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Tumor relapse and metastasis are the major causes of mortality associated with urothelial cancer. In the tumor microenvironment, negative regulatory molecules and various immune cell subtypes suppress antitumor immunity. The inflammatory microenvironment, associated with neutrophils and neutrophil extracellular traps (NETs), promotes tumor metastasis. However, no drugs are currently available to specifically inhibit neutrophils and NETs. In this study, we first demonstrated that icaritin (ICT), a Chinese herbal remedy that is a first-line treatment for advanced and incurable hepatocellular carcinoma, reduces NETs caused by suicidal NETosis and prevents neutrophil infiltration in the tumor microenvironment. Mechanistically, ICT binds to and inhibits the expression of PADI2 in neutrophils, thereby suppressing PADI2-mediated histone citrullination. Moreover, ICT inhibits ROS generation, suppresses the MAPK signaling pathway, and inhibits NET-induced tumor metastasis. Simultaneously, ICT inhibits tumoral PADI2-mediated histone citrullination, which consequently suppresses the transcription of neutrophil-recruiting genes such as GM-CSF and IL-6. The downregulation of IL-6 expression, in turn, forms a regulatory feedback loop through the JAK2/STAT3/IL-6 axis. Through a retrospective study of clinical samples, we found a correlation between neutrophils, NETs, UCa prognosis, and immune evasion. Combining ICT with immune checkpoint inhibitors may have synergistic effects. In summary, our study demonstrated that ICT could be a novel inhibitor of NETs and a novel UCa treatment.

The effects of inclination angle θ and unloading rate of confining pressure Uc on the unloading-induced slip behaviors of shale fractures were investigated by conducting triaxial unloading-induced fracture slip experiments. The variations in mechanical stability, frictional behavior, and morphology variation of shale fractures were systematically explored. The results show that with the continuous unloading of confining pressure, the fractures were initiated to slip, then entered the quasi-static slip stage, and eventually entered the dynamic slip stage in sequence. The occurrence of stick-slip events in the quasi-static slip stage was strongly influenced by the θ and Uc. As θ increases from 30° to 50°, the stick-slip events occurred from 0 to 3 times and from 1 to 3 times for Uc = 0.1 MPa/min and 1 MPa/min, respectively. The θ and Uc have a great influence on the interaction mode of the fractures, which directly affects the frictional behavior of the fractures. The slipping failure behavior of the fracture surfaces is mainly controlled by θ, while Uc plays different roles for the samples with different θ. With the increase in θ, the interaction form between asperities during the slip process may be changed into non-tight contact stage. The increase in θ may enhance or weanken the anisotropy of JRC, depending on whether the Uc reached a certain rate between 0.1 MPa/min and 1 MPa/min. Our results may shed light on the seismicity mitigation and safe exploitation of shale gas.

Silicate-modified polyurethane (PU/WG) is an effective organic–inorganic hybrid-grouting material that blocks water and reinforces weak formations. In deep high-temperature formations, owing to environmental impacts, PU/WG raw materials are heated before grouting. To elucidate the basic characteristics of PU/WG grouting materials in deep, high-temperature environments, we investigated the effects of raw material temperature on the curing time and strength of PU/WG by considering different mass ratios during the curing time test. Furthermore, the influence of raw material temperature on the micro-structure of PU/WG was analysed from a microscopic perspective using scanning electron microscopy. Energy-dispersive X-ray spectroscopy revealed the composition and curing mechanism of PU/WG. The results indicated that as the raw material temperature increased from 24 to 60°C, the peak strength decreased from 41.65 to 14.51 MPa, and the peak strain decreased from 27.03 % to 8.83 %. Based on the experimental results of the curing time testing and strength test, we established a PU/WG curing time-variation model considering the coupling of raw material temperature and mass ratio and provided an optimisation scheme for the PU/WG strength, which provides effective guidance for grouting time design in high-temperature environments.

Underground hydrogen storage (UHS) and compressed air energy storage (CAES) are two viable large-scale energy storage technologies for mitigating the intermittency of wind and solar power. Therefore, it is meaningful to compare the properties of hydrogen and air with typical thermodynamic storage processes. This study employs a multi-physical coupling model to compare the operations of CAES and UHS, integrating gas thermodynamics within caverns, thermal conduction, and mechanical deformation around rock caverns. Gas thermodynamic responses are validated using additional simulations and the field test data. Temperature and pressure variations of air and hydrogen within rock caverns exhibit similarities under both adiabatic and diabatic simulation modes. Hydrogen reaches higher temperature and pressure following gas charging stage compared to air, and the ideal gas assumption may lead to overestimation of gas temperature and pressure. Unlike steel lining of CAES, the sealing layer (fibre-reinforced plastic FRP) in UHS is prone to deformation but can effectively mitigates stress in the sealing layer. In CAES, the first principal stress on the surface of the sealing layer and concrete lining is tensile stress, whereas UHS exhibits compressive stress in the same areas. Our present research can provide references for the selection of energy storage methods.

Karst cave causes geological disasters in tunneling engineering, which brings great risks to subway construction. The microtremor survey has become one of the main methods for karst cave detection in urban areas due to its convenience and great detection depth. However, the microtremor survey lacks high-frequency signals, resulting in poor detection accuracy on the shallow layer. An advanced method called mixed-source surface wave (MSW) method is proposed by imposing active sources during the continuous passive surface wave survey. MSW is applied to the detection of beaded karst caves (i.e. two or three karst caves at different depths in the same location) in Ji'nan, China. The influences of ambient noise, array type, and other factors on the detection accuracy were studied. Experimental results show that the detection depth and accuracy of MSW are much better than those of passive surface wave method. The inversion accuracy of linear array perpendicular to road is better than the triangle array and L-shaped array. The accuracy of the linear array along the road is worst. The detection accuracy of MSW is similar to that of combined active–passive surface wave methods. However, the basic principle of MSW is easier to understand, and its operation is more convenient. The two-dimensional measurement results show that the MSW method can well reflect the size and location of the beaded karst cave and provide important references for the practical engineering.

Abstract. Hepatitis B virus (HBV) represents the commonest etiologic agent of acute-on-chronic liver failure (ACLF) in most Asian countries. Nucleos(t)ide analogs (NAs) are effective in the treatment of chronic HBV infections, but may also exacerbate the disease and stimulate its development into HBV-associated ACLF if not used appropriately. The current study aimed to assess the prevalence and severity of HBV-associated ACLF as a result from irregular medication of NAs (IMNA). A total of 1134 individuals with HBV-associated ACLF in nine hospitals in Heilongjiang Province were enrolled in this study between 2005 and 2015. Among these, 777 chronic hepatitis B (CHB) and 357 HBV-associated liver cirrhosis cases were classified based on various predisposing factors, including IMNA, HBV reactivation (HBVR), infections, treatment drugs, alcohol use and others (hepatitis C virus, hepatitis E virus, gastrointestinal bleeding and unknown reasons). The percentage and improvement rate were examined. Among individuals with HBV-associated ACLF and CHB, IMNA was found in 9.01%, HBVR in 46.20%, infections in 9.52%, treatment drugs in 14.67%, alcohol in 11.71%, and others in 24.58% as predisposing factors. Improvement rates in cases with IMNA, HBVR, infections, treatment drugs, alcohol and others were 41.43%, 58.50%, 58.11%, 56.14%, 53.85%, and 65.97%, respectively. Multivariable analysis showed that IMNA, others, infections, hepatic encephalopathy and hepatorenal syndrome were associated with prognosis. Only IMNA independently predicted HBV-associated ACLF prognosis. Overall, our study demonstrated that the percentage of IMNA-induced HBV-associated ACLF was 12.61%, and worse disease conditions resulted from IMNA compared with other factors. Thus, the suitability of treatment with NAs should be thoroughly evaluated.

Various diseases and failures inevitably appear on expressway roadways in water-rich strata under the long-term erosion of water. It is very difficult to support the surrounding rock of a water-rich roadway because water will corrode the anchorage bond and weaken the surrounding rock mass. In the process of supporting, damage and fracture of anchor bolt often appear in water-rich roadway. In order to study the stability analysis of a support anchor bolt in the process of surrounding rock fracture evolution and the relationship between the prestressed value and the length of the anchor bolt, this paper studied the fracture evolution law of surrounding rock and the progressive debonding law of the bolt are studied by RFPA3D numerical simulation and used MATLAB software to calculate and draw several graphs to reveal the mechanism by analytical method. The following main conclusions were drawn: (1) the change and attenuation of the surrounding rock stress have a certain influence on the stability of the supporting bolt. The existence of confining pressure (horizontal stress) has a significant impact on the ultimate pullout force of anchor bolts. (2) With the gradual destruction of the surrounding rock, the shear stress, horizontal stress, and vertical stress in the surrounding rock are gradually reduced to zero, and the change speed of the surrounding rock is fast at the shallow surface and slow at the deep. (3) The interface shear stress tends to a low stable value after debonding, which means the value of friction resistance is relatively stable in different positions. (4) The frictional resistance after interface debonding is an important condition to maintain the balance of higher anchorage force. If there is no friction resistance, when the axial force of the anchor bolt reaches the initial critical value, the interface debunking process will develop catastrophically and cannot be stabilized until complete failure, even if the axial force no longer increases.

The slurry–earth pressure balance dual-mode shield has an earth pressure balance (EPB) and slurry shield functions. Based on a shield tunnel project of Guangzhou Metro Line 12 in China, this study investigates the clogging prevention of a slurry–earth pressure balance dual-mode shield in a composed stratum with medium–coarse sand and argillaceous siltstone. The results show that the slurry mode was not applicable to the composed stratum with medium–coarse sand and argillaceous siltstone. The excavated soil accumulated easily in the slurry chamber, causing shield clogging. The total thrust force of the shield increased significantly, the tunneling speed gradually decreased to 0, and the torque of the cutterhead increased slightly after the slurry shield was clogged. The fluctuation in the total thrust force, the cutterhead torque, and the tunneling speed also increased significantly. The EPB mode is recommended for composed strata with medium–coarse sand and argillaceous siltstone. The dispersible foam agent and water needed to be used for soil conditioning. The injection amount of foam and water was determined according to the status of the mud discharged by the screw conveyor. Water absorption can be used to characterize the water absorption capacity of particles larger than 0.15 mm. The ideal soil state was that the consistency index of the particles smaller than 0.15 mm was less than 0.5 to prevent the EPB shield from clogging. The water absorption of soil with a particle larger than 0.15 mm should be removed when calculating the consistency index.

When a slurry shield tunnel boring machine (TBM) encounters sticky ground during tunneling, mud cakes often occur on the cutter head due to the high stickiness of soil. The mud cakes caused several negative issues, such as high torque demand, advancement rate reduction, and additional costs. Existing studies have largely focused on Earth pressure balance TBMs; research on formation and mitigation measures of mud cakes in slurry shield TBMs is limited. Therefore, this study proposes the addition of dispersant to the slurry to prevent mud cakes during the tunneling of slurry shield TBMs by reducing stickiness of excavated clay. The basic properties of slurry were measured experimentally, and the effectiveness of dispersant in reducing the potential for mud cakes was investigated through mixing tests and viscosity experiments. A statistical analysis of the data was performed to determine relationships between slurry properties and material behaviors. The results showed that the slurry with dispersant had a lower viscosity and formed filter cakes more quickly, thereby meeting the performance requirements of a supporting fluid for slurry shield TBMs. Further, dispersant effectively reduced the empirical stickiness ratio and suspension viscosity. Therefore, a slurry with an appropriate dispersant content could effectively reduce the potential for mud cake formation.

Many numerical methods are carried out to study the nonlinear failure behaviors of the rock; however, the numerical simulation methods for the failed rock are still in the research stage. This paper establishes the damage constitutive equation by combining the bilinear strain softening constitutive model with energy dissipation principles, as well as the energy failure criterion of mesoscopic elements based on the strain energy density theory. When the strain energy stored by an element exceeds a fixed value, the element enters the damage state and the damage degree increases with increasing energy dissipation. Simultaneously, the material properties of the damaged element change until it becomes an element with certain residual strength. As the load increases, the damage degree of an element increases. When the strain energy stored by an element exceeds the established value of the energy criterion, the element is defined to be failed. As the number of failed elements constantly increases, failed elements interconnect and form macrocracks. The rock fracture calculation program on the basis of the preceding algorithm is successfully applied to the fracture simulation process in Brazilian splitting, tensile tests with build-in crack and tunnel excavation.

The harmonious development of urban rail transit, underground space engineering, and social economy is the key to regional sustainable development. Based on synergetic theory, this paper constructs the coupling coordination evaluation system of “rail transport-social economy” composite system at the scale of a city cluster. With this system, the coupling and coordinated development pattern and characteristics of “rail transit-social economy” in the Yangtze River Delta city cluster from 2002 to 2020 were analyzed. The paper makes a horizontal comparison with the Beijing-Tianjin-Hebei city cluster and the Pearl River Delta city cluster, as well as analyzes the differences in development and existing problems, and puts forward policy suggestions for rail and urban underground space development. The results show that: (1) The rail transit of 11 cities in the Yangtze River Delta shows a “step by step” development pattern. That is “national central city, provincial city, second-tier city, third-tier city, etc.”, accompanied by periodic changes of coupling and coordination degree. In addition, there is also the phenomenon of unbalanced development within the region; (2) From 2002 to 2020, the development of rail transit in the three city clusters shows a situation of “the overall supply is lacking and lags behind the social economy for a long time”. Among them, the Pearl River Delta city cluster has the most serious lags. Multi-channel financing, speeding up the construction of the rail transit scale according to local conditions, and improving operating efficiency are considered to be the keys to solve this problem; (3) In general, the coupling between rail transit and the social economy in the Yangtze River Delta city cluster is better than that in the Beijing-Tianjin-Hebei city cluster and the Pearl River Delta city cluster, but the coordination is at a slight disadvantage.

With the rapid growth of scientific publications, research paper recommendation which suggests relevant research papers to users can bring great benefits to researchers. In this paper, we focus on the problem of recommending conference papers to the conference attendees. While most of the related existing methods depend on the content-based filtering, we propose a unified conference paper recommendation method named $CPRec$ , which exploits both the contents and the authorship information of the papers. In particular, besides the contents, we exploit the relationships between a user and the authors of a paper for recommendation. In our method, we extract several features for a user-paper pair from the citation network, the coauthor network, and the contents, respectively. In addition, we derive a user’s pairwise preference towards the conference papers from the user’s bookmarked papers in each conference. Furthermore, we employ a pairwise learning to rank model which exploits the pairwise user preference to learn a function that predicts a user’s preference towards a paper based on the extracted features. We conduct a recommendation performance evaluation using real-world data and the experimental results demonstrate the effectiveness of our proposed method.

Shotcrete is an essential preliminary support means in New Austrian Tunneling Method (NATM) construction and plays a very important role in controlling the stability of surrounding rock. The accelerator is a necessary admixture in shotcrete and its quality can greatly affect shotcrete performance. This paper proposes a new liquid accelerator characterized by short initial and final setting time, small dosage, and good adaptability to cement. Laboratory tests and field tests are conducted to verify the influence of this liquid accelerator on performance of shotcrete. Numerical simulation is carried out to study the strength growth of shotcrete with time and interaction between the strength and stress release of surrounding rock. The results show that the initial and final setting time of this liquid accelerator is 2 minutes and 4 minutes respectively. Its dosage is just 1.5% to 4% of the cement quantity. Adding this liquid accelerator can effectively improve the early strength and reduce the later strength loss of shotcrete, and therefore enhance the supporting effects of shotcrete on surrounding rock. In the field application, it is an ideal liquid accelerator for shotcrete, characterized by little resilience, no slurry shedding, and low dust.

Many numerical methods are carried out to study the nonlinear failure behaviors of the rock; however, the numerical simulation methods for the failed rock are still in the research stage. This paper establishes the damage constitutive equation by combining the bilinear strain softening constitutive model with energy dissipation principles, as well as the energy failure criterion of mesoscopic elements based on the strain energy density theory. When the strain energy stored by an element exceeds a fixed value, the element enters the damage state and the damage degree increases with increasing energy dissipation. Simultaneously, the material properties of the damaged element change until it becomes an element with certain residual strength. As the load increases, the damage degree of an element increases. When the strain energy stored by an element exceeds the established value of the energy criterion, the element is defined to be failed. As the number of failed elements constantly increases, failed elements interconnect and form macrocracks. The rock fracture calculation program on the basis of the preceding algorithm is successfully applied to the fracture simulation process in Brazilian splitting and intermediate crack tensile tests.

Al has significant effect on properties of minerals. We reported crystal structure and elasticity of phase H, an important potential water reservoir in the mantle, which contains different Al using first principles simulations for understanding the effect of Al on the phase H. The crystal and elastic properties of Al end-member phase H (Al2O4H2) are very different from Mg end-member (MgSiO4H2) phase H and two aluminous phase H (Mg0.875Si0.875Al0.25O4H2 (12.5at%Al) and Mg0.75Si0.75Al0.5O4H2 (25at% Al)). However differences between Mg end-member phase H and aluminous phase H are slight except for the O-H bond length and octahedron volume. Al located at different crystal positions (original Mg or Si position) of aluminous phase H has different AlO6 octahedral volumes. For three Al-bearing phase H, bulk modulus (K), shear modulus (G), compressional wave velocity (Vp) and shear wave velocity (Vs) increase with increasing Al content. Under high pressure, density of phase H increases with increasing Al content. The Al content affects the symmetry of the phase H and then affects the density and elastic constants of phase H. The total ground energy of phase H also increases with increasing Al content. So an energy barrier for the formation of solid solution of phase H with δ-phase AlOOH is expected. However, if the phase H with δ-phase AlOOH solid solution does exit in the mantle, it may become an important component of the mantle or leads to a low velocity layer at the mantle.

The U-shaped girder is a type of open thin-walled structure, which is used in urban rail transit engineering. Although it employs polypropylene fiber concrete to avoid cracks, the girder is still easier to crack than other traditional structures owing to its special open thin-walled cross section. In this study, a cracking accident of a U-shaped girder, which happened during the prestressed steel tensioning, was studied by field investigation and mechanical analysis through the finite element (FE) method. An outline of the cracks was presented. The nonlinear material properties of the polypropylene fiber concrete and steel were discussed and used in the finite element model. The effects of the main design parameters, such as the flange slab thickness, anchorage position, and prestressed steel layout, were evaluated based on the results of the FE analysis. The results indicate that the extremely low rigidity of the web and oversize of the web longitudinal prestressed steels are the main reasons for the cracks. The risk of cracks can be reduced by increasing the thickness of the flange slab and changing the anchorage position and prestressed steel layout. Some suggestions are provided for avoiding cracks based on the results of the research.

Abstract Background The management of locally recurrent gynecological carcinoma remains a challenge due to the limited availability of data. This study aims to share our institutional experience in using definitive radiotherapy (RT) for the treatment of locally recurrent cervical and endometrial carcinoma. Methods The study retrospectively reviewed 20 patients in our hospital completing salvage 3D image-based HDR brachytherapy, with or without EBRT, for locally recurrent cervical and endometrial carcinoma after surgery. The Kaplan–Meier method was applied to estimate the disease-free survival (DFS) and overall survival (OS). The toxicities were assessed by CTCAEv5. Results During a median observation period of 21 months, the study reported a tumor objective response rate of 95%. The 3-year DFS and OS rates were 89.4% and 90.9%, respectively. The EBRT combined with brachytherapy achieved a median cumulative dose of 88 Gy to CTV D90. 14 patients received concurrent and/or systemic chemotherapy. Two patients suffered locoregional recurrence after salvage treatment, one of whom only received salvage brachytherapy for prior RT history. The analysis identified significant predictors for DFS, including tumor histology and FIGO stage. 5 patients observed acute grade 1–2 rectal (15%) or genitourinary (10%) toxicities. Late toxicities including grade 1–2 rectal bleeding (10%) and grade 2 pelvic fracture (5%) were seen in 3 patients. Conclusions 3D image-guided brachytherapy combined with EBRT shows effective tumor control and acceptable toxicity profile for women with locally recurrent gynecologic cancer. The success in managing vaginal recurrence is notably influenced by histologic subtype and FIGO staging.

Researches have shown that microwave radiation could cause oxidative stress injury in male reproductive system, and blueberry anthocyanins had excellent oxidation resistance. Our study aimed to investigate the protective effect of blueberry anthocyanins (100, 200 and 400 mg/kg/d) on testicular tissue damage in Wistar rats exposed to 2.856 GHz microwave and the optimal dose. We found that blueberry anthocyanins could ameliorate the decrease of sperm motility and sex hormone levels and testicular tissue structure damage caused by microwave radiation, increase SIRT1 expression and decrease FoxO1 expression, increase GSH/GSSG, SOD and inhibit MDA. The LDH, SDH and ATP synthase were increased, and Caspase-3 expression was decreased, and the high-dose of blueberry anthocyanins (400 mg/kg/d) had the best protective effect. These results suggested that blueberry anthocyanins could inhibit oxidative stress injury induced by 2.856 GHz microwave radiation in rat testicular tissue by regulating SIRT1/FoxO1 pathway, enhance energy metabolism and reduce cell apoptosis.

Inhalation of aerosolized uranium is recognized as a principal mode of exposure, posing significant risks of damage to the lungs, kidneys, and other vital organs. To enhance nuclide elimination from the body, chelating agents are employed; however, single-component chelators often exhibit limited spectral activity and low effectiveness, resulting in toxicologically relevant concentrations. We have developed a composite chelating agent composed of 3,4,3-Li(1,2-HOPO), DFP, and HEDP in optimized ratios, demonstrating marked improvements in eliminating inhaled uranium. The selection of these components was initially guided by an agarose gel dynamics method, focusing on uranium binding and removal efficacy. Optimization of the formula was conducted through response surface methodology in a cellular model. The compound’s ability to enhance survival rates in mice subjected to acute uranium inhalation was confirmed, showing a dose-dependent improvement in survival in severely affected mice. Comparative assessments indicated that this multifaceted chelating agent substantially surpasses the uranium tissue clearance achieved by individual chelating agents.

Following the coronavirus disease-2019 outbreak caused by severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), there is an ongoing need to seek drugs that target COVID-19. First off, novel drugs have a long development cycle, high investment cost, and are high risk. Second, novel drugs must be evaluated for activity, efficacy, safety, and metabolic performance, contributing to the development cycle, investment cost, and risk. We searched the Cochrane COVID-19 Study Register (including PubMed, Embase, CENTRAL, ClinicalTrials.gov, WHO ICTRP, and medRxiv), Web of Science (Science Citation Index, Emerging Citation Index), and WHO COVID-19 Coronaviral Disease Global Literature to identify completed and ongoing studies as of February 20, 2024. We evaluated the pharmacological effects, in vivo and in vitro data of the 16 candidates in the paper. The difficulty of studying these candidates in clinical trials involving COVID-19 patients, dosage of repurposed drugs, etc. is discussed in detail. Ultimately, Metformin is more suitable for prophylactic administration or mildly ill patients; the combination of Oseltamivir, Tamoxifen, and Dexamethasone is suitable for moderately and severely ill patients; and more clinical trials are needed for Azvudine, Ribavirin, Colchicine, and Cepharanthine to demonstrate efficacy.

In order to investigate the effects of different drying methods on the properties of porous starch. The present study used four drying methods, namely hot air drying (HD), spray drying (SPD), vacuum freeze drying (FD) and supercritical carbon dioxide drying (SCD) to prepare maize and kudzu porous starch. Findings indicated that the physicochemical properties (e.g., morphology, crystallinity, enthalpy value, porosity, surface area and water absorption capacity as well as dye absorption capacity, particle size) of porous starch were significantly affected by the drying method. Compared with other samples, SCD-treated porous starch exhibited the highest surface areas of the starch (2.943 and 3.139 m2/g corresponding to kudzu and maize, respectively), amylose content (22.02 % and 16.85 % corresponding to kudzu and maize, respectively), MB and NR absorption capacity (90.63 %, 100.26 % and 90.63 %, 100.26 %, corresponding to kudzu ad maize, respectively), and thermal stability, whereas HD-treated porous starch showed the highest water-absorption capacity (123.8 % and 131.31 % corresponding to kudzu and maize, respectively). The dye absorption of the maize and kudzu porous starch was positively correlated with surface area, according to Pearson's correlation analysis. Therefore, in this study, our aim was to explore the effects of different drying methods on the Structure and properties of porous starch, and provide reference for selecting the best drying method for its application in different fields.

Chinese herbs are a huge treasure trove of natural products and an important source of many active molecules. The theory of traditional Chinese medicine compatibility (TCMC) is widely applied in clinical practice, but its mechanism is still ambiguous. This study aims to open a new window for this predicament by studying the interaction between the main active ingredients from a drug pair. Carrier-free assembly of natural products improves the shortcomings of traditional nanodelivery systems and opens a new path for the development of new nanomaterials. The drug pair “Pueraria and Hedyotis diffusa” has been commonly used in clinical practice, with a predominant therapeutic effect. This study is devoted to the study of the binary small molecule co-assembly of the main active molecules from the drug pair. In this study, we introduce a carrier-free composite gel, formed by the co-assembly of puerarin (PUE) and deacetylasperulosidic acid (DAA) via non-covalent bonds including π–π packing, intermolecular hydrogen bonding, and C=O π interactions. With a strain point 7-fold higher than that of P gel, the P − D gel exhibited favorable rheological properties. The survival rate of SW1990 cells in the P − D group was only 21.39% when the concentration of administration reached 200 μM. It thus demonstrated activity in inhibiting SW1990 cells’ survival, suggesting potential in combating pancreatic cancer. Furthermore, this research offers a valuable concept for enhancing the mechanical properties and bioactivity of hydrogel materials through the utilization of a multi-component natural small molecule co-assembly approach. More importantly, this provides new ideas and methods for the treatment of pancreatic cancer and the analysis of traditional Chinese medicine compatibility theory.

Wheat (Triticum aestivum) is one of the most important staple crops worldwide. To ensure its global supply, the timing and duration of its growth cycle needs to be closely monitored in the field so that necessary crop management activities can be arranged in a timely manner. Also, breeders and plant researchers need to evaluate growth stages (GSs) for tens of thousands of genotypes at the plot level, at different sites and across multiple seasons. These indicate the importance of providing a reliable and scalable toolkit to address the challenge so that the plot-level assessment of GS can be successfully conducted for different objectives in plant research. Here, we present a multimodal deep learning model called GSP-AI, capable of identifying key GSs and predicting the vegetative-to-reproductive transition (i.e., flowering days) in wheat based on drone-collected canopy images and multiseasonal climatic datasets. In the study, we first established an open Wheat Growth Stage Prediction (WGSP) dataset, consisting of 70,410 annotated images collected from 54 varieties cultivated in China, 109 in the United Kingdom, and 100 in the United States together with key climatic factors. Then, we built an effective learning architecture based on Res2Net and long short-term memory (LSTM) to learn canopy-level vision features and patterns of climatic changes between 2018 and 2021 growing seasons. Utilizing the model, we achieved an overall accuracy of 91.2% in identifying key GS and an average root mean square error (RMSE) of 5.6 d for forecasting the flowering days compared with manual scoring. We further tested and improved the GSP-AI model with high-resolution smartphone images collected in the 2021/2022 season in China, through which the accuracy of the model was enhanced to 93.4% for GS and RMSE reduced to 4.7 d for the flowering prediction. As a result, we believe that our work demonstrates a valuable advance to inform breeders and growers regarding the timing and duration of key plant growth and development phases at the plot level, facilitating them to conduct more effective crop selection and make agronomic decisions under complicated field conditions for wheat improvement.

Porous starch is a denatured starch product with high porosity, a large specific surface area, and strong adsorption. It is widely used in medicine, food, and chemical industries. Native starch includes types A, B, and C. In this study, the various starch materials, including potato maize, and kudzu starch, were used to prepare different crystal types of porous starch with α-amylase and glucoamylase. The structural and chemical characteristics of the porous starch were measured using Fourier-transform infrared spectroscopy, scanning electron microscopy, X-ray diffraction, and differential scanning calorimetry. The results showed that maize , potato and kudzu starches were typically A, B, and C types, respectively. Compared to the native starch, the three types of porous starch treated with α-amylase and Glucoamylase cause varying degrees of destruction of the surface of the starch. Moreover, investigating the reaction factors which are expected to affect the water adsorption capacity were studied systematically, including the mass ratio of α-amylase to glucoamylase (m α-amylase/m glucoamylase), the mass ratio of the total amount of enzymes to starch (m enzyme/m St), enzymatic reaction temperature, and enzymatic reaction time. The results suggested that A-type starch has higher enzymolysis efficiency than other types of starch and can be used to produce ideal cavity and pore-size starch granules with potential applications in many fields.

Abstract Health hazards from long-term exposure to microwaves, especially the potential for changes in cognitive function, are attracting increasing attention. The purpose of this study was to explore changes in spatial learning and memory and synaptic structure and to identify differentially expressed proteins in hippocampal and serum exosomes after long-term exposure to 2.856 and 9.375 GHz microwaves. The spatial reference learning and memory abilities and the structure of the DG area were impaired after long-term exposure to 2.856 and 9.375 GHz microwaves. We also found a decrease in SNARE-associated protein Snapin and an increase in charged multivesicular body protein 3 in the hippocampus, indicating that synaptic vesicle recycling was inhibited and consistent with the large increase in presynaptic vesicles. Moreover, we investigated changes in serum exosomes after 2.856 and 9.375 GHz microwave exposure. The results showed that long-term 2.856 GHz microwave exposure could induce a decrease in calcineurin subunit B type 1 and cytochrome b-245 heavy chain in serum exosomes. While the 9.375 GHz long-term microwave exposure induced a decrease in proteins (synaptophysin-like 1, ankyrin repeat and rabankyrin-5, protein phosphatase 3 catalytic subunit alpha and sodium-dependent phosphate transporter 1) in serum exosomes. In summary, long-term microwave exposure could lead to different degrees of spatial learning and memory impairment, EEG disturbance, structural damage to the hippocampus, and differential expression of hippocampal tissue and serum exosomes.

Although the wide variety of bioactivities of curcumin has been reported by researchers, the clinical application of curcumin is still limited due to its poor aqueous solubility. In view of this, a series of dimethylaminomethyl-substituted curcumin derivatives were designed and synthesized (compounds 1–15). Acetate of these derivatives were prepared (compounds 1a–15a). The Mannich reaction and aldol condensation reaction are the main reactions involved in this study. Compounds 6, 10, 12, 3a, 5a, 6a, 7a, 8a, 10a, 11a, 12a, 13a, 14a, and 15a exhibited better in vitro anti-inflammatory activity compared to curcumin in the RAW264.7 cell line. Compounds 5, 1a, 5a, 8a, and 12a exhibited better in vitro antioxidant activity compared to curcumin in the PC 12 cell line. Compounds 11, 13, 5a, 7a, and 13a exhibited better in vitro radiation protection compared to curcumin in the PC 12 cell line. The aqueous solubilities of all the curcumin derivative acetates were greatly improved compared to curcumin.

Orychophragmus violaceus (L.) O. E. Schulz (Brassicaceae) is widely distributed and plentiful in China and has been widely used for its application in ornamental, oil, ecology, foraging, and food. Recent studies have revealed that the main components of Orychophragmus violaceus include flavonoids, alkaloids, phenylpropanoids, phenolic acids, terpenoids, etc., which have pharmacological activities such as antioxidation, antiradiation, antitumor, hepatic protection, antiferroptosis, anti-inflammatory, and antibacterial. In this paper, the nutritional value, chemical compositions, pharmacological activity, and application value of Orychophragmus violaceus are summarized by referring to the relevant domestic and international literature to provide a reference for further research, development, and utilization of Orychophragmus violaceus in the future.

LR004 is a novel chimeric (human/mouse) monoclonal antibody developed for the treatment of advanced colorectal carcinoma with detectable epidermal growth factor receptor (EGFR) expression. We aimed to investigate the preclinical pharmacokinetics (PK) and in vivo biodistribution of LR004. The PK profiles of LR004 were initially established in rhesus monkeys. Subsequently, 125I radionuclide-labeled LR004 was developed and the biodistribution, autoradiography, and NanoSPECT/CT of 125I-LR004 in xenograft mice bearing A431 tumors were examined. The PK data revealed a prolonged half-life and nonlinear PK characteristics of LR004 within the dose range of 6–54 mg/kg. The radiochemical purity of 125I-LR004 was approximately 98.54%, and iodination of LR004 did not affect its specific binding activity to the EGFR antigen. In a classical biodistribution study, 125I-LR004 exhibited higher uptake in highly perfused organs than in poorly perfused organs. Prolonged retention properties of 125I-LR004 in tumors were observed at 4 and 10 days. Autoradiography and NanoSPECT/CT confirmed the sustained retention of 125I-LR004 at the tumor site in xenograft mice. These findings demonstrated the adequate tumor targeting capabilities of 125I-LR004 in EGFR-positive tumors, which may improve dosing strategies and future drug development.