Diagnostic value of a novel salivary gland ultrasound scoring system in IgG4-related sialadenitis.

OBJECTIVES: To develop a novel ultrasound scoring system for the major salivary glands in patients with immunoglobulin G4-related sialadenitis (IgG4-RS) and assess its diagnostic value in a multicenter cohort of Chinese patients. METHODS: Twenty clinicians (rheumatologists, stomatologists, and radiologists) participated. The study was conducted in four steps: (1) defining the ultrasonography (US) elements, (2) developing a novel ultrasound scoring system for US of the salivary glands, (3) evaluation of inter- and intra-reader reliabilities using the new ultrasound scoring system, and (4) assessing the diagnostic value of this novel ultrasound scoring system in IgG4-RS patients in a Chinese multicenter cohort. RESULTS: A novel ultrasound scoring system for the salivary glands was developed, with total scores ranging from 0 to 34. The inter- and intra-reader reliabilities of the ultrasound scoring system were excellent (0.972 and 0.940, respectively). A total of 470 people were recruited in this study; 187 patients were diagnosed with IgG4-RS, and the remaining 283 people were diagnosed with non-IgG4-RS. Patients with IgG4-RS had significantly higher US scores than the non-IgG4-RS group (mean US score=16 vs. 4, P < 0.001). The calculated area under the curve (AUC) for the total US score was 0.852 (95% CI: 0.814-0.891). The total US scores≥9 showed a sensitivity of 75.4% and a specificity of 91.9%. Association analysis showed a positive correlation between total US scores and serum IgG4 levels and hypocomplementemia (r=0.221, r=0.349; P = 0.002) and a negative correlation between total US scores and serum C3 and C4 levels (r=-0.210, r=-0.303; P = 0.005, P < 0.001). CONCLUSIONS: A novel semiquantitative ultrasound scoring system for patients with IgG4-RS was developed, with good diagnostic performance. The inter- and intra-reader reliabilities were excellent. US scores were correlated with IgG4, C3, and C4 levels and hypocomplementemia.

Divergent Synthesis of 17-nor-Cephalotane Diterpenoids through Developed Ynol-diene Cyclization.

On the basis of a novel ynol-diene cyclization developed as a rapid access to tropone unit, the first divergent strategy to 17-nor-cephalotane diterpenoids has been successfully established. Combining with a bioinspired stereoselective dual hydrogenation, the divergent total synthesis of (+)-3-deoxyfortalpinoid F, (+)-harringtonolide, (-)-fortalpinoids M/N/P, and analog (-)-20-deoxocephinoid P have been achieved in 14-17 linear longest steps starting from commercially available materials.

Evaluation of early arterial wall lesions by elastography parameters in spontaneously hypertensive rats.

BACKGROUND: Arterialsclerosis caused by hypertension can lead to many complications, such as heart attack, stroke and so on. Early diagnosis and treatment of arterialsclerosis can prevent cardiovascular and cerebrovascular diseases and improve the prognosis. The present study aimed to explore the value of ultrasonography in evaluating the early lesion of the local arterial wall in hypertensive rats and identify useful elastography parameters. METHODS: A total of 24 spontaneously hypertensive rats (SHR), 10-, 20-, 30-, and 40-weeks-old, were used in this study, with 6 rats in each group. Blood pressure was recorded using the Animal Noninvasive Blood Pressure Measurement System (Kent company, model CODA, USA), and the local elasticity of the abdominal aorta of rats was measured using a ultrasound diagnostic instrument (VINNO, Suzhou city, China). According to the histopathological results, SHR were divided into two groups: the normal arterial elasticity and the early arterial wall lesions. Mann-Whitney U test was used to compare the differences in elastic parameters and influencing factors between the above two groups, and receiver operating characteristic curve (ROC) was used to analyze and judge the value of each elastic parameter in evaluating early arterial lesions. RESULTS: A total of 22 cases were divided into two groups: 14 in the normal arterial elasticity and 8 in the early arterial wall lesions. The differences in age, blood pressure, pulse wave velocity (PWV), compliance coefficient (CC), distensibility coefficient (DC), and elasticity parameter (EP) between the two groups were compared. The differences in PWV, CC, DC and EP were statistically significant. Subsequently, the ROC curve analysis was performed for the above four evaluation indexes of arterial elasticity; the results were as follows: the area under the curve of PWV, CC, DC, and EP was 0.946, 0.781, 0.946, and 0.911, respectively. CONCLUSIONS: Early arterial wall lesions can be evaluated by ultrasound measurement of local PWV. PWV and DC can accurately evaluate the early arterial wall lesions in SHR, and the combined application of the two can improve the sensitivity and specificity of the approach.

Status, evaluation, and influencing factors of biosecurity levels in pig farms in China.

BACKGROUND: Animal diseases have always been a serious threat to livestock breeding, and the establishment of a biosecurity barrier is important for disease prevention and control. Based on the investigations conducted in seven provinces located farms, this study aimed to explore the current biosecurity levels of farms in China, construct a biosecurity evaluation system, calculate the biosecurity levels of farms using the rank sum ratio comprehensive evaluation method, and develop an empirical analysis of the factors influencing biosecurity levels. RESULTS: The results show that the greater the cost of biosecurity invested, the greater the level of biosecurity. Male farmers, educational attainment and participation in technical training had a significant positive effect on biosecurity levels. In addition, biosecurity levels first decreased and then increased as the scale of farming increased. The study also found that the more people in the household engaged in farming, the higher the biosecurity level of the farm. And farms that joined cooperatives had higher levels of biosecurity. CONCLUSION: The rank sum ratio method can evaluate the index system, so as to obtain a comprehensive index RSR value that can be compared, and the operation steps are simple and effective. By taking measures such as improving the comprehensive quality of farmers and increasing the investment in human, material and financial resources for biosecurity, the biosecurity level of farms can be effectively improved and animal diseases can be effectively prevented and controlled.

Enantioselective Total Synthesis of (-)-Cephalotanin B.

Cephalotaxus diterpenoids are attractive natural products with intriguing molecular frameworks and promising biological features. As a structurally unusual member, (-)-cephalotanin B possesses an extraordinarily congested heptacyclic skeleton, three lactone units, and nine consecutive stereocenters. Herein, we report an enantioselective total synthesis of (-)-cephalotanin B based on a divergent asymmetric Michael addition reaction, a novel Pauson-Khand/deacyloxylation process discovered in the development of a second-generation stereoselective Pauson-Khand reaction protocol, and an epoxide-opening/elimination/dual-lactonization cascade to construct the challenging propeller-shaped A-B-C ring system as key transformations.

The Anaphase-Promoting Complex/Cyclosome Is a Cellular Ageing Regulator.

The anaphase-promoting complex/cyclosome (APC/C) is a complicated cellular component that plays significant roles in regulating the cell cycle process of eukaryotic organisms. The spatiotemporal regulation mechanisms of APC/C in distinct cell cycle transitions are no longer mysterious, and the components of this protein complex are gradually identified and characterized. Given the close relationship between the cell cycle and lifespan, it is urgent to understand the roles of APC/C in lifespan regulation, but this field still seems to have not been systematically summarized. Furthermore, although several reviews have reported the roles of APC/C in cancer, there are still gaps in the summary of its roles in other age-related diseases. In this review, we propose that the APC/C is a novel cellular ageing regulator based on its indispensable role in the regulation of lifespan and its involvement in age-associated diseases. This work provides an extensive review of aspects related to the underlying mechanisms of APC/C in lifespan regulation and how it participates in age-associated diseases. More comprehensive recognition and understanding of the relationship between APC/C and ageing and age-related diseases will increase the development of targeted strategies for human health.

Enantioselective Total Synthesis of (-)-Spiroxins A, C, and D.

Spiroxins A, C, and D are metabolites that have been identified in the marine fungal strain LL-37H248. Their unique polycyclic structures and intriguing biological activities make them attractive targets for the synthetic community. Based on a scalable enantioselective epoxidation of 5-substituted naphthoquinone, an oxidation/spiroketalization cascade, ortho-selective chlorination of the phenol unit, and oxime-ester-directed acetoxylation, an enantioselective total synthesis of (-)-spiroxins A and C and the first total synthesis of (-)-spiroxin D have been achieved.

Total Synthesis of (+)-3-Deoxyfortalpinoid†F, (+)-Fortalpinoid†A, and (+)-Cephinoid†H.

3-Deoxyfortalpinoid F, fortalpinoid A, and cephinoid H are members of the Cephalotaxus diterpenoids class of natural products, which feature diverse chemical structures and valuable biological activities. We report herein the development of a diastereoselective Pauson-Khand reaction as an effective pathway to access the core tetracyclic skeleton, which is found widely in Cephalotaxus diterpenoids. Furthermore, we enabled the construction of the tropone moiety through a ring-closing metathesis/elimination protocol. Based on the developed strategy, asymmetric synthesis of the title compounds has been achieved for the first time.

The open reading frame 02797 from Candida tropicalis encodes a novel NADH-dependent aldehyde reductase.

Owing to its high-temperature tolerance, robustness, and wide use of carbon sources, Candida tropicalis is considered a good candidate microorganism for bioconversion of lignocellulose to ethanol. It also has the intrinsic ability to in situ detoxify aldehydes derived from lignocellulosic hydrolysis. However, the aldehyde reductases that catalyze this bioconversion in C. tropicalis remain unknown. Herein, we found that the uncharacterized open reading frame (ORF), CTRG_02797, from C. tropicalis encodes a novel and broad substrate-specificity aldehyde reductase that reduces at least seven aldehydes. This enzyme strictly depended on NADH rather than NADPH as the co-factor for catalyzing the reduction reaction. Its highest affinity (Km), maximum velocity (Vmax), catalytic rate constant (Kcat), and catalytic efficiency (Kcat/Km) were observed when reducing acetaldehyde (AA) and its enzyme activity was influenced by different concentrations of salts, metal ions, and chemical protective additives. Protein localization assay demonstrated that Ctrg_02797p was localized in the cytoplasm in C. tropicalis cells, which ensures an effective enzymatic reaction. Finally, Ctrg_02797p was grouped into the cinnamyl alcohol dehydrogenase (CADH) subfamily of the medium-chain dehydrogenase/reductase family. This research provides guidelines for exploring more uncharacterized genes with reduction activity for detoxifying aldehydes.

A comparative study of short-term efficacy and safety for thyroid micropapillary carcinoma patients after microwave ablation or surgery.

Background: Although papillary thyroid microcarcinoma (PTMC) has a high incidence and excellent clinical outcome, debate continues as to the therapeutic approach that would be most appropriate after confirming the diagnosis. Methods: We retrospectively analyzed the medical records of 311 patients with T1aN0M0 PTMC between January 2013 and September 2018. In all, 168 underwent microwave ablation (MWA), and 143 underwent surgery. MWA was performed using extensive ablation with hydrodissection. The surgery comprised thyroid lobectomy (TL) with unilateral central lymph node dissection (CND). We examined clinical outcomes during mean follow-up periods of 824 ± 452 days for the TL group and 753 ± 520 days for the MWA group. Results: Postprocedural follow-up revealed that, in the MWA group, the tumors had completely disappeared in 34 patients, and the remainder were reduced to necrotic or carbonized tissue. The incidence of transient hypoparathyroidism was significantly lower in the MWA group than in the TL group (p < .001). In addition, during the follow-up, we found no statistically significant differences between the two groups (TL vs MWA) for PTMC recurrence (1 vs 2 cases), lymph node metastasis (5 vs 5 cases), or disease-free survival [2001 days (5.5 years) vs 1702 days (4.7 years)] (p = .659, p = .795, and p = .974, respectively). Conclusions: If low-risk thyroid carcinoma (i.e., T1N0M0 PTMC) is accurately diagnosed early, MWA could be a minimally invasive alternative to surgery based on our short-term follow-up regarding recurrence and the low rates of complications and disease-free survival.

YKL107W from Saccharomyces cerevisiae encodes a novel aldehyde reductase for detoxification of acetaldehyde, glycolaldehyde, and furfural.

The aldehyde reductases from the short-chain dehydrogenase/reductase (SDR) family were identified as a series of critical enzymes for the improved tolerance of Saccharomyces cerevisiae to the aldehydes by catalyzing the detoxification reactions of aldehydes. Herein, we report that a novel aldehyde reductase Ykl107wp deduced from YKL107W from S. cerevisiae belongs to the classical SDR group and can catalyze the reduction reactions of acetaldehyde (AA), glycolaldehyde (GA), furfural (FF), formaldehyde (FA), and propionaldehyde (PA) but cannot reduce the six representative ketones. Ykl107wp displayed the best maximum velocity (Vmax), catalytic rate constant (Kcat), catalytic efficiency (Kcat/Km), and highest affinity (Km) to acetaldehyde. The optimum pH of Ykl107wp was 6.0 for the reduction of AA and 7.0 for the reduction of GA and FF, and the optimum temperatures were 40, 35, and 30 °C for the reduction of AA, GA, and FF, respectively. Ykl107wp for the reduction of AA was greatly affected by metal ions, chemical additives, and salts and showed poor thermal and pH stability, but its stability was slightly affected by a substrate. Ykl107wp was localized in endoplasmic reticulum and prevented the yeast cells from damage caused by furfural via the detoxification of furfural to furfural alcohol. This research provides guidelines for the study of uncharacterized classical SDR aldehyde reductases and exploration of their protective mechanisms on the corresponding organelles.

Enantioselective Total Synthesis of Pseudopteroxazole and Ileabethoxazole.

Enantioselective total syntheses of pseudopteroxazole (1) and ileabethoxazole (2) are presented. The two original stereocenters were constructed in excellent enantioselectivity and good diastereoselectivity through Carreira's asymmetric dual catalytic allylation, which shows potential for accessing diastereoisomers at C2 and C3 of 1 and 2. Cationic cyclizations of 13 and 24 demonstrated an effective pathway for the construction of the opposite configurations at C1 in 1 and 2. Additionally, an approach for the introduction of methyl at C4 is a feasible solution for structural modifications at C4 in 1 and 2.

Functions of aldehyde reductases from Saccharomyces cerevisiae in detoxification of aldehyde inhibitors and their biotechnological applications.

Bioconversion of lignocellulosic biomass to high-value bioproducts by fermentative microorganisms has drawn extensive attentions worldwide. Lignocellulosic biomass cannot be efficiently utilized by microorganisms, such as Saccharomyces cerevisiae, but has to be pretreated prior to fermentation. Aldehyde compounds, as the by-products generated in the pretreatment process of lignocellulosic biomass, are considered as the most important toxic inhibitors to S. cerevisiae cells for their growth and fermentation. Aldehyde group in the aldehyde inhibitors, including furan aldehydes, aliphatic aldehydes, and phenolic aldehydes, is identified as the toxic factor. It has been demonstrated that S. cerevisiae has the ability to in situ detoxify aldehydes to their corresponding less or non-toxic alcohols. This reductive reaction is catalyzed by the NAD(P)H-dependent aldehyde reductases. In recent years, detoxification of aldehyde inhibitors by S. cerevisiae has been extensively studied and a huge progress has been made. This mini-review summarizes the classifications and structural features of the characterized aldehyde reductases from S. cerevisiae, their catalytic abilities to exogenous and endogenous aldehydes and effects of metal ions, chemical protective additives, and salts on enzyme activities, subcellular localization of the aldehyde reductases and their possible roles in protection of the subcellular organelles, and transcriptional regulation of the aldehyde reductase genes by the key stress-response transcription factors. Cofactor preference of the aldehyde reductases and their molecular mechanisms and efficient supply pathways of cofactors, as well as biotechnological applications of the aldehyde reductases in the detoxification of aldehyde inhibitors derived from pretreatment of lignocellulosic biomass, are also included or supplemented in this mini-review.

Advances in the Synthesis of Lignan Natural Products.

Lignans comprise a family of secondary metabolites existing widely in plants and also in human food sources. As important components, these compounds play remarkable roles in plants' ecological functions as protection against herbivores and microorganisms. Meanwhile, foods rich in lignans have revealed potential to decrease of risk of cancers. To date, a number of promising bioactivities have been found for lignan natural products and their unnatural analogues, including antibacterial, antiviral, antitumor, antiplatelet, phosphodiesterase inhibition, 5-lipoxygenase inhibition, HIV reverse transcription inhibition, cytotoxic activities, antioxidant activities, immunosuppressive activities and antiasthmatic activities. Therefore, the synthesis of this family and also their analogues have attracted widespread interest from the synthetic organic chemistry community. Herein, we outline advances in the synthesis of lignan natural products in the last decade.

Protecting-group-free synthesis of taiwaniaquinone H using a one-pot thermal ring expansion/4π-electrocyclization strategy.

A strategy to the 6-5-6 tricyclic scaffold of taiwaniaquinoids was established on the basis of a one-pot thermal ring expansion/4π-electrocyclization process. The efficiency of this methodology has been demonstrated through its application in the total synthesis of taiwaniaquinone H, which has been accomplished in three steps and 14% overall yield in a protecting-group-free manner starting from commercially available materials.

Total synthesis of asterredione.

The first total synthesis of asterredione was efficiently accomplished over five linear steps and in 21.5% overall yield. As the crucial step, the 2-quaternary 1,3-cyclopentenedione skeleton of asterredione was readily achieved using the Darzens/ring-expansion strategy developed in our laboratory. The structure of synthesized asterredione was fully confirmed by X-ray crystallography.

Indirect prediction of liver fibrosis by quantitative measurement of spleen stiffness using the FibroScan system.

OBJECTIVES: To evaluate quantitative measurement of spleen stiffness for indirect assessment of liver fibrosis in patients with chronic hepatitis B and to correlate spleen stiffness with liver stiffness using pathologic examination as a reference standard. METHODS: Sixty patients with clinically confirmed chronic hepatitis B (n = 54) and liver cirrhosis (n = 6) were enrolled. Quantitative stiffness measurements (kilopascals) were obtained from spleen and liver parenchyma with the FibroScan system (Echosens, Paris, France). Correlation analyses were performed between spleen and liver stiffness and between spleen stiffness and liver fibrosis stages. The diagnostic performance of spleen stiffness for indirect prediction of liver fibrosis was estimated by receiver operating characteristic curves. RESULTS: Both spleen and liver stiffness increased as liver fibrosis progressed. Spleen stiffness values had a positive correlation with liver stiffness values in all patients (Pearson r = 0.810; P < .001). The correlation between spleen stiffness and fibrosis stages was statistically significant (Spearman r = 0.833; P < .001). The areas under the receiver operating characteristic curves for spleen stiffness were 0.902 (95% confidence interval [CI], 0.825-0.978) for stage S1 (fibrous portal expansion and limited perisinusoidal or lobular fibrosis) or higher, 0.927 (95% CI, 0.852-1.0) for S2 (periportal fibrosis and few fibrous septa but intact architecture) or higher, 0.962 (95% CI, 0.918-1.0) for S3 (numerous fibrous septa with architectural distortion but no obvious cirrhosis) or higher, and 0.983 (95% CI, 0.957-1.0) for S4 (cirrhosis) (all P < .001). The differences between the areas under the curves for spleen and liver stiffness in liver fibrosis staging were not statistically significant (P = .115-.756). CONCLUSIONS: Quantitative measurement of spleen stiffness is a feasible and promising technique for estimating liver fibrosis. The overall diagnostic performance of spleen stiffness for liver fibrosis staging is comparable with that of liver stiffness.

Dietary nutrition, intestinal microbiota dysbiosis and post-weaning diarrhea in piglets.

Weaning is a critical transitional point in the life cycle of piglets. Early weaning can lead to post-weaning syndrome, destroy the intestinal barrier function and microbiota homeostasis, cause diarrhea and threaten the health of piglets. The nutritional components of milk and solid foods consumed by newborn animals can affect the diversity and structure of their intestinal microbiota, and regulate post-weaning diarrhea in piglets. Therefore, this paper reviews the effects and mechanisms of different nutrients, including protein, dietary fiber, dietary fatty acids and dietary electrolyte balance, on diarrhea and health of piglets by regulating intestinal function. Protein is an essential nutrient for the growth of piglets; however, excessive intake will cause many harmful effects, such as allergic reactions, intestinal barrier dysfunction and pathogenic growth, eventually aggravating piglet diarrhea. Dietary fiber is a nutrient that alleviates post-weaning diarrhea in piglets, which is related to its promotion of intestinal epithelial integrity, microbial homeostasis and the production of short-chain fatty acids. In addition, dietary fatty acids and dietary electrolyte balance can also facilitate the growth, function and health of piglets by regulating intestinal epithelial function, immune system and microbiota. Thus, a targeted control of dietary components to promote the establishment of a healthy bacterial community is a significant method for preventing nutritional diarrhea in weaned piglets.

DNDMH-mediated direct nitration of aryl alkenes.

N-nitro type reagents have been demonstrated as mild nitration tools in recent years. This work presents an exploration of direct nitration of aryl alkenes mediated by DNDMH, a novel N-nitro type reagent developed in our previous study. It exhibits herein a new property of DNDMH as an effective direct nitration reagent for aryl alkenes, through probably the delivery of nitro radicals with the aid of TEMPO and Cu(OAc)2.

Quantitative ultrasound parameters from scattering and propagation may reduce the biopsy rate for breast tumor.

Breast cancer has become the most common cancer worldwide, and early screening improves the patient's survival rate significantly. Although pathology with needle-based biopsy is the gold standard for breast cancer diagnosis, it is invasive, painful, and expensive. Meanwhile it makes patients suffer from misplacement of the needle, resulting in misdiagnosis and further assessment. Ultrasound imaging is non-invasive and real-time, however, benign and malignant tumors are hard to differentiate in grayscale B-mode images. We hypothesis that breast tumors exhibit characteristic properties, which generates distinctive spectral patterns not only in scattering, but also during propagation. In this paper, we propose a breast tumor classification method that evaluates the spectral pattern of the tissues both inside the tumor and beneath it. First, quantitative ultrasonic parameters of these spectral patterns were calculated as the representation of the corresponding tissues. Second, parameters were classified by the K-Nearest Neighbor machine learning model. This method was verified with an open access dataset as a reference, and applied to our own dataset to evaluate the potential for tumors assessment. With both datasets, the proposed method demonstrates accurate classification of the tumors, which potentially makes it unnecessary for certain patients to take the biopsy, reducing the rate of the painful and expensive procedure.