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Mitochondrion-lysosome interactions have garnered significant attention in recent research. Numerous studies have shown that mitochondrion-lysosome interactions, including mitochondrion-lysosome contact (MLC) and mitophagy, are involved in various biological processes and pathological conditions. Single fluorescent probes are termed a pivotal chemical tool in unraveling the intricate spatiotemporal interorganelle interplay in live cells. However, current chemical tools are insufficient to deeply understand mitochondrion-lysosome dynamic interactions and related diseases, Moreover, the rational design of mitochondrion-lysosome dual-targeting fluorescent probes is intractable. Herein, we designed and synthesized a pH-sensitive fluorescent probe called INSA , which could simultaneously light up mitochondria (red emission) and lysosomes (green emission) for their internal pH differences. Employing INSA , we successfully recorded long-term dynamic interactions between lysosomes and mitochondria. More importantly, the increasing mitochondrion-lysosome interactions in ferroptotic cells were also revealed by INSA . Further, we observed pH variations in mitochondria and lysosomes during ferroptosis for the first time. In brief, this work not only introduced a pH-sensitive fluorescent probe INSA for the disclosure of the mitochondrion-lysosome dynamic interplays but also pioneered the visualization of the organellar pH alternation in a specific disease model.

Inter-organelle interactions play a vital role in diverse biological processes. Thus, chemical tools are highly desirable for understanding the spatiotemporal dynamic interplay among organelles in live cells and in vivo . However, designing such tools is still a great challenge due to the lack of universal design strategies. To break this bottleneck, herein, a novel unimolecular platform integrating the twisted intramolecular charge transfer (TICT) and aggregation-induced emission (AIE) dual mechanisms was proposed. As a proof of concept, two organelles, lipid droplets (LDs) and mitochondria, were selected as models. Also, the first TICT-AIE integration molecule, BETA-1 , was designed for simultaneous and dual-color imaging of LDs and mitochondria. BETA-1 can simultaneously target LDs and mitochondria due to its lipophilicity and cationic structure and emit cyan fluorescence in LDs and red fluorescence in mitochondria. Using BETA-1 , for the first time, we obtained long-term tracking of dynamic LD-mitochondrion interactions and identified several impressive types of dynamic interactions between these two organelles. More importantly, the increase in LD-mitochondrion interactions during ferroptosis was revealed with BETA-1 , suggesting that intervening in the LD-mitochondrion interactions may modulate this cell death. BETA-1 was also successfully applied for in vivo imaging of LD-mitochondrion interactions in C. elegans . This study not only provides an effective tool for uncovering LD-mitochondrion interactions and deciphering related biological processes but also sheds light on the design of new probes with an integrated TICT-AIE mechanism for imaging of inter-organelle interactions.

RNA imaging is of great importance for understanding its complex spatiotemporal dynamics and cellular functions. Considerable effort has been devoted to the development of small-molecule fluorescent probes for RNA imaging. However, most of the reported studies have mainly focused on improving the photostability, permeability, long emission wavelength, and compatibility with live-cell imaging of RNA probes. Less attention has been paid to the selectivity and detection limit of this class of probes. Highly selective and sensitive RNA probes are still rarely available. In this study, a new set of styryl probes were designed and synthesized, with the aim of upgrading the detection limit and maintaining the selectivity of a lead probe QUID-1 for RNA. Among these newly synthesized compounds, QUID-2 was the most promising candidate. The limit of detection (LOD) value of QUID-2 for the RNA was up to 1.8 ng/mL in solution. This property was significantly improved in comparison with that of QUID-1 . Further spectroscopy and cell imaging studies demonstrated the advantages of QUID-2 over a commercially available RNA staining probe, SYTO RNASelect, for highly selective and sensitive RNA imaging. In addition, QUID-2 exhibited excellent photostability and low cytotoxicity. Using QUID-2 , the global dynamics of RNA were revealed in live cells. More importantly, QUID-2 was found to be potentially applicable for detecting RNA granules in live cells. Collectively, our work provides an ideal probe for RNA imaging. We anticipate that this powerful tool may create new opportunities to investigate the underlying roles of RNA and RNA granules in live cells.

Benzothiazolium and benzoxazolium are common groups for the construction of hemicyanine dyes; however, their isosteric analogue benzoselenazolium have rarely been studied. Here, we report the development of the first benzoselenazolium-based hemicyanine dye for the selective detection of G-quadruplexes. This molecule, SEMA-1, was validated as a red-emitting and activatable fluorescent probe whose fluorescence would only be activated in the presence of G-quadruplexes in buffer solution. Consistent with this, SEMA-1 was found to accumulate in nucleoli and could be used to detect the high abundance of nucleolar rDNA and rRNA G-quadruplexes in fixed HeLa cells. On the other hand, due to the retained mitochondrial membrane potential in live HeLa cells, SEMA-1 was captured by mitochondria and had the potential to detect the mitochondrial G-quadruplexes. Collectively, this work demonstrates the value of developing G-quadruplex-specific fluorescent probes from novel benzoselenazolium-based hemicyanine scaffold., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

The mitochondrial DNA G-quadruplex (mtDNA G4) is a potential regulatory element for the regulation of mitochondrial functions; however, its relevance and specific roles in diseases remain largely unknown. Here, we engineered a set of chemical probes, including MitoISCH , an mtDNA G4-specific fluorescent probe, together with MitoPDS , a mitochondria-targeted G4-stabilizing agent, to thoroughly investigate mtDNA G4s. Using MitoISCH to monitor previously intractable dynamics of mtDNA G4s, we surprisingly found that their formation was prevalent only in endothelial and cancer cells that rely on glycolysis for energy production. Consistent with this, promotion of mtDNA G4 folding by MitoPDS in turn caused glycolysis-related gene activation and glycolysis enhancement. Remarkably, this close relationship among mtDNA G4s, glycolysis, and cancer cells further allowed MitoISCH to accumulate in tumors and label them in vivo. Our work reveals an unprecedented link between mtDNA G4s and cell glycolysis, suggesting that mtDNA G4s may be a novel cancer biomarker and therapeutic target deserving further exploration.

Because of the lack of facile and accurate methods to track stress granule (SG) dynamics in live cells and in vivo , in-depth studies of the biological roles of this attractive membraneless organelle have been limited. Herein, we report the first small-molecule probe, TASG , for the selective, convenient and real-time monitoring of SGs. This novel molecule can simultaneously bind to SG RNAs, the core SG protein G3BP1, and their complexes, triggering a significant enhancement in fluorescence intensity, making TASG broadly applicable to SG imaging under various stress conditions in fixed and live cells, ex vivo and in vivo . Using TASG , the complicated endogenous SG dynamics were revealed in both live cells and C. elegans . Collectively, our work provides an ideal probe that has thus far been absent in the field of SG investigations. We anticipate that this powerful tool may create exciting opportunities to investigate the underlying roles of SGs in different organisms.

Objective: To study clinical pathological characteristics, immunohistochemical, molecular genetical changes and prognosis in pediatric eosinophilic solid and cystic renal cell carcinoma (ESC RCC) with TSC2 gene mutations. Methods: The tissue samples were collected from two pediatric ESC RCC patients between 2017 and 2018. The tissues were subjected to histological examination and immunohistochemistry using EnVision system. The TFE3, TFEB gene rearrangements were tested using FISH and molecular genetic study. The paraffin sections were used for DNA extraction, PCR amplification and NGS sequencing. Results: The two patients with ESC RCC were both male, aged at 9 years and 8 months, and 13 years, respectively. The tumors were from the right kidney, 5 cm and 7 cm in size, respectively, with solid and cystic changes in cross section, and grey-reddish or grey-whitish fish meat appearance. Microscopic observation revealed the tumors had fibrous capsules, which were infiltrated by the tumor cells. The tumor cells were diffusely distributed, round-shaped, or polygon-shaped, and had voluminous cytoplasm, eosinophilic cytoplasm, various sizes of vacuoles and clear cell-like appearance. There were papillary structures in some areas, with visible fiber septa. The nuclei were round and vesicular, with multi-nucleated cells and megakaryocytes. The mitoses were not seen. A few cystic structures were visible in different sizes, and capsule walls were covered with a single layer of spike-like tumor cells. Thick-walled blood vessels were seen in the stroma, with focal lymphocytic infiltration, eosinophilic necrosis, calcifications and cholesterol crystals. Immunohistochemistry of the tumor cells was positive for PAX8 (diffuse), CK20 (focal), CKpan (focal), CK10 (1 focal, 1 diffuse), INI1, vimentin, CD68, and Ki-67 (5%~10%); the tumor cells were negative for HMB45, S-100, Melan A, p53, desmin, TFE3, CK7, CK19, EMA, CD56, CgA, Syn, CD30, CD117, WT1 and SMA. Molecular genetic study showed that TFE3 and TFEB gene rearrangements were not detected by FISH. NGS sequencing showed TSC2 p.Lys574Ter (0.198) was found in patient one and TSC2 p.Arg406Ter (0.355) in patient two. Conclusions: ESC RCC in children is a rare disease, and can be misdiagnosed easily. It has unique pathological characteristics, and immunohistochemical, molecular and genetic changes. The prognosis is relatively good.

Ubiquitin ligase Cullin7 has been has been suggested to act as an oncogene in some tumors; however, the prognostic role of Cullin7 has not been evaluated in cancer patients. In this study, we observed that the expression of Cullin7 mRNA was significantly higher in epithelial ovarian cancer (EOC) compared with normal ovarian surface tissues. In addition, Cullin7 expression was related to FIGO stage (p = .001) and lymph node metastasis (p = .033). Furthermore, Cullin7 overexpression inhibited the migration and invasion of ovarian cancer cells. These results suggest that Cullin7 may serve as an indicator of poor prognosis in patients with EOC.

Background: The findings of epidemiologic studies on the association between egg consumption and ovarian cancer risk remain conflicting. The aim of this meta-analysis was to investigate whether an association exists between egg intake and ovarian cancer risk in epidemiologic studies., Methods: A literature search was carried out using PUBMED, EMBASE, and Cochrane Library Central database for all medical literature published in English-language journals up to August 2013. Before meta-analysis, between-study heterogeneity and publication bias were assessed using adequate statistical tests. Fixed-effect and random-effect models were used to estimate summary relative risks (RR) and the corresponding 95% confidence intervals (CIs). Subgroup analyses and sensitivity analysis were also performed., Results: A total of 12 eligible studies (six case-control studies and six cohort studies) were included, involving 629,453 subjects and 3728 ovarian cancer cases. We found that high egg intake (comparing the highest with the lowest category) was associated with a significant increased risk of ovarian cancer (RR = 1.21, 95% CI [1.06, 1.38]). When we examined whether the associations differed by study type, statistically significant effect of egg intake on ovarian cancer was observed among case-control studies (RR = 1.22, 95% CI [1.03, 1.43]), but not among cohort studies (RR = 1.20, 95% CI [0.97, 1.48])., Conclusions: Our findings suggest that egg consumption may increase ovarian cancer risk. Additional studies, especially large prospective cohort studies, are warranted to confirm the findings., (Copyright © 2014 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background: Non-Hodgkin lymphoma is the fourth most common malignant tumors in children, Burkitt lymphoma (BL) accounts for 30-50% of all pediatric lymphomas. The aim of this study was to investigate the clinicopathologic features, immunophenotype, Epstein-Barr virus (EBV) infection and c-myc gene rearrangement of sporadic BL in children., Methods: Ninety-two cases of pediatric BL were retrospectively analyzed for clinical features, immunohistochemistry, EBV-encoded RNA (EBER) status by in situ hybridization and c-myc gene rearrangement by fluorescence in situ hybridization., Results: In the 92 cases, male is predominant in sex distribution (M: F = 3.38:1). The average age at diagnosis was 4.97 years. Polypoid BL showed a lower clinical stage (P = 0.002), and advanced clinical stage and low serum albumin level at diagnosis were associated with poor outcome (P = 0.024 and 0.053, respectively). The positive expression of CDl0, B-cell lymphoma-6, MUMl and EBER were 95.7% (88 cases), 92.4% (85 cases), 22.8% (21 cases), 41.3% (38 cases), respectively. The expression of MUM1 were not associated with EBV infection status (P = 1.000). c-myc gene rearrangement was detected in 94.6% (87/92). Clinical treatment information for 54 cases was collected, 21 patients died of tumor after surgery alone, 33 patients received surgery and chemotherapy, and of which six patients died shortly afterwords (MUM1 positive expression in 3 cases, P = 0.076)., Conclusions: The anatomical location, growth pattern and serum albumin level of BL were associated with biological behavior. MUM1 may be a potential adverse prognostic marker, and not associated with EBV infection status.

Objective: To investigate the molecular genetic features and diagnostic aspects of sporadic Burkitt's lymphoma (BL) in children., Methods: Tissue microarray was constructed to include 64 cases of pediatric BL and 6 cases of pediatric diffuse large B-cell lymphoma (DLBCL). Immunohistochemistry and fluorescence in-situ hybridization for c-myc, bcl-2, bcl-6, IgH, myc/IgH and bcl-2/IgH gene were performed. Cases of pediatric Burkitt's lymphomas were subclassified into three groups based on their cellular orgins: the germinal center (GC) group, the late-germinal center (late-GC) group and the post-germinal center (post-GC) group., Results: Among 64 Burkitt's lymphomas studied, expression of CD20, CD10, bcl-6, bcl-2 and MUM1 by immunohistochemistry were 100% (64 cases), 98.4% (63 cases), 96.9% (62 cases), 0 (0 cases) and 23.4% (15 cases), respectively. Various gene rearrangements were found involving the c-myc 93.1% (54/58 cases) and IgH 82.8% (48/58 cases). Detailed rearrangements are as follows: 46 cases (85.2%) myc/IgH gene translocation along with c-myc and IgH gene rearrangement; 4 cases (7.4%) c-myc gene rearrangement without IgH and myc/IgH abnormality; 4 cases (7.4%) without c-myc, IgH or myc/IgH gene rearrangement. No case showed bcl-2 gene abnormality (100%). Fifty nine cases showed normal bcl-6 gene status. One case had bcl-6 gene rearrangement and amplification with the pathologic and immunophenotypic characteristics of BL, leading to a revised pathological diagnosis of B-cell lymphoma, unclassifiable with features intermediate between diffuse large B-cell lymphoma and Burkitt's lymphoma (DLBCL/BL). Two cases showed c-myc gene rearrangement. Two cases showed bcl-6 gene amplification and 6 DLBCL cases had a normal status of bcl-2/IgH., Conclusions: A majority of pediatric sporadic BL arise from the germinal center B cells, most of which have c-myc gene rearrangement. It is useful to distinguish BL and DLBCL by multiple genes detection.

Objective: To study the clinicopathologic features, immunohistochemical findings, EBV and c-myc gene status of intra-abdominal non-Hodgkin B-cell lymphoma occurring in children., Methods: Seventy-four cases of pediatric intra-abdominal non-Hodgkin B-cell lymphoma were retrieved from the archival file. The cases were classified according to the 2008 WHO classification. Tissue microarray including tumor tissues from all the 74 cases was produced. Immunohistochemical study (SP method) for CD20, CD3, CD79a, CD10, bcl-6, MUM1, bcl-2, CD43, CD38 and Ki-67 was performed. In-situ hybridization for Epstein-Barr virus-encoded RNA (EBER) and fluorescence in-situ hybridization for c-myc gene were also carried out., Results: Amongst the 74 cases studied, 65 of them (87.8%) were Burkitt lymphoma (BL), 4 cases (5.4%) were diffuse large B-cell lymphoma (DLBCL) and the remaining 5 cases (6.8%) showed features in-between DLBCL and BL (DLBCL/BL). The patients often presented with abdominal pain, abdominal masses, ileus and intussusception. The ileocecal bowel wall and mesenteric lymph nodes were commonly involved. The lymphoma cells were of high histologic grade and suggested an aggressive clinical behavior. The staining for CD20 and CD79a were positive in all of the cases, while CD3 was negative. The positive rates of CD10, bcl-6, bcl-2, MUM1, CD43, CD38 and EBER in BL were 96.9% (63 cases), 95.4% (62 cases), 0 (0 case), 23.1% (15 cases), 70.8% (46 cases), 96.9% (63 cases) and 41.5% (27 cases), respectively. Fifty-four cases carried translocation of c-myc gene. As for DLBCL, the positive cases of CD10, bcl-6, bcl-2, MUM1, CD43, CD38 and EBER were 3 cases, 2 cases, 3 cases, 2 cases, 2 cases, 2 cases and 0 case, respectively. One of these cases showed c-myc gene translocation. Amongst the 4 cases of DLBCL, 2 of them belonged to germinal center B-cell-like subtype, while the remaining 2 cases were of non-germinal center B-cell-like subtype. The expression rates of CD10, bcl-6, bcl-2, MUM1, CD43, CD38 and EBER in DLBCL/BL were 5/5, 4/5, 0, 3/5, 5/5, 3/5 and 0, respectively. Three of the cases were positive for c-myc gene translocation., Conclusions: The majority of pediatric intra-abdominal non-Hodgkin B-cell lymphoma belonged to BL. They have characteristic clinical presentation and sites of predilection and are often associated with an aggressive clinical behavior. Thorough morphologic assessment, immunohistochemistry and in-situ hybridization play an important role in subtyping this group of lymphoid malignancy.