Cobalt-Catalyzed Asymmetric Deuteration of α-Amidoacrylates for Stereoselective Synthesis of α,ß-Dideuterated α-Amino Acids.

A cobalt-catalyzed deuteration of amidoacrylates using deuterated methanol afforded α,ß-dideuterio-α-amino esters in excellent enantiomeric ratios (mostly >95 : 5) and almost complete deuteration (99 %). The new protocol was used to prepare dideuterio-α-amino acid fragments in some drugs. Furthermore, the stereoselective deuteration was applied in a concise synthesis of dideuterio l-DOPA.

Temporal dynamics of negative air ion concentration and its relationship with environmental factors: Results from long-term on-site monitoring.

Negative air ions (NAIs) play an important role in evaluating forest health effects and promoting human physical and mental health. In this paper, long-term on-site monitoring of NAI concentration, air temperature, and relative humidity was conducted in real time over 24 h, from July 2019 to March 2021, to explore the temporal dynamic patterns of NAIs. We found that the daily dynamics of NAI concentration showed a bimodal curve. The peak concentrations usually occurred in the early morning (5:00-7:00) and afternoon (15:00-17:00), and the lowest concentrations usually occurred at noon (11:00-13:00). At the monthly scale, NAI concentrations were relatively high in February and August and low in May and December, and at the seasonal scale, NAI concentration was significantly higher in summer than in other seasons. Autumn had the second highest NAI concentration. There was no significant difference in NAI concentration between winter and spring. A comprehensive analysis shows that the AQI was the most key factor affecting NAI concentrations compared to temperature and relative humidity, especially the two indicators of particulate matter and ozone, and that NAI concentration had a negative correlation with these indicators and was significantly higher under favorable air quality conditions than under polluted air conditions. NAI concentrations and air temperature showed marked piecewise characteristics, with NAIs increasing linearly with rising temperature only if the Ta was separated into three ranges of -5 °C-10 °C, 10 °C-30 °C, and 30 °C-40 °C. With rising relative humidity, NAI concentration increased in accordance with a quadratic function. Our research provides new insights into the NAI temporal dynamics patterns and its driving factors, and will aid in scheduling outdoor recreation and forest health activities for urban people.

The utility of diffusion-weighted imaging and ADC values in the characterization of mumps orchitis and seminoma.

BACKGROUND: Diffusion-weighted imaging (DWI) can quantitatively reflect the diffusion characteristics of tissues, providing a theoretical basis for qualitative diagnosis and quantitative analysis of a disease. PURPOSE: To characterize testicular lesions that present as a hypointense signal on magnetic resonance imaging (MRI) T2-weighted images using DWI. MATERIAL AND METHODS: Study participants were divided into three groups. Group A were healthy controls (n = 35), group B included patients with mumps orchitis (n = 20), and group C included patients with seminoma (n = 15). DWI sequences used b-values of 0, 1000, and 2000 s/mm2. Apparent diffusion coefficient (ADC) values between 1000 and 2000 s/mm2 were calculated by MRI postprocessing software. The Kruskal-Wallis test and receiver operating characteristic analysis were performed to evaluate how well ADC values distinguished between mumps orchitis and seminoma. RESULTS: Normal testicular tissue showed a hyperintense signal on DWI and hypointensity on the ADC map: mean ADC value was 0.77 (0.69-0.85) ± 0.08 ×10-3 mm2/s. Mumps orchitis and seminoma showed slight hyperintensity on DWI: mean ADC values were 0.85 (0.71-0.99) ± 0.15 ×10-3 mm2/s and 0.43 (0.39-0.47) ± 0.04 × 10-3 mm2/s, respectively. There were statistically significant differences in mean ADC values between normal testicular tissue and seminoma and between mumps orchitis and seminoma. The cutoff ADC value for differentiating seminoma from mumps orchitis was 0.54 × 10-3 mm2/s. The sensitivity, specificity, and Youden Index for diagnosing seminoma were 99%, 31%, and 30%, respectively. CONCLUSION: High b-value DWI has potential utility for differentiating mumps orchitis from seminoma in the clinical setting.

MRI findings of an atypical testicular epidermoid cyst: A case report.

INTRODUCTION: Typical testicular epidermoid cysts (TECs) manifestate as a target sign or onion skin sign on ultrasonography and magnetic resonance (MR) imaging. Clinicians are increasingly aware of the imaging characteristics of typical TECs, which allow accurate diagnosis and successful treatment while preserving the testicle, but atypical TECs are likely to be misdiagnosed as a malignant intratesticular neoplasm, leading to complete testicular resection. PATIENT CONCERNS: A 26 year-old male patient complained of a painless enlargement of the left testicle that had been present for 1 month. The patient had no recent medical history of scrotal trauma or systemic infection. DIAGNOSIS: A round 48 mm × 45 mm × 43 mm mass was seen inside the left testicle. T2-weighted images of the lesion showed a thin hypointense capsule. T1-weighted images of the lesion showed a hyperintense nodule on the cyst wall, which appeared hypointense on T2-weighted and SPAIR images. After Gd-DTPA injection, the lesion was not enhanced; however, the nodule was enhanced on THRIVE images. These manifestations were consistent with a benign intratesticular lesion, and MR imaging diagnosed atypical TEC, which was confirmed by pathology after surgery. INTERVENTIONS: The patient was treated with organ-sparing surgery with testicular enucleation. OUTCOMES: The patient was re-examined with ultrasonography 3 months after surgery. The left residual testicular tissue appeared normal, and reproductive function was preserved. CONCLUSION: Urologists must be aware of the clinical and MR imaging characteristics of atypical TECs and the utility of preoperative MR imaging for the diagnosis of testicular lesions to ensure that organ-sparing surgery is performed rather than unnecessary orchiectomy.

Differentiation of testicular seminoma and nonseminomatous germ cell tumor on magnetic resonance imaging.

Magnetic resonance imaging (MRI) has excellent soft tissue resolution, as well as multidirectional and multisequence scanning technology, making it an important supplementary method in the diagnosis of testicular tumor.To explore the utility of preoperative MRI for the differential diagnosis of testicular seminoma and nonseminomatous germ cell tumors (NSGCTs).The medical records from 39 patients with testicular tumors that were examined preoperatively with MRI and treated with urologic surgery at our institution between January 2015 and March 2019 were retrospectively reviewed. Testicular tumors were confirmed by pathology and classified as seminoma (n = 20) or NSGCT (n = 19). Two radiologists analyzed the testicular tumors on preoperative MRI for morphology: multiple nodules or a single mass; presence/absence of a capsule; signal compared to the normal contralateral testicle (isointense, hypointense, hyperintense, or mixed); enhancement; septa; and hemorrhagic or cystic degeneration. Characteristics of seminomas and NSGCT were compared using the Chi-square or Fischer exact test.MRI showed that the majority (95%; 19/20) of seminomas were nodular. There were significant differences in the presence/absence of a capsule (P = .001), T1-weighted imaging (T1WI) signal intensity (P = .047), T2-weighted imaging (T2WI) signal intensity (P < .001), septa (P < .001), and hemorrhagic or cystic degeneration (P < .001) between seminomas and NSGCT.Seminomas were more likely to have no capsule, isointensity on T1WI, hypointensity on T2WI, and had narrow obviously enhanced fibrovascular septa without hemorrhagic or cystic degeneration; NSGCT was more likely to have a capsule, a mainly mixed signal on T1WI and T2WI, most of them had no fibrovascular septa, and hemorrhagic or cystic degeneration was common in malignant NSGCT.This study suggests that preoperative MRI can distinguish seminoma from NSGCT. We propose that preoperative MRI of the scrotum is an effective technique that should be widely adopted for the management of scrotal disease.

Novel aromatic sulfonyl naphthalene-based boronates as 20S proteasome inhibitors.

A novel series of non-peptide proteasome inhibitors (PIs) that act on chymotrypsin-like (ChT-L) of the proteasome were developed. These PIs bearing 4-aromatic sulfonyl naphthalene-based scaffold and Leu-boronic moiety as covalent bonding group displayed far better activity than PI-8182 for inhibiting ChT-L in preliminary biological activity test. The results showed that 2a (IC50 = 6.942 µM, MCF-7) and 2c (IC50 = 6.905 µM, MCF-7) displayed higher anti-proliferative activities than Bortezomib (IC50 = 18.37 µM, MCF-7) under our experimental conditions. Furthermore, in the microsomal stability assay, 2a demonstrated excellent metabolic stability profiles with 56% remaining after 40 min, as compared to Bortezomib of which approximately 30% was remaining. The compounds 2a, 2c emerged as promising lead compounds for the development of novel non-peptide boronate PIs.

Design, synthesis and biological evaluation of novel non-peptide boronic acid derivatives as proteasome inhibitors.

A novel series of non-peptide proteasome inhibitors bearing the 1, 4-naphthoquinone scaffold and boronic acid warhead was developed. In the biological evaluation on the chymotrypsin-like activity of human 20S proteasome, five compounds showed IC50 values in the nanomolar range. Docking experiments into the yeast 20S proteasome rationalized their biological activities and allowed further optimization of this interesting class of inhibitors. Within the cellular proliferation inhibition assay and western blot analysis, compound 3e demonstrated excellent anti-proliferative activity against solid tumor cells and clear accumulation of ubiquitinated cellular proteins. Furthermore, in the microsomal stability assay compound 3e demonstrated much improved metabolic stability compared to bortezomib, emerging as a promising lead compound for further design of non-peptide proteasome inhibitors.

Discovery of novel covalent proteasome inhibitors through a combination of pharmacophore screening, covalent docking, and molecular dynamics simulations.

The ubiquitin-proteasome pathway plays a pivotal role in the regulation of cellular protein processing and degradation. Proteasome inhibitors (PIs) have enormous potential to treat multiple myeloma, solid tumors, parasites, inflammation, and immune diseases, which is spurring the development of new types of PIs with enhanced efficacy, fewer side effects, and reduced drug resistance. Nevertheless, virtual screening for covalent PIs has rarely been reported because calculating the covalent binding energy is a challenging task. The aim of this study was to discover new covalent inhibitors of the 20S proteasome. The structures of PIs were manually divided into two parts: a noncovalent binding part resulting from virtual screening, and an epoxyketone group that was pre-selected as a covalent binding part. The SPECS database was screened by noncovalent docking and a pharmacophore model built with the 20S proteasome. After validating the covalent conjugation, 88 hits with epoxyketone were covalently docked into the 20S proteasome to analyze the intermolecular interactions. Four compounds were selected after multiple filtration and validations. Molecular dynamics simulations were performed to check the stability of the noncovalent and covalent docked ligand-enzyme complexes and investigate the interaction patterns of the screened inhibitors. Finally, two compounds with novel aromatic backbones, reasonable interactions, and stable covalent binding modes were retained. These compounds can serve as potential hits for further biological evaluation.