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ABSTRACTLiver cancer, one of the most common malignant tumors, has seriously threatened people’s physical and mental health. The paper was conducted to investigate the functions of two different anesthesia methods on Tumor necrosis factor-α (TNF-α), C-reactive protein (CRP) and T lymphocyte subsets in patients undergoing liver cancer resection, and to explore the liver function impact of patients undergoing liver cancer surgery. 80 liver cancer patients were split into propofol intravenous anesthesia group and sevoflurane inhalation anesthesia group. The patient’s operation-related indicators and changes in TNF-α, CRP and T lymphocyte subsets before anesthesia, after anesthesia, 1 day after anesthesia, and 3 days after anesthesia were calculated. The levels of TNF-α and CRP in the two groups after operation were clearly higher than those before anesthesia, but there was no obvious difference between the two groups. After operation, the TNF-α of the propofol intravenous anesthesia group was lower than the sevoflurane inhalation anesthesia group. The CD3+, CD4+ and CD4+/CD8+ levels in both groups recovered to the pre-anaesthesia level 3 days after the operation. The levels of ALT, AST, ALB and TBIL returned to normal at d4 in both propofol intravenous anesthesia and sevoflurane inhalation anesthesia groups. Compared with evoflurane inhalation anesthesia for patients with liver cancer, intravenous anesthesia with propofol can reduce the body’s inflammatory response to a certain extent, has weak inhibitory effect on T lymphocyte immune function, and a smaller effect on liver function.

Primary diabetes care and diabetic retinopathy (DR) screening persist as major public health challenges due to a shortage of trained primary care physicians (PCPs), particularly in low-resource settings. Here, to bridge the gaps, we developed an integrated image–language system (DeepDR-LLM), combining a large language model (LLM module) and image-based deep learning (DeepDR-Transformer), to provide individualized diabetes management recommendations to PCPs. In a retrospective evaluation, the LLM module demonstrated comparable performance to PCPs and endocrinology residents when tested in English and outperformed PCPs and had comparable performance to endocrinology residents in Chinese. For identifying referable DR, the average PCP’s accuracy was 81.0% unassisted and 92.3% assisted by DeepDR-Transformer. Furthermore, we performed a single-center real-world prospective study, deploying DeepDR-LLM. We compared diabetes management adherence of patients under the unassisted PCP arm (n= 397) with those under the PCP+DeepDR-LLM arm (n= 372). Patients with newly diagnosed diabetes in the PCP+DeepDR-LLM arm showed better self-management behaviors throughout follow-up (P< 0.05). For patients with referral DR, those in the PCP+DeepDR-LLM arm were more likely to adhere to DR referrals (P< 0.01). Additionally, DeepDR-LLM deployment improved the quality and empathy level of management recommendations. Given its multifaceted performance, DeepDR-LLM holds promise as a digital solution for enhancing primary diabetes care and DR screening.

Combining photodynamic therapy (PDT) with chemodynamic therapy (CDT) has been proven to be a promising strategy to improve the treatment efficiency of cancer, because of the synergistic therapeutic effect arising between the two modalities. Herein, we report an inorganic nanoagent based on ternary NiCoTi-layered double hydroxide (NiCoTi-LDH) nanosheets to realize highly efficient photodynamic/chemodynamic synergistic therapy. The NiCoTi-LDH nanosheets exhibit oxygen vacancy-promoted electron-hole separation and photogenerated hole-induced O2-independent reactive oxygen species (ROS) generation under acidic circumstances, realizing in situpH-responsive PDT. Moreover, due to the effective conversion between Co3+and Co2+caused by photogenerated electrons, the NiCoTi-LDH nanosheets catalyze the release of hydroxyl radicals (·OH) from H2O2through Fenton reactions, resulting in CDT. Laser irradiation enhances the catalyzed ability of the NiCoTi-LDH nanosheets to promote the ROS generation, resulting in a better performance than TiO2nanoparticles at pH 6.5. In vitroand in vivoexperimental results show conclusively that NiCoTi-LDH nanosheets plus irradiation lead to efficient cell apoptosis and significant inhibition of tumor growth. This study reports a new pH-responsive inorganic nanoagent with oxygen vacancy-promoted photodynamic/chemodynamic synergistic performance, offering a potentially appealing clinical strategy for selective tumor elimination.

The aggregation behavior of ubiquitous dissolved black carbon (DBC) largely affects the fate and transport of its own contaminants and the attached contaminants. However, the photoaging processes and resulting effects on its colloidal stability remain yet unknown. Herein, dissolved biochars (DBioCs) were extracted from common wheat straw biochar as a proxy for an anthropogenic DBC. The influences of UV radiation on their aggregation kinetics were systematically investigated under various water chemistries (pH, electrolytes, and protein). The environmental stability of the DBioCs before and after radiation was further verified in two natural water samples. Hamaker constants of pristine and photoaged DBioCs were derived according to Derjaguin–Landau–Verwey–Overbeek (DLVO) prediction, and its attenuation (3.19 ± 0.15 × 10–21J to 1.55 ± 0.07 × 10–21J after 7 days of radiation) was described with decay kinetic models. Pearson correlation analysis revealed that the surface properties and aggregation behaviors of DBioCs were significantly correlated with radiation time (p< 0.05), indicating its profound effects. Based on characterization and experimental results, we proposed a three-stage mechanism (contended by photodecarboxylation, photo-oxidation, and mineral exposure) that DBioCs might experience under UV radiation. These findings would provide an important reference for potential phototransformation processes and relevant behavioral changes that DBC may encounter.

Great efforts have been devoted to the development of novel and multifunctional wound dressing materials to meet the different needs of wound healing. Herein, we covalently grafted quaternary ammonium groups (QAGs) containing 12-carbon straight-chain alkanes to the dextran polymer skeleton. We then oxidized the resulting product into oxidized quaternized dextran (OQD). The obtained OQD polymer is rich in antibacterial QAGs and aldehyde groups. It can react with glycol chitosan (GC) via the Schiff-base reaction to form a multifunctional GC@OQD hydrogel with good self-healing behavior, hemostasis, injectability, inherent superior antibacterial activity, biocompatibility, and excellent promotion of healing of methicillin-resistant Staphylococcus aureus(MRSA)-infected wounds. The biosafe and nontoxic GC@OQD hydrogel with a three-dimensional porous network structure possesses an excellent swelling rate and water retention capacity. It can be used for hemostasis and treating irregular wounds. The designed GC@OQD hydrogel with inherent antibacterial activity possesses good antibacterial efficacy on both S. aureus(Gram-positive bacteria) and Escherichia coli(Gram-negative bacteria), as well as MRSAbacteria, with antibacterial activity greater than 99%. It can be used for the treatment of wounds infected by MRSAand significantly promotes the healing of wounds. Thus, the multifunctional antibacterial GC@OQD hydrogel has the potential to be applied in clinical practice as a wound dressing.

Stacked autoencoders (SAEs) have been widely used in soft sensing of industrial process data. However, most of them extract features by minimizing the reconstruction error of the input data at each layer, leading to accumulated loss. Moreover, the extraction of quality-related features is crucial for soft sensing. To address these issues, this article first introduces a novel stacked dual-guided autoencoder (SDGAE) to better characterize intricate data patterns and learn quality-associated features. Compared to SAE, the idea of SDGAE lies in stacking a series of hierarchical dual-guided autoencoder (DGAE), aiming to allow each DGAE to accurately reconstruct the original input data. It also enables the model to simultaneously extract features that are highly correlated with the output variable by introducing a supervisor term. Furthermore, practical scenarios typically involve limited labeled data and a substantial volume of unlabeled data, which renders the network deficient in adequate generalization capabilities. To address this predicament, we further propose a deep semi-supervised SDGAE (SSDGAE), it is able to obtain useful feature representations and structural information from unlabelled data in the pretraining phase in addition to the labeled data as SDGAE is able to do. Finally, the proposed methods are verified on two real industrial cases for its effectiveness and superiority. The results indicate that our approach can simultaneously utilize both labeled and unlabeled data to enhance the predictive performance of quality variables.

Introduction: Detecting a pulse correctly is a key process in nuclear detection. Because the radiation emission is a random process, it is hard to design a suitable peak-detection approach in FPGA. The error detection will influence the final energy spectrum and flood histogram. In order to improve the result of nuclear detection, this paper proposes a novel method for nuclear signal peak-detection, which can improve both the effective counting rate and the quality of pulses in real-time. Methods: The main method is to establish a normalized reference pulse regardless of waveform through the least squares method. By calculating the loss between the incoming data stream and normalized reference pulse, this algorithm retains the pulses whose loss is below the threshold. We select the threshold based on statistical methods. The algorithm is implemented on field programmable gate array (FPGA) successfully, and this process is able to work in real-time. Conclusion: The result shows that the effective counting rate can improve about 19.8% and more than 99% pile-up and error pulses will be suppressed. By analyzing reserved pulses, the energy spectrum and flood histogram could be well rectified. The energy resolution increases 11% compared with traditional algorithm. Furthermore, due to this new algorithm, the low-energy threshold can be lower.

MTBH, a novel hesperetin derivative, possesses in vivo hepatoprotective effects against carbon tetrachloride (CCl4)-induced acute liver injury in Institute of Cancer Research (ICR) mice. This study investigated the pharmacokinetics and tissue distribution of MTBH and its conjugated metabolites in rats after a single dose of MTBH. Male Sprague–Dawley (SD) rats were orally administered (25, 50, 100 mg/kg) or intravenously administered (25 mg/kg) MTBH and blood samples were withdrawn at specific times. Moreover, after a single oral dose of MTBH (200 mg/kg), tissues (heart, liver, spleen, lung, kidney, stomach, intestine, brain and muscle) were collected at scheduled time points. The concentration of MTBH in plasma and tissues was assayed by HPLC before and after hydrolysis with β-glucuronidase or sulfatase. The glucuronides/sulfates were extensively present in the plasma, moreover, the free form was detectable in the plasma, but in a small amount equivalent to nearly 0.85–1.46 % of the amount of glucuronides/sulfates, the absolute bioavailability of MTBH was approximately 31.27 %. In tissues, the free form appeared in all tissues examined, with trace amount in brain and muscle, and considerable concentration in stomach and lung. Glucuronides/sulfates were the major forms in intestine, kidney and liver, whereas not detectable in heart, brain and muscle. The liver and intestine were found likely to accumulate MTBH at a high concentration among all tissues. The free form of MTBH was present in the circulation and all assayed organs, whereas its glucuronides/sulfates were the major forms in plasma and intestine, kidney and liver after a single dose.

ABSTRACTBackgroundDrug-induced seizures are a common occurrence in clinical practice, with research indicating that around 6% of initial seizures are due to drug toxicity. The use of antibiotics is one such cause of drug-related seizures. Previous systematic review has identified specific antibiotics that pose a risk of seizures, but a comprehensive analysis of a large patient sample is needed to determine the risk associated with various drugs.ObjectiveThis study aimed to evaluate the association between seizures and various antibiotics that are presently accessible.MethodsTo identify potential risk signals from the US Food and Drug Administration adverse event reporting system (FAERS) database, a disproportionality analysis was conducted. The reporting odds ratio (ROR) using the frequency approach and the information component (IC) using the Bayesian approach were used to detect signals. The median time-to-onset of seizure, as well as the Weibull distribution parameters were calculated to analyze the onset time.ResultsA total of 14,407,157 FAERS reports were analyzed.10 antibiotics were associated with seizures that were defined by 41 preferred terms. Onset time were aligned with the wear out failure type profile.ConclusionThis study identified 10 antibiotics that showed significant associations with seizures. Imipenem-cilastatin had the highest seizure ROR.

The current optical anticounterfeit strategies that rely on multimode luminescence in response to the photon or thermal stimuli have significant importance in the field of anticounterfeiting and information encryption. However, the dependence on light and heat sources might limit their flexibility in practical applications. In this work, Er3+single-doped CaF2phosphors that show multistimuli-responsive luminescence have been successfully prepared. The as-obtained CaF2:Er3+phosphor exhibits green photoluminescence (PL) and color-tunable up-conversation (UC) luminescence from red to green due to the cross-relaxation of Er3+ions. Additionally, as-obtained CaF2:Er3+phosphors also display green mechano-luminescence behavior, which is induced by the contact electrification between the CaF2particles and PDMS polymers, enabling the phosphor to flexibly respond to mechanical stimuli. Moreover, feasible anticounterfeiting schemes with the capability of multistimuli-responsive and flexible decryption have been constructed, further expanding the application of optical materials in the field of advanced anticounterfeiting and information encryption.

Patients with higher levels of serum PRL had higher risks for both all-cause and cardiovascular disease (CVD) mortality, and PRL may be considered as a potential biomarker of mortality among patients with type 2 diabetes.A positive association between serum prolactin levels and the risks of all-cause and CVD mortality among patients with type 2 diabetes was found, and findings were consistent among patients with different characteristics at baseline and in different sub-cohorts.An increasing level of PRL during follow-ups may add prognostic value for all-cause and CVD mortality.Graphical Abstract

Purpose: To investigate the association between circulating osteocalcin and incident cardiovascular diseases in a community-based cohort, and further assess whether the association differs by different glycemic stages. Methods: This cohort study included 1428 participants (626 men and 802 women) aged 50–80 years, without baseline cardiovascular diseases, and with osteocalcin data available. Circulating total osteocalcin levels were measured by electrochemiluminescence immunoassay. Multivariate Cox proportional hazards models were used to assess the relationship between osteocalcin levels and different glycemic stages with cardiovascular events. Results: At baseline, 437 participants were normoglycaemia and 991 participants were hyperglycaemia. Median circulating osteocalcin levels were 16.43 (13.34–20.19) and 21.66 (17.95–26.11) ng/mL in men and women, respectively. During a mean follow-up of 7.6 years, 144 cases of cardiovascular diseases occurred (10.1%). The risk of incident cardiovascular diseases linearly increased with a decrease in baseline osteocalcin quartiles (quartile 1 versus quartile 4: hazard ratio 2.44, 95% confidence interval 1.07–5.55) in women, while not in men (Pinteraction on sex= 0.028). Subgroup analyses showed that the association was more predominant in participants with baseline hyperglycaemia. Besides, the joint effect of baseline decreased osteocalcin levels and hyperglycaemia resulted in higher risks of future cardiovascular diseases. Conclusions: Low baseline osteocalcin levels were associated with high risks of cardiovascular diseases in middle-aged and elderly women, which were more predominant among those with baseline hyperglycaemia.

Over the last decades, bone tissue engineering has increasingly become a research focus in the field of biomedical engineering, in which biomaterials play an important role because they can provide both biomechanical support and osteogenic microenvironment in the process of bone regeneration. Among these biomaterials, two-dimensional (2D) nanomaterials have recently attracted considerable interest owing to their fantastic physicochemical and biological properties including great biocompatibility, excellent osteogenic capability, large specific surface area, and outstanding drug loading capacity. In this review, we summarize the state-of-the-art advances in 2D nanomaterials for bone tissue engineering. Firstly, we introduce the most explored biomaterials used in bone tissue engineering and their advantages. We then highlight the advances of cutting-edge 2D nanomaterials such as graphene and its derivatives, layered double hydroxides, black phosphorus, transition metal dichalcogenides, montmorillonite, hexagonal boron nitride, graphite phase carbon nitride, and transition metal carbonitrides (MXenes) used in bone tissue engineering. Finally, the current challenges and future prospects of 2D nanomaterials for bone tissue regeneration in process of clinical translation are discussed.

The Controller Area Network (CAN) dominates in-vehicle networking systems in modern vehicles. CAN was designed with low-latency and reliability as key features. Authenticity of a CAN frame was not considered in the design, thus, most in-vehicle network nodes inherently trust received messages as coming from a legitimate source. As a result, it is trivial to program (or hack) a network node to spoof traffic. Authentication is challenging for CAN and related protocols, such as SAE J1939, due to limited frame sizes and high bus utilization. Adding a message authentication code (MAC) as a separate message can unduly stress the real-time delivery of safety-critical messages. Although this stressor is well-known, the impact of authentication protocols on real-time message delivery in CAN has not yet been thoroughly examined. In this paper, we provide the first comprehensive analysis of real-time schedulability analysis applied to authentication schemes for CAN, CAN Flexible Data-rate (CAN FD), and CAN extra long payload (CAN XL). We formulate the response time analysis for addition of MACs and periodic transmission of MACs, and we examine their impact on two case studies and through evaluation with randomized schedulability experiments over a wide range of message sets.

Purpose: Accurate localization of radioactive materials is critical to nuclear safety and nuclear security. A coded aperture imaging system provides a visualization solution. However, the correlation method has poor reconstruction performance for sources with low counts and for extended sources. Methods: In this study, a Monte Carlo optimization-based MLEM algorithm (MC-MLEM) is proposed. The system matrix was obtained by accurate Monte Carlo simulation, so the physical effects such as mask penetration that affect the imaging process were taken into account in the MLEM algorithm. In the simulation process, the normalization of the system matrix was realized by controlling the source at different position of the source plane to have the same activity and emission angle. Results: The experimental results showed that compared with the correlation method, the MC-MLEM algorithm could improve the signal-to-noise ratio and angular resolution and locate the source position quickly and accurately under low count conditions. Furthermore, the MC-MLEM algorithm could reconstruct the shape of the extended source and the expected activity ratio of cold-hot sources with large activity differences. Conclusion: The MC-MLEM algorithm improved the imaging results and enhanced the reconstruction performance.

The ultralow delay tracking system, which enables seamless actuation in visual feedback applications, draws increasing attention in the fields of robotics and factory automation (FA). Tracking accuracy and rotational robustness are critical in robotics and FA applications. In the real-time scene, the change (e.g., object moving) continues in the real space when tracking processing is performed in the virtual (computing) space. However, existing research focuses primarily on the image-processing accuracy of still images, with few works paying attention to tracking errors introduced by the change that occurs during the processing period. However, making the algorithm robust to rotation comes with a complex model, preventing the whole system from reaching an ultralow delay. This research aims to develop a 1-ms rotation-robust Lucas Kanade (LK)-based tracking algorithm and processing architecture, focusing on minimizing the error between the virtual space’s output and the true state in real space. To achieve the above target, this article proposes: 1) temporal prediction-based temporal iterative tracking (TIT), which compensates for temporal change with temporal prediction, significantly reducing real-time processing error and 2) temporal prediction-based parallel motion estimation, which breaks the data dependency of translation and rotation estimations by temporal prediction, allowing translation and rotation estimation to be performed parallelly with low delay. The proposed methods are implemented as a practical system by integrating a high-speed camera and a field programmable gate array (FPGA). Algorithm evaluation shows that the proposed method outperforms the other five related methods in terms of real-time tracking performance. Hardware evaluation shows that the designed rotation-robust LK-based tracking system supports sensing and processing a 1000-fps sequence with a delay of less than 1 ms/frame while costing resources less than 30%. A video demonstration is available at https://wcms.waseda.jp/em/6422257c9c402.

Isoniazid (INH) and rifampicin (RIF) are co-administered in tuberculosis treatment but can cause neurotoxicity, and the mechanism is not known. To explore this mechanism, we employed an integrated approach using metabolomics analysis (MA) and proteomics analysis (PA). Male mice were divided into three groups and administered vehicle (control group), or co-administered INH (120 mg/kg) and RIF (240 mg/kg), for 7 or 14 days. Mice brains were collected for mass spectrometry-based PA and MA plus lipidomics analysis. Measurement of brain levels of malondialdehyde and superoxide dismutase revealed time-dependent brain injury after exposure to INH+RIF for 7 and 14 days. Also, 422 proteins, 35 metabolites, and 21 lipids were dysregulated and identified. MA demonstrated “purine metabolism,” “phenylalanine, tyrosine and tryptophan biosynthesis,” “biosynthesis of unsaturated fatty acids,” “phenylalanine metabolism,” and “arginine biosynthesis” to be disturbed significantly. PA demonstrated pathways such as “lipids,” “amino acids,” and “energy metabolism” to be disrupted. Peroxisome proliferator-activated receptor (PPAR) pathways were changed in energy metabolism, which led to the neurotoxicity induced by INH+RIF. Immunohistochemical analyses of PPARs in mice brains verified that PPAR-α and -γ expression was downregulated. PPAR-α and -γ activation might be a key target for alleviating INH+RIF-induced neurotoxicity.

Although phototherapy has attracted extensive attention in antitumor field in recent years, its therapeutic effect is usually unsatisfactory because of the complexity and variability of the tumor microenvironment (TME). Herein, we report novel CoSn(OH)6@CoOOH hollow carriers with oxidase properties that can enhance phototherapy. Hollow CoSn(OH)6@CoOOH nanocubes (NCs) with a particle size of ∼160 nm were synthesized via a two-step process of coprecipitation and etching. These NCs can react with O2to generate singlet oxygen without hydrogen peroxide and consume glutathione, and their hollow structure can be utilized to carry drug molecules. After loading indocyanine green (ICG) and 1,2-bis(2-(4,5-dihydro-1H-imidazol-2-yl)propan-2-yl) diazene dihydrochloride (AIPH), the resulting nanosystem (HCIA) exhibited enhanced phototherapy effects through the catalytic activity of oxidase, production of alkyl radicals, and consumption of glutathione. Cell and mouse experiments showed that HCIA combined with near-infrared laser irradiation significantly inhibited the growth of 4T1 tumors. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that PI3K-Akt and MAPK signaling pathways were highly relevant to this therapeutic system. Such hollow NCs with oxidase activity have considerable potential for the design of multifunctional drug delivery vehicles for tumor therapy.

1-ms vision systems represent an extreme case of temporal development in video sensing techniques. Moreover, a 1-ms dual-hand tracking system leverages the dexterous functionality of hands and thus serves as a seamless and intuitive interface for Human-Computer Interaction. Deep CNN is promising for high tracking robustness, however, neither GPU-based nor FPGA-based implementation addresses the tracking task with ultra-high-speed. This paper proposes: (a) A paradigm to directly map a deep CNN as a hardwired circuit, so the entire network runs in parallel and high processing speed is obtained. The network is exempted from memory access since all intermediate neural values are implicitly represented in hardware states. And condensed binarization is used to reduce resource utilization; (b) Hardware design of the hardwired network on FPGA, inside which kernel-adapted convolutional trees are devised to maximize the parallelism. The speed bottleneck of the network is therefore removed by implementing convolutional layers as fine-grained pipelines with unified components; (c) FPGA-GPU hetero complementation, which utilizes an auxiliary GPU network to compensate for accuracy of the FPGA network without affecting its speed. The quick primary results on FPGA are intermittently refined using delayed but accurate hints from GPU. Implementation results show that the proposed method reaches 973fps and consumes merely 1.30ms to process on $640\times 480$ images, while the accuracy is only 4.7% lower compared with the general method on test sequences. Video demonstrations are available at https://wcms.waseda.jp/em/5f9d020f136e7.

Nanoparticles that employ stimuli-responsive polymeric delivery carriers have emerged as intelligent nanoplatforms with great potential in cancer theranostics, mainly including cancer diagnosis, controlled/triggered drug delivery, and real-time monitoring of therapeutic response. Particularly, tumor microenvironment (TME)-responsive polymeric nanocarriers in response to weak acidity, hypoxia, reactive oxygen species (ROS), glutathione (GSH), or tumor enzymes in the TME show great promise in facilitating tumor accumulation, enhancing tumor penetration, prolonging tumor retention, and achieving controlled drug release, thereby improving the efficiency of tumor therapy. Besides, the combination of chemotherapy and phototherapy presents a promising endeavor for the treatment of tumors, which allows for the integration of the advantages of each treatment modality, addressing the shortcomings of the two methods, and amplifying the efficacy of tumor treatment while reducing adverse reactions. This review focuses on the latest progress in the development of TME-responsive polymeric nanoparticles for synergetic chemo-photo therapy, and discusses the critical challenges and future considerations involved in the fabrication of TME-responsive nanocarriers.

RING finger E3 ligases play an important role in regulating plant growth and development by mediating substrate degradation. In this study, we identified TaGW2L, encoding a Grain width and weight2 (GW2)-like RING finger E3 ligase, as a novel positive regulator of heading date in wheat (Triticum aestivumL.). TaGW2L exhibited high amino acid sequence similarities with TaGW2 homoeologs, particularly in the conserved RING finger domain. Expression analysis indicated that TaGW2Lwas constitutively expressed in various wheat tissues. TaGW2L showed transactivation activity in yeast and could interact with the ubiquitin-conjugating enzymes E2s. An in vitroubiquitination assay verified that TaGW2L possessed a similar E3 ligase activity to TaGW2. Overexpression of the TaGW2L-7Ahomoeolog in wheat led to a significantly earlier heading date under both natural conditions and long-day conditions. Transcriptome analysis revealed that multiple known genes positively regulating wheat heading were significantly upregulated in the TaGW2L-7A-overexpression plants compared with the wild-type control. Together, our findings shed light on the role of TaGW2Lin wheat heading date and provide potential applications of TaGW2Lfor the adaptation improvement of crops.

The high conductivity of electrocatalyst can eliminate the Schottky energy barrier at the interface of heterogeneous phases during an electrocatalytic reaction and accelerate the rapid electron transfer to the catalytic active center. Therefore, the electronic conductivity is a vital parameter for oxygen reduction reaction (ORR). Covalent triazine frameworks (CTFs) have shown great potential application as electrocatalysts in ORR with a merit of the diverse building blocks. However, the intrinsic low conductivity and high impedance of CTFs could be significant setbacks in electrocatalytic application. Herein, CTFs were constructed by introducing F and N co-modification for efficient 2e−ORR. Compared with the pristine CTF, the co-presence of F, N could increase the conductivity obviously by 1000-fold. As a result, F-N-CTF exhibits enhanced catalytic performance of H2O2generation and selectivity towards reaction pathways. This work reveals the importance of conductivity optimization for CTFs and provides guidance for designing high conductivity non-metallic organic semiconductor catalysts for 2e−ORR.

This study explored the exclusive characteristics of octogenarians treated with radical resection for colorectal cancer.

•Inhibiting or silencing SMOX can alleviate LPS-induced hepatocyte injury.•Inhibiting SMOX can alleviate the inflammation and fibrosis in mouse liver.•Inhibiting or silencing SMOX can inhibit the nuclear transfer of β-catenin.•SMOX may be a target to alleviate hepatocyte inflammation and fibrosis and block HCC.

Poly(methyl methacrylate) (PMMA) bone cement has been widely used in orthopedic surgeries including total hip/knee replacement, vertebral compression fracture treatment, and bone defect filling. However, aseptic loosening of the interface between PMMA bone cement and bone often leads to failure. Hence, the development of modified PMMA that facilitates the growth of bone into the modified PMMA bone cement is key to reducing the incidence of aseptic loosening. In this study, MgAl-layered double hydroxide (LDH) microsheets modified PMMA (PMMA&LDH) bone cement with superior osseointegration performance has been synthesized. The maximum polymerization reaction temperature of PMMA&LDH decreased by 7.0 and 11.8 °C, respectively, compared with that of PMMA and PMMA&COL-I (mineralized collagen I modified PMMA). The mechanical performance of PMMA&LDH decreased slightly in comparison with PMMA, which is beneficial to alleviate stress-shielding osteolysis, and indirectly promote osseointegration. The superior osteogenic ability of PMMA&LDH has been demonstrated in vivo, which boosts bone growth by 2.17- and 18.34-fold increments compared to the PMMA&COL-I and PMMA groups at 2 months, postoperatively. Moreover, transcriptome sequencing revealed four key osteogenic pathways: p38 MAPK, ERK/MAPK, FGF, and TGF-β, which were further confirmed by IPA, qPCR, and Western blot assays. Hence, LDH-modified PMMA bone cement is a promising biomaterial to enhance bone growth with potential applications in relevant orthopedic surgeries.

Phototherapy and sonodynamic therapy (SDT) are widely used for the synergistic treatment of tumors and have received considerable attention. However, an inappropriate tumor microenvironment, including pH, H2O2, oxygen, and glutathione levels, can reduce the therapeutic effects of synergistic phototherapy and SDT. Here, a novel Bi‐based soluble microneedle (MN) is designed for the CT imaging of breast tumors and starvation therapy/gas therapy‐enhanced phototherapy/SDT. The optimized Bi/BiVO4Schottky heterojunction serves as the tip of the MN, which not only has excellent photothermal conversion ability and CT contrast properties, but its heterojunction can also avoid the rapid combination of electrons and hole pairs, thereby enhancing the photodynamic/sonodynamic effects. A degradable MN with excellent mechanical properties is fabricated by optimizing the ratios of poly(vinyl alcohol), poly(vinyl pyrrolidone), and sodium hyaluronate. Glucose oxidase (GOx) and diallyl trisulfide are loaded into the MN to achieve tumor starvation and gas therapy, respectively; And the controlled release of GOxand H2S can be achieved under ultrasound or near‐infrared laser irradiation. The in vitro and in vivo results demonstrate that this multifunctional MN can achieve high therapeutic efficacy through starvation therapy/gas therapy‐enhanced phototherapy/SDT. The designed multifunctional MN provides a prospective approach for synergistic phototherapy and SDT. An intelligent and soluble microneedle (MN) that exhibits excellent mechanical properties, outstanding CT imaging capacity, and the ability to control the release of GOxand H2S is reported. Such an MN can achieve high therapeutic efficacy through starvation and gas therapy‐enhanced phototherapy/sonodynamic therapy (SDT). The related enhancement mechanism is evaluated using Western blotting analysis.

ABSTRACTThe slowly activating delayed rectifier K+current (IKs) plays a key role in the repolarization of ventricular action potential in the human heart and is formed by the pore-forming α-subunit encoded by KCNQ1 (Kv7.1) and β-subunit encoded by KCNE1. Evidence suggested that IKswas regulated through protein kinase C (PKC) pathway, but the mechanism is controversial. This study was designed to identify the specific PKC isoform involved in the long-term regulation of IKscurrent. The IKscurrent was recorded using whole-cell patch-clamp technique in human embryonic kidney (HEK) 293B cell co-transfected with human KCNQ1/KCNE1 genes. The results revealed that both chronic activation of Ang II and PMA reduced the IKscurrent in a long-term regulation (about 24 hours). Further evidence showed that PKCε knockdown by siRNA antagonized the AngII-induced chronic inhibition on the IKscurrent, whereas knockdown of cPKC (PKCα and PKCβ) attenuated the inhibition effect of PMA on the current. Moreover, the forward transport inhibition of the channel with brefeldin A alleviated the Ang II-induced chronic inhibition on IKscurrent, while the channel endocytosis inhibition with dynasore alleviated both Ang II and PMA-induced chronic inhibition on IKscurrent. The above results showed that PKCε activation promoted the channel endocytosis and inhibited the channel forward transport to the plasma membrane, while cPKC activation only promoted the channel endocytosis, which both down regulated the channel current.

MicroRNA (miRNA) expression is perturbed in various diseases. Herein, we have aimed to develop a novel and rapid fluorescence-based assay for detecting microRNA-21 (miR-21) activity based on FAM molecular signal amplification and graphene oxide (GO) quenching. In this system, a single stranded DNA (ssDNA) with a phosphate group at the 5′-end is labeled with a FAM molecular label at the 3′-end. In the presence of miR-21, this ssDNA forms a DNA/RNA duplex, which is cleaved by λ exonuclease (λ-exo), releasing FAM and resulting in fluorescence signal amplification at 530 nm. However, the DNA/RNA duplex is not generated in the absence of miR-21, which impedes λ-exo cleavage; subsequently, GO quenches the fluorescence intensity. The results show a detection limit of 0.02 nM and a wide linear range of 0.02–5 nM. The high sensitivity and easy operability of this assay can be applied for detecting miR-21 during clinical diagnosis of certain diseases and in biological research.

Ultrathin transition metal chalcogenide (TMC) nanosheets with ultrahigh photothermal conversion efficiency (η) and excellent stability are strongly desired in the application of photothermal therapy (PTT). However, the current synthetic methods of ultrathin TMC nanosheets have issues in obtaining uniform morphology, good dispersion, and satisfactory PTT behavior. Herein, ultrathin nanosheets of CoFe-selenide (CFS) with a finely controlled structure were prepared viaa topological structural transformation process from an ultrathin CoFe-layered double hydroxide (LDH) precursor, followed by surface modification with poly(ethylene glycol) (PEG). The as-prepared CFS-PEG nanosheets inherit the ultrathin morphology of CoFe-LDH and exhibit an outstanding photothermal performance with a η of 74.5%, which is the first rank level of reported two-dimensional (2D) TMC nanosheet materials. The CFS-PEG nanosheets possess a satisfactory photoacoustic (PA) imaging capability with an ultralow detection limit (5 ppm) and simultaneously superior T2magnetic resonance imaging (MRI) performance with a large transverse MR relaxivity value (r2) of 347.7 mM–1s–1. Moreover, in vitroand in vivoassays verify superior anticancer activity with a dramatic photoinduced cancer cell apoptosis and tumor ablation. Therefore, a successful paradigm is provided for rational design and preparation of ultrathin TMC nanosheets in this work, holding enormous potential in cancer theranostics.

The intricate balance of neural stem cell (NSC) amplification and neurogenesis is central to nervous system development. Dopamine D1 receptor (DRD1) is a typical G protein‐coupled receptor (GPCR) mainly expressed in neurogenic area, with high constitutive activity. The receptor appears in the embryonic period before the formation of mature synaptic contacts, which indicates that dopamine receptor and its constitutive activity play crucial roles in the embryonic brain development. Here, we found that DRD1 was enriched in human NSCs. Inhibition of the receptor activity by its inverse agonists promoted human NSCs proliferation and impeded its differentiation. These results were also mimicked by genetic knockdown of DRD1, which also blocked the effects of inverse agonists, suggesting a receptor‐dependent manner. More interestingly, knock‐in A229T mutant with reduced DRD1 constitutive activity by CRISPR‐Cas9 genome editing technology resulted into increased endogenous human NSCs proliferation. These results were well reproduced in human cerebral organoids, and inhibition of the DRD1 constitutive activity by its inverse agonists induced the expansion and folding of human cerebral organoids. The anatomic analysis uncovered that decreasing the constitutive activity of DRD1 by its inverse agonists promoted the NSCs proliferation and maintenance that led to hindered cortical neurogenesis. Further mechanistic studies revealed that the PKC‐CBP pathway was involved in the regulation by DRD1. Thus, our findings indicate that the constitutive activity of DRD1 and possibly other GPCRs plays an important role in the development of human nervous system. Dopamine D1 receptor (DRD1) possesses the constitutive activity in human neural stem cells under normal physiological conditions. This activity maintains a basal level of neurogenic gene expression through the activation of PKC‐CBP signaling pathway. Functional interfering the constitutive activity of DRD1 with its inverse agonist or the genetic mutant leads to the decrease in the above signaling and consequent NSC excessive proliferation and cerebral organoid expansion.

In 2014, J. Pipan and M. Schechter discussed periodic solutions for second-order Hamiltonian systems with resonance. In this paper, we will generalize their results. To this end, we will first establish an index theory for second-order linear Hamiltonian systems with coefficient matrix in L1. Then we propose generalized assumptions. We also investigate multiple solutions for symmetric second-order Hamiltonian systems.

Herein, boron nitride (BN) is modified by bio-inspired dopamine chemistry to increase thermal conductivity of natural rubber (NR) dielectric elastomer. With in situ self-polymerization of dopamine, poly(dopamine) (PDA) is coated on the BN platelets surface. After PDA modification, the BN platelets are homogeneously dispersed in polymeric matrix, resulted in enhanced mechanical properties, thermal conductivity and dielectric properties. The NR composites acquire the maximum thermal conductivity coefficient (0.46 W/mK), which is approximately 460% of pure NR without thermal conductive filler (0.10 W/mK). Moreover, the NR composites exhibit high dielectric strength and large energy density due to the PDA modification on BN platelets.

•Expounding the expression, immunoinfiltration and prognostic significance of CHSTs in gastric cancer.•Constructing a prognostic nomogram with CHST14 as a key molecule in gastric cancer.•CHST14 promotes gastric cancer cell proliferation, invasion, migration and EMT through the activation of the Wnt/β-catenin signaling pathway.

Graphical Abstract

The apocrine glands (AGs) are not considered to be primarily involved in hidradenitis suppurativa (HS). This study investigated the potential role of AGs in HS pathogenesis using immunohistochemistry and single-cell sequencing of nonlesional skin (NLS) and early lesional skin (LS) from patients with HS (n = 12) and healthy controls (HC, n = 8). AG cell destruction was more frequent and AG size was significantly reduced in the NLS and LS. Barrier-related genes (e.g., claudin 1 and E-cadherin) were downregulated in the AGs of the NLS and LS. Damaged AGs in the LS primarily recruit and activate neutrophils via the CXCL-CXCR and SAA1-FPR2 pathways. Elevated levels of specific keratins (KRT18 and KRT19) released from damaged AGs were observed on the skin surface of patients and were associated with disease severity. KRT19 was also detected in the dermis of the NLS and LS and was surrounded by neutrophils and macrophages. Moreover, serum KRT19 levels in patients (n = 20) were significantly negatively correlated with the age at HS onset. Collectively, our findings provide previously unreported evidence that the AGs are damaged and release specific keratins in early HS lesions, indicating a crucial role of the AGs in HS pathogenesis.

The hydrophobicity of coal limits the adsorption of microorganisms and the efficiency of biological desulfurization was influenced, while the surfactant can enhance the interaction of the four phases, air, water, bacteria, and coal grain. In this experiment, three types of surfactant, anionic (SDS), cationic (DTAB), and nonionic (Tween 20), were investigated at 30 °C, and the cell concentration, pH value, leaching time, and coal biodesulfurization rate of the coal desulfurization system were detected. It is shown that the total desulfurization rate approached 29.7% in 16 days when 1100 mg/L Tween 20 was added in the shaking test, which represented the optimum efficiency. Further column leaching desulfurizating experiments showed that the desulfurization rate of the experimental group with Tween 20 (12.75%) was notably higher than that of the control group (8.32%). Along with the processing of desulfurization, the cell concentration decreased at first, and then rapidly increased, and finally stayed constant. The pH value of coal water slurry increased. The leaching time increased with the process of the desulfurization system. We concluded that the nonionic surfactant has a significant effect on coal biodesulfurization.

AbstractCurrently, the high-purity single crystal diamond preparation is still a challenging task, which restricts the application of diamond in electronics. In this paper, the chemical vapor deposition (CVD) IIa type single crystal diamond was prepared on the IIa type high pressure high temperature (HPHT) substrate by combining the chamber design with the plasma purifying technology, and the performance of diamond detectors using both IIa type single crystal diamonds were compared based on the defect analysis. The dislocations in diamonds were directly observed by synchrotron radiation X-ray white-beam topography. The CVD diamond shows the comparatively low dislocation density resulting from the high-quality HPHT diamond substrate. No observable NV impurity could be found in photoluminescence (PL) spectrum. The trace impurity of substitutional nitrogen (Ns) was characterized by electron paramagnetic resonance (EPR). It shows the very low concentration in the CVD diamond (2.1 ppb) compared with the several tens ppb in HPHT diamond. This value is comparable with the electronic-grade diamond reported by Element Six. Furthermore, both of the HPHT and CVD single crystal diamonds were packaged as the α-particle radiation detectors with the typical sandwich structure and used Ni/Al (50 nm/500 nm) as metal electrodes. The energy resolution of HPHT and CVD diamond detectors were 2.04% and 0.86%, respectively. Based on Schottky contact and defect regulation, at 0 voltage, the CVD diamond detector achieved response of α-particle radiation and the charge collection efficiency (CCE) was 10.76%. Under positive voltage, the CCE of HPHT and CVD diamond detectors were 38.11% and 86.65%, respectively. The deep level trapping effect of Ns impurities on charge carriers resulted in low CCE of HPHT diamond detector. The spatial polarization effect caused by defects leaded to the formation of an internal electric field, which was the main reason affecting the transport of charge carriers in CVD diamond.

Although CeO2nanomaterials have been widely explored as nanozymes for catalytic therapy, they still suffer from relatively low activities. Herein, the catalyzing generation and stabilization of oxygen vacancies on CeO2nanorods by Pt nanoclusters via H2gas reduction under mild temperature (350 °C) to obtain Pt/CeO2−x, which can serve as a highly efficient nanozyme for catalytic cancer therapy, is reported. The deposited Pt on CeO2by the atomic layer deposition technique not only can serve as the catalyst to generate oxygen vacancies under mild temperature reduction through the hydrogen spillover effect, but also can stabilize the generated oxygen vacancies. Meanwhile, the oxygen vacancies also provide anchoring sites for Pt forming strong metal‐support interactions and thus preventing their agglomerations. Importantly, the Pt/CeO2−xreduced at 350 °C (Pt/CeO2−x‐350R) exhibits excellent enzyme‐mimicking catalytic activity for generation of reactive oxygen species (e.g., ·OH) as compared to other control samples, including CeO2, Pt/CeO2, and Pt/CeO2−xreduced at other temperatures, thus achieving excellent performance for tumor‐specific catalytic therapy to efficiently eliminate cancer cells in vitro and ablate tumors in vivo. The excellent enzyme‐mimicking catalytic activity of Pt/CeO2−x‐350R originates from the good catalytic activities of oxygen vacancy‐rich CeO2−xand Pt nanoclusters. The catalyzing generation and stabilization of oxygen vacancies on CeO2nanorods by Pt nanoclusters via H2gas reduction under mild temperature (350 °C) is proposed to obtain Pt/CeO2−x, which can serve as a highly efficient nanozyme for catalytic cancer therapy.

Local anesthetics (LAs) may generate neurotoxicity in neurons. In the current study, we explored the mechanisms by which microRNA-132 (miR-132) regulated the neurotoxicity of human neuroblastoma cells (SH-SY5Y) induced by bupivacaine (BUP).