Modulating carbon dots from aggregation-caused quenching to aggregation-induced emission and applying them in sensing, imaging and anti-counterfeiting.

Aggregation Induced Emission Carbon Dots (AIE-CDs) address the problem of conventional CDs being quenched in the solid-state. However, there are still challenges in comprehending the luminescence mechanism. This work proposed a strategy for preparing green, yellow, and near-infrared CDs by modifying the functional groups on the precursor from hydroxyl and amino to p-methylenediamine, in which electronic supply capacity determined the redshift. Additionally, The CDs' properties transformed from Aggregation-Caused Quenching (ACQ) to AIE was realized by substituting non-rotatable hydroxyl or amino groups with the rotatable p-methylenediamine on the precursor. The resulting CDs were then applied in multifield. C-CDs was used for ratiometric detection of Al3+ and F- in pure water through three methods including fluorometer, test strip and smartphone. R-CDs was used for imaging cell nucleus and zebrafish. NIR-CDs (λem = 676 nm) exhibits dual emission, AIE and phosphorescent characteristics was used for triple anti-counterfeiting and binary information encryption. In summary, our finding presented a strategy for preparing multicolor CDs, proposed a mechanism for the transition of CDs from ACQ to AIE, and explore their multiple applications in anti-counterfeiting, information encapsulation, sensing and imaging.

Advancements of carbon dots: From the perspective of medicinal chemistry.

Carbon dots (CDs) exhibit great potential in medicinal chemistry due to its excellent optical properties, biocompatibility and scalability, which have attracted significant interest. Based on their specific synthesis and modification, this review provided an overview of the evolution of the synthesis of CDs and reviewed the discovery and development of their optical properties. This review examines recent advances of CDs in medicinal chemistry, with a particular focus on the use of CDs as drugs and carriers for photodynamic and photothermal therapies in the field of neurological disorders, cancer, bacterial, viral, and further in combination with imaging for diagnostic and therapeutic integration. Finally, this review addresses the challenges and limitations of CDs in medicinal chemistry. This review provides a comprehensive overview of the development process of CDs and their applications in various aspects of medicinal chemistry, thereby offers insights to the development of CDs in the field of medicinal chemistry.

Shock wave generated by composite energetic material driven by electrical non-penetrating wire explosion plasma.

Underwater shock wave technology can realize dynamic rock fracture, which is helpful to increase oil and gas reservoir permeability. It can realize the efficient exploitation of medium and low maturity oil and gas resources. In practical application, the shock wave parameters require not only high intensity but also safety and controllability. To meet these requirements, insensitive composite energetic materials driven by electrical wire explosion plasma were proposed, which is one of the most promising methods. However, when in use, the load assembly process containing wires and energetic materials is complex. In this paper, a new type of energetic material load is proposed, using non-penetrating wire to drive composite energetic material. It can simplify the production process of the energetic load and produce acceptable shock wave parameters. The test results show that both the energy deposition of the wire and the shock wave intensity decrease under a non-penetrating wire structure. However, the shock wave intensity is still higher than that of the underwater electrical wire explosion. Based on schlieren diagnosis, it is found that the composite energetic material is gradually driven, and the energy release is not concentrated. In addition, the "non-wire" structure driving condition was discussed in contrast. Under this condition, the process of ionization channel establishment in composite energetic materials is random. The shock wave intensity is weak because the composite energetic material is in the process of slow detonation.

Salicylaldehyde-derived piperazine-functionalized hydrazone ligand-based Pt(II) complexes: inhibition of EZH2-dependent tumorigenesis in pancreatic ductal adenocarcinoma, synergism with PARP inhibitors and enhanced apoptosis.

Piperazine is an important functional unit of many clinically approved drugs, including chemotherapeutic agents. In the current study, methyl piperazine was incorporated and eight salicylaldehyde-derived piperazine-functionalized hydrazone ONN-donor ligands (L) and their Pt(II) complexes (L-PtCl) were prepared. The structures of all these ligands (L1-L8) and Pt(II) complexes (C1-C8) were determined using 1H and 13C NMR, UV-vis, FT-IR and HR-ESI MS analyses, whereas the structures of C1, C5, C6, C7 and C8 were determined in the solid state using single crystal X-ray diffraction analysis. Solution state stabilities of C3, C4, C5 and C6 were determined via time-dependent UV-vis spectroscopy. All these complexes (C1-C8) were studied for their anticancer effect in pancreatic ductal adenocarcinoma cells, including BxPC3, MIAPaCa-2 and PANC1 cells. C1-C8 displayed a potential cytotoxic effect in all these cancer cells, among which C5, C6 and C8 showed the strongest inhibitory effect in comparison with standard chemotherapeutic agents, including 5-fluorouracil (5-FU), cisplatin (CP), oxaliplatin and doxorubicin (DOX). C5, C6 and C8 suppressed the growth of pancreatic cancer cells in a dose-dependent manner. Moreover, C5, C6 and C8 inhibited clonogenic potential and invasion ability and induced apoptosis in PANC1 cells. Importantly, C5, C6 and C8 synergized the anticancer effect with PARP inhibitors, including olaparib, veliparib and niraparib, in pancreatic cancer cells, thus suggesting an important role of C5, C6 and C8 in induction of apoptosis in combination with PARP inhibitors. C5 combined with PARP inhibitors induced caspase3/7 activity and suppressed ATP production. Mechanistically, C5, C6 and C8 inhibited EZH2 protein expression to suppress EZH2-dependent tumorigenesis. Overall, these results highlighted the importance of these piperazine-functionalized Pt(II) complexes as potential anticancer agents to suppress pancreatic ductal adenocarcinoma tumorigenesis by targeting the EZH2-dependent pathway.

A biomechanical study of a polymer material bundled rib fracture fixator.

BACKGROUND: Rib fractures are one of the most common blunt injuries, accounting for approximately 10% of all trauma patients and 60% of thoracic injuries. Multiple rib fractures, especially flail chest, can cause local chest wall softening due to the loss of rib support, leading to paradoxical breathing, severe pain, and a high likelihood of accompanying lung contusions. OBJECTIVE: This study investigates the mechanical properties of a new polymer material rib internal fixator to provide theoretical data for its clinical use. METHODS: We conducted in vitro mechanical tests on 20 fresh caudal fin sheep ribs, using different fracture models across four randomly assigned groups (five ribs per group). The fixators were assessed using non-destructive three-point bending, torsion, and unilateral compression tests, with results averaged. Additionally, finite element analysis compared stress and strain in the polymer fixators and titanium alloy rib plates during bending and torsion tests. RESULTS: In vitro tests showed that the polymer fixators handled loads effectively up to a maximum without increase beyond a certain displacement. Bending and torsion tests via finite element analysis showed the polymer material sustained lower maximum equivalent stresses (84.455 MPa and 14.426 MPa) compared to titanium alloy plates (219.88 MPa and 46.47 MPa). CONCLUSION: The polymer rib fixator demonstrated sufficient strength for rib fracture fixation and was superior in stress management compared to titanium alloy plates in both bending and torsion tests, supporting its potential clinical application.

A gas spark switch electrode impact pressure test platform.

The discharge arc of a high-current gas spark switch has a strong mechanical effect on the electrode and adjacent objects. The measurement of this mechanical effect on the electrode plays a very important role in switch design and the theoretical study of spark discharge. However, in traditional stress measurement systems, the spatial electromagnetic interference caused by the discharge and the high electrode voltage affects the measurement accuracy and can even damage the experimental instrument. In this paper, an electrode impact stress measurement system based on PVDF piezoelectric film is designed to measure the electrode stress under a strong spatial electromagnetic field and high voltage. The experimental results show that the system can measure the impact pressure of high-voltage and high-current gas spark switch electrodes. The starting time of the stress measurement waveform shows that the shock to the electrode is formed in the initial stage of current buildup. The measured results clearly show the high magnetic field force component in the electrode impact pressure waveform. The shock waveforms induced by different pulse capacitor values, breakdown voltages, and loads are examined. It is found that the shock stress waveforms applied to the electrodes are affected by the peak value of the current, dI/dt, and the discharge duration.

Co-targeting CDK 4/6 and C-MYC/STAT3/CCND1 axis and inhibition of tumorigenesis and epithelial-mesenchymal-transition in triple negative breast cancer by Pt(II) complexes bearing NH3 as trans-co-ligand.

In search of potential anticancer agents, we synthesized SNO-donor salicylaldimine main ligand-based Pt(II) complexes bearing NH3 as co-ligand at trans-position (C1-C6). These complexes showed similarity in structure with transplatin as the two N donor atoms of the main ligand and NH3 co-ligand were coordinated to Pt in trans position to each other. Each complex with different substituents on the main ligand was characterized thoroughly by detailed spectroscopic and spectrophotometric methods. Four of these complexes were studied in solid state by single crystal X-ray analysis. The stability of reference complex C1 was measured in solution state in DMSO­d6 or its mixture with D2O using 1H NMR methods. These complexes were further investigated for their anticancer activity in triple-negative-breast (TNBC) cells including MDA-MB-231, MDA-MB-468 and MDA-MB-436 cells. All these complexes showed satisfactory cytotoxic effect as revealed by the MTT results. Importantly, the highly active complex C4 anticancer effect was compared to the standard chemotherapeutic agents including cisplatin, oxaliplatin and 5-fluorouracil (5-FU). Functionally, C4 suppressed invasion, spheroids formation ability and clonogenic potential of cancer cells. C4 showed synergistic anticancer effect when used in combination with palbociclib, JQ1 and paclitaxel in TNBC cells. Mechanistically, C4 inhibited cyclin-dependent kinase (CDK)4/6 pathway and targeted the expressions of MYC/STAT3/CCND1/CNNE1 axis. Furthermore, C4 suppressed the EMT signaling pathway that suggested a role of C4 in the inhibition of TNBC metastasis. Our findings may pave further in detailed mechanistic study on these complexes as potential chemotherapeutic agents in different types of human cancers.

Tunable Dual Self-Healing Composite Coatings with Self-Assembled Structures Regulated by Janus Nanoparticles.

The durability of concrete structures can be enhanced in a convenient and permanent manner through the surface protection of cementitious materials with composite polymer coatings. However, polymer coatings are susceptible to various mechanical and physical deterioration in complex and variable environments. In this paper, the theory of polymer microstructure regulation was employed to improve the sustainability of the protective performance of composite coatings. The self-assembled core-shell structure regulated by amphiphilic Janus nanoparticles is employed to modify the tunable polystyrene acrylate-polysiloxane self-healing coatings. The results demonstrate that the adhesion strength of the prepared self-assembled coating reached 3.7 MPa, which is sufficient to resist the damage to the microstructure of cementitious materials caused by physical erosion, seepage, and ionic corrosion. The self-healing coating, regulated by Janus particles, exhibited a residual creep of only 57.03% and a maximum loss angle tangent of 0.381. Furthermore, the material exhibited a superior shape memory function due to the presence of strong hydrogen bonding. The regulated self-healing coating repaired the polymer structural damage under mechanical and thermal deformation by bridging and filling effects. The coating demonstrated a tensile strength recovery of up to 71.23% in a wetted state, accompanied by a rapid restoration of its electrochemical properties and corrosion resistance. Furthermore, the self-healing emulsion penetrates the substrate defects and forms numerous polymer crystalline particles that effectively fill the microcracks.

Design, synthesis of combretastatin A-4 piperazine derivatives as potential antitumor agents by inhibiting tubulin polymerization and inducing autophagy in HCT116 cells.

A series of combretastatin A-4 (CA-4) derivatives were designed and synthesized, which contain stilbene core structure with different linker, predominantly piperazine derivatives. These compounds were evaluated for their cytotoxic activities against four cancer cell lines, HCT116, A549, AGS, and SK-MES-1. Among them, compound 13 displayed the best effectiveness with IC50 values of 0.227 µM and 0.253 µM against HCT116 and A549 cells, respectively, showing low toxicity to normal cells. Mechanistic studies showed that 13 inhibited HCT116 proliferation via arresting cell cycle at the G2/M phase through disrupting the microtubule network and inducing autophagy in HCT116 cells by regulating the expression levels of autophagy-related proteins. In addition, 13 displayed antiproliferative activities against A549 cells through blocking the cell cycle and inducing A549 cells apoptosis. Because of the poor water solubility of 13, four carbohydrate conjugates were synthesized which exhibited better water solubility. Further investigations revealed that 13 showed positive effects in vivo anticancer study with HCT116 xenograft models. These data suggest that 13 could be served as a promising lead compound for further development of anti-colon carcinoma agent.

Utilization and value-adding of waste: Fabrication of porous material from chitosan for phosphate capture and energy storage.

Efficient removal and recycling of phosphorus from complex water matrices using environmentally friendly and sustainable materials is essential yet challenging. To this end, a novel bio-based adsorbent (DX-FcA-CS) was developed by coupling oxidized dextran-crosslinked chitosan with ferrocene carboxylic acid (FcA). Detailed characterization revealed that the incorporation of FcA reduced the total pore area of DX-FcA-CS to 7.21 m2·g-1, one-third of ferrocene-free DX-CS (21.71 m2·g-1), while enhancing thermal stability and PO43- adsorption performance. Adsorption kinetics and isotherm studies demonstrated that the interaction between DX-FcA-CS and PO43- followed a pseudo-second-order kinetic model and Langmuir model, indicating chemical and monolayered adsorption mechanisms, respectively. Moreover, DX-FcA-CS exhibited excellent anti-interference properties against concentrated co-existing inorganic ions and humic acid, along with high recyclability. The maximum adsorption capacity reached 1285.35 mg·g-1 (∼428.45 mg P g-1), three times that of DX-CS and surpassing many other adsorbents. PO43--loaded DX-FcA-CS could be further carbonized into electrode material due to its rich content of phosphorus and nitrogen, transforming waste into a valuable resource. These outstanding characteristics position DX-FcA-CS as a promising alternative for phosphate capture and recycling. Overall, this study presents a viable approach to designing environmentally friendly, recyclable, and cost-effective biomaterial for wastewater phosphate removal and value-added applications.

Demystifying COVID-19 mortality causes with interpretable data mining.

While COVID-19 becomes periodical, old individuals remain vulnerable to severe disease with high mortality. Although there have been some studies on revealing different risk factors affecting the death of COVID-19 patients, researchers rarely provide a comprehensive analysis to reveal the relationships and interactive effects of the risk factors of COVID-19 mortality, especially in the elderly. Through retrospectively including 1917 COVID-19 patients (102 were dead) admitted to Xiangya Hospital from December 2022 to March 2023, we used the association rule mining method to identify the risk factors leading causes of death among the elderly. Firstly, we used the Affinity Propagation clustering to extract key features from the dataset. Then, we applied the Apriori Algorithm to obtain 6 groups of abnormal feature combinations with significant increments in mortality rate. The results showed a relationship between the number of abnormal feature combinations and mortality rates within different groups. Patients with "C-reactive protein > 8 mg/L", "neutrophils percentage > 75.0 %", "lymphocytes percentage < 20%", and "albumin < 40 g/L" have a 2 × mortality rate than the basic one. When the characteristics of "D-dimer > 0.5 mg/L" and "WBC > 9.5 × 10 9 /L" are continuously included in this foundation, the mortality rate can be increased to 3 × or 4 × . In addition, we also found that liver and kidney diseases significantly affect patient mortality, and the mortality rate can be as high as 100%. These findings can support auxiliary diagnosis and treatment to facilitate early intervention in patients, thereby reducing patient mortality.

Cosmetically Approved Short-Chain Alcohol/Triethyl Citrate/Water Surfactant-Free Microemulsions and Potential Application to Transdermal Penetration of α-Arbutin.

Surfactant-free microemulsions (SFMEs) exhibited remarkable advantages and potential, attributed to their similarity to traditional surfactant-based microemulsions and the absence of surfactants. Herein, a novel SFME was developed utilizing cosmetically approved materials, such as short-chain alcohol as an amphi-solvent, triethyl citrate (TEC) as the nonpolar phase, and water as the polar phase. 1,2-Pentanediol (PtDO)/TEC/water combination can form the largest monophasic zone, accounting for ∼74% of the total phase diagram area, due to an optimal hydrophilic (water)-lipophilic (TEC) balance. Comparable to surfactant-based microemulsion, PtDO/TEC/water SFME can also be categorized into three types: water-in-oil, discontinuous, and oil-in-water. As TEC or water is increased, or PtDO is decreased, the nanoaggregates in PtDO/TEC/water SFME grow from <5 nm to tens of nanometers. The addition of α-arbutin (ABN) does not disrupt PtDO/TEC/water SFME, but rather enhances its formation, resulting in a larger monophasic area and consistent size (2.8-3.8 nm) through participating in interface assembly. Furthermore, ABN-loaded PtDO/TEC/water SFME exhibits remarkable resistance to dilution, exceptional stability, and minimal irritation. Notably, PtDO/TEC/water SFME significantly boosts ABN's solubility in water by 2 times, its percutaneous penetration rate by 3-4 times, and enables a slow-release DPPH• radical scavenging effect. This SFME serves as a safe and cosmetically suitable nanoplatform for the delivery of bioactive substances.

Ganglioside GM3-based anticancer vaccines: Reviewing the mechanism and current strategies.

Ganglioside GM3 is one of the most common membrane-bound glycosphingolipids. The over-expression of GM3 on tumor cells makes it defined as a tumor-associated carbohydrate antigen (TACA). The specific expression property in cancers, especially in melanoma, make it become an important target to develop anticancer vaccines or immunotherapies. However, in the manner akin to most TACAs, GM3 is an autoantigen facing with problems of low immunogenicity and easily inducing immunotolerance, which means itself only cannot elicit a powerful enough immune response to prevent or treat cancer. With a comparative understanding of the mechanisms that how immune system responses to the carbohydrate vaccines, this review summarizes the studies on the recent efforts to development GM3-based anticancer vaccines.

Research progress of fullerenes and their derivatives in the field of PDT.

In contemporary studies, the predominant utilization of C60 derivatives pertains to their role as photosensitizers or agents that scavenge free radicals. The intriguing coexistence of these divergent functionalities has prompted extensive investigation into water-soluble fullerenes. The photodynamic properties of these compounds find practical applications in DNA cleavage, antitumor interventions, and antibacterial endeavors. Consequently, photodynamic therapy is progressively emerging as a pivotal therapeutic modality within the biomedical domain, owing to its notable levels of safety and efficacy. The essential components of photodynamic therapy encompass light of the suitable wavelength, oxygen, and a photosensitizer, wherein the reactive oxygen species generated by the photosensitizer play a pivotal role in the therapeutic mechanism. The remarkable ability of fullerenes to generate singlet oxygen has garnered significant attention from scholars worldwide. Nevertheless, the limited permeability of fullerenes across cell membranes owing to their low water solubility necessitates their modification to enhance their efficacy and utilization. This paper reviews the applications of fullerene derivatives as photosensitizers in antitumor and antibacterial fields for the recent years.

Enhancing the tumor penetration of multiarm polymers by collagenase modification.

Tumor penetration is a critical determinant of the therapy efficacy of nanomedicines. However, the dense extracellular matrix (ECM) in tumors significantly hampers the deep penetration of nanomedicines, resulting in large drug-untouchable areas and unsatisfactory therapy efficacy. Herein, we synthesized a third-generation PAMAM-cored multiarm copolymer and modified the polymer with collagenase to enhance its tumor penetration. Each arm of the copolymer was a diblock copolymer of poly(glutamic acid)-b-poly(carboxybetaine), in which the polyglutamic acid block with abundant side groups was used to link the anticancer agent doxorubicin through the pH-sensitive acylhydrazone linkage, and the zwitterionic poly(carboxybetaine) block provided desired water solubility and anti-biofouling capability. The collagenase was conjugated to the ends of the arms via the thiol-maleimide reaction. We demonstrated that the polymer-bound collagenase could effectively catalyze the degradation of the collagen in the tumor ECM, and consequently augmented the tumor penetration and antitumor efficacy of the drug-loaded polymers.

Progress on synthesis and structure-activity relationships of lamellarins over the past decade.

Lamellarins are polyaromatic alkaloids isolated from marine organisms, including mollusks, tunicates, and sponges. Currently, over 60 structurally distinct natural lamellarins have been reported, and most of them exhibit promising biological activities, such as topoisomerase inhibition, mitochondrial function inhibition, multidrug resistance reversing, and anti-HIV activity. There has also been a significant progress on the synthetic study of lamellarins which has been regularly updated by numerous medicinal chemists as well. This review provides a detailed summary of the synthesis, pharmacology, and structural modification of lamellarins over the past decades.

G-4 inhibits triple negative breast cancer by inducing cell apoptosis and promoting LCN2-dependent ferroptosis.

Compound G-4 is a derivate of cyclin-dependent kinase inhibitor Rocovitine and showed strong sensitivity to triple negative breast cancer (TNBC) cells. In this study, the antitumor activity, mechanism and possible targets of G-4 in TNBC were investigated. Flow cytometry and immunoblotting showed that G-4 not only arrested the S phase of the cell cycle, but also induced apoptosis in TNBC cells via the mitochondrial pathway through inhibiting epidermal growth factor receptor (EGFR), AKT and MAPK pathways. In addition, G-4 induced the iron-mutagenesis process in TNBC cells and down-regulated differentially expressed gene lipid carrier protein 2 (LCN2) by RNA-seq. Moreover, G-4 elevated levels of cytosolic reactive oxygen species (ROS), lipid ROS, Fe and malondialdehyde (MDA), but decreased levels of superoxide dismutase (SOD) and glutathione (GSH), consistent with the effects of iron-mutagenic agonists Erastin and RSL3, which were inhibited by the iron inhibitor ferrostatin-1 (Fer-1). Furthermore, a LCN2 knockdown cell model was established by siRNA transfection, the IC50 of G-4 was increased nearly 100-fold, accompanied by a trend of no ferroptosis characteristic index. The results indicated that G-4 suppressed the malignant phenotype of TNBC, induced apoptosis by inhibiting EGFR pathway and promoted LCN2-dependent ferroptosis.

Ferrocene crosslinked and functionalized chitosan microspheres towards bio-based Fenton-like system for the removal of organic pollutants.

Dye-containing wastewater treatment has been a major long-term global challenge. For this purpose, a novel bio-based microspheres (CS-FC) with high specific surface area (63.24 m2·g-1) and nano-channels (17.95 nm) was prepared using chitosan as the framework and ferrocene as a crosslinking active group. CS-FC not only has the ability to rapidly enrich methyl orange (MO) through hydrogen-bonding and electrostatic attraction, but also almost completely degrades it in the presence of H2O2/K2S2O8 through a synergistic radical/non-radical mechanism under the activating effect of ferrocene. Without H2O2/K2S2O8, the maximum MO adsorption capacity of CS-FC is in the range 871-1050 mg·g-1, and conforms to a Langmuir isothermal model with pseudo-second-order kinetics. In the presence of H2O2/K2S2O8, the removal of MO dramatically increased from 32 % to nearly 100 % after incubation for 60 min, due to the simultaneous formation of highly reactive 1O2 and ·OH. The significant contribution from 1O2 endowed CS-FC/H2O2/K2S2O8 with high universality for degrading various organic pollutants (including azo dyes and antibiotics), a wide pH window (2-8), and low sensitivity to co-existing ions. Such cost-effective, recyclable porous bio-based microspheres are suitable for heterogeneous Fenton-like catalysis in organic wastewater treatment that rely on synergistic radical/non-radical reaction pathways.

Effect of glycosylation on the affinity of the MTB protein Ag85B for specific antibodies: towards the design of a dual-acting vaccine against tuberculosis.

BACKGROUND: To create a dual-acting vaccine that can fight against tuberculosis, we combined antigenic arabino-mannan analogues with the Ag85B protein. To start the process, we studied the impact of modifying different parts of the Ag85B protein on its ability to be recognized by antibodies. RESULTS: Through our research, we discovered that three modified versions of the protein, rAg85B-K30R, rAg85B-K282R, and rAg85B-K30R/K282R, retained their antibody reactivity in healthy individuals and those with tuberculosis. To further test the specificity of the sugar AraMan for AraMan antibodies, we used Human Serum Albumin glycosylated with AraMan-IME and Ara3Man-IME. Our findings showed that this specific sugar was fully and specifically modified. Bio-panning experiments revealed that patients with active tuberculosis exhibited a higher antibody response to Ara3Man, a sugar found in lipoarabinomannan (LAM), which is a major component of the mycobacterial cell wall. Bio-panning with anti-LAM plates could eliminate this increased response, suggesting that the enhanced Ara3Man response was primarily driven by antibodies targeting LAM. These findings highlight the importance of Ara3Man as an immunodominant epitope in LAM and support its role in eliciting protective immunity against tuberculosis. Further studies evaluated the effects of glycosylation on the antibody affinity of recombinant Ag85B and its variants. The results indicated that rAg85B-K30R/K282R, when conjugated with Ara3Man-IME, demonstrated enhanced antibody recognition compared to unconjugated or non-glycosylated versions. CONCLUSIONS: Coupling Ara3Man to rAg85B-K30R/K282R could lead to the development of effective dual-acting vaccines against tuberculosis, stimulating protective antibodies against both AraMan and Ag85B, two key tuberculosis antigens.

How does full-cost insurance for wheat affect pesticide use? From the perspective of the differentiation of farmers' production scale.

Theoretically, agricultural insurance influences farmers' use of pesticides by changing the expected income of agricultural production. Full-cost insurance, with high guarantee and high compensation characteristics, may significantly affect farmers' pesticide use. First, this paper constructs a production function to characterize and compare the marginal incomes of insured and uninsured farmers under risk uncertainty and analyses how insured farmers can increase marginal income by increasing or reducing factor inputs. Considering scale differentiation, it discusses pesticide use strategies different types of farmers may adopt to maximize household utility. Second, using survey data of the pilot counties of full-cost insurance for wheat in Henan Province, China, the simultaneous equation model is used for empirical testing. The results reveal the following: (i) Farmers' insurance participation and pesticide application behaviour are not mutually independent. (ii) For the whole sample, full-cost insurance for wheat has a significant pesticide reduction effect. (iii) However, considering scale differentiation, pesticide application decreases significantly among insured ordinary farmers but does not change significantly among insured large-scale farmers. Third, policy measures are proposed to activate the green development function of agricultural insurance.