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Abstract A fundamental objective of genomics is to track variations in gene expression program. While metabolic RNA labeling-based single-cell RNA sequencing offers insights into temporal biological processes, its limited applicability only to in vitro models challenges the study of in vivo gene expression dynamics. Herein, we introduce Dyna-vivo-seq, a strategy that enables time-resolved dynamic transcription profiling in vivo at the single-cell level by examining new and old RNAs. The new RNAs can offer an additional dimension to reveal cellular heterogeneity. Leveraging new RNAs, we discern two distinct high and low metabolic labeling populations among proximal tubular (PT) cells. Furthermore, we identify 90 rapidly responding transcription factors during the acute kidney injury in female mice, highlighting that high metabolic labeling PT cells exhibit heightened susceptibility to injury. Dyna-vivo-seq provides a powerful tool for the characterization of dynamic transcriptome at the single-cell level in living organism and holds great promise for biomedical applications.

Abstract Medullary thyroid carcinoma (MTC) is a rare type of thyroid malignancy that accounts for approximately 1–2% of all thyroid cancers (TCs). MTC include hereditary and sporadic cases, the former derived from a germline mutation of rearrangement during transfection (RET) proto-oncogene, whereas somatic RET mutations are frequently present in the latter. Surgery is the standard treatment for early stage MTC, and the 10-year survival rate of early MTC is over 80%. While for metastatic MTC, chemotherapy showing low response rate, and there was a lack of effective systemic therapies in the past. Due to the high risk (ca. 15–20%) of distant metastasis and limited systemic therapies, the 10-year survival rate of patients with advanced MTC was only 10–40% from the time of first metastasis. Over the past decade, targeted therapy for RET has developed rapidly, bringing hopes to patients with advanced and progressive MTC. Two multi-kinase inhibitors (MKIs) including Cabozantinib and Vandetanib have been shown to increase progression-free survival (PFS) for patients with metastatic MTC and have been approved as choices of first-line treatment. However, these MKIs have not prolonged overall survival (OS) and their utility is limited due to high rates of off-target toxicities. Recently, new generation TKIs, including Selpercatinib and Pralsetinib, have demonstrated highly selective efficacy against RET and more favorable side effect profiles, and gained approval as second-line treatment options. Despite the ongoing development of RET inhibitors, the management of advanced and progressive MTC remains challenging, drug resistance remains the main reason for treatment failure, and the mechanisms are still unclear. Besides, new promising therapeutic approaches, such as novel drug combinations and next generation RET inhibitors are under development. Herein, we overview the pathogenesis, molecular genetics and current management approaches of MTC, and focus on the recent advances of RET inhibitors, summarize the current situation and unmet needs of these RET inhibitors in MTC, and provide an overview of novel strategies for optimizing therapeutic effects.

Semiconductor photocatalysts often exhibit low CO2 reduction activity due to inherent limitations. Photothermal (PTT) processes have emerged as crucial for enhancing this activity, yet investigations in this area remain sparse. This study introduces a novel CoFe2O3.5S0.5 photothermal catalyst, synthesized via hydrothermal methods with particle sizes ranging from 5 to 10 nm. Comparative analysis reveals that the CO yield from the as-prepared catalyst surpasses that of CoFe2O4 by 8.9 times, achieving 100% selectivity. The integration of sulfur significantly boosts near-infrared light absorption and promotes the conversion of light to thermal energy, enabling the catalyst to reach 185 °C within 300 ss. This rapid temperature escalation facilitates the swift separation of charge carriers. Additionally, the adsorption of CO2 and the dynamics of surface intermediates were thoroughly examined using in situ FTIR spectroscopy and theoretical models, identifying COOH* as the pivotal intermediate and the bottleneck in the reaction pathway. Our findings rectify gaps in prior studies and offer a foundational reference for further exploration of product selectivity in the photocatalytic reduction of CO2.

Extensive use of the neonicotinoid insecticides acetamiprid (ACE) and flonicamid (FLO) in agriculture poses severe environmental and ecological risks. Microbial remediation is considered a feasible approach to address these issues. Many ACE-and FLO-degrading microorganisms have been isolated and characterized, but few reviews have concentrated on the underlying degradation mechanisms. In this review, we describe the microbial degradation pathways of ACE and FLO and assess the toxicity of ACE, FLO and their metabolites. Especially, we focus on the enzymes involved in degradation of ACE and FLO, including cytochrome P450s, nitrile hydratases, amidases, and nitrilases. Those studies reviewed here further our understanding of the enzymatic mechanisms of microbial degradation of ACE and FLO, and aid in the application of microbes to remediate environmental ACE and FLO contamination.

The production of 2,5-furandicarboxylic acid (FDCA) through green reaction routes is of crucial scientific value for the production of sustainable polymers. This study explores the active centers in cobalt-nitrogen-doped carbon (Co-N/C) for FDCA production. It was established that Co-Nx synergistically along with the nitrogen-doped carbon acted as centers for 5-hydroxymethylfurfural (HMF) oxidation. This study demonstrates a sustainable method for FDCA production from HMF without using precious metals, organic solvents, and harsh basic environments. Co-N/C catalyst displayed a high FDCA yield of ∼90% in an aqueous medium under mildly basic conditions in 34 h with 100% HMF conversion. An innovative strategy of stepwise base addition has been proposed to effectively accelerate the generation reaction of FDCA. The detrimental effects of high heating rate and calcination temperature on the active centers were also thoroughly investigated. Through DFT simulations it was established that Co-Nx aided in the activation of oxygen for HMF oxidation.

The poly (lactic-co-glycolic acid) (PLGA) based nanoparticles have been applied for drug delivery due to their simple preparation, biodegradability, and ideal biocompatibility. In this study, the factors affecting the degradation of PLGA-based nanoparticles are reviewed, encompassing the ratio of PLA to PGA, relative molecular weight, crystallinity, and preparation process of PLGA nanoparticles. The drug release behavior of PLGA-based nanoparticles, such as the degradation environment, encapsulated drug properties of polymers, and drug loading rates, are also discussed. Since gastrointestinal cancer is one of the major global threats to human health, this paper comprehensively summarizes the application of PLGA nanoparticles in gastrointestinal cancers from diagnosis, chemotherapy, radiotherapy, and novel tumor treatment methods (immunotherapy, gene therapy, and photothermal therapy). Finally, the future application of PLGA-based drug delivery systems in treating gastrointestinal cancers is discussed. The bottleneck of application status and the prospect of PLGA-nanoparticles in gastrointestinal tumor application are presented. To truly realize the great and wide application of PLGA-based nanoparticles, collaborative progress in the field of nanomaterials and life sciences is needed.

The catalytic fast pyrolysis process is a promising method for converting biomass waste into bio-oil, where the catalyst plays a crucial role in determining the yield and quality of the products. In this study, ultrafine iron nanoparticles were incorporated onto a montmorillonite substrate through the pyrolyzing coordinated polymer method to enhance liquid fuel production via catalytic pyrolysis of biomass waste. The catalyst showed a uniform distribution of iron on the montmorillonite surface, indicating that the incorporation was successful. Catalytic pyrolysis led to an increase in liquid yields and a decrease in gas product yields compared to direct pyrolysis. The highest bio-oil yield obtained was 56.9% during the catalytic pyrolysis of corncob, which was found to be particularly well-suited for the production of bio-oil. Furthermore, the proposed reaction pathway was based on identifying the composition of the bio-oil, which was further supported by quantum chemical calculations of chemical bond strength and the likelihood of free radical attacks. These findings demonstrate the potential of using montmorillonite-supported ultrafine iron nanoparticles to enhance bio-oil yield and quality in biomass pyrolysis processes.

Neuropathic pain (NP) is caused by a lesion or disease of the somatosensory system and is characterized by abnormal hypersensitivity to stimuli and nociceptive responses to non-noxious stimuli, affecting approximately 7–10% of the general population. However, current first-line drugs like non-steroidal anti-inflammatory agents and opioids have limitations, including dose-limiting side effects, dependence, and tolerability issues. Therefore, developing new interventions for the management of NP is urgent. In this study, we discovered that the high-frequency terahertz stimulation (HFTS) at approximately 36 THz effectively alleviates NP symptoms in mice with spared nerve injury. Computational simulation suggests that the frequency resonates with the carbonyl group in the filter region of Kv1.2 channels, facilitating the translocation of potassium ions. In vivo and in vitro results demonstrate that HFTS reduces the excitability of pyramidal neurons in the anterior cingulate cortex likely through enhancing the voltage-gated K+ and also the leak K+ conductance. This research presents a novel optical intervention strategy with terahertz waves for the treatment of NP and holds promising applications in other nervous system diseases.

Abstract Zinc-ion hybrid supercapacitors (ZHSCs) are attracting significant attention due to their high energies/power densities, safety, and low cost. In this review, recent advances in the development of ZHSCs are summarized. Particular emphasis is placed on state-of-the-art cathodes (including carbon, metal oxides, MXenes, and redox-active polymers), anodes (including Zn-based composites and Zn-free materials) and electrolytes for ZHSCs. Furthermore, the latest research on functional ZHSC devices with miniaturized ZHSCs, fiber-shaped ZHSCs, self-chargeable ZHSCs and self-healing devices is reported. Finally, further developments with ZHSCs are envisaged for future research in this thriving field.

Mismanaged plastics, upon entering the environment, undergo degradation through physicochemical and/or biological processes. This process often results in the formation of microplastics (MPs), the most prevalent form of plastic debris (

Chondrosarcoma (CHS) is a malignant bone tumor with insensitivity to both radiotherapy and chemotherapy, and a high recurrence rate. However, the latent mechanism of recurrent CHS (Re-CHS) remains elusive. Here, we discovered that FBXO22 was highly expressed in clinical samples of Re-CHS. FBXO22 played a significant role in various cancers. However, the role of FBXO22 in Re-CHS remained unclear. Our research demonstrated that suppressing FBXO22 abated the proliferation and migration of CHS cells and facilitated their apoptosis. In addition, suppressing FBXO22 raised the expression of PD-L1 in Re-CHS. All these findings provide new evidence for using FBXO22 and PD-L1 as combined targets to prevent and treat Re-CHS, which may prove to be a novel strategy for immunotherapy of CHS, especially Re-CHS.

Objective Recurrent giant cell tumor (RGCT) of the spine represents a clinical challenge for surgeons, and the treatment strategy remains controversial. This study aims to describe the long‐term follow‐up outcomes and compare the efficacy of en bloc spondylectomy versus piecemeal spondylectomy in treating RGCT of the thoracolumbar spine. Methods A total of 32 patients with RGCT of the thoracolumbar spine treated from June 2012 to June 2019 were retrospectively reviewed. A total of 15 patients received total en bloc spondylectomy (TES) with wide or marginal margin while 17 patients received total piecemeal spondylectomy (TPS) with intralesional margin. Postoperative Eastern Cooperative Oncology Group Performance Score (ECOG‐PS), Frankel classification and recurrence‐free survival (RFS) were evaluated after surgery. Survival curves were estimated by the Kaplan–Meier method and differences were analyzed with the log‐rank test. Multivariate analysis was performed with Cox regression to identify the independent prognostic factors affecting RFS. Results During a median follow‐up of 41.9 ± 17.5 months, all patients with compromised neurologic functions exhibit significant improvement, with the mean ECOG‐PS decreasing from 1.5 ± 1.3 to 0.13 ± 0.3 (p

Abstract The surge in anthropogenic CO2 emissions from fossil fuel dependence demands innovative solutions, such as artificial photosynthesis, to convert CO2 into value-added products. Unraveling the CO2 photoreduction mechanism at the molecular level is vital for developing high-performance photocatalysts. Here we show kinetic isotope effect evidence for the contested protonation pathway for CO2 photoreduction on TiO2 nanoparticles, which challenges the long-held assumption of electron-initiated activation. Employing isotopically labeled H2O/D2O and in-situ diffuse reflectance infrared Fourier transform spectroscopy, we observe H+/D+-protonated intermediates on TiO2 nanoparticles and capture their inverse decay kinetic isotope effect. Our findings significantly broaden our understanding of the CO2 uptake mechanism in semiconductor photocatalysts.

Unmanned Aerial Vehicles (UAVs) have garnered widespread attention in reconnaissance and search operations due to their low cost and high flexibility. However, when multiple UAVs (multi-UAV) collaborate on these tasks, a limited communication range can restrict their efficiency. This paper investigates the problem of multi-UAV collaborative reconnaissance and search for static targets with a limited communication range (MCRS-LCR). To address communication limitations, we designed a communication and information fusion model based on belief maps and modeled MCRS-LCR as a multi-objective optimization problem. We further reformulated this problem as a decentralized partially observable Markov decision process (Dec-POMDP). We introduced episodic memory into the reinforcement learning framework, proposing the CNN-Semantic Episodic Memory Utilization (CNN-SEMU) algorithm. Specifically, CNN-SEMU uses an encoder–decoder structure with a CNN to learn state embedding patterns influenced by the highest returns. It extracts semantic features from the high-dimensional map state space to construct a smoother memory embedding space, ultimately enhancing reinforcement learning performance by recalling the highest returns of historical states. Extensive simulation experiments demonstrate that in reconnaissance and search tasks of various scales, CNN-SEMU surpasses state-of-the-art multi-agent reinforcement learning methods in episodic rewards, search efficiency, and collision frequency.

In a highly competitive electricity spot market, virtual power plants (VPPs) that aggregate dispersed resources face various uncertainties during market transactions. These uncertainties directly impact the economic benefits of VPPs. To address the uncertainties in the economic optimization of VPPs, scenario analysis is employed to transform the uncertainties of wind turbines (WTs), photovoltaic (PV) system outputs, and electricity prices into deterministic problems. The objective is to maximize the VPP’s profits in day-ahead and intra-day markets (real-time balancing market) by constructing an economic optimization decision model based on two-stage stochastic programming. Gas turbines and electric vehicles (EVs) are scheduled and traded in the day-ahead market, while flexible energy storage systems (ESS) are deployed in the real-time balancing market. Based on simulation analysis, under the uncertainty of WTs and PV system outputs, as well as electricity prices, the proposed model demonstrates that orderly charging of EVs in the day-ahead stage can increase the revenue of the VPP by 6.1%. Additionally, since the ESS can adjust the deviations in day-ahead bid output during the intra-day stage, the day-ahead bidding strategy becomes more proactive, resulting in an additional 3.1% increase in the VPP revenue. Overall, this model can enhance the total revenue of the VPP by 9.2%.

Strawberry red core root rot disease affects the growth and yield of strawberry (Fragaria ananassa Duch), which leads to economic losses in China. The study employed a tissue separation method to isolate and identify the causal agent responsible for strawberry red core root rot. This was achieved by the observation of its morphological characteristics, sequencing analyses, and pathogenicity tests. The sensitivity of five chemical fungicides against the two species of Fusarium was determined using the mycelial growth rate method, and the biological characteristics of the two species were examined. The pathogens were identified as Fusarium solani and Fusarium oxysporum. The optimal conditions for the mycelial growth of F. solani and F. oxysporum were determined to be potato sucrose agar at 25 °C and pH 6, and potato dextrose agar at 30 °C and pH 8, respectively, with a 24:24 light cycle. The most suitable carbon and nitrogen sources for the mycelial growth of F. solani were sucrose and sodium nitrate (NaNO3), while for F. oxysporum, they were glucose and peptone. A fungicide sensitivity test indicated that Prochloraz had a good inhibitory effect on the growth of F. solani and F. oxysporum with EC50 values of 0.088 mg L−1 and 0.162 mg. The growth inhibition effect of Azoxystrobin to F. solani and Carbendazim to F. oxysporum was not obvious. This study provides a theoretical basis for further research on strawberry red core root disease and its prevention.

BackgroundCarotid atherosclerotic ischemic stroke threatens human health and life. The aim of this study is to establish a radiomics model of perivascular adipose tissue (PVAT) around carotid plaque for evaluation of the association between Peri-carotid Adipose Tissue structural changes with stroke and transient ischemic attack.MethodsA total of 203 patients underwent head and neck computed tomography angiography examination in our hospital. All patients were divided into a symptomatic group (71 cases) and an asymptomatic group (132 cases) according to whether they had acute/subacute stroke or transient ischemic attack. The radiomic signature (RS) of carotid plaque PVAT was extracted, and the minimum redundancy maximum correlation, recursive feature elimination, and linear discriminant analysis algorithms were used for feature screening and dimensionality reduction.ResultsIt was found that the RS model achieved the best diagnostic performance in the Bagging Decision Tree algorithm, and the training set (AUC, 0.837; 95%CI: 0.775, 0.899), testing set (AUC, 0.834; 95%CI: 0.685, 0.982). Compared with the traditional feature model, the RS model significantly improved the diagnostic efficacy for identifying symptomatic plaques in the testing set (AUC: 0.834 vs. 0.593; Z = 2.114, p = 0.0345).ConclusionThe RS model of PVAT of carotid plaque can be used as an objective indicator to evaluate the risk of plaque and provide a basis for risk stratification of carotid atherosclerotic disease.

Waste plastics pose significant environmental risks due to their non-biodegradable nature and accumulation in the environment. The pandemic has exacerbated this issue by increasing the production of plastic medical waste such as surgical masks. This study developed Ni/Al-MOF-derived catalysts for pyrolysis, an effective plastic waste utilization technology. By optimizing conditions, the study successfully converted waste surgical masks, made primarily of polypropylene, into gasoline or diesel range chemicals. The oil yield from polypropylene waste reached 72.8 % using Ni/Al-MOF-derived catalysts with 5 % Ni loading at 450°C, while surgical masks yielded 58.9 % oil under the same conditions. Catalyst characterization revealed a high surface area and evenly distributed Ni particles in MOF-derived Al2O3, maximizing catalytic performance. This catalyst provides a promising solution for converting waste surgical masks into liquid fuels, reducing the environmental impact of plastic products, and promoting plastic waste recycling.

BackgroundMultiple clinical studies have found a significant correlation between elevated galectin-3 (Gal-3) in circulation and the diagnosis and severity of peripheral arterial disease (PAD). The current study used the Mendelian randomization (MR) technique to evaluate the possible causal relationship between Gal-3 and PAD.MethodsGenome-wide association study (GWAS) data of Gal-3 and PAD were obtained through the MR-Base platform. Then, using Gal-3 as the exposure and PAD as the outcome, a two-sample MR analysis was performed utilizing several regression techniques, including MR-Egger regression, inverse variance weighted (IVW), weighted median, and weighted mode.ResultsSix single-nucleotide polymorphisms (SNPs) were identified and designated as instrumental variables (IVs) that exhibited significant correlations with Gal-3 (linkage disequilibrium r2

For the three-dimensional conductive host, the uneven lithium deposition and the dependence on the pore structure and lithiophility are a great challenge for lithium metal anodes. Herein, we employed facial chemical etching techniques on brass foil to fabricate three-dimensional copper hosts with diverse pore structures and lithiophilities, thus intending to understand the lithium depositing mechanisms in porous hosts. The copper host with a more pronounced pore structure exhibits the lower polarization voltage induced by its large specific surface area, which reduces the local current density and provides a great deal of pathway for lithium ion diffusion. Meanwhile, it exhibits high nucleation overpotential and a short lifespan due to a reduced number of favorable lithium nucleation sites caused by the reduced lithiophilic zinc sites and a marked increase in the routes between nucleation sites. Therefore, the appropriate pore structure needs a consideration of efficient balance between the nucleation overpotential, the polarization voltage, and Coulombic efficiency. This insight underscores the pivotal role of well-suited pore structures in three-dimensional hosts, providing profound guidance for the efficient design of advanced host for lithium metal anode.

Developing low-cost and high-activity catalysts is one of the keys to promoting the catalytic pyrolysis of waste plastics to fuels for plastic recycling. This work studied the effect of clay as the catalyst on mixed plastic pyrolysis for fuel and energy recovery. Four kinds of clay, including nanoclay, montmorillonite, kaolin, and hydrotalcite, were used as catalysts for the pyrolysis of mixed plastic consisted of polyethylene terephthalate, polystyrene, polypropylene, low-density polyethylene, and high-density polyethylene. The product yield and distribution varied with different clay in pyrolysis. The highest yield of oil was 71.0 % when using montmorillonite as the catalyst. While the highest contents of gasoline range hydrocarbons and diesel range hydrocarbons in the oil were achieved when using kaolin and nanoclay, respectively as catalysts. For the gas products, the CO, C2H4, C2H6, C3H6, and C4H10 increased with decreased CO2 in the gaseous products when using clay as catalysts. In general, the mild acidity of clay catalyst was essential to improve the oil yields and the proportion of the gasoline or diesel range fuels in the catalytic pyrolysis of mixed plastic waste.

Vitamin D deficiency is associated with various diseases such as obesity, digestive problems, osteoporosis, depression, and infections, and has therefore emerged as a topic of great interest in public healthcare. The quantitative assessment of 25-hydroxyvitamin D (25-OH VD) in human serum may accurately reflect the nutritional status of vitamin D in the human body, which is significant for the prevention and treatment of vitamin D-deficient patients. In this study, we developed an assay for quantitative detection of 25-OH VD based on the 25-OH VD monoclonal antibody (mAb), and identified the optimal process parameters. The following process settings were found to be suitable for the test strips: pH of 7.6, 1-Ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) ratio of 1:2000, and the anti-25-OH VD mAb ratio was 1:8. The equilibration time of the immune dynamic assay was 15 min. Under optimal conditions, the quantum dot nanoparticle-based fluorescent immunochromatographic assay (QDs-FICA) exhibited dynamic linear detection of 25-OH VD in PBS, from 5 ng/mL to 100 ng/mL, and the strip quantitative curve could be represented by the following regression equation: y = −0.02088 logx)+1.444 (R2 = 0.9050). The IC50 of the QDs-FICA was 39.6 ± 1.33 ng/mL. The specificity of the QDs-FICA was evaluated by running several structurally related analogues, including 25-OH VD2, 25-OH VD3, 1,25-OH2VD3, 1,25-OH2VD2, VD2, and VD3. The coefficients of variation were all below 10%. The shelf life of the test strips in this study was about 160 days at room temperature. Briefly, this study is the first to perform QDs-FICA for the rapid visual and quantitative detection of 25-OH VD, with great potential significance for clinical diagnosis of vitamin D-associated diseases.

Abstract High‐capacity O3‐type layered sodium oxides are considered one of the most promising cathode materials for the next generation of Na‐ion batteries (NIBs). However, these cathodes usually suffer from low high‐rate capacity and poor cycling stability due to structure deformation, native air sensitivity, and interfacial side reactions. Herein, a multi‐site substituted strategy is employed to enhance the stability of O3‐type NaNi0.5Mn0.5O2. Simulations indicate that the Ti substitution decreases the charge density of Ni ions and improves the antioxidative capability of the material. In addition, the synergistic effect of K+ and Ti4+ significantly reduces the formation energy of Na+ vacancy and delivers an ultra‐low lattice strain during the repeated Na+ extraction/insertion. In situ characterizations verify that the complicated phase transformation is mitigated during the charge/discharge process, resulting in greatly improved structure stability. The co‐substituted cathode delivers a high‐rate capacity of 97 mAh g−1 at 5 C and excellent capacity retention of 81% after 400 cycles at 0.5 C. The full cell paired with commercial hard carbon anode also exhibits high capacity and long cycling life. This dual‐ion substitution strategy will provide a universal approach for the new rational design of high‐capacity cathode materials for NIBs.

Abstract Oncolytic viruses (OVs) represent a new class of multi-modal immunotherapies for cancer, with OV-elicited antitumor immunity being key to their overall therapeutic efficacy. Currently, the clinical effectiveness of OV as monotherapy remains limited, and thus investigators have been exploring various combinations with other anti-cancer agents and demonstrated improved therapeutic efficacy. As cancer cells have evolved to alter key signaling pathways for enhanced cell proliferation, cancer progression and metastasis, these cellular and molecular changes offer promising targets for rational cancer therapy design. In this regard, key molecules in relevant signaling pathways for cancer cells or/and immune cells, such as EGFR-KRAS (e.g., KRASG12C), PI3K-AKT-mTOR, ERK-MEK, JAK-STAT, p53, PD-1-PD-L1, and epigenetic, or immune pathways (e.g., histone deacetylases, cGAS-STING) are currently under investigation and have the potential to synergize with OV to modulate the immune milieu of the tumor microenvironment (TME), thereby improving and sustaining antitumor immunity. As many small molecule modulators of these signaling pathways have been developed and have shown strong therapeutic potential, here we review key findings related to both OV-mediated immunotherapy and the utility of small molecule modulators of signaling pathways in immuno-oncology. Then, we focus on discussion of the rationales and potential strategies for combining OV with selected modulators targeting key cellular signaling pathways in cancer or/and immune cells to modulate the TME and enhance antitumor immunity and therapeutic efficacy. Finally, we provide perspectives and viewpoints on the application of novel experimental systems and technologies that can propel this exciting branch of medicine into a bright future.

Abstract Background Immune checkpoint inhibitors have shown promise in microsatellite instability-high/mismatch repair deficient (MSI-H/dMMR) advanced colorectal cancer (CRC) immunotherapy, and many clinical trials have been conducted. Objective To evaluate the efficacy and safety of PD-1/PD-L1 inhibitors in advanced CRC. Method PubMed, Web of Science, Embase, and The Cochrane Library were searched for relevant studies up to September 2021. A retrospective cross-sectional data analysis was performed and Stata 16 software was used for analyses. Results Sixteen studies including 1503 patients were analyzed. The objective response rate (ORR) of anti-PD-1/PD-L1 was 23% (95% CI 0.14, 0.31); the overall 1-year survival rate (OSR) was 57% (95% CI 0.42, 0.73). The ORR of MSI-H/dMMR advanced CRC was 37% (95% CI 0.25, 0.48) and that of microsatellite stable/mismatch repair proficient (MSS/pMMR) disease was 11% (95% CI 0.06, 0.16). The ORR was 42% in the BRAF mutant subgroup and 19% in the RAS mutant group. The ORR was 14% in the PD-L1 ( +) subgroup and 32% in the PD-L1(-) subgroup. The rate of adverse effects was 85% (95% CI 0.80, 0.91). Conclusion Anti-PD-1/PD-L1 therapy in MSI-H/dMMR advanced CRC was associated with improved survival. Anti PD-1/PD-L1 combined with antiangiogenic drugs, targeted agents, or chemotherapy might be effective in MSS mCRC. Immunotherapy was effective for the BRAF mutant and KRAS/NRAS(RAS) mutant CRC. Low expression of PD-L1 was a potential predictive marker for positive response and outcome. The high incidence of adverse events at 85% was worthy of further investigation. Further analysis with a higher number of high-quality studies is needed to verify the conclusions.

Currently, the original Miedema mixing enthalpy model yields calculation results that exhibit some discrepancies when compared to experimental data. Therefore, improving the precision of the Miedema model is essential to advance its development and application in developing samarium–cobalt permanent magnet alloys. To address this issue, the enthalpies of mixing for Sm–(Co, Cu, Fe, Zr) binary alloys were calculated using the modified model. In addition, the mixing enthalpy (Δ H ), excess entropy ( S ^E ), excess Gibbs free energy ( G ^E ), component activity ( α ) and binary Gibbs free energy of Sm–Co and Sm–Fe were calculated. The results indicate that the improved Miedema model more accurately matches the experimental values. Sm– (Co, Fe, Cu) binary alloys tend to form intermetallic compounds easily, whereas Sm–Zr does not. The Δ H , S ^E and G ^E of Sm-(Co, Fe) are negative, and the activity of each component shows a considerable negative deviation from Raoult’s law in contrast to that of an ideal solution. In the range of 1550 ∼ 1620 K, the Gibbs free energy of SmCo _5 and Sm _2 Co _17 reactions is negative with the Sm _2 Co _17 phase being thermodynamically more stable than the SmCo _5 phase.

Abstract While DNA-directed nano-fabrication enables the high-resolution patterning for conventional electronic materials and devices, the intrinsic self-assembly defects of DNA structures present challenges for further scaling into sub-1 nm technology nodes. The high-dimensional crystallographic defects, including line dislocations and grain boundaries, typically lead to the pattern defects of the DNA lattices. Using periodic line arrays as model systems, we discover that the sequence periodicity mainly determines the formation of line defects, and the defect rate reaches 74% at 8.2-nm line pitch. To suppress high-dimensional defects rate, we develop an effective approach by assigning the orthogonal sequence sets into neighboring unit cells, reducing line defect rate by two orders of magnitude at 7.5-nm line pitch. We further demonstrate densely aligned metal nano-line arrays by depositing metal layers onto the assembled DNA templates. The ultra-scaled critical pitches in the defect-free DNA arrays may further promote the dimension-dependent properties of DNA-templated materials.

Circulating tumor cells (CTCs), as important liquid biopsy target, can provide valuable information for cancer progress monitoring and individualized treatment. However, current isolation platforms incapable of balancing capture efficiency, specificity, cell viability, and gentle release have restricted the clinical applications of CTCs. Herein, inspired by the structure and functional merits of natural membrane interfaces, we established an antibody-engineered red blood cell (RBC-Ab) affinity interface on microfluidic chip for high-performance isolation and release of CTCs. The lateral fluidity, pliability, and anti-adhesion property of the RBC microfluidic interface enabled efficient CTCs capture (96.5%), high CTCs viability (96.1%), and high CTCs purity (average 4.2-log depletion of leukocytes). More importantly, selective lysis of RBCs by simply changing the salt concentration was utilized to destroy the affinity interface for efficient and gentle release of CTCs without nucleic acid contamination. Using this chip, CTCs were successfully detected in colon cancer samples with 90% sensitivity and 100% specificity (20 patients and 10 healthy individuals). After the release process, KRAS gene mutations of CTCs were identified from all the 5 cancer samples, which was consistent with the results of tissue biopsy. We expect this RBC interface strategy will inspire further biomimetic interface construction for rare cell analysis.

Abstract Glioblastoma (GBM) patients present poor prognosis. Deubiquitination by deubiquitinating enzymes (DUBs) is a critical process in cancer progression. Ubiquitin-specific proteases (USPs) constitute the largest sub-family of DUBs. Evaluate the role of USP32 in GBM progression and provide a potential target for GBM treatment. Clinical significance of USP32 was investigated using Gene Expression Omnibus databases. Effects of USP32 on cell growth and metastasis were studied in vitro and in vivo. Differentially expressive genes between USP32-knockdown U-87 MG cells and negative control cells were detected using RNA sequencing and used for Gene Ontology and Kyoto Encyclopedia of Genes and Genomic pathway enrichment analyses. Finally, RT-qPCR was used to validate the divergent expression of genes involved in the enriched pathways. USP32 was upregulated in GBM patients, being correlated to poor prognosis. USP32 downregulation inhibited cell growth and metastasis in vitro. Furthermore, USP32 knockdown inhibited tumorigenesis in vivo. In addition, UPS32 was identified as a crucial regulator in different pathways including cell cycle, cellular senescence, DNA replication, base excision repair, and mismatch repair pathways. USP32 acts as an oncogene in GBM through regulating several biological processes/pathways. It could be a potential target for GBM treatment.

Objective: To discuss the techniques and methods in respective operation of brain gliomas located in eloquent brain region under awake anesthesia state Methods: 21 patients admitted into Department of Neurosurgery of the First Affiliated Hospital of Xiamen University were chosen as subject. Diagnosed with brain gliomas, they received operation with neuronavigation, intraoperative ultrasonography for locating the lesion and intraoperative direct electric stimulation for functional mapping of the eloquent brain region after receiving awake anesthesia. All patients were followed up from post-surgical 3 months to 18 months. Results: Applied with MRI scanning during post-surgical 60–90d, resection results shows that 5 cases (23.8%) received total resection of lesions, 10 cases (47.6%) received subtotal resection while 6 cases (28.6%) received partial resection. Post-surgical performance shows 8 cases (38.1%) of transitory postoperative aphasia, 5 cases(23.8%) of transitory postoperative dyskinesia and 1 case(4.8%) of permanent dyskinesia. Recovery was achieved in the patients except for the 1 case of permanent dyskinesia. Conclusions: Comprehensive application of awake anesthesia, neuronavigation, intraoperative ultrasonography and intraoperative direct electrical stimulation facilitates recognition of clear position relationship between gliomas and eloquent brain region, and maximum safe resection of gliomas in eloquent brain region with maximal protection of brain function.

Abstract The current study aimed to determine whether breed and feed efficiency affect the molecular mechanisms regulating beneficial and non-beneficial fatty acid profiles in subcutaneous adipose tissue of beef steers. Fatty acid profiling and RNA-Seq based transcriptome analysis were performed on subcutaneous adipose tissues collected from beef steers with three divergent breeds (Angus, ANG, n = 47; Charolais, CHAR, n = 48; Kinsella Composite, KC, n = 48) and different residual feed intake (RFI, a measure of feed efficiency). The comparison of fatty acid profiles showed that KC had higher beneficial FAs compared to the other two breeds. Distinct FA profiles between H-RFIfat and L-RFIfat steers was more obvious for KC steers, where H-RFIfat steers tended to have higher proportion of healthy FAs and lower proportion of the unhealthy FAs. A higher number of differentially expressed (DE) genes were observed for KC steers, whereas ANG and CHAR steers had a lower number of DE genes between H- and L-RFIfat steers. The association analyses of the gene expressions and FA profiles showed that 10 FA metabolism-associated genes together with the one upstream regulator (SREBF1) were associated with the proportion of C18:2n-6, total n-6, PUFA and PUFA/SFA for KC steers but not the other two breeds. Subcutaneous adipose tissue FA profiles and healthy FA index differed in cattle with divergent feed efficiency and such variation was unique for the three examined cattle breeds. Key FA metabolism-associated genes together with SREBF1 which is the upstream regulator of a set of genes involved in lipid metabolism may be of importance for genetic selection of meat with higher healthy FA index in beef cattle.

The difficulties associated with polyetheretherketone (PEEK) implants and soft tissue integration for craniomaxillofacial bone repair have led to a series of complications that limit the clinical benefits. In this study, 3D printed multi-stage microporous PEEK implants coated with bFGF via polydopamine were fabricated to enhance PEEK implant-soft tissue integration. Multistage microporous PEEK scaffolds prepared by sulfonation of concentrated sulfuric acid were coated with polydopamine, and then used as templates for electrophoretic deposition of bFGF bioactive factors. Achieving polydopamine and bFGF sustained release, the composite PEEK scaffolds possessed good mechanical properties, hydrophilicity, protein adhesion properties. The in vitro results indicated that bFGF/polydopamine-loaded PEEK exhibited good biocompatibility to rabbit embryonic fibroblasts (REF) by promoting cell proliferation, adhesion, and migration. Ribonucleic acid sequencing (RNA-seq) revealed that bFGF/polydopamine-loaded PEEK implants significantly upregulated the expression of genes and proteins associated with soft tissue integration and activated Wnt/β-catenin signaling in biological processes, but related expression of genes and proteins was significantly downregulated when the Wnt/β-catenin signaling was inhibited. Furthermore, in vivo bFGF/polydopamine-loaded PEEK implants exhibited excellent performance in improving the growth and adhesion of the surrounding soft tissue. In summary, bFGF/polydopamine-loaded PEEK implants possess soft tissue integration properties by activating the Wnt/β-catenin signaling, which have a potential translational clinical application in the future.

The influence of bilingual education and experience on an individual’s information-processing ability has recently been a hot issue in international studies. Previous studies have found that bilingual experience affects executive function, but the results remain controversial. Executive function refers to the conscious control of purposeful behavior. It is responsible for processing high-level action controls, including such sub-functions as inhibitory control, cognitive switching, and working memory updating. Emotion, as an essential factor in daily life, also has a complex interaction with executive function. This paper explores whether the bilingual cognitive advantage effect can continue in the more complex conditions of emotional interference. To investigate the specific electrophysiological characteristics of the participants at different stages of cognitive processing, we used a combination of the behavioral and ERP experiments in which the positive, neutral, and negative emotional stimuli were selected as emotional interference conditions and the emotional Simon paradigm, the cognitive switching of emotion paradigm, and the emotional N-back paradigm was adopted. The results show that the main effect of the N1 component amplitude is significant. Specifically, the amplitude of the N1 component in the proficient bilinguals is significantly smaller than that of the non-proficient bilinguals, while the main effects of other component groups are not significant, indicating that under the condition of emotional interference, the influence of bilingual experience on executive function only exists in the early attention stage and that the bilingual experience can improve the individual’s attentional control and speed up attention processing in the early attention stage.

Dynamic multi-target assignment is a key technology that needs to be supported in order to improve the strike effectiveness during the coordinated attack of the missile swarm, and it is of great significance for improving the intelligence level of the new generation of strike weapon groups. Changes in ballistic trajectory during the penetration of multi-warhead missiles may cause the original target assignment scheme to no longer be optimal. Therefore, reassigning targets based on the real-time position of the warhead plays an important role in improving the effectiveness of the strike. In this paper, the dynamic multi-target assignment decision modeling method combining combat simulation and deep reinforcement learning was discussed, and an intelligent decision-making training framework for multi-target assignment was designed based on deep reinforcement learning. In conjunction with the typical combat cases, the warhead combat process was also divided into the penetration phase and the multi-target assignment phase, the model framework and reward function against the multi-target assignment of the missile were devised, and the SAC algorithm was employed to conduct application research on intelligent decision modeling for multi-target assignment. Preliminary test results suggest that the intelligent decision-making model based on deep reinforcement learning provides better combat effects than the traditional decision model based on knowledge engineering.

Abstract Epigenetic mechanisms play vital roles not only in cancer initiation and progression, but also in the activation, differentiation and effector function(s) of immune cells. In this review, we summarize current literature related to epigenomic dynamics in immune cells impacting immune cell fate and functionality, and the immunogenicity of cancer cells. Some important immune-associated genes, such as granzyme B, IFN-γ, IL-2, IL-12, FoxP3 and STING, are regulated via epigenetic mechanisms in immune or/and cancer cells, as are immune checkpoint molecules (PD-1, CTLA-4, TIM-3, LAG-3, TIGIT) expressed by immune cells and tumor-associated stromal cells. Thus, therapeutic strategies implementing epigenetic modulating drugs are expected to significantly impact the tumor microenvironment (TME) by promoting transcriptional and metabolic reprogramming in local immune cell populations, resulting in inhibition of immunosuppressive cells (MDSCs and Treg) and the activation of anti-tumor T effector cells, professional antigen presenting cells (APC), as well as cancer cells which can serve as non-professional APC. In the latter instance, epigenetic modulating agents may coordinately promote tumor immunogenicity by inducing de novo expression of transcriptionally repressed tumor-associated antigens, increasing expression of neoantigens and MHC processing/presentation machinery, and activating tumor immunogenic cell death (ICD). ICD provides a rich source of immunogens for anti-tumor T cell cross-priming and sensitizing cancer cells to interventional immunotherapy. In this way, epigenetic modulators may be envisioned as effective components in combination immunotherapy approaches capable of mediating superior therapeutic efficacy.

PurposeNoninvasively assessing the tumor biology and microenvironment before treatment is greatly important, and glypican-3 (GPC-3) is a new-generation immunotherapy target for hepatocellular carcinoma (HCC). This study investigated the application value of a nomogram based on LI-RADS features, quantitative contrast-enhanced MRI parameters and clinical indicators in the noninvasive preoperative prediction of GPC-3 expression in HCC.Methods and materialsWe retrospectively reviewed 127 patients with pathologically confirmed solitary HCC who underwent Gd-EOB-DTPA MRI examinations and related laboratory tests. Quantitative contrast-enhanced MRI parameters and clinical indicators were collected by an abdominal radiologist, and LI-RADS features were independently assessed and recorded by three trained intermediate- and senior-level radiologists. The pathological and immunohistochemical results of HCC were determined by two senior pathologists. All patients were divided into a training cohort (88 cases) and validation cohort (39 cases). Univariate analysis and multivariate logistic regression were performed to identify independent predictors of GPC-3 expression in HCC, and a nomogram model was established in the training cohort. The performance of the nomogram was assessed by the area under the receiver operating characteristic curve (AUC) and the calibration curve in the training cohort and validation cohort, respectively.ResultsBlood products in mass, nodule-in-nodule architecture, mosaic architecture, contrast enhancement ratio (CER), transition phase lesion-liver parenchyma signal ratio (TP-LNR), and serum ferritin (Fer) were independent predictors of GPC-3 expression, with odds ratios (ORs) of 5.437, 10.682, 5.477, 11.788, 0.028, and 1.005, respectively. Nomogram based on LI-RADS features (blood products in mass, nodule-in-nodule architecture and mosaic architecture), quantitative contrast-enhanced MRI parameters (CER and TP-LNR) and clinical indicators (Fer) for predicting GPC-3 expression in HCC was established successfully. The nomogram showed good discrimination (AUC of 0.925 in the training cohort and 0.908 in the validation cohort) and favorable calibration. The diagnostic sensitivity and specificity were 76.9% and 92.3% in the training cohort, 76.8% and 93.8% in the validation cohort respectively.ConclusionThe nomogram constructed from LI-RADS features, quantitative contrast-enhanced MRI parameters and clinical indicators has high application value, can accurately predict GPC-3 expression in HCC and may help noninvasively identify potential patients for GPC-3 immunotherapy.

Functionalized membranes have high potential value in a broad range of practical applications, and the functional groups at the membrane edge play a vital role in the permeability of the membranes. Here, based on an edge-functionalized graphene oxide (GO) membrane model, we theoretically report that high-frequency terahertz stimulation at the frequency near 44.0 THz can significantly enhance the water permeability of the membrane by nearly five times. Its mechanism was revealed to be that the stimulation amplified the C-O stretching of the functional groups and suppressed other vibration modes of the groups. As a result, the modulation of edge functional groups brings down the energy barricade of the membrane and allows water molecules to penetrate the GO membrane more easily. These findings provide a new perspective for enhancing membrane permeability by modulating particular functional groups such as the carboxyl on the edge of the GO membrane.

In recent years, the role of tumor budding in gastric cancer has received increased attention across a number of disciplines. Several studies have found associations between tumor budding and the prediction of lymph node metastasis in early gastric cancer, prognosis of advanced gastric cancer, predictors of therapeutic response to immune checkpoint inhibitors, such as microsatellite instability (MSI), and therapeutic targets of molecular targeted therapy, such as human epidermal growth factor receptor 2 (HER-2). Therefore, tumor budding is a major element in the formulation of risk stratification and precision medicine strategies for patients with gastric cancer.

The park-integrated energy system can achieve the optimal allocation, dispatch, and management of energy by integrating various energy resources and intelligent control and monitoring. Flexible load participation in scheduling can reduce peak and valley load, optimize load curves, further improve energy utilization efficiency, and reduce system costs. Based on this, firstly, a flexible power-load model is established considering the translatable load, transferable load, and reducible load; and a thermal flexible load model is established based on the fuzziness of user perception of temperature in this study; then, the mixed integer linear programming method is adopted, and the sum of the carbon transaction cost, operation and maintenance cost, compensation cost, power purchase cost, gas purchase cost, wind and light abandonment penalty cost and investment cost of the system is minimized as the objective function, and the configuration of the integrated energy system is optimized, and the optimal capacity of each equipment and the output of each period are obtained. Finally, taking an industrial park in Liaoning Province of China as an example, the analysis is carried out. The example results show that by scheduling the flexible electrical load and flexibly adjusting the indoor temperature, renewable energy consumption can be promoted, and electricity load and heat-load curves can be optimized to increase the installed capacity of wind turbines, reduce the capacity of gas turbines, batteries, and heat-storage tanks, improve system economy, and improve the penetration rate of renewable energy.

Microalgae have high lipid accumulation capacity, high growth rate and high photosynthetic efficiency which are considered as one of the most promising alternative sustainable feedstocks for producing lipid-based biofuels. However, commercialization feasibility of microalgal biofuel production is still conditioned to the high production cost. Enhancement of lipid accumulation in microalgae play a significant role in boosting the economics of biofuel production based on microalgal lipid. The major challenge of enhancing microalgal lipid accumulation lies in overcoming the trade-off between microalgal cell growth and lipid accumulation. Substantial approaches including genetic modifications of microalgal strains by metabolic engineering and process regulations of microalgae cultivation by integrating multiple optimization strategies widely applied in industrial microbiology have been investigated. In the present review, we critically discuss recent trends in the application of multiple molecular strategies to construct high performance microalgal strains by metabolic engineering and synergistic strategies of process optimization and stress operation to enhance microalgal lipid accumulation for biofuel production. Additionally, this review aims to emphasize the opportunities and challenges regarding scaled application of the strategic integration and its viability to make microalgal biofuel production a commercial reality in the near future.

Abstract Given the continuous and growing demand for point of care (POC) diagnostic tests, attention has been shifted toward integration and miniaturization of laboratory protocols into “sample‐in‐answer‐out” devices. Microfluidic technologies have been considered an ideal solution to address the requirements of POC diagnostics since many laboratory functions can be miniaturized and incorporated onto a single integrated chip. In this review, we summarize the advances of integrated microfluidic devices for POC diagnostics in the last 3 years. Particularly, we summarize current materials used for microfluidic chip fabrication, discuss the innovation of versatile integrated microfluidic devices, especially the strategies for simplifying sample preparation in manual or self‐driven systems, and new detection methods of microfluidic chips. In addition, we describe new integrated microfluidic devices for POC diagnostics of protein‐targeted immunodiagnostics, nucleic acid molecular tests, and small molecule metabolites analysis. We also provide future perspectives and current challenges for clinical translation and commercialization of these microfluidic technologies.

Background: Osteosarcoma (OS) is a kind of solid tumor with high heterogeneity at tumor microenvironment (TME), genome and transcriptome level. In view of the regulatory effect of metabolism on TME, this study was based on four metabolic models to explore the intertumoral heterogeneity of OS at the RNA sequencing (RNA-seq) level and the intratumoral heterogeneity of OS at the bulk RNA-seq and single cell RNA-seq (scRNA-seq) level.Methods: The GSVA package was used for single-sample gene set enrichment analysis (ssGSEA) analysis to obtain a glycolysis, pentose phosphate pathway (PPP), fatty acid oxidation (FAO) and glutaminolysis gene sets score. ConsensusClusterPlus was employed to cluster OS samples downloaded from the Target database. The scRNA-seq and bulk RNA-seq data of immune cells from GSE162454 dataset were analyzed to identify the subsets and types of immune cells in OS. Malignant cells and non-malignant cells were distinguished by large-scale chromosomal copy number variation. The correlations of metabolic molecular subtypes and immune cell types with four metabolic patterns, hypoxia and angiogenesis were determined by Pearson correlation analysis.Results: Two metabolism-related molecular subtypes of OS, cluster 1 and cluster 2, were identified. Cluster 2 was associated with poor prognosis of OS, active glycolysis, FAO, glutaminolysis, and bad TME. The identified 28608 immune cells were divided into 15 separate clusters covering 6 types of immune cells. The enrichment scores of 5 kinds of immune cells in cluster-1 and cluster-2 were significantly different. And five kinds of immune cells were significantly correlated with four metabolic modes, hypoxia and angiogenesis. Of the 28,608 immune cells, 7617 were malignant cells. The four metabolic patterns of malignant cells were significantly positively correlated with hypoxia and negatively correlated with angiogenesis.Conclusion: We used RNA-seq to reveal two molecular subtypes of OS with prognosis, metabolic pattern and TME, and determined the composition and metabolic heterogeneity of immune cells in OS tumor by bulk RNA-seq and single-cell RNA-seq.

This paper presents a comprehensive review of the research studies on direct energy system effect on aircraft composite structures to develop a good understanding of state-of-the-art research and development in this area. The review begins with the application of composite materials in the aircraft structures and highlights their particular areas of application and limitations. An overview of directed energy system is given. Some of the commonly used systems in this category are discussed and the working principles of laser energy systems are described. The experimental and numerical studies reported regarding the aircraft composite structures subject to the effect of directed energy systems, especially the laser systems are reviewed in detail. In particularly, the general effects of laser systems and the relevant damage mechanisms against the composite structures are reported. The review draws attention to the recent research and findings in this field and is expected to guide engineers/researchers in future theoretical, numerical, and experimental studies.

Leaf rolling is an important agronomic trait in wheat (Triticum aestivum L.). Moderate leaf rolling keeps leaves upright and maintains the relatively normal photosynthesis of plants under drought stress. However, the molecular mechanism of wheat leaf rolling remains unclear. Here, we identified a candidate gene TaMYB5-3A that regulates leaf rolling by using a genome-wide association study (GWAS) in a panel of 323 wheat accessions. Phenotype analysis indicated that the leaves of tamyb5 mutants were flatter than that of the wild type under drought condition. A nucleotide variation in the TaMYB5-3A coding region resulted in a substitution of Thr to Lys, which corresponds to two alleles SNP-3A-1 and SNP-3A-2. The leaf rolling index (LRI) of the SNP-3A-1 genotype was significantly lower than that of the SNP-3A-2 genotype. In addition, TaMYB5-3A alleles were associated with canopy temperature (CT) in multiple environments. The CT of the SNP-3A-1 genotype was lower than that of the SNP-3A-2 genotype. Gene expression analysis showed that TaMYB5-3A was mainly expressed in leaves and down-regulated by PEG and ABA treatment. TaMYB5 induces TaNRL1 gene expression through the direct binding to the AC cis-acting element of the promoter of the target gene, which was validated by EMSA (electrophoretic mobility shift assay). Our results revealed a crucial molecular mechanism in wheat leaf rolling and provided the theoretical basis and a gene resource for crop breeding.

Abstract Small molecule inhibitors (SMIs) of key signalling pathways are known to induce multiple types of regulated cell death, including immunogenic cell death (ICD). The resulting antitumor immunity helps to overcome the resistance of cancer cells to cell death, resulting in improved cancer therapy. SMIs, especially those inducing multimodal cell death and ICD, can be critical components in rational combinations for cancer immunotherapy.

To formulate fluids with flowback water, produced water directly to improve the utilization rate of recycling and reduce the adsorption damage of slick water to reservoirs, a high salt tolerance and low adsorption drag reducer was designed and prepared by introducing polar cation fragments to enhance the non-covalent interactions between the chains. The drag reducer was characterized by IR and NMR. Friction resistance and viscosity tests were conducted to evaluate its salt resistance property. Static adsorption and dynamic adsorption retention tests were carried out to evaluate the damage of this reducer to shale reservoirs. The introduction of cation units into the molecular structure can weak the shielding effect of metal cations to some extent, so the drag reducer can keep a stable molecular structure and good resistant reducing performance under high salinity. The enhancement of non-covalent interaction between chains decreased the free polarity sites, further reduced the possibility of hydrogen bonding between drag reducer molecules and shale. In high salinity condition, both the adsorption capacity of the drag reducer on the shale surface and the average damage rate to the core permeability are low. Compared with the conventional salt-tolerant system, the overall liquid cost was reduced by 17% and the production per well increased by 44%. The application of this slick water system has achieved remarkable results.

Gastric cancer, which has a high incidence and poor prognosis, remains a therapeutic challenge. Recently, neoadjuvant therapy has attracted increasing attention due to high recurrence rate and low survival rate after resection in most patients with advanced stage. Clinical trials show that neoadjuvant approaches confer a significant survival advantage for resectable locally advanced gastric cancer. The specific advantages of chemoradiotherapy compared with chemotherapy have not been clarified; optimal regimens and cycles, particularly in the preoperative setting, should be studied further; and trials aimed at determining the role of targeted and immunological therapies should be conducted.

Abstract Background Emerging evidence has shown that dysregulated expression of long noncoding RNAs (lncRNAs) is implicated in liver hepatocellular carcinoma (HCC). However, the role and molecular mechanism of differentially expressed lncRNAs in HCC has not been fully explained. Methods The expression profiles of lncRNAs in HCC samples were derived from microarrays analysis or downloaded from The Cancer Genome Atlas (TCGA), and their correlation with prognosis and clinical characteristics were further analyzed. Silencing of lncRNA ZFPM2-AS1 was conducted to assess the effect of ZFPM2-AS1 in vitro. The miRcode and Target Scan databases were used to determine the lncRNA-miRNA-mRNA interactions. The biological functions were demonstrated by luciferase reporter assay, western blotting, PCR and rescue experiments. Results The expression level of lncRNA ZFPM2-AS1 was significantly higher in HCC tissues than in adjacent normal tissues, and higher ZFPM2-AS1 was remarkably related to poor survival. Functionally, silencing of lncRNA ZFPM2-AS1 inhibited cell proliferation, migration, invasion and promoted cell apoptosis in vitro. Bioinformatics analysis based on the miRcode and TargetScan databases showed that lncRNA ZFPM2-AS1 regulated GDF10 expression by competitively binding to miR-139. miR-139 and downregulated GDF10 reversed cell phenotypes caused by lncRNA ZFPM2-AS1 by rescue analysis. Conclusions ZFPM2-AS1, an upregulated lncRNA in HCC, was associated with malignant tumor phenotypes and worse patient survival. ZFPM2-AS1 regulated the progression of HCC by acting as a competing endogenous RNA (ceRNA) to competitively bind to miR-139 and regulate GDF10 expression. Our study provides new insight into the posttranscriptional regulation mechanism of lncRNA ZFPM2-AS1 and suggests that ZFPM2-AS1/miR-139/GDF10 may act as a potential therapeutic target and prognostic biomarker for HCC.

Single-cell RNA-seq can reveal accurate and precise cell types and states. Here the authors present an scRNA-seq platform, Paired-seq, which uses differential flow resistance to achieve 95% cell utilisation efficiency for improved cell-free RNA removal and gene detection.