Background:Combined hepatocellular and cholangiocarcinoma(CHC) is a unique subtype of liver cancer comprising both hepatocellular carcinoma(HCC) and intrahepatic cholangiocarcinoma(ICC);however,its ...cellular origin remains unclear.The purpose of this study was to investigate the clinicopathologic features and the clonal relationship between HCC and ICC in 34 patients with CHC.Methods:The clinicopathologic features and prognosis of the 34 CHC patients were compared with those of 29 patients with separated HCC and ICC(5HC).Loss of heterozygosity(LOH) at 10 highly polymorphic microsatellite markers was detected in 16 CHC and 10 SHC tissues for determination of the clonal origin of CHC.Expression of hepatocyte markershepatocyte paraffin 1(Hep Par 1) and glypican 3(GPC3)and cholangiocyte markerscytokeratin(CK)7 and 19in tumor tissues was examined by immuno histochemical analysis.Results:In the 16 CHC specimens,the difference in LOH patterns between HCC and ICC was less than 30%,suggesting the same clonal origin of HCC and ICC.Consistent with this finding,immunohistochemical analysis revealed that hepatocyte markers(Hep Par 1 and GPC3) and cholangiocyte markers(CK7 and CK19) were simultaneously expressed in both the HCC and ICC components in 52.9%of CHC specimens,suggesting that the two components shared a similar phenotype with hepatic progenitor cells(HPCs).On the contrary,in all 10 SHC cases,the difference in LOH patterns between the HCC and ICC components was greater than 30%,suggesting different clonal origins of HCC and ICC.Overall survival and disease-free survival were shorter for patients with CHC than for patients with SHC(P < 0.05).Conclusions:Our results suggest that the HCC and ICC components of CHC may originate from the same clone,having the potential for dual-directional differentiation similar to HPCs.CHC tended to exhibit the biological behaviors of both HCC and ICC,which may enhance the infiltrative capacity of tumor cells,leading to poor clinical outcomes for patients with CHC.
ARF suppresses aberrant cell growth upon c-Myc overexpression by activating p53 responses. Nevertheless, the precise mechanism by which ARF specifically restrains the oncogenic potential of c-Myc ...without affecting its normal physiological function is not well understood. Here, we show that low levels of c-Myc expression stimulate cell proliferation, whereas high levels inhibit by activating the ARF/p53 response. Although the mRNA levels of ARF are induced in both scenarios, the accumulation of ARF protein occurs only when ULF-mediated degradation of ARF is inhibited by c-Myc overexpression. Moreover, the levels of ARF are reduced through ULF-mediated ubiquitination upon DNA damage. Blocking ARF degradation by c-Myc overexpression dramatically stimulates the apoptotic responses. Our study reveals that ARF stability control is crucial for differentiating normal (low) versus oncogenic (high) levels of c-Myc expression and suggests that differential effects on ULF- mediated ARF ubiquitination by c-Myc levels act as a barrier in oncogene-induced stress responses.
•ARF stability is differentially regulated by c-Myc levels•ARF is degraded upon DNA damage by ULF•Myc overexpression prevents DNA damage-induced ARF degradation•ARF stabilization is critical for p53-mediated apoptosis upon Myc overexpression
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The synthesis of porphyrin and chlorin derivatives has attracted significant attention due to their numerous applications. Herein, we report an environment friendly oxidant- and catalyst-free ...electrooxidative cross-coupling approach for multiple coupling reactions to synthesize meso C–N, C–O, and C–S substituted porphyrin and chlorin derivatives. For C–N cross-coupling reactions, diaminated porphyrins were obtained as the main products, while using 4-bromo-2,6-dimethyl aniline resulted in monoaminated product. Similarly, electrochemical catalysis of porphyrins with phenol and thiophene produced meso-disubstituted porphyrins in moderate yields under a smaller current. Chlorins were also applicable, and 20-substituted products were efficiently produced regioselectively. To the best of our knowledge, this work represents the first example of electrooxidative C–X cross-coupling of porphyrins and chlorins.
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IJS, KILJ, NUK, PNG, UL, UM
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Resistance phenomena during chemotherapy of tumor has been severely hampering the applications of chemotherapeutics. Due to advantage of drug repurposing, discovery of new ...chemosensitizers based on approved drugs is an effect strategy to find new candidates. Herein, we found antidepressant drug – sertraline, could sensitize drug-resistant gastric cancer cell (SGC-7901/DDP) with the IC50 value of 18.73 μM. To understand the structure–activity relationship and improve the activity, 30 derivatives were synthesized and evaluated. The IC50 value of the best compound was improved to 5.2 μM. Moreover, we found apoptosis induction and cell cycle arrest was the reason for the cell death of the drug-resistant cells after treatment of sertraline and derivatives, and PI3K/Akt/mTOR pathway was involved.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Tetramethylammonium trifluoromethylselenate (Me4NSeCF3) has been confirmed as an excellent precursor of selenofluorophosgene for amines in the preparation of selenocarbamoyl fluorides, selenoureas, ...and heterocycles under catalyst- and additive-free conditions. Reactions of Me4NSeCF3 with secondary amines at room temperature provided exclusively selenocarbamoyl fluorides in moderate to high yields, while the same reactions with primary amines afforded selenoureas in good yields. When Me4NSeCF3 was similarly mixed with amines containing adjacent amino, hydroxyl or thiol groups, five- and six-membered heterocycles were produced. The reaction featured simplicity, rapidness, high efficiency, a broad substrate scope, and good functional group tolerance, offering a convenient access to a variety of selenocarbonylated compounds, which were otherwise difficult to synthesize by other approaches.
We introduce Quafu-Qcover, an open-source cloud-based software package developed for solving combinatorial optimization problems using quantum simulators and hardware backends. Quafu-Qcover provides ...a standardized and comprehensive workflow that utilizes the quantum approximate optimization algorithm (QAOA). It facilitates the automatic conversion of the original problem into a quadratic unconstrained binary optimization (QUBO) model and its corresponding Ising model, which can be subsequently transformed into a weight graph. The core of Qcover relies on a graph decomposition-based classical algorithm, which efficiently derives the optimal parameters for the shallow QAOA circuit. Quafu-Qcover incorporates a dedicated compiler capable of translating QAOA circuits into physical quantum circuits that can be executed on Quafu cloud quantum computers. Compared to a general-purpose compiler, our compiler demonstrates the ability to generate shorter circuit depths, while also exhibiting superior speed performance. Additionally, the Qcover compiler has the capability to dynamically create a library of qubits coupling substructures in real-time, utilizing the most recent calibration data from the superconducting quantum devices. This ensures that computational tasks can be assigned to connected physical qubits with the highest fidelity. The Quafu-Qcover allows us to retrieve quantum computing sampling results using a task ID at any time, enabling asynchronous processing. Moreover, it incorporates modules for results preprocessing and visualization, facilitating an intuitive display of solutions for combinatorial optimization problems. We hope that Quafu-Qcover can serve as an instructive illustration for how to explore application problems on the Quafu cloud quantum computers.
With the rapid advancement of quantum computing, hybrid quantum–classical machine learning has shown numerous potential applications at the current stage, with expectations of being achievable in the ...noisy intermediate-scale quantum (NISQ) era. Quantum reinforcement learning, as an indispensable study, has recently demonstrated its ability to solve standard benchmark environments with formally provable theoretical advantages over classical counterparts. However, despite the progress of quantum processors and the emergence of quantum computing clouds, implementing quantum reinforcement learning algorithms utilizing parameterized quantum circuits (PQCs) on NISQ devices remains infrequent. In this work, we take the first step towards executing benchmark quantum reinforcement problems on real devices equipped with at most 136 qubits on the BAQIS Quafu quantum computing cloud. The experimental results demonstrate that the policy agents can successfully accomplish objectives under modified conditions in both the training and inference phases. Moreover, we design hardware-efficient PQC architectures in the quantum model using a multi-objective evolutionary algorithm and develop a learning algorithm that is adaptable to quantum devices. We hope that the Quafu-RL can be a guiding example to show how to realize machine learning tasks by taking advantage of quantum computers on the quantum cloud platform.
Slow transit constipation is a common condition that would be difficult to treat in clinical practice with a widespread incidence in the population. Pharmacotherapy and surgery are common treatment ...modalities. However, the clinical effect is limited, and patients still suffer from it. As the researchers strived in this field for decades, the profound relationship between slow transit constipation and fecal microbiota transplantation has comprehensively been sustained. It is very pivotal to maintain intestinal homeostasis, the structure function and metabolic function of symbiotic bacteria, which can inhibit the engraftment of intestinal pathogens. This mini review explains the treatment effects and possible mechanisms of the fecal microbiota transplantation in treating slow transit constipation. Simultaneously, it is found that there is significant improvement in the disease by adjusting the intestinal microbes like fecal microbiota transplantation. Fecal microbiota transplantation has efficient therapeutic effects in slow transit constipation compared with traditional therapies.
Ginsenoside Rg1 is a valuable bioactive molecule but its high polarity and low concentration in complex mixtures makes it a challenge to separate Ginsenoside Rg1 from other saponins with similar ...structures, resulting in low extraction efficiency. The successful development of effective Rg1 molecularly imprinted polymers that exhibit high selectivity and adsorption may offer an improved method for the enrichment of active compounds. In this work, molecularly imprinted polymers were prepared with two different methods, precipitation polymerization or surface imprinted polymerization. Comparison of the adsorption abilities showed higher adsorption of the surface molecularly imprinted polymers prepared by surface imprinted polymerization, 46.80 mg/g, compared to the 27.74 mg/g observed for the molecularly imprinted polymers prepared by precipitation polymerization. Therefore, for higher adsorption of the highly polar Rg1, surface imprinted polymerization is a superior technique to make Rg1 molecularly imprinted polymers. The prepared surface molecularly imprinted polymers were tested as a solid‐phase extraction column to directionally enrich Rg1 and its analogues from ginseng tea and total ginseng extracts. The column with surface molecularly imprinted polymers showed higher enrichment efficiency and better selectivity than a C18 solid‐phase extraction column. Overall, a new, innovative method was developed to efficiently enrich high‐polarity bioactive molecules present at low concentrations in complex matrices.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
We presented a benchtop technique that can fabricate reconfigurable, three-dimensional (3D) microfluidic devices made from a soft paper-polymer composite. This fabrication approach can produce ...microchannels at a minimal width of 100 μm and can be used to prototype 3D microfluidic devices by simple bending and stretching. The entire fabrication process can be finished in 2 hours on a laboratory bench without the need for special equipment involved in lithography. Various functional microfluidic devices (e.g., droplet generator and reconfigurable electronic circuit) were prepared using this paper-polymer hybrid microfluidic system. The developed method can be applied in a wide range of standard applications and emerging technologies such as liquid-phase electronics.
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