Sulfenylation of C–H bonds for C–S bond formation under metal‐free conditions has become established as a powerful tool in organic chemistry. Various sulfenylation reagents such as thiols, ...disulfides, sulfinic acids, and so on have been employed for sulfenynlation reactions. In this review we mainly summarize the recent advances (2014 to the present) in this area and also discuss the mechanisms.
Sulfenylation of C–H bonds has recently come to receive more and more attention. In this Microreview, recent advances in sulfenylation of C–H bonds for C–S bond formation under metal‐free conditions are reviewed.
This study investigates the optimization problem of an infinite stage discrete time Markov decision process (MDP) with a long‐run average metric considering both mean and variance of rewards ...together. Such performance metric is important since the mean indicates average returns and the variance indicates risk or fairness. However, the variance metric couples the rewards at all stages, the traditional dynamic programming is inapplicable as the principle of time consistency fails. We study this problem from a new perspective called the sensitivity‐based optimization theory. A performance difference formula is derived and it can quantify the difference of the mean‐variance combined metrics of MDPs under any two different policies. The difference formula can be utilized to generate new policies with strictly improved mean‐variance performance. A necessary condition of the optimal policy and the optimality of deterministic policies are derived. We further develop an iterative algorithm with a form of policy iteration, which is proved to converge to local optima both in the mixed and randomized policy space. Specially, when the mean reward is constant in policies, the algorithm is guaranteed to converge to the global optimum. Finally, we apply our approach to study the fluctuation reduction of wind power in an energy storage system, which demonstrates the potential applicability of our optimization method.
In order to enhance the controlled‐release property of starch‐based polyurethane (SPU) coating, polyurethane/montmorillonite (SPU/MMT) composite coatings for controlled‐release urea were prepared by ...in‐situ polymerization with a rotating drum. The effect of MMT on morphology, structure, physico‐chemical properties, especially controlled‐release property of the as‐prepared composite coatings were studied in detail. The results showed that MMT particles dispersed well in SPU matrix, and the obtained SPU/MMT composite coatings possessed more tough and compact morphology with less‐visible holes compared with SPU coating. With the content of MMT rising to 3%, the time needed for 75% nitrogen release increased to 49 days, much longer than 14 days of SPU coating. Further, the nitrogen release mechanism underlying the structure and properties of SPU/MMT composite coatings were discussed and elucidated. According to the analysis, the superior controlled‐release property of SPU/MMT coatings originated from the impermeablity to water molecules of layered MMT acting as mechanical barriers to increase the diffusion path and resistance, the enhanced crosslinking density and hydrophobicity of composite system due to the introduction of MMT, as well as the improved mechanical properties hindering the formation of cracks and enlargement of the holes on the surface of composite coatings.
Background
Pembrolizumab (Pembro) in combination with chemotherapy has been approved for the treatment of pretreated advanced NSCLC in the United States and China for its significant efficacy. ...However, the cost‐effectiveness is unknown considering Pembro's high price. The impact of programmed death ligand 1 (PD‐L1) test on the cost‐effectiveness is also unknown. The current study assessed the cost‐effectiveness of combination therapy for nonsquamous NSCLC from the United States and China public payers’ perspective.
Materials and Methods
A literature‐based Markov model was conducted using KEYNOTE‐189 trial data to compare cost and quality‐adjusted life years (QALYs) of three treatment strategies for nonsquamous NSCLC: Pembro‐chemotherapy combination and chemotherapy strategy without PD‐L1 test, and treatment strategy according to their PD‐L1 status.
Results
In base case analysis, the combination strategy generated an additional 0.78 QALYs and 0.59 QALYs over chemotherapy in the United States and China respectively, resulting in an ICER of $132 392/QALY in the United States and $92 533/QALY in China. In the PD‐L1 ≥1% base case, the ICERs were $77 754/QALY and $56 768/QALY respectively in the United States and China for PD‐L1 test strategy. In the PD‐L1 ≥50% base case, the ICERs were $44 731/QALY and $34 388/QALY respectively in the United States and China for PD‐L1 test strategy. Lowering Pembro price can also partly decrease the ICERs.
Conclusion
Compared with chemotherapy, the combination strategy is not cost‐effective for the treatment of NSCLC in the American and Chinese health care system at WTP threshold of $100 000/QALY for the United States and $27 351/QALY for China. Using PD‐L1 test for patient selection and price reduction could improve the cost‐effective probabilities of immunotherapy for nonsquamous NSCLC.
A literature‐based Markov model was conducted using KEYNOTE‐189 trial data.The patient population was differentiated by PD‐L1 test.Different PD‐L1 positivity thresholds were applied to the model (1% or 50%).The combination strategy yielded superior health outcomes but not cost‐effective.Using PD‐L1 test for patient selection can improve the cost‐effective probability.
Based on previous studies about microflora regulation and immunity enhancement activities of polysaccharides from
Nannf. var.
(Nannf.) L. T. Shen (CPP), there is little study on intestinal mucosal ...immunity, which is a possible medium for contacting microflora and immunity. In the present study, the BALB/c mice were divided into five groups (eight mice in each group), including a normal group (Con), a model control group (Model), and model groups that were administered CPP (50, 100, 200 mg/kg/d) orally each day for seven days after intraperitoneal injection of 60 mg/kg BW/d cyclophosphamide (CP) for three days. CPP recovered the spleen index and restored the levels of IFN-γ, IL-2, IL-10, as well as serum IgG. In addition, it elevated ileum secretory immunoglobulin A (sIgA), the number of
and acetic acid content in cecum. These results indicated that CPP plays an important role in the protection against immunosuppression, especially mucosa immune damage, and the inhibition of pathogenic bacteria colonization, which could be considered a potential natural source of immunoregulator.
Photothermal therapy (PTT) is one of the most promising approaches to combat multidrug‐resistant bacteria with less potential to induce resistance and systemic toxicity. However, uncontrollable ...distribution of photothermal agents leads to lethal temperatures for normal cells, and failure to offer timely and effective antibacterial stewardship. A pH switchable nanoplatform for persistent luminescence imaging‐guided precise PTT to selectively destroy only pathological cells while protecting nearby normal cells in bacterial infected microenvironment is shown. The PLNP@PANI‐GCS is fabricated by grafting polyaniline (PANI) and glycol chitosan (GCS) onto the surface of persistent luminescence nanoparticles (PLNPs). It takes advantage of the long persistent luminescence of PLNPs to realize autofluorescence‐free imaging, the pH‐dependent light–heat conversion property of PANI to get a stronger photothermal effect at pH 6.5 than pH 7.4, and the pH environment responsive surface charge transition of GCS. Consequently, PLNP@PANI‐GCS enables effective response to bacterial‐infected acid region and electrostatic bonding to bacteria in vivo, ensuring the spatial accuracy of near‐infrared light irradiation and specific heating directly to bacteria. In vivo imaging‐guided PTT to bacterial infection abscess shows effective treatment. PLNP@PANI‐GCS has great potential in treating multidrug‐resistant bacterial infection with low possibility of developing microbial drug resistance and little harm to normal cells.
A pH switchable nanoplatform is developed for in vivo persistent luminescent imaging and precise photothermal therapy of bacterial infections. This nanoplatform exhibits specific photothermal therapy to acidic bacterial‐infected regions but no damage to normal tissues.
Highlights ► We successfully prepared hyaluronic acid coated, paclitaxel loaded, nanostructured lipid carriers (HA-NLCs) via electrostatic attraction. ► The in vitro cytotoxicity of HA-NLCs was ...superior to that of Taxol® in B16, CT26 and HCT116 cell lines. ► The in vivo antitumor effect of HA-NLCs in B16-bearing Kunming mice was extremely promising. ► HA-NLC prepared via electrostatic attraction was an effective carrier for delivering paclitaxel PTX to tumors overexpressing CD44.
In this study, an acidic polysaccharide from
Nannf. var.
(Nannf.) L. T. Shen (WCP-I) and its main fragment, WCP-Ia, obtained after pectinase digestion, were structurally elucidated and found to ...consist of a rhamnogalacturonan I (RG-I) region containing both arabinogalactan type I (AG-I) and type II (AG-II) as sidechains. They both expressed immunomodulating activity against Peyer's patch cells. Endo-1,4-β-galactanase degradation gave a decrease of interleukine 6 (IL-6) production compared with native WCP-I and WCP-Ia, but exo-α-l-arabinofuranosidase digestion showed no changes in activity. This demonstrated that the stimulation activity partly disappeared with removal of β-d-(1→4)-galactan chains, proving that the AG-I side chain plays an important role in immunoregulation activity. WCP-Ia had a better promotion effect than WCP-I in vivo, shown through an increased spleen index, higher concentrations of IL-6, transforming growth factor-β (TGF-β), and tumor necrosis factor-α (TNF-α) in serum, and a slight increment in the secretory immunoglobulin A (sIgA) and CD4
/CD8
T lymphocyte ratio. These results suggest that β-d-(1→4)-galactan-containing chains in WCP-I play an essential role in the expression of immunomodulating activity. Combining all the results in this and previous studies, the intestinal immune system might be the target site of WCP-Ia.
Getah virus (GETV) is a neglected mosquito-borne Alphavirus that causes pyrexia, body rash, and leg oedema in horses and foetal death and reproductive disorders in pigs. Infected animals may play a ...critical role in the amplification and circulation of the virus. The present study aimed to investigate GETV infection in clinically infected cattle and vector mosquito species in northeastern China.
Serum samples were collected from beef cattle that presented sudden onset of fever in forest grazing areas, and metagenomic sequencing was conducted, revealing 29 contigs from ten serum samples matching the GETV genome. Quantitative RT-PCR (RT-qPCR) was performed with GETV RNA from 48 beef cattle serum samples, showing that the overall prevalence of GETV in the beef cattle samples was 6.25% (3/48). Serological investigation indicated that GETV neutralizing antibodies were detected in 83.3% (40/48, 95% CI 67-100) of samples from the study region. The GETV JL1808 strain was isolated from clinically infected cattle showing fever. Sequence comparisons showed high identity with the HuN1 strain, a highly pathogenic swine epidemic isolate obtained in Hunan province in 2017, at the nucleotide level (99.5%) and at the deduced amino acid level (99.7-99.9%). The phylogenetic analysis of JL1808 clustered in Group III, and also revealed a close genetic relationship with the HuN1 strain. Additionally, about 12,000 mosquitoes were trapped in this region. The presence of GETV infection was detected in mosquitoes, suggesting that the minimum infection rate (MIR) was 1.50‰, with MIRs of 1.67‰ in Culex pseudovishnui, 1.60‰ in Culex tritaeniorhynchus, and 1.21‰ in Anopheles sinensis.
To the best of our knowledge, this is the first report of GETV infection in cattle. These results demonstrated that a highly pathogenic, mosquito-borne swine GETV can infect and circulate in cattle, implying that it is necessary to conduct surveillance of GETV infection in animals in northeastern China.
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