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Fluorescence imaging-guided surgery is one of important techniques to realize precision surgery. Although second near-infrared window (NIR-II) fluorescence imaging has the advantages of high resolution and large penetration depth in surgical navigation, its major drawback is that NIR-II images cannot be detected by our naked eyes, which demands a high hand-eye coordination for surgeons and increases the surgical difficulty. On the contrary, visible fluorescence can be observed by our naked eyes but has poor penetration. Here, we firstly propose a kind of NIR-II and visible fluorescence hybrid navigation surgery assisted via a cocktail of aggregation-induced emission nanoparticles (AIE NPs). NIR-II imaging helps to locate deep targeted tissues and judge the residual, and visible fluorescence offers an easily surgical navigation. We apply this hybrid navigation mode in different animals and systems, and verify that it can accelerate surgical process and compatible with a visible fluorescence endoscopy. To deepen the understanding of lymph node (LN) labelling, the distribution of NPs in LNs after local administration is initially analyzed by NIR-II fluorescence wide-filed microscopy, and two fates of the NPs are summarized. An alternative strategy which combines indocyanine green and berberine is also reported as a compromise for rapidly clinical translation.

Pancreatic cancer is the most lethal tumor. CA125 (gene symbol MUC16) is an important serum marker for pancreatic cancer diagnosis and treatment. High serum CA125 is related to metabolic tumor burden and poor prognosis. The circulating Treg subset is another independent prognostic factor for pancreatic cancer. Our unpublished data indicated that the circulating Treg proportion might be related to the serum CA125 level. However, the potential relationship and underlying mechanism of MUC16 and Treg in pancreatic cancer tissues remain unclear. In this study, we found that pancreatic cancer tissues were positive for both MUC16 C terminal (MUC16c) and Foxp3 expression and that their expression was correlated. MUC16c released into the cytoplasm via EGF induction significantly increased IL-6 expression and secretion. The PI3K/AKT pathway may participate in the regulation of IL-6 expression and secretion. By treating CD4+ T cells with IL-6 or co-culturing the cells with pancreatic cancer cells, tumor-derived IL-6 was identified to promote Foxp3 expression and Treg differentiation, which was significantly inhibited by the JAK2 inhibitor AG-490. In sum, our study demonstrated that the relationship between the MUC16c level and Foxp3 expression in the local tumor environment was consistent with that of the serum CA125 level and circulating Treg proportion in the systemic environment. MUC16c promoted Foxp3 expression and tumor-associated Treg enrichment in tumor tissues through tumor-secreted IL-6 activation of the JAK2/STAT3 pathway. These findings may provide deeper insight into potential pancreatic cancer therapy approaches.

Alcohol consumption likely induces gastric carcinogenesis through deregulation of RNA polymerase (Pol) III genes and oxidative damage. Transcription factor IIB-related factor 1 (BRF1) overexpression alleviates RNA Pol III transcription inhibition through breast cancer susceptibility gene 1 (BRCA1). Myeloperoxidase (MPO) involvement in cancer is induced by alcohol-mediated oxidative damage. BRCA1/2 and MPO play key roles in DNA repair. BRCA1 and BRCA2 exert different roles in homologous recombination repair. By using human gastric cancer (GC) biopsies, we investigated the prognostic value of these proteins upon alcohol induction. In total, high expression of BRF1 (P = 0.010) and positive cell infiltration of MPO (P = 0.004) in tumor tissues as well as positive expression of BRCA1 (P

Nanoparticles (NPs) assisted photothermal therapy (PTT) is a promising cancer treatment modality and has attracted the attention of the scientific mainstream. However, developing bio-excretable NPs that exhibit efficient optical properties and specific tumor targeting capability simultaneously is difficult. Herein, we develop a kind of hybrid nanovesicles consisting of bio-excretable aggregation-induced emission (AIE) NPs and tumor cell-derived “exosome caps” (TT3-oCB NP@EXOs) with enhanced second near-infrared (NIR-II, 900–1700 nm) fluorescence property and PTT functionality via electroporation. Compared with TT3-oCB NPs, TT3-oCB NP@EXOs exhibit excellent biocompatibility, specific targeting ability in vitro, homing to homologous tumors in vivo, and prolonged circulation time. Furthermore, TT3-oCB NP@EXOs were utilized as biomimetic NPs for NIR-II fluorescence imaging-guided PTT of tumors, due to their high and stable photothermal conversion capacity under 808 nm irradiation. Therefore, with the validation of other AIE NPs with poor targeting property, the tumor cell-derived EXO/AIE NP hybrid nanovesicles may provide an alternative artificial targeting strategy for improving tumor diagnosis and PTT.

It has long been suggested that the Eocene climate in East Asia was characterized by three latitudinally distributed zones, one middle arid zone and two humid zones to its north and south. The middle arid zone was firstly proposed based on the widespread red beds and evaporites in a NWW-trending zone of China. However, this long-standing model has recently been challenged by increasing doubts about the effectiveness of these arid-climate indicators. The Qaidam Basin, as one of the Eocene evaporites-bearing basins in China, can be studied to test whether the bedded evaporites can validly indicate arid climate. Over 300-m halite beds have been found in the late Eocene Upper Xiaganchaigou (UXG) Formation in a local saline center (Shizigou area) of the Qaidam Basin. Its coexistence with source rocks and limited distribution, together with the absence of red beds, make it difficult to explain the halite genesis with the conventional climatic-controlled playa model. Based on stratigraphic correlation, lithological and mineralogical observation, and oxygen, carbon and chlorine isotopic analysis, we identify several characteristics about the Shizigou saline center: (1) undulated lake floor; (2) shallow water; (3) limited hydrothermal impact; (4) evaporation-induced precipitation; (5) high eolian influence; and (6) fluctuated climate background. According to these investigations, we suggest a new model for the genesis of the bedded halite in the Qaidam Basin, the tectonic-climatic model. The key point for this model is that the undulated topography caused by tectonic activity and the fluctuated climate together leaded to the hydrological isolation of the Shizigou area. The Shizigou area was isolated from the larger brackish Qaidam paleolake for independent evaporation during arid climate stage while connected with it during humid climate stage, causing alternatively water influx and evaporation and inducing the occurrence of interbedded halite and source rocks. Thus, the widespread bedded halite in the Eocene strata over China may indicate fluctuated rather than arid climate in East Asia.

Ellagic acid (EA), a natural plant polyphenol, is usually used as a functional additive in variety of health foods. However, the potential toxicity of EA to human health should be paid enough attention. To clarify its biological toxicity in vivo, this study explored the binding mechanism of EA with bovine serum albumin (BSA) by means of spectroscopic approaches and molecular docking insimulative physiological conditions. The results showed that the mixture of BSA with EA could spontaneously cause the formation of BSA-EA complex through electrostatic interaction under simulative physiological conditions (0.01 mol·L−1Tris-HCl, 0.015 mol L−1 NaCl, pH = 7.4). Molecular docking experiments revealed that EA was primarily bound to the hydrophobic pocket of the site I (subdomain IIA) of BSA. It has been reported that the binding of small functional molecules to serum albumins remarkably impacts their absorption, distribution, metabolism, and excretion features. Therefore, this study might be helpful for human to have an in-depth understanding of the biological effect of EA in vivo and guide human to take it safely and reasonably.

Background L-type sarcoma (liposarcoma + leiomyosarcoma) is the most common subtype of soft tissue sarcoma (STS). Leiomyosarcoma (LMS) and dedifferentiated LPS (DDLPS) are more aggressive with worse outcomes than well-differentiated sarcoma. Efforts have thus been made to decipher the difference of oncogenesis between DDLPS and LMS, and assist in the choice of treatment. Methods WES was conducted on 32 STS (20 LMS and 12 DDLPS) and matched peripheral blood. Somatic SNVs and indels were identified by GATK tools. Recurrent somatic copy-number alterations (SCNA) were called using Control-FREEC and GISTIC2.0. We further conducted RNA-Seq on 8 DDLPS samples and 8 LMS samples, and use STAR-Fusion to reveal the distinct chromosome rearrangement patterns of LMS and DDLPS samples. Results We identified top 20 highly variable genes between LMS and DDLPS. 55% LMS (n = 11) carry deletions or mutations of TP53. All DDLPS carry wildtype TP53, but chromosome 12q14–15 region which encodes MDM2, CDK4 and HMGA2 are highly amplified in all DDLPS samples, suggesting distinct mechanisms of TP53 pathway inactivation. Hippo pathway is reported to be involved in resistance to cytotoxic drugs and modulate tumour immunogenicity. In our study, 70% LMS (n = 14) and 58% DDLPS (n = 7) carry at least one Hippo pathway alterations, top variable genes in LMS include DCHS1, LLGL1, AJUBA et al. Among 8 LMS and 8 DDLPS who underwent RNA-Seq, we identified 4 fusion transcripts in 3 LMS and 36 fusion transcripts in 8 DDLPS (P = 0.007). Fusion transcripts involving chromosome 12 (Chr12) are only identified in DDLPS, including 10 interchromosomal and 12 intrachromosomal rearrangements. MDM2 and RAB3IP are the most common fusion partners. There was also significant correlation between MDM2/CDK4 co-amplification and Chr12 rearrangement (P Conclusions LMS and DDPLS carry distinct mutagenic patterns, ranging from SNVs to gross genomic instability. Chromosome rearrangement of DDLPS, particularly in Chr12, result in both gene amplification and fusion events, and these neoantigens produced by gene fusion may open up alternative avenues for immunotherapy. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.

Objective The prevalence of osteoporosis is higher among patients with Wilson disease (WD) than the general public, of which the cause is still unclear. The purpose of this research is to analyze the possible causes for the high prevalence and connection between penicillamine and bone mineral density. Methods Eight-four WD patients (44 males and 40 females) and 76 controls (27 males and 49 females) were enrolled in this study. The patients were diagnosed via mutation analysis of ATP7B. Dual-energy X-ray Analysis (DXA) was used to evaluate the bone mineral density (BMD). Serum phosphate, calcium, magnesium, parathyroid hormone, calcitonin, osteocalcin, 25-(OH)-Vitamin D as well as alkaline phosphatase were measured to evaluate the bone turnover activity. Based on the information on imaging, laboratory test and previous medical history, we analyzed the correlations between BMD, bone turnover activity and patients' age, gender, clinical manifestations and maximum dosage of penicillamine. Results Fifty-eight patients received a DXA scan. The prevalence of osteoporosis in WD patients was 27.58% (16/58) whereas that in the controls was 19.74% (15/76). BMD, T. score and Z score of lumbar vertebrae as well as BMD, Z score of hip neck were significantly lower in WD patients. 25(OH)-Vitamin D, serum phosphate, serum calcium and ALP were significantly higher in WD patients than the controls. But among patients who have received different maximum daily dosage of penicillamine, larger dose was associated with lower BMD. Age, gender and clinical manifestations did not affect BMD among WD patients. Conclusion WD patients have a higher prevalence of osteoporosis, lower BMD and higher bone turnover activity compared with controls. The use of penicillamine is an important precipitating factor.