Phase Reentrances and Solid Deformations in Confined Colloidal Crystals.

A simple geometric constraint often leads to novel, complex crystalline phases distinct from the bulk. Using thin-film charge colloidal crystals, a model system with tunable interactions, we study the effects of geometric constraints. Through a combination of experiments and simulations, we systematically explore phase reentrances and solid deformation modes concerning geometrical confinement strength, identifying two distinct categories of phase reentrances below a characteristic layer number, N_{c}: one for bcc bulk-stable and another for fcc bulk-stable systems. We further verify that the dominant thermodynamic origin is the nonmonotonic dependence of solids' free energy on the degree of spatial confinement. Moreover, we discover transitions in solid deformation modes between interface-energy and bulk-energy dominance: below a specific layer number, N_{k}, geometric constraints generate unique soft deformation modes adaptive to confinement. These findings on the N-dependent thermodynamic and kinetic behaviors offer fresh insights into understanding and manipulating thin-film crystal structures.

Characterization of the Estrogen Response Helps to Predict Prognosis and Identify Potential Therapeutic Targets in Cholangiocarcinoma.

Cholangiocarcinoma (CCA) is an aggressive malignancy originating from the epithelium of the bile duct. The prognosis of patients is poor regardless of radical resection and chemoradiotherapy. The current classification and prognostic model of CCA are unable to satisfy the requirements for predicting the clinical outcome and exploring therapeutic targets. Estrogen signaling is involved in diverse cancer types, and it has long been established that CCA could be regulated by estrogen. In our study, estrogen response was identified to be significantly and stably correlated with poor prognosis in CCA. Employing several algorithms, CCA was classified into ES cluster A and B. ES cluster B was mainly composed of patients with fluke infection and overlapped with CCA cluster 1/2, and ES cluster A was mainly composed of patients without fluke infection and overlapped with CCA cluster 3/4. COMT and HSD17B1 were identified to be responsible for the differential estrogen response between ES clusters A and B, and the estrogen response may be correlated with the differentiation and cancer stemness of CCA at the single-cell level. Complement activation and the expression of C3 and C5, which are mainly expressed by CCA cells, were significantly downregulated in ES cluster B. An estrogen response risk score (ESRS) model was constructed to predict the prognosis of CCA, followed by a nomogram integrating ESRS and clinical features. Finally, altered pathways, applicable drugs and sensitivity to chemical drugs were analyzed specific to the estrogen response. In summary, our results provide insights into the role of the estrogen response in CCA progression as well as applicable drugs and potential therapeutic targets in estrogen metabolism, the complement system and ESRS-related pathways.

[Artificial intelligence-based fluorescence method versus traditional flow cytometry in detection of sperm DNA fragmentation index].

OBJECTIVE: To compare the result of the artificial intelligence (AI) recognition-based fluorescence method and that of traditional flow cytometry in the examination of the sperm DNA fragmentation index (DFI) and assess the reliability of the AI-based fluorescence detection. METHODS: Using flow cytometry and the AI-based fluorescence method, we examined the sperm DFI in the semen samples collected from 338 outpatients. We analyzed the correlation between the results and compared the positive rates detected by the two methods. We repeated the AI-based fluorescence method twice for each semen sample to observe its technical stability in the detection of sperm DFI. RESULTS: The result of flow cytometry was well correlated with that of the AI-based fluorescence method in the detection of sperm DFI (R2 = 0.7131), but poorly correlated for low-concentration, sticky semen and some other extreme samples (R2 = 0.2065). No statistically significant difference was found between the two methods in the positive rate of detection. The AI-based fluorescence method exhibited an excellent technical stability (R2 = 0.9671). CONCLUSION: The AI-based fluorescence method has an excellent technical stability in the detection of sperm DFI and the result is not significantly different from that of traditional flow cytometry.

Coupling and Coordinating Relationship between Agricultural Eco-Efficiency and Food Security System in China.

Carbon peaking, carbon neutrality goals and food security are the basis of sustainable development, and exploring the coordination relationship between China's agricultural eco-efficiency and food security system has a major significance for the implementation of relevant strategies. This paper is based on collaboration research on the synergistic relationship between agricultural eco-efficiency and food security systems using methods such as entropy weight method, coupling coordination model, spatial autocorrelation model, etc., revealing the evolution-driven mechanism of the coupling coordination degree. This study found that a higher level of coupling coordination always occurs in those areas with high standard farmland construction and large grain production scale, while economically developed areas appear to have a lower overall coordination level limited by endowment constraints and division of labor in development planning. It shows a positive spatial correlation in terms of geographical distance between agricultural eco-efficiency and food security, and the positive spillover effect gradually increases but is not strong overall. China should combine regional resource endowment and development planning, pay attention to the improvement of large-scale and standardized agricultural production, continue to strengthen the development of clean agricultural production, and achieve food security under the constraints of the carbon peaking and carbon neutrality goals.

Extracellular Matrix Characterization in Gastric Cancer Helps to Predict Prognosis and Chemotherapy Response.

The extracellular matrix (ECM) plays a central role in the formation of the tumor microenvironment. The deposition of the ECM is associated with poor prognosis in a variety of tumors. Aberrant ECM deposition could undermine the effect of chemotherapy and immunotherapy. However, there is no systematic analysis on the relationship between the ECM and prognosis or chemotherapy effect. In the present study, we applied the gene set variation analysis (GSVA) algorithm to score 2199 canonical pathways in 2125 cases of probe or sequencing data and identified the core matrisome as the driving factor in gastric cancer progression. We classified gastric cancer samples into three clusters according to the composition of the ECM and evaluated clinical and multi-omics characterization of ECM phenotypes. The ECM score was evaluated by GSVA score of core matrisome and a higher ECM score predicted poor prognosis of gastric cancer [Hazard Ratio (HR), 2.084; p-value < 2 × 10-16]. In The Cancer Genome Atlas (TCGA) cohort and KUGH, YUSH, and KUCM cohorts, we verified that patients with a low ECM score could benefit from chemotherapy. By contrast, patients with a high ECM score did not achieve satisfactory response from chemotherapy. Determining the characteristics of the ECM microenvironment might help to predict the prognosis and chemotherapy response of patients with gastric cancer, and help to resolve the enigma of chemoresistance acquisition, as well as providing inspiration to develop combination therapy.

Revealing thermally-activated nucleation pathways of diffusionless solid-to-solid transition.

Solid-to-solid transitions usually occur via athermal nucleation pathways on pre-existing defects due to immense strain energy. However, the extent to which athermal nucleation persists under low strain energy comparable to the interface energy, and whether thermally-activated nucleation is still possible are mostly unknown. To address these questions, the microscopic observation of the transformation dynamics is a prerequisite. Using a charged colloidal system that allows the triggering of an fcc-to-bcc transition while enabling in-situ single-particle-level observation, we experimentally find both athermal and thermally-activated pathways controlled by the softness of the parent crystal. In particular, we reveal three new transition pathways: ingrain homogeneous nucleation driven by spontaneous dislocation generation, heterogeneous nucleation assisted by premelting grain boundaries, and wall-assisted growth. Our findings reveal the physical principles behind the system-dependent pathway selection and shed light on the control of solid-to-solid transitions through the parent phase's softness and defect landscape.

Fast crystal growth at ultra-low temperatures.

It is believed that the slow liquid diffusion and geometric frustration brought by a rapid, deep quench inhibit fast crystallization and promote vitrification. Here we report fast crystal growth in charged colloidal systems under deep supercooling, where liquid diffusion is extremely low. By combining experiments and simulations, we show that this process occurs via wall-induced barrierless ordering consisting of two coupled steps: the step-like advancement of the rough interface that disintegrates frustration, followed by defect repairing inside the newly formed solid phase. The former is a diffusionless collective process, whereas the latter controls crystal quality. We further show that the intrinsic mechanical instability of a disordered glassy state subject to the crystal growth front allows for domino-like fast crystal growth even at ultra-low temperatures. These findings contribute to a deeper understanding of fast crystal growth and may be useful for applications related to vitrification prevention and crystal-quality control.

Revealing roles of competing local structural orderings in crystallization of polymorphic systems.

Most systems have more than two stable crystalline states in the phase diagram, which is known as polymorphism. Crystallization in such a system is often under strong influence of competing orderings linked to those crystals. However, how such competition affects crystal nucleation and ordering toward the final crystalline state is largely unknown. This is primarily because the competition takes place locally and thus is masked by large positional fluctuations. We develop a unique method to correctly identify local symmetries by removing their distortions due to positional fluctuations. This allows us to experimentally access the spatiotemporal fluctuations of local symmetries at a single-particle level in crystallization of a charged colloidal system near the body-centered cubic-face-centered cubic border. Thus, we successfully reveal the crucial roles of competing ordering in the initial selection of polymorphs and the final grain boundary motion toward the most stable state from a microscopic perspective.

Erratum: Cenicriviroc ameliorates the severity of graft-versus host disease through inhibition of CCR5 in a rat model of liver transplantation.

[This corrects the article on p. 3438 in vol. 11, PMID: 31312356.].

Cenicriviroc ameliorates the severity of graft-versus-host disease through inhibition of CCR5 in a rat model of liver transplantation.

Acute graft-versus-host disease (aGVHD) is one of the major complications after liver transplantation (LTx), which is induced by over-activation of T helper lymphocytes. Cenicriviroc (CVC) exerts its anti-inflammatory effect through inhibition of C-C chemokine receptor 5 (CCR5). However, whether CVC ameliorates aGVHD after liver transplantation remains unknown. In the present study, a rat aGVHD liver transplantation model (LTx-aGVHD) was constructed. CVC was intravenously injected from day 7 to day 14 after LTx. Liver and intestine samples were harvested to evaluate GVHD severity. Peripheral blood mononuclear cells (PBMCs) were collected and CCR5 antibodies were prepared to further explore the molecular mechanism in vitro. CVC significantly decreased the severity of GVHD associated skin and intestine injury. Quality of life of the LTx-GVHD rats was improved after CVC treatment. Flow cytometry further confirmed diminished peripheral donor-derived Th cells after CVC treatment. Molecularly, CVC treatment showed similar anti-inflammatory effects to CCR5 antibody injection. The level of CCR5, C-C motif chemokine ligand 5 (CCL5), and pro-inflammatory cytokines in the liver and intestines were inhibited after CVC treatment. Thus, CVC deactivated Th lymphocytes and decreased the severity of LTx-aGVHD through inhibition of CCR5.

CCDC26 knockdown enhances resistance of gastrointestinal stromal tumor cells to imatinib by interacting with c-KIT.

Accumulating evidence indicates that long noncoding RNAs (lncRNAs) are involved in diseases such as cancer. However, little is known about the role of lncRNAs in gastrointestinal stromal tumors (GIST). In the present study, we explored the biological function of the lncRNA coiled-coil domain-containing 26 (CCDC26) in imatinib resistance of GIST. We found that human GIST-882 cells with lower CCDC26 expression were less sensitive to imatinib compared with GIST-T1 cells with higher CCDC26 expression. CCDC26 expression decreased in a time-dependent manner in the presence of imatinib. Moreover, small interfering RNA (siRNA) knockdown of CCDC26 increased GIST cell sensitivity to imatinib. The RNA pull-down experiment showed that CCDC26 can interact with c-KIT and that CCDC26 knockdown can upregulate c-KIT expression. We also found that inhibiting c-KIT induced resistance to imatinib. Lastly, we proved that inhibiting c-KIT can reverse CCDC26 knockdown-mediated imatinib resistance in GIST. We suggest that CCDC26 knockdown can induce imatinib resistance in GIST cells by downregulating c-KIT expression. Our results provide a novel insight into imatinib resistance in GIST.

DUSP4 promotes doxorubicin resistance in gastric cancer through epithelial-mesenchymal transition.

Chemoresistance limits treatment efficacy in gastric cancer and doxorubicin resistance is common in gastric cancer cells. Dual specificity phosphatase 4 (DUSP4) has been associated with tumor progression. This study aimed to investigate the mechanism of DUSP4 regulating doxorubicin resistance in gastric cancer cells. Cell Counting Kit-8 (CCK-8) and 5-ethynyl-2'-deoxyuridine (EdU) incorporation assay were used to measure cell viability and proliferation in gastric cancer cells treated with doxorubicin. The expression of DUSP4, E-cadherin and Vimentin protein was detected by Western blotting. Overexpression of DUSP4 was more resistant to doxorubicin in gastric cancer cells. Knockdown of DUSP4 increased the sensitivity of gastric cancer cells to doxorubicin. Moreover, up-regulation of DUSP4 promoted the Epithelial-Mesenchymal Transition (EMT) in gastric cancer cells, but blocking the EMT using a Twist siRNA increased the sensitivity of gastric cancer cells to doxorubicin and confirmed the EMT was involved in DUSP4-mediated doxorubicin resistance. These findings demonstrated that DUSP4 could enhance doxorubicin resistance by promoting EMT in gastric cancer cells.

Association of human cytomegalovirus viremia with human leukocyte antigens in liver transplantation recipients.

Human cytomegalovirus (HCMV) reactivation is a common complication after liver transplantation (LT). Here, we investigated whether human leukocyte antigen (HLA)-matching was related to HCMV infection and subsequent graft failure after LT for hepatitis B virus  cirrhosis. This retrospective study reviewed 91 LT recipients. All the patients were grouped according to HLA-A, HLA-B, and HLA-DR locus matching. Clinical data were collected, including complete HLA-typing, HCMV viremia, graft failure, and the time of HCMV viremia. HLA typing was performed using a sequence-specific primer-polymerase chain reaction  kit. HCMV was detected by pp65 antigenemia using a commercial kit. The incidence of HCMV infection post-LT was 81.32%. Graft failure was observed in 16 of 91 (17.6%) patients during the 4-year study. The incidence of HCMV viremia was 100% (5/5), 91.4% (32/35), and 72.5% (37/51) in HLA-A two locus, one locus, and zero locus compatibility, respectively. Nevertheless, the degree of the HLA-A, HLA-B, or HLA-DR match did not influence the time of HCMV viremia, graft failure, or the time of graft failure after a diagnosis of HCMV viremia (all P > 0.05). An interesting discovery was that the risk of HCMV viremia tended to be higher in patients with better HLA-A compatibility. Graft failure, time of HCMV viremia, and graft failure after a diagnosis of HCMV viremia appear to be independent of HLA allele compatibility.

[The study on high-resolution HLA and human cytomegalovirus (HCMV) viremia in bone marrow transplantation recipients].

OBJECTIVE: To study the correlation between high-resolution HLA-A * 1101, HLA-A * 0201, HLA-A * 2402, HLA-B * 4001, HLA-DRB1 * 0901 with HCMV pp65 antigenemia after bone marrow transplantation (BMT) in China. METHODS: 48 recipients doing BMT during 2009. 2-2010. 10 were selected in my hospital; HCMV pp65 was detected by ELISA or immunohistochemical methods. The frequency of HLA-A * 1101, HLA-A * 0201, HLA-A * 2402, HLA-B * 4001, HLA-DRB1 * 0901 alleles were determined by Polymerase chain reaction-sequence based typing (PCR - SBT). RESULTS: (1) The BMT recipients were HCMV pp65 antigenic positive(100%); (2) The positive rate of HLA-A * 1101, HLA-A * 0201, HLA-A * 2402, HLA-B * 4001 showed no obvious difference between 12 lower antigenemia group and 36 higher antigenemia group, the positive rate: HLA-A * 1101 were 33.3% (8/24) and 20.8% (15/72), HLA-A * 0201 were 4.2% (1/24) and 13.9% (10/72), HLA-A * 2402 were 12.5% (3/24) and 19.4% (14/72), HLA-B* 4001 were 16.7% (4/24) and 12.5% (9/72); (3) HLA-DRB1 * 0901 positive rate in higher antigenemia group was higher than the lower (P = 0.048), the positive rate were 4.2% (1/24) and 19.4% (14/72); (4) HLA-DRB1 * 0901 recipients were higher pp65 antigenemia than HLA-A * 2402 recipients (P = 0.007) and HLA-A * 1101 recipients (P = 0.028), HLA-A * 0201 recipients were higher pp65 antigenemia than HLA-A * 2402 (P = 0.02), the pp65 antigenemia showed no obvious difference among the rest of high-resolution HLA groups (P > 0.05). CONCLUSION: HLA-DRB1 * 0901 alleles might be correlated with BMT recipients happened higher pp65 antigenemia, HLA-A * 2402 alleles might be correlated with BMT recipients happened lower pp65 antigenemia.