Hard Copper Boride with Exceptional Conductivity.

Copper and boron seldom engage in reaction at ambient pressure. The few reports on copper-doped boron compounds that exist in the literature often lack definitive stoichiometry. Here, we report successful synthesis of Cu_{2-δ}B_{25} single crystals (δ∼0.03, indicating Cu understoichiometry) via a high-pressure melting method using copper and ß-rhombohedral boron as precursors. Crystals thus synthesized are characterized by a tetragonal boron sublattice, within which Cu atoms are either partially or fully situated at different interstices between B_{12} icosahedra. The crystals possess a high Vickers hardness of 26.5 GPa and an unusually high electrical conductivity of 1.19×10^{5} S/m-the highest conductivity among the icosahedron-based borides. Hall measurements reveal a notable p-n conduction type transition around 30 GPa. This transition, alongside the remarkable conductivity, is potentially modulated by the copper content and its valence states within the structure. The synthesis of Cu_{2-δ}B_{25} not only broadens the spectrum of hard materials but also opens new avenues for innovative modulation of electronic properties in boron-rich compounds, with promising technological implications.

SIRT6 Inhibits Anoikis of Colorectal Cancer Cells by Down-Regulating NDRG1.

Anoikis, a form of apoptosis resulting from the loss of cell-extracellular matrix interaction, is a significant barrier to cancer cell metastasis. However, the epigenetic regulation of this process remains to be explored. Here, we demonstrate that the histone deacetylase sirtuin 6 (SIRT6) plays a pivotal role in conferring anoikis resistance to colorectal cancer (CRC) cells. The protein level of SIRT6 is negatively correlated with anoikis in CRC cells. The overexpression of SIRT6 decreases while the knockdown of SIRT6 increases detachment-induced anoikis. Mechanistically, SIRT6 inhibits the transcription of N-myc downstream-regulated gene 1 (NDRG1), a negative regulator of the AKT signaling pathway. We observed the up-regulation of SIRT6 in advanced-stage CRC samples. Together, our findings unveil a novel epigenetic program regulating the anoikis of CRC cells.

Protective properties of extracellular vesicles in sepsis models: a systematic review and meta-analysis of preclinical studies.

BACKGROUND: Multiple preclinical studies have reported a beneficial effect of extracellular vesicles (EVs), especially mesenchymal stem cells derived EVs (MSC-EVs), in the treatment of sepsis. However, the therapeutic effect of EVs is still not universally recognized. Therefore, we conducted this meta-analysis by summarizing data from all published studies that met certain criteria to systematically review the association between EVs treatment and mortality in animal models of sepsis. METHODS: Systematic retrieval of all studies in PubMed, Cochrane and Web of Science that reported the effects of EVs on sepsis models up to September 2022. The primary outcome was animal mortality. After screening the eligible articles according to inclusion and exclusion criteria, the inverse variance method of fixed effect model was used to calculate the joint odds ratio (OR) and 95% confidence interval (CI). Meta-analysis was performed by RevMan version 5.4. RESULTS: In total, 17 studies met the inclusion criteria. Meta-analysis of those studies showed that EVs treatment was associated with reduced mortality in animal models of sepsis (OR 0.17 95% CI: 0.11,0.26, P < 0.001). Further subgroup analysis showed that the mode of sepsis induction, the source, dose, time and method of injection, and the species and gender of mice had no significant effect on the therapeutic effect of EVs. CONCLUSION: This meta-analysis showed that MSC-EVs treatment may be associated with lower mortality in animal models of sepsis. Subsequent preclinical studies will need to address the standardization of dose, source, and timing of EVs to provide comparable data. In addition, the effectiveness of EVs in treating sepsis must be studied in large animal studies to provide important clues for human clinical trials.

Elabela, a Novel Peptide, Exerts Neuroprotective Effects Against Ischemic Stroke Through the APJ/miR-124-3p/CTDSP1/AKT Pathway.

Elabela (ELA), which is the second endogenous peptide ligand of the apelin receptor (APJ) to be discovered, has been widely studied for potential use as a therapeutic peptide. However, its role in ischemic stroke (IS), which is a leading cause of disability and death worldwide and has limited therapeutic options, is uncertain. The aim of the present study was to investigate the beneficial effects of ELA on neuron survival after ischemia and the underlying molecular mechanisms. Primary cortical neurons were isolated from the cerebral cortex of pregnant C57BL/6J mice. Flow cytometry and immunofluorescence showed that ELA inhibited oxygen-glucose deprivation (OGD) -induced apoptosis and axonal damage in vitro. Additionally, analysis of the Gene Expression Omnibus database revealed that the expression of microRNA-124-3p (miR-124-3p) was decreased in blood samples from patients with IS, while the expression of C-terminal domain small phosphatase 1 (CTDSP1) was increased. These results indicated that miR-124-3p and CTDSP1 were related to ischemic stroke, and there might be a negative regulatory relationship between them. Then, we found that ELA significantly elevated miR-124-3p expression, suppressed CTDSP1 expression, and increased p-AKT expression by binding to the APJ receptor under OGD in vitro. A dual-luciferase reporter assay confirmed that CTDSP1 was a direct target of miR-124-3p. Furthermore, adenovirus-mediated overexpression of CTDSP1 exacerbated neuronal apoptosis and axonal damage and suppressed AKT phosphorylation, while treatment with ELA or miR-124-3p mimics reversed these effects. In conclusion, these results indicated that ELA could alleviate neuronal apoptosis and axonal damage by upregulating miR-124-3p and activating the CTDSP1/AKT signaling pathway. This study, for the first time, verified the protective effect of ELA against neuronal injury after ischemia and revealed the underlying mechanisms. We demonstrated the potential for the use of ELA as a therapeutic agent in the treatment of ischemic stroke.

A novel isoform of hydroxyacyl-CoA dehydrogenase inhibits cell proliferation.

Hydroxyacyl-CoA dehydrogenase (HADH) catalyzes the third reaction of mitochondrial ß-oxidation cascade, while the regulation of its expression and function remains to be elucidated. Using the quantitative translation initiation sequencing (QTI-seq), we have identified that murine Hadh mRNA has two alternative translation start codons. We demonstrated that translation from upstream start codon encodes the mitochondrial isoform of HADH, while translation from downstream start codon produces a short isoform (HADH-S) with predominant nuclear localization. Moreover, overexpression of HADH-S inhibits the proliferation of mouse embryonic fibroblasts. Overall, our results identify a novel isoform of HADH participating in cell proliferation.

TNK2-AS1 upregulated by YY1 boosts the course of osteosarcoma through targeting miR-4319/WDR1.

Mounting research papers have suggested that long non-coding RNAs (lncRNAs) elicit important functions in the progression of osteosarcoma (OS). This study focused on the role of TNK2-AS1 in OS. TNK2-AS1 was powerfully expressed in OS tissues and cell lines. In addition, TNK2-AS1 downregulation inhibited proliferative, migratory, and invasive capacities while promoting apoptosis in OS cells. miR-4319 was removed by TNK2-AS1 and therefore TNK2-AS1 elevated WDR1 expression in OS cells. miR-4319 had an inhibitory influence on OS progression, while WDR1 was a contributor to OS progression. Rescue assays certified that TNK2-AS1 promoted malignant phenotypes in vitro and the growth in vivo of OS cells by upregulating WDR1. In depth, we found that YY1 accelerated the transcription of TNK2-AS1 in OS cells, and that its role in OS also depended on TNK2-AS1-regulated WDR1. In conclusion, TNK2-AS1 was positively modulated by YY1 and aggravated the development of OS by 'sponging' miR-4319 to elevate WDR1. The findings highlighted that TNK2-AS1 might be a promising target for the treatment of OS.

YTHDF1-regulated expression of TEAD1 contributes to the maintenance of intestinal stem cells.

N6-methyladenosine (m6A) mRNA modification has been defined as a crucial regulator in various biological processes. Recent studies indicated an essential role of YTHDF1, an m6A reader, in the maintenance of intestinal stem cells (ISCs), while the detailed mechanism remains to be explored. By searching our m6A sequencing, RNA sequencing, and ribosome profiling data, we identified the transcriptional enhanced associate domain 1 (TEAD1) as a direct target of YTHDF1. We confirmed the presence of m6A modifications in TEAD1 mRNA and its binding with YTHDF1. Knockdown of either m6A methyltransferase METTL3 or YTHDF1 reduced the translation of TEAD1. TEAD1 was highly expressed in ISCs, while depletion of TEAD1 inhibited proliferation and induced differentiation of organoids. Overexpression of TEAD1 reversed the impaired stemness elicited by YTHDF1 depletion. These findings identify TEAD1 as a functional target of m6A-YTHDF1 in sustaining intestinal stemness.

Experimental Study of Somatic Variants of Osteosarcoma by Whole-Exome Sequencing.

BACKGROUND This study aimed to investigate the role of gene mutation site distribution, biological function, pathway enrichment, and gene association analysis in the occurrence, development, and migration of osteosarcoma. MATERIAL AND METHODS Somatic mutation screening was performed using the whole-exome sequencing of osteosarcoma samples, and the distribution of mutations was demonstrated by Circos diagrams. Metascape was used to analyze the GO and KEGG signal pathway enrichment of the genes harboring protein coding alterations, and GeneMANIA was used to analyze the interaction of mutated genes. RESULTS The results showed that the protein coding alterations were found throughout the whole genome in 3 osteosarcoma samples. A large number of identical or related biological processes and pathways were found in osteosarcoma samples. The GeneMANIA analysis of the 10 mutations shared by 3 samples showed that the target gene minichromosome maintenance complex component 4 (MCM4) and 3 lateral genes were most functional, and were all related to DNA replication. The analysis of GO and KEGG signal pathway enrichment showed that the mutated genes were involved mainly in tumor-related metabolic pathways. Three mutated genes were involved in the cell process, and 2 mutated genes were involved in the metabolic process. Known driver gene mutations were also observed in the samples. CONCLUSIONS The gene analysis confirmed that patients with osteosarcoma had a wide range of common gene mutations related to each other, which are involved in tumor-related metabolic pathways. These findings provide a basis for further gene-targeted therapy and pathway research.

Mid- to long-term effects of two different biological reconstruction techniques for the treatment of humerus osteosarcoma involving caput humeri.

BACKGROUND: The proximal humerus is one of the most common sites of primary or metastatic malignant tumors. Reconstruction of the shoulder after tumor resection is controversial and challenging. When intra-articular resection is performed, biological reconstruction (osteoarticular allograft and autologous bone implantation) may be the first choice rather than prosthetic reconstruction. OBJECTIVE: To observe the mid- to long-term effects of oncologic, reconstructive, and functional outcomes of two different biological reconstruction methods for resection of humerus osteosarcoma involving caput humeri. METHODS: This was a retrospective study of 13 consecutive patients who underwent humeral reconstruction of osteosarcoma including caput humeri using osteoarticular allograft (n = 7) and tumor bone inactivated and reimplantation (TBIR, n = 6) in our clinic between 2007 and 2017. Patients' general information, resection and reconstruction techniques, oncological and functional outcomes, and complications were collected and evaluated. Different complications of implantations were compared and analyzed for the different biological methods. RESULTS: The study included ten males and three females with an average age of 19.15 years. The operation time was about 3.65 h with an average blood loss of 631 ml. The resection tumor bones were 13-45 cm (23.54 cm on average). The mean follow-up period was 5.27 years. The shoulder movement was 10-70° (average, 44.00°) in abduction, 0-30° (average, 14.17°) in flexion, and 0-20° (average, 11.90°) in extention at the last follow-up. The complications included fracture in four TBIR patients and two allograft patients with an average of 2.67 years postoperation. Fracture rate was higher and appeared time was earlier in TBIR patients than in allograft patients (p = 0.04); caput humeri absorption occurred in all seven allograft patients and three TBIR patients at an average of 3.10 years after surgery; severe graft bone resorption appeared in five TBIR patients and two allograft patients at an average of 2.57 years of follow-up. CONCLUSIONS: Humerus biological reconstruction involving caput humeri was associated with a high complication rate and acceptable limb function in the mid to long term. New combined biological methods should be explored and adopted in the future.

Deep gene selection method to select genes from microarray datasets for cancer classification.

BACKGROUND: Microarray datasets consist of complex and high-dimensional samples and genes, and generally the number of samples is much smaller than the number of genes. Due to this data imbalance, gene selection is a demanding task for microarray expression data analysis. RESULTS: The gene set selected by DGS has shown its superior performances in cancer classification. DGS has a high capability of reducing the number of genes in the original microarray datasets. The experimental comparisons with other representative and state-of-the-art gene selection methods also showed that DGS achieved the best performance in terms of the number of selected genes, classification accuracy, and computational cost. CONCLUSIONS: We provide an efficient gene selection algorithm can select relevant genes which are significantly sensitive to the samples' classes. With the few discriminative genes and less cost time by the proposed algorithm achieved much high prediction accuracy on several public microarray data, which in turn verifies the efficiency and effectiveness of the proposed gene selection method.

Prognostic Effect of TP53 and PKD Co-Mutations in Patients with Resected Epidermal Growth Factor Receptor-Mutated Lung Adenocarcinoma.

BACKGROUND: The impact of specific co-mutations in epidermal growth factor receptor (EGFR)-mutated lung adenocarcinoma is unclear. METHODS: Tissues from 147 consecutive patients with resected EGFR-mutated lung adenocarcinomas treated at Sun Yat-Sen University Cancer Center were analyzed by next-generation sequencing (NGS). Associations between mutation status, patient baseline characteristics, and survival outcomes (disease-free survival [DFS] and overall survival [OS]) after surgical resection were analyzed. RESULTS: TP53 and protein kinase D (PKD) mutations were the two most frequently observed co-mutations in this cohort. Dual PKD/EGFR and TP53/EGFR mutations were found in 39 (27%) and 72 patients (49%), respectively, with dual TP53/EGFR mutations more commonly observed in male patients (P = 0.021). Both TP53 (hazard ratio [HR] 2.08, 95% confidence interval [CI] 1.23-3.54, P = 0.007) and PKD co-mutations (HR 1.72, 95% CI 1.01-2.93, P = 0.044) were associated with shorter DFS, but not OS, in univariate analysis. In multivariate analysis, patients harboring PKD/TP53 co-mutations had shorter DFS compared with PKD-/TP53- cases (HR 2.49, 95% CI 1.15-5.37, P = 0.02). In a subgroup of never-smokers, TP53 co-mutations were associated with significantly worse OS (HR 50.11, 95% CI 2.39-1049.83, P = 0.012). CONCLUSION: TP53 and PKD mutations were the two most frequently observed co-mutations in resected EGFR-mutated lung adenocarcinoma. Both mutations were associated with poorer prognoses in affected patients.

[Determination of plasma protein binding rates of nine compounds of Inula cappa extraction based on method of equilibrium dialysis].

To determine the plasma protein binding rate of the nine compounds in Inula cappa extraction by the method of equilibrium dialysis. The proteins in plasma samples were precipitated by methanol, and the ultra-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS) was developed for determination of the concentrations of the nine active compounds, namely chlorogenic acid, scopolin, neochlorogenic acid, cryptochlorogenic acid, 1,3-O-dicaffeoylquinic acid, galuteolin, 3,4-O-dicaffeoylquinic acid, 3,5-O-dicaffeoylquinic acid, 4,5-O-dicaffeoylquinic acid, with the internal standard of puerarin. We found that all components have a good linearity(r≥0.999), and accuracy, precision, extraction recovery and stability conformed to the requirements of determination, without endogenous compounds disturbing within the range of optimum concentration. This suggested that the method was stable and reliable, and could be used for the determination of the plasma protein binding rates of the nine active compounds in rat and human plasma of I. cappa. The plasma protein binding rates of the nine active compounds in rat and human plasma respectively were(41.07±0.046)%-(94.95±0.008)%, and(37.66±0.043)%-(97.46±0.013)%. According to the results, there were differences in the plasma protein binding rates of the nine compounds in I. cappa extraction between rat and human.

[Absorption of Inula cappa extract based on everted intestinal sac method].

To investigate the absorptive characteristics of Inula cappa extract based on the rat everted intestinal sac method in vitro. Nine representative ingredients in I. cappa extract were selected as the study objects. An UPLC-MS/MS method was established to determine and detect their cumulative absorption amount for expounding the absorptive characteristics of ingredients in different intestinal sections. According to the results， the transport mechanism of 8 compounds showed passive diffusion by the reverted gut sac method. And scopolin was actively transported in the intestine. The best absorption site of chlorogenic acid was duodenum. The best absorption site of cryptochlorogenic acid， 1，3-O-dicaffeoylquinic acid， luteolin-7-glucoside and 3，4-O-dicaffeoylquinic acid were jejunum. The best absorption site of neochlorogenic acid， scopolin， 4，5-O-dicaffeoylquinic acid and 3，5-O-dicaffeoylquinic acid was ileum. The absorption of all the compounds was affected by pH and bile. All of the nine ingredients in I. cappa extract could be absorbed in intestines， but with differences in the absorption rate， the best absorptive site and mechanism， indicating that the intestinal absorption of I. cappa extract was selective.

[Metabolism of Inula cappa extract by rat intestinal bacteria in vitro].

To investigate the metabolism of major components in Inula cappa by rat intestinal bacteria in vitro. I. cappa extract was incubated for 24 h with rat intestinal bacteria under anaerobic environment. After the samples were precipitated by n-butanol, UPLC-Q-TOF-MS/MS was applied for the qualitative analysis of the metabolites, combined with data software such as Metabolite Tools, Data Analysis and so on. The potential metabolites in rat intestinal bacteria were analyzed by comparing the total ion current of the test samples and blank samples and analyzing the quasi-molecular ion and fragment ion of all chromatograms. The results injected that fourteen metabolites were detected in rat intestinal flora. Various types of metabolic reactions happen to caffeoylquinic acid in intestinal flora, including isomerization, hydrolyzation, there were also methylation, hydrogenation and acetylation of caffeic acid. At the same time, a methylate of dicaffeoylquinic acid was also detected. Presumably, caffeoylquinic acids were gradually transformed into more hydrophobic metabolites with smaller molecular mass, which were better absorbed by the intestinal tract.

Investigation on the IL-18 -607A/C and -137C/G on the susceptibility of ischemic stroke.

OBJECTIVE: We conducted a case-control study with 322 cases and 322 controls to assess the role of the two common SNPs in the promoter of IL-18 gene. METHODS: Polymerase chain reaction restriction fragment length of polymorphism (PCR-RFLP) was taken to genotype -607A/C and -137C/G in the promoter of the IL-18 gene. RESULTS: By comparing cases and control subjects, we found that IS cases were more likely to have higher BMI, higher proportion of hypertension, and have higher proportion of smokers and drinkers. We found that IL-18 -607CC genotype (OR=1.70, 95% CI=1.03-2.81) and C allele (OR=1.26, 95% CI=1.01-1.58) were significantly more frequent in IS patients when compared with AA genotype. We did not find significant association between IL-18 -607A/C gene polymorphism and BMI, hypertension, smoking and drinking on the risk of IS. CONCLUSION: Our study suggests that polymorphisms in IL-18 -607A/C can influence the development of IS, and this gene polymorphism is associated with risk of IS in a Chinese population.

RRHGE: a novel approach to classify the estrogen receptor based breast cancer subtypes.

BACKGROUND: Breast cancer is the most common type of cancer among females with a high mortality rate. It is essential to classify the estrogen receptor based breast cancer subtypes into correct subclasses, so that the right treatments can be applied to lower the mortality rate. Using gene signatures derived from gene interaction networks to classify breast cancers has proven to be more reproducible and can achieve higher classification performance. However, the interactions in the gene interaction network usually contain many false-positive interactions that do not have any biological meanings. Therefore, it is a challenge to incorporate the reliability assessment of interactions when deriving gene signatures from gene interaction networks. How to effectively extract gene signatures from available resources is critical to the success of cancer classification. METHODS: We propose a novel method to measure and extract the reliable (biologically true or valid) interactions from gene interaction networks and incorporate the extracted reliable gene interactions into our proposed RRHGE algorithm to identify significant gene signatures from microarray gene expression data for classifying ER+ and ER- breast cancer samples. RESULTS: The evaluation on real breast cancer samples showed that our RRHGE algorithm achieved higher classification accuracy than the existing approaches.

Comprehensive analysis of disulfidptosis-related lncRNAs for predicting prognosis and response of immunotherapy in pancreatic adenocarcinoma.

Background: Pancreatic adenocarcinoma (PAAD) is a common and deadly tumor. Currently, there is a severe lack of therapeutic options. As a novel mode of cell death, increasing evidence reveals the important role of the disulfidptosis in cancer. However, few studies have utilized disulfidptosis-related long-stranded non-coding RNAs (DRlncRNAs) to investigate the prognosis of PAAD. Methods: We comprehensively analyzed the expression and prognostic value of 958 DRlncRNAs in PAAD using data from The Cancer Genome Atlas (TCGA). We established and validated a new DRlncRNAs-related prognostic index by least absolute shrinkage and selection operator (LASSO) and COX regression analysis. In addition, we built a nomogram consisting of risk score, age, gender, tumor grade and stage to validate the clinical feasibility of the index. We further evaluated the value of the index in terms of PAAD functional pathways, tumor microenvironment (TME) and tumor mutations. Results: We designed a risk model for five DRlncRNAs and demonstrated its accuracy using receiver operating characteristic (ROC) curves. COX regression suggested that the model may be an independent predictor of cancer prognosis. Tumor immune infiltration analysis revealed that low-risk subgroups had higher extent of immune infiltration, higher sensitivity to immunotherapy and a higher TME score. This is helpful for us to discover more precise immunotherapy for PAAD patients. Conclusions: In conclusion, we established a DRlncRNA index comprising of five DRlncRNAs, which may provide new insights for clinical diagnosis and precision therapy.

An intelligent ratiometric fluorescent assay based on MOF nanozyme-mediated tandem catalysis that guided by contrary logic circuit for highly sensitive sarcosine detection and smartphone-based portable sensing application.

As the well-known test-indicator for early prostate cancer (PCa), sarcosine (SA) is closely related to the differential pathological process, which makes its accurate determination increasingly significant. Herein, we for the first time expanded the peroxidase (POD)-like property of facile-synthesized Zn-TCPP(Fe) MOF to fluorescent substrates and exploited it to ratiometric fluorescent (RF) sensing. By harnessing the effective catalytic oxidation of MOF nanozyme toward two fluorescent substrates (Scopoletin, SC; Amplex Red, AR) with contrary changes, and target-responsive (SA + SOx)/MOF/(SC + AR) tandem catalytic reaction, we constructed the first MOF nanozyme-based RF sensor for the quantitative determination of SA. Superior to previous works, the operation of this RF sensor is under the guidance of AND-(AND^NAND) contrary logic circuit. The dual-channel binary output changes (from 1/0 to 0/1) not only enable the intelligent logical recognition of SA, bringing strengthened reliability and accuracy, but also manifest the proof-of-concept discrimination of PCa individuals and healthy ones. Through recording the fluorescence alterations of SC (F465) and AR (F585), two segments of linear relationships between ratiometric values (F585/F465) and varied contents of SA are realized successfully. The LOD for SA could reach to as low as 39.98 nM, which outperforms all nanozyme-originated SA sensors reported till now. Moreover, this sensor also demonstrates high selectivity and satisfactory performance in human serum samples. Furthermore, the portable sensing of SA is realized under the assistance of smartphone-based RGB analysis, demonstrating the potential of point-of-care diagnostics of PCa in the future.

Clinical features and multiomics profiles indicate coagulation and platelet dysfunction in COVID-19 viral sepsis.

Increased cases of sepsis during COVID-19 in the absence of known bacterial pathogens highlighted role of viruses as causative agents of sepsis. In this study, we investigated clinical, laboratory, proteomic, and metabolomic characteristics of viral sepsis patients (n = 45) and compared them to non-sepsis patients with COVID-19 (n = 186) to identify molecular mechanisms underlying the pathology of viral sepsis in COVID-19. We identified unique metabolomic and proteomic signatures that suggest a substantial perturbation in the coagulation, complement, and platelet activation pathways in viral sepsis. Our proteomic data indicated elevated coagulation pathway protein (fibrinogen), whereas a decrease in many of the complement proteins was observed. These alterations were associated with the functional consequences such as susceptibility to secondary bacterial infections and potentially contributing to both local and systemic disease phenotypes. Our data provide novel aspect of COVID-19 pathology that is centered around presence of sepsis phenotype in COVID-19.

Combined effects of mixing ratios and tree size: how do mixed forests respond to climate and drought events?

Although the relationship between biodiversity and ecosystem functionality (BEF) has been studied comprehensively, how the mixing ratio of tree species in mixed forests affects the response of trees to climate and drought remains an unexplored and rather unknown question. Hence, we established tree-ring chronologies for Pinus tabuliformis Carr. (P) and Quercus variabilis Blume. (Q) mixed forests with different mixing ratios. In the temperate region of China, we investigated three mixing ratios: 90% P and 10% Q (P9Q1), 60% P and 40% Q (P6Q4), and 20% P and 80% Q (P2Q8). We collected tree ring samples using three tree size categories: dominant, intermediate, and suppressed trees. We explored the climate sensitivity of these trees and their drought tolerance indices-resilience (Rs), resistance (Rt), and recovery (Rc) under two drought conditions: short-term drought (1993 drought) and long-term drought (1999-2015 drought). P6Q4 made P. tabuliformis more sensitive to the Palmer drought severity index (PDSI) from the previous year than the other two ratios. The effect of the mixing ratio on drought response was insignificant under short-term drought in both tree species. Rt, Rc, and Rs of P. tabuliformis decreased with an increasing Q. variabilis:P. tabuliformis ratio in long-term drought. Rt, Rc, and Rs of Q. variabilis were the highest in P6Q4. The sensitivity of trees to PDSI varied among classes and was influenced by the mixing ratio. Dominant trees were most sensitive to PDSI in P6Q4 and P2Q8, whereas intermediate and suppressed trees were more sensitive to PDSI in P9Q1. The impact of tree size on drought tolerance indices varied according to drought type and mixing ratio. These findings showed that the mixing ratio has a confounding effect on the drought sensitivity of temperate tree species. Differences in hydrological niches allow Q. variabilis to benefit from mixing with P. tabuliformis. Mixing with optimal proportion of P. tabuliformis maximizes the drought resilience of Q. variabilis. Additionally, weakly competitive species (P. tabuliformis) do not benefit from mixed forests during prolonged water deficits. This result complements previous arguments that species mixing reduces the biological vulnerability of individuals. This study emphasizes the importance of species selection based on the biological and physiological characteristics of tree species in the afforestation of mixed forests. It highlights the critical role of species mixing ratios in the resistance of mixed forest ecosystems to climate change, which may provide a reference for sustainable forest management.