Direct N-Glycosylation of Amides/Amines with Glycal Donors.

Direct N-glycosylation between glycals and amides/amines was achieved with exclusive stereoselectivity in moderate to high yields. Various amides, amines, and 3,4-O-carbonate-glycals were tolerated, and unique ß-N-glycosides were obtained. The strategy was based on palladium-catalyzed decarboxylative allylation, and the high 1,4-cis-selectivity was proposed because of the hydrogen bonding effect. Notably, all the synthesized products were subjected to preliminary bioactivity studies, revealing that three compounds were cytotoxic to tumor cells and nontoxic to normal human cells.

Odorless Isocyanide Chemistry: One-Pot Synthesis of Heterocycles via the Passerini and Postmodification Tandem Reaction Based on the in Situ Capture of Isocyanides.

This paper reports the tandem reaction strategy of the Passerini/Staudinger/aza-Wittig reaction based on the in situ capture of isocyanides. According to this strategy, isocyanides are synthesized in situ and immediately work as the substrate for the Passerini reaction and postmodification tandem reaction in one pot. In addition, two types of new compounds, 5-oxo-3,5-dihydrobenzo[ e][1,4]oxazepines and 6-oxo-5,6-dihydro-2 H-1,4-oxazines, were synthesized using the tandem reaction strategy that includes five-step transformations in one pot.

Thermo-thickening behavior and its mechanism in a chitosan-graft-polyacrylamide aqueous solution.

A novel thermo-thickening behavior of a chitosan-g-polyacrylamide (CS-g-PAM, GPAM) aqueous solution is reported for the first time in this work. The viscosity of GPAM aqueous solutions significantly increases above a critical temperature upon heating, as observed in dynamic and steady rheological experiments. Differing from the widely reported hydrophobic modified CS, GPAM was prepared by grafting hydrophilic polyacrylamide side chains onto the CS backbone, therefore the thermo-thickening behavior of the GPAM aqueous solution could not be explained by the usual thermo-thickening mechanism induced by the additional hydrophobic moiety or LCST segment. The origin of the thermo-thickening in GPAM solutions was explored using transmission electron microscopy (TEM), dynamic light scattering (DLS), and nuclear magnetic resonance (NMR) tests of the GPAM solution. A transformation from a hydrogen bonding (H-bonding) aggregate to a hydrophobic aggregate upon heating was confirmed to be responsible for the thermo-thickening. The heating initiates a transformation of large loose H-bonding aggregates into abundant small compact ones formed by self-assembled hydrophobic chitosan backbones, resulting in aggregate associations and thus flocculated aggregate networks. Some factors of the thermo-thickening were investigated and discussed in detail, including the heating history, concentration, grafting ratio, and length of the PAM side chain. Besides the influence caused by the heating history, this thermo-thickening process is influenced by kinetic factors, including the mobility of the macromolecule chains and the formation of new aggregate networks that are dependent on the number of hydrophobic clusters.

The special optical properties and application of the heterocyclic compound diethyl 6-anilino-5H-2,3-dithia-5,7-diazacyclopenta(cd)indene-1,4-dicarboxylate.

The heterocyclic compound diethyl 6-anilino-5H-2,3-dithia-5,7-diazacyclopenta(cd)indene-1,4-dicarboxylate (D1) was found to form highly emissive aggregates in polar solvents, and the aggregate emission can be tuned by the simple addition of water to a dimethylsulfoxide solution. A theoretical study based on Density functional theory (DFT) calculations, shows that intermolecular interactions of D1 with solvent may be potential factors in the fluorescence change. In addition, the phenyl ring in D1 plays an important role because of its response to solvent. In the non-aggregated state, deprotonation of the N-H of D1 can proceed easily on the addition of base, and the deprotonated compound might interact with Ag(+), resulting in a significant change in color and fluorescence quenching, which make it a potential chemosensor for the selective detection of trace amounts of Ag(+).

Facile synthesis of 2-vinylindolines via a phosphine-mediated α-umpolung/Wittig olefination/cyclization cascade process.

A novel phosphine-mediated α-umpolung/Wittig olefination/cyclization cascade process between o-aminobenzaldehydes and Morita-Baylis-Hillman (MBH) carbonates has been ingeniously developed. This protocol serves as a practical tool for the facile synthesis of a broad range of 2-vinylindolines in moderate to good yields under mild reaction conditions. The applicability of this method was demonstrated with gram-scale reaction and various transformations of the corresponding product.

Clinical Efficacy of Epidural Injections of Local Anesthetic Alone or Combined with Steroid for Neck Pain: A Systematic Review and Meta-Analysis.

Aims: To compare the effectiveness of cervical epidural injections of local anesthetic with vs. without a steroid. Methods: Three databases (PubMed, Embase, and Cochrane library) were used to search and assess all clinical randomized controlled trials regarding the clinical efficacy of epidural injections from January 01, 2009, to October 31, 2020. Cochrane review criteria and the Interventional Pain Management Techniques-Quality Appraisal of Reliability and Risk of Bias Assessment instrument were used to evaluate the methodologic quality of the included studies. Qualitative and quantitative analyses were performed according to best evidence synthesis principles and by single-arm meta-analysis, respectively. Results: Based on the search criteria, 4 RCTs were qualitatively and quantitatively analyzed in the single-arm meta-analysis. Treatment with lidocaine alone or with the steroid resulted in decreases of 4.46 and 4.29 points, respectively, in pain scores and of 15.8 and 14.46 points, respectively, in functional scores at 6 months. Similar trends were observed at the 1-year follow-up: pain scores decreased by 4.27 and 4.14 points, while functional scores decreased by 15.94 and 14.44 points in patients with neck pain who received lidocaine without or with the steroid, respectively. In the 3 studies that reported 2-year follow-up data, patients with neck pain treated with lidocaine or lidocaine + steroid showed 4.2- and 4.14-point decreases, in pain score and 15.92- and 14.89-point decreases, respectively, in functional scores. Conclusions: The studies showed level I (strong) evidence for short- and long-term improvements in pain relief and functionality with cervical epidural injections of local anesthetic alone or with a steroid in the management of neck pain.

The landscape of bispecific T cell engager in cancer treatment.

T cell-based immunotherapies have revolutionized treatment paradigms in various cancers, however, limited response rates secondary to lack of significant T-cell infiltration in the tumor site remain a major problem. To address this limitation, strategies for redirecting T cells to treat cancer are being intensively investigated, while the bispecific T cell engager (BiTE) therapy constitutes one of the most promising therapeutic approaches. BiTE is a bispecific antibody construct with a unique function, simultaneously binding an antigen on tumor cells and a surface molecule on T cells to induce tumor lysis. BiTE therapy represented by blinatumomab has achieved impressive efficacy in the treatment of B cell malignancies. However, major mechanisms of resistance to BiTE therapy are associated with antigen loss and immunosuppressive factors such as the upregulation of immune checkpoints. Thus, modification of antibody constructs and searching for combination strategies designed to further enhance treatment efficacy as well as reduce toxicity has become an urgent issue, especially for solid tumors in which response to BiTE therapy is always poor. In particular, immunotherapies focusing on innate immunity have attracted increasing interest and have shown promising anti-tumor activity by engaging innate cells or innate-like cells, which can be used alone or complement current therapies. In this review, we depict the landscape of BiTE therapy, including clinical advances with potential response predictors, challenges of treatment toxicity and resistance, and developments of novel immune cell-based engager therapy.

Excellent Response to Atezolizumab After Clinically Defined Hyperprogression Upon Previous Treatment With Pembrolizumab in Metastatic Triple-Negative Breast Cancer: A Case Report and Review of the Literature.

Immunotherapy with immune checkpoint inhibitors (ICIs), including programmed cell death protein-1 (PD-1) and programmed cell death ligand-1 (PD-L1) inhibitors, has revolutionized the systematic treatment of advanced and metastatic solid tumors. However, the response rate to ICIs is unsatisfactory, and unexpected hyperprogressive disease (HPD) is even observed in a small subgroup of patients. Patients with HPD usually have worsening clinical symptoms and poorer survival, and therapeutic strategies are extremely limited. Here, we presented a patient with HPD who had used a PD-L1 inhibitor and was highly responsive to the sequential use of a PD-1 inhibitor. A 67-year-old woman with metastatic triple-negative breast cancer was treated with pembrolizumab plus chemotherapy after progression on previous multiple-line chemotherapy treatments. After 2 cycles of treatments, she rapidly developed HPD, as confirmed by radiological evaluation and worsening symptoms. At that time, pembrolizumab was discontinued, and she switched to the PD-L1 inhibitor atezolizumab plus chemotherapy. This patient partially responded to atezolizumab plus chemotherapy without experiencing severe drug-related adverse effects. This is the first reported case of metastatic breast cancer in a patient with radiologically confirmed HPD after pembrolizumab therapy in which successful rechallenge with atezolizumab relieved clinical symptoms. Further studies with larger sample sizes involving a deeper translational investigation of HPD are needed to confirm the efficacy and mechanism of sequential application of different ICIs for the clinical management of HPD.

Adjuvant therapy fails to show survival benefit for patients with spindle cell carcinoma: Evidence from the surveillance, epidemiology, and end results database.

BACKGROUND: Spindle cell carcinoma (SpCC) is a rare tumor type with poor prognosis, and standard treatment modalities are not available yet. However, large-scale studies on this topic are sparse. In this study, data from the surveillance, epidemiology, and end results (SEER) database were used to determine cancer-specific survival (CSS) rates of SpCC and to investigate the impact of different therapeutic strategies including surgery with or without chemotherapy, radiotherapy, or chemoradiotherapy on patient outcome. METHODS: A total of 665 cases of SpCC, diagnosed from 1996 to 2015, were extracted from the SEER database. Kaplan-Meier survival curves and log-rank tests were used to assess CSS rates and differences on survival curves. Multiple COX-proportional hazards models were used to analyze the association between various treatments and prognosis of SpCC patients classified by organs or systems. RESULTS: Different treatments for SpCC in different organ or system were associated with prognosis of SpCC patients. Surgery alone exhibits survival benefit, whereas adjuvant therapy fails to show survival benefit for patients with SpCC. CONCLUSIONS: The prognosis of SpCC patients varied significantly with different clinical treatments. Adjuvant radiotherapy or chemotherapy did not show survival benefit, even increasing the risk of mortality for SpCC patients.

Effect of strip shelterwood-cuts on the crown morphology plasticity of natural regenerated Pinus tabuliformis saplings in northeastern China.

The study analysed the effect of shelterwood-cut strips on the outermost crown profiles and crown characteristics of naturally regenerated Pinus tabuliformis saplings in northeastern China. A total of 49 regenerated saplings from shelterwood-cut strips and 30 from uncut strips were collected. Nonlinear quantile regression was used to develop the outermost crown profile model for the saplings from the shelterwood-cut and uncut strips. The quantile value suitable for describing the outermost crown profiles of the two types of strips was selected using nonparametric boundary regression. The difference in crown morphologies between the shelterwood-cut strips and uncut strips was compared. The results showed that with the same diameter at breast height, the crown radii of the uncut strip saplings were larger than those of the shelterwood-cut strip saplings within the range of 0.2-1.0 for the relative depth into the crown. The largest crown radius of the saplings from the uncut strips was larger than that of the saplings from the shelterwood-cut strips. The inflection points of the shelterwood-cut strip sapling crowns were larger than those of the uncut strip sapling crowns. The crown volume of the small uncut strip saplings was larger than that of the shelterwood-cut strip saplings, and the difference in crown volume decreased with increasing sapling size. The saplings in the early stage of the uncut strips showed a greater growth rate than those of the shelterwood-cut strips, but their growth rate slowed over the long term according to branch-length annual growth. The present study provides a reference for forest management strategy decision making in promoting natural regeneration.

The complete chloroplast genome sequence of Prunus sibirica.

In this study, the chloroplast genome sequence of Prunus sibirica was obtained from the whole genome sequencing data of Prunus sibirica. Its length is 158,248 bp, which consists of 86,331 bp large single-copy region (LSC), 26,408 bp two reverse repeat regions (IR) and 19,101 bp small single-copy region (SSC). GC content of the whole chloroplast genome is 36.71%. Those of LSC region, SSC region, and IR region were 35, 30, and 43%, respectively. There are 131 unique genes in the chloroplast genome, including 90 protein-coding genes, 33 tRNA genes, and 8 rRNA genes. A maximum-likelihood phylogenetic tree was generated from the chloroplast genomes of 10 species of Rosaceae and 11 peripheral plants. The results showed that Prunus sibirica belongs to Rosaceae and is sister to Prunus salicina.

Open-Air Stereoselective Construction of C-Aryl Glycosides.

A new methodology of stereoselective C-glycosylation has been developed with 3,4-O-carbonate glycals and boronic acids, catalyzed by 1,2-bis(phenylsulfinyl)ethane palladium(II) acetate under open-air conditions at room temperature. This mild method is simple in operation, wide in substrate range, and tolerant in alcoholic/phenolic hydroxyl and amino groups. High to excellent yields were observed for all substrates tested, with the driving force mainly contributed by decarboxylation. Meanwhile, the high 1,4-trans-selectivity was achieved by steric effects as proposed.

Efficient regioselective synthesis of indole N-carboximidamides and N-carboximidoates by a sequential Aza-Wittig/Ag(I)-catalyzed cyclization.

An efficient Ag(I)-catalyzed regioselective cyclization of (2-alkynylphenyl)guanidine or (2-alkynylphenyl)isourea to indole N-carboximidamides or N-carboximidoates has been developed. The approach has the advantages of high regioselectivity, mild reaction conditions, easily accessible starting materials, and good yields.

Diethyl 3-amino-4-[(triphenyl-phosphor-anyl-idene)amino]thieno[2,3-b]thio-phene-2,5-dicarboxyl-ate.

The asymmetric unit of the title compound, C(30)H(27)N(2)O(4)PS(2), consists of two crystallographically independent mol-ecules. The thieno[2,3-b]thio-phene ring systems are planar. One of the terminal ethyl groups is disordered over two positions; the site occupancy factors are ca 0.7 and 0.3. The crystal structure is stabilized by N-H⋯N, N-H⋯O and C-H⋯O hydrogen bonds.

3-(4-Chloro-phen-yl)-2-(diisopropyl-amino)-1-benzofuro[3,2-d]pyrimidin-4(3H)-one.

In the mol-ecule of the title compound, C(22)H(22)ClN(3)O(2), the three fused rings of the benzofuro[3,2-d]pyrimidine system are almost coplanar. This ring system is oriented with respect to the substituted benzene ring at a dihedral angle of 79.05 (3)°. Intra-molecular C-H⋯N hydrogen bonding results in the formation of a six-membered ring. In the crystal structure, π-π stacking inter-actions involving the furan, pyrimidinone and benzene rings are present [centroid-to-centroid distances in the range 3.258 (1)-3.870 (1) Å].

[Treatment of petrochemical secondary effluent by ozone-biological aerated filter].

The advanced treatment of petrochemical secondary wastewater by ozone- aerated biological filter was carried out in this study. The effect of pH on ozonation and the removal of COD and UV254 by the ozone-aerated biological filter combined process were investigated. In addition, the variation of relative molecular mass distribution of organics and the characteristics of three-dimensional fluorescence spectra of the wastewater were also investigated. The results showed that the suitable operating conditions of the ozonation unit were: ozone dosage 10 mg x L(-1), contact time 4 min and slightly alkaline pH. Ozonation can transfer macromolecular organics into small molecular organics, resulting in a 15% increase in the percentage of the organics with small relative molecular mass (less than 1 000). The biodegradability of the petrochemical secondary effluent was significantly improved by ozonation, making it more suitable for the treatment by aerated biological filter. The removal efficiency of COD and UV254 were 40.8% and 45.8% when the hydraulic retention time was 3 hours and the gas to water ratio was 3:1 for BAF. The average COD of the petrochemical wastewater was 86.5 mg x L(-1) while the average COD of the effluent of the combined process was 49.4 mg x L(-1) when it was operated under optimal conditions.

[Soil moisture characteristics at the boundary of forestland-grassland in hilly area of Loess Plateau].

In this paper, the spatial distribution pattern of soil moisture at the boundary of forestland-grassland in hilly area of Loess Plateau was studied in dry season of June and rainy season of August 2004. The results showed that the variance coefficient of soil moisture content was smaller, and the difference of moisture content between soil layers was less significant in forestland than in grassland in June while reversed in August. There was a weak or medium differentiation of moisture content in different soil layers at the boundary of forestland-grassland. The edge effect area at the boundary was from 2 m (0. 4 of tree height) outside forestland to 2 m inside forestland in June, and from 2 m outside forestland to 4 m (0. 8 of tree height) inside forestland in August. The forestland-grassland landscape could be divided into 3 parts, i.e., grassland area, forest edge area, and forestland area, and the vertical distribution of soil moisture in these three parts showed different traits. In June, soil moisture content increased with increasing soil depth, with a smaller increment in grassland than in forestland, but in August, it was reversed. The vertical distribution of soil moisture at forest edge area showed an in-between feature.

[Spatial heterogeneity of soil moisture after raining at forest-grassland landscape boundary in hilly area of Loess Plateau].

Soil moisture is a main factor limiting vegetation restoration in semi-arid region. In this paper, the spatial variability of different layers soil moisture after raining at the forest-grassland boundary in hilly area of Loess Plateau were studied by traditional and geostatistical analysis methods. The results showed that the moisture content in surface (0 - 10 cm) and subsurface soil layer (10 - 20 cm) of grassland was higher than that of forestland. The two layers soil moisture content at forest-grassland boundary showed a small variation but an obvious ecological distribution. By using moving split-window techniques, it was obtained that the width of edge influence in surface and subsurface layer was 8 and 6 m, respectively. Geostatistical analyses showed that the spatial distribution of two layers soil moisture had a pure nugget effect in grassland, linear model in forestland, and spherical model in forest-grassland boundary. The spatial heterogeneity of two layers soil moisture was higher at forest-grassland boundary than at forestland and grassland, which had a stronger spatial dependence and autorelation. Kriging maps expressed the spatial structural characters. The distribution of soil moisture in two layers showed a strip shape near forest edge, and a patch shape far from the edge.

[Natural regeneration of Pinus sylvestris var. mongolica plantation on sandy land].

By employing comparison analysis and field survey, the natural regeneration of Mongolian pine plantations on sandy soil was investigated. In plantation areas where regeneration can take place naturally, natural regeneration of Mongolian pine varied temporally and spatially. Natural regeneration wasn't temporally continuous; it had a close relationship with autumn precipitation in particular years. In spatial aspect, there were three regeneration types: regeneration in forest gaps, regeneration on edges of a forest, regeneration under young broadleaf forest. There was no significant difference between the growth of regeneration saplings and plantation trees.

Observation of three-photon enhanced four-photon absorption.

We report the measurement of instantaneous resonant four-photon absorption in the polydiacetylene-PTS [polymer poly(bis para-toluene sulfonate) of 2,4-hexadyine-1,6 diol]. Although normally too weak to be observable, an exact degeneracy between three- and four-photon absorption into the dominant exciton and two-photon states, respectively, resonantly enhances this effect so that it can be measured (four-photon coefficient alpha(4)=0.01 cm(5)/GW(3)) at its peak wavelength of 1900 nm. Femtosecond measurements from 1200 to 2200 nm of two- and three-photon absorption, and the nonlinear refractive index coefficient are also reported.