 in cancer immunotherapy studies and provide the helpful guidance for clinical operation of PD‐L1 inhibition drugs.

Abstract An efficient integration of electrochromic and electrochemical devices into one flexible entity enables both energy storage and energy‐saving dual‐functionalities. For this purpose, achieving both high electrochromic and electrochemical performance is the key aspect. Herein, a new 3D architecture is successfully made by knotting W17O47@PEDOT (poly(3,4‐ethylenedioxythiophene)):PSS (poly(styrenesulfonate)) nanowires with NaWO3 nanoknots, and interestingly, the 3D W17O47/(NaWO3‐knots)@PEDOT:PSS cathode thus‐made simultaneously exhibits a large optical modulation (79.7% at 633 nm), an ultra‐long cycling life (76% of original optical modulation retained after 12 400 cycles), and a high areal capacitance (55.1 mF cm−2 at 0.1 mA cm−2). Our density functional theory (DFT) calculations demonstrate that the much improved dual‐functional performance is correlated to the raised electronic conductivity and ion adsorption at the W17O47/(NaWO3 nanoknots) interface, together with the ion adsorption of PEDOT:PSS in the 3D‐knotted architecture. As a proof‐of‐concept application, different‐sized flexible dual‐functional electrochromic/electrochemical devices (FDEDs) were assembled and investigated for various application scenarios, including a smart window (15 cm × 10 cm), a wearable wristband (20 cm × 2.5 cm), and a smart eyeglass. The smart window made of the FDED enables a large temperature difference of 27.6°C confirm‐tested in model houses, where the energy source also powers three light‐emitting diodes (LEDs). The understandings of the key governing principles in the electrodes and dual‐functionalities provide a timely foundation for the new generation flexible multifunctional devices.

Abstract Background Inherited susceptibility accounts for nearly one‐third of colorectal cancer (CRC) predispositions and has an 80%‐100% lifetime risk of this disease. However, there are few data about germline mutations of hereditary CRC‐related genes in Chinese patients with CRC. This study aimed to assess the prevalence of gene mutations related to cancer susceptibility among Chinese patients with CRC, differences between Chinese and Western patients, and the phenotype‐genotype correlation. Methods We retrospectively collected tumor samples from 526 patients with CRC under 70 years old who underwent hereditary CRC genetic testing. A series of bioinformatic analyses, as well as statistical comparisons, were performed. Results We found that 77 patients (14.6%) harbored functional variants of the 12 genes. The mutation frequencies of the top 5 mutated genes were 6.5% for MutL homolog 1 (MLH1), 5.1% for MutS homolog 2 (MSH2), 1.0% for MSH6, 0.8% for PMS1 homolog 2 (PMS2), and 0.8% for APC regulator of the WNT signaling pathway (APC). Our data showed much higher rates of mutations of MSH6 and PMS2 genes among all mismatch repair (MMR) genes as compared with those in Western populations. Mutations in MLH1, MSH2, and MSH6 were found to be mutually exclusive. Patients with MLH1 or MSH2 mutations had higher frequencies of personal history of cancer (MLH1: 20.6% vs. 8.7%; MSH2: 25.9% vs. 8.6%) and family history of cancer than those without these mutations (MLH1: 73.5% vs. 48.4%; MSH2: 70.4% vs. 48.9%), and the lesions were more prone to occur on the right side of the colon than on the left side (MLH1: 73.5% vs. 29.3%; MSH2: 56.0% vs. 31.0%). The proportion of stage I/II disease was higher in patients with MLH1 mutations than in those without MLH1 mutations (70.6% vs. 50.7%), and the rate of polyps was higher in patients with APC mutations than in those with wild‐type APC (75.0% vs. 17.4%). Conclusion These results provide a full‐scale landscape of hereditary susceptibility over 12 related genes in CRC patients and suggest that a comprehensive multi‐gene panel testing for hereditary CRC predisposition could be a helpful analysis in clinical practice.

Abstract Purpose To identify how Epstein‐Barr virus (EBV) status combined with molecular profiling predicts the prognosis of gastric cancer patients and their associated clinical actionable biomarkers. Experimental Design A next‐generation sequencing assay targeting 295 cancer‐related genes was performed in 73 EBV‐associated gastric cancer (EBVaGC) and 75 EBV‐negative gastric cancer (EBVnGC) specimens and these results were compared with overall survival (OS). Results PIK3CA, ARID1A, SMAD4, and PIK3R1 mutated significantly more frequently in EBVaGC compared with their corresponding mutation rate in EBVnGC. As the most frequently mutated gene in EBVnGC (62.7%), TP53 also displayed a mutation rate of 15.1% in EBVaGC. PIK3R1 was revealed as a novel mutated gene (11.0%) associated almost exclusively with EBVaGC. PIK3CA, SMAD4, PIK3R1, and BCOR were revealed to be unique driver genes in EBVaGC. ARID1A displayed a significantly large proportion of inactivated variants in EBVaGC. A notable finding was that integrating the EBV status with tumor mutation burden (TMB) and large genomic instability (LGI) categorized the tumors into four distinct molecular subtypes and optimally predicted patient prognosis. The corresponding median OSs for the EBV+/TMB‐high, EBV+/TMB‐low, EBV‐/LGI‐, and EBV‐/LGI+ subtypes were 96.2, 75.3, 44.4, and 20.2 months, respectively. The different subtypes were significantly segregated according to distinct mutational profiles and pathways. Conclusions Novel mutations in PIK3R1 and TP53 genes, driver genes such as PIK3CA, SMAD4, PIK3R1, BCOR, and ARID1A, and distinguished genomic profiles from EBVnGC were identified in EBVaGC tumors. The classification of gastric cancer by EBV, TMB, and LGI could be a good prognostic indicator, and provides distinguishing, targetable markers for treatment.

With the advancement of China’s industrial construction, the field of engineering management has also attracted more attention. However, China’s engineering management major is currently in a growing stage due to the issue of the opening years, and the teaching and practice setting of each course is also in an immature stage, which makes China’s engineering management majors present more and more problems. The truancy rate has been increasing year by year, the students’ dominant position in the class has become objectified, and their trust in teachers has decreased. Students’ learning shows the characteristics of individualization and diversity. Higher requirements are put forward for teachers’ teaching quality, and schools lack an effective supervision mechanism. In order to solve these problems better, it is imperative to reform and innovate the course teaching of engineering management majors. The core of engineering education accreditation is to confirm that engineering graduates meet established quality standards recognized by the industry. It is a unique method to test whether the course teaching of engineering management majors is qualified and attracts many scholars to discuss it. Engineering education accreditation has attracted many scholars to discuss it because it is a unique means to test the qualifications of engineering management students’ course teaching. This study was based on an in-depth exploration of the teaching practice of engineering management courses and combines artificial intelligence with an engineering education certification. Through the research and analysis of colleges and universities, the research finally showed that the engineering management professional course teaching of engineering education certification under the background of artificial intelligence can promote the attendance of students in school by about 20%. The achievement of course teaching objectives has increased by about 13% and the comprehensive ability level of graduates has increased by about 8%. It improved the overall level of students and the teaching quality and efficiency of engineering management courses and also promoted the development of college education so that today’s engineering management graduates can better meet the needs of today’s society.

The aim was to optimize the extraction process of Akebia trifoliata seed oil. Using Akebia trifoliata seed as raw material, the oil extraction rate was used as index. The effect of flash extraction on the yield of Akebia trifoliata seed oil was investigated. Taking the liquid-material ratio, extraction voltage, and extraction time as the investigation factors and the oil extraction rate of Akebia trifoliata seed as the response value and on the basis of the single-factor test, the extraction process of Akebia trifoliata seed oil was optimized by the Box-Behnken response surface method. The oil yields of Akebia trifoliata seeds from different origins in China were compared. The experimental results showed that the optimum technological conditions for flash extraction of Akebia trifoliata seed oil were as follows: liquid-material ratio, 12 : 1; extraction voltage, 150 V; extraction time, 90 s; and oil yield of Akebia trifoliata seed, 19.83%. For comparison, it is found that the oil yield of Akebia trifoliata seed produced in Qujing of Yunnan is relatively the highest, followed by Tongren of Guizhou and Zhangjiajie of Hunan; the oil yield of Akebia trifoliata seed produced in Shimian of Sichuan is the lowest. The flash extraction process of Akebia trifoliata seed oil is reasonable, and the oil yield of Akebia trifoliata seed produced in Qujing of Yunnan, China, is relatively the highest. It provides a theoretical and experimental reference for the research and development of Akebia trifoliata seed oil.

Abstract Immune checkpoint inhibitors (ICIs) have shown significant efficacy in various solid tumors, but only a small subgroup of patients benefit from them because of immune resistance. Oncorine (formerly H101), a recombinant human adenovirus type 5, has direct anticancer properties and enhances cell‐mediated immune responses. At present, few studies on the role of Oncorine in reversing resistance to ICIs have been reported. Here, we present a case with recurrent non‐small cell lung cancer (NSCLC). The patient developed resistance to nivolumab therapy. After trying immunotherapy plus chemotherapy or antiangiogenesis therapy, the patient only obtained a transient response. The patient then received experimental treatment with Oncorine together with nivolumab and anlotinib. She experienced symptomatic improvement with a performance status score of 1, and achieved stable disease despite partial lung tissue necrosis. This was a successful exploration of oncolytic viruses reversing immune resistance.

Abstract Sweetcane (Erianthus arundinaceus [Retzius] Jeswiet) is an ecologically dominant warm‐season perennial grass native to southern China. It traditionally plays an important role in sugarcane breeding due to its excellent biological traits and genetic relatedness to sugarcane. Recent studies have shown that sweetcane has a great potential in bioenergy and environmental remediation. The objective of this paper is to review the current research on sweetcane biology, phenology, biogeography, agronomy, and conversion technology, in order to explore its development as a bioenergy crop with environmental remediation potential. Sweetcane is resistant to a variety of stressors and can adapt to different growth environments. It can be used for ecological restoration, soil and water conservation, contaminated land repairing, nonpoint source pollutants barriers in buffer strips along surface waters, and as an ornamental and remediation plant on roadsides and in wetlands. Sweetcane exhibits higher biomass yield, calorific value and cellulose content than other bioenergy crops under the same growth conditions, thereby indicating its superior potential in second‐generation biofuel production. However, research on sweetcane as a bioenergy plant is still in its infancy. More works need be conducted on breeding, cultivation, genetic transformation, and energy conversion technologies.

Abstract It has been proposed that the circadian rhythm generally plays important roles in tumor suppression, but there is also evidence that disruption of the canonical circadian pathway has anticancer effects. In this study, we systematically analyzed the aberrances of circadian clock genes across cancers based on data from The Cancer Genome Atlas (TCGA). These data showed that the frequencies of mutations and copy number alterations in core clock genes (PER1/2/3, CLOCK, CRY1/2, and ARNTL) were low, but that the expression levels of core clock genes were downregulated by the higher levels of DNA methylation in most tumors. The circadian clock index (CCI) was established through a principal component analysis, and this measure well represents the overall expression of the core clock genes. In fact, the CCI was significantly lower in hepatocellular carcinoma with HBV infection than in other cancers. Furthermore, pathways such as the MAPK, JAK‐STAT, and immune‐related signaling pathways were enriched in tumors with high CCI values. Interestingly, the CCI was generally positively related to the immunophenoscores and immunophenotypes of tumors. Additionally, the expression levels of core clock genes and the CCI were also generally positively related to survival across cancers. Taken together, the results of this study provide a comprehensive analysis of circadian clock aberrances in cancer, and the results should aid further investigations of the molecular mechanisms of cancer and the development of therapeutic strategies.

Dedicated bus lanes (DBLs) have been widely utilized to ensure public transport priority. To improve overall road efficiency, various control methods of multiplexing DBL are developed and discussed. In this study, we focus on the control method which is based on the connected-automated vehicle (CAV) technology, and the proposed method is validated by using microscopic traffic simulation. The simulation results show that two proposed control methods of multiplexing DBL can reduce the average delay and the average number of stops and increase the travel speed. In comparison, the real-time control method based on the CAV technology offers better effects than the improved signal light control method.

Adipogenesis is the process through which preadipocytes differentiate into adipocytes. During this process, the preadipocytes cease to proliferate, begin to accumulate lipid droplets, and develop morphologic and biochemical characteristics of mature adipocytes. Mesenchymal stem cells (MSCs) are a type of adult stem cells known for their high plasticity and capacity to generate mesodermal and nonmesodermal tissues. Many mature cell types can be generated from MSCs, including adipocyte, osteocyte, and chondrocyte. The differentiation of stem cells into multiple mature phenotypes is at the basis for tissue regeneration and repair. Cancer stem cells (CSCs) play a very important role in tumor development and have the potential to differentiate into multiple cell lineages. Accumulating evidence has shown that cancer cells can be induced to differentiate into various benign cells, such as adipocytes, fibrocytes, osteoblast, by a variety of small molecular compounds, which may provide new strategies for cancer treatment. Recent studies have reported that tumor cells undergoing epithelial-to-mesenchymal transition can be induced to differentiate into adipocytes. In this review, molecular mechanisms, signal pathways, and the roles of various biological processes in adipose differentiation are summarized. Understanding the molecular mechanism of adipogenesis and adipose differentiation of cancer cells may contribute to cancer treatments that involve inducing differentiation into benign cells.

Abstract Objectives Although the genomic landscape of small‐cell carcinoma of the oesophagus (SCCE) has been dissected, its transcriptome‐level aberration and immune microenvironment status are unknown. Methods Using ultra‐deep whole transcriptome sequencing, we analysed the expression profile of nine paired SCCE samples and compared the transcriptome with public transcriptomic data set of normal oesophageal mucosa and other cancer types. Based on the transcriptome data, the immune signatures were investigated. The genomic data of 55 SCCE samples were also applied for immune checkpoint blockade therapy (ICBT) biomarker evaluation including microsatellite instability (MSI) status, tumor mutation burden (TMB) and neoantigen burden (TNB). Also, we evaluated the CD8, CD68 and programmed death‐ligand 1 (PD‐L1) in 62 retrospective SCCE samples with IHC assay. Results Differential expression analysis revealed that the cell cycle, p53, and Wnt pathways are significantly deregulated in SCCE. Immune microenvironment analysis showed that high leucocyte infiltration and adaptive immune resistance did occur in certain individuals, while the majority showed a relatively suppressive immune status. Immune checkpoints such as CD276 and LAG‐3 were upregulated, and higher M2 macrophage infiltration in tumor tissues. Furthermore, normal tissues adjacent to the tumors of SCCE presented a more activated inflammatory status than tumor‐free healthy controls. These observations showed that ICBT might benefit SCCE patients. As the critical biomarker of ICBT, TMB of SCCE was 3.64 with the predictive objective response rate 13.2%, while the PD‐L1‐positive rate was 43%. Conclusions Our study systematically characterized the immune microenvironment in small‐cell carcinoma of the esophagus and provided evidence that several patients with SCCE may benefit from immune checkpoint blockade therapy.

Abstract Objectives Anti‐PD‐1 immune checkpoint blockade represents the onset of a new era in cancer immunotherapy. However, robust predictors are necessary for screening patients with immune checkpoint‐responsive oesophageal squamous cell carcinoma (ESCC). Methods We obtained biopsy samples from an ESCC patient with mixed responses. The expression of CD4, CD8, CD68, PD‐L1, RBPJL and IL‐16 was analysed by immunohistochemistry, and the correlation with prognostic value was obtained from the GEPIA portal. T‐cell functions were examined by flow cytometry, MTS and transwell assays. The secreted cytokines were identified using an Inflammation Array Kit. The concentration of soluble IFN‐γ was measured by enzyme‐linked immunosorbent assay. The clinical benefit of RBPJL was examined in a PBMC xenograft mouse model. Results The patient had an exceptional clinical response with shrinkage of the primary oesophageal and lung metastatic lesions as well as enlargement of liver metastatic lesions after toripalimab monotherapy. Four liver‐specific gene mutations were identified. RBPJL showed better response to toripalimab in the PBMC cell‐derived xenograft (CDX) ESCC model. Conditional medium from RBPJL overexpression induced chemotaxis and proliferation of T lymphocytes, as well as Th2/Th1 differentiation through the RBPJL‐NF‐κB‐IL‐16 axis in vitro. These functions were all inhibited by the p.P476S mutation of RBPJL (RBPJL (p.P476S)). Conclusions We report for the first time that RBPJL (p.P476S) promotes tumor growth in ESCC and inhibits the efficacy of anti‐PD‐1 therapy through blunting T‐cell responses. Our findings provide a potential new predictor for evaluating the efficacy of anti‐PD‐1 therapy in ESCC patients.

Abstract It is urgent to explore effective diagnostic and prognostic biomarkers for hepatocellular carcinoma (HCC). Now, both lncRNAs and lipid metabolism are involved in tumor pathogenesis. Long noncoding RNA, RP11‐466I1.1, could likely be linked to lipid metabolism according to our bioinformatics analysis, yet studies about RP11‐466I1.1 expression in tumors and its potential functions are still lacking. We aimed to explore the expression and correlations with clinical features of a long noncoding RNA, RP11‐466I1.1, and further analyze its diagnostic and prognostic values in hepatocellular carcinoma. Expression levels of RP11‐466I1.1 were detected by quantitative real‐time PCR (qRT‐PCR) in tissue and serum level, and expression differences were analyzed by independent 2‐tailed t tests. Clinical features were obtained, and their correlations with RP11‐466I1.1 were analyzed by chi‐squared test. Receiver operating characteristic (ROC) curve was performed to assess the diagnostic value. Kaplan‐Meier method and log‐rank test were used to evaluate the prognostic value of RP11‐466I1.1. Results showed that RP11‐466I1.1 was upregulated in HCC tissues (P

Purpose. To investigate the risk factors for persistent or recurrent central serous chorioretinopathy (CSC). Materials and Methods. Consecutive treatment-naïve CSC patients were included from January 2017 to October 2018. All patients were asked to complete questionnaires, addressing previously described risk factors for the development of CSC. Patients were divided into two groups: those with acute CSC, who were in the first episode, with spontaneous resolution of subretinal fluid within 3 months, and with no recurrence within 1 year; and those with persistent or recurrent CSC, the remaining patients. Results. In total, 138 patients were enrolled: 20 (14.5%) with acute CSC and 118 (85.5%) with persistent or recurrent CSC. Using multivariate analysis, male sex (odds ratio (OR), 95% confidence interval: 5.63 [1.02–31.02]; p=0.047), older age (OR: 1.14 [1.03–1.25]; p=0.008), and higher Insomnia Severity Index score (OR: 1.30 [1.05–1.60]; p=0.015) were found to be independently associated with persistent or recurrent CSC. Conclusions. Male sex, age, and sleep disorders are risk factors for persistent or recurrent CSC in the natural history. These patients may require early photodynamic therapy. Treatment for sleep disorders is strongly recommended. All CSC patients may require careful and periodic follow-up.