Cinobufotalin Capsule Combined with Zoledronic Acid in the Treatment of Pain Symptoms and Clinical Efficacy in Prostate Cancer Patients with Bone Metastases: A Retrospective Study.

OBJECTIVE: To retrospectively analyse the effects of cinobufotalin capsule combined with zoledronic acid on pain symptoms and clinical efficacy of prostate cancer patients with bone metastases. METHODS: Patients with prostate cancer with bone metastasis admitted to our hospital from January 2021 to December 2022 were selected as study subjects. They were divided into the control group (treated with zoledronic acid) and the combined group (cinobufotalin capsules were added on the control group basis) according to different recorded treatment methods. The efficacies of the two groups after matching, lumbar L1-4 bone mineral density (BMD), serum calcium, serum phosphorus, visual analogue scale (VAS) score and Karnofsky performance status (KPS) score before and after treatment were compared, and adverse reactions were statistically analysed. RESULTS: A total of 102 patients were included in the study, encompassing 52 patients in the combined group and 50 patients in the control group. After 1:1 preference score matching, 64 patients were included in the two groups. No significant difference in baseline data was found between the two groups (p > 0.05). The total effective rate of the combination group was higher than that of the control group (p < 0.05). No significant differences in L1-4 bone mineral density, serum calcium and phosphorus, VAS score and KPS score were observed between the two groups prior to treatment (p > 0.05). After treatment, the L1-4 bone mineral density (BMD) and KPS score of the combined group decreased to less than those of the control group, the VAS score was lower than that of the control group, and the serum calcium and phosphorus level increased but less than that of the control group (p < 0.05). No significant difference in adverse reactions was found between the two groups (p > 0.05). CONCLUSIONS: Cinobufotalin capsule combined with zoledronic acid had ideal efficacy in the treatment of prostate cancer in patients with bone metastasis. This approach could improve their bone density and quality of life, improve their calcium and phosphorus metabolism, reduce their pain symptoms and provide increased safety. It may have an important guiding role in formulating future clinical treatment plans for patients with prostate cancer and bone metastasis.

Effects of plant taxonomic position on soil nematode communities in Antarctica.

Antarctica terrestrial ecosystems are facing the most threats from global climate change, which is altering plant composition greatly. These transformations may cause major reshuffling of soil community composition, including functional traits and diversity, and therefore affect ecosystem processes in Antarctica. We used high-throughput sequencing analysis to investigate soil nematodes under 3 dominant plant functional groups (lichens, mosses, and vascular plants) and bare ground in the Antarctic region. We calculated functional diversity of nematodes based on their diet, life histories, and body mass with kernel density n-dimensional hypervolumes. We also calculated taxonomic and functional beta diversity of the nematode communities based on Jaccard dissimilarity. The presence of plants had no significant effect on the taxonomic richness of nematodes but significantly increased nematode functional richness. The presence of plants also significantly decreased taxonomic beta diversity (homogenization). Only mosses and vascular plants decreased nematode functional beta diversity, which was mostly due to a decreased effect of the richness difference component. The presence of plants also increased the effect of deterministic processes potentially because environmental filtering created conditions favorable to nematodes at low trophic levels with short life histories and small body size. Increasing plant cover in the Antarctic due to climate change may lead to increased diversity of nematode species that can use the scarce resources and nematode taxonomic and functional homogenization. In a future under climate change, community restructuring in the region is possible.

Efectos de la posición taxonómica de las plantas sobre las comunidades de nemátodos del suelo en la Antártida Resumen Los ecosistemas terrestres de la Antártida enfrentan las mayores amenazas del cambio climático global, que está alterando gravemente la composición de plantas. Estas transformaciones pueden provocar una reorganización importante de la composición de la comunidad del suelo, incluyendo atributos y diversidad funcionales, y por lo tanto afectar los procesos ecosistémicos en la Antártida. Utilizamos análisis de secuenciación de alto rendimiento para investigar nemátodos del suelo debajo de tres grupos funcionales de plantas dominantes (líquenes, musgos y plantas vasculares) y de suelo desnudo en la región de la Antártida. Calculamos la diversidad funcional de nemátodos con base en su dieta, historia de vida y masa corporal mediante hipervolúmenes n­dimensionales de densidad del núcleo. También calculamos la diversidad beta taxonómica y funcional de las comunidades de nemátodos con base en la disimilitud de Jacard. La presencia de plantas no tuvo efecto significativo sobre la riqueza taxonómica de nemátodos, pero incrementó su riqueza funcional significativamente. La presencia de plantas también disminuyó la diversidad beta taxonómica (homogenización) significativamente. Solo musgos y plantas vasculares disminuyeron la diversidad beta funcional de nemátodos, lo cual se debió principalmente a un menor efecto del componente de diferencia de riqueza. La presencia de plantas también incrementó el efecto de los procesos determinísticos posiblemente porque el filtrado ambiental creó condiciones favorables para los nemátodos de niveles tróficos inferiores con historias de vida corta y tamaño corporal pequeño. El incremento de la cobertura de plantas en la Antártida debido al cambio climático puede conducir a una mayor diversidad de especies de nemátodos que pueden utilizar los escasos recursos y a la homogenización taxonómica y funcional de los nemátodos. En un futuro bajo el cambio climático, es posible la reestructuración comunitaria en la región.

Interactive effects of exercise intensity and recovery posture on post-exercise hypotension.

Post-exercise reduction in blood pressure, termed post-exercise hypotension (PEH), is relevant for both acute and chronic health reasons and potentially for peripheral cardiovascular adaptations. We investigated the interactive effects of exercise intensity and recovery postures (seated, supine, and standing) on PEH. Thirteen normotensive men underwent a VO2max test on a cycle ergometer and 5 exhaustive constant load trials to determine critical power (CP) and the gas exchange threshold (GET). Subsequently, work-matched exercise trials were performed at two discrete exercise intensities (10% > CP and 10% < GET), with one hour of recovery in each of three postures. For both exercise intensities, standing posture resulted in a more substantial PEH (all P < 0.01). For both standing and seated recovery postures, the higher exercise intensity led to larger reductions in systolic, diastolic and mean arterial pressures (all P < 0.01), whereas in the supine recovery posture, the reduction in diastolic and mean arterial pressures was unaffected by prior exercise intensity (both P > 0.05). PEH is more pronounced during recovery from exercise performed above critical power versus below GET. However, the effect of exercise intensity on PEH is largely abolished when recovery is performed in the supine posture.

Comparative Genomics of Lotus japonicus Reveals Insights into Proanthocyanidin Accumulation and Abiotic Stress Response.

Lotus japonicus, is an important perennial model legume, has been widely used for studying biological processes such as symbiotic nitrogen fixation, proanthocyanidin (PA) biosynthesis, and abiotic stress response. High-quality L. japonicus genomes have been reported recently; however, the genetic basis of genes associated with specific characters including proanthocyanidin distribution in most tissues and tolerance to stress has not been systematically explored yet. Here, based on our previous high-quality L. japonicus genome assembly and annotation, we compared the L. japonicus MG-20 genome with those of other legume species. We revealed the expansive and specific gene families enriched in secondary metabolite biosynthesis and the detection of external stimuli. We suggested that increased copy numbers and transcription of PA-related genes contribute to PA accumulation in the stem, petiole, flower, pod, and seed coat of L. japonicus. Meanwhile, According to shared and unique transcription factors responding to five abiotic stresses, we revealed that MYB and AP2/ERF play more crucial roles in abiotic stresses. Our study provides new insights into the key agricultural traits of L. japonicus including PA biosynthesis and response to abiotic stress. This may provide valuable gene resources for legume forage abiotic stress resistance and nutrient improvement.

Using an In Vivo Mouse Model to Determine the Exclusion Criteria of Preexisting Anti-AAV9 Neutralizing Antibody Titer of Pompe Disease Patients in Clinical Trials.

The efficacy of adeno-associated virus (AAV)-based gene therapy is dependent on effective viral transduction, which might be inhibited by preexisting immunity to AAV acquired from infection or maternal delivery. Anti-AAV neutralizing Abs (NAbs) titer is usually measured by in vitro assay and used for patient enroll; however, this assay could not evaluate NAbs' impacts on AAV pharmacology and potential harm in vivo. Here, we infused a mouse anti-AAV9 monoclonal antibody into Balb/C mice 2 h before receiving 1.2 × 1014 or 3 × 1013 vg/kg of rAAV9-coGAA by tail vein, a drug for our ongoing clinical trials for Pompe disease. The pharmacokinetics, pharmacodynamics, and cellular responses combined with in vitro NAb assay validated the different impacts of preexisting NAbs at different levels in vivo. Sustained GAA expression in the heart, liver, diaphragm, and quadriceps were observed. The presence of high-level NAb, a titer about 1:1000, accelerated vector clearance in blood and completely blocked transduction. The AAV-specific T cell responses tended to increase when the titer of NAb exceeded 1:200. A low-level NAbs, near 1:100, had no effect on transduction in the heart and liver as well as cellular responses, but decreased transduction in muscles slightly. Therefore, we propose to preclude patients with NAb titers > 1:100 from rAAV9-coGAA clinical trials.

Warming enhances the negative effects of shrub removal on phosphorus mineralization potential.

Shrubs have developed various mechanisms for soil phosphorus utilization. Shrub encroachment caused by climate warming alters organic phosphorus mineralization capability by promoting available phosphorus absorption and mediating root exudates. However, few studies have explored how warming regulates the effects of dominant shrubs on soil organic phosphorus mineralization capability. We provide insights into warming, dominant shrub removal, and their interactive effects on the soil organic phosphorus mineralization potential in the Qinghai-Tibetan Plateau. Real-time polymerase chain reaction was used to quantify the soil microbial phosphatase genes (phoC and phoD), which can characterize the soil organic phosphate mineralization potential. We found that warming had no significant effect on the soil organic phosphate-mineralized components (total phosphate, organic phosphate, and available phosphate), genes (phoC and phoD), or enzymes (acid and alkaline phosphatases). Shrub removal negatively influenced the organic phosphate-mineralized components and genes. It significantly decreased soil organic phosphate mineralization gene copy numbers only under warming conditions. Warming increased fungal richness and buffered the effects of shrub removal on bacterial richness and gene copy numbers. However, the change in the microbial community was not the main factor affecting organic phosphate mineralization. We found only phoC copy number had significant correlation to AP. Structural equation modelling revealed that shrub removal and the interaction between warming and shrub removal had a negative direct effect on phoC copy numbers. We concluded that warming increases the negative effect of shrub removal on phosphorus mineralization potential, providing a theoretical basis for shrub encroachment on soil phosphate mineralization under warming conditions.

Stretch-Induced Conductivity Enhancement in Highly Conductive and Tough Hydrogels.

The resistance of gels and elastomers increases significantly with tensile strain, which reduces conductive stability and restricts their use in stable and reliable electronics. Here, highly conductive tough hydrogels composed of silver nanowires (AgNWs), liquid metal (LM), and poly(vinyl alcohol) (PVA) are fabricated. The stretch-induced orientations of AgNWs, deformable LM, and PVA nanocrystalline create conductive pathways, enhancing the mechanical properties of the hydrogels, including increased ultimate fracture stress (13-33 MPa), strain (3000-5300%), and toughness (390.9-765.1 MJ m-3 ). Notably, the electrical conductivity of the hydrogels is significantly improved from 4.05 × 10-3 to 24 S m-1 when stretched to 4200% strain, representing a 6000-fold enhancement. The incorporation of PVA nanocrystalline, deformable LM, and AgNWs effectively mitigates stress concentration at the crack tip, thereby conferring crack propagation insensitivity and fatigue resistance to the hydrogels. Moreover, the hydrogels are designed with a reversible crosslinking network, allowing for water-induced recycling.

Study of the Dielectric and Corona Resistance Properties of PI Films Modified with Fluorene Moiety/Aluminum Sec-Butoxide.

With the policy tilt and increased investment in research and development in the world, new energy vehicle technology continues to progress and the drive motor power density continues to improve, which puts forward higher requirements for the comprehensive performance of the core insulating material enameled wire enamel for drive motors. Polyimide (PI) has excellent electrical insulation properties, and heat resistance is often used to drive the motor winding insulation. To further improve the corona resistance and insulating properties of PI wire enamel varnish, in this paper, firstly, fluorene groups with a rigid conjugated structure were introduced into the molecular chain of the PI film by molecular structure modulation, and then uniformly dispersed alumina nanoclusters (AOCs) were introduced into the PI matrix by using an in situ growth process to inhibit the migration of high-energy electrons. The quantum size effect of the alumina nanoclusters was exploited to synergistically enhance the suppression and scattering of energetic moving electrons by PI-based composite films. The results show that the breakdown field strength of the PI-based composite film (MPI/1.0 vol% AOC) reaches 672.2 kV/mm, and the corona resistance life reaches 7.9 min, which are, respectively, 1.55 and 2.19 times higher than those of the initial PI film. A PI-based composite film with excellent insulating and corona resistance properties was obtained.

Intranasal Epitope-Polymer Vaccine Lodges Resident Memory T Cells Protecting Against Influenza Virus.

Intranasal vaccines, unlike injectable vaccines, boost immunity along the respiratory tract; this can significantly limit respiratory virus replication and shedding. There remains a need to develop mucosal adjuvants and vaccine delivery systems that are both safe and effective following intranasal administration. Here, biopolymer particles (BP) densely coated with repeats of MHC class I restricted immunodominant epitopes derived from influenza A virus namely NP366 , a nucleoprotein-derived epitope and PA224 , a polymerase acidic subunit derived epitope, are bioengineered. These BP-NP366 /PA224 can be manufactured at a high yield and are obtained at ≈93% purity, exhibiting ambient-temperature stability. Immunological characterization includes comparing systemic and mucosal immune responses mounted following intramuscular or intranasal immunization. Immunization with BP-NP366 /PA224 without adjuvant triggers influenza-specific CD8+ T cell priming and memory CD8+ T cell development. Co-delivery with the adjuvant poly(I:C) significantly boosts the size and functionality of the influenza-specific pulmonary resident memory CD8+ T cell pool. Intranasal, but not intramuscular delivery of BP-NP366 /PA224 with poly(I:C), provides protection against influenza virus challenge. Overall, the BP approach demonstrates as a suitable antigen formulation for intranasal delivery toward induction of systemic protective T cell responses against influenza virus.

Contrasting responses of α- and ß-multifunctionality to aboveground plant community in the Qinghai-Tibet Plateau.

The aboveground plant communities are crucial in driving ecosystem functioning, particularly being the primary producers in terrestrial ecosystems. Numerous studies have investigated the impacts of aboveground plant communities on multiple ecosystem functions at α-scale. However, such critical effects have been unexplored at ß-scale and the comparative assessment of the effects and underlying mechanisms of aboveground plant communities on α- and ß-multifunctionality has been lacking. In this study, we examined the effects of aboveground plant communities on soil multifunctionality both at α- and ß-scale in the alpine meadow of the Tibetan Plateau. Additionally, we quantified the direct effects of aboveground plant communities, as well as the indirect effects mediated by changes in biotic and abiotic factors, on soil multifunctionality at both scales. Our findings revealed that: 1) Aboveground plant communities had significantly positive effects on α-multifunctionality whereas, ß-multifunctionality was not affected significantly. 2) Aboveground plant communities directly influence α- and ß-multifunctionality in contrasting ways, with positive and negative effects, respectively. Apart from the direct effects of plant community, we found that soil water content and bacterial ß-diversity serving as the primary predictors for the responses of α- and ß-multifunctionality to the presence of aboveground plant communities, respectively. And ß-soil biodiversity appeared to be a stronger predictor of multifunctionality relative to α-soil biodiversity. Our findings provide novel insights into the drivers of ecosystem multifunctionality at different scales, highlight the importance of maintaining biodiversity at multiple scales and offer valuable knowledge for the maintenance of ecosystem functioning and the restoration of alpine meadow ecosystems.

Electrically enhanced adsorption efficiency of aluminum nitride nanotube for sulfate ion removal from water.

Herein, the adsorption performance of sulfate ion in water on aluminum nitride nanotube(AlNNT) under the influence of an electric field was investigated using the density functional theory (DFT) calculation method. The model structure stability, adsorption energy, electronic and thermodynamic properties of sulfate ion adsorbed on the surface of AlNNT were studied. The calculation results indicate that sulfate ion reacts with multi-atoms on the surface of AlNNT, forming ionic bonds and undergoing chemical adsorption. As the electric field intensity increases, the adsorption energy and the transfer of electrons from sulfate ion to AlNNT increase, leading to a higher degree of hybridization of atomic orbitals and enhanced multi-atom interactions. Additionally, the thermodynamic data suggests that the adsorption between sulfate ion and AlNNT under electric field can occur spontaneously, the process of which is exothermic. The results of present study are expected to propose a novel method for separation and removal of sulfate pollutants from water.

Perineuronal Nets Alterations Contribute to Stress-Induced Anxiety-Like Behavior.

Anxiety disorder is one of the most common mental disorders worldwide, affecting nearly 30% of adults. However, its underlying molecular mechanisms are still unclear. Here we subjected mice to chronic restraint stress (CRS), a paradigm known to induce anxiety-like behavior in mice. CRS mice exhibited anxiety-like behavior and reduced synaptic transmission in the medial prefrontal cortex (mPFC). Notably, Wisteria Floribunda agglutinin (WFA) staining showed a reduction of perineuronal nets (PNNs) expression in the mPFC of CRS mice. And the mRNA and protein levels of aggrecan (ACAN), a core component of PNNs, were also reduced. Parallelly, enzymatic digestion of PNNs in the mPFC by injecting Chondroitinase ABC (chABC) resulted in anxiety-like behavior in mice. Fluoxetine (FXT) is a clinically prescribed antidepressant/anxiolytic drug. FXT treatment in CRS mice not only ameliorated their deficits in behavior and synaptic transmissions, but also prevented CRS-induced reduction of PNNs and ACAN expressions. This study demonstrates that proper PNNs level is critical to brain functions, and their decline may serve as a pathological mechanism of anxiety disorders.

Nanoconfined polymerization limits crack propagation in hysteresis-free gels.

Consecutive mechanical loading cycles cause irreversible fatigue damage and residual strain in gels, affecting their service life and application scope. Hysteresis-free hydrogels within a limited deformation range have been created by various strategies. However, large deformation and high elasticity are inherently contradictory attributes. Here we present a nanoconfined polymerization strategy for producing tough and near-zero-hysteresis gels under a large range of deformations. Gels are prepared through in situ polymerization within nanochannels of covalent organic frameworks or molecular sieves. The nanochannel confinement and strong hydrogen bonding interactions with polymer segments are crucial for achieving rapid self-reinforcement. The rigid nanostructures relieve the stress concentration at the crack tips and prevent crack propagation, enhancing the ultimate fracture strain (17,580 ± 308%), toughness (87.7 ± 2.3 MJ m-3) and crack propagation strain (5,800%) of the gels. This approach provides a general strategy for synthesizing gels that overcome the traditional trade-offs of large deformation and high elasticity.

Low-Hysteresis and High-Toughness Hydrogels Regulated by Porous Cationic Polymers: the Effect of Counteranions.

Service life and range of polymer materials is heavily reliant on their elasticity and mechanical stability under long-term loading. Slippage of chain segments under load leads to significant hysteresis of the hydrogels, limiting its repeatability and mechanical stability. Achieving the desired elasticity exceeding that of rubber is a great challenge for hydrogels, particularly when subjected to large deformations. Here, low-hysteresis and high-toughness hydrogels were developed through controllable interactions of porous cationic polymers (PCPs) with adjustable counteranions, including reversible bonding of PCP frameworks/polymer segments (polyacrylamide, PAAm) and counteranions/PAAm. This strategy reduces chain segment slippage under load, endowing the PCP-based hydrogels (PCP-gels) with good elasticity under large deformations (7 % hysteresis at a strain ratio of 40). Furthermore, due to the enlarged chain segments entanglement by PCP, the PCP-gels exhibit large strain (13000 %), significantly enhanced toughness (68 MJ m-3 ), high fracture energy (43.1 kJ m-2 ), and fatigue resistance. The unique properties of these elastic PCP-gels have promising applications in the field of flexible sensors.

Poly(Ionic Liquid) Double-Network Elastomers with High-Impact Resistance Enhanced by Cation-π Interactions.

With the continuous development of impact protection materials, lightweight, high-impact resistance, flexibility, and controllable toughness are required. Here, tough and impact-resistant poly(ionic liquid) (PIL)/poly(hydroxyethyl acrylate) (PHEA) double-network (DN) elastomers are constructed via multiple cross-linking of polymer networks and cation-π interactions of PIL chains. Benefiting from the strong noncovalent cohesion achieved by the cation-π interactions in PIL chains, the prepared PIL DN elastomers exhibit extraordinary compressive strength (95.24 ± 2.49 MPa) and toughness (55.98 ± 0.66 MJ m-3) under high-velocity impact load (5000 s-1). The synthesized PIL DN elastomer combines strength and flexibility to protect fragile items from impact. This strategy provides a new research idea in the field of the next generation of safety and protective materials.

Lipid-laden foam cells in the pathology of atherosclerosis: shedding light on new therapeutic targets.

INTRODUCTION: Lipid-laden foam cells within atherosclerotic plaques are key players in all phases of lesion development including its progression, necrotic core formation, fibrous cap thinning, and eventually plaque rupture. Manipulating foam cell biology is thus an attractive therapeutic strategy at early, middle, and even late stages of atherosclerosis. Traditional therapies have focused on prevention, especially lowering plasma lipid levels. Despite these interventions, atherosclerosis remains a major cause of cardiovascular disease, responsible for the largest numbers of death worldwide. AREAS COVERED: Foam cells within atherosclerotic plaques are comprised of macrophages, vascular smooth muscle cells, and other cell types which are exposed to high concentrations of lipoproteins accumulating within the subendothelial intimal layer. Macrophage-derived foam cells are particularly well studied and have provided important insights into lipid metabolism and atherogenesis. The contributions of foam cell-based processes are discussed with an emphasis on areas of therapeutic potential and directions for drug development. EXERT OPINION: As key players in atherosclerosis, foam cells are attractive targets for developing more specific, targeted therapies aimed at resolving atherosclerotic plaques. Recent advances in our understanding of lipid handling within these cells provide insights into how they might be manipulated and clinically translated to better treat atherosclerosis.

LncRNA INHEG promotes glioma stem cell maintenance and tumorigenicity through regulating rRNA 2'-O-methylation.

Glioblastoma (GBM) ranks among the most lethal of human cancers, containing glioma stem cells (GSCs) that display therapeutic resistance. Here, we report that the lncRNA INHEG is highly expressed in GSCs compared to differentiated glioma cells (DGCs) and promotes GSC self-renewal and tumorigenicity through control of rRNA 2'-O-methylation. INHEG induces the interaction between SUMO2 E3 ligase TAF15 and NOP58, a core component of snoRNP that guides rRNA methylation, to regulate NOP58 sumoylation and accelerate the C/D box snoRNP assembly. INHEG activation enhances rRNA 2'-O-methylation, thereby increasing the expression of oncogenic proteins including EGFR, IGF1R, CDK6 and PDGFRB in glioma cells. Taken together, this study identifies a lncRNA that connects snoRNP-guided rRNA 2'-O-methylation to upregulated protein translation in GSCs, supporting an axis for potential therapeutic targeting of gliomas.

Research Progress of Dihydroquercetin in the Treatment of Skin Diseases.

Skin is a barrier to maintaining the stability of the human environment and preventing the invasion of pathogens. When skin tissue is exposed to the external environment, it will inevitably develop defects due to trauma, injury, burns, ulcers, surgery, and chronic diseases. Rapid skin repair is the key to reducing infection, relieving pain, and improving quality of life. Dihydroquercetin is a kind of flavonoid that has a wide range of pharmacological activities and can improve skin repair, skin inflammation, skin cancer, and so on. In this paper, the application of dihydroquercetin in medical dressings and the research progress in the treatment of skin-related diseases are reviewed, so as to provide reference for further developing dihydroquercetin as a drug for the treatment of skin diseases.

Small molecular inhibitors for KRAS-mutant cancers.

Three rat sarcoma (RAS) gene isoforms, KRAS, NRAS, and HRAS, constitute the most mutated family of small GTPases in cancer. While the development of targeted immunotherapies has led to a substantial improvement in the overall survival of patients with non-KRAS-mutant cancer, patients with RAS-mutant cancers have an overall poorer prognosis owing to the high aggressiveness of RAS-mutant tumors. KRAS mutations are strongly implicated in lung, pancreatic, and colorectal cancers. However, RAS mutations exhibit diverse patterns of isoforms, substitutions, and positions in different types of cancers. Despite being considered "undruggable", recent advances in the use of allele-specific covalent inhibitors against the most common mutant form of RAS in non-small-cell lung cancer have led to the development of effective pharmacological interventions against RAS-mutant cancer. Sotorasib (AMG510) has been approved by the FDA as a second-line treatment for patients with KRAS-G12C mutant NSCLC who have received at least one prior systemic therapy. Other KRAS inhibitors are on the way to block KRAS-mutant cancers. In this review, we summarize the progress and promise of small-molecule inhibitors in clinical trials, including direct inhibitors of KRAS, pan-RAS inhibitors, inhibitors of RAS effector signaling, and immune checkpoint inhibitors or combinations with RAS inhibitors, to improve the prognosis of tumors with RAS mutations.