Palladium-Catalyzed Electrooxidative Double C-H Arylation.

The electrochemical transition metal-catalyzed cross-dehydrogenative reaction has emerged as a promising platform to achieve a sustainable and atom-economic organic synthesis that avoids hazardous oxidants and minimizes undesired byproducts and circuitous functional group operations. However, a poor mechanistic understanding still prevents the widespread adoption of this strategy. In this regard, we herein present an electrochemical palladium-catalyzed oxidative coupling strategy to access biaryls in the absence of a stoichiometric chemical oxidant. The robust palladaelectrocatalysis considerably suppresses the occurrence of homocoupling and oxygenation, being compatible even with electron-deficient arenes. Late-stage functionalization and Boscalid precursor synthesis further highlighted the practical importance of our electrolysis. Remarkably, mechanistic studies including the evaluation of the reaction order of each component by variable time normalization analysis (VTNA) and initial rate analysis, H/D exchange experiment, kinetic isotope effect, and stoichiometric organometallic experiments provided strong support for the involvement of transmetalation between two organopalladium complexes in the turnover limiting step. Therefore, matching the concentrations or lifetimes of two distinct organopalladium intermediates is revealed to be a pivot to the success of electrooxidative catalysis. Moreover, the presence of cationic copper(II) seems to contribute to the stabilization of the palladium(0) catalyst instead of playing a role in the oxidation of the catalyst.

Localization Performance Analysis and Algorithm Design of Reconfigurable Intelligent Surface-Assisted D2D Systems.

The research on high-precision and all-scenario localization using the millimeter-wave (mmWave) band is of great urgency. Due to the characteristics of mmWave, blockages make the localization task more complex. This paper proposes a cooperative localization system among user equipment (UEs) assisted by reconfigurable intelligent surfaces (RISs), which considers device-to-device (D2D) communication. RISs are used as anchor points, and position estimation is achieved through signal exchanges between UEs. Firstly, we establish a localization model based on this system and derive the UEs' positioning error bound (PEB) as a performance metric. Then, a UE-RIS joint beamforming design is proposed to optimize channel state information (CSI) with the objective of achieving the minimum PEB. Finally, simulation analysis demonstrates the advantages of the proposed scheme over RIS-assisted base station positioning, achieving centimeter-level accuracy with a 10 dBm lower transmission power.

Proliferating cell nuclear antigen impairs the nuclear import of influenza A virus PB2 and suppresses virus replication.

The genome of Influenza A virus (IAV) transcribes and replicates in the nucleus of cells and the viral ribonucleoprotein (vRNP) complex plays an important role in viral replication. As a major component of the vRNP complex, the polymerase basic protein 2 (PB2) is translocated to the nucleus via its nuclear localization signals mediated by the importins. Herein, it was identified proliferating cell nuclear antigen (PCNA) as an inhibitor of nuclear import of PB2 and subsequent viral replication. Mechanically, PCNA interacted with PB2 and inhibited the nuclear import of PB2. Furthermore, PCNA decreased the binding efficiency of PB2 with importin alpha (importin α) and the K738, K752, and R755 of PB2 were identified as the key sites binding with PCNA and importin α. Furthermore, PCNA was demonstrated to retrain the vRNP assembly and polymerase activity. Taken together, the results demonstrated that PCNA impaired the nuclear import of PB2, vRNP assembly and polymerase activity, which negatively regulated virus replication.

Dynamic evaluation of postoperative survival in intrahepatic cholangiocarcinoma patients who did not undergo lymphadenectomy: a multicenter study.

BACKGROUND: The prognosis of Intrahepatic cholangiocarcinoma (ICC) patients who did not undergo lymphadenectomy is difficult to assess. This study aims to have a dynamic evaluation on the postoperative survival of ICC patients by calculating conditional survival. METHODS: Relevant data were from patients treated in 12 large-scale hospitals from December 2011 to December 2017. The influence of relevant clinical baseline data on the prognosis of ICC patients was analyzed by Cox regression. Conditional survival (CS) is a method that may predict the prognostic probability dynamically. For a patient with x years of survival, the 1-year CS (CS1) may be calculated as CS1= OS(x + 1)/OS(x). RESULT: A total of 361 patients who met the criteria were included in the study. Conditional survival (CS) means that the patients' prognosis varies with survival time, meanwhile, relevant factors affecting the prognosis have a time-varying effect. The probability of survival assessed by CS1 increased year by year and the 1,2,3-year survival improved from 68.4% to 87.8%, while the postoperative actuarial OS decreased from 69.4% at 1 years to 36.9% at 3 years. CONCLUSIONS: In terms of CS, the estimated survival for ICC varies with the increase of survival time after excision. Patients who live longer were likely to live longer. At the same time, with the passage of time, the role of the original adverse factors of the tumor would gradually decrease. Conditional survival allows a more accurate assessment of ICC patients who did not undergo lymphadenectomy.

Impact of antithrombotic drugs on the accuracy of fecal occult blood testing for advanced colorectal neoplasia screening: a meta-analysis and systematic review.

BACKGROUND: The current meta-analysis was conducted to determine whether antithrombotic drug use would affect the diagnostic accuracy of fecal occult blood testing for advanced colorectal neoplasia. METHODS: Articles published between 2000 and 2019 were systematically retrieved and screened according to the inclusion and exclusion criteria by two reviewers independently. Pooled analyses were conducted with a fixed-effect model if no apparent heterogeneity (I2 ≥ 50%) was found between studies; otherwise, the random effects model would be used. Sensitivity analysis and subgroup analysis were also conducted using Review Manager 5.3. RESULTS: Pooled analysis revealed that aspirin and nonsteroidal anti-inflammatory drugs were associated with a decrease in the positive predictive value of fecal occult blood testing for advanced colorectal neoplasia screening, with a RR of 0.89 (95% CI: 0.84-0.94) and 0.88 (95% CI: 0.84-0.93, p<0.001) respectively. Subgroup analysis based on data limited to high-quality studies, fecal immunochemical testing, or in Caucasians also showed that the use of aspirin/NSAID drugs decreased the accuracy for advanced colorectal neoplasia screening. CONCLUSION: Aspirin/NSAIDs and direct oral anticoagulants rather than warfarin may decrease the diagnostic accuracy of fecal occult blood testing for advanced colorectal neoplasia screening.

Joint Optimization of Bandwidth and Power Allocation in Uplink Systems with Deep Reinforcement Learning.

Wireless resource utilizations are the focus of future communication, which are used constantly to alleviate the communication quality problem caused by the explosive interference with increasing users, especially the inter-cell interference in the multi-cell multi-user systems. To tackle this interference and improve the resource utilization rate, we proposed a joint-priority-based reinforcement learning (JPRL) approach to jointly optimize the bandwidth and transmit power allocation. This method aims to maximize the average throughput of the system while suppressing the co-channel interference and guaranteeing the quality of service (QoS) constraint. Specifically, we de-coupled the joint problem into two sub-problems, i.e., the bandwidth assignment and power allocation sub-problems. The multi-agent double deep Q network (MADDQN) was developed to solve the bandwidth allocation sub-problem for each user and the prioritized multi-agent deep deterministic policy gradient (P-MADDPG) algorithm by deploying a prioritized replay buffer that is designed to handle the transmit power allocation sub-problem. Numerical results show that the proposed JPRL method could accelerate model training and outperform the alternative methods in terms of throughput. For example, the average throughput was approximately 10.4-15.5% better than the homogeneous-learning-based benchmarks, and about 17.3% higher than the genetic algorithm.

Preoperative prediction of intrahepatic cholangiocarcinoma lymph node metastasis by means of machine learning: a multicenter study in China.

BACKGROUND: Hepatectomy is currently the most effective modality for the treatment of intrahepatic cholangiocarcinoma (ICC). The status of the lymph nodes directly affects the choice of surgical method and the formulation of postoperative treatment plans. Therefore, a preoperative judgment of lymph node status is of great significance for patients diagnosed with this condition. Previous prediction models mostly adopted logistic regression modeling, and few relevant studies applied random forests in the prediction of ICC lymph node metastasis (LNM). METHODS: A total of 149 ICC patients who met clinical conditions were enrolled in the training group. Taking into account preoperative clinical data and imaging features, 21 indicators were included for analysis and modeling. Logistic regression was used to filter variables through multivariate analysis, and random forest regression was used to rank the importance of these variables through the use of algorithms. The model's prediction accuracy was assessed by the concordance index (C-index) and calibration curve and validated with external data. RESULT: Multivariate analysis shows that Carcinoembryonic antigen (CEA), Carbohydrate antigen19-9 (CA19-9), and lymphadenopathy on imaging are independent risk factors for lymph node metastasis. The random forest algorithm identifies the top four risk factors as CEA, CA19-9, and lymphadenopathy on imaging and Aspartate Transaminase (AST). The predictive power of random forest is significantly better than the nomogram established by logistic regression in both the validation group and the training group (Area Under Curve reached 0.758 in the validation group). CONCLUSIONS: We constructed a random forest model for predicting lymph node metastasis that, compared with the traditional nomogram, has higher prediction accuracy and simultaneously plays an auxiliary role in imaging examinations.

D2D-Assisted Multi-User Cooperative Partial Offloading in MEC Based on Deep Reinforcement Learning.

Mobile edge computing (MEC) and device-to-device (D2D) communication can alleviate the resource constraints of mobile devices and reduce communication latency. In this paper, we construct a D2D-MEC framework and study the multi-user cooperative partial offloading and computing resource allocation. We maximize the number of devices under the maximum delay constraints of the application and the limited computing resources. In the considered system, each user can offload its tasks to an edge server and a nearby D2D device. We first formulate the optimization problem as an NP-hard problem and then decouple it into two subproblems. The convex optimization method is used to solve the first subproblem, and the second subproblem is defined as a Markov decision process (MDP). A deep reinforcement learning algorithm based on a deep Q network (DQN) is developed to maximize the amount of tasks that the system can compute. Extensive simulation results demonstrate the effectiveness and superiority of the proposed scheme.

Rhodaelectro-Catalyzed peri-Selective Direct Alkenylations with Weak O-Coordination Enabled by the Hydrogen Evolution Reaction (HER).

Direct C-H functionalizations by electrocatalysis is dominated by strongly coordinating N(sp2 )-directing groups. In sharp contrast, direct electrocatalytic transformations of weakly-coordinating phenols remain underdeveloped. Herein, electrooxidative peri C-H alkenylations of challenging 1-naphthols were achieved by versatile rhodium(III) catalysis via user-friendly constant current electrolysis. The rhodaelectrocatalysis employed readily-available alkenes and a protic reaction medium and features ample scope, good functional group tolerance and high site- and stereoselectivity. The strategy was successfully applied to high-value, nitrogen-containing heterocycles, thereby providing direct access to uncommon heterocyclic motifs based on the dihydropyranoquinoline skeleton.

Distal Ruthenaelectro-Catalyzed meta-C-H Bromination with Aqueous HBr.

While electrochemical ortho-selective C-H activations are well established, distal C-H activations continue to be underdeveloped. In contrast, we herein describe the electrochemical meta-C-H functionalization. The remote C-H bromination was accomplished in an undivided cell by RuCl3 ⋅3 H2 O with aqueous HBr. The electrohalogenation proceeded under exogenous ligand- and electrolyte-free conditions. Notably, pyrazolylarenes were meta-selectively brominated at the benzenoid moiety, rather than on the electron-rich pyrazole ring for the first time. Mechanistic studies were suggestive of an initial ruthenacycle formation, and a subsequent ligand-to-ligand hydrogen transfer (LLHT) process to liberate the brominated product.

Electrochemical C-H Amidation of Heteroarenes with N-Alkyl Sulfonamides in Aqueous Medium.

The construction of C-N bonds by free radical reactions represents a powerful synthetic approach for direct C-H amidations of arenes or heteroarenes. Developing efficient and more environmentally friendly synthetic methods for C-H amidation reactions remains highly desirable. Herein, metal-free electrochemical oxidative dehydrogenative C-H amidations of heteroarenes with N-alkylsulfonamides have been accomplished. The catalyst- and chemical-oxidant-free C-H amidation features an ample scope and employs electricity as the green and sole oxidant. A variety of heteroarenes, including indoles, pyrroles, benzofuran and benzothiophene, thereby underwent this C(sp2 )-H nitrogenation. Cyclic voltammetry studies and control experiments provided evidence for nitrogen-centered radicals being directly generated under metal-free electrocatalysis.

Electro-oxidative Intermolecular Allylic C(sp3)-H Aminations.

The oxidative intermolecular nitrogenation of C(sp3)-H bonds represents one of the most straightforward strategies to construct nitrogen-containing molecules. However, a sacrificial chemical oxidant is generally required. Herein, we describe electrochemical oxidative intermolecular allylic C(sp3)-H aminations in an undivided cell by electric current. The cross-dehydrogenative amination proceeded efficiently with ample scope under metal- and chemical oxidant-free reaction conditions, giving molecular H2 as the only byproduct.

The storage stability of Bacillus subtilis spore displaying cysteine protease of Clonorchis sinensis and its effect on improving the gut microbiota of mice.

Bacillus subtilis (B. subtilis) spore can serve as an ideal vehicle for expressing heterologous antigens, and elicit specific immune responses by oral administration. In previous studies, we successfully constructed the recombinant B. subtilis spores expressing cysteine protease of Clonorchis sinensis (C. sinensis, B.s-CsCP), and confirmed that oral administration of B.s-CsCP could elicit good protective immune responses in mice. In this study, Gram staining was used to observe the morphology of B.s-CsCP in different form, and the storage of liquid spores and lyophilized spores at different temperatures was compared. The mice were orally immunized with three different doses of spores (2×108, 1×109, and 5×109 CFU/day) for three times in total at biweekly interval. Then, antibody levels of mice were measured, the safety of spores was evaluated, and the changes of gut microbiota after oral gavage of spores (1×109 dose) were investigated. Results showed that B. subtilis was a typical Gram-positive bacterium, and its spore had good resistance to chemical dye. Liquid B. subtilis spores resuspended in sterile water could be stored for a long time at 4 °C or below, while lyophilized spores could be well stored even at RT and better at lower temperatures. Oral administration of B. subtilis spores to mice could stimulate both local mucosal and systemic immune responses in a dose-dependent manner without toxic side effects. Besides, beneficial bacteria producing butyrate such as Odoribacter were increased, while potential pathogens such as Escherichia-Shigella were decreased in mice intestine. Therefore, our work further confirmed that B. subtilis spores expressing CsCP could be a promising oral vaccine against C. sinensis with the advantages of stability, safety, easy storage, and promotion of intestinal health.Key Points• Recombinant CsCP B. subtilis spores could be easily preserved in either liquid or freeze-dried state.• Oral immunization of recombinant spores in mice could increase both local and system immune levels in a dose-dependent manner.• Oral administration of recombinant spores increased the number of beneficial bacteria and reduced the number of harmful bacteria in the intestinal tract of mice.

Acquirement of HRP conjunct IgG anti-IgMs from most widely cultured freshwater fishes in China and its immunoreactivity.

Until now, custom-made or commercial polyclonal antibody against only one kind of fish IgM limited application of the antibody. During our research on development of vaccine against infection of Clonorchis sinensis (C. sinensis) in several kinds of fish, we were conscious of the urgency of secondary antibody to evaluate immune effect and screen C. sinensis infection with immunological technology instead of labor-intensive and time-consuming squash or artificial digestion of fish flesh. So that, we purified IgM of grass carp, bighead carp, crucian carp, common carp and tilapia which were widely cultured freshwater fishes in most areas of China. On this basis, we generated HRP-conjunct rabbit IgG anti-fish IgMs with high titers. IgM of other freshwater fishes including oshima, yellow catfish, bream, silver carp and so on could be recognized by the IgG sensitively. Additionally, The ELISA detection displayed that the IgG could be more specific and sensitive than custom-made rabbit IgG anti-grass carp IgM. The acquirement of HRP-conjunct rabbit IgG anti-fish IgMs was the cornerstone for studying the immune system of teleost fish, developing immunoassay methods and evaluation of fish vaccine with more convenience.

Electrooxidative Rhodium-Catalyzed [5+2] Annulations via C-H/O-H Activations.

Electrooxidative annulations involving mild transition metal-catalyzed C-H activation have emerged as a transformative strategy for the rapid construction of five- and six-membered heterocycles. In contrast, we herein describe the first electrochemical metal-catalyzed [5+2] cycloadditions to assemble valuable seven-membered benzoxepine skeletons by C-H/O-H activation. The efficient alkyne annulation featured ample substrate scope, using electricity as the only oxidant. Mechanistic studies provided strong support for a rhodium(III/I) regime, involving a benzoxepine-coordinated rhodium(I) sandwich complex as the catalyst resting state, which was re-oxidized to rhodium(III) by anodic oxidation.

Evaluation of immune response to Bacillus subtilis spores expressing Clonorchis sinensis serpin3.

Clonorchis sinensis (C. sinensis) is one of the most serious food-borne parasites, which can lead to liver fibrosis or cholangiocarcinoma. Effective measures for clonorchiasis prevention are still urgently needed. Bacillus subtilis (B. subtilis) is an effective antigen delivery platform for oral vaccines. Chonorchis sinensis serpin (CsSerpin) was proved to be potential vaccine candidates. In this study, CsSerpin3 was displayed on the surface of B. subtilis spore and recombinant spores were orally administrated to BALB/C mice. CsSerpin3-specific IgA levels in faecal, bile and intestinal mucous increased at 4-8 weeks after the first administration compared with those in control groups. The mucus production and the number of goblet cells in intestinal mucosa elevated in B.s-CotC-CsSerpin3 (CotC, coat protein of B. subtilis spore) spores treated group compared to those in blank control. No significant difference in the activities of glutamic-pyruvic transaminase/ alanine aminotransferase and glutamic oxalacetic transaminase/aspartate aminotransferase were observed between groups. There was no side effect inflammation and observable pathological damage in the liver tissue of mice after administration. Moreover, collagen deposition and Ishak score were statistically reduced in B.s-CotC-CsSerpin3 spores treated mice. In conclusion, B. subtilis spores displaying CsSerpin3 could be investigated further as an oral vaccine against clonorchiasis.

Oral delivery of Bacillus subtilis spores expressing Clonorchis sinensis paramyosin protects grass carp from cercaria infection.

Clonorchis sinensis (C. sinensis), an important fishborne zoonotic parasite threatening public health, is of major socioeconomic importance in epidemic areas. Effective strategies are still urgently expected to prevent against C. sinensis infection. In the present study, paramyosin of C. sinensis (CsPmy) was stably and abundantly expressed on the surface of Bacillus subtilis spores. The recombinant spores (B.s-CotC-CsPmy) were incorporated in the basal pellets diet in three different dosages (1 × 105, 1 × 108, 1 × 1011 CFU/g pellets) and orally administrated to grass carp (Ctenopharyngodon idella). The immune responses and intestinal microbiota in the treated grass carp were investigated. Results showed that specific anti-CsPmy IgM levels in sera, skin mucus, bile, and intestinal mucus, as well as mRNA levels of IgM and IgZ in the spleen and head kidney, were significantly increased in B.s-CotC-CsPmy-1011 group. Besides, transcripts levels of IL-8 and TNF-αin the spleen and head kidney were also significantly elevated than the control groups. Moreover, mRNA levels of tight junction proteins in the intestines of B.s-CotC-CsPmy-1011 group increased. Potential pathogenetic bacteria with lower abundance and higher abundances of candidate probiotics and bacteria associated with digestion in 1 × 1011 CFU/g B.s-CotC-CsPmy spores administrated fishes could be detected compared with control group. The amount of metacercaria in per gram fish flesh was statistically decreased in 1 × 1011 CFU/g B.s-CotC-CsPmy spores orally immunized group. Our work demonstrated that B. subtilis spores presenting CsPmy on the surface could be a promising effective, safe, and needle-free candidate vaccine against C. sinensis infection for grass carp.

Granular activated carbon-supported titanium dioxide nanoparticles as an amendment for amending copper-contaminated sediments: Effect on the pH in sediments and enzymatic activities.

The problem of heavy metal pollution in sediments attracts increasing attention with the process of industrialization. In this study, a novel sediments amendment granular activated carbon (GAC)-supported titanium dioxide nanoparticles (GATN) was synthesized to amend copper (Cu)-contaminated sediments. The effect of the amendments on the potential mobility and bioavailability of Cu was evaluated by the concentration of Cu in the overlying water and the chemical speciations of Cu in sediments. After 35 days of incubation, GATN and GAC were separated from the GATN-amended sediments and the GAC-amended sediments. The European Community Bureau of Reference (BCR) sequence extraction procedure was performed on the separated sediments. Compared with the control group, the addition of 20% GATN amended sediments for 35 days, the Cu concentration in the overlying water decreased by 90.75%. Compared with original sediments, the exchangeable fraction and reducible fraction of Cu decreased from 42.30% to 17.36%-3.63% and 6.57%, respectively, and the oxidizable fraction and residual fraction of Cu increased from 13.57% to 26.77%-33.21% and 56.58%, respectively. The potential mobility and bioavailability of Cu were significantly reduced. According to the BCR sequence extraction results of the remaining sediments after the separation of the GATN, the Cu adsorbed on the GATN surface is mainly an oxidizable fraction, which is generated by the complexation reaction of hydroxyl (-OH) and Cu2+. Meanwhile, the present of GATN also can enhance the remediation capacity of sediments, which plays an important role during the amendment process. The pH was measured after GATN-amended sediments adding. Results showed that GATN improved their remediation capacity of sediments by optimizing the pH in sediments. The enzyme activity-experiment indicated that GATN effectively reduces the biological toxicity of Cu in Cu-contaminated sediments. Results verified that GATN, as a sediments amendment, has good application potential.

Effect of modified graphene oxide on Cu and phosphorus in eutrophic river sediments.

Ulansuhai nur is located in the cold and dry area of China, and the management of heavy metals in the sediments is related to water safety in the lower places of the Yellow River. Graphene oxide (GO) is modified to obtain magnetic graphene oxide (G-F) and chitosan grafted graphene oxide (G-N-C) materials, which are used to immobilize Cu in the sediments. The modified materials are characterized by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), and X-ray diffractometer (XRD). G-F respectively reduces the concentration of Cu in the overlying and interstitial water by 61.5-66.3% and 22.4-47.1%, which is more effective than GO and G-N-C. Experiments are designed to determine the effect of phosphates concentration on immobilizing Cu in the sediments by modified materials. The results show that a low concentration of phosphates solution is beneficial to the immobilization of Cu in the sediments, and the capability of G-F to immobilize Cu is higher than that of GO and G-N-C. G-F presents a lower increase in organic phosphorus in the sediments than GO and G-N-C. In summary, the modified materials can immobilize Cu in the sediments, potentially reduce the water body eutrophication, and improve the lake ecological environment.

FeOOH Nanocubes Anchored on Carbon Ribbons for Use in Li/O2 Batteries.

A composite of FeOOH nanocubes anchored on carbon ribbons has been synthesized and used as a cathode material for Li/O2 batteries. Fe2+ ion-exchanged resin serves as a precursor for both FeOOH nanocubes and carbon ribbons, which are formed simultaneously. The as-prepared FeOOH cubes are proposed to have a core-shell structure, with FeOOH as the shell and Prussian blue as the core, based on information from XPS, TEM, and EDS mapping. As a cathode material for Li/O2 batteries, FeOOH delivers a specific capacity of 14816 mA h g-1 cathode with a cycling stability of 67 cycles over 400 h. The high performance is related to the low overpotential of the oxygen reduction/evolution reaction on FeOOH. The cube structure, the supporting carbon ribbons, and the -OOH moieties all contribute to the low overpotential. The discharge product Li2 O2 can be efficiently decomposed in the FeOOH cathode after a charging process, leading to higher cycling stability. Its high activity and stability make FeOOH a good candidate for use in non-aqueous Li/O2 batteries.