Epidermal growth factor receptor activating mutations serve as core driver lesions of non-small cell lung cancer, while early EGFR inhibitors are restricted by T790M resistance and weak blood-brain barrier penetration. This review systematically sorts multi-layer pharmacological effects, clinical advantages and acquired resistance subtypes of third-generation targeted agent osimertinib based on domestic and global Phase III clinical data. Osimertinib forms stable covalent binding with mutant EGFR to block MAPK and PI3K/Akt oncogenic cascades, and exerts dual anti-tumor effects via direct tumor apoptosis induction and long-term remodeling of immunosuppressive microenvironment. Large clinical trials verify its prominent control efficacy for primary lesions and intracranial metastases, yet long-term monotherapy easily generates four categories of drug resistance represented by C797S mutation and MET amplification. This paper summarizes stratified combined intervention schemes matching different resistance phenotypes, which provide standardized theoretical references for dynamic individualized targeted treatment and novel EG inhibitor development. Novel liquid biopsy monitoring technology further optimizes the whole-process precision medication management of osimertinib in clinical practice.

As core subsets of extracellular vesicles, exosomes mediate intercellular signal communication and carry diverse biomolecules that faithfully reflect the phenotypic characteristics of parent cells. In oncology research, exosomes exert two opposing biological effects on tumor progression and clinical intervention. This paper systematically sorts the dual regulatory functions of exosomes and summarizes their translational prospects for tumor liquid biopsy and targeted drug delivery. Tumor-derived exosomes remodel local and distant tumor microenvironments, suppress anti-tumor immune responses, facilitate angiogenesis and epithelial-mesenchymal transition, and transmit drug-resistant traits to sensitive tumor cells. Meanwhile, exosomes with intact lipid bilayer structures can protect internal nucleic acids and proteins from enzymatic degradation, serving as stable non-invasive biomarkers for early tumor screening and efficacy monitoring. Genetically modified engineered exosomes can load chemotherapeutics, small interfering RNAs and immune regulators to achieve tumor-specific targeted delivery. This paper systematically elaborates the molecular mechanisms, clinical diagnostic value, therapeutic potential and translational bottlenecks of exosomes in precision oncology. Current evidence proves exosome-based liquid biopsy supports early tumor detection, primary lesion tracing and dynamic efficacy evaluation. However, standardized separation protocols, unified quality control standards and long-term safety evaluation systems have not been fully established, restricting large-scale clinical transformation. Follow-up interdisciplinary research needs to form unified technical specifications to promote the clinical application of exosome-based diagnosis and treatment integrated strategies.

With the rapid growth of the global aging population, the incidence of Alzheimer's disease (AD) has been increasing year by year. This progressive, irreversible and insidious neurodegenerative disease will lead to progressive cognitive deterioration, posing a major public health threat to seniors and bringing heavy burdens to families and society. However, its complex and multi-dimensional pathogenesis has not been fully clarified, and major bottlenecks still exist in early screening, accurate diagnosis, and radical treatment. This paper systematically reviews the progression of AD, categorizing it into three stages: the subjective cognitive decline, mild cognitive impairment and AD dementia and describes its progression from early latent symptoms to severe functional impairment in middle and late stages. Based on this, this article deeply analyzes the multiple and interrelated pathogenic mechanisms of AD from four dimensions: canonical amyloid-tau proteinopathy, cerebral metabolic dysfunction, cerebral white matter structural impairment and systemic inducing factors. The study summarizes current mainstream interventions, pointing out key dilemmas including delayed diagnosis, single-target therapeutic limitations, and comorbidity interference, and lack of curative drugs. Additionally, this paper reviews cutting-edge research fields: diabetes-associated pathological pathways, DTI imaging, AI-assisted diagnosis, gut-brain axis regulation, and new targeted treatments. The study shows that AD is a complex disease driven by multiple factors, systems and mechanisms, and a single intervention is difficult to overcome the current predicament. This paper offers a comprehensive theoretical reference for AD early warning, pathological mechanism research, precision diagnosis and treatment, and translational medical development.

Forest fragmentation is a major threat to biodiversity as it divides continuous forests into smaller and more isolated patches surrounded by human-modified land. This process reduces habitat area, increases edge effects, restricts species movement, and weakens ecological processes such as dispersal, recolonization, gene flow, and functional diversity. This paper reviews evidence on the ecological impacts of forest fragmentation and evaluates connectivity-based restoration as a management strategy. It argues that restoring fragmented forests requires more than protecting isolated forest remnants or increasing tree cover: effective restoration should increase inter-patch connectivity and combine corridor construction with matrix management. Restoration corridors aim at reconnecting forest patches and supporting the restoration of functional diversity, while matrix management is intended to enhance the permeability of the surrounding landscape through strategically adding arboreal elements such as living fences, riparian vegetation, woodland islets, and isolated trees, which serve as stepping stones for organisms. The paper also emphasizes the importance of multispecies planning, since different organisms respond differently to corridors and matrix conditions. Overall, it is suggested that an integrated strategy of corridor restoration and matrix improvement may beneficially restore ecological function in fragmented forest landscapes. Future research should focus on whether structural connectivity leads to stable movement patterns, gene flow, and long-term recovery of ecosystem functions.

In response to increasing concerns about environmental factors linked to Autism Spectrum Disorder (ASD), thimerosal, an ethylmercury-based vaccine stabilizer, has received considerable attention. This paper evaluates multinational observational evidence on whether thimerosal exposure from pediatric vaccines is associated with ASD risk. Accordingly, six eligible studies from the USA, UK, Denmark, and Japan were selected in accordance with PRISMA 2020 guidelines, and study characteristics, exposure definitions, ASD diagnostic criteria, and effect estimates were extracted. Because study design and exposure measurement varied substantially, reported odds ratios, risk ratios, and hazard ratios were transformed to the natural-log scale and pooled using a generic inverse-variance random-effects model. In addition, risk of bias was assessed using the Newcastle-Ottawa Scale and visualized with robvis. The results showed a log effect of 0.19, with a 95% confidence interval of -0.49 to 0.88, corresponding to a pooled ratio of 1.21 with a 95% confidence interval of 0.61 to 2.41 and P=0.502, indicating no statistically significant association. However, heterogeneity was high, with I2=89.72% and P<0.001, mainly driven by two low-precision studies that suggested an increased risk. Notably, reduction of heterogeneity after removal of outliers did not change the overall finding of no significant or causal association between thimerosal exposure from pediatric vaccines and increased ASD risk.

Alzheimer's disease (AD) ranks among the most prevalent neurodegenerative diseases globally, and definitive diagnosis is frequently accomplished subsequent to substantial brain damage. Conventional diagnostic methods, including positron emission tomography (PET) imaging and cerebrospinal fluid (CSF) analysis, yield satisfactory diagnostic performance but suffer from high costs and invasiveness. In recent years, blood biomarkers such as amyloid-beta (Aβ), phosphorylated tau (p-tau), and neurofilament light chain (NfL) have emerged as promising tools for earlier and more accessible diagnosis. However, interpreting complex biomarker data remains challenging. Each marker reflect distinct neurodegenerative problem. Artificial intelligence (AI) and machine learning techniques may improve diagnostic accuracy by analyzing multiple biomarkers simultaneously and identifying hidden biological patterns. This paper reviews the role of AI-assisted blood biomarker analysis in the early diagnosis of Alzheimer's disease, discusses major biomarkers currently used in research, summarizes recent findings, and evaluates the opportunities and limitations of AI-based diagnostic approaches. Although several challenges remain, including dataset bias and clinical implementation difficulties, AI-assisted blood testing represents a promising direction for improving large-scale screening and early intervention for Alzheimer's disease. It may also reduce reliance on costly, invasive examinations in healthcare.

Diabetic nephropathy is a common microvascular complication of diabetes that is one of the main causes of end-stage renal disease around the world. At present, there are no particular targeted therapeutic drugs that have been used in clinical trials. Astragaloside IV (AS-IV) has good protective effects on the kidneys and is now one of the hot topics in research on DKD pharmacology. AS-IV has several targets in the molecular regulatory network of diabetic kidney disease (DKD), and by activating the SIRT1/PGC1α/Nrf1 and Nrf2-ARE/TFAM pathways, it can reduce renal oxidative stress and mitochondrial damage; by inhibiting the activation of the NLRP3 inflammasome and downregulating IL-6, TNF -α, etc., it can reduce inflammatory infiltration in the kidney; by regulating the TXNIP-NLRP3-GSDMD signaling axis, it can prevent pyroptosis of renal tubules and podocytes; and by targeting the HIF-1α/HMOX1 pathway, it can improve iron accumulation in renal tubular epithelial cells and prevent iron death. Most of the current evidence is obtained from in vitro cell and DKD animal model experiments. There is a lack of extensive data on the human clinical trials of AS-IV monomers, and the exact mechanism of multi-channel cross-regulation has not been fully determined yet. In the future, it is necessary to enhance the development of AS-IV preparations, conduct multi-centre clinical trials, explore more deeply the renal protective molecular network of this drug, and advance the clinical application of traditional Chinese medicine monomers in precision treatment for diabetic nephropathy.

Immune checkpoint inhibitors have triggered a revolutionary transformation in comprehensive treatment of malignant tumors and drastically prolonged the survival cycle of patients with advanced malignancies. Nevertheless, a considerable proportion of patients fail to achieve durable therapeutic benefits, owing to the intrinsically low overall objective response rate across most solid tumors and the widespread emergence of acquired drug resistance during long-term medication, which severely limits the popularization and long-term clinical application of this immunotherapy strategy. Against this backdrop, developing natural immunomodulatory substances with mild toxic side effects, definite regulatory effects and wide availability has become an urgent research hotspot in oncology adjuvant therapy. Centered on published cellular experiments, animal in vivo assays and preliminary clinical observational data, this review comprehensively and hierarchically elaborates the multi-dimensional anti-tumor immune regulatory mechanisms of ursolic acid. By simultaneously blocking NF-κB and STAT3 signaling cascades, ursolic acid reconstructs suppressive tumor immune microenvironment, facilitating the polarization shift of tumor-associated macrophages from immune-tolerant M2 phenotype to anti-tumor M1 subtype. Meanwhile, it strengthens the tumoricidal function of natural killer cells and suppresses tumor cell PD-L1 expression, thereby alleviating T cell exhaustion and restoring anti-tumor adaptive immunity. Multiple preclinical animal studies have confirmed its potent anti-neoplastic efficacy and outstanding in vivo biosafety. The translational transformation of ursolic acid is hindered by ambiguous direct molecular binding targets, poor oral bioavailability and the absence of large-scale prospective clinical trials. This paper lays systematic theoretical foundations for designing novel combination immunotherapy schemes that incorporate ursolic acid as a safe auxiliary intervention agent.

Traditional small-molecule anticancer inhibitors primarily block single protein activities and are vulnerable to mutation-mediated drug resistance. Proteolysis-targeting chimera (PROTAC) technology induces the ubiquitin-proteasome-dependent clearance of oncogenic proteins and provides a promising new strategy for precision cancer therapy. This paper summarizes the molecular basis, degradation mechanism, design principles, and translational progress of PROTAC degraders in cancer treatment. PROTACs consist of a target ligand, an E3 ubiquitin ligase ligand and a connecting linker, and they exert unique event-driven antitumor effects by inducing ternary complex formation and target ubiquitination. Representative ER, AR, BTK, BCL-xL, and BRD4 degraders have shown promising preclinical or clinical activity, especially in drug-resistant tumors. Current challenges include poor oral pharmacokinetic properties, incomplete tumor selectivity, uncertain long-term safety, and emerging resistance mechanisms related to ubiquitin signaling. Optimized ligand-linker design, tumor-selective E3 ligases, prodrug strategies and biomarker-guided clinical trials are expected to greatly promote the clinical development of PROTAC-based anticancer therapies.

The two linked ecological crises of the Anthropocene for forest ecosystems are climate change and biological invasion. This review presents the synthesis of how climate change promotes the spread of invasive alien species (IAS) in boreal and temperate forests that have been cold-climate controlled environments in the past. The combined effect of these stressors is explained by the Fluctuating Resource Availability Theory; ecosystem vulnerability is directly related to the reduced availability of resources resulting from severe weather and tree loss. These "resource pulses" help the invasive species spread rapidly after disturbance. Canadian goldenrod is an invasive species that can adapt to changes in the environment quickly, produce allelopathic chemicals to inhibit other plants. Invaders have replaced native plants, formed a monoculture, changed the carbon cycle and reduced biodiversity. In the event of a severe forest degradation, it will be a carbon source. Economic damage is about $1.4 trillion in lost GDP worldwide each year, and health risks come from allergens released by expanded allergenic pollen of weed populations in some colonised areas, affecting up to 12% of the population. Early detection via predictive distribution models for climate-informed risk zoning; integrated control combining mechanical, chemical and biological methods, emphasizing sustainable biological control; and post-invasion forest restoration focused on ecosystem resilience. The most economical method for preventing both deliberate and accidental introduction is still in use. Under prolonged warming in the future, ecosystems will continue to degrade without the concerted efforts of countries to reduce emissions and control invasive alien species.