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Although organic–inorganic hybrid Mn2+halides have advanced significantly, achieving high stability and narrow-band emission remains enormously challenging owing to the weak ionic nature and soft crystal lattice of the halide structure. To address these issues, we proposed a cationic engineering strategy of long-range cation π···π stacking and C–H···π interactions to simultaneously improve the crystal structural stability and rigidity. Herein, two organic zero-dimensional (0D) manganese halide hybrids of (BACQ)2MnX4[BACQ = 4-(butylamino)-7-chloroquinolin-1-ium; X = Cl and Br] were synthesized. (BACQ)2MnX4display strong green-light emissions with the narrowest full width at half-maximum (fwhm) of 39 nm, which is significantly smaller than those of commercial green phosphor β-SiAlON:Eu2+and most of reported manganese halides. Detailed Hirshfeld surface analyses demonstrate the rigid environment around the [MnX4]2–units originating from the interactions between [BACQ]+. The rigid crystal structure weakens the electron–phonon coupling and renders narrow fwhm of these manganese halides, which is further confirmed by temperature-dependent emission spectra. Remarkably, (BACQ)2MnX4realizes outstanding structural and luminescence stabilities in various extreme environments. Benefiting from the excellent performance, these Mn2+halides are used to assemble light-emitting diodes with a wide color gamut of 105% of the National Television System Committee 1931 standard, showcasing the advanced applications in liquid-crystal-display backlighting.

The lymphocyte-specific protein tyrosine kinase (LCK) plays a crucial role in both T-cell development and activation. Dysregulation of LCK signaling has been demonstrated to drive the oncogenesis of T-cell acute lymphoblastic leukemia (T-ALL), thus providing a therapeutic target for leukemia treatment. In this study, we introduced a sophisticated virtual screening strategy combined with biological evaluations to discover potent LCK inhibitors. Our initial approach involved utilizing the PLANET algorithm to assess and contrast various scoring methodologies suitable for LCK inhibitor screening. After effectively evaluating PLANET, we progressed to devise a virtual screening workflow that synergistically combines the strengths of PLANET with the capabilities of Schrödinger’s suite. This integrative strategy led to the efficient identification of four potential LCK inhibitors. Among them, compound 1232030-35-1 stood out as the most promising candidate with an IC50of 0.43 nM. Further in vitrobioassays revealed that 1232030-35-1 exhibited robust antiproliferative effects on T-ALL cells, which was attributed to its ability to suppress the phosphorylations of key molecules in the LCK signaling pathway. More importantly, 1232030-35-1 treatment demonstrated profound in vivoantileukemia efficacy in a human T-ALL xenograft model. In addition, complementary molecular dynamics simulations provided deeper insight into the binding kinetics between 1232030-35-1 and LCK, highlighting the formation of a hydrogen bond with Met319. Collectively, our study established a robust and effective screening strategy that integrates AI-driven and conventional methodologies for the identification of LCK inhibitors, positioning 1232030-35-1 as a highly promising and novel drug-like candidate for potential applications in treating T-ALL.

The increasing demands in optoelectronic applications have driven the advancement of organic–inorganic hybrid metal halides (OIMHs), owing to their exceptional optical and scintillation properties. Among them, zero-dimensional (0D) low-toxic manganese-based scintillators have garnered significant interest due to their exceptional optical transparency and elevated photoluminescence quantum yields (PLQYs), making them promising for colorful light-emitting diodes and X-ray imaging applications. In this study, two OIMH single crystals of (Br-PrTPP)2MnBr4(Br-PrTPP = (3-bromopropyl) triphenylphosphonium) and (Br-BuTPP)2MnBr4(Br-BuTPP = (4-bromobutyl) triphenylphosphonium) were prepared via a facile saturated crystallization method. Benefiting from the tetrahedrally coordinated [MnBr4]2–polyhedron, both of them exhibited strong green emissions peaked at 517 nm owing to the d–d electron transition of Mn2+with near-unity PLQYs of 99.33 and 86.85%, respectively. Moreover, benefiting from the high optical transparencies and remarkable luminescence properties, these manganese halides also exhibit excellent radioluminescent performance with the highest light yield of up to 68,000 photons MeV–1, negligible afterglow (0.4 ms), and linear response to X-ray dose rate with the lowest detection limit of 45 nGyairs–1. In X-ray imaging, the flexible film made by the composite of (Br-PrTPP)2MnBr4and PDMS shows an ultrahigh spatial resolution of 12.78 lp mm–1, which provides a potential visualization tool for X-ray radiography.

To explore the coupled effect of temperature Tand strain rate $$\dot{\varepsilon }$$ ε˙ on the deformation features of AZ31 Mg alloy, mechanical behaviors and microstructural evolutions as well as surface deformation and damage features were systematically examined under uniaxial tension at Tspanning from 298 to 523 K and $$\dot{\varepsilon }$$ ε˙ from 10−4to 10−2s−1. The increase in Tor the decrease in $$\dot{\varepsilon }$$ ε˙ leads to the marked decrease in flow stress, the appearance of a stress quasi-plateau after an initially rapid strain hardening, and even to the occurrence of successive strain softening. Correspondingly, the plastic deformation modes of AZ31 Mg alloy transform from the predominant twinning and a limited amount of dislocation slip into the enhanced non-basal slip and the dynamic recrystallization (DRX) together with the weakened twinning. Meanwhile, the cracking modes also change from along grain boundaries (GBs) and at twin boundaries (TBs) or the end of twins into nearby GBs where the DRX has occurred. The appearance of a stress quasi-plateau, the formation of large-sized cracks nearby GBs, and the occurrence of continuous strain softening, are intimately related to the enhancement of the non-basal slip and the DRX.

Optimization of grain boundary engineering (GBE) process is explored in a Fe–20Cr–19Mn–2Mo–0.82 N high-nitrogen and nickel-free austenitic stainless steel, and its intergranular corrosion (IGC) property after GBE treatment is experimentally evaluated. The proportion of low Σ coincidence site lattice (CSL) boundaries reaches 79.4% in the sample processed with 5% cold rolling and annealing at 1423 K for 72 h; there is an increase of 32.1% compared with the solution-treated sample. After grain boundary character distribution optimization, IGC performance is noticeably improved. Only Σ3 boundaries in the special boundaries are resistant to IGC under the experimental condition. The size of grain cluster enlarges with increasing fraction of low ΣCSL boundaries, and the amount of Σ3 boundaries interrupting the random boundary network increases during growth of the clusters, which is the essential reason for the improvement of IGC resistance.

Acute kidney injury (AKI) is defined as sudden loss of renal function characterized by increased serum creatinine levels and reduced urinary output with a duration of 7 days. Ferroptosis, an iron-dependent regulated necrotic pathway, has been implicated in the progression of AKI, while ferrostatin-1 (Fer-1), a selective inhibitor of ferroptosis, inhibited renal damage, oxidative stress and tubular cell death in AKI mouse models. However, the clinical translation of Fer-1 is limited due to its lack of efficacy and metabolic instability. In this study we designed and synthesized four Fer-1 analogs (Cpd-A1, Cpd-B1, Cpd-B2, Cpd-B3) with superior plasma stability, and evaluated their therapeutic potential in the treatment of AKI. Compared with Fer-1, all the four analogs displayed a higher distribution in mouse renal tissue in a pharmacokinetic assay and a more effective ferroptosis inhibition in erastin-treated mouse tubular epithelial cells (mTECs) with Cpd-A1 (N-methyl-substituted-tetrazole-Fer-1 analog) being the most efficacious one. In hypoxia/reoxygenation (H/R)- or LPS-treated mTECs, treatment with Cpd-A1 (0.25 μM) effectively attenuated cell damage, reduced inflammatory responses, and inhibited ferroptosis. In ischemia/reperfusion (I/R)- or cecal ligation and puncture (CLP)-induced AKI mouse models, pre-injection of Cpd-A1 (1.25, 2.5, 5 mg·kg−1·d−1, i.p.) dose-dependently improved kidney function, mitigated renal tubular injury, and abrogated inflammation. We conclude that Cpd-A1 may serve as a promising therapeutic agent for the treatment of AKI.

Low-density δ-quenching and partitioning (δ-QP) steels with excellent strength and ductility have been recently developed. However, there are still rare reports on the formability of δ-QP steels, which are critical for satisfying the manufacture of structural parts during the application in automotive industry. In the present work, an 1180 MPa Fe–Mn–Al–C–Nb δ-QP steel with a high ductility was adopted for the stretch–flangeability study. The δ-QP steel was developed by separated quenching and partitioning processes. A good hole expansion ratio (HER) of 34.9 ± 0.9% was obtained in the quenched steel, but it has been further increased to 52.2% by the tempering treatment. The improved stretch–flangeability was attributed to the enhanced austenite stability and deformation uniformity. On the one hand, the stability of austenite was increased by carbon partitioning during tempering, which reduced crack possibility via the suppression of the fresh martensite formation. On the other hand, the tempering treatment released the internal stress caused by martensitic transformation and reduced the difference in strength among different phases, resulting in an increase in the resistance to crack initiation and propagation.

With the emergence and development of unmanned aerial vehicles (UAVs), different sensors have become more miniaturized and intelligent. UAVs equipped with various sensors are now an important approach for acquiring spatial data. Many advantages, such as low cost, short revisiting cycle, flexibility and high precision, have made UAVs powerful tools in geological, agricultural, ecological and forestry growth monitoring, as well as evaluation. Now, UAVs are a hotspot in scientific research. Their application in mining areas (MA), although still in its infancy, is developing rapidly in terms of speed, scale and service scope. This research examines aspects such as UAV platforms, different sensors and their application fields, as well as reviewing the advances of scientific research in MA at the present time. By combining current research and the functions of multiple sensors, an application framework for UAV monitoring in MA is constructed. Finally, the challenge and prospects for the development of UAVs and sensors are also considered. This research hopes to provide a technical reference, expanding the knowledge and recognition of UAV monitoring in MA, as well as an assessment of applications in mining, reclamation and environment.

Exploring highly efficient blue-emissive lead-free halide materials is a significant and challenging objective in the study of luminescent materials. This study reports the synthesis of a new zero-dimensional (0D) hybrid zinc halide of [CYP]ZnBr4(CYP = 1-cyclohexylpiperazine) containing an isolated [ZnBr4]2–tetrahedron. [CYP]ZnBr4exhibits strong blue light emission with a high photoluminescence quantum yield (PLQY) of 79.22%, surpassing all previously reported 0D zinc halide counterparts. According to the theoretical and experimental studies, the blue light emission is attributed to intrinsic self-trapped excitons resulting from strong electron–phonon coupling and structural deformation. Importantly, [CYP]ZnBr4demonstrates excellent structural and luminescence stability toward high temperatures (180 °C) over at least half a month. High luminescence efficiency and stability enable [CYP]ZnBr4to be an efficient blue phosphor to fabricate white light-emitting diodes (LEDs), which produces high-quality white light with a color rendering index (CRI) of 93.1 and a correlated color temperature (CCT) of 5304 K, closely resembling natural sunlight. This white LED also exhibits consistent performance and stability across different drive currents, suggesting the potential for high-power optoelectronic applications. Overall, this study paves the way for the utilization of 0D hybrid halides in advanced solid-state lighting applications.

The effects of silicon oxide additive on the transformation characteristics of sodium and sulfur in coal ash under atmospheric and elevated pressure were investigated in this study. The results indicated that silicon oxide additive significantly inhibited the release of sodium under high pressure. The sodium content in ash with 4% of silicon oxide additive was 3.5% at 0.1 MPa, which was higher than that without additive. However, the sodium content increased to 5.4% without additive and 6.9% with 4% additive at 4 MPa, respectively. The sodium mainly existed in the forms of NaAlSiO4and NaAlSi3O8at 0.1 MPa, and the content of NaAlSiO4increased with increasing additive dosage, which weakened the agglomeration of ash. The decomposition of low melting point mineral CaSO4was inhibited at 4 MPa, and the formation of Na6Ca2Al6Si6O24(SO4)2from NaAlSiO4and CaSO4was promoted significantly with increasing additive dosage. Furthermore, the inhibition mechanism of sodium and sulfur released from coal ash by silicon oxide under high pressure was proposed.

Lead halide perovskites have been explored as a new kind of promising X-ray with wide applications in radiation-associated fields, but low light yield and serious toxicity extremely restrict further applications. To address these issues, we herein demonstrated one new zero-dimensional (0D) organic–inorganic hybrid cuprous halide of [BAPMA]Cu2Br5(BAPMA = N,N-Bis(3-aminopropyl) methylamine) containing discrete [Cu4Br10]6–tetramers as excellent lead-free scintillators. Upon UV light excitation, [BAPMA]Cu2Br5displays highly efficient broadband yellowish-green light emission with one dominant peak at 526 nm, a large Stokes shift of 244 nm, and a high photoluminescent quantum yield of 53.40%. Significantly, this broadband light emission can also be excited by higher-energy X-ray as radioluminescence with a high scintillation light yield of 43,744 photons/MeV. The detection limit of 0.074 μGyair/s is also far less than the required value for regular medical diagnostics of 5.5 μGyair/s. The solution-assembled hybrid structure facilely enables the [BAPMA]Cu2Br5-based scintillation screen to display high-performance X-ray imaging with a spatial resolution of 15.79 lp/mm showcasing potential application in X-ray radiography. In brief, combined merits of low toxicity and cost, negligible self-absorption, a low detection limit, considerable light yield, and spatial resolution highlight the excellent scintillation performance of 0D hybrid cuprous halide.

Hernandezine (Her) is a bisbenzylisoquinoline alkaloid extracted from the traditional Chinese herbal medicine Thalictrum glandulosissimum. Evidence shows that Her is a natural agonist of adenosine monophosphate (AMP)-activated protein kinase (AMPK) and induces apoptosis and autophagy in tumor cells. In this study, we investigated the role of autophagy in Her-induced cell death in human pancreatic cancer cell lines. We showed that Her dose-dependently suppressed cell proliferation, promoted autophagy and induced autophagic death in pancreatic ductal adenocarcinoma (PDAC) cell lines Capan-1 and SW1990. The IC50values of Her in inhibition of Capan-1 and SW1990 cells were 47.7 μM and 40.1 μM, respectively. Immunoblotting showed that Her (1−40 μM) promoted the conversion of LC3-I to LC3-II, and Her exerted concentration-dependent and time-dependent effects on autophagy activation in PDAC cells. In transmission electron microscopy and fluorescence image analysis, we found that autophagic vacuoles were significantly increased in Her-treated cells. Knockdown of ATG5, a key gene in the autophagy pathway, alleviated the activation of autophagy by Her. These results demonstrated that Her induced autophagy in PDAC cells. Intensely activated autophagy could promote cell death. The autophagy inhibitors, BafA1 and HCQ significantly inhibited Her-induced cell death, implying that Her induced autophagic cell death in PDAC cells. Moreover, we showed that Her activated autophagy by increasing the phosphorylation of AMPK and decreasing the phosphorylation of mTOR/p70S6K. Knockdown of AMPKα relieves the autophagic cell death induced by Her. Furthermore, Her concentration-dependently enhanced reactive oxygen species (ROS) generation in PDAC cells. Antioxidants could reduce the phosphorylation of AMPK and suppress autophagic cell death induced by Her. Our study provides evidence for the development of Her as a therapeutic agent for the treatment of pancreatic cancer.

Halide perovskite nanocrystal (PNC) of 3D CsPbX3as a scintillator has aroused intensive attention with advanced applications in radiation detection and X-ray imaging. However, the low light yield and serious toxicity of Pb2+severely hinder advanced optoelectronic applications. To reduce these fatal shortcomings, a family of new environmentally friendly 0D hybrid lead-free indium halides of [DADPA]InX6·H2O (DADPA = 3,3′-diaminodipropylamine; X = Cl and Br) was prepared. Upon UV excitation, these halides display strong broadband yellow-orange light emissions, and the photoluminescence quantum yield (PLQY) can be optimized up to near unity through the Sb3+-doping strategy. Significantly, high PLQY, negligible self-absorption and low attenuation ability toward X-ray render extraordinary scintillation performance with a high light yield of 51 875 photons MeV−1and ultralow detection limit of 98.3 nGyairs−1, which is far superior to typical 3D PNC scintillators. Additionally, the ultra-high spatial resolution of 25.15 lp mm−1, negligible afterglow time (2.75 ms) and robust radiant stability demonstrates excellent X-ray imaging performance. To the best of our knowledge, this is the first report on X-ray scintillation based on 0D indium halide materials.

X-ray scintillators as functional energy materials possess the powerful ability to convert high-energy radiation into visible light with wide applications in various nuclear radiation fields. In this regard, three-dimensional (3D) lead perovskite nanocrystal-based X-ray scintillators have attracted extensive attention, but their low light yield and serious toxicity extremely restrict their further applications. To address these issues, a family of 0D hybrid cuprous halides of A2Cu4X6(A = PTPP, TPA; X = Br, I) based on discrete [Cu4X6]2−nanoclusters were demonstrated as highly desirable lead-free scintillators. Upon excitation of both ultraviolet and blue light, these halide nanoclusters displayed that self-trapped excitons induced broadband light emissions from green to red with near-unity photoluminescent quantum yield (PLQY, 93.1%) andlarge Stokes shifts (>1.3 eV). Significantly, the high PLQY, negligible self-absorption, and strong X-ray attenuation from [Cu4X6]2−nanoclusters endowed them with extraordinary radioluminescence properties. The linear radioluminescence intensity response to a wide range of X-ray dose rates gave an acceptable detection limit of 0.7563 µGyairs−1, which was lower than the required value for regular medical diagnostics (5.5 µGyairs−1). X-ray imaging demonstrated an ultrahigh spatial resolution of 14.83 lp mm−1and negligible afterglow (1.3 ms), showcasing potential applications in X-ray radiography. Overall, the combined superiorities of nontoxicity, high light yield, excellent stability, and good radiation hardness make cuprous halide nanoclusters excellent scintillators.

Pancreatic ductal adenocarcinoma (PDAC) is an extremely aggressive malignancy prone to recurrence and metastasis. Studies show that tumor cells with increased invasive and metastatic potential are more likely to undergo ferroptosis. SMAD4 is a critical molecule in the transforming growth factor β (TGF-β) pathway, which affects the TGF-β-induced epithelial-mesenchymal transition (EMT) status. SMAD4 loss is observed in more than half of patients with PDAC. In this study, we investigated whether SMAD4-positive PDAC cells were prone to ferroptosis because of their high invasiveness. We showed that SMAD4 status almost determined the orientation of transforming growth factor β1 (TGF-β1)-induced EMT via the SMAD4-dependent canonical pathway in PDAC, which altered ferroptosis vulnerability. We identified glutathione peroxidase 4 (GPX4), which inhibited ferroptosis, as a SMAD4 down-regulated gene by RNA sequencing. We found that SMAD4 bound to the promoter of GPX4 and decreased GPX4 transcription in PDAC. Furthermore, TGF-β1-induced high invasiveness enhanced sensitivity of SMAD4-positive organoids and pancreas xenograft models to the ferroptosis inducer RAS-selective lethal 3 (RSL3). Moreover, SMAD4 enhanced the cytotoxic effect of gemcitabine combined with RSL3 in highly invasive PDAC cells. This study provides new ideas for the treatment of PDAC, especially SMAD4-positive PDAC.

Autophagy-lysosome system plays a variety of roles in human cancers. In addition to being implicated in metabolism, it is also involved in tumor immunity, remodeling the tumor microenvironment, vascular proliferation, and promoting tumor progression and metastasis. Transcriptional factor EB (TFEB) is a major regulator of the autophagy-lysosomal system. With the in-depth studies on TFEB, researchers have found that it promotes various cancer phenotypes by regulating the autophagolysosomal system, and even in an autophagy-independent way. In this review, we summarize the recent findings about TFEB in various types of cancer (melanoma, pancreatic ductal adenocarcinoma, renal cell carcinoma, colorectal cancer, breast cancer, prostate cancer, ovarian cancer and lung cancer), and shed some light on the mechanisms by which it may serve as a potential target for cancer treatment.

Rewritable luminescent paper is particularly crucial, considering the ultrahigh paper consumption and confidential information security, but a highly desirable stimuli-responsive smart luminescent material with excellent water solubility has rarely been studied. Herein, a new type of rewritable paper made by highly efficient green light emissive zero-dimensional (0D) organic manganese halides is rationally designed by virtue of the reversible photoluminescence (PL) off–on switching. Specifically, the green emission can be linearly quenched by water vapor in a wide humidity range and again recovered in a dry atmosphere, which make it a smart hydrochromic PL off–on switching and humidity sensor. Benefiting from the reversible luminescence off–on switch and excellent water solubility, rewritable luminescent paper is realized through water-jet security printing technology on 0D halide-coated commercial paper with high resolution. The printed/written information can be easily cleaned by slight heating with outstanding “write–erase–write” cycle capabilities. In addition, multiple light source-induced coincident green light emissions further provide convenience to realize anti-counterfeiting, encryption and decryption of confidential information, and so forth. This work highlights the superiority of dynamic ionic-bonded 0D organic manganese halides as reversible PL switching materials in rewritable luminescent paper, high-security-level information printing, storage and protection technologies, and so forth.

GSK3B is the mRNA form of glycogen synthase kinase 3 beta (GSK-3β), which is a critical repressor of Wnt/β-catenin signaling pathway and generally inhibited in cancer cells. Plenty of researches have disclosed that circular RNAs, namely circRNAs exert important functions in the progression of various human malignancies including lung adenocarcinoma (LUAD). Therefore, we attempted to explore whether there existed certain circRNAs that could mediate LUAD development by regulating GSK3B expression and Wnt/β-catenin pathway. In the present research, circ-GSK3B (hsa_circ_0066903) was found to be significantly down-regulated in LUAD tissues and cells and it suppressed the proliferation, migration and stemness of LUAD cells. Furthermore, it was discovered that circ-GSK3B competitively sponged miR-3681-3p and miR-3909 to elevate GSK3B expression. Circ-GSK3B could impair the binding ability of FKBP51 to GSK-3β to inhibit the phosphorylation of GSK-3βS9, resulting in the inactivation of Wnt/β-catenin signaling. In addition, the regulatory effect of circ-GSK3B on LUAD tumorigenesis and cell progression was testified through in vitro and in vivo rescue experiments. In conclusion, circ-GSK3B suppressed LUAD development through up-regulating and activating GSK3B.

Traditional white light-emitting diode (WLED) is mainly depending on coating broadband yellow phosphors (520–700 nm) on blue emitting LED chip (440–460). However, too strong blue light and absence of cyan light results in incongruous emission strength and low color rendering index (CRI), which cause serious damage to retina of eye. To overcome these shortcomings, cyan light emitting phosphor is highly desirable for the full-visible-spectrum LED with high CRI, but bright cyan phosphor remains rare. Herein, a new 0D hybrid copper(I) halide of [TMPDA]Cu2I6(TMPDA = N,N,2,2-tetramethyl-1,3-propylenediamine) single crystal is reported as a cyan light emitter with mominant emission wavelength at 489 nm, photoluminescence quantum yield of 26.66 % and large Stokes shift of 198 nm exceeding most of organic-inorganic metal halides. Remarkably, the single crystals display stable emission in various polar organic solvents and high temperature with sufficient emitting stability. More significantly, this 0D cuprous halide act as down-conversion cyan phosphor to fabricate WLED with a high CRI of 95 by reducing the cyan gap. In this study, we demonstrate an optical engineering strategy to prepare efficient cyan light emitting 0D cuprous halide and assembly high-performance WLED.

In this study, we propose a drainage pipe pile under vacuum consolidation to integrate foundation treatment and pile foundation engineering in soft soil areas. To study its bearing capacity characteristics and foundation treatment performance, single pile static load tests, vane shear tests, and water content tests were carried out for ordinary piles, perforated piles, and drainage pipe piles under conditions of static and vacuum consolidation. Based on the results, the concept of strong and weak reinforcement areas was proposed and used for bearing capacity prediction. The results showed that the drainage pipe pile did not become silted under vacuum consolidation. The single pile bearing capacity was much higher than that of an ordinary pile, and the pile side friction was exerted mainly in the middle and lower parts. Good results were achieved using the shear strength at the junction of the strong and weak reinforcement areas to estimate the ultimate bearing capacity of a single pile. This study provided important insights into the design and construction of drainage pipe piles in a soft soil foundation.

When tunnels are constructed in coastal cities, they will inevitably undercross a river. Exploring the influence of rivers on tunnelling-induced deformation in costal soft soil is of great significance for controlling excessive settlement and protecting surrounding buildings. This paper presents a case study of twin tunnels undercrossing a river in soft soil in Hangzhou, China. The soft soil of Hangzhou refers to cohesive soil in a soft plastic or fluid plastic state with high natural water content, high compressibility, low bearing capacity, and low shear strength. Considering the influence of the river, the research region was divided into two parts, inside and outside the river-affected area, based on monitoring data of the Zizhi Tunnel. The development law of surface settlement is divided into three stages. In the first and second stages, the surface settlement within and outside the river-affected area showed a similar trend: the settlement increased and the growth rate of settlement in the second stage was smaller within the river-affected area. In the third stage, the surface settlement continued to increase within the river-affected area, while it converged outside the river-affected area. Within the river-affected area, there was an asynchronization of the sinking rate and stability of vault settlements and surface settlements. A numerical model was established by simulating different reinforcements of the tunnel. The numerical model revealed that the ground movement is influenced by the distribution and amount of the excess pore water pressure. The excess pore pressure was concentrated mostly in the range of 1.0Ht–3.0Ht(Htis the tunnel height) before the tunnel face, especially within the river-affected area. Inside the river-affected area, the dissipation of excess pore water pressure needs more time, leading to slow stabilization of surface settlement. When undercrossing a river, a cofferdam is necessary to reduce excessive ground deformation by dispersing the distribution of excess pore water pressure.

Considering low photoluminescence quantum yield (PLQY < 5%) of blue emissive CsPbCl3bulk crystal and the high toxicity of Pb2+, it is significant to explore new single crystalline lead-free perovskites with highly efficient blue light emission. Herein, two new zero-dimensional (0D) hybrid indium halides of [H2EP]2InCl6·Cl·H2O·C3H6O and [H3AEP]InCl6··H2O (EP = 1-ethylpiperazine, AEP = N-aminoethyl piperazine) were prepared. Remarkably, these 0D indium halides display unusual blue light emissions (about 430 nm) with a highest PLQY of 13.44%. To the best of our knowledge, this work represents one of the first higher energy blue light emitters in hybrid indium perovskites, which would advance the research on lead-free hybrid halides for next-generation luminescent materials.

Uniaxial tensile tests were carried out at room temperature (RT) and 250 °C, respectively, to investigate the effect of short-range ordering (SRO) on the mechanical properties and deformation micromechanism of fine-grained (FG) Cu–Mn alloys with high stacking fault energy. The results show that at RT, with the increase in SRO degree, the strength of FG Cu–Mn alloys is improved without a loss of ductility, and corresponding deformation micromechanism is mainly manifested by a decrease in the size of dislocation cells. In contrast, at a high temperature of 250 °C, the SRO degree becomes violently enhanced with increasing Mn content, and the deformation microstructures thus transform from dislocation cells to planar slip bands and even to deformation twins, significantly enhancing the work hardening capacity of the alloys and thus achieving a better strength-ductility synergy of FG Cu–Mn alloys.

As biological ceramic composites, mollusk shells exhibit an excellent strength–toughness combination that should be dependent on aragonite/organic matrix interfaces. The mechanical properties and fracture mechanisms of the nacreous structure in the Cristaria plicata(C. plicata) shell and crossed-lamellar structures in the Cymbiola nobilis(C. nobilis) shell were investigated, focusing on the critical role of the organic matrix/aragonite interface bonding that can be adjusted by heat treatments. It is found that heat treatments have a negative impact on the fracture behavior of the nacreous structure in the C. plicatashell, and both the bending and shear properties decrease with increasing heat-treatment temperature because of the loss of water and organic matrix. In contrast, for the crossed-lamellar structure in C. nobilisshell, the water loss in heat treatment slightly decreases its bending properties. When the organic matrix is melted after an appropriate heat treatment at 300°C for 15 min, its bending properties can be greatly enhanced; in this case, remarkable toughening mechanisms involving crack deflection and the fiber pull-out are exhibited, although the interfacial bonding strength reduces. Therefore, an appropriate heat treatment would bring about a positive impact on the fracture behavior of crossed-lamellar structure in the C. nobilisshell. The major research findings have provided an important inspiration that the inducement of moderately weak interfaces rather than all strong interfaces might enhance the comprehensive mechanical properties of fiber-reinforced ceramic composites.

Gas–liquid (G–L) reactive crystallization is a major technology for advanced materials construction, which requires a short diffusion path on the interface to ensure the reactant supply and stable crystal nucleation under ultrahigh supersaturation. Herein, a covalent organic framework (COF) membrane with homo hierarchical pore structures was proposed as an effective interfacial material for the regulation of confined reactive crystallization. By combining the ordered nanopores of COFs and micropores of anodic aluminum oxide (AAO), the COF membrane simultaneously provided an excellent nanoscale diffusion–reaction regulation network as the molecular-level confined G–L reactive interface and adjustable submicrometer gas mass transfer channels. The highly selective construction of CaCO3superstructures was then achieved. When the submicrometer primary pore size rpof the constructed COF membrane ranged from 120 to 1.6 nm, the diffusion mechanism of CO2varied from viscous flow diffusion to Knudsen diffusion. The growth orientation of CaCO3crystals was well confined to obtain spindle-shaped crystals with high selectivity. Meanwhile, the crystal selectivity factor (cube/sphere) increased from 0 to 3.53 under the low interfacial nuclear barrier. Thus, the COF membrane with coupled micro-nanostructures successfully screened the directional preparation conditions for diverse CaCO3superstructures, which also paved a meaningful path for the functional application of COFs in accurate mass transfer control and confined chemical reactions.

Accurate cooling crystallization control has a significant impact on terminal crystal product quality. Herein, a hollow fiber membrane-assisted cooling crystallization (MACC) was investigated to achieve nucleation induction and self-seeding operation. Poly(tetrafluoroethylene) (PTFE) and polyethersulfone (PES) membranes with thermal conduction properties were introduced to accelerate the nucleation at a supercooled membrane surface, and the detached crystal seeds were then transferred into the crystallizer. A polymeric membrane can achieve nucleation control and hinder the potential secondary nucleation, which has been validated by online detection experiments. This advantage rendered excellent MACC performance in the manufacture of high-purity thiourea crystals, which possessed the desired morphology, a large mean size (>1.35 mm), high purity (>99.5 wt %), and narrower size distribution.

Background: Laparoscopic liver resection (LLR) has now been established as a safe and minimally invasive technique that is deemed feasible for treating hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). However, the role of LLR in treating combined hepatocellular-cholangiocarcinoma (cHCC-CC) patients has been rarely reported. This study aimed to assess the efficacy of LLR when compared with open liver resection (OLR) procedure for patients with cHCC-CC. Methods: A total of 229 cHCC-CC patients who underwent hepatic resection (34 LLR and 195 OLR patients) from January 2014 to December 2018 in Zhongshan Hospital, Fudan University were enrolled and underwent a 1:2 propensity score matching (PSM) analysis between the LLR and OLR groups to compare perioperative and oncologic outcomes. Overall survival (OS) and recurrence-free survival (RFS) parameters were assessed by the log-rank test and the sensitivity analysis. Results: A total of 34 LLR and 68 OLR patients were included after PSM analysis. The LLR group displayed a shorter postoperative hospital stay (6.61 vs.8.26 days; p value&lt; 0.001) when compared with the OLR group. No significant differences were observed in the postoperative complications’ incidence or a negative surgical margin rate between the two groups (p value= 0.409 and p value= 1.000, respectively). The aspartate aminotransferase (AST), alanine aminotransferase (ALT), and inflammatory indicators in the LLR group were significantly lower than those in the OLR group on the first and third postoperative days. Additionally, OS and RFS were comparable in both the LLR and OLR groups (p value= 0.700 and p value= 0.780, respectively), and similar results were obtained by conducting a sensitivity analysis. Conclusion: LLR can impart less liver function damage, better inflammatory response attenuation contributing to a faster recovery, and parallel oncologic outcomes when compared with OLR. Therefore, LLR can be recommended as a safe and effective therapeutic modality for treating selected cHCC-CC patients, especially for those with small tumors in favorable location.

Low-dimensional organic–inorganic hybrid metal halide materials have been extensively studied due to their excellent optoelectronic performances. Herein, by using the facile wet-chemistry method, we designed one new hybrid cadmium bromide of (H3AEP)2CdBr6·2Br based on discrete octahedral [CdBr6]4–units. Remarkably, the bulk crystal of (H3AEP)2CdBr6·2Br exhibits strong broadband orange–red light emission from the radiative recombination of self-trapped excitons (STEs) with a high photoluminescence quantum yield (PLQY) of 9%. Benefiting from the highly efficient luminescent performance, this 0D cadmium perovskite can be utilized as an excellent down-conversion red phosphor to assemble a white light-emitting diode, and a high color rendering index (CRI) of 93 is realized. As far as we know, this is the first orange–red light-emitting hybrid cadmium perovskite which promotes the full-color display in this system.

Herein, a new organic–inorganic hybrid cuprous iodide of [(Me)2-DABCO]Cu6I8was prepared and structurally characterized with a novel three-dimensional (3D) [Cu6I8]2–framework. Significantly, this 3D cuprous iodide displays infrequent broadband red-to-near-infrared light emission (600–1000 nm) stemming from the radiative recombination of self-trapped excitons.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers, with a minimal difference between its incidence rate and mortality rate. Advances in oncology over the past several decades have dramatically improved the overall survival of patients with multiple cancers due to the implementation of new techniques in early diagnosis, therapeutic drugs, and personalized therapy. However, pancreatic cancers remain recalcitrant, with a 5-year relative survival rate of <9%. The lack of measures for early diagnosis, strong resistance to chemotherapy, ineffective adjuvant chemotherapy and the unavailability of molecularly targeted therapy are responsible for the high mortality rate of this notorious disease. Genetically, PDAC progresses as a complex result of the activation of oncogenes and inactivation of tumor suppressors. Although next-generation sequencing has identified numerous new genetic alterations, their clinical implications remain unknown. Classically, oncogenic mutations in genes such as KRASand loss-of-function mutations in tumor suppressors, such as TP53, CDNK2A, DPC4/SMAD4,and BRCA2, are frequently observed in PDAC. Currently, research on these key driver genes is still the main focus. Therefore, studies assessing the functions of these genes and their potential clinical implications are of paramount importance. In this review, we summarize the biological function of key driver genes and pharmaceutical targets in PDAC. In addition, we conclude the results of molecularly targeted therapies in clinical trials and discuss how to utilize these genetic alterations in further clinical practice.

Mollusk shells generally consist of several macro-layers with different microstructures. To explore the specific role that different macro-layers play in the overall mechanical properties of shells, the microstructures, hardness distribution, and three-point bending behavior in the deep-sea Nautilusshell were investigated. It is found that the shell presents a hierarchical structure comprising three layers in thickness, that is, the outer, middle, and inner layers, which exhibit homogeneous, prismatic, and nacreous structures, respectively. Among them, the homogeneous structure in the outer layer is harder, which is beneficial for the shell to enhance resistance to wear and perforation. Furthermore, both the bending strength and fracture energy for group Up (loading from outer to inner surfaces) are far higher than those for group Down (loading from inner to outer surfaces), indicating that the inner nacreous layer is not only stronger but also tougher. Cracks tend to deflect at the interfaces in nacreous structure, and nacreous structure is thereby more resistant to breakage. Hence, the nacreous structure in the inner layer could protect the shell from breaking catastrophically in the deep sea with high pressure. In brief, the combination of a harder outside layer and a tougher inside layer provides an effective protective structure for the deep-sea shell, and the excellent environment adaptability of Nautilusshell can thus be interpreted in terms of its ingenious microstructure arrangement.

The cold-rolled Fe-8Mn-6Al-0.4C duplex low-density steel was annealed at different conditions to obtain ferrite + austenite duplex microstructure. The excellent mechanical properties (i.e., elongation of 52%, tensile strength of 785 MPa, and a product of tensile strength and elongation of 40.9 GPa·%) have been obtained by adjusting the volume fraction and the stability of austenite. The microstructure of the experimental steels was analyzed by scanning electron microscopy (SEM) and electron back-scatter diffraction (EBSD), and the volume fraction of austenite was estimated by the X-ray diffraction (XRD). The results show that the distribution of austenite grain size is inhomogeneous, and that the mechanical stability of austenite is mainly affected by the alloying partitioning and the variation of grain size during the annealing process. The increase of elongation is attributed to the degradation in mechanical stability of austenite, which can efficiently promote an occurrence of transformation induced plasticity (TRIP) effect.

Recently, two-dimensional (2D) hybrid lead halide perovskite has been widely utilized as a preferred platform of optoelectronic material with tailorable compositions, structures, and intrinsic broadband emission properties, and this achievement significantly promotes the research desirability to explore a new type of halide prototype to mimic the 2D perovskite model. Herein, we first performed a systematic approach on one-dimensional (1D) perovskite and realized comparable performances in both structural and property modulations. Specifically, by choosing diversified organic cations as a structural design strategy, we successfully constructed a series of 1D APbBr3(A = DBU, 1,8-diazabicyclo[5.4.0]undec-7-ene; DMTHP, 5,5-dimethyl-1,4,5,6-tetrahydropyrimidine; DBN, 1,5-diazabicyclo[4.3.0]-5-nonene; EPD, 1-ethylpiperidine) homologues based on identical 1D face-shared octahedral [PbBr3]−chains. This structural model features large accommodation ability for a variety of organic blocks enabling diversified photoluminescence (PL) properties from broadband yellow to white light emissions. Most remarkably, [DBU]PbBr3displays broadband yellow (0.47, 0.45) and white (0.32, 0.36) light emissions from two excited centers corresponding to distinct self-trapped excitons (STEs). These efficient dual light emissions were verified by high photoluminescence quantum yields (PLQYs) of 5.47 and 5.17%, respectively. The multiple advantages of unified crystal lattice, tailorable chemical composition, and tunable PL performance enable this 1D APbBr3perovskite to be an emerging and standard structural prototype to diversify and optimize the optoelectronic properties with potential in single-component white-light-emitting diodes.

Commercially available rare-earth-doped inorganic oxide materials have been widely applied as X-ray scintillators, but the fragile characteristics, high detection limit, and harsh preparation condition seriously restrict their wide applications. Furthermore, it remains a huge challenge to realize X-ray flexible imaging technology for real-time monitoring of the curving interface of complex devices. To address these issues, we herein report two isostructural cuprous halides of zero-dimensional (0D) [AEPipz]CuX3·X·H2O (AEPipz = N-aminoethylpiperazine, X = Br and I) with controllable size to nanosize crystal as highly efficient scintillators toward flexible X-ray imaging. These cuprous halides exhibit highly efficient cyan photoluminescence and radioluminescence emissions with the highest quantum yield of 92.1% and light yield of 62,400 photons MeV–1, respectively, surpassing most of the commercially available inorganic scintillators. Meanwhile, the ultralow detection limit of 95.7 nGyairs–1was far below the X-ray dose required for diagnosis (5.5 μGyairs–1). More significantly, the flexible film is facilely assembled with excellent foldability and high crack resistance, which further acts as a scintillation screen achieving a high spatial resolution of 17.4 lp mm–1in X-ray imaging, demonstrating the potential application in wearable radiation radiography. The combined advantages of high light yield, low detection limit, and excellent flexibility promote these 0D cuprous halides as the most promising X-ray scintillators.

In this article, double carbon shell hollow spheres which provide macropores (mC) for ultrasmall Fe3O4nanoparticle (10–20 nm) encapsulation individually were first prepared (Fe3O4@mC). The well-constructed Fe3O4@mC electrode materials offer the feasibility to study the volume change, aggregation, and pulverization process of the active Fe3O4nanoparticles for Li-ion storage in a confined space. Fe3O4@mC exhibits excellent electrochemical performances and delivers a high capacity of 645 mA h g–1at 2 A g–1after 1000 cycles. Even at 10 A g–1or after 1000 cycles at 2 A g–1, the porous carbon structure was well maintained and no obvious aggregation and pulverization of the Fe3O4nanoparticles was observed, although the volume of the active Fe3O4particles was expanded to 40–60 nm compared to that of the original particles (10–20 nm). This can be due to the in situ embedment of one Fe3O4nanoparticle into one macropore individually. The uniform dispersion and confinement of the Fe3O4nanoparticles in the macropores of the carbon shell could effectively accommodate severe volume variations upon cycling and prevent self-aggregation and spreading out from the carbon shell during the expansion process of the nanoscale Fe3O4particles, leading to improved capacity retention. Our work confirms the effectiveness for pulverization control by confining Fe3O4nanoparticles individually into macropores to improve its Li-ion storage properties, providing a novel strategy for the design of new-structured anode materials for Li-ion batteries.

Organic-inorganic hybrid molecular fluorescent materials have attracted much attention due to their application potential in white LEDs and high-definition displays. However, achieving high thermal stability for the fields of lighting/displays remains greatly challenging based on the hybrid molecular materials. Herein, we reported a crystalline state 1D rigid rare-earth hybrid coordinate polymer molecular crystal [(CH3CH2)4N]Tb[CH2(SO3)2] (1) along with high quantum yield (QY) 75.2%. Interestingly, this hybrid molecular crystal remains stable up to 728 K (∼455 °C). Remarkably, it exhibits excellent fluorescence thermal stability at high temperatures (150 °C, >95% and 150–200 °C, >82%) and a high thermal activation energy of 568.7 meV. Besides, the fabricated n-UV chips based white-LED by 1, commercial red Y2O3:Eu3+and blue BaMgAl10O17:Eu2+phosphor emits white light with color coordinates (CIE, 0.33, 0.32), high color rendering index (CRI) of 91.2, and correlated color temperature (CCT) 5623 K. These results reveal that this ultrahigh thermal stability hybrid molecular crystal as a green phosphor has great potential applications for displays or WLEDs. Therefore, this study opens a new avenue to develop novel rare-earth phosphors and gives new visions for hybrid molecular fluorescent materials.

A quantitative water detection method is urgently needed in storage facilities, space exploration, and the chemical industry. Although numerous physical techniques have been widely utilized to determine the water content, they still suffer from many disadvantages such as highly expensive special instruments, complicated analysis processes, etc. Hence, a convenient, rapid, and sensitive water analysis method is highly desirable. Herein, we developed a visual fluorescence sensing technology for water detection based on reversible PL off-on switching of organic–inorganic hybrid zero-dimensional (0D) manganese halides. In this work, a family of hybrid manganese halides were synthesized through a facile solution method, namely, [NH4(18-Crown-6)]2MnBr4, [Ca(18-Crown-6)·3H2O](18-Crown-6)MnBr4, [NH4(dibenzo-18-Crown-6)]2MnBr4, and [Ca(dibenzo-18-Crown-6)·2H2O]MnBr4. Excited by UV light, these highly crystalline manganese halides exhibit strong green light emissions from the d–d electron transition of Mn2+with near-unity photoluminescence quantum yield and submillisecond lifetime. Benefiting from the dynamic and weak ionic bonding interactions, these 0D manganese halides display reversible water-response on/off luminescence switching but fail in any other aprotic solvents. Therefore, these 0D hybrid manganese halides can be explored as ultrafast visual fluorescence probes to detect the trace amount of water in organic solvents with multiple superiorities of rapid response time (< 2 s), ultralow detection limit (9.71 ppm), excellent repeatability, etc. The reversible water-response luminescent on/off switching also provides a binary optical gate with advanced applications in anticounterfeiting and information security, etc.

Cooling crystallization is an important separation process and particuology technology that requires accurate nucleation control strategies. Herein, we introduced the polymeric hollow fiber membrane with proper thermal properties as the effective nucleation induction interface during cooling crystallization. The heterogeneous nucleation control mechanism was introduced based on classical nucleation theory and the thermal transfer process. Interfacial properties and the thermal conductivity of two kinds of polymeric membranes, polytetrafluoroethylene (PTFE) and polyethersulfone (PES), were measured and simulated with the developed model. These two membranes possessed different nucleation induction periods, nucleation rates and crystallization performances, which validated that the hollow fiber membrane module could effectively accelerate the nucleation process compared to conventional cooling crystallization owing to the shorter nucleation induction period and the reduced solution surface tension. Due to the higher hydrophobicity and the lower roughness of the membrane surface, the PTFE membrane possessed a more moderate performance in generating stable heterogeneous nucleation than the one of PES membrane. Thus, the adjustable membrane property enabled the hollow fiber membrane-assisted cooling crystallization to possess the accurate nucleation control and desired terminal particle products.

Aryl-ether cleavage and benzylic quaternary ammonium (QA) group degradation are promoted by C═O groups in most commercial anion exchange membrane materials. Herein, a novel strategy of converting C═O groups to the electron-donating C-NH2linkages in conventional poly(arylene ether ketone)s is proposed by reductive amination via Leuckart reaction. Density functional theory (DFT) calculations indicate that the model compound containing C-NH2linkage exhibits much higher barrier heights for aryl-ether cleavage and QA group degradation by enhancing the electronic cloud density on both the ether-connected carbon and the benzylic carbon. The C-NH2linkages also induce hydrogen bond networks in the membranes, which enhance intermolecular interaction and provide additional hydroxide transport sites. As a result, the C-NH2linkage membranes exhibit excellent hydroxide conductivity (108.2 mS cm–1at 80 °C) and tensile strength (48.4 MPa) with high elongation at break (50.8%). The C-NH2linkage membranes also show outstanding alkaline stability with no detectable backbone degradation even in 4 M KOH at 80 °C for 400 h, which is at the top-level among the state-of-the-art main chain architecture AEMs. This study proposes a new strategy for the synthesis of highly stable AEMs based on electron-donating C-NH2link backbone.

In recent years, low-dimensional lead halides have emerged as some of most attractive photoelectric materials due to their intrinsic broadband emissions with a potential application in white-light emitting diodes. To achieve the desired performance, tremendous research has emphasized the modulation of inorganic components as optical centers; however, less work has paid attention to the direct contribution of the organic components. Herein, we successfully assembled two new hybrid lead halides of [H2BPP]Pb2X6(X = Br, 1, and Cl, 2) containing one-dimensional double [Pb2X6]2–chains using optically active 1,3-bis(4-pyridyl)-propane (BPP) as an organic cation. Under UV-light excitation, compounds 1and 2exhibit broadband yellowish-green emissions, which were verified by promising photoluminescence quantum efficiencies (PLQEs) of 8.10% and 4.84%, respectively. The broadband light emissions are derived from the combination of dual higher-energy blue and lower-energy yellow light spectra, which can be attributed to the individual contributions of the organic and inorganic components, respectively, according to the time-resolved and temperature-dependent emission spectra as well as theoretical calculations. This work proves the great contribution of organic components to the photophysical properties and provides a new design strategy to realize broadband light emission by rationally combining the dual-emitting properties of different assembly blocks.

In recent years, two-dimensional (2D) hybrid lead halide perovskites based on corner-shared [PbX6] octahedrons have received extensive attention with important potentials in single-component white-light emitting diodes (WLEDs) due to the soft and distorted crystal lattices. However, limited research focused on the one-dimensional (1D) perovskites although they possess similar structural superiorities to achieve this performance. Herein, by using different types of organic amine cations as structural direction reagents, we report one new type of hybrid 1D perovskites of APbCl3(A = (DTHPE)0.5, DMTHP, DBN) based on the same 1D face-shared octahedral [PbCl3]−chains. Upon UV light excitation, these 1D APbCl3perovskites exhibit intrinsic broad-band bluish white-light emissions covering entire visible light spectra with the highest photoluminescence quantum yield (PLQY) of 6.99%, which catches up with the values of previously reported 2D perovskites. Through the systematical studies of time-resolved, temperature-dependent PL emissions, theoretical calculations, and so on, these broad-band light emissions can be ascribed to the radiative transition within conjugated organic cations. The facile assembly process, intrinsic broad-band light emissions, and high PLQYs enable these 1D APbCl3perovskites as new types of promising candidates in fabricating single-component WLEDs.

The key to realizing practical applications of Li–S batteries lies in scalable fabrication of cathode materials with high sulfur-loading and strong binding of lithium polysulfides (LiPSs). We report a scalable CeO2–CNT@C porous membrane with a large porosity of 90%. Introducing CNTs is critical to increase the porosity and construct porous networks with CNTs as the skeleton and CeO2-doped carbon as the shell. The macropores can improve the transport of Li+and electrolyte, while the porous networks possess high polysulfide-adsorbing and electron-transferring ability. The CeO2–CNT@C membrane can serve as an Al foil-free cathode and an interlayer for Li–S batteries. Moreover, CeO2can immobilize LiPSs and can alleviate its shuttle effect. The Li–S batteries with a sulfur loading of 6.2 mg cm–2deliver a capacity of 847 mA h g–1after 100 cycles, showing a high areal capacity of 5.25 mA h cm–2at a low electrolyte/sulfur ratio of 5.2 μL mg–1.

One of the major challenges of immune checkpoint blockade (ICB) is the poor penetration of antibody for solid tumor treatment. Herein, peptides with deeper penetration capability are used to develop a click reaction-assisted peptide immune checkpoint blockade (CRICB) strategy that could in situconstruct assemblies, enabling enhanced accumulation and prolonged PD-L1 occupancy, ultimately realizing high-performance tumor inhibition. First, the free DBCO-modified targeting peptide (TP) efficiently recognizes and binds PD-L1 in a deep solid tumor. Upon a reagent-free click reaction with a subsequently introduced azide-tethered assembled peptide (AP), the click reaction results in spontaneous self-aggregation in situwith enhanced accumulation and prolonged occupancy. In addition, the penetration of TP-AP (121.2 ± 15.5 μm) is significantly enhanced compared with that of an antibody (19.9 ± 5.6 μm) in a solid tumor tissue. More importantly, significant immunotherapy effects and negligible side effects are observed in 4T1 and CT26 tumor-bearing mice models treated with TP-AP, suggesting the high-performance tumor inhibition attributed to the CRICB strategy. In summary, this CRICB strategy manifest the preferable effects of immune checkpoint blockade, thereby extending the biomedical application of assembling peptides.

Natural compound valepotriate exhibits inhibitory activity against a number of cancers, but the effect of valepotriate against pancreatic cancer is unclear, and the structure–activity relationship of valepotriate has not been characterized. In this study, we performed a structure-based similarity search and found 16 hit compounds. Among the 16 hits, (1S,6S,7R)-6-(acetyloxy)-1-[(3-methylbutanoyl)oxy]-4a,5,6,7a-tetrahydro-1H-spiro[cyclopenta[c]pyran-7,2’-oxiran]-4-ylmethyl 3-methylbutanoate (denoted as Amcp) exhibited superior anticancer activity against human pancreatic cancer BxPC-3 and SW1990 cells. The anti-proliferation activity of Amcp was validated in human pancreatic cancer BxPC-3 and SW1990 cells in vitro. Amcp more effectively induced apoptosis in BxPC-3 and SW1990 cells than gemcitabine. At a concentration of 15 μM, Amcp significantly suppressed the PI3K/AKT pathway and disrupted the mitochondrial membrane equilibrium through modulation of Noxa and Mcl-1 balance in both cell lines. Meanwhile, knockdown of Noxa substantially attenuated Amcp-induced reduction of cell viability and anti-apoptotic protein Mcl-1 level in BxPC-3 cells. In addition, Amcp showed synergistic anticancer effects when combined with gemcitabine in BxPC-3 cells. To conclude, this work not only suggests that Amcp possesses a dual-inhibitory activity towards PI3K/AKT pathway and Mcl-1, but also enlightens further development of bioactive valepotriate derivatives.

Antisolvent crystallization is an important purification technology for the pharmaceutical and fine chemical industries. Herein, we investigated the mass-transfer mechanism of membrane-assisted antisolvent crystallization (MAAC) and developed a multistage operation to reinforce the manufacturing features of antisolvent crystallization. Computational fluid dynamics simulation results via a developed mathematics model and the experimental images via in situ detection technology jointly illustrated the advantages of MAAC for accurate mass-transfer control. Further, a three-stage MAAC process was investigated to reveal the process control performance. The diverse functional regions of multistage MAAC under different antisolvent addition strategies were then highlighted by manufacturing the crystal products with a narrow size distribution, a uniform aspect ratio, and the desired morphology. Multistage MAAC that intensifies the product capacity under a stable control is a promising direction for new-generation antisolvent crystallization.