Clinical treatment strategy and follow-up of lymphoepithelioma-like carcinoma: a retrospective study.

Aim: To investigate the clinical features, diagnosis and treatment of lymphoepithelioma-like carcinoma (LELC).Materials & methods: The clinical data of 114 LELC patients were retrospectively analyzed.Results: Ninety-eight patients (86.0%) were Epstein-Barr virus-encoded small RNA (EBER) positive detected by situ hybridization. A 67.1% (51/76) patients had PD-L1 expression. The 5-year overall survival rate of EBER negative patients was 51.6% while the rate of positive patients was 84.8% (p = 0.015). The 5-year progression free survival rate of EBER negative patients was 40.2% while the rate of positive patients was 70.2% (p = 0.004).Conclusion: The progression of LELC is relatively slow and present a better prognosis. The occurrence of tumor is closely related to Epstein-Barr virus infection and PD-L1 is highly expressed in tumor cells.

Lymphoepithelioma-like carcinoma (LELC) is a rare and special malignant tumor. The characteristics of it are not clear. We collected the data of 114 LELC patients. Then we found this tumor grew slowly. Eighty six percent of patients had been infected with EBV. Through microscopic observation, we found that 67.1% of patients had PD-L1 expression in tumor tissue. These characteristics can help people predict how long LELC patients will live and choose useful treatments.

The heterogeneity of cellular metabolism in the tumour microenvironment of hepatocellular carcinoma with portal vein tumour thrombus.

Given the growing interest in the metabolic heterogeneity of hepatocellular carcinoma (HCC) and portal vein tumour thrombus (PVTT). This study comprehensively analysed the metabolic heterogeneity of HCC, PVTT, and normal liver samples using multi-omics combinations. A single-cell RNA sequencing dataset encompassing six major cell types was obtained for integrated analysis. The optimal subtypes were identified using cluster stratification and validated using spatial transcriptomics and fluorescent multiplex immunohistochemistry. Then, a combined index based meta-cluster was calculated to verify its prognostic significance using multi-omics data from public cohorts. Our study first depicted the metabolic heterogeneity landscape of non-malignant cells in HCC and PVTT at multiomics levels. The optimal subtypes interpret the metabolic characteristics of PVTT formation and development. The combined index provided effective predictions of prognosis and immunotherapy responses. Patients with a higher combined index had a relatively poor prognosis (p <0.001). We also found metabolism of polyamines was a key metabolic pathway involved in conversion of metabolic heterogeneity in HCC and PVTT, and identified ODC1 was significantly higher expressed in PVTT compared to normal tissue (p =0.03). Our findings revealed both consistency and heterogeneity in the metabolism of non-malignant cells in HCC and PVTT. The risk stratification based on cancer-associated fibroblasts and myeloid cells conduce to predict prognosis and guide treatment. This offers new directions for understanding disease development and immunotherapy responses.

Perioperative impact of liver cirrhosis on robotic liver resection for hepatocellular carcinoma: a retrospective cohort study.

BACKGROUND: The safety and efficacy of robotic liver resection (RLR) for patients with hepatocellular carcinoma (HCC) have been reported worldwide. However, the exact role of RLR in HCC patients with liver cirrhosis is not sufficiently determined. METHODS: We conducted a retrospective study on consecutive patients with cirrhosis or non-cirrhosis who received RLR for HCC from 2018 to 2023. Data on patients' demographics and perioperative outcomes were collected and analyzed. Propensity score matching (PSM) analysis was performed. Multivariate logistic regression analysis was performed to determine the risk factors of prolonged postoperative length of stay (LOS) and morbidity. RESULTS: Of the 571 patients included, 364 (64%) had cirrhosis. Among the cirrhotic patients, 48 (13%) were classified as Child-Pugh B. After PSM, the cirrhosis and non-cirrhosis group (n = 183) had similar operative time, estimated blood loss, postoperative blood transfusion, LOS, overall morbidity (p > 0.05). In addition, the intraoperative and postoperative outcomes were similar between the two groups in the subgroup analyses of patients with tumor size ≥ 5 cm, major hepatectomy, and high/expert IWATE difficulty grade. However, patients with Child-Pugh B cirrhosis had longer LOS and more overall morbidity than that of Child-Pugh A. Child-Pugh B cirrhosis, ASA score > 2, longer operative time, and multiple tumors were risk factors of prolonged LOS or morbidity in patients with cirrhosis. CONCLUSION: The presence of Child-Pugh A cirrhosis didn't significantly influence the difficulty and perioperative outcomes of RLR for selected patients with HCC. However, even in high-volume center, Child-Pugh B cirrhosis was a risk factor for poor postoperative outcomes.

The spontaneous activities of the multiple demand network are related to individual differences in indirect replies comprehension.

This study aims to investigate the brain networks engaged in the comprehension of indirect language, as well as the individual difference in this capacity. Specially, we aim to determine whether the difference is solely influenced by the difference in individuals' default network (DN)/language network or whether it also relies on the networks associated with processing of complex cognitive tasks, particularly the multiple demand network (MDN). Conversational indirectness scale (CIS) scores in the interpretation dimension were used as a behavioral indicator of the indirect comprehension tendency. Reading time difference between indirect replies and direct replies collected through a self-paced reading experiment was deemed as a behavioral indicator of comprehension speed of indirect replies comprehension. The two behavioral indicators were combined with resting-state functional magnetic resonance imaging (rs-fMRI). The behaviour-rfMRI analysis showed that ALFF value of right SPL and the functional connectivity (FC) between the right SPL and right IPL/SMA/ITG/Precuneus/bilateral IFG were positively correlated with the interpretation dimension of CIS scores. In addition, the ALFF value of right fusiform gyrus, the FC between the right fusiform gyrus and right precuneus, and the FCs between right SPL and right IPL/Precuneus/IFG were negatively correlated with indirect replies comprehension speed. Overlapping of these regions with large-scale brain network revealed that the right SPL was mainly located in the MDN, and the right fusiform gyrus was mainly located in the language network. Additionally, the areas showing functional connectivity with these regions were primarily located in the MDN, with a smaller subset located in the DN. Our findings suggest that the ability of individuals to actively and rapidly acquire indirect meaning relies not only on the support of the DN and the language network, but also requires collective support from the MDN.

Prognostic value of peripheral blood neutrophil/lymphocyte ratio, platelet/lymphocyte ratio, pan-immune-inflammation value and systemic immune-inflammation index for the efficacy of immunotherapy in patients with advanced gastric cancer.

Aim: The study aimed to assess the value of pretreatment peripheral blood neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), pan-immune-inflammation value (PIV) and systemic immune-inflammation index (SII) for predicting immunotherapy prognosis and efficacy in advanced gastric cancer (GC). Methods: A total of 84 advanced GC patients received immunotherapy were retrospectively collected. The optimal cut-off values were determined by receiver operating characteristic curves. The univariate and multivariate analysis investigated the effects of NLR, PLR, PIV and SII on patients prognosis. Results: NLR, PLR, PIV and SII had predictive value of efficacy. NLR ≥3.65 was an independent risk factor for worse outcomes. Conclusion: NLR, PLR, PIV and SII have predictive value of efficacy and NLR ≥3.65 suggests a poor prognosis following immunotherapy in advanced GC.

Immunotherapy can make gastric cancer patients live longer. However, not all patients live longer. We need simple, inexpensive and effective indicators to find patients who can live longer with immunotherapy. Routine blood test is common in our daily lives. Previous studies reported that some indicators in routine blood test can predict the prognosis and efficacy of surgery in gastric cancer patients. But it is not clear in immunotherapy for advanced gastric cancer patients. In our trial, we found that some indicators in routine blood test can help predict the effect of immunotherapy in patients with advanced gastric cancer and screen which patients will live longer with immunotherapy.

Prostate cancer-associated transcript 6 (PCAT6) promotes epithelial-mesenchymal transition and stemness and worsens prognosis in patients with colorectal cancer.

Approximately 20% of colorectal cancer (CRC) patients are first diagnosed with metastatic colorectal cancer (mCRC) because they develop symptoms at an advanced stage. Despite advancements in treatment, patients with metastatic disease still experience inferior survival rates. Our objective is to investigate the association between long noncoding RNAs (lncRNAs) and prognosis and to explore their role in mCRC. In this study, we find that elevated expression of PCAT6 is independently linked to unfavourable survival outcomes in The Cancer Genome Atlas (TCGA) data, and this finding is further confirmed in CRC samples obtained from Fudan University Shanghai Cancer Center. Cell lines and xenograft mouse models are used to examine the impact of PCAT6 on tumor metastasis. Knockdown of PCAT6 is observed to impede the metastatic phenotype of CRC, as evidenced by functional assays, demonstrating the suppression of epithelial-mesenchymal transition (EMT) and stemness. Our findings show the significance of PCAT6 in mCRC and its potential use as a prognostic biomarker.

RNA-seq analysis reveals changes in mRNA expression during development in Daphnia mitsukuri.

Temporal transcriptional variation is a major contributor to functional evolution and the developmental process. Parthenogenetic water fleas of the genus Daphnia (Cladocera) provide an ideal model to characterize gene expression patterns across distinct developmental stages. Herein, we report RNA-seq data for female Daphnia mitsukuri at three developmental stages: the embryo, juvenile (three timepoints) and adult. Comparisons of gene expression patterns among these three developmental stages and weighted gene co-expression network analysis based on expression data across developmental stages identified sets of genes underpinning each of the developmental stages of D. mitsukuri. Specifically, highly expressed genes (HEGs) at the embryonic developmental stage were associated with cell proliferation, ensuring the necessary foundation for subsequent development; HEGs at the juvenile stages were associated with chemosensory perception, visual perception and neurotransmission, allowing individuals to enhance detection of potential environmental risks; HEGs at the adult stage were associated with antioxidative defensive systems, enabling adults to mount an efficient response to perceived environmental risks. Additionally, we found a significant overlap between expanded gene families of Daphnia species and HEGs at the juvenile stages, and these genes were associated with visual perception and neurotransmission. Our work provides a resource of developmental transcriptomes, and comparative analyses that characterize gene expression dynamics throughout development of Daphnia.

Study on the predictive value of pretreatment peripheral blood inflammatory markers regarding immunotherapy in patients with inoperable advanced or locally advanced oesophageal squamous cell carcinoma.

OBJECTIVE: To explore the effects of pretreatment peripheral blood panimmune-inflammation value (PIV), systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) on the efficacy and prognostic value of immunotherapy in patients with inoperable advanced or locally advanced oesophageal squamous cell carcinoma (ESCC). METHODS: Clinical data of 107 inoperable advanced or locally advanced ESCC patients were retrospectively analysed between May 2019 and August 2023, the receiver operating characteristic curves (ROCs) of PIV, SII, NLR, and PLR in patients prior to immunotherapy were plotted, and their optimal cutoff values were determined. The risk factors were determined by univariate and multivariate analyses in groups based on the optimal cut-off values. RESULTS: Peripheral blood PIV, SII and PLR before immunotherapy had predictive value for the optimal efficacy of immunotherapy in patients with inoperable advanced or locally advanced ESCC; patients with PIV ≥415.885, SII ≥834.295 and NLR ≥3.740 had a low objective response rate (ORR), disease control rate (DCR), a short progression-free survival (PFS) and overall survival (OS) after immunotherapy (p < 0.05). Patient tumour stage, distant lymph node metastasis, lung metastasis, liver metastasis, PIV, SII, and NLR were risk factors affecting PFS and OS (p < 0.05). Tumour stage and SII were independent risk factors affecting PFS and OS (p < 0.05). CONCLUSION: In patients with inoperable advanced or locally advanced ESCC, peripheral blood PIV, SII, and NLR have predictive value for immunotherapy outcome, SII is an independent risk factor affecting the survival prognosis, and SII ≥834.295 suggests a poor prognosis from immunotherapy.

MiR-9-enriched mesenchymal stem cells derived exosomes prevent cystitis-induced bladder pain via suppressing TLR4/NLRP3 pathway in interstitial cystitis mice.

BACKGROUND: Inflammatory response of central nervous system is an important component mechanism in the bladder pain of interstitial cystitis/bladder pain syndrome (IC/BPS). Exosomes transfer with microRNAs (miRNA) from mesenchymal stem cell (MSCs) might inhibit inflammatory injury of the central nervous system. Herein, the purpose of our study was to explore the therapeutic effects by which extracellular vesicles （EVs） derived from miR-9-edreched MSCs in IC/BPS and further investigate the potential mechanism to attenuate neuroinflammation. METHODS: On the basis of IC/BPS model, we used various techniques including bioinformatics, cell and molecular biology, and experimental zoology, to elucidate the role and molecular mechanism of TLR4 in regulating the activation of NLRP3 inflammasome in bladder pain of IC/BPS, and investigate the mechanism and feasibility of MSC-EVs enriched with miR-9 in the treatment of bladder pain of IC/BPS. RESULTS: The inflammatory responses in systemic and central derived by TLR4 activation were closely related to the cystitis-induced pelvic/bladder nociception in IC/BPS model. Intrathecal injection of miR-9-enreched MSCs derived exosomes were effective in the treatment of cystitis-induced pelvic/bladder nociception by inhibiting TLR4/NF-κb/NLRP3 signal pathway in central nervous system of IC/BPS mice. CONCLUSIONS: This study demonstrated that miR-9-enreched MSCs derived exosomes alleviate neuroinflammaiton and cystitis-induced bladder pain by inhibiting TLR4/NF-κb/NLRP3 signal pathway in interstitial cystitis mice, which is a promising strategy against cystitis-induced bladder pain.

Free light-shape focusing in extreme-ultraviolet radiation with self-evolutionary photon sieves.

Extreme-ultraviolet (EUV) radiation is a promising tool, not only for probing microscopic activities but also for processing nanoscale structures and performing high-resolution imaging. In this study, we demonstrate an innovative method to generate free light-shape focusing with self-evolutionary photon sieves under a single-shot coherent EUV laser; this includes vortex focus shaping, array focusing, and structured-light shaping. The results demonstrate that self-evolutionary photon sieves, consisting of a large number of specific pinholes fabricated on a piece of Si3N4 membrane, are capable of freely regulating an EUV light field, for which high-performance focusing elements are extremely lacking, let alone free light-shape focusing. Our proposed versatile photon sieves are a key breakthrough in focusing technology in the EUV region and pave the way for high-resolution soft X-ray microscopy, spectroscopy in materials science, shorter lithography, and attosecond metrology in next-generation synchrotron radiation and free-electron lasers.

A single carbon nanotube-entangled high-performance buckypaper with tunable fracture mode.

It is well known that the traditional buckypaper (BP) is composed of a certain number of short carbon nanotubes (CNTs) intertwined with each other and sliding always happens when the BP is under tensile and impact loading, which results in inferior mechanical properties compared to single CNTs. In this work, a highly-entangled single-wire BP (SWBP) structure is constructed by a modified self-avoiding random walk approach. The in-plane mechanical properties and impacting behaviors of the SWBPs with different entanglement degrees and interface frictions are systematically investigated via newly developed coarse-grained molecular dynamics (CGMD) simulation. A coarse-grained method can effectively reflect the inter-tube van der Waals (vdW) interactions and the mechanical behaviors of CNTs, including tension, bending and adhesion. In this work, from the tensile simulations of the SWBP, the results showed that the self-locking mechanism between entangled CNTs could significantly enhance the tensile resistance of the film. Besides, the mechanical properties of the SWBP are highly dependent on the entanglement degree and the interface friction between CNTs. Furthermore, two distinct fracture modes, ductile fracture and brittle fracture, are revealed, which can be efficiently controlled by changing the related friction between CNTs. From the impacting simulations, it is found that the impacting performance can be effectively tuned by adjusting the entanglement degree of the film. In addition, the kinetic energy of the projectile could be rapidly dissipated through the stretching and bending of CNTs in the SWBP. This work provides an in-depth understanding of the effect of interface friction and entanglement degree on the mechanical properties of the buckypaper and provides a reference for the preparation of strong CNT-based micromaterials.

Short-term and long-term outcomes after robotic versus open hepatectomy in patients with large hepatocellular carcinoma: a multicenter study.

BACKGROUND: Robotic hepatectomy (RH) is currently widely accepted and it is associated with some benefits when compared to open hepatectomy (OH). However, whether such benefits can still be achieved for patients with large hepatocellular carcinoma (HCC) remain unclear. This study aimed to evaluate the short-term and long-term outcomes of patients undergoing RH or OH. METHODS: Perioperative and survival data from patients with large HCC who underwent RH or OH between January 2010 and December 2020 were collected from eight centres. Propensity score matching (PSM) was performed to minimise potential biases. RESULTS: Using predefined inclusion criteria, 797 patients who underwent OH and 309 patients who underwent RH were enroled in this study. After PSM, 280 patients in the robotic group had shorter operative time (median 181 vs. 201 min, P <0.001), lower estimated blood loss (median 200 vs. 400 ml, P <0.001), and shorter postoperative length of stay (median 6 vs. 9 days, P <0.001) than 465 patients in the open group. There were no significant differences between the two groups in overall survival and recurrence-free survival. Cox analysis showed AFP greater than 400 ng/ml, tumour size greater than 10 cm, and microvascular invasion were independent risk factors for overall survival and recurrence-free survival. After PSM, subgroup analysis showed that patients with a huge HCC (diameter >10 cm) who underwent RH had significantly lower estimated blood loss (median 200.0 vs. 500.0 min, P <0.001), and shorter length of stay (median 7 vs. 10 days, P <0.001) than those who underwent OH. CONCLUSION: Safety and feasibility of RH and OH for patients with large HCC were comparable. RH resulted in similar long-term survival outcomes as OH.

Pathologic Complete Response After Gastric Artery Chemoembolization Combined With Tislelizumab for Neoadjuvant Therapy of Locally Advanced Gastric Cancer: A Case Report.

Gastric cancer is the most common type of gastrointestinal cancer in China which about 80% of patients are locally advanced or advanced when diagnosed. Surgery along brings high recurrence rate for locally advanced gastric cancer (LAGC), and neoadjuvant therapies are needed. The use of programmed cell death-1 (PD-1)/programmed death-ligand 1 inhibitor nowadays improved the disease-free survival for LAGC, however, only <35% of patients achieved pathologic complete response (pCR) after neoadjuvant therapy nowadays. Therefore, new regimens are needed to be investigated. Gastric artery chemoembolization is applied to metastasis gastric cancer and researches showed interventional therapy can enhance the antitumor effect of PD-1 inhibitor. Here, for the first time, we combined gastric artery chemoembolization with tislelizumab (a PD-1 inhibitor) for neoadjuvant therapy of a patient with LAGC. The patient achieved pCR after a D2 resection and tumor regression grade score was 1. After surgery, the patient received tislelizumab 200 mg per 3 weeks, and showed no sign of recurrence after 6 months of follow-up. The study indicated the use of tislelizumab and gastric artery chemoembolization for neoadjuvant therapy may bring a better pCR rate and prognosis of LAGC.

Outcomes of Robotic Versus Laparoscopic Pancreatoduodenectomy Following Learning Curves of Surgeons: A Multicenter Study on 2255 Patients.

OBJECTIVE: This study aimed to compare robotic pancreatoduodenectomy (RPD) with laparoscopic pancreatoduodenectomy (LPD) in operative and oncologic outcomes. BACKGROUND: Previous studies comparing RPD with LPD have only been carried out in small, single-center studies with variable quality. METHODS: Consecutive patients from nine centers in China who underwent RPD or LPD between 2015 and 2022 were included. A 1:1 propensity score matching (PSM) was used to minimize bias. RESULTS: Of the 2,255 patients, 1158 underwent RPD and 1097 underwent LPD. Following PSM, 1006 patients were enrolled in each group. The RPD group had significantly shorter operative time (270.0 vs. 305.0 minutes, P<0.001), lower intraoperative blood transfusion rate (5.9% vs. 12.0%, P<0.001), lower conversion rate (3.8% vs. 6.7%, P=0.004), and higher vascular reconstruction rate (7.9% vs. 5.6%, P=0.040) than the LPD group. There were no significant differences in estimated blood loss, postoperative length of stay, perioperative complications, and 90-day mortality. Patients who underwent vascular reconstruction had similar outcomes between the two groups, although they had significantly lower estimated blood loss (300.0 vs. 360.0 mL; P=0.021) in the RPD group. Subgroup analysis on pancreatic ductal adenocarcinoma (PDAC) found no significant differences between the two groups in median recurrence-free survival (14.3 vs. 15.3 mo, P=0.573) and overall survival (24.1 vs. 23.7 mo, P=0.710). CONCLUSIONS: In experienced hands, both RPD and LPD are safe and feasible procedures with similar surgical outcomes. RPD had the perioperative advantage over LPD especially in vascular reconstruction. For PDAC patients, RPD resulted in similar oncological and survival outcomes as LPD.

RNASEH1-AS1 induced by H3K27ac stabilizes ANXA2 mRNA to promote the progression of colorectal cancer through recruiting BUD13.

Colorectal cancer (CRC) is a malignant tumor with high morbidity and mortality. It is well-accepted that dysregulated lncRNAs are closely related to the development of CRC. In this study, the function and mechanism of RNASEH1-AS1 in CRC were investigated. RT-qPCR and western blot detected the expression of targeted genes in tissues and cells. CCK-8, clone formation, wound healing assay, and Transwell were applied to evaluate CRC cell malignant behaviors. ChIP, RIP, and RNA pull-down validated interactions among RNASEH1-AS1, H3K27ac, CBP, BUD13, and ANXA2. Nucleoplasmic separation and FISH assay determined the location of RNASEH1-AS1 in CRC cells. IHC assay was used to detect Ki-67 expression in tumor tissues from mice. RNASEH1-AS1 was highly expressed in CRC tumor tissues and cells. RNASEH1-AS1 silencing effectively suppressed the viability, proliferation, migration, and invasion of CRC cells. In addition, CBP-mediated H3K27ac increased RNASEH1-AS1 expression in CRC cells and RNASEH1-AS1 could elevate ANXA2 expression through recruiting BUD13. Furthermore, RNASEH1-AS1 silencing inhibited malignant phenotypes of CRC cells and tumor growth in mice through decreasing ANXA2 expression and inactivating the Wnt/ß-catenin pathway. Our results revealed that RNASEH1-AS1 induced by CBP-mediated H3K27ac activated Wnt/ß-catenin pathway to promote CRC progression through recruiting BUD13 to stabilize ANXA2 mRNA, which provides substantial evidence of RNASEH1-AS1 in CRC. Targeting RNASEH1-AS1 might alleviate CRC progression.

A Fresh Perspective on the Impact of ZnTiO3 Coupling on the Microstructure and Photocatalytic Properties of TiO2 Fabricated at Varied Temperatures.

ZnTiO3/TiO2 composite photocatalysts were synthesized via the sol-gel technique, and the impact of varying heat treatment temperatures (470, 570, 670 °C) on their crystalline arrangement, surface morphology, elemental composition, chemical state, specific surface area, optical characteristics, and photocatalytic efficacy was systematically investigated. The outcomes revealed that, as the temperature ascends, pure TiO2 undergoes a transition from anatase to rutile, ultimately forming a hybrid crystal structure at 670 °C. The incorporation of ZnTiO3 engenders a reduction in the TiO2 grain dimensions and retards the anatase-to-rutile phase transition. Consequently, the specimens manifest a composite constitution of anatase and ZnTiO3. In contrast, for pure TiO2, the specimen subjected to 670 °C annealing demonstrates superior photocatalytic performance due to its amalgamated crystal arrangement. The degradation efficacy of methylene blue (MB) aqueous solution attains 91% within a 60-min interval, with a calculated first-order reaction rate constant of 0.039 min-1. Interestingly, the ZnTiO3/TiO2 composite photocatalysts exhibit diminished photocatalytic activity in comparison to pristine TiO2 across all three temperature variations. Elucidation of the photocatalytic mechanism underscores that ZnTiO3 coupling augments the generation of photogenerated charge carriers. Nonetheless, concurrently, it undermines the crystalline integrity of the composite, yielding an excess of amorphous constituents that impede the mobility of photoinduced carriers. This dual effect also fosters escalated recombination of photogenerated charges, culminating in diminished quantum efficiency and reduced photocatalytic performance.

Climate has contributed to population diversification of Daphnia galeata across Eurasia.

Climate is a fundamental abiotic factor that plays a key role in driving the evolution, distribution and population diversification of species. However, there have been few investigations of genomic signatures of adaptation to local climatic conditions in cladocerans. Here, we have provided the first high-quality chromosome-level genome assembly (~143 Mb, scaffold N50 12.6 Mb) of the waterflea, Daphnia galeata, and investigated genomic variation in 22 populations from Central Europe and Eastern China. Our ecological-niche models suggested that the historic distribution of D. galeata in Eurasia was significantly affected by Quaternary climate fluctuations. We detected pronounced genomic and morphometric divergences between European and Chinese D. galeata populations. Such divergences could be partly explained by genomic signatures of thermal adaptation to distinct climate regimes: a set of candidate single-nucleotide polymorphisms (SNPs) potentially associated with climate were detected. These SNPs were in genes significantly enriched in the Gene ontology terms "determination of adult lifespan" and "translation repressor activity", and especially, mthl5 and SOD1 involved in the IIS pathway, and EIF4EBP2 involved in the target of the rapamycin signalling pathway. Our study indicates that certain alleles might be associated with particular temperature regimes, playing a functional role in shaping the population structure of D. galeata at a large geographical scale. These results highlight the potential role of molecular variation in the response to climate variation, in the context of global climate change.