Tuberculosis (TB), a chronic infectious disease caused by Mycobacterium tuberculosis, is primarily airborne and remains a global health problem, especially in resource-limited countries and regions. The emergence of drug resistance in M. tuberculosis has rendered the existing means ineffective in the treatment of TB. Therefore, research in new therapeutic directions has become imperative. In this review, we outline functional peptides in terms of the mechanisms of action, anti-TB attempts, advantages and disadvantages, and latest advances, aiming to analyze the research progress in anti-TB peptides. Furthermore, we investigate the potential applications of bioactive compounds found in traditional Chinese Medicine within the context of peptides.

ObjectiveTo investigate the effects of salidroside （SAL） on the impaired bioactivity of endothelial progenitor cells （EPCs） in atherosclerotic （As） mice and the potential mechanisms regarding AMP-activated protein kinase （AMPK）. MethodsAtherosclerosis was induced in 8-week-old male ApoE^-/- mice with high-fat diet. Intragastric administration of SAL was given to one mice group to investigate the effects of SAL on aortic plaque burden， plasma NO level， the migration and angiogenic capabilities of bone marrow-derived EPCs （BM-EPCs）. The proliferation， migration and vasculogenic properties of EPCs isolated from As mice were investigated in vitro. AMPK-sh-RNA or the AMPK inhibitor Compound C was used to investigate the role of AMPK/Akt/eNOS pathway in the regulatory effects of SAL. ResultsCompared with As group， NO level was significantly elevated in SAL group. The sizes of atherosclerotic plaques at the aortic root were reduced with smaller lipid cores in SAL group compared with As group. Moreover， the migration and angiogenesis capacity of EPCs markedly decreased in As mice， while SAL treatment reversed these impairments. Incubation with SAL at concentrations of 20， 40， and 80 μmol/L for 48 hours significantly promoted the proliferation， migration， and angiogenesis of EPCs. AMPK-sh-RNA transfection abrogated the 20 μmol/L SAL improvement in EPC biological activities. Western blot analysis further demonstrated that treatment with Compound C blocked the activation of AMPK/Akt/eNOS signaling pathway induced by SAL. ConclusionSAL upregulates the biological functions of EPCs through activating the AMPK/Akt/eNOS signaling pathway， thereby ameliorating EPC dysfunction during the pathological progression of atherosclerosis.

Zoledronic acid (ZA), a nitrogen-containing bisphosphonate with established clinical utility in osteoporosis management, exhibits emerging antitumor potential in estrogen receptor-positive breast cancer. However, the molecular mechanisms underlying its nonapoptotic anticancer effects remain poorly characterized. This study revealed that ZA induced ferroptosis in ER+ breast cancer cells through dual suppression of cystine-glutamate antiporter SLC7A11 and glutathione peroxidase 4 (GPX4), key repressors of ferroptosis. Pharmacological inhibition of ferroptosis using Ferrostatin-1 significantly attenuated ZA-induced cytotoxicity, while combinatorial treatment with the GPX4 inhibitor RSL3 synergistically enhanced lipid peroxidation and cell death. Mechanistically, ZA activated the Hippo-YAP signaling pathway, promoting YAP phosphorylation, proteasomal degradation, and cytoplasmic retention, thereby silencing SLC7A11 and GPX4. We established a novel metabolic vulnerability in hormone-responsive malignancies.These findings position ZA as a bifunctional ferroptosis inducer in ER+ breast cancer, offering a promising strategy to overcome endocrine resistance.

This paper aims to summarize Professor ZHOU Shaohua's clinical experience in treating Parkinson's disease （PD） based on the "disease-symptom-syndrome integration" approach. It is believed that kidney essence deficiency is the root cause of the disease， and phlegm-stasis accumulating toxin is the key factor for its deterioration. PD could be divided into the prodromal stage， early stage and middle-late stage. In the prodromal stage， treatment focuses on tonifying the kidney and replenishing marrow， choosing Zuogui Pill （左归丸） or Yougui Pill （右归丸） to prescribe with modifications according to accompanying non-motor symptoms such as constipation and rapid eye movement sleep behavior disorder. For the early stage， the disease is differentiated into three syndromes， liver-kidney yin deficiency with stirring wind， spleen-kidney yang deficiency， and excessive phlegm turbidity， then following the principle of "calming wind by regulating blood first"， the basic prescriptions of Dading Fengzhu Pill （大定风珠）， Yougui Pill （右归丸） and Jinshui Liujun Decoction （金水六君煎） are applied respectively， combined with Siwu Decoction （四物汤） to nourish blood and extinguish wind. For the middle-late stage， therapies of tonifying the kidney and conso-lidating original qi are combined with detoxifying and resolving turbidity， prescribing fleshy and nourishing medicinals such as deer-horn glue （Cervus nippon Temminck） and turtle shell glue （Colla Carapacis et Plastri Testudinis）， together with Huanglian Jiedu Decoction （黄连解毒汤） to clear heat， detoxify and resolve turbidity， implementing simultaneous tonification and elimination. Integrated traditional Chinese and western medicine intervention is emphasized for non-motor symptoms including orthostatic hypotension and dysphagia.

Acute myeloid leukemia (AML) is a highly heterogeneous hematological malignancy characterized by an abnormal proliferation of primitive and naive myeloid cells in the bone marrow and peripheral blood. Patients vary enormously in molecular biological features, clinical manifestations and prognosis, leading to therapeutic difficulties. Increasing evidence indicates that the tumor microenvironment plays an important role in the development and progression of AML. Immunometabolism reveals the metabolic network of immune cells, which has important implications in tumor research. This work reviews the research progress on the metabolic alterations of immune cells in the AML microenvironment and the therapeutic strategies targeting immune metabolism in AML to present a part of the blueprint of immune metabolism regulation in the bone marrow microenvironment of AML.

Objective: To explore the feasibility of constructing a lung cancer early-warning risk model based on facial image features, providing novel insights into the early screening of lung cancer. Methods: This study included patients with pulmonary nodules diagnosed at the Physical Examination Center of Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine from November 1, 2019 to December 31, 2024, as well as patients with lung cancer diagnosed in the Oncology Departments of Yueyang Hospital of Integrated Traditional Chinese and Western Medicine and Longhua Hospital during the same period. The facial image information of patients with pulmonary nodules and lung cancer was collected using the TFDA-1 tongue and facial diagnosis instrument, and the facial diagnosis features were extracted from it by deep learning technology. Statistical analysis was conducted on the objective facial diagnosis characteristics of the two groups of participants to explore the differences in their facial image characteristics, and the least absolute shrinkage and selection operator (LASSO) regression was used to screen the characteristic variables. Based on the screened feature variables, four machine learning methods: random forest, logistic regression, support vector machine (SVM), and gradient boosting decision tree (GBDT) were used to establish lung cancer classification models independently. Meanwhile, the model performance was evaluated by indicators such as sensitivity, specificity, F1 score, precision, accuracy, the area under the receiver operating characteristic (ROC) curve (AUC), and the area under the precision-recall curve (AP). Results: A total of 1 275 patients with pulmonary nodules and 1 623 patients with lung cancer were included in this study. After propensity score matching (PSM) to adjust for gender and age, 535 patients were finally included in the pulmonary nodule group and the lung cancer group, respectively. There were significant differences in multiple color space metrics (such as R, G, B, V, L, a, b, Cr, H, Y, and Cb) and texture metrics [such as gray-levcl co-occurrence matrix (GLCM)-contrast (CON) and GLCM-inverse different moment (IDM)] between the two groups of individuals with pulmonary nodules and lung cancer (P < 0.05). To construct a classification model, LASSO regression was used to select 63 key features from the initial 136 facial features. Based on this feature set, the SVM model demonstrated the best performance after 10-fold stratified cross-validation. The model achieved an average AUC of 0.8729 and average accuracy of 0.799 0 on the internal test set. Further validation on an independent test set confirmed the model’s robust performance (AUC = 0.823 3, accuracy = 0.729 0), indicating its good generalization ability. Feature importance analysis demonstrated that color space indicators and the whole/lip Cr components (including color-B-0, wholecolor-Cr, and lipcolor-Cr) were the core factors in the model’s classification decisions, while texture indicators [GLCM-angular second moment (ASM)_2, GLCM-IDM_1, GLCM-CON_1, GLCM-entropy (ENT)_2] played an important auxiliary role. Conclusion The facial image features of patients with lung cancer and pulmonary nodules show significant differences in color and texture characteristics in multiple areas. The various models constructed based on facial image features all demonstrate good performance, indicating that facial image features can serve as potential biomarkers for lung cancer risk prediction, providing a non-invasive and feasible new approach for early lung cancer screening.

ObjectiveTo investigate the heterogeneity and transcriptomic characteristics of T-cell subsets in the liver of mice with nonalcoholic steatohepatitis （NASH） at the single-cell level using single-cell RNA sequencing （scRNA-seq）， and to provide a reference for studying the mechanism of action of T cells in NASH. MethodsSix male C57BL/6 mice were randomly divided into control group fed with regular diet and NASH group fed with methionine-choline-deficient （MCD） diet， with three mice in each group， and liver tissue was collected for scRNA-seq after 6 weeks of modeling. Specific differentially expressed genes were analyzed between T-cell subsets， and related analyses were performed， including dimension clustering， cell type annotation， t-distributed stochastic neighbor embedding （t-SNE）， violin plot， gene ontology （GO） functional enrichment analysis， and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis. Immunofluorescent staining was used to observe the expression of the T cell marker Tcrα and the specific marker genes Tcf7 and Cxcr6 in the liver of mice in the two groups. The independent-samples t test was used for comparison of continuous data between two groups. ResultsTwo T cell subsets were identified in the liver of mice， and the percentage of cluster 6 decreased from 58.5% in the control group to 48.7% in the NASH group. The top four specific genes were Nsg2， Cd8b1， Cd8a， and Tcf7. Tcf7， a characteristic marker gene for cluster 6， was expressed in 65% of cells in cluster 6， and therefore， cluster 6 was defined as Tcf7⁺ T cells. The GO and KEGG enrichment analyses showed that the differentially expressed genes of cluster 6 were involved in T cell activation， leukocyte adhesion， binding ubiquitin-like protein ligase， and the signaling pathways for Th17， Th1， and Th2 cell differentiation. The percentage of cluster 7 increased from 41.5% in the control group to 51.3% in the NASH group. The top four specific genes of cluster 7 were Cd40lg， Tcrg-C1， Il2rα， and Cxcr6. Cxcr6 was expressed in 90% of cells in cluster 7， and therefore， cluster 7 was defined as Cxcr6⁺ T cells. The GO and KEGG enrichment analyses showed that cluster 7 was involved in T cell activation， cytokine production， the T cell receptor signaling pathway， and the Th17 cell differentiation and MAPK signaling pathway. Immunofluorescence assay showed that compared with the control group， the NASH group showed a significant reduction in the area with positive co-expression of Tcf7 protein and Tcrα protein （1.80%±0.67% vs 0.33%±0.13%， P<0.05） and a significant increase in the area with positive co-expression of Cxcr6 protein and Tcrα protein （0.50%±0.09% vs 2.66%± 0.33%， P<0.001）. ConclusionThere is a reduction in the percentage of Tcf7⁺ T cells and an increase in the percentage of Cxcr6⁺ T cells in NASH mice， revealing the characteristics and differences of T cells in the liver of NASH mice.

Antibody-drug conjugate (ADC), a novel class of antineoplastic agents, combines tumor-specific targeting with potent cytotoxic activity. In recent years, ADC has achieved notable advances in the treatment of non-small cell lung cancer (NSCLC), particularly within therapeutic sequencing after failure of first-line therapy or the emergence of resistance. This paper will systematically review the efficacy and safety evidence of representative ADC in NSCLC, and further to discuss progress and challenges in ADC structural optimization, toxicity management, biomarker identification, and combination strategies, aiming to provide a comprehensive theoretical foundation and practical reference for clinical practice and future research.
.
Humans ; Carcinoma, Non-Small-Cell Lung/drug therapy* ; Immunoconjugates/chemistry* ; Lung Neoplasms/drug therapy* ; Drug Resistance, Neoplasm/drug effects* ; Antineoplastic Agents/chemistry*

Ischemic stroke (IS) is a globally life-threatening disease. Presently, few therapeutic medicines are available for treating IS, and rt-PA is the only drug approved by the US Food and Drug Administration (FDA) in the US. In fact, many agents showing excellent neuroprotection but no blood flow-improving activity in animals have not achieved ideal clinical efficacy, while thrombolytic drugs only improving blood flow without neuroprotection have limited their wider application. To address these challenges and meet the huge unmet clinical need, we have designed and identified a novel compound AAPB with dual effects of neuroprotection and cerebral blood flow improvement. AAPB significantly reduced cerebral infarction and neural function deficit in tMCAO rats, pMCAO rats, and IS rhesus monkeys, as well as displayed exceptional safety profiles and excellent pharmacokinetic properties in rats and dogs. AAPB has now entered phase I of clinical trials fighting IS in China.

Cold tumors have a poor response to tumor immunotherapy due to low immune cell infiltration and the ability to evade immune attacks. Converting cold tumors into hot tumors can enhance the clinical effectiveness of anti-tumor immunotherapy. High-intensity focused ultrasound (HIFU) as a non-invasive treatment can damage tumors through mechanical effects, but there is a lack of research on its cytotoxic mechanisms at the cellular level and its role in inducing anti-immune responses. In this study, the role of HIFU in triggering tumor ferroptosis by disrupting the GSH/GSSG balance through mechanochemical action and the associated anti-tumor immune priming effect were investigated. The use of a nano-enhancer loaded with PFOB combined with HIFU could enhance ferroptosis in triple-negative breast cancer at a specific stage of tumor growth (UTGR = 0) while promoting the conversion of a cold tumor into a hot tumor, thereby improving the immune response. Overall, this provides valuable guidance for the clinical application of HIFU in tumor immunotherapy.