Protective effects of butyric acid during heat stress on the survival, immune response, histopathology, and gene expression in the hepatopancreas of juvenile pacific shrimp (L. Vannamei).

This study looked at the effects of adding butyric acid (BA) to the diets of juvenile Pacific shrimp and how it affected their response to survival, immunity, histopathological, and gene expression profiles under heat stress. The shrimp were divided into groups: a control group with no BA supplementation and groups with BA inclusion levels of 0.5 %, 1 %, 1.5 %, 2 %, and 2.5 %. Following the 8-week feeding trial period, the shrimp endured a heat stress test lasting 1 h at a temperature of 38 °C. The results showed that the control group had a lower survival rate than those given BA. Interestingly, no mortality was observed in the group receiving 1.5 % BA supplementation. Heat stress had a negative impact on the activities of alkaline phosphatase (AKP) and acid phosphatase (ACP) in the control group. Still, these activities were increased in shrimp fed the BA diet. Similar variations were observed in AST and ALT fluctuations among the different groups. The levels of triglycerides (TG) and cholesterol (CHO) increased with high temperatures but were reduced in shrimp-supplemented BA. The activity of an antioxidant enzyme superoxide dismutase (SOD) increased with higher BA levels (P < 0.05). Moreover, the groups supplemented with 1.5 % BA exhibited a significant reduction in malondialdehyde (MDA) content (P < 0.05), suggesting the potential antioxidant properties of BA. The histology of the shrimp's hepatopancreas showed improvements in the groups given BA. Conversely, the BA significantly down-regulated the HSPs and up-regulated MnSOD transcript level in response to heat stress. The measured parameters determine the essential dietary requirement of BA for shrimp. Based on the results, the optimal level of BA for survival, antioxidant function, and immunity for shrimp under heat stress is 1.5 %.

Cephalotane diterpenoids: structural diversity, biological activity, biosynthetic proposal, and chemical synthesis.

Covering: up to the end of 2023Cephalotane diterpenoids are a unique class of natural products exclusive to the genus Cephalotaxus, featuring a rigid 7,6,5,6-fused tetracyclic architecture. The study of cephalotanes dates back to the 1970s, when harringtonolide (1), a Cephalotaxus troponoid with a peculiar norditerpenoid carbon skeleton, was first discovered. In recent years, prototype C20 diterpenoids proposed as cephalotane were disclosed, which triggered intense studies on this diterpenoid family. To date, a cumulative total of 105 cephalotane diterpenoids with great structural diversity and biological importance have been isolated. In addition, significant advances have been made in the field of total synthesis and biosynthesis of cephalotanes in recent years. This review provides a complete overview of the chemical structures, bioactivities, biosynthetic aspects, and completed total synthesis of all the isolated cephalotane diterpenoids, which will help guide future research on this class of compounds.

Highly modified cephalotane-type diterpenoids from Cephalotaxus fortunei var. alpina and C. sinensis.

Cephalotanes are a rare class of diterpenoids occurring exclusively in Cephalotaxus plants. The intriguing structures and promising biological activities for this unique compound class prompt us to investigate C. fortunei var. alpina and C. sinensis, leading to the isolation of six undescribed cephalotane-type diterpenoids and/or norditerpenoids, ceforloids A-F (1-6). Their structures were elucidated by comprehensive analysis of spectroscopic data, including ECD and single-crystal X-ray diffraction studies, as well as quantum chemical calculations. Compound 1 possesses an unprecedented norditerpenoid skeleton featuring an unusual acetophenone moiety, and originated putatively from a disparate biogenetic pathway. Compounds 4 and 5 incorporate a unique 12,13-p-hydroxybenzylidene acetal motif. Compound 6 is a rare cephalotane-type diterpenoid glycoside. Immunosuppressive assays showed that compounds 2 and 6 exhibited mild suppressive activity against the activated T and B lymphocytes proliferation. These findings not only expanded the structural diversity of this small group of diterpenoids, but also explored their potential as novel structures for the development of immunosuppressive agents.

Ultrasensitive Electrochemiluminescence Sensor Utilizing Aggregation-Induced Emission Active Probe for Accurate Arsenite Quantification in Rice Grains.

Arsenic (As) constitutes a substantial threat to global ecosystems and public health. An accurate quantification of inorganic arsenite (As(III)) in rice grains is crucial for ensuring food safety and human well-being. Herein, we constructed an electrochemiluminescence (ECL) biosensor utilizing aggregation-induced emission (AIE) active Pdots for the sensitive detection of As(III) in rice. We synthesized tetraphenylethylene-based AIE-active Pdots, exhibiting stable and highly efficient ECL emission in their aggregated states. Owing to the overlap of spectra, we employed an electrochemiluminescence resonance energy transfer (ECL-RET) system, with the Pdots as the donor and black hole quencher (BHQ) as the acceptor. Upon the introduction of As(III), the conformational changes of As(III)-specific aptamer could trigger the detachment of BHQ-labeled DNA aptamer from the electrode surface, leading to the recovery of the ECL signal. The target-induced "signal-on" bioassay enabled the sensitive and specific detection of As(III) with a linear range of 10 pM to 500 nM, with an ultralow limit of detection (LOD) of 5.8 pM/0.4 ppt. These values significantly surpass those of existing sensors designed for As(III) quantification in rice. Furthermore, by employing amylase hydrolysis for efficient extraction, we successfully applied our sensor to measure As(III) in actual rice samples sourced from diverse regions of China. The results obtained using our sensor were in close agreement with those derived from the reference method of HPLC-ICP-MS. This study not only presents a sensitive and reliable method for detecting arsenite but also underscores its potential applications in enhancing food safety, agriculture practices, and environmental monitoring.

Two-tiered mutualism improves survival and competitiveness of cross-feeding soil bacteria.

Metabolic cross-feeding is a pervasive microbial interaction type that affects community stability and functioning and directs carbon and energy flows. The mechanisms that underlie these interactions and their association with metal/metalloid biogeochemistry, however, remain poorly understood. Here, we identified two soil bacteria, Bacillus sp. BP-3 and Delftia sp. DT-2, that engage in a two-tiered mutualism. Strain BP-3 has low utilization ability of pyruvic acid while strain DT-2 lacks hexokinase, lacks a phosphotransferase system, and is defective in glucose utilization. When strain BP-3 is grown in isolation with glucose, it releases pyruvic acid to the environment resulting in acidification and eventual self-killing. However, when strain BP-3 is grown together with strain DT-2, strain DT-2 utilizes the released pyruvic acid to meet its energy requirements, consequently rescuing strain BP-3 from pyruvic acid-induced growth inhibition. The two bacteria further enhance their collective competitiveness against other microbes by using arsenic as a weapon. Strain DT-2 reduces relatively non-toxic methylarsenate [MAs(V)] to highly toxic methylarsenite [MAs(III)], which kills or suppresses competitors, while strain BP-3 detoxifies MAs(III) by methylation to non-toxic dimethylarsenate [DMAs(V)]. These two arsenic transformations are enhanced when strains DT-2 and BP-3 are grown together. The two strains, along with their close relatives, widely co-occur in soils and their abundances increase with the soil arsenic concentration. Our results reveal that these bacterial types employ a two-tiered mutualism to ensure their collective metabolic activity and maintain their ecological competitive against other soil microbes. These findings shed light on the intricateness of bacterial interactions and their roles in ecosystem functioning.

Highly Modified Sesquiterpene Lactones with Cytotoxic Activities from Strobocalyx chunii.

Three new germacranolide sesquiterpene lactones (SLs), strochunolides A-C (1-3, respectively), and a new guaianolide SL, strochunolide D (4), were isolated from Strobocalyx chunii and structurally characterized. Compound 1 is the first example of a dihomo-germacranolide SL, characterized by an unprecedented 6/10/5 tricyclic scaffold incorporating an additional fused δ-lactone C-ring. The structure of a known germacranolide SL, spicatolide C (5), was revised as its 8-epimer. Compound 3 exhibited potent in vitro cytotoxic activity against the HL-60 cell line, with an IC50 value of 0.18 ± 0.01 µM.

Natural Microbial Reactor-Based Sensing Platform for Highly Sensitive Detection of Inorganic Arsenic in Rice Grains.

Rice is a major dietary source of inorganic arsenic (iAs), a highly toxic arsenical that accumulates in rice and poses health risks to rice-based populations. However, the availability of detection methods for iAs in rice grains is limited. In this study, we developed a novel approach utilizing a natural bacterial biosensor, Escherichia coli AW3110 (pBB-ArarsR-mCherry), in conjunction with amylase hydrolysis for efficient extraction, enabling high-throughput and quantitative detection of iAs in rice grains. The biosensor exhibits high specificity for arsenic and distinguishes between arsenite [As(III)] and arsenate [As(V)] by modulating the concentration of PO43- in the detection system. We determined the iAs concentrations in 19 rice grain samples with varying total As concentrations and compared our method with the standard technique of microwave digestion coupled with HPLC-ICP-MS. Both methods exhibited comparable results, without no significant bias in the concentrations of As(III) and As(V). The whole-cell biosensor demonstrated excellent reproducibility and a high signal-to-noise ratio, achieving a limit of detection of 16 µg kg-1 [As(III)] and 29 µg kg-1 [As(V)]. These values are considerably lower than the maximum allowable level (100 µg kg-1) for infant rice supplements established by the European Union. Our straightforward sensing strategy presents a promising tool for detecting iAs in other food samples.

Feasibility evaluation of intravoxel incoherent motion diffusion-weighted imaging in the diagnosis of skull-base invasion in nasopharyngeal carcinoma.

Objective: This study aimed to evaluate the feasibility of intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) in the diagnosis of skull-base invasion (SBI) in nasopharyngeal carcinoma (NPC). Materials and methods: A total of 50 patients pathologically diagnosed with NPC and a group of 40 controls comprised of those with either normal nasopharynx or patients with nasopharyngitis underwent conventional MRI and IVIM-DWI scans with 3 different groups of b values. Among the 50 patients, 36 patients diagnosed with SBI in NPC were included in the case group according to SBI criteria. All subjects (including those in the control group and case group) were divided into the b1, b2, and b3 groups based on their b values. The pure diffusion coefficient (D), perfusion-related incoherent microcirculation (D*), and microvascular volume fraction (f) values obtained in each measurement area of each group were tested for variance. Next,2 groups of b-value parameters with statistically significant data in the 3 groups were randomly selected for use in both the control group and the case group. A t-test was performed on the D, D*, and f values obtained by measuring each area of the skull base, and the area under the curve (AUC) of the receiver operating characteristic (ROC) was used to evaluate the diagnostic efficacy of the D, D*, and f values. Results: There was no statistical significance among the D, D*, and f values of the b1 and b3 groups (P>0.05), and the differences in parameters between the b1 and b2 groups were statistically significant(P < 0.05),and the differences in parameters between the b3 and b2 groups were also statistically significant(P < 0.05).The f value of the case group, which was obtained using the b1 and b2 parameters in each area of the skull base, was lower than that of the control group (P <0.05).The D, D*, and f values of the case group obtained by the b1 and b2 parameters in the pars petrosa of the temporal bone (including the foramen lacerum) were lower than those of the control group (P<0.05).When the parameters of the b1 group were used in the corpus of sphenoid bone (including the foramen ovale), the D, D*, and f values of the control group and the case group were compared, yielding a statistically significant difference (P<0.05).When the parameters of the b1 group were used, the diagnostic efficacy of the f value in each area of the skull base was the highest (AUC=0.908-0.991), followed by the D* value (AUC=0.624-0.692). Conclusion: When the number of b values <200 s/mm2 in IVIM-DWI accounts for more than half of the selected b values, IVIM-DWI is highly stable for the diagnosis of SBI in NPC. The D, D*, and f values of the bone and muscle areas of the skull base in patients with SBI of NPC showed a downward trend, and the f value had the best diagnostic performance, followed by the D* value, while the D value had the worst. Thus, IVIM-DWI can be used as a noninvasive method in the diagnosis of SBI in NPC.

Cephalotane-type C20 diterpenoids from Cephalotaxus fortunei var. alpina.

Seventeen new cephalotane-type diterpenoids, fortalides A-Q (1-17), along with five known analogues, were isolated from the seeds of Cephalotaxus fortunei var. alpina. Their structures were determined by extensive spectroscopic methods, as well as electronic circular dichroism (ECD) and X-ray crystallographic data analyses. Some isolates exhibited unusual structural features that were first found in cephalotane-type diterpenoids, such as the occurrence of the 7-oxabicyclo[4.1.1]octane moiety in 14 and 15 and the cis-arrangement of 3-OH and Me-19 in 9. Besides, the antiplasmodial activity of these compounds was evaluated in this study.

Evaluation of cardiac safety of hydroxyrutaecarpine, hERG channel inhibitor / 药学学报

Drug-induced long QT syndrome (LQTS) has become an important clinical research topic, and the occurrence of acquired long QT syndrome (acLQTS) is mainly caused by drug inhibition of the human ether-α-go-go related gene (hERG) channel. The hERG gene encodes the α subunit of the fast-activating delayed rectifying potassium ion channel (Ikr), which plays an important role in the process of action potential phase 3 repolarization and is also the target of most antiarrhythmic drugs. The purpose of this study was to investigate the effect of hydroxyrutaecarpine (HRU) on the hERG channel and to evaluate its cardiotoxicity. The whole cell patch clamp technique was used to detect the effects of HRU on the current and kinetics of the hERG channel, and to confirm the binding site on the hERG channel. PCR was used to determine the effect of HRU on hERG mRNA expression. Western blotting was used to detect the effects of HRU on the expression of hERG protein and transcription factor Sp1. Immunofluorescence was used to confirm the effects of HRU on localization and expression of hERG protein and transcription factor Sp1. Studies have shown that transient HRU can inhibit hERG current and shorten the inactivation time constant. Its binding sites to the hERG channel are F656 and Y652. After incubation for 24 h, HRU can reduce the expression of hERG protein, inhibit the hERG current, reduce the level of hERG mRNA, and reduce the expression of transcription factor Sp1 in the nucleus and hERG protein in the cytoplasm. Immunofluorescence experiments also showed the same results suggesting that the inhibition of Sp1 expression by HRU is the cause of the decreased expression of hERG mRNA. In conclusion, the acute inhibition of HRU accelerates the channel inactivation process and reduces the inactivation time constant by binding to the F656 and Y652 sites in the hERG channel, thus reducing the hERG current. In addition, HRU also inhibits the expression of hERG protein, mainly by inhibiting the expression of transcription factor Sp1, the transcription function of hERG channel protein is down-regulated, so that the hERG protein is reduced.

Accuracy Analysis of Feature-Based Automatic Modulation Classification via Deep Neural Network.

A feature-based automatic modulation classification (FB-AMC) algorithm has been widely investigated because of its better performance and lower complexity. In this study, a deep learning model was designed to analyze the classification performance of FB-AMC among the most commonly used features, including higher-order cumulants (HOC), features-based fuzzy c-means clustering (FCM), grid-like constellation diagram (GCD), cumulative distribution function (CDF), and raw IQ data. A novel end-to-end modulation classifier based on deep learning, named CCT classifier, which can automatically identify unknown modulation schemes from extracted features using a general architecture, was proposed. Features except GCD are first converted into two-dimensional representations. Then, each feature is fed into the CCT classifier for modulation classification. In addition, Gaussian channel, phase offset, frequency offset, non-Gaussian channel, and flat-fading channel are also introduced to compare the performance of different features. Additionally, transfer learning is introduced to reduce training time. Experimental results showed that the features HOC, raw IQ data, and GCD obtained better classification performance than CDF and FCM under Gaussian channel, while CDF and FCM were less sensitive to the given phase offset and frequency offset. Moreover, CDF was an effective feature for AMC under non-Gaussian and flat-fading channels, and the raw IQ data can be applied to different channels' conditions. Finally, it showed that compared with the existing CNN and K-S classifiers, the proposed CCT classifier significantly improved the classification performance for MQAM at N = 512, reaching about 3.2% and 2.1% under Gaussian channel, respectively.

Cephalodiones A-D: Compound Characterization and Semisynthesis by [6+6] Cycloaddition.

Cephalodiones A-D (1-4), the first example of C19 -norditerpenoid dimers, were isolated and fully characterized from a Cephalotaxus plant. These new skeletal natural products shared a unique tricyclo[6.4.1.12,7 ]tetradeca-3,5,9,11-tetraene-13,14-dione core that was capped in both ends with rigid multicyclic ring systems either C2 -symmetrically or asymmetrically. Compounds 1-4 were proposed to be biosynthetically produced by the [6+6]-cycloaddition of two identical C19 -norditerpenoid troponoids, which was validated by the semisyntheses of dimers 2-4. Moreover, some compounds showed significant inhibition on Th17 cell differentiation.

17- nor-Cephalotane-Type Diterpenoids from Cephalotaxus fortunei.

Seventeen new 17- nor-cephalotane-type diterpenoids, fortalpinoids A-Q (1-17), were isolated from the seeds of Cephalotaxus fortunei var. alpine. Compound 12 represents the first 17- nor-cephalotane-type diterpenoid featuring an 8-oxabicyclo[3.2.1]oct-2-ene moiety. The absolute configuration of fortunolide A (18) was determined for the first time, and the structure of cephinoid Q was revised to 14- epi-cephafortoid A (24) by X-ray crystallographic data analysis. Some of the compounds showed significant cytotoxicity against A549 and HL-60 cells, and the structure-activity relationship of this compound class is discussed.

Maximumins A-D, Rearranged Labdane-Type Diterpenoids with Four Different Carbon Skeletons from Amomum maximum.

Four highly rearranged labdane-type diterpenoids, maximumins A-D (1-4) possessing different new carbon skeletons, together with a biosynthetically related known analog 5 were isolated from Amomum maximum. The structures of new compounds with absolute configurations were characterized by spectroscopic and computational approaches. The plausible biogenetic pathways for 1-4 were proposed. These compounds showed moderate to weak activities against nuclear factor kappa B (NF-κB).

Cardiac safety evaluation of berberine combining with berberine-derived medicine / 药学学报

Drug-induced cardiotoxicity is a serious concern in recent years, and acquired long QT syndrome (LQTS) is an important manifestation of cardiotoxicity. hERG gene encodes the α subunit of the rapidly activated delayed rectifier potassium channel (Ikr), which plays an important role in action potential phase 3 repolarization. Drug inhibition of Ikr/hERG channel leads to prolonged QT interval, accompanied by Tdp malignant arrhythmia, which can cause sudden death. We studied the effect of berberines on the hERG K+ channels after combination with rosuvastatin and glibenclamide, and evaluated the cardiac safety of these drugs in combination. Whole cell patch clamp technique was used to detect the effect of the combinations of these drugs on hERG current on HEK293 cells stably expressing hERG gene. The results showed that the inhibitory effects of berberine or dihydroberberberine combined with rosuvastatin on hERG current were higher than single drug (P<0.05), but the combination had no effect on the kinetics of hERG channel. Berberine or dihydroberberberine combined with glibenclamide had higher inhibitory effects on hERG current than the application of single drug (P<0.05) while the time constant of hERG channel inactivation was shortened after the combination (P<0.05). In addition, the combination of berberine and glibenclamide inhibited hERG channel activation (P<0.05). In conclusion, our results demonstrated that the combination of berberine with rosuvastatin or glibenclamide significantly inhibited hERG current and the inhibition effects were higher than the application alone. Therefore, when the two drugs that have inhibitory effects on the hERG channel are combined, the risk of inducing prolonged QT interval is significantly increased, and therefore reducing cardiac safety.

Discussions on the development of biomechanics based on applications and grants of NSFC / 医用生物力学

Biomechanics, one important sub-discipline of mechanics, is an interdisciplinary subject involved in mechanics, biology and medical science, and it is closely associated with life health and clinic medicine. In this paper, applications and grants of normal projects and youth science foundation projects of National Natural Science Foundation of China (NSFC) on biomechanics from year 2012 to 2016 are introduced. Research directions and research teams of biomechanics are mainly discussed, and some suggestions are given for the development of biomechanics in China.