N-Type Doping of Naphthalenediimide-Based Random Donor-Acceptor Copolymers to Enhance Transistor Performance and Structural Crystallinity.

An integrated strategy of molecular design and conjugated polymer doping is proposed to improve the electronic characteristics for organic field effect transistor (OFET) applications. Here, a series of soluble naphthalene diimide (NDI)-based random donor-acceptor copolymers with selenophene π-conjugated linkers and four acceptors with different electron-withdrawing strengths (named as rNDI-N/S/NN/SS) are synthesized, characterized, and used for OFETs. N-type doping of NDI-based random copolymers using (12a,18a)-5,6,12,12a,13,18,18a,19-octahydro-5,6-dimethyl-13,18[1',2']-benzenobisbenzimidazo[1,2-b:2',1'-d]benzo[i][2.5]benzodiazocine potassium triflate adduct (DMBI-BDZC) is successfully demonstrated. The undoped rNDI-N, rNDI-NN, and rNDI-SS samples exhibit ambipolar charge transport, while rNDI-S presents only a unipolar n-type characteristic. Doping with DMBI-BDZC significantly modulates the performance of rNDI-N/S OFETs, with a 3- to 6-fold increase in electron mobility (µe) for 1 wt % doped device due to simultaneous trap mitigation, lower contact resistance (RC), and activation energy (EA), and enhanced crystallinity and edge-on orientation for charge transport. However, the doping of intrinsic pro-quinoidal rNDI-NN/SS films exhibits unchanged or even reduced device performance. These findings allow us to manipulate the energy levels by developing conjugated copolymers based on various acceptors and quinoids and to optimize the dopant-polymer semiconductor interactions and their impacts on the film morphology and molecular orientation for enhanced charge transport.

m6A regulator-mediated methylation modification highlights immune infiltration patterns for predicting risk in hepatocellular carcinoma.

BACKGROUND: Increasing studies have demonstrated the biological function of RNA N6-methyladenosine (m6A) modifications in tumorigenesis. However, the potential role of m6A modifications in the tumor immune microenvironment (TIME) of hepatocellular carcinoma (HCC) remains unclear. METHODS: Herein, 23 m6A regulators were fetched and introduced into consensus clustering to identify distinct m6A modification patterns and develop m6A-based molecular signatures. Then, a principal component analysis algorithm was employed to construct an m6A-based scoring system to further quantify m6A modification patterns in individual tumors. Immunophenoscore (IPS) was used to estimate the immunotherapeutic response of patients. RESULTS: Three different m6A modification patterns with distinct prognoses and biological signatures were identified among 611 HCC samples. The TIME characteristics of these three patterns were consistent with three known immune profiles: immune-oasis, immune-excluded, and immune-inflamed phenotypes. Identifying m6A modification patterns within individual tumors based on the m6Ascore, developed under the m6A-related signature genes, contributed to elaborating biological processes, clinical outcomes, immune cell infiltration, immunotherapeutic effects, and genetic variations. The low-m6Ascore subtype, characterized by immunosuppression, suggested an immune-suppressed phenotype and a low probability of benefiting from immunotherapy. Finally, the potential function of PRDM4 in HCC was explored. CONCLUSION: This study comprehensively elucidated the indispensable role of m6A modification patterns in the complexity of TIME. The quantitative identification of m6A modification patterns in individual tumors will contribute to optimizing precision immunotherapy.

Tuning Ambipolarity of the Conjugated Polymer Channel Layers of Floating-Gate Free Transistors: From Volatile Memories to Artificial Synapses.

Three-terminal synaptic transistor has drawn significant research interests for neuromorphic computation due to its advantage of facile device integrability. Lately, bulk-heterojunction-based synaptic transistors with bipolar modulation are proposed to exempt the use of an additional floating gate. However, the actual correlation between the channel's ambipolarity, memory characteristic, and synaptic behavior for a floating-gate free transistor has not been investigated yet. Herein, by studying five diketopyrrolopyrrole-benzotriazole dual-acceptor random conjugated polymers, a clear correlation among the hole/electron ratio, the memory retention characteristic, and the synaptic behavior for the polymer channel layer in a floating-gate free transistor is described. It reveals that the polymers with balanced ambipolarity possess better charge trapping capabilities and larger memory windows; however, the high ambipolarity results in higher volatility of the memory characteristics, namely poor memory retention capability. In contrast, the polymer with a reduced ambipolarity possesses an enhanced memory retention capability despite showing a reduced memory window. It is further manifested that this enhanced charge retention capability enables the device to present artificial synaptic characteristics. The results highlight the importance of the channel's ambipolarity of floating-gate free transistors on the resultant volatile memory characteristics and synaptic behaviors.

An asymmetric 2,3-fluoranthene imide building block for regioregular semiconductors with aggregation-induced emission properties.

For organic semiconductors, the development of electron-deficient building blocks has lagged far behind that of the electron-rich ones. Moreover, it remains a significant challenge to design organic molecules with efficient charge transport and strong solid-state emission simultaneously. Herein, we describe a facile synthetic route toward a new π-acceptor imide building block, namely 2,3-fluoranthene imide, based on which four regioregular small molecules (F1-F4) are synthesized by tuning the imide orientations and the central linkage bridges. All molecules exhibit attractive aggregation-induced emission (AIE) characteristics with strong far-red emission in the powder state, and F3 shows the highest photoluminescence quantum yield of 5.9%. F1 and F3 with a thiophene bridge present an obvious p-type characteristic, while for F3 with an outward imide orientation, the maximum hole mobility from a solution-processed field-effect transistor (FET) device reaches 0.026 cm2 V-1 s-1, being ∼104 times higher than the value of F1 with an inward imide orientation. By using a fluorinated thiophene bridge, the resulting F2 and F4 can be turned into n-type semiconductors, showing an electron mobility of ∼1.43 × 10-4 and ∼3.34 × 10-5 cm2 V-1 s-1, respectively. Our work not only demonstrates that asymmetric 2,3-fluoranthene imide is a promising building block for constructing organic materials with high carrier mobility and strong solid-state emission, but also highlights the importance of regioregular structures in the materials' properties.

Systemic Sequential Therapy of CisGem, Tislelizumab, and Lenvatinib for Advanced Intrahepatic Cholangiocarcinoma Conversion Therapy.

Intrahepatic cholangiocarcinoma (CCA), always diagnosed at an advanced stage in recent years, is of high aggression and poor prognosis. There is no standard treatment beyond first-line chemotherapy and no molecular-targeted agents or immune checkpoint inhibitors approved for advanced intrahepatic CCA. Hence, we firstly report an original therapeutic strategy for a 60-year-old patient diagnosed with intrahepatic CCA categorized as Stage IIIB (T3N1M0) by the American Joint Committee on Cancer staging system. After histopathological examination and next-generation sequencing, the patient was treated with four courses of novel systemic sequential therapy (intravenous gemcitabine 1,000 mg/m2 and cisplatin 25 mg/m2 on days 1 and 8; oral lenvatinib 8 mg/day from days 1 to 21; intravenous tislelizumab 200 mg on day 15). Then, the patient achieved partial response and was operated on right hemihepatectomy, cholecystectomy, and abdominal lymph node dissection. Without any perioperative complications, the patient was discharged from our hospital in perfect condition. Thereafter, the patient continued to use this new regimen 1 month after surgery for adjuvant therapy and was confirmed without recurrence when we followed up. In a word, we found an effective therapeutic regimen for preoperative advanced intrahepatic CCA conversion therapy, which may become a new approach in cancer treatment in the future.

Mesenchymal Stem Cells Engineered by Nonviral Vectors: A Powerful Tool in Cancer Gene Therapy.

Due to their "tumor homing" and "immune privilege" characteristics, the use of mesenchymal stem cells (MSCs) has been proposed as a novel tool against cancer. MSCs are genetically engineered in vitro and then utilized to deliver tumoricidal agents, including prodrugs and bioactive molecules, to tumors. The genetic modification of MSCs can be achieved by various vectors, and in most cases viral vectors are used; however, viruses may be associated with carcinogenesis and immunogenicity, restricting their clinical translational potential. As such, nonviral vectors have emerged as a potential solution to address these limitations and have gradually attracted increasing attention. In this review, we briefly revisit the current knowledge about MSC-based cancer gene therapy. Then, we summarize the advantages and challenges of nonviral vectors for MSC transfection. Finally, we discuss recent advances in the development of new nonviral vectors, which have provided promising strategies to overcome obstacles in the gene modulation of MSCs.

Efficacy of licartin combined with transcatheter hepatic arterial chemoembolization in the treatment of middle-advanced primary liver cancer.

PURPOSE: To explore the clinical efficacy and safety of Licartin combined with transcatheter hepatic arterial chemoembolization (TACE) in the treatment of middle-advanced primary liver cancer. METHODS: The clinical data of 112 patients with middle-advanced primary liver cancer treated in our hospital from March 2015 to March 2017 were collected. Fifty-six patients underwent TACE combined with Licartin (Licartin+TACE group), while the remaining 56 patients were treated with TACE alone (TACE group). The short-term efficacy, peripheral hemogram, liver function, alpha fetoprotein (AFP) level, count of circulating tumor cells (CTCs) and cluster of differentiation (CD)147 phenotype before and after treatment were assessed in both groups, the incidence of adverse reactions was compared, and the postoperative survival and disease development were recorded during follow-up. RESULTS: At 2 weeks after treatment, the levels of ALT and AST were significantly higher in Licartin + TACE group than those in TACE group (p<0.05). After treatment, the white blood cell count (WBC) and platelet count (PLT) obviously declined in both groups, and they were obviously lower in Licartin + TACE group than those in TACE group (p<0.05). After treatment, the count of CTCs evidently declined in both groups compared with that before treatment (p<0.05), and it was evidently lower in Licartin + TACE group than in TACE group (p<0.001). All patients were followed up for 3-36 months. In Licartin + TACE group and TACE group, the mean overall survival (OS) was 13.1±3.6 months and 11.3±2.8 months, respectively, and the mean progression-free survival (PFS) was 7.9±1.4 months and 6.1±1.2 months, respectively. At the end of follow-up, the Kaplan-Meier survival curves were plotted and log-rank test found that the OS rate was remarkably superior in Licartin + TACE group to that in TACE group (p=0.047), but the PFS rate had no statistically significant difference between the two groups (p=0.372). CONCLUSIONS: Licartin combined with TACE has better efficacy than TACE alone in the treatment of middle-advanced primary liver cancer, with tolerable adverse reactions, which prolongs patients' survival time.

miR­448 targets Rab2B and is pivotal in the suppression of pancreatic cancer.

Improvements in survival rates for pancreatic cancer have been slow and the morality rate continues to increase in patients. MicroRNA (miR)­448 is reported to be significantly downregulated in several types of cancer. In this study, Rab2B is target of miR­488 was confirmed by bioinformatics analysis and validated using a luciferase reporter assay. A total of 72 cases of pancreatic cancer in patients diagnosed at The First Affiliated Hospital, School of Medicine, Zhejiang University (Hangzhou, China) were enrolled, and cancer specimens and their adjacent normal tissues were collected for analysis. The expression levels of miR­448 and Rab2B in these tissues and in pancreatic cancer cell lines were quantified using reverse transcription­polymerase chain reaction analysis. miR­448 overexpression was achieved by cell transfection. Protein expression was assessed using western blot analysis. Cell viability, cell cycle and apoptosis were analyzed using CCK­8 assay and flow cytometry, respectively. The results revealed a negative correlation between miR­448 and Rab2B in the pancreatic tissues and cell lines. The results of bioinformatics analysis indicated that miR­448 directly targeted Rab2B. Aberrant miR­448 levels in PANC­1 cells downregulated the expression of Rab2B, and significantly decreased cell proliferation and promoted apoptosis of cancer cells. It was also found that miR­448 mimics resulted in G0/G1 cell cycle arrest and affected the expression of cell cycle regulators, including cyclin D1, p21 and p27. In addition, the miR­448 mimics led to inactivation of the Akt/Mammalian target of rapamycin signaling pathway. The miR­448 mimics induced apoptosis and activated the expression of caspase­3, caspase­9 and poly(ADP­ribose) polymerase. The results suggested that miR­448 was a negative regulator of Rab2B and promoted cell cycle arrest and apoptosis in pancreatic cancer.

Successful treatment of a giant ossified benign mesenteric schwannoma.

Primary benign schwannoma of the mesentery is extremely rare. To date, only 9 cases have been reported in the English literature, while mesenteric schwannoma with ossified degeneration has not been reported thus far. In the present study, we present the first giant ossified benign mesenteric schwannoma in a 58-year-old female. Ultrasound, computed tomography and magnetic resonance imaging were used, but it was still difficult to determine the definitive location and diagnose the mass. By laparotomy, a 10.0 cm × 9.0 cm × 9.0 cm giant mass was found in the mesentery and was then completely resected. Microscopically, the tumour located in the mesentery mainly consisted of spindle-shaped cells with a palisading arrangement. Some areas of the tumour were ossified, and a true metaplastic bone formation was observed, with the presence of bone lamellae and osteoblasts. Immunohistochemical investigation of the tumour located in the mesentery showed that the staining for the S-100 protein was strongly positive, while the stainings of SMA, CD34, CD117 and DOG-1 were negative. The cell proliferation index, measured with Ki67 staining, was less than 3%. Finally, a giant ossified benign mesenteric schwannoma was diagnosed. After surgery, the patient was followed up for a period of 43 mo, during which she remained well, with no evidence of tumour recurrence.

Successful treatment of a pancreatic schwannoma by spleen-preserving distal pancreatectomy.

Schwannomas are neurogenic tumors that arise from the neural sheaths of peripheral nerves. These tumors can be located in any area of the human body; the most common locations are the head, neck, trunk and extremities. Pancreatic schwannomas are very rare. Over the past 40 years, only 67 cases of pancreatic schwannomas have been reported in the English literature. Here we present a case of pancreatic schwannoma in a 62-year-old male. The tumor was revealed by ultrasound and computed tomography in the neck and body of the pancreas. An accurate diagnosis was difficult to obtain preoperatively. The patient consented to the performance of a laparotomy, and the mass was found in the neck and body of the pancreas and successfully treated using a spleen-preserving distal pancreatectomy with splenic artery and vein preservation. The procedure has only been reported in one other case of pancreatic schwannoma; here we present the second reported case. Macroscopically, the tumor was well circumscribed, gray-white in color and 3.3 cm × 2.8 cm in size. Microscopically, the tumor cells were spindle-shaped and had a palisading arrangement with no atypia, which are results compatible with a benign tumor. Both hypercellular and hypocellular areas were visible. Immunohistochemically, the tumor cells were strongly positive for S-100 protein. The tumor was definitively diagnosed as a schwannoma of the pancreatic neck and body. The patient was followed for 72 mo and has been doing well without any complications.

Clinical significance of mitofusin-2 and its signaling pathways in hepatocellular carcinoma.

BACKGROUND: The mitochondrial GTPase mitofusin-2 (MFN2) gene encodes a mitochondrial membrane protein that can induce apoptosis of hepatocellular carcinoma (HCC) via the mitochondrial apoptotic pathway, as validated in our previous research. However, little is known of the clinical significance of MFN2 expression and its signaling pathways in HCC. METHODS: MFN2 mRNA expression in tumor and adjacent non-tumor tissues from 115 patients with HCC was investigated using quantitative real-time PCR. The association of the MFN2 mRNA expression level with clinical and pathological parameters was evaluated statistically, while a comparative microarray analysis was used to identify MFN2 signaling pathways in HepG2 cells. RESULTS: MFN2 was significantly (p < 0.0001) downregulated in HCC tissues. Low MFN2 expression was significantly correlated with sex and preoperative alpha-fetoprotein (p < 0.05). Both a Kaplan-Meier survival curve and multivariate analyses showed that MFN2 was related to overall survival. A comparative gene expression microarray revealed 211 upregulated (58 %) and 153 downregulated (42 %) genes. Eighteen pathways were identified as the most significant pathways correlated with MFN2. CONCLUSIONS: Low MFN2 expression in HCC indicated a worse overall survival. Crucial signaling molecules such as PI3K-AKT, cytokine receptor, and focal adhesion may participate in MFN2-mediated signaling pathway changes in HCC.

Castleman disease mimicked pancreatic carcinoma: report of two cases.

Castleman disease (CD) is an uncommon benign lymphoproliferative disorder, which usually presents as solitary or multiple masses in the mediastinum. Peripancreatic CD was rarely reported. Herein, we report two cases of unicentric peripancreatic CD from our center. A 43-year-old man and a 58-year-old woman were detected to have a pancreatic mass in the routine medical examinations. Both of them were asymptomatic. The computed tomography and ultrasonographic examination revealed a mild enhancing solitary mass at the pancreatic head/neck. No definite preoperative diagnosis was established and Whipple operations were originally planned. The intraoperative frozen section diagnosis of both patients revealed lymphoproliferation. Then the local excisions of mass were performed. Histological examination revealed features of CD of hyaline-vascular type. No recurrence was found during the follow-up period. CD should be included in the differential diagnosis of pancreatic tumors. Local excision is a suitable surgical choice.

[Dual, triple, and quadruple oral tacrolimus-based immunosuppression regimens after orthotopic liver transplantation: a randomised comparative study of regimens].

OBJECTIVE: To investigate the effects of tacrolimus-based immunosuppression regimens after orthotopic liver transplantation and search a reasonable regimen of combination therapy and suitable blood concentration of tacrolimus. METHODS: Ninety-four adult recipients of cadaveric livers were randomly divided into 3 groups to undergo different tacrolimus-based immunosuppression regimens: dual (tacrolimus + glucocorticoid), triple [tacrolimus + mycophenolate mofetil (MMF) + glucocorticoid]; quadruple [tacrolimus + MMF + glucocorticoid in addition of induction treatment by daclizumab]. The efficacy and safety of the 3 groups 6 months after the transplantation were compared. RESULTS: The frequencies of acute rejection were 25.9%, 11.1%, and 7.5% for the dual, triple, and quadruple therapy groups, that of the quadruple therapy group being significantly lower than that of the dual therapy group (P = 0.038). There were no significant differences in the rates Three months after transplantation, the levels of ALT and total cholesterol of the dual therapy groups were significantly higher than those of the quadruple therapy group (P(ALT) = 0.011, P(Tch) = 0.002). Within the first month post-operatively the concentration of tacrolimus of the triple therapy group could be controlled at the level 8 ng x ml(-1)-13 ng x ml(-1). CONCLUSIONS: Quadruple tacrolimus-based immunosuppression regimen is the most effective and safest, followed by the triple therapy and dual therapy. Low-dose tacrolimus combination therapy provides an effective protection to the liver graft with mild drug toxicity to the patient.

Primary liver cancer in the elderly: report of 125 cases.

OBJECTIVES: To understand the characteristics of primary liver cancer (PLC) in the elderly and summarize the experience in treatment of such patients. METHODS: The clinical data of PLC in the elderly group (>/=60 years, 125 patients) and the young group (0.05). CONCLUSIONS: Hepatectomy is a choice of treatment for PLC in the elderly based on their liver function. AFP and B-ultrasonography are important methods for the diagnosis of PLC in the elderly.