In Situ Nucleosome Assembly for Single-Molecule Correlative Force and Fluorescence Microscopy.

Nucleosomes constitute the primary unit of eukaryotic chromatin and have been the focus of numerous informative single-molecule investigations regarding their biophysical properties and interactions with chromatin-binding proteins. Nucleosome reconstitution on DNA for these studies typically involves a salt dialysis procedure that provides precise control over the placement and number of nucleosomes formed along a DNA tether. However, this protocol is time-consuming and requires a substantial amount of DNA and histone octamers as inputs. To offer an alternative strategy, an in situ nucleosome reconstitution method for single-molecule force and fluorescence microscopy that utilizes the histone chaperone Nap1 is described. This method enables users to assemble nucleosomes on any DNA template without the need for strong nucleosome positioning sequences, adjust nucleosome density on demand, and use fewer reagents. In situ nucleosome formation occurs within seconds, offering a simpler experimental workflow and a convenient transition into single-molecule measurements. Examples of two downstream assays for probing nucleosome mechanics and visualizing the behavior of individual proteins on chromatin are further described.

In-Situ Synthesized Gel Polymer Electrolyte Enable High Capacity and Long-Cycle-Life Lithium Metal Batteries.

Solid-state lithium-metal batteries (SSLMBs) have attracted great attention due to their outstanding advantages in safety, electrochemical stability and interfacial compatibility. However, the low ionic conductivity and narrow electrochemical window restrict their practical application. Herein, in-situ polymerization electrolytes (IPEs) crosslinked by acrylonitrile (AN) and ethylene glycol dimethacrylate (EGDMA) exhibit the superior ionic conductivity of 1.77×10-3 S cm-1 at 25 °C, the ultrahigh lithium transference number (tLi+) of 0.784 and the wider electrochemical stable window (ESW) of 5.65 V. The IPEs make the symmetrical Li||Li cells achieve the highly stable lithium stripping/plating cycling for over 3000 h at 0.1 mA cm-2. Meanwhile, IPE endows the solid-state LiFePO4||Li batteries with an excellent long-cycle performance over 700 cycles at 2.5 C with a capacity retention ratio over 95 %, as well as 1000 cycles at 1 C and superior capacity retention of 85 %. More importantly, the in-situ polymerized electrolytes containing polyacrylonitrile (PAN) open up a new frontier to promote the practical application of solid-state batteries with high safety and high energy density via in-situ solidification technology.

Multidisciplinary team quality improves the survival outcomes of locally advanced rectal cancer patients: A post hoc analysis of the STELLAR trial.

PURPOSE: We sought to determine the association between multidisciplinary team (MDT) quality and survival of patients with locally advanced rectal cancer. METHODS: In a post hoc analysis of the randomized phase III STELLAR trial, 464 patients with distal or middle-third, clinical tumor category cT3-4 and/or regional lymph node-positive rectal cancer who completed surgery were evaluated. Disease-free survival (DFS) and Overall survival (OS) were stratified by Multidisciplinary team (MDT) quality, which was also included in the univariable and multivariable analyses of DFS and OS. RESULTS: According to the univariable analyses, a significantly worse DFS was associated with a fewer specialized medical disciplines participating in MDT (<5 vs ≥ 5; P=0.049),a lower frequency of MDT meetings ( 200; P=0.039). In addition, a lower number of specialized medical disciplines participating in MDT (<5 vs ≥ 5; P<0.001), a lower frequency of MDT meetings ( 200; P=0.001) were the variables associated with OS. These 3 factors were considered when assessing MDT quality, which was classified into 2 categories: high quality or general quality. Patients treated in hospitals with high MDT quality had longer 3-year OS (90.5 % vs 78.1 %; P=0.001) and similar 3-year DFS (70.3 % vs 61.3 %; P=0.109) compared to those treated in hospitals of the general MDT quality group. Furthermore, multivariable analyses revealed a significance for DFS (HR, 1.648; 95 % CI, 1.143-2.375; P=0.007) and OS (HR, 2.771; 95 % CI, 1.575-4.877; P<0.001) in MDT quality. CONCLUSIONS: The use of hospitals with optimized multidisciplinary infrastructure had a significant influence on survival of patients with locally advanced rectal cancer.

Post-hoc analysis of clinicopathological factors affecting lateral lymph node metastasis based on STELLAR study for rectal cancer.

PURPOSE: In post-hoc analyses of phaseIII randomized controlled study(STELLAR), to analyzethe prognostic impact oflateral pelvic lymph node (LPLN)metastasis in locally advanced rectal cancer (LARC). METHODS: LPLN metastasis was defined as a short diameter > 7 mm on magnetic resonance imaging (MRI).The studyincluded 591 patients with LARC.All patients received neoadjuvant (chemo)radiotherapy combined withradical resection. RESULTS: Among 591 patients, 99 (16.8 %) were diagnosed with LPLN metastasis, mostly with unilateral metastasis (79.8 %), with internal iliac lymph node metastasis being more common (81.8 %).Significant differences were found among with and without LPLN metastasis in rectal segmentation (P=0.001),N disease (P<0.001), mesenteric LN metastasis or not (P=0.030). The median follow-up timewas 34.0 months, three-year disease-free survival (DFS),overall survival (OS), andmetastasis-free survival (MFS)were significantly lower in LPLN metastaticgroup than those in LPLN non-metastaticgroup (51.4 % vs. 68.2 %, P<0.001; 71.8 % vs. 84.2 %, P=0.006; 60.8 % vs. 80.1 %,P<0.001), respectively; while there were no significant differences in locoregional recurrence(11.4 % vs. 8.5 %, P=0.564). Multivariate analysis found that LPLN metastasis was an independent prognostic factor affecting DFS (P=0.005), OS (P=0.036),MFS (P=0.001).No significantly survival benefit was observed for the short-term radiotherapy based total neoadjuvant therapy compared to long-term concurrent chemoradiotherapy. CONCLUSIONS: LPLN metastasis observed byMRI should be considered in LARC patients, especially in populations with lowrectal cancer, N2 disease, and mesenteric LN metastasis. LPLN metastasis diagnosed by MRI is a significant and independent risk factor and is associated with worse DFS, OS, MFS.

Isolation of an α-glucosidase Inhibitor from Houttuynia cordata Thunb. and Its In vitro and In vivo Hypoglycemic Bioactivity.

The Houttuynia cordata Thunb. belongs to the Saururaceae family and is a well-known medicine and food homologous plant. Herein, the isolation of an α-glucosidase inhibitor from Houttuynia cordata Thunb. and characterization of its in vitro and in vivo hypoglycemic bioactivities are reported. We optimized the extraction conditions and isolated neochlorogenic acid (nCGA), which has α-glucosidase inhibitory activity from Houttuynia cordata Thunb. for the first time. nCGA competed with glucose for the α-glucosidase binding site, with a 50% inhibitory concentration (IC50) of 0.711 mg/mL. In vivo experiments in zebrafish showed that effects of nCGA on blood glucose varied by its concentrations. In particular, 4 mg/L nCGA significantly decreased the blood glucose level and inhibited effects of α-glucosidase in zebrafish. This work provides a theoretical basis for the extraction of hypoglycemic active ingredients from Houttuynia cordata Thunb. and a foundation for the development of natural and effective α-glucosidase inhibitors.

Differential dynamics specify MeCP2 function at nucleosomes and methylated DNA.

Methyl-CpG-binding protein 2 (MeCP2) is an essential chromatin-binding protein whose mutations cause Rett syndrome (RTT), a severe neurological disorder that primarily affects young females. The canonical view of MeCP2 as a DNA methylation-dependent transcriptional repressor has proven insufficient to describe its dynamic interaction with chromatin and multifaceted roles in genome organization and gene expression. Here we used single-molecule correlative force and fluorescence microscopy to directly visualize the dynamics of wild-type and RTT-causing mutant MeCP2 on DNA. We discovered that MeCP2 exhibits distinct one-dimensional diffusion kinetics when bound to unmethylated versus CpG methylated DNA, enabling methylation-specific activities such as co-repressor recruitment. We further found that, on chromatinized DNA, MeCP2 preferentially localizes to nucleosomes and stabilizes them from mechanical perturbation. Our results reveal the multimodal behavior of MeCP2 on chromatin that underlies its DNA methylation- and nucleosome-dependent functions and provide a biophysical framework for dissecting the molecular pathology of RTT mutations.

Neuronal rhythmicity and cortical arousal in a mouse model of absence epilepsy.

OBJECTIVES: Absence seizures impair psychosocial function, yet their detailed neuronal basis remains unknown. Recent work in a rat model suggests that cortical arousal state changes prior to seizures and that single neurons show diverse firing patterns during seizures. Our aim was to extend these investigations to a mouse model with studies of neuronal activity and arousal state to facilitate future fundamental investigations of absence epilepsy. METHODS: We performed in vivo extracellular single unit recordings on awake head-fixed C3H/HeJ mice. Mice were implanted with tripolar electrodes for cortical electroencephalography (EEG). Extracellular single unit recordings were obtained with glass micropipettes in the somatosensory barrel cortex, while animals ambulated freely on a running wheel. Signals were digitized and analyzed during seizures and at baseline. RESULTS: Neuronal activity was recorded from 36 cortical neurons in 19 mice while EEG showed characteristic 7-8 Hz spike-wave discharges. Different single neurons showed distinct firing patterns during seizures, but the overall mean population neuronal firing rate during seizures was no different from pre-seizure baseline. However, the rhythmicity of neuronal firing during seizures was significantly increased (p < 0.001). In addition, beginning 10s prior to seizure initiation, we observed a progressive decrease in cortical high frequency (>40 Hz) EEG and an increase in lower frequency (1-39 Hz) activity suggesting decreased arousal state. SIGNIFICANCE: We found that the awake head-fixed C3H/HeJ mouse model demonstrated rhythmic neuronal firing during seizures, and a decreased cortical arousal state prior to seizure onset. Unlike the rat model we did not observe an overall decrease in neuronal firing during seizures. Similarities and differences across species strengthen the ability to investigate fundamental key mechanisms. Future work in the mouse model will identify the molecular basis of neurons with different firing patterns, their role in seizure initiation and behavioral deficits, with ultimate translation to human absence epilepsy.

Preoperative short-course radiotherapy followed by chemotherapy and PD-1 inhibitor administration for locally advanced rectal cancer: A study protocol of a randomized phase II/III trial (STELLAR II study).

AIM: For patients with locally advanced rectal cancer, previous STELLAR studies have shown that a new adjuvant treatment paradigm of short-course radiotherapy followed by neoadjuvant chemotherapy can achieve pathological complete response rates superior to those of standard care; however, the 3-year DFS is inferior to neoadjuvant concurrent radiotherapy. Recent studies have shown that immune checkpoint inhibitors may improve the prognosis of rectal cancer and have good synergy with radiotherapy. Therefore, neoadjuvant chemotherapy combined with immune checkpoint inhibitors after a short course of radiotherapy has the potential to further improve complete response rates and prognosis. METHOD: The STELLAR II study is a multicentre, open label, two-arm randomized, phase II/III trial of short-course radiotherapy followed by neoadjuvant chemotherapy concurrent with immunotherapy for locally advanced rectal cancer. A total of 588 patients with locally advanced rectal cancer (LARC) will be randomly assigned to the experimental and control groups. The experimental group will receive short-course radiotherapy and neoadjuvant chemotherapy in combination with sindilizumab, while the control group will receive short-course radiotherapy and neoadjuvant chemotherapy. Both groups will subsequently receive either total rectal mesenteric resection or a watch & wait (W&W) strategy. The phase II primary endpoint is the complete remission rate, and the secondary endpoints include grade 3-4 adverse events, perioperative complications, R0 resection rate, overall survival, local recurrence rate, distant metastasis rate and quality of life score. A seamless phase II/III randomized controlled design will be used to investigate the effectiveness and safety of the TNT strategy with the addition of immunotherapy. The trial opened, and the first patient was recruited on 31 August 2022. Trial registration number and date of registration: ClinicalTrials.gov NCT05484024, 29 July 2022. DISCUSSION: The STELLAR II trial will prospectively evaluate the efficacy of TNT treatment strategies that incorporate immune checkpoint inhibitors. The trial will yield important information to guide routine management of patients with local advanced rectal cancer.

Piezoelectric Enhancement in P(VDF-TrFE) Copolymer Films via Controlled and Template-Induced Epitaxy.

The surge in wearable electronics and Internet of Things technologies necessitates the development of both flexible sensors and a sustainable, efficient, and compact power source. The latter further challenges conventional batteries due to environmental pollution and compatibility issues. Addressing this gap, piezoelectric energy harvesters emerge as one kind of promising alternative to convert mechanical energy from ambient sources to electrical energy to charge those low-energy-consumption electronic devices. Despite slightly lower piezoelectric performance compared with those inorganic materials, piezoelectric polymers, notably poly(vinylidene fluoride-co-trifluoroethylene) P(VDF-TrFE), offer compelling properties for both flexible mechanical energy harvesting and self-powered strain/stress sensing, though their piezoelectric performance is expected to be further enhanced via varieties of modulation strategies of microstructures. Herein, we reported the controlled epitaxy process of micrometer-thick copolymer films with the cooperation of friction-transferred poly(tetrafluoroethylene) templates and precise modulation of the annealing conditions. Epitaxial P(VDF-TrFE) films present averaged d33 piezoelectric coefficient of -58.2 pC/N between 50 Hz and 1 kHz with good electromechanical and thermal stability. Owing to the nature of anisotropic crystallization, the epitaxial films exhibit an anisotropic transverse piezoelectric property. Epitaxial films were further utilized for mechanical energy harvesting and monitoring of human pulsation and respiration. This study provided a feasible route for the development of high-performance flexible piezoelectric devices to meet the requirement of flexible electronics.

Evaluating and diagnosing ecosystem health of the "three-lake" watershed in Yuxi, Yunnan, China from 2010 to 2020 by PSR-KDE.

To carry out the diagnosis and evaluation of the ecosystem health in Yuxi three-lake watershed, this paper presents the changing trend of its health state, and predicts the future development. This also provides ideas for maintaining the regional ecosystem health, and then gradually improves the ecological environment quality. Taking Fuxian Lake, Qilu Lake and Xingyun Lake (the three-lake watershed) in Yuxi City, Yunnan Province, Southwest China as the research object, a model combining pressure-state-response and kernel density estimation (PSR-KDE) adopts to diagnose and evaluate the ecosystem health of the "three lake" watershed from 2010 to 2020, and the distribution map of ecosystem health index has obtained by the evaluation indexes integration based on GIS spatial analysis. Hence, the evaluation results have visualized on the map. The results show that: The distribution of ecosystem health index in the study area was 0.1530-0.7045 in 2010, 0.2056-0.7512 in 2015, and 0.2248-0.7662 in 2020. 0.12% was in the pathological area in 2010. After 2015, the pathological condition of ecosystem health has completely solved, and the proportion of unhealthy ecosystems was 11.95% in 2010, 7.38% in 2015, and 5.97% in 2020. The ecosystem health index of the study region was 0.5523 in 2010, 0.5807 in 2015, and 0.5815 in 2020, it indicates that the ecosystem was in a sub-health state. From 2010 to 2020, the ecosystem health around Qilu Lake was the most worrying, followed by the northwest of Fuxian Lake and the northern and southern regions of Xingyun Lake. The ecosystem health of the three-lake watershed showed significant improvement from 2010 to 2020. The study ecosystem health assessment and early warning in the three-lake watershed is significant to the ecological environment protection and management of the plateau lake basin, the restoration of the territorial space ecology and the economic development of the surrounding area.

The impact of land use on eco-environment in the Dianchi Basin.

(1) Studying the dynamic correlation between land use and the eco-environment in the Dianchi Basin is important for improving the basin's spatial layout and enhancing ecological development and conservation; (2) Through dynamic analysis and comprehensive evaluation of land use, the introduction of ecological and environmental quality index, and the use of FLUS models, the impacts on eco-environments in the Dianchi Basin for the recent 20 years were analyzed; (3) The past two decades witnessed a constant increase in the construction land in the Dianchi Basin and a decline in the farmland at an average annual rate of 0.93 %; The utilization level of land in the Dianchi Basin presented a negative correlation with the quality of the area's eco-environment, which reduces first and then increases; When natural production becomes a priority, both the construction land and farmland have witnessed growth. However, when ecological protection becomes a priority, it is projected that by 2035, the Dianchi Basin will achieve its highest eco-environmental quality index; (4) Studying how the change of land use types affects eco-environment is crucial for optimizing the current allocation of land resources and promoting sustainable development in the basin.

Understanding how junction resistances impact the conduction mechanism in nano-networks.

Networks of nanowires, nanotubes, and nanosheets are important for many applications in printed electronics. However, the network conductivity and mobility are usually limited by the resistance between the particles, often referred to as the junction resistance. Minimising the junction resistance has proven to be challenging, partly because it is difficult to measure. Here, we develop a simple model for electrical conduction in networks of 1D or 2D nanomaterials that allows us to extract junction and nanoparticle resistances from particle-size-dependent DC network resistivity data. We find junction resistances in porous networks to scale with nanoparticle resistivity and vary from 5 Ω for silver nanosheets to 24 GΩ for WS2 nanosheets. Moreover, our model allows junction and nanoparticle resistances to be obtained simultaneously from AC impedance spectra of semiconducting nanosheet networks. Through our model, we use the impedance data to directly link the high mobility of aligned networks of electrochemically exfoliated MoS2 nanosheets (≈ 7 cm2 V-1 s-1) to low junction resistances of ∼2.3 MΩ. Temperature-dependent impedance measurements also allow us to comprehensively investigate transport mechanisms within the network and quantitatively differentiate intra-nanosheet phonon-limited bandlike transport from inter-nanosheet hopping.

Transformer with difference convolutional network for lightweight universal boundary detection.

Although deep-learning methods can achieve human-level performance in boundary detection, their improvements mostly rely on larger models and specific datasets, leading to significant computational power consumption. As a fundamental low-level vision task, a single model with fewer parameters to achieve cross-dataset boundary detection merits further investigation. In this study, a lightweight universal boundary detection method was developed based on convolution and a transformer. The network is called a "transformer with difference convolutional network" (TDCN), which implies the introduction of a difference convolutional network rather than a pure transformer. The TDCN structure consists of three parts: convolution, transformer, and head function. First, a convolution network fused with edge operators is used to extract multiscale difference features. These pixel difference features are then fed to the hierarchical transformer as tokens. Considering the intrinsic characteristics of the boundary detection task, a new boundary-aware self-attention structure was designed in the transformer to provide inductive bias. By incorporating the proposed attention loss function, it introduces the direction of the boundary as strongly supervised information to improve the detection ability of the model. Finally, several head functions with multiscale feature inputs were trained using a bidirectional additive strategy. In the experiments, the proposed method achieved competitive performance on multiple public datasets with fewer model parameters. A single model was obtained to realize universal prediction even for different datasets without retraining, demonstrating the effectiveness of the method. The code is available at https://github.com/neulmc/TDCN.

Knot Architecture for Biocompatible and Semiconducting 2D Electronic Fiber Transistors.

Wearable devices have generally been rigid due to their reliance on silicon-based technologies, while future wearables will utilize flexible components for example transistors within microprocessors to manage data. Two-dimensional (2D) semiconducting flakes have yet to be investigated in fiber transistors but can offer a route toward high-mobility, biocompatible, and flexible fiber-based devices. Here, the electrochemical exfoliation of semiconducting 2D flakes of tungsten diselenide (WSe2) and molybdenum disulfide (MoS2) is shown to achieve homogeneous coatings onto the surface of polyester fibers. The high aspect ratio (>100) of the flake yields aligned and conformal flake-to-flake junctions on polyester fibers enabling transistors with mobilities µ ≈1 cm2 V-1 s-1 and a current on/off ratio, Ion/Ioff ≈102-104. Furthermore, the cytotoxic effects of the MoS2 and WSe2 flakes with human keratinocyte cells are investigated and found to be biocompatible. As an additional step, a unique transistor 'knot' architecture is created by leveraging the fiber diameter to establish the length of the transistor channel, facilitating a route to scale down transistor channel dimensions (≈100 µm) and utilize it to make a MoS2 fiber transistor with a human hair that achieves mobilities as high as µ ≈15 cm2 V-1 s-1.

Incomplete transcripts dominate the Mycobacterium tuberculosis transcriptome.

Mycobacterium tuberculosis (Mtb) is a bacterial pathogen that causes tuberculosis (TB), an infectious disease that is responsible for major health and economic costs worldwide1. Mtb encounters diverse environments during its life cycle and responds to these changes largely by reprogramming its transcriptional output2. However, the mechanisms of Mtb transcription and how they are regulated remain poorly understood. Here we use a sequencing method that simultaneously determines both termini of individual RNA molecules in bacterial cells3 to profile the Mtb transcriptome at high resolution. Unexpectedly, we find that most Mtb transcripts are incomplete, with their 5' ends aligned at transcription start sites and 3' ends located 200-500 nucleotides downstream. We show that these short RNAs are mainly associated with paused RNA polymerases (RNAPs) rather than being products of premature termination. We further show that the high propensity of Mtb RNAP to pause early in transcription relies on the binding of the σ-factor. Finally, we show that a translating ribosome promotes transcription elongation, revealing a potential role for transcription-translation coupling in controlling Mtb gene expression. In sum, our findings depict a mycobacterial transcriptome that prominently features incomplete transcripts resulting from RNAP pausing. We propose that the pausing phase constitutes an important transcriptional checkpoint in Mtb that allows the bacterium to adapt to environmental changes and could be exploited for TB therapeutics.

All-fiber hectowatt radially polarized laser system.

A high-power all-fiber radially polarized laser system is demonstrated, in which an integrated nanograting mode convertor (S-wave plate) is used for the generation of radially polarized beam. Experimentally, a 1-W radially polarized beam was used as the seed laser, whose mode purity and mode extinction ratio (MER) were 96.5% and 98.3%, respectively. A single-stage few-mode fiber amplifier was employed to boost the 1-W seed laser to an average power of 113.2 W, when the pump power was 160 W. The corresponding slope efficiency and beam quality factor (M2) were approximately 72% and 2.3%, respectively. Moreover, the mode purity and MER of the amplified radially polarized laser were measured to be 95.7% and 97%, respectively. To the best of our knowledge, this is the highest output power from an all-fiber radially polarized laser system without obvious degradations of the mode purity and MER.

Quantitative analysis of printed nanostructured networks using high-resolution 3D FIB-SEM nanotomography.

Networks of solution-processed nanomaterials are becoming increasingly important across applications in electronics, sensing and energy storage/generation. Although the physical properties of these devices are often completely dominated by network morphology, the network structure itself remains difficult to interrogate. Here, we utilise focused ion beam - scanning electron microscopy nanotomography (FIB-SEM-NT) to quantitatively characterise the morphology of printed nanostructured networks and their devices using nanometre-resolution 3D images. The influence of nanosheet/nanowire size on network structure in printed films of graphene, WS2 and silver nanosheets (AgNSs), as well as networks of silver nanowires (AgNWs), is investigated. We present a comprehensive toolkit to extract morphological characteristics including network porosity, tortuosity, specific surface area, pore dimensions and nanosheet orientation, which we link to network resistivity. By extending this technique to interrogate the structure and interfaces within printed vertical heterostacks, we demonstrate the potential of this technique for device characterisation and optimisation.

When Force Met Fluorescence: Single-Molecule Manipulation and Visualization of Protein-DNA Interactions.

Myriad DNA-binding proteins undergo dynamic assembly, translocation, and conformational changes while on DNA or alter the physical configuration of the DNA substrate to control its metabolism. It is now possible to directly observe these activities-often central to the protein function-thanks to the advent of single-molecule fluorescence- and force-based techniques. In particular, the integration of fluorescence detection and force manipulation has unlocked multidimensional measurements of protein-DNA interactions and yielded unprecedented mechanistic insights into the biomolecular processes that orchestrate cellular life. In this review, we first introduce the different experimental geometries developed for single-molecule correlative force and fluorescence microscopy, with a focus on optical tweezers as the manipulation technique. We then describe the utility of these integrative platforms for imaging protein dynamics on DNA and chromatin, as well as their unique capabilities in generating complex DNA configurations and uncovering force-dependent protein behaviors. Finally, we give a perspective on the future directions of this emerging research field.

Targeting PAK4 reverses cisplatin resistance in NSCLC by modulating ER stress.

Chemoresistance poses a significant impediment to effective treatments for non-small-cell lung cancer (NSCLC). P21-activated kinase 4 (PAK4) has been implicated in NSCLC progression by invasion and migration. However, the involvement of PAK4 in cisplatin resistance is not clear. Here, we presented a comprehensive investigation into the involvement of PAK4 in cisplatin resistance within NSCLC. Our study revealed enhanced PAK4 expression in both cisplatin-resistant NSCLC tumors and cell lines. Notably, PAK4 silencing led to a remarkable enhancement in the chemosensitivity of cisplatin-resistant NSCLC cells. Cisplatin evoked endoplasmic reticulum stress in NSCLC. Furthermore, inhibition of PAK4 demonstrated the potential to sensitize resistant tumor cells through modulating endoplasmic reticulum stress. Mechanistically, we unveiled that the suppression of the MEK1-GRP78 signaling pathway results in the sensitization of NSCLC cells to cisplatin after PAK4 knockdown. Our findings establish PAK4 as a promising therapeutic target for addressing chemoresistance in NSCLC, potentially opening new avenues for enhancing treatment efficacy and patient outcomes.

Establishment of Coloproctitis Cancer Model in Mice and Evaluation of Therapeutic Effect of Chinese Medicine.

Colorectal cancer (CRC) is a common malignancy of the digestive system and has become the third most common malignancy worldwide and the second leading cause of malignancy-related death. Ulcerative coloproctitis (UC) is a precancerous lesion, and UC-associated CRC (UC-CRC) is the most common subtype of CRC. Therefore, a reasonable UC-CRC model is the cornerstone and guarantee of new drug development. Traditional Chinese medicine (TCM) has been widely used in the treatment of UC-CRC due to its good efficacy. As a classic tonic prescription of TCM, Liujunzi decoction (LJZD) has been widely used in the treatment of UC-CRC. In this study, a UC-CRC model was established by combining azomethane and dextran sulfate sodium, and the LJZD was administered. The data confirmed that LJZD can effectively inhibit cancer transition in UC-CRC by using mouse body weight, colorectal length, pathological and inflammatory factors, colorectal barrier function, and cancer markers. This protocol provides a system for evaluating the efficacy of TCM in the prevention and treatment of UC-CRC.