Stereochemistry of Chiral 2-Substituted Chromanes: Twist of the Dihydropyran Ring and Specific Optical Rotation.

Chiral 2-substituted chromanes are important substructures in organic synthesis and appear in numerous natural products. Herein, the correlation between specific optical rotations (SORs) and the stereochemistry at C2 of chiral 2-substituted chromanes was investigated through data mining, quantum-chemical calculations using density functional theory (DFT), and mechanistic analyses. For 2-aliphatic (including acyloxy and alkenyl) chromanes, the P-helicity of the dihydropyran ring usually corresponds to a positive SOR; however, 2-aryl chromanes with P-helicity tend to exhibit negative SORs. 2-Carboxyl (including alkoxycarbonyl and carbonyl) chromanes often display small experimental SORs, and theoretical calculations for them are prone to error because of the fluctuating conformational distribution with computational parameters. Several typical compounds were discussed, including detailed descriptions of the asymmetric synthesis, absolute configuration (AC) assignment methods, and systematic conformational analysis. We hope this work will enrich the knowledge of the stereochemistry of chiral 2-substituted chromanes.

Benzobis(imidazole) derivatives as STAT3 signal inhibitors with antitumor activity.

Polycyclic aromatic systems have been considered good biological probes, but some may also be good scaffolds for drug development. In this study, a series of benzobis(imidazole) derivatives were identified as STAT3 signal inhibitors, among which compound 24 showed significant inhibition of IL-6 induced JAK/STAT3 signalling pathway activation. Moreover, 24 inhibited cancer cell growth and migration, and induced cell apoptosis as well as cycle arrest in human hepatocellular carcinoma cells (HepG2) and oesophageal carcinoma cells (EC109). Compound 24 also displayed obvious antitumor activity in a mouse HepG2 cell xenograft tumor model without affecting the body weight. These results confirmed that 24 was a potential STAT3 signal inhibitor with certain antitumor activity.

A nonneglectable stereochemical factor in drug development: Atropisomerism.

Chirality is one of the key factors affecting the medicinal efficacy of compounds. In addition to central chirality, sterically hindered chiral axes commonly appear in drugs and the resulting chirality is known as atropisomerism. With developments in medicinal chemistry, atropisomerism has attracted increasing attention. This review discusses the classification, biological activity, pharmacokinetics, toxicity and side effects of atropisomers, and can serve as a reference in the research and development of potential chiral drugs.

Correlations between the ECD spectra and absolute configuration of bridged-ring lactones: revisiting Beecham's rule.

Bridged lactones frequently appear as structural fragments in natural products. To elucidate their stereochemistry using electronic circular dichroism (ECD) spectra, Beecham correlated the sign of the Cotton effect (CE) from the n → π* transition of lactones at approximately 220 nm with the skeleton of bridged lactones. By combining experimental and theoretical ECD analyses of various bridged lactones using time-dependent density functional theory calculations and a methodology for extracting core structures, Beecham's rule was revisited and revised to define the scope of application. Both the position of the ß-C atom in the larger lactone system and the additive contribution of groups at ß-C exerted effects on the sign of the CE. The revised rule provides an alternative way to interpret experimental ECD data in addition to quantum-chemical calculation for various bridged lactones.

[Applications of machine learning in clinical decision support in the omic era].

With the development of the omic technologies, the acquisition approaches of various biological data on different levels and types are becoming more mature. As a large amount of data will be produced in the process of diagnosis and treatment of diseases, it is necessary to utilize the artificial intelligence such as machine learning to analyze complex, multi-dimensional and multi-scale data and to construct clinical decision support tools. It will provide a method to figure out rapid and effective programs in diagnosis and treatment. In this process, the choice of artificial intelligence seems to be particularly important, such as machine learning. The article reviews the type and algorithm of machine learning used in clinical decision support, such as support vector machines, logistic regression, clustering algorithms, Bagging, random forests and deep learning. The application of machine learning and other methods in clinical decision support has been summarized and classified. The advantages and disadvantages of machine learning are elaborated. It will provide a reference for the selection between machine learning and other artificial intelligence methods in clinical decision support.

[Influence of attachment type on stress distribution of implant-supported removable partial dentures].

OBJECTIVE: To compare influences of different retention attachments on stress among supporting structures. METHODS: By 3-dimensional laser scanner and reverse engineering computer aided design (CAD) software, a basic partially edentulous digital model with mandibular premolar and molar missing was established. Implant attachment and removable partial dentures (RPD) were added into the basic model to build three kinds of models: RPD only, RPD + implant + Locator attachment, and RPD + implant + Magfit attachment. Vertical and inclined loads were put on artificial teeth unilaterally. By means of 3-dimensional finite element analysis, the stress distribution and displacement of the main supportive structures were compared. RESULTS: A complete 3-dimensional finite element model was established, which contained tooth structure, and periodontal structures. The displacement of the denture was smaller in Locator (9.38 µm vertically, 45.48 µm obliquely) and Magfit models (9.54 µm vertically, 39.45 µm obliquely) compared with non-implant RPD model (95.27 µm vertically, 155.70 µm obliquely). Compared with the two different attachments, cortical bone stress value was higher in Locator model (Locator model 10.850 MPa vertically, 43.760 MPa obliquely; Magfit model 7.100 MPa vertically, 19.260 MPa obliquely).The stress value of abutment periodontal ligamentin Magfit model (0.420 MPa vertically) was lower than that in Locator model (0.520 MPa vertically). CONCLUSION: The existence of implant could reduce maximum von Mises value of each supportive structure when Kennedy I partially edentulous mandible was restored. Comparing the structure of Magfit and Locator attachment, the contact of Magfit attachment was rigid, while Locator was resilient. Locator attachment could improve stability of the denture dramatically. Locator had stronger effect on defending horizontal movement of the denture.

[Identification of disease targets for precision medicine by integrative analysis of multi-omics data].

With the development and improvement of high-throughput sequencing technologies, the acquisition and processing approaches of various biological omics data on different levels are becoming more mature. Despite several new disease-associated factors have been discovered based on single omics data analysis, identification of disease targets by integrative analysis of multi-omics data is still growing. Since life is a complex regulatory system in which the regulation of gene mutations, epigenetic alterations, abnormal gene expression as well as anomalous variations in signal pathway are related with the occurrence and development of diseases, it is obvious that finding therapeutic factors using single omics data analysis has its limitation. Systematical studies of clinical and pathological mechanisms and identification of optimal therapeutic targets through integrative analysis of multi-omics data from different levels and resources have become an important research direction of precision medicine, which would provide innovative perspectives on disease study and new theoretical basis for early diagnosis, personalized treatment and medicine guide. In this review, we introduce new technologies and research progresses in screening therapeutic targets using systematic omics such as genomics, transcriptomics and epigenomics, and also discusse new strategies and advantages of integrative analysis among them.

Recovering from prolonged cardiac arrest induced by electric shock: A case report.

BACKGROUND: Cardiac arrest (CA) induced by electric shock is a rare occurrence, particularly in cases of prolonged CA. Currently, there is limited literature on similar incidents, and we present a relevant case report. CASE SUMMARY: A 27-year-old Asian male man, experiencing respiratory CA due to electric shock, was successfully restored to sinus rhythm after 50 min of cardiopulmonary resuscitation and 8 electrical defibrillation sessions. In the subsequent stages, the patient received multiple organ function protection measures, leading to a successful recovery and eventual discharge from the hospital. CONCLUSION: Prolonging resuscitation time can enhance the chances of survival for patients, this study provide valuable insights into the management of electric shock-induced CA.

Discovery, Optimization, and Evaluation of Novel N-(Benzimidazol-5-yl)-1,3,4-thiadiazol-2-amine Analogues as Potent STAT3 Inhibitors for Cancer Treatment.

Signal transducer and activator of transcription 3 (STAT3) is an attractive target for cancer therapy. However, identifying potent and selective STAT3 small-molecule inhibitors with drug-like properties remains challenging. Based on a scaffold combination strategy, compounds with a novel N-(benzimidazol-5-yl)-1,3,4-thiadiazol-2-amine scaffold were designed and their inhibition of the interleukin-6 (IL-6)/JAK/STAT3 pathway was tested in HEK-Blue IL-6 reporter cells. After optimization of lead compound 12, compound 40 was identified as a selective STAT3 inhibitor that directly binds the SH2 domain to inhibit STAT3 phosphorylation, translocation, and downstream gene transcription. Compound 40 exhibited antiproliferative activities against STAT3-overactivated DU145 (IC50 value = 2.97 µM) and MDA-MB-231 (IC50 value = 3.26 µM) cancer cells and induced cell cycle arrest and apoptosis. In the DU145 xenograft model, compound 40 showed in vivo antitumor efficacy following intraperitoneal administration, with a tumor growth inhibition rate of 65.3% at 50 mg/kg, indicating promise for further development.

Specific chiroptical sensing of cysteine via ultrasound-assisted formation of disulfide bonds in aqueous solution.

Cysteine (Cys) can serve as a biomarker to indicate diseases or disorders, and its chiral sensing has attracted increasing attention. Herein, we established an ultrasound-facilitated chiral sensing method for Cys using 4-chloro-7-nitro-1,2,3-benzoxadiazole (NBD-Cl) and electronic circular dichroism (ECD) spectroscopy. The formation of chiral disulfide bonds induced degenerate exciton coupling between two NBD chromophores, resulting in intense Cotton effects (CEs) of the sensing product. The anisotropy factor (g) was linearly correlated with the enantiomeric excess of Cys across the visible region (400-500 nm), and other natural amino acids or biothiols did not interfere with the detection. This ultrasound-promoted efficient and specific chiral sensing method of Cys has potential for application in the diagnosis of related diseases.

[Clinical observation of the 2-unit cantilever metal plate resin bonded fixed partial dentures].

OBJECTIVE: To observe a short term effect of clinical application of the 2-unit metal plate resin bonded fixed partial dentures (RBFPDs). METHODS: Sixteen patients were restored with the 2-unit cantilever metal plate RBFPDs during the period of 2005 to 2009. Retention and margin integrity of RBFPDs, and health condition of abutments were evaluated immediately after cementation and every 6-12 months period later. RESULTS: A total of 20 RBFPDs were made for all 16 patients. The observation period vary from 15 months to 53 months. The mean observation period was 34 months. There were 1 RBFPDs debonded. The debonding rate was 5%. CONCLUSION: The 2-unit cantilever metal plate RBFPDs could achieve a favorable clinical outcome in the short term.

MXene Enabling the Long-Term Superior Thermo-Oxidative Resistance for Elastomers.

The ability of long-term thermo-oxidative resistance is very important for elastomers in application. However, many conventional antioxidants are difficult to realize the long-term thermo-oxidative resistance. To overcome this limitation, a design strategy is introduced by combing elastomers with MXene and natural rubber (NR) is chosen as a model material. MXene is efficient in absorbing oxygen and the generated free radicals in the NR matrix and can inhibit the diffusion of oxygen toward the interior. Moreover, MXene, like graphene and carbon black, absorbs molecular chains, inhibiting the migration of MXene toward the surface of the sample. Such characteristics of MXene endow NR/MXene with the long-term outstanding thermo-oxidative resistance. For example, after three days of the thermo-oxidative process for NR/MXene, the tensile strength is 19 MPa and the retention of tensile strength is 63%, which far exceeds the effects of conventional antioxidants. This work not only provides a good guide for the universal design of elastomers with long-term thermo-oxidative resistance but also expands the application of MXene.

Manure amendment increased the abundance of methanogens and methanotrophs but suppressed the type I methanotrophs in rice paddies.

Methane (CH4) emission is the consequence of CH4 production and consumption performed by methanogens and methanotrophs, respectively. Fertilization is an important factor that regulates the behavior of methanogens and methanotrophs; however, the effect of manure and rice straw addition combined with inorganic fertilizers on these communities is not well understood. This study aimed to explore how manure and rice straw amendments together with inorganic fertilizers influenced the methanogenic and methanotrophic communities in a 31-year fertilized rice paddy. Manure amendment significantly increased the abundance of mcrA and pmoA genes by 61.2% and 63.3% compared with the unfertilized control, whereas inorganic NPK fertilization alone or rice straw addition did not affect their abundances. Manure and rice straw amendments greatly decreased the Shannon index and ACE index of the methanogenic communities, whereas inorganic NPK fertilization alone increased the ACE index of the methanotrophic communities compared with the unfertilized control. Methanosarcinaceae and Methylococcaceae dominated at the family level, representing 23.1-35.0% and 48.7-67.2% of the total reads, for the methanogenic and methanotrophic communities, respectively. Application of manure together with inorganic fertilizers suppressed the Methanocellales methanogens and the type I methanotrophs (Methylococcus and Methylobacter). Fertilization greatly altered the community structure of methanogens and methanotrophs, and manure addition had more apparent effects than rice straw. Moreover, total nitrogen, soil organic carbon, available phosphorus, and available potassium correlated significantly to the abundance, composition, and community structure of methanogens and methanotrophs. In conclusion, our study revealed that long-term manure amendment in combination with inorganic fertilizers significantly increased the abundance of methanogens and methanotrophs, but suppressed the type I methanotrophs in rice paddies.

Methane emissions responding to Azolla inoculation combined with midseason aeration and N fertilization in a double-rice cropping system.

Methane (CH4) is an important greenhouse gas (GHG), and paddy fields are major sources of CH4 emissions. This pot experiment was conducted to investigate the integrated effects of Azolla inoculation combined with water management and N fertilization on CH4 emissions in a double-rice cropping system of Southern China. Results indicated that midseason aeration reduced total CH4 emissions by 46.9%, 38.6%, and 42.4%, followed by N fertilization with 32.5%, 17.0%, and 29.5% and Azolla inoculation with 32.5%, 17.0%, and 29.5%, on average, during the early, late, and annual rice growing seasons, respectively. The CH4 flux peaks and total CH4 emissions observed in the late rice growing season were significantly higher than those in the early rice growing season. Additionally, CH4 fluxes correlated negatively to soil redox potential (Eh) and dissolved oxygen (DO) concentration. Azolla inoculation and N fertilization greatly increased the rice grain yields, whereas midseason aeration had distinct effects on grain yields in both rice seasons. The highest annual rice grain yields of approximately 110 g pot-1 were obtained in the Azolla inoculation and N fertilization treatments. In terms of yield-scaled CH4 emission, Azolla inoculation combined with midseason aeration and N fertilization generated the lowest yield-scaled CH4 emissions both in the early and in the late rice growing seasons, as well as during the annual rice cycle. In contrast, the highest yield-scaled CH4 emission was obtained in the treatment employed continuous flooding, without Azolla and no N application. Our results demonstrated that Azolla inoculation, midseason aeration, and N fertilization practices mitigated total CH4 emissions by 18.5-42.4% during the annual rice cycle. We recommend that the combination of Azolla inoculation, midseason aeration, and appropriate N fertilization can achieve lower CH4 emissions and yield-scaled CH4 emissions in the double-rice growing system.

[Effects of pins and bonding agents on the tensile strengths of Ni/Cr alloy bonded to enamel].

OBJECTIVE: To evaluate the effects of pin retention form and different bonding agents on the tensile bond and re-bond strength of Ni/Cr alloy to the enamel. METHODS: Sixty bovine permanent incisors were randomly divided into 6 equal groups by the variables of the numbers (0, 1 or 2) of pins to be prepared and bonding agents (Panavia F and Super-Bond C&B). The pin 1mm in diameter and 1mm in depth was prepared vertically to each enamel surface in the groups to be with pins. Cast Ni/Cr alloys cylinders were made and bonded to respective enamels using two different agents. Tensile strengths were tested. After residual visible resin on the debond surfaces being removed, specimens were re-bonded and tested in the same way as initial bonding. RESULTS: The tensile strength of Super-Bond C&B groups (11.82 MPa) was significantly higher than those of Panavia F groups (9.28 MPa, P<0.001). There was no significant difference of the tensile strength among the groups with one pin, two pins or without pins (P=0.394). There was no significant difference between the bond and re-bond tensile strength (P=0.969). CONCLUSION: Super-Bond C&B has significantly higher tensile strength than Panavia F, and is good for the retention of resin bonded fixed partial denture. Pins, which are vertical to the bonding surfaces have little effect on the tensile strength. The re-bonding can be successfully achieved by removing the residual visible resin and sandblasting the metal surfaces and the tensile strength is unchanged.

[Influence of retention-form design on the retention of resin-bonded fixed partial dentures].

OBJECTIVE: To evaluate the influence of retention-form design of resin bonded fixed partial dentures (RBFPDs). METHODS: Forty-five metal replicas of posterior metal RBFPDs were divided into 3 groups(n=15):C shape(control group), C shape + axial groove, C shape + pin hole. All the replicas were luted with Panavia F cement and subgroup of 5 specimens were subject to 70 N compressive load cycling for 0 cycles, 240,000 cycles , and 1,200,000 cycles respectively .Half of the cycles was on the central fossa of the pontics and half on the buccal inclined surface of the lingual cusp. Forces for dislodgment of the specimens were applied along the long axis of the abutment at a cross head speed of 1.0 mm /min. The separation forces were recorded as maximum retention force at the time of dislodgement. RESULTS: Separation forces of the C shape group (566.82+/-71.59 N)0.05). After 1,200,000 cycles, the retention force of the RBFPDs decreased significantly (P<0.001). CONCLUSION: To compare with axial groove, the design of pinhole retention form was conduced to the improvement of the retention force and durability of RBFPDs.

Variations of the nirS-, nirK-, and nosZ-denitrifying bacterial communities in a northern Chinese soil as affected by different long-term irrigation regimes.

Denitrification causes nitrogen loss from agricultural soils and emission of nitrous oxide (N2O). Water addition leads to an increase in soil moisture which greatly influenced soil denitrification. However, it is unclear how irrigation management affected the denitrifying bacterial communities in agricultural systems. In the present study, we investigated the abundance, diversity, and composition of the nirS-, nirK-, and nosZ-denitrifying bacterial communities in the soil under different long-term irrigation regimes by using real-time PCR (qPCR) and Illumina MiSeq sequencing approaches. Results showed that the abundance of nosZ gene was 3.94-6.01 and 35.09-60.21 times more than that of nirS and nirK genes, and the abundance of nirS gene was 5.84-15.30 times higher than that of nirK gene, respectively, in different irrigation treatments. However, the Alpha diversity indices of the nirK-denitrifying bacterial community were higher than those of the nirS- and nosZ-denitrifying bacterial communities. Proteobacteria was the predominant phylum for all the denitrifying bacterial communities, and significant differences were observed in relative abundance of Alphaproteobacteria and Betaproteobacteria in predominant class between different irrigation treatments for the nirS- and nosZ-denitrifying bacterial communities, respectively. Irrigation significantly affected the abundance, Shannon and Invsimpson indices, and structure of the nirS- and nosZ-denitrifying bacterial communities, whereas it only minor influenced the structure of the nirK-denitrifying bacterial community. Furthermore, the shifts in abundance, diversity, and structure of the nirS- and nosZ-denitrifying bacterial communities correlated significantly with the soil property variations; however, no soil property was significantly correlated with the abundance and Alpha diversity index of the nirK-denitrifying bacterial community. Our results demonstrate that different long-term irrigation regimes greatly altered the abundance, diversity, and structure of the nirS- and nosZ- rather than the nirK-denitrifying bacterial communities.

[Effects of long-term different fertilization regimes on the abundance and community structure of ammonia oxidizers in paddy soils]. / 长期不同施肥制度对水稻土氨氧化微生物数量和群落结构的影响.

Ammonia oxidation, driven by the ammonia oxidizers, is the rate-limiting step of nitrification and plays a key role in soil nitrogen cycling. In this study, real-time PCR and Illumina MiSeq sequencing approaches were used to investigate the effects of long-term different fertilization regimes on the abundance and community structure of ammonia oxidizers, targeting the amoA genes, in a 30-year located experimental paddy soil in Ningxiang County, Hunan Province. Four treatments were compared, including control without fertilizer (CK), fertilizers NPK (CF), 70% NPK plus 30% manure (CFM1), and 40% NPK plus 60% manure (CFM2). The results showed that the abundance of amoA genes in AOA and AOB was in the range of 3.09×107-8.37×107 and 1.04×107-7.03×107 copies·g-1 dry soil, respectively. Fertilization significantly increased the AOA and AOB abundances. However, no significant difference was observed in AOB abundance between CFM2 and CK. Manure fertilization rate greatly affected the α diversity index of AOB rather than AOA. The Shannon index of AOA and ACE and Chao1 indexes of AOB observed in CFM1 were significantly higher than that in CK, respectively. Thaumarchaeota and Crenarchaeota were the predominant AOA phyla and Nitrosospira, environmental_samples_norank, Bacteria_unclassified and Nitrosomonadales_unclassified were the main AOB genus groups which accounted for 83.4% and 97.8% of the total AOA and AOB amoA gene reads, respectively. Venn diagram indicated that manure fertilization rate had a stronger effect on the OTU number of AOB amoA gene than that of AOA in different treatments, but it slightly altered the proportion of shared AOA and AOB amoA gene reads. Furthermore, there were pronounced differences in the community structure of AOB among different treatments than that of AOA. These results suggested that manure fertilization rate significantly affected the abundance, diversity and community structure of AOA and AOB. The Shannon index of AOA and the abundance and ACE and Chao1 indexes of AOB in CFM1 were significantly higher than that in the rest treatments, respectively. Our results provided basis for further exploring the response mechanism of ammonia oxidizers to different fertilization strategies and the roles of ammonia oxidizers in nitrogen transformation in agricultural systems.

[Effects of legume-oat intercropping on abundance and community structure of soil N2-fixing bacteria]. / 豆科作物间作燕麦对土壤固氮微生物丰度和群落结构的影响.

In this study, real-time PCR and high-throughput sequencing approaches were employed to investigate the abundance and community structure of N2-fixing bacteria in a field experiment with three planting patterns (Oat monoculture, O; Soybean-oat intercropping, OSO; Mung bean-oat intercropping, OMO). The results showed that soil chemical properties varied significantly in different soil samples (P＜0.05). The abundance of nifH gene varied from 1.75×1010 to 7.37×1010 copies·g-1 dry soil in all soil samples. The copy numbers of nifH gene in OSO and OMO were 2.18, 2.64, and 1.92, 2.57 times as much as that in O at jointing and mature stages, with a significant decline from jointing to mature stage for all treatments (P＜0.05). Rarefaction curve and cove-rage results proved the nifH gene sequencing results were reliable, and the diversity index showed that the N2-fixing bacteria diversity of OSO was much higher than that of O. Azohydromonas, Azotobacter, Bradyrhizobium, Skermanella and other groups that could not be classified are the dominant genera, with significant differences in proportion of these dominant groups observed among all soil samples (P＜0.05). Venn and PCA analysis indicated that there were greater differences of nifH gene communities between jointing and mature stages; however, the OSO and OMO had similar communities in both stages. All these results confirmed that legume-oat intercropping significantly increased the abundance and changed the community composition of N2-fixing bacteria in oat soils.

[Selenium (Se)uptake and transformation mechanisms and physiological function in plant: A review]. / æ¤ç‰©ç¡’å¸æ”¶è½¬åŒ–æœºåˆ¶åŠç”Ÿç†ä½œç”¨ç ”ç©¶è¿›å±•.

Selenium (Se) is an essential nutrient for many organisms, including microbe, animal and human, but the Se uptake and transformation mechanisms and physiological roles in plant still are controversial until now. Se could improve the growth and tolerance of plant at an appropriate le-vel, but could be toxic at higher levels. Research concerning Se uptake and metabolism in plant were promoted by Se biofortification and Se phytoremediation induced by the issues of Se deficiency in food and Se pollution in special areas. Recently, the results of Se uptake and transformation in plant have indicated that there are significant differences of Se accumulation and physiological roles in various plants and significant influence of soil conditions on Se uptake of plant. In addition, the process of Se metabolism in Se hyperaccumulators and its regulation were revealed gradually with the studies on improvement of Se uptake in plant. According to the results of Se biofortification in crop and Se phytoremediation so far, we summarized the advances in the studies with the reference to Se distribution in environment, the detail process of Se uptake, key regulators of transformation and its physiological roles in plant. We hope this can provide a novel insight to further research upon Se in plant.