Performance of ATT and UDFF in the diagnosis of non-alcoholic fatty liver: An animal experiment.

Objective: To establish a Bama minipigs model with Non-Alcoholic Fatty Liver (NAFL) induced by a high-fat diet and investigate the application of attenuation coefficient (ATT) and ultrasound-derived fat fraction (UDFF) in the diagnosis of NAFL. Methods: Six-month-old male Bama minipigs were randomly divided into normal control and high-fat groups (n = 3 pigs per group), and fed with a control diet and high-fat diet for 32 weeks. Weight and body length were measured every four weeks, followed by quantitative ultrasound imaging (ATT and UDFF), blood biochemical markers, and liver biopsies on the same day. Using the Non-Alcoholic Fatty Liver Disease (NAFLD) Activity Score (NAS) as a reference, we analyzed the correlation between ATT, UDFF, and their score results. Results: Compared with the normal control group, the body weight, body mass index (BMI), and serum levels of triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) in the High-fat group were significantly different at Week 12 (P < 0.05). Spearman correlation analysis showed that the ATT value was significantly correlated with NAS score (r = 0.76, P < 0.001), and the UDFF value was significantly correlated with NAS score (r = 0.80, P < 0.001). The optimal cut-off value of ATT and UDFF were 0.59 dB/cm/MHz and 5.5%, respectively. These values are optimal for diagnosis of NAFL in Bama minipig model. Conclusion: ATT and UDFF have a high correlation with steatosis, and can be used as a non-invasive method for early screening of hepatic steatosis, which can dynamically monitor the change of disease course.

Enhanced in vitro bioavailability of resveratrol-loaded emulsion stabilized by ß-lactoglobulin-catechin with excellent antioxidant activity.

The study aimed to fabricate ß-Lactoglobulin-catechin (ß-La-Ca) conjugates as a natural designed antioxidant emulsifier to improve the physicochemical stability of resveratrol emulsion delivery system. Fourier transform infrared (FT-IR) and fluorescence spectroscopy analysis confirmed the formation of conjugates using free radical grafting. The antioxidant ability of emulsion was evaluated by DPPH scavenging activities and ORAC experiments. The emulsion stabilized by ß-La-Ca conjugates exhibited strong antioxidant activity with ORAC value of 2541.39 ± 29.58 µmol TE/g, which was significantly higher than that by ß-Lactoglobulin alone with 387.96 ± 23.45 µmol TE/g or their mixture with 948.23 ± 32.77 µmol TE/g. During the whole simulated gastrointestinal digestion, emulsion stabilized by ß-La-Ca conjugates exhibited excellent oxidative stability that the lipid was mainly digested in the small intestine. This behavior attributed to the greater stability of resveratrol to chemical transformation leading to a higher overall bioavailability in vivo. These results suggested that the ß-La-Ca conjugates could be used to fabricate the emulsion-based delivery system to improve the oxidative stability and bioavailability of chemically labile hydrophobic bioactive compounds.

Assessing the impact of Chlorantraniliprole (CAP) pesticide stress on oilseed rape (Brassia campestris L.): Residue dynamics, enzyme activities, and metabolite profiling.

This study investigates the effects of chlorantraniliprole (CAP) pesticide stress on oilseed rape through comprehensive pot experiments. Assessing CAP residue variations in soil and oilseed rape (Brassia campestris L.), enzyme activities (POD, CPR, GST), and differential metabolites, we unveil significant findings. The average CAP residue levels were 18.38-13.70 mg/kg in unplanted soil, 9.94-6.30 mg/kg in planted soil, and 0-4.18 mg/kg in oilseed rape samples, respectively. Soil microbial influences and systemic pesticide translocation into oilseed rape contribute to CAP residue variations. Under the influence of CAP stress, oilseed rape displays escalated enzyme activities (POD, CPR, GST) and manifests 57 differential metabolites. Among these, 32 demonstrate considerable downregulation, mainly impacting amino acids and phenolic compounds, while 25 exhibit noteworthy overexpression, primarily affecting flavonoid compounds. This impact extends to 24 metabolic pathways, notably influencing amide biosynthesis, as well as arginine and proline metabolism. These findings underscore the discernible effects of CAP pesticide stress on oilseed rape.

The global patent landscape of emerging infectious disease monkeypox.

BACKGROUND: Monkeypox is an emerging infectious disease with confirmed cases and deaths in several parts of the world. In light of this crisis, this study aims to analyze the global knowledge pattern of monkeypox-related patents and explore current trends and future technical directions in the medical development of monkeypox to inform research and policy. METHODS: A comprehensive study of 1,791 monkeypox-related patents worldwide was conducted using the Derwent patent database by descriptive statistics, social network method and linear regression analysis. RESULTS: Since the 21st century, the number of monkeypox-related patents has increased rapidly, accompanied by increases in collaboration between commercial and academic patentees. Enterprises contributed the most in patent quantity, whereas the initial milestone patent was filed by academia. The core developments of technology related to the monkeypox include biological and chemical medicine. The innovations of vaccines and virus testing lack sufficient patent support in portfolios. CONCLUSIONS: Monkeypox-related therapeutic innovation is geographically limited with strong international intellectual property right barriers though it has increased rapidly in recent years. The transparent licensing of patent knowledge is driven by the merger and acquisition model, and the venture capital, intellectual property and contract research organization model. Currently, the patent thicket phenomenon in the monkeypox field may slow the progress of efforts to combat monkeypox. Enterprises should pay more attention to the sharing of technical knowledge, make full use of drug repurposing strategies, and promote innovation of monkeypox-related technology in hotspots of antivirals (such as tecovirimat, cidofovir, brincidofovir), vaccines (JYNNEOS, ACAM2000), herbal medicine and gene therapy.

Compromised dynamic cerebral autoregulation is a hemodynamic marker for predicting poor prognosis even with good recanalization after endovascular thrombectomy.

PURPOSE: In patients undergoing endovascular thrombectomy (EVT) with acute ischemic stroke (AIS), dynamic cerebral autoregulation (dCA) may minimize neurological injury from blood pressure fluctuations. This study set out to investigate the function of dCA in predicting clinical outcomes following EVT. METHODS: 43 AIS of the middle cerebral or internal carotid artery patients underwent with EVT, and 43 healthy individuals (controls) were enrolled in this case control research. The dCA was evaluated using transcranial Doppler 12 h and five days after EVT. The transfer function analysis was used to derive the dCA parameters, such as phase, gain, and coherence. The modified Rankin scale (mRS) at 3 months after EVT was used to assess the clinical outcomes. Thefavorable outcome group was defined with mRS ≤2 and the unfavorable outcome group was defined with mRS score of 3-6. Logistic regression analysis was performed to determine the risk factors of clinical outcomes. RESULTS: A significant impairment in dCA was observed on the ipsilateral side after EVT, particularly in patients with unfavorable outcomes. After 5 days, the ipsilateral phase was associated with poor functional outcomes (adjusted odds ratio [OR] = 0.911, 95% confidence interval [CI]: 0.854-0.972; P = 0.005) and the area under the curve (AUC) (AUC, 0.878, [95% CI: 0.756-1.000] P < 0.001) (optimal cutoff, 35.0°). Phase change was an independent predictor of clinical outcomes from 12 h to 5 days after EVT (adjusted OR = 1.061, 95% CI: 1.016-1.109, P = 0.008). CONCLUSIONS: dCA is impaired in patients with AIS after EVT. Change in dCA could be an independent factor related to the clinical outcomes.

Suppressing the Thermal Quenching Effect via a Cluster Conformer in Copper(I)-Iodide Coordination Polymeric Phosphors for High-Power White LED Lighting.

High-power LED lighting is a crucial challenge due to the notorious thermal quenching (TQ) effect of traditional phosphors at high operating currents, which would result in poor device performance and hamper practical optoelectronic application. Herein, we demonstrate ligand engineering of a cubane- versus staircase-like [Cu4I4] conformer as a node in coordination polymers, which remarkably suppresses the TQ effect of cluster-based photoluminescence. For complex 1 (the formula [Cu4I4(bbimb)2]n) with the cubane-like [Cu4I4] conformer as a node, the metallophilicity interaction enables ultrabright triplet emission with a photoluminescence quantum yield over 82%, and the phonon-assisted detrapping process of excitons effectively suppresses the TQ effect in the wide temperature range. In contrast, the staircase-like [Cu4I4] conformer as a node in complex 2 (the formula [Cu4I4(bbtmb)2]n) exhibits a serious TQ effect over the investigated temperature. Phosphor-converted white LEDs (pc-wLEDs) were fabricated by integrating the cluster-based coordination polymers as a color converter, and their electroluminescence performances were investigated under high bias currents. The prototype pc-wLED device by incorporating the phosphor with the suppressed TQ effect exhibits a continuous rise in brightness under a high bias current of 300 mA. The results demonstrate that ligand engineering of the cluster conformer via suppressing the TQ effect proves efficient in designing an ideal color converter for high-power pc-wLED lighting.

Reactive Oxygen Species Activate a Ferritin-Linked TRPV4 Channel under a Static Magnetic Field.

Magnetogenetics has shown great potential for cell function and neuromodulation using heat or force effects under different magnetic fields; however, there is still a contradiction between experimental effects and underlying mechanisms by theoretical computation. In this study, we aimed to investigate the role of reactive oxygen species (ROS) in mechanical force-dependent regulation from a physicochemical perspective. The transient receptor potential vanilloid 4 (TRPV4) cation channels fused to ferritin (T4F) were overexpressed in HEK293T cells and exposed to static magnetic fields (sMF, 1.4-5.0 mT; gradient: 1.62 mT/cm). An elevation of ROS levels was found under sMF in T4F-overexpressing cells, which could lead to lipid oxidation. Compared with the overexpression of TRPV4, ferritin in T4F promoted the generation of ROS under the stimulation of sMF, probably related to the release of iron ions from ferritin. Then, the resulting ROS regulated the opening of the TRPV4 channel, which was attenuated by the direct addition of ROS inhibitors or an iron ion chelator, highlighting a close relationship among iron release, ROS production, and TRPV4 channel activation. Taken together, these findings indicate that the produced ROS under sMF act on the TRPV4 channel, regulating the influx of calcium ions. The study would provide a scientific basis for the application of magnetic regulation in cellular or neural regulation and disease treatment and contribute to the development of the more sensitive regulatory technology.

Ca2+ Overload Decreased Cellular Viability in Magnetic Hyperthermia without a Macroscopic Temperature Rise.

Magnetic hyperthermia is a crucial medical engineering technique for treating diseases, which usually uses alternating magnetic fields (AMF) to interplay with magnetic substances to generate heat. Recently, it has been found that in some cases, there is no detectable temperature increment after applying an AMF, which caused corresponding effects surprisingly. The mechanisms involved in this phenomenon are not yet fully understood. In this study, we aimed to explore the role of Ca2+ overload in the magnetic hyperthermia effect without a perceptible temperature rise. A cellular system expressing the fusion proteins TRPV1 and ferritin was prepared. The application of an AMF (518 kHz, 16 kA/m) could induce the fusion protein to release a large amount of iron ions, which then participates in the production of massive reactive oxygen radicals (ROS). Both ROS and its induced lipid oxidation enticed the opening of ion channels, causing intracellular Ca2+ overload, which further led to decreased cellular viability. Taken together, Ca2+ overload triggered by elevated ROS and the induced oxidation of lipids contributes to the magnetic hyperthermia effect without a perceptible temperature rise. These findings would be beneficial for expanding the application of temperature-free magnetic hyperthermia, such as in cellular and neural regulation, design of new cancer treatment methods.

Correlations of religious beliefs with anxiety and depression of Chinese adolescents.

Objective: This study was designed to investigate the prevalence of religious belief and its relationship with psychiatric symptoms among Chinese adolescents. Methods: This study recruited 11,603 adolescents in Grades 7-9 from March 21 to 31, 2020 in five cities in China. The religious beliefs of adolescents were collected by asking whether they held religious beliefs and what type of religious beliefs they held. The Patient Health Questionnaire-9 (PHQ-9) and the Generalized Anxiety Disorder-7 Scale (GAD-7) were used to assess depressive and anxiety symptoms in all adolescents. Demographics, religious beliefs, and mental health status were collected through the professional version of Wenjuanxing. Results: Of 11,069 valid questionnaires collected, 847 (7.7%) reported holding religious beliefs. Adolescents with religious beliefs showed significantly more severe symptoms of depression and anxiety compared to those without religious beliefs (both p<0.05). Logistic regression analysis revealed that religious belief was a risk factor for symptoms of depression (OR = 1.37, 95%CI: 1.16-1.61, p < 0.001) and anxiety (OR = 1.49, 95%CI: 1.23-1.79, p < 0.001) after controlling age, gender, and parental marital status. Conclusions: Our findings suggest that religiousness in adolescents was associated with a higher likelihood of depression/more intense depressive symptoms. In addition, religious Chinese adolescents should be provided with more resources to help them cope with mental health concerns.

Diet Mediate the Impact of Host Habitat on Gut Microbiome and Influence Clinical Indexes by Modulating Gut Microbes and Serum Metabolites.

The impact of external factors on the human gut microbiota and how gut microbes contribute to human health is an intriguing question. Here, the gut microbiome of 3,224 individuals (496 with serum metabolome) with 109 variables is studied. Multiple analyses reveal that geographic factors explain the greatest variance of the gut microbiome and the similarity of individuals' gut microbiome is negatively correlated with their geographic distance. Main food components are the most important factors that mediate the impact of host habitats on the gut microbiome. Diet and gut microbes collaboratively contribute to the variation of serum metabolites, and correlate to the increase or decrease of certain clinical indexes. Specifically, systolic blood pressure is lowered by vegetable oil through increasing the abundance of Blautia and reducing the serum level of 1-palmitoyl-2-palmitoleoyl-GPC (16:0/16:1), but it is reduced by fruit intake through increasing the serum level of Blautia improved threonate. Besides, aging-related clinical indexes are also closely correlated with the variation of gut microbes and serum metabolites. In this study, the linkages of geographic locations, diet, the gut microbiome, serum metabolites, and physiological indexes in a Chinese population are characterized. It is proved again that gut microbes and their metabolites are important media for external factors to affect human health.

Quality changes in Chinese high-quality indica rice under different storage temperatures with varying initial moisture contents.

The planting area of high-quality indica rice varieties has been growing rapidly in China. However, the storage characteristics of these varieties remains unclear. In this research, different moisture contents (13.5, 14.5, and 15.5%) of high-quality rice (variety Xiadao No.1) were stored at different temperatures (15, 20, 25, and 30°C) for 360 d, and then evaluated for lipid metabolism, redox enzyme activities, fatty acid composition, and sensory attributes. With the prolongation of storage, rice displayed an upward trend in fatty acid value, malondialdehyde content, and cooked rice hardness and a downward trend in contents of total fat and non-starch lipid, peroxidase and catalase activities, and sensory score of cooked rice. The change trends of these quality parameters were aggravated by elevating storage temperature and moisture content. Linoleic acid content of rice generally decreased with prolonged storage. After 300 d of storage, rice with initial moisture content of 13.5% at 30°C showed a fatty acid value of higher than 30 mg KOH/100 g, while rice of other two initial moisture contents reached similar level at 25°C. After the whole storage period, only rice with initial moisture contents of 13.5 and 14.5% stored at 15°C had a sensory score of higher than 60. These results suggested that the aging process of high-quality rice can be inhibited by decreasing the storage temperature and initial moisture content. These results can provide reference for grain storage enterprises to select proper storage condition to store high-quality rice.

Tolerogenic CD11c+dendritic cells regulate CD4+Tregs in replacing delayed ischemic preconditioning to alleviate ischemia-reperfusion acute kidney injury.

Ischemia-reperfusion injury (IRI) is one of the primary clinical causes of acute kidney injury (AKI). The key to IRI lies in immune-inflammatory damage, where dendritic cells (DCs) play a central role in eliciting immune responses within the context of inflammation induced by ischemia-reperfusion. Our previous study has confirmed that delayed ischemic preconditioning (DIPC) can reduce the kidney injury by mediating DCs to regulate T-cells. However, the clinical feasibility of DIPC is limited, as pre-clamping of the renal artery is not applicable for the prevention and treatment of ischemia-reperfusion acute kidney injury (I/R-AKI) in clinical patients. Therefore, the infusion of DCs as a substitute for DIPC presents a more viable strategy for preventing renal IRI. In this study, we further evaluated the impact and mechanism of infused tolerogenic CD11c+DCs on the kidneys following IRI by isolating bone marrow-derived dendritic cells and establishing an I/R-AKI model after pre-infusion of DCs. Renal function was significantly improved in the I/R-AKI mouse model after pre-infused with CD11c+DCs. The pro-inflammatory response and oxidative damage were reduced, and the levels of T helper 2 (Th2) cells and related anti-inflammatory cytokines were increased, which was associated with the reduction of autologous DCs maturation mediated by CD11c+DCs and the increase of regulatory T-cells (Tregs). Next, knocking out CD11c+DCs, we found that the reduced immune protection of tolerogenic CD11c+DCs reinfusion was related to the absence of own DCs. Together, pre-infusion of tolerogenic CD11c+DCs can replace the regulatory of DIPC on DCs and T-cells to alleviate I/R-AKI. DC vaccine is expected to be a novel avenue to prevent and treat I/R-AKI.

The deep learning framework iCanTCR enables early cancer detection using the T cell receptor repertoire in peripheral blood.

T cells recognize tumor antigens and initiate an anti-cancer immune response in the very early stages of tumor development, and the antigen specificity of T cells is determined by the T cell receptor (TCR). Therefore, monitoring changes in the TCR repertoire in peripheral blood may offer a strategy to detect various cancers at a relatively early stages. Here, we developed the deep learning framework iCanTCR to identify cancer patients based on the TCR repertoire. The iCanTCR framework uses TCRß sequences from an individual as an input and outputs the predicted cancer probability. The model was trained on over 2000 publicly available TCR repertoires from eleven types of cancer and healthy controls. Analysis of several additional publicly available datasets validated the ability of iCanTCR to distinguish cancer patients from non-cancer individuals and demonstrated the capability of iCanTCR for the accurate classification of multiple cancers. Importantly, iCanTCR precisely identified individuals with early-stage cancer with an area under the curve (AUC) of 86%. Altogether, this work provides a liquid biopsy approach to capture immune signals from peripheral blood for non-invasive cancer diagnosis.

Systemically functional characterization of regiospecific flavonoid O-methyltransferases from Glycine max.

Plants produce diverse flavonoids for defense and stress resistance, most of which have health benefits and are widely used as food additives and medicines. Methylation of the free hydroxyl groups of flavonoids, catalyzed by S-adenosyl-l-methionine-dependent O-methyltransferases (OMTs), significantly affects their physicochemical properties and bioactivities. Soybeans (Glycine max) contain a rich pool of O-methylated flavonoids. However, the OMTs responsible for flavonoid methylation in G. max remain largely unknown. We screened the G. max genome and obtained 22 putative OMT-encoding genes that share a broad spectrum of amino acid identities (25-96%); among them, 19 OMTs were successfully cloned and heterologously expressed in Escherichia coli. We used the flavonoids containing the free 3, 5, 7, 8, 3', 4' hydroxyl group, such as flavones (luteolin and 7, 8-dihydroxyflavone), flavonols (kaempferol and quercetin), flavanones (naringenin and eriodictyol), isoflavonoids (daidzein and glycetein), and caffeic acid as substrates, and 15 OMTs were proven to catalyze at least one substrate. The methylation activities of these GmOMTs covered the 3, 7, 8, 3', 4'- hydroxyl of flavonoids and 7, 4'- hydroxyl of isoflavonoids. The systematic characterization of G. max flavonoid OMTs provides insights into the biosynthesis of methylated flavonoids in soybeans and OMT bioparts for the production of methylated flavonoids via synthetic biology.

The protein methyltransferase TrSAM inhibits cellulase gene expression by interacting with the negative regulator ACE1 in Trichoderma reesei.

Protein methylation is a commonly posttranslational modification of transcriptional regulators to fine-tune protein function, however, whether this regulation strategy participates in the regulation of lignocellulase synthesis and secretion in Trichoderma reesei remains unexplored. Here, a putative protein methyltransferase (TrSAM) is screened from a T. reesei mutant with the ability to express heterologous ß-glucosidase efficiently even under glucose repression. The deletion of its encoding gene trsam causes a significant increase of cellulase activities in all tested T. reesei strains, including transformants of expressing heterologous genes using cbh1 promotor. Further investigation confirms that TrSAM interacts with the cellulase negative regulator ACE1 via its amino acid residue Arg383, which causes a decrease in the ACE1-DNA binding affinity. The enzyme activity of a T. reesei strain harboring ACE1R383Q increases by 85.8%, whereas that of the strains with trsam or ace1 deletion increases by more than 100%. By contrast, the strain with ACE1R383K shows no difference to the parent strain. Taken together, our results demonstrate that TrSAM plays an important role in regulating the expression of cellulase and heterologous proteins initiated by cbh1 promotor through interacting with ACE1R383. Elimination and mutation of TrSAM and its downstream ACE1 alleviate the carbon catabolite repression (CCR) in expressing cellulase and heterologous protein in varying degrees. This provides a new solution for the exquisite modification of T. reesei chassis.

Intrarelationships between suboptimal health status and anxiety symptoms: A network analysis.

BACKGROUND: Suboptimal health status is a global public health concern of worldwide academic interest, which is an intermediate health status between health and illness. The purpose of the survey is to investigate the relationship between anxiety statuses and suboptimal health status and to identify the central symptoms and bridge symptoms. METHODS: This study recruited 26,010 participants aged <60 from a cross-sectional study in China in 2022. General Anxiety Disorder-7 (GAD-7) and suboptimal health status short form (SHSQ-9) were used to quantify the levels of anxiety and suboptimal health symptoms, respectively. The network analysis method by the R program was used to judge the central and bridge symptoms. The Network Comparison Test (NCT) was used to investigate the network differences by gender, place of residence, and age in the population. RESULTS: In this survey, the prevalence of anxiety symptoms, SHS, and comorbidities was 50.7 %, 54.8 %, and 38.5 %, respectively. "Decreased responsiveness", "Shortness of breath", "Uncontrollable worry" were the nodes with the highest expected influence. "Irritable", "Exhausted" were the two symptom nodes with the highest expected bridge influence in the network. There were significant differences in network structure among different subgroup networks. LIMITATIONS: Unable to study the causal relationship and dynamic changes among variables. Anxiety and sub-health were self-rated and may be limited by memory bias. CONCLUSIONS: Interventions targeting central symptoms and bridge nodes may be expected to improve suboptimal health status and anxiety in Chinese residents. Researchers can build symptom networks for different populations to capture symptom relationships.

Hepatic Snai1 and Snai2 promote liver regeneration and suppress liver fibrosis in mice.

Liver injury stimulates hepatocyte replication and hepatic stellate cell (HSC) activation, thereby driving liver regeneration. Aberrant HSC activation induces liver fibrosis. However, mechanisms underlying liver regeneration and fibrosis remain poorly understood. Here, we identify hepatic Snai1 and Snai2 as important transcriptional regulators for liver regeneration and fibrosis. Partial hepatectomy or CCl4 treatment increases occupancies of Snai1 and Snai2 on cyclin A2 and D1 promoters in the liver. Snai1 and Snai2 in turn increase promoter H3K27 acetylation and cyclin A2/D1 expressions. Hepatocyte-specific deletion of both Snai1 and Snai2, but not one alone, suppresses liver cyclin A2/D1 expression and regenerative hepatocyte proliferation after hepatectomy or CCl4 treatments but augments CCl4-stimulated HSC activation and liver fibrosis. Conversely, Snai2 overexpression in the liver enhances hepatocyte replication and suppresses liver fibrosis after CCl4 treatment. These results suggest that hepatic Snai1 and Snai2 directly promote, via histone modifications, reparative hepatocyte replication and indirectly inhibit liver fibrosis.

Biosynthesis of the highly oxygenated tetracyclic core skeleton of Taxol.

Taxol is a widely-applied anticancer drug that inhibits microtubule dynamics in actively replicating cells. Although a minimum 19-step biosynthetic pathway has been proposed and 16 enzymes likely involved have been characterized, stepwise biosynthetic reactions from the well-characterized di-oxygenated taxoids to Taxol tetracyclic core skeleton are yet to be elucidated. Here, we uncover the biosynthetic pathways for a few tri-oxygenated taxoids via confirming the critical reaction order of the second and third hydroxylation steps, unearth a taxoid 9α-hydroxylase catalyzing the fourth hydroxylation, and identify CYP725A55 catalyzing the oxetane ester formation via a cascade oxidation-concerted acyl rearrangement mechanism. After identifying a acetyltransferase catalyzing the formation of C7-OAc, the pathway producing the highly-oxygenated 1ß-dehydroxybaccatin VI with the Taxol tetracyclic core skeleton is elucidated and its complete biosynthesis from taxa-4(20),11(12)-diene-5α-ol is achieved in an engineered yeast. These systematic studies lay the foundation for the complete elucidation of the biosynthetic pathway of Taxol.

Potential pathological mechanisms and pharmacological interventions for cadmium-induced miscarriage.

The prevalence of cadmium (Cd) contamination has emerged as a significant global concern. Exposure to Cd during pregnancy is associated with adverse pregnancy outcomes, including miscarriage. However, there is currently a lack of comprehensive summaries on Cd-induced miscarriage. Therefore, it is imperative to further strengthen research into in vivo studies, clinical status, pathological mechanisms, and pharmacological interventions for Cd-induced miscarriage. This study systematically presents the current knowledge on animal models and clinical trials investigating Cd exposure-induced miscarriage. The underlying mechanisms involving oxidative stress, inflammation, endocrine disruption, and placental dysfunction caused by Cd-induced miscarriage are also extensively discussed. Additionally, potential drug interventions such as melatonin, vitamin C, and vitamin E are highlighted for their pharmacological role in mitigating adverse pregnancy outcomes induced by Cd.

Chronic exposure to 3,6-dichlorocarbazole exacerbates non-alcoholic fatty liver disease in zebrafish by disrupting lipid metabolism and inducing special lipid biomarker accumulation.

Most previous studies have focused primarily on the adverse effects of environmental chemicals on organisms of good healthy. Although global prevalence of non-alcoholic fatty liver disease (NAFLD) has reached approximately 25%, the impact of environmentally persistent organic chemicals on organisms with NAFLD is substantially unknown. Polyhalogenated carbazoles (PHCZs) as emerging contaminants have been frequently detected in the environment and organisms. In this study, we investigated the impact of the most frequently detected PHCZs, 3,6-dichlorocarbazole (36-CCZ), on zebrafish with high-fat diet (HFD)-induced NAFLD. After 4 weeks exposure to environmentally relevant concentrations of 36-CCZ (0.16-0.45 µg/L), the accumulation of lipid in zebrafish liver dramatically increased, and the transcription of genes involved in lipid synthesis, transport and oxidation was significantly upregulated, demonstrating that 36-CCZ had exacerbated the NAFLD in zebrafish. Lipidomic analysis indicated that 36-CCZ had significantly affected liver lipid metabolic pathways, mainly including glycerolipids and glycerophospholipids. Additionally, fifteen lipids were identified as potential lipid biomarkers for 36-CCZ exacerbation of NAFLD, including diacylglycerols (DGs), triglycerides (TGs), phosphatidylcholines (PCs), phosphatidylethanolamines (PEs), phosphatidic acid (PA), and phosphatidylinositol (PI). These findings demonstrate that long-term exposure to 36-CCZ can promote the progression of NAFLD, which will contribute to raising awareness of the health risks of PHCZs.