Strategies for enhancing non-small cell lung cancer treatment: Integrating Chinese herbal medicines with epidermal growth factor receptor-tyrosine kinase inhibitors therapy.

Non-small cell lung cancer (NSCLC) poses a global health threat, and epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) such as gefitinib, afatinib, and osimertinib have achieved significant success in clinical treatment. However, the emergence of resistance limits the long-term efficacy of these treatments, necessitating urgent exploration of novel EGFR-TKIs. This review provides an in-depth summary and exploration of the resistance mechanisms associated with EGFR-TKIs, with a specific focus on representative drugs like gefitinib, afatinib, and osimertinib. Additionally, the review introduces a therapeutic strategy involving the combination of Chinese herbal medicines (CHMs) and chemotherapy drugs, highlighting the potential role of CHMs in overcoming NSCLC resistance. Through systematic analysis, we elucidate the primary resistance mechanisms of EGFR-TKIs in NSCLC treatment, emphasizing CHMs as potential treatment medicines and providing a fresh perspective for the development of next-generation EGFR-TKIs. This comprehensive review aims to guide the application of CHMs in combination therapy for NSCLC management, fostering the development of more effective and comprehensive treatment modalities to ultimately enhance patient outcomes.

Prescribed Fixed-Time Control for Constrained Uncertain Nonlinear Cyber-Physical Systems Against Deception Attacks.

In this note, a novel prescribed fixed-time adaptive tracking control scheme is developed to cope with the fixed-time tracking control issue for a category of constrained MIMO nonlinear cyber-physical systems (CPSs) with exogenous perturbations, which suffer from deception attacks started in controller-actuator (C-A) channel. Distinguished from the conservative dynamic surface control (DSC) schemes with a linear filter, a novel nonlinear filter is designed in our strategy, which can tackle the intrinsic issue of explosion of computational complexity and promote the system performance. Besides, a new barrier Lyapunov function (BLF) is designed to ulteriorly enhance the tracking performance on the basis of the prescribed performance function (PPF) approach. Prominently, the proposed control strategy could accommodate the exogenous interferences and deception attacks simultaneously. Furthermore, we have substantiated that the developed approach can not only make certain that all the tracking errors of the resulting closed-loop system, including output tracking errors and virtual tracking errors, enter a prespecified small region near equilibrium point with fixed-time convergence rate, but also guarantee them obey the corresponding constraints throughout the entire control operation, where the regulation time and the tracking accuracy level keep prior known and could be prespecified arbitrarily. Finally, the validity and effectiveness of the proposed control scheme are illustrated through a representative application instance.

Construction of vector vortex beams on hybrid-order Poincaré sphere through highly scattering media.

Vector vortex beams (VVBs) have attracted extensive attention due to their unique properties and their wide applications in fields such as optical manipulation and optical imaging. However, the wavefronts of the vector vortex beams are highly scrambled when they encounter highly scattering media (HSM), such as thick biological tissues, which greatly prevents the applications of VVBs behind HSM. To address this issue, we propose a scheme to construct VVBs of freewill position on the surface of hybrid-order Poincaré sphere (HyOPS) through HSM. With the measurement of two orthogonal scalar transmission matrices, the conjugated wavefronts for constructing orbital angular momentum beams with arbitrary topological charge in right and left circularly polarized states through HSM can be calculated, respectively. When an input wavefront superimposed by the two conjugated wavefronts with an appropriate ratio and phase delay, impinges on the HSM, the desired VVB can be created through HSM. To demonstrate the viability of our scheme, a series of VVBs on different locations of various HyOPSs have been reconstructed through a ZnO scattering layer experimentally. Furthermore, to characterize the polarization distribution of the generated beams, the polarization maps of these beams are derived by measuring the four Stokes parameters, which agree well with the theoretical distributions. This work will promote the applications of VVBs in highly scattering environments.

Study for Photo-Induced Enhanced Raman Spectroscopy with Laser-Induced Periodic Surface Structures on Lithium Niobate on Insulator.

Femtosecond laser irradiation (FLI) of laser-induced periodic surface structures (LIPSSs) has proven to be an efficient and robust strategy for surface modification in nanoscale. Lithium niobate on insulator (LNOI) retains the excellent optoelectric properties of bulk lithium niobate and features intrinsic roughness and defects, exhibiting promising potential in the applications of surface-enhanced Raman spectroscopy (SERS) and photo-induced enhancement Raman spectroscopy (PIERS). Herein, we proposed a novel LNOI-LIPSSs-AgNPs substrate that exhibited an increased SERS enhancement by a factor of 3.7 relative to that without LIPSSs. More remarkably, with UV pre-irradiation, a PIERS amplification up to 8.1 times in comparison to SERS was achieved. Detailed and comprehensive analyses of the enhancement mechanisms prove the synergy between the electromagnetic mechanism and chemical mechanism. Additionally, the PIERS substrate exhibits advantages of high-fabrication efficiency, long-term stability, excellent detection universality, and multicyclic self-cleaning ability, which may trigger new applications in various branches of analytical science.

The relationship between ischemic penumbra progression and the oxygen content of cortex microcirculation in acute ischemic stroke.

The precise oxygen content thresholds of ischemic deep parenchymal (OCIDP) and that in cortical microcirculation (OCCM), which leads to ischemic penumbra converting into the infarcted core, remain uncertain. This study employed an invasive fiber-optic oxygen meter and a newly developed oxygen-responsive probe called RuA3-Cy5-rtPA (RC-rtPA) based on recombinant tissue-type plasminogen activator (rtPA) to examine the oxygen content thresholds. A mouse model of middle cerebral artery occlusion was generated and animals were randomly divided into a sham, 24-h reperfusion after 3-h ischemia (IR 3-h), and IR 6-h groups, all of which were sacrificed following reperfusion. Stroke severity was evaluated based on the infarction area, neurological symptoms, microcirculation perfusion, and microemboli in microcirculation. OCIDP was characterized based on its extent and distribution, whereas OCCM was measured using RC-rtPA. During ischemia, stroke severity escalation manifested as increasing infarction area, severe neurologic symptoms, and poorer microcirculation perfusion with more microthrombi depositions. OCIDP presented rapid decline following artery occlusion along with a gradual increase in the hypoxic area. Within 3 â€‹h following ischemia induction, the ischemic tissue that experienced hypoxia could be rescued, and this reversibility would disappear after 6 â€‹h. Within 6 â€‹h, OCCM continued to decrease. A significant decrease in oxygen content in cortical venules and cortical parenchyma was observed. These findings assist in establishing the extent of the ischemic penumbra at the microcirculation level and offer a foundation for assessing the ischemic penumbra that could respond positively to reperfusion therapy beyond the typical time window.

The Tick Saliva Peptide HIDfsin2 TLR4-Dependently Inhibits the Tick-Borne Severe Fever with Thrombocytopenia Syndrome Virus in Mouse Macrophages.

Ticks transmit a variety of pathogens to their hosts by feeding on blood. The interactions and struggle between tick pathogens and hosts have evolved bilaterally. The components of tick saliva can directly or indirectly trigger host biological responses in a manner that promotes pathogen transmission; however, host cells continuously develop strategies to combat pathogen infection and transmission. Moreover, it is still unknown how host cells develop their defense strategies against tick-borne viruses during tick sucking. Here, we found that the tick saliva peptide HIDfsin2 enhanced the antiviral innate immunity of mouse macrophages by activating the Toll-like receptor 4 (TLR4) signaling pathway, thereby restricting tick-borne severe fever with thrombocytopenia syndrome virus (SFTSV) replication. HIDfsin2 was identified to interact with lipopolysaccharide (LPS), a ligand of TLR4, and then depolymerize LPS micelles into smaller particles, effectively enhancing the activation of the nuclear factor kappa-B (NF-κB) and type I interferon (IFN-I) signaling pathways, which are downstream of TLR4. Expectedly, TLR4 knockout completely eliminated the promotion effect of HIDfsin2 on NF-κB and type I interferon activation. Moreover, HIDfsin2 enhanced SFTSV replication in TLR4-knockout mouse macrophages, which is consistent with our recent report that HIDfsin2 hijacked p38 mitogen-activated protein kinase (MAPK) to promote the replication of tick-borne SFTSV in A549 and Huh7 cells (human cell lines) with low expression of TLR4. Together, these results provide new insights into the innate immune mechanism of host cells following tick bites. Our study also shows a rare molecular event relating to the mutual antagonism between tick-borne SFTSV and host cells mediated by the tick saliva peptide HIDfsin2 at the tick-host-virus interface.

Integrative Chinese-Western medicine strategy to overcome docetaxel resistance in prostate cancer.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese Medicines (TCMs) have emerged as a promising complementary therapy in the management of prostate cancer (PCa), particularly in addressing resistance to Docetaxel (DTX) chemotherapy. AIM OF THE REVIEW: This review aims to elucidate the mechanisms underlying the development of resistance to DTX in PCa and explore the innovative approach of integrating TCMs in PCa treatment to overcome this resistance. Key areas of investigation include alterations in microtubule proteins, androgen receptor and androgen receptor splice variant 7, ERG rearrangement, drug efflux mechanisms, cancer stem cells, centrosome clustering, upregulation of the PI3K/AKT signaling pathway, enhanced DNA damage repair capability, and the involvement of neurotrophin receptor 1/protein kinase C. MATERIALS AND METHODS: With "Prostate cancer", "Docetaxel", "Docetaxel resistance", "Natural compounds", "Traditional Chinese medicine", "Traditional Chinese medicine compound", "Medicinal plants" as the main keywords, PubMed, Web of Science and other online search engines were used for literature retrieval. RESULTS: Our findings underscore the intricate interplay of molecular alterations that collectively contribute to the resistance of PCa cells to DTX. Moreover, we highlight the potential of TCMs as a promising complementary therapy, showcasing their ability to counteract DTX resistance and enhance therapeutic efficacy. CONCLUSION: The integration of TCMs in PCa treatment emerges as an innovative approach with significant potential to overcome DTX resistance. This review not only provides insights into the mechanisms of resistance but also presents new prospects for improving the clinical outcomes of patients with PCa undergoing DTX therapy. The comprehensive understanding of these mechanisms lays the foundation for future research and the development of more effective therapeutic interventions.

Tm,Ho:YLF waveguide lasers at 2.05†µm.

In this work, we report on the first, to our knowledge, 2.05-µm laser based on femtosecond-laser direct written (FsLDW) Tm,Ho:YLF cladding waveguides. A channel waveguide with a 90-µm diameter "fiber-like" low-index cladding is fabricated in a 6 at. % Tm3+, 0.4 at. % Ho3+:LiYF4 crystal by FsLDW. Pumped by Ti:sapphire laser at 795.1 nm, the fabricated waveguide supports efficient lasing oscillation at 2050 nm with a maximum output power of 47.5 mW, a minimum lasing threshold of 181 mW, and a slope efficiency of 20.1%. The impacts of cavity conditions and polarizations of the pump light on the obtained lasing performance are well studied. The experimental results obtained in this study demonstrate the great potential of utilizing Tm,Ho:YLF and FsLDW for the development of durable mid-infrared lasers featuring compact designs.

CRKL but not CRKII contributes to hemin-induced erythroid differentiation of CML.

Destruction of erythropoiesis process leads to various diseases, including thrombocytopenia, anaemia, and leukaemia. miR-429-CT10 regulation of kinase-like (CRKL) axis involved in development, progression and metastasis of cancers. However, the exact role of miR-429-CRKL axis in leukaemic cell differentiation are still unknown. The current work aimed to uncover the effect of miR-429-CRKL axis on erythropoiesis. In the present study, CRKL upregulation was negatively correlated with miR-429 downregulation in both chronic myeloid leukaemia (CML) patient and CR patient samples. Moreover, CRKL expression level was significantly decreased while miR-429 expression level was increased during the erythroid differentiation of K562 cells following hemin treatment. Functional investigations revealed that overexpression and knockdown of CRKL was remarkably effective in suppressing and promoting hemin-induced erythroid differentiation of K562 cells, whereas, miR-429 exhibited opposite effects to CRKL. Mechanistically, miR-429 regulates erythroid differentiation of K562 cells by downregulating CRKL via selectively targeting CRKL-3'-untranslated region (UTR) through Raf/MEK/ERK pathway. Conversely, CRKII had no effect on erythroid differentiation of K562 cells. Taken together, our data demonstrated that CRKL (but not CRKII) and miR-429 contribute to development, progression and erythropoiesis of CML, miR-429-CRKL axis regulates erythropoiesis of K562 cells via Raf/MEK/ERK pathway, providing novel insights into effective diagnosis and therapy for CML patients.

FKF1b controls reproductive transition associated with adaptation to geographical distribution in maize.

Maize (Zea mays subspecies mays) is an important commercial crop across the world, and its flowering time is closely related to grain yield, plant cycle and latitude adaptation. FKF1 is an essential clock-regulated blue-light receptor with distinct functions on flowering time in plants, and its function in maize remains unclear. In this study, we identified two FKF1 homologs in the maize genome, named ZmFKF1a and ZmFKF1b, and indicated that ZmFKF1a and ZmFKF1b independently regulate reproductive transition through interacting with ZmCONZ1 and ZmGI1 to increase the transcription levels of ZmCONZ1 and ZCN8. We demonstrated that ZmFKF1b underwent artificial selection during modern breeding in China probably due to its role in geographical adaptation. Furthermore, our data suggested that ZmFKF1bHap_C7 may be an elite allele, which increases the abundance of ZmCONZ1 mRNA more efficiently and adapt to a wider range of temperature zone than that of ZmFKF1bHap_Z58 to promote maize floral transition. It extends our understanding of the genetic diversity of maize flowering. This allele is expected to be introduced into tropical maize germplasm to enrich breeding resources and may improve the adaptability of maize at different climate zones, especially at temperate region.

Construction of an Injectable Composite Double-Network Hydrogel as a Liquid Embolic Agent.

Conventional embolists disreputably tend to recanalization arising from the low filling ratio due to their rigidity or instability. As a result, intelligent hydrogels with a tunable modulus may meaningfully improve the therapeutic efficacy. Herein, an injectable composite double-network (CDN) hydrogel with high shear responsibility was prepared as a liquid embolic agent by cross-linking poly(vinyl alcohol) (PVA) and carboxymethyl chitosan (CMC) via dynamic covalent bonding of borate ester and benzoic-imine. A two-dimensional nanosheet, i.e., layered double hydroxide (LDH), was incorporated into the network through physical interactions which led to serious reduction of yield stress for the injection of the hydrogel and the capacity for loading therapeutic agents like indocyanine green (ICG) and doxorubicin (DOX) for the functions of photothermal therapy (PTT) and chemotherapy. The CDN hydrogel could thus be transported through a thin catheter and further in situ strengthened under physiological conditions, like in blood, by secondarily cross-linking with phosphate ions for longer degradation duration and better mechanical property. These characteristics met the requirements of arterial interventional embolization, which was demonstrated by renal embolism operation on rabbits, and meanwhile favored the inhibition of subcutaneous tumor growth on an animal model. Therefore, this work makes a breakthrough in the case of largely reducing the embolism risks, thus affording a novel generation for interventional embolization.

Polymer-Protein Assemblies with Tunable Vesicular and Hierarchical Nanostructures.

The construction of variable structured multi-protein nano-assemblies is of great interest for the development of protein-based therapeutic systems. This study showcases the synthesis of polymer-protein assemblies with tunable structure like single- and multi-layer polymer-crosslinked protein vesicles, Janus protein vesicles and other hierarchical-structured assemblies by utilizing a dynamic template-assistant intermittent-assembly approach. The generalization of the methodology helps the protein assemblies to gain notable functional complexity. And we demonstrate compelling evidence highlighting the substantial impact of the topological morphology of protein nanoaggregates on their cellular uptake capacity.

Theoretical and Experimental Investigation of Surface Textures in Vibration-Assisted Micro Milling.

Vibration-assisted micro milling is a promising technique for fabricating engineered mi-cro-scaled surface textures. This paper presents a novel approach for theoretical modeling of three-dimensional (3D) surface textures produced by vibration-assisted micro milling. The proposed model considers the effects of tool edge geometry, minimum uncut chip thickness (MUCT), and material elastic recovery. The surface texture formation under different machining parameters is simulated and analyzed through mathematical modeling. Two typical surface morphologies can be generated: wave-type and fish scale-type textures, depending on the phase difference between tool paths. A 2-degrees-of-freedom (2-DOF) vibration stage is also developed to provide vibration along the feed and cross-feed directions during micro-milling process. Micro-milling experiments on copper were carried out to verify the ability to fabricate controlled surface textures using the vibration stage. The simulated and experimentally generated surfaces show good agreement in geometry and dimensions. This work provides an accurate analytical model for vibration-assisted micro-milling surface generation and demonstrates its feasibility for efficient, flexible texturing.

Oxygen and pH responsive theragnostic liposomes for early-stage diagnosis and photothermal therapy of solid tumours.

The development of cancer treatment is of great importance, especially in the early stage. In this work, we synthesized a pH-sensitive amphiphilic ruthenium complex containing two alkyl chains and two PEG chains, which was utilized as an oxygen sensitive fluorescent probe for co-assembly with lipids to harvest a liposomal delivery system (RuPC) for the encapsulation of a photothermal agent indocyanine green (ICG). The resultant ICG encapsulated liposome (RuPC@ICG) enabled the delivery of ICG into cells via a membrane fusion pathway, by which the ruthenium complex was localized in the cell membrane for better detection of the extracellular oxygen concentration. Such characteristics allowed ratiometric imaging to distinguish the tumour location from normal tissues just 3 days after cancer cells were implanted, by monitoring the hypoxia condition and tracing the metabolism. Moreover, the pH sensitivity of the liposomes favoured cell uptake, and improved the anti-tumour efficiency of the formulation in vivo under NIR irradiation. Assuming liposomal systems have fewer safety issues, our work not only provides a facile method for the construction of a theragnostic system by combining phototherapy with photoluminescence imaging, but hopefully paves the way for clinical translation from bench to bedside.

Co-Expression of JcNAC1- and JcZFP8-Improved Agronomic Traits of Tobacco and Enhanced Drought Resistance through NbbHLH1 and NbbHLH2.

Previous studies have identified numerous transcription factors involved in drought response, each of which play different roles in plants. The objective of the present study was to evaluate the effectiveness of two transcription factors on drought response in Jatropha curcas L., JcNAC1 and JcZFP8. The overexpression of these transcription factors in tobacco (Nicotiana benthamiana L.) improved drought resistance, but JcZFP8 delayed germination and JcNAC1 reduced biomass and yield. By constitutively co-expressing these two genes in tobacco, drought resistance was improved, and the negative effects of each of them were overcome. The transgenic plants with double-gene co-expression showed stronger drought tolerance with 1.76-fold greater accumulation of proline and lower H2O2 and malondialdehyde (MDA) content to 43 and 65% of wildtype (WT) levels, respectively. The expression levels of NbbHLH1 and NbbHLH2 genes upregulated linearly with the increased drought tolerance of double genes co-expression plants. In drought conditions, the leaf water contents of bhlh1, bhlh2, and bhlh1bhlh2 deletion mutants obtained by CRISPR-CAS9 knockout technique were maintained at 99%, 97%, and 97% of WT. The bhlh1bhlh2 was found with lower germination rate but with higher reactive oxygen levels (1.64-fold H2O2 and 1.41-fold MDA levels). Thus, the co-expression of two transcription factors with different functions overcame the adverse traits brought by a single gene and enhanced the shared drought-tolerant traits, which can provide guidance on theory and selection of gene combinations for the application of multi-gene co-expression in agriculture in the future.

Nd:YSAG waveguide-grating vortex laser: design and implementation.

In this work, we fabricate a hybrid waveguide-grating vortex laser in Nd:YSAG by using femtosecond laser direct writing (FsLDW). The detailed parameters of the hybrid structure are fixed by optical simulation. In experiments, an efficient vortex beam is produced in the passive operation at 1064 nm. Under optical pumping at 808 nm, a dual-wavelength waveguide laser at 1060/1062 nm as well as a waveguide-grating vortex laser at 1060 nm are obtained. The laser performance and diffraction properties of the generated vortex laser are detailed, studied, and discussed, providing meaningful reference results toward the practical applications of FsLDW and waveguide-grating structures in integrated photonics.

Enantioselective Michael Addition of Malononitrile to Unsaturated Ketones Catalyzed by Rare-Earth Metal Amides RE[N(SiMe3)2]3 with Phenoxy-Functionalized TsDPEN Ligands.

The catalytic enantioselective Michael addition of α,ß-unsaturated ketones with malononitrile was well established using rare-earth metal amides RE[N(SiMe3)2]3 (RE = Y, Eu, Sm, Nd, La) with chiral phenoxy-functionalized TsDPEN ligands. The combination of lanthanum amide La[N(SiMe3)2]3 and chiral TsDPEN ligand H3L1 [H3L1 = N-((1R,2R)-2-((3,5-di-tert-butyl-2-hydroxybenzyl)amino)-1,2-diphenylethyl)-4-methylbenzenesulfonamide] in a 1:1.5 molar ratio was proved to be the optimal partner in THF, which provided the desired ß-carbonyl dinitriles in excellent yields and good to high enantioselectivities after 12 h at -15 °C.

Robust Interval Prediction of Intermittent Demand for Spare Parts Based on Tensor Optimization.

Demand for spare parts, which is triggered by element failure, project schedule and reliability demand, etc., is a kind of sensing data to the aftermarket service of large manufacturing enterprises. Prediction of the demand for spare parts plays a crucial role in inventory management and lifecycle quality management for the aftermarket service of large-scale manufacturing enterprises. In real-life applications, however, demand for spare parts occurs randomly and fluctuates greatly, and the demand sequence shows obvious intermittent distribution characteristics. Additionally, due to factors such as reporting mistakes made by personnel or environmental changes, the actual data of the demand for spare parts are prone to abnormal variations. It is thus hard to capture the evolutional pattern of the demand for spare parts by traditional time series forecasting methods. The reliability of prediction results is also reduced. To address these concerns, this paper proposes a tensor optimization-based robust interval prediction method of intermittent time series for the aftersales demand for spare parts. First, using the advantages of tensor decomposition to effectively mine intrinsic information from raw data, a sequence-smoothing network based on tensor decomposition and a stacked autoencoder is proposed. Tucker decomposition is applied to the hidden features of the encoder, and the obtained core tensor is reconstructed through the decoder, thus allowing us to smooth outliers in the original demand sequence. An alternating optimization algorithm is further designed to find the optimal sequence feature representation and tensor decomposition factors for the extraction of the evolutionary trend of the intermittent series. Second, an adaptive interval prediction algorithm with a dynamic update mechanism is designed to obtain point prediction values and prediction intervals for the demand sequence, thereby improving the reliability of the forecast. The proposed method is validated using the actual aftersales data from a large engineering manufacturing enterprise in China. The experimental results demonstrate that, compared with typical time series prediction methods, the proposed method can effectively grab the evolutionary trend of various intermittent series and improve the accuracy of predictions made with small-sample intermittent series. Moreover, the proposed method provides a reliable elastic prediction interval when distortion occurs in the prediction results, offering a new solution for intelligent planning decisions related to spare parts in practical maintenance.

Screening of anti-cancer compounds from Vaccariae Semen by lung cancer A549 cell fishing and UHPLC-LTQ Orbitrap MS.

Vaccariae Semen, derived from the dried ripe seed of Vaccaria segetalis (Neck.) Garcke, has various therapeutic characteristics in traditional Chinese medicine (TCM), containing promoting blood circulation and unblocking meridians. It exhibits significant anti-cancer activity and is therapeutically utilized to treat and reduce chemotherapy adverse effects in cancer patients, notably those with lung cancer. However, the active ingredients responsible for its anti-lung cancer efficacy remain unknown. In this study, we used A549 cell fishing in conjunction with UHPLC-LTQ Orbitrap MS to screen for anti-lung cancer active components in Vaccariae Semen. The cell counting Kit-8 (CCK-8) assay revealed that the n-butanol extract substantially reduced A549 cell growth. Through the cell fishing assay, we found 14 A549 cell-binding compounds in the n-butanol extract, all of which were identified as triterpenoid saponins. The total saponins of Vaccariae Semen were subsequently purified using macroporous adsorption resin (MAR), and they showed a significant inhibitory effect on the proliferation of A549 lung cancer cells, as well as alterations in cell morphology, apoptosis, and fragmentation. In conclusion, saponins were discovered as the key active components responsible for the anti-lung cancer activity of Vaccariae Semen.