Glial cell line-derived neurotrophic factor (GDNF) is essential for colonization and expansion of turbot (Scophthalmus maximus) germ cells in recipients and in vitro culture.

Germ cell transplantation (GCT) is a promising biotechnology that enables the production of donor-derived gametes in surrogate recipients. It plays a crucial role in the protection of endangered species, the propagation of elite species with desired traits, and long-term preservation of genetic resources. This significance is particularly pronounced when GCT is synergistically employed with cryopreservation techniques. However, GCT often encounters challenges due to low colonization rates and, in some cases, complete loss of donor cells in recipients. Glial cell line-derived neurotrophic factor (GDNF) plays a pivotal role in sustaining the self-renewal of spermatogonial stem cells (SSCs) in mammals. Additionally, it has been shown to promote the proliferation of spermatogonia in vitro cultures in certain animal species. In turbot (Scophthalmus maximus), we found that the expressions of gdnf and gfrα1a were predominantly observed in spermatogonia rather than somatic cells, which differed from their expression patterns in mammals. The efficiency of exogenous spermatogonia transplantation in Japanese flounder (Paralichthys olivaceus) larvae could be substantially enhanced by incubating donor cells from turbot with 100 ng/ml GDNF prior to transplantation. This led to a noteworthy increase in the colonization rate, rising from 33%-50%-61.5%. Additionally, the addition of 20 ng/ml GDNF in cell medium could also promote the proliferation of turbot germ cells in vitro. These results demonstrated the gdnf in turbot testis expression characteristics and suggested that addition of GNDF could be an effective way to improve the GCT efficiency and promote the germ cells expansion during in vitro culture.

Metabolic engineering of glycolysis in Escherichia coli for efficient production of patchoulol and τ-cadinol.

Glucose metabolism suppresses the microbial synthesis of sesquiterpenes with a syndrome of "too much of a good thing can be bad". Here, patchoulol production in Escherichia coli was increased 2.02 times by engineering patchoulol synthase to obtain an initial strain. Knocking out the synthetic pathway for cyclic adenosine monophosphate relieved glucose repression and improved patchoulol titer and yield by 27.7 % and 43.1 %, respectively. A glycolysis regulation device mediated by pyruvate sensing was constructed which effectively alleviated overflow metabolism in a high-glucose environment with 10.2 % greater patchoulol titer in strain 070QA. Without fine-tuning the glucose-feeding rate, patchoulol titer further increased to 1675.1 mg/L in a 5-L bioreactor experiment, which was the highest level reported in E. coli. Using strain 070QA as a chassis, the τ-cadinol titer reached 15.2 g/L, representing the first report for microbial production of τ-cadinol. These findings will aid in the industrial production of sesquiterpene.

Comprehensive untargeted lipidomic analysis of sea buckthorn using UHPLC-HR-AM/MS/MS combined with principal component analysis.

Sea buckthorn is an important ecological and economic plant which has multiple bioactivities. The fruits and seeds of sea buckthorn are rich in oil. However, there are few studies on the differences of lipid profiles of sea buckthorn varieties. Herein, the lipidomic fingerprints of sea buckthorn was established. First, a mixture solvent of methanol and chloroform (2:1, v/v) was selected to extract the lipid of the flesh and seed of sea buckthorn. Then, global lipidomic analysis of different varieties of sea buckthorn was conducted. A total of 16 lipid classes and 112 lipid molecular species were determined. Several molecular species, such as PE (phosphatidylethanolamine) 18:1/18:3, PE18:0/18:1, PE18:0/18:2, etc. were selected as the potential biomarkers to classify the samples. Our study provides a scientific basis for quality control of sea buckthorn and promotes the development of sea buckthorn oil.

Kinetic and mechanism of the reaction between Cl and several mono-methyl branched alkanes.

Branched alkanes are ubiquitous in the troposphere and play an important role in the chemical processes. In this work, the rate constants and products for the reaction of Cl atoms with 3-methylhexane and 2-methylheptane were measured at room temperature (298 ± 0.2 K) and atmospheric pressure using a conventional relative rate method. The rate constants of 3-methylhexane and 2-methylheptane in units of cm3/(mol·sec) are (3.09 ± 0.31) × 10-10 and (3.67 ± 0.40) × 10-10, respectively. Furthermore, the corresponding atmospheric lifetime of the studied branched alkanes with Cl was 6.92-89.90 hours and 5.82-75.69 hours, respectively. The estimated atmospheric lifetimes indicated that the reaction with Cl atoms could be the most important atmospheric degradation pathway for 3-methylhexane and 2-methylheptane. Primary gas-phase products of the reactions were identified and quantified, and particle-phase products were also obtained. The atmosphere oxidation mechanism of Cl atoms with 3-methylhexane and 2-methylheptane is proposed. The SOA yields of 3-methylhexane and 2-methylheptane from the reaction of Cl atoms were determined to be 7.96% ± 0.89% and 13.35% ± 1.50% respectively. Overall, the results reveal that the primary loss process of branched alkanes is the reaction with Cl atoms, which impacts its degradation on a regional scale.

The joint action of biochar and plant roots on U-stressed soil remediation: Insights from bacteriomics and metabolomics.

Although biological remediation of U-stressed soil has been studied for a long time, the combined effects of biochar and plant roots are rarely discussed and its influence on rhizosphere microecology are still unknown. Based on pot experiments, we explored the combined efforts of biochar addition and plant roots on U-stressed rhizosphere soil in several ways, including soil physicochemical properties, soil enzyme activities, uranium chemical speciation, bacterial community structure and metabolic pathways. Our results indicates that the content of DTPA-extractable U decreased by 49.31% after biochar and plant roots application, whereas plant roots only treatment just decreased by 25.46%. Further research has found that the pH, CEC, enzyme activities and nutritional level of rhizosphere soil were more significantly improved after biochar and plant roots application. Meanwhile, the abundance and diversity of bacterial community was also upregulated, which was also suggested by the stronger metabolisms of lipids, carbohydrate, nucleotides as well as amino acids. Correlation analyses also certified the positive associations between soil properties, bacterial communities and metabolism. We speculated that the uranium immobilization was mainly attributed to the direct fixation of biochar for its alkalinity, CEC, DOC, etc. and the joint action of biochar and plant roots for their stimulating effects on bacteria. Our findings suggested that combination of biochar and plant roots could limit bioaccessibility of U in a larger extend than plant roots only, which may be a better strategy for rapid remediation of U-streesed soil.

Dysfunction of visual novelty detection in physical but not social anhedonia in a non-clinical sample

Background/objective: Despite its obvious motivational impairment, anhedonia as a transdiagnostic psychopathological construct is accompanied by deficits in attention function. Previous studies have identified voluntary attention anomalies in anhedonia, but its involuntary attention has received less study. Method: Using a visual novelty oddball task, the current event-related potential study assessed electrophysical correlates underlying mismatch detection in anhedonia with a non-clinical sample. Well-matched healthy control (N = 28; CNT), social anhedonia (N = 27; SA), and physical anhedonia (N = 26; PA) groups were presented standard, target, and perceptually novel stimuli while their EEG was recording. Results: The PA group relative to the CNT group exhibited a reduced N2 to novel stimuli but not to target stimuli. In contrast, the SA group as compared to the other two groups showed comparable N2 responses to both target and novel stimuli. Control analyses indicated that these patterns were unaffected by depression symptoms. Conclusions: These findings suggest that anhedonia is a heterogenous construct associated with impairments in early detection of visual novelty in physical but not social anhedonia, highlighting that dysfunction in involuntary attention may play a mediating role in the development, maintenance, and consequences of anhedonia-related psychopathology. (AU)

Glucose Oxidase of a Crucifer-Specialized Insect: A Potential Role in Suppressing Plant Defense via Modulating Antagonistic Plant Hormones.

Glucose oxidase (GOX) is a representative compound found in most insect saliva that can suppress plant-defensive responses. However, little is known about the origin and role of GOX in the crucifer-specialized pest Plutella xylostella. In this study, we showed obvious regurgitation from the larval gut of P. xylostella and identified abundant peptides highly similar to known GOX. Three PxGOX genes were verified with PxGOX2 preferentially expressed in the gut. The heterologously expressed PxGOX2 confirmed its function to be a GOX, and it was detected in plant wounds together with the gut regurgitant. Further experiments revealed that PxGOX2 functioned as an effector and may suppress defensive responses in plant through the production of H2O2, which modulates levels of antagonistic salicylic acid and jasmonic acid. However, excessive H2O2 in the host plant may be neutralized by peroxidase, thus forming defensive feedback. Our findings provided new insights into understanding the GOX-mediated insect-plant interactions.

Efficacy and safety of acupuncture for vocal nodules: A systematic review and meta-analysis with trial sequential analysis.

In this study, we aim to evaluate the efficacy and safety of acupuncture for vocal nodules, concerning qualitive overall efficacy and quantitative improvement on quality of voice. Four English and four Chinese databases were searched up to December 10th, 2022. Risk of bias among the included trials were evaluated by the Cochrane ROB tool. Systematic reviews and meta-analyses were conducted based on the Cochrane systematic review method by using RevMan 5.4 Software, and trial sequential analyses were performed by TSA 0.9. Meta-influence analyses, subgroup-analyses, meta-regression, and evaluation of publication bias were performed for exploration of heterogeneity by Stata V.14. Quality of the results was accessed through the GRADE-pro GDT. Cluster analyses and correlation coefficient were performed by R 4.1.3. Finally, 15 trials involving 1,888 participants were included. Results showed that compared with western medicine alone or Chinese herbal medicine alone, acupuncture alone yielded significantly (p<0.05) higher clinical effective rate and more improvement on scores of voice analyses. However, reduction on scores of grade, roughness, and breathiness and voice handicap index during follow-ups, and results of clinical effective rate suggested that acupuncture was inferior to voice training. In addition, meta-regression and sub-group analyses firstly revealed advanced efficacies of acupuncture when performed with local and remote acupoints, compared with local acupoints only. Acupuncture specified adverse event was denied in six trials while it was not mentioned in other nine trials. Results of cluster analyses and correlation coefficient showed that Kai yin yi hao and He gu (LI-4) were the most frequently applied matching-acupoints in trials. In conclusion, compared with western medicine (level of evidence: low ⨁⨁◯◯, GRADE C) and Chinese herbal medicine (level of evidence: moderate ⨁⨁⨁◯, GRADE B), acupuncture is safe and of better efficacy for patients with vocal nodules, while there is also need for RCTs with improvements on designing and interventions in experimental and controls.

BIBR1532 inhibits proliferation and enhances apoptosis in multiple myeloma cells by reducing telomerase activity.

Background: Multiple myeloma (MM) is a rare haematological disorder with few therapeutic options. BIBR1532, a telomerase inhibitor, is widely used in cancer treatment and has promising outcomes. In this study, we investigated the efficacy and mechanism of action of BIBR1532 in MM. Methods: K562 and MEG-01 cells were cultured with BIBR1532 at different concentrations. After 24 and 48 h, cell survival was analyzed. Next, these cells were cultured with 25 and 50 µM BIBR1532 for 48 h, then, cell proliferation, apoptosis, and the expression of the telomerase activity related markers were tested by 5-Ethynyl-2'-deoxyuridine (EdU) staining, flow cytometric analysis, western blot and quantitative real-time PCR (qRT-PCR), respectively. Expression of Bcl-xL, Bad, Survivin, phosphorylation of PI3K, AKT, mTOR, ERK1/2, and MAPK were tested via western blotting. Further experiments were conducted to evaluate the synergistic effects of BIBR1532 and doxorubicin (Dox) or bortezomib (Bor). Results: BIBR1532 inhibited K562 and MEG-01 cell survival in a dose- and time-dependent manner. In addition, BIBR1532 hindered cell proliferation while promoting apoptosis, and this effect was enhanced by increasing the BIBR1532 concentration. Moreover, BIBR1532 inhibited TERT and c-MYC expression, PI3K, AKT, mTOR phosphorylation, and facilitated ERK1/2 and MAPK phosphorylation. Additionally, BIBR1532 combined with Dox or Bor showed synergistic effects in MM treatment. Conclusion: BIBR1532 inhibits proliferation and promotes apoptosis in MM cells by inhibiting telomerase activity. Additionally, BIBR1532 combined with Dox or Bor exhibited synergistic effects, indicating that BIBR1532 may be a novel medicine for the treatment of MM.

Acupuncture Combined with Voice Training Improved Voice Function in Patients with Primary Muscular Tension Dysphonia (MTD): A Randomized, Three-Armed, Open-Label Clinical Trial.

Objective: This randomized controlled trial aimed to evaluate the clinical efficacy of acupuncture combined with voice training for treating patients with primary muscular tension dysphonia (MTD) (Qi stagnation and blood stasis type in traditional Chinese medicine). Methods: A total of 108 patients with primary MTD (Qi stagnation and blood stasis type) were recruited in this study. The participants were randomly divided into 3 equal groups: a test group and two control groups (control groups 1 and 2). An additional 38 participants without primary MTD were recruited as the healthy group. Control group 1 received acupuncture sessions 3 times per week on alternate days on the Hegu (LI 4), Taichong (LR 3), Open Voice No. 1 point, and Open Voice No. 2 points. Control group 2 received a 40-minute voice training session once weekly. The test group received both treatments. The total treatment course for all groups was 30 days. The healthy participants did not receive any interventions. The physiological and functional voice improvements after treatment were compared between all 3 MTD groups and healthy participants. The Voice Handicap Index (VHI-10), the VHI-10 emotional score, the Chinese Medicine Symptom Score Scale (TCM), and the Grade Roughness Breathiness Asthenia Strain (GRBAS) were used to evaluate the changes in the voice after treatment. A laryngeal muscle blood oxygen monitoring was used to measure the blood oxygen saturation (SO2) of the suprahyoid and infrahyoid muscles, and a stroboscopic laryngoscopy was used to measure the dysphonia severity index (DSI). Acoustic voice analysis was used to measure the maximum phonation time (MPT), the jitter, and the shimmer. Result: The SO2 levels of the laryngeal muscle were significantly higher in the healthy subjects than in pretreatment MTD patients and were correlated with the VHI-10 and DSI scores. A significant improvement in the physiological and functional scores, the total VHI-10, the GRBAS score, the voice acoustic analysis indices, MPT, jitter, shimmer, and DSI, was noted after treatment in all 3 MTD groups (P < 0.05). However, the posttreatment scores in the test group were significantly higher compared to control group 2, whose score were superior than that in control group 1 (P < 0.05). Both the test group and control group 1 showed a significant increase in the SO2 levels of the laryngeal muscles after treatment, where the test group had a higher elevation than control group 1. No significant difference was noted in the posttreatment SO2 of the laryngeal muscles in control group 2 (P > 0.05). Conclusion: Acupuncture monotherapy or in combination with voice training can reduce the anxiety emotion, relieve MTD-associated systemic symptoms, and increase the SO2 levels of the laryngeal muscle. This combination is a promising approach for the treatment of MTD. This trial is registered with ChiCTR2200061469.

Efficacy of Acupuncture for Chronic Spontaneous Urticaria : A Randomized Controlled Trial.

BACKGROUND: The effectiveness of acupuncture for patients with chronic spontaneous urticaria (CSU), reported in a few small-scale studies, is not convincing. OBJECTIVE: To investigate whether acupuncture leads to better effects on CSU than sham acupuncture or waitlist control. DESIGN: A multicenter, randomized, sham-controlled trial. (Chinese Clinical Trial Registry: ChiCTR1900022994). SETTING: Three teaching hospitals in China from 27 May 2019 to 30 July 2022. PARTICIPANTS: 330 participants diagnosed with CSU. INTERVENTION: Participants were randomly assigned in a 1:1:1 ratio to receive acupuncture, sham acupuncture, or waitlist control over an 8-week study period (4 weeks for treatment and another 4 weeks for follow-up). MEASUREMENTS: The primary outcome was the mean change from baseline in the Weekly Urticaria Activity Score (UAS7) at week 4. Secondary outcomes included itch severity scores, self-rated improvement, and Dermatology Life Quality Index scores. RESULTS: The mean change in UAS7 (range, 0 to 42) for acupuncture from baseline (mean score, 23.5 [95% CI, 21.8 to 25.2]) to week 4 (mean score, 15.3 [CI, 13.6 to 16.9]) was -8.2 (CI, -9.9 to -6.6). The mean changes in UAS7 for sham acupuncture and waitlist control from baseline (mean scores, 21.9 [CI, 20.2 to 23.6] and 22.1 [CI, 20.4 to 23.8], respectively) to week 4 (mean scores, 17.8 [CI, 16.1 to 19.5] and 20.0 [CI, 18.3 to 21.6], respectively) were -4.1 (CI, -5.8 to -2.4) and -2.2 (CI, -3.8 to -0.5), respectively. The mean differences between acupuncture and sham acupuncture and waitlist control were -4.1 (CI, -6.5 to -1.8) and -6.1 (CI, -8.4 to -3.7), respectively, which did not meet the threshold for minimal clinically important difference. Fifteen participants (13.6%) in the acupuncture group and none in the other groups reported adverse events. Adverse events were mild or transient. LIMITATION: Lack of complete blinding, self-reported outcomes, limited generalizability because antihistamine use was disallowed, and short follow-up period. CONCLUSION: Compared with sham acupuncture and waitlist control, acupuncture produced a greater improvement in UAS7, although the difference from control was not clinically significant. Increased adverse events were mild or transient. PRIMARY FUNDING SOURCE: The National Key R&D Program of China and the Science and Technology Department of Sichuan Province.

Preliminary species diversity and community phylogenetics of wood-inhabiting basidiomycetous fungi in the Dabie Mountains, Central China reveal unexpected richness.

Wood-inhabiting fungi have important economic values as well as playing a major ecological role in forest ecosystem cycles. The Dabie Mountains, at the junction of Henan, Hubei, and Anhui Provinces, Central China, provide an ideal climate and favorable niches for the speciation and diversification of various forms of life including fungi. We studied the species diversity and community phylogenetics of wood-inhabiting basidiomycetous fungi that revealed 175 wood-inhabiting basidiomycetous species, of which 20 represented unidentified species, based on morphological and phylogenetic analyses of 575 specimens collected from ten sampling sites. These species belonged to two classes, 11 orders, 42 families, and 106 genera of Basidiomycota, and included 12 edible species, 28 medicinal species, four poisonous species, and seven forest pathogens. Four types of fungal distribution pattern at the genus level were recognized for 65 genera, while another 41 genera could not be placed in any known distribution pattern. The five sampling sites in the eastern part of the Dabie Mountains had significantly higher species diversity and phylogenetic diversity of wood-inhabiting basidiomycetous fungi than those in the western part, and thus deserve priority in terms of conservation. The community of wood-inhabiting basidiomycetous fungi in the Dabie Mountains is generally affected by a combination of habitat filtering and competitive exclusion. This study provides a basis on which to build actions for the comprehensive recognition, utilization, and conservation of wood-inhabiting basidiomycetous fungi in the region.

Adverse perinatal pregnancy outcomes in women with schizophrenia: A systematic review and meta-analysis.

INTRODUCTION: Schizophrenia is a severe mental illness that affects a significant proportion of the global population, particularly those of childbearing age. Several studies have attempted to find an association between schizophrenia and obstetric complications, with varying results. OBJECTIVE: The primary objective of this systematic review and meta-analyses was to summarize the relationship between maternal schizophrenia and perinatal pregnancy outcomes. DATA SOURCES: PubMed, Web of Science and Ovid EMBASE were searched from January 2001 to September 2022 using keywords related to pregnancy, women, schizophrenia. STUDY SELECTION: A total of 23 independent studies across 21,253 individuals with schizophrenia were identified and included in the analysis. DATA EXTRACTION: The following data were extracted: author, year of publication, country/continent of data collection, study design, demographic characteristics, diagnoses criteria, related complications. Data were analyzed using random-effects pairwise meta-analysis and were reported as prevalence and odd ratios (OR). Statistical heterogeneity was quantified with the I2 statistic. RESULTS: The prevalence of adverse perinatal pregnancy outcomes was represented in descending order: cesarean section (26.0 %); labor induction (24.0 %); small for gestational age (10.5 %); gestational diabetes mellitus (9.2 %); preterm birth (9.1 %); low birth weight (7.8 %); preterm rupture of membranes (6.1 %); 1-Minute Apgar Score < 7 (5.6 %); large for gestational age (5.5 %); birth defect (5.4 %); antepartum hemorrhage (4.4 %);preeclampsia/eclampsia (4.8 %); postpartum hemorrhage (3.9 %); 5-Minute Apgar Score < 7 (3.6 %); gestational hypertension (3.3 %); placental abruption (1.0 %); placenta previa (0.6 %); thromboembolic disease (0.4 %); neonatal mortality (0.3 %) (P ≤ 0.05). There was a higher risk of adverse outcomes including gestational diabetes mellitus, preeclampsia/eclampsia, placental abruption, thromboembolic disease, preterm birth, birth defect, 1-Minute Apgar score < 7, small for gestational age, low birth weight and neonatal mortality compared with non-schizophrenia population (P ≤ 0.05). CONCLUSIONS: Women with schizophrenia are at higher risk of adverse perinatal pregnancy outcomes. It is imperative that research efforts continue to focus on the reproductive safety of women with schizophrenia during their childbearing years.

Sensitive quantitation of ultra-trace toxic aconitines in complex matrices by perfusion nano-electrospray ionization mass spectrometry combined with gas-liquid microextraction.

The accurate analysis of ultra-trace (e.g. <10-4 ng/mL) substances in complex matrices is a burdensome but vital problem in pharmaceutical analysis, with important implications for precise quality control of drugs, discovery of innovative medicines and elucidation of pharmacological mechanisms. Herein, an innovative constant-flow perfusion nano-electrospray ionization (PnESI) technique was developed firstly features significant quantitative advantages in high-sensitivity ambient MS analysis of complex matrix sample. More importantly, double-labeled addition enrichment quantitation strategies of gas-liquid microextraction (GLME) were proposed for the first time, allowing highly selective extraction and enrichment of specific target analytes in a green and ultra-efficient (>1000-fold) manner. Using complex processed Aconitum herbs as example, PnESI-MS directly enabled the qualitative and absolute quantitative analysis of the processed Aconitum extracts and characterized the target toxic diester alkaloids with high sensitivity, high stability, wide linearity range, and strong resistance to matrix interference. Further, GLME device was applied to obtain the highly specific enrichment of the target diester alkaloids more than 1000-fold, and accurate absolute quantitation of trace aconitine, mesaconitine, and hypaconitine in the extracts of Heishunpian, Zhichuanwu and Zhicaowu was accomplished (e.g., 0.098 pg/mL and 0.143 pg/mL), with the quantitation results well below the LODs of aconitines from any analytical instruments available. This study built a systematic strategy for accurate quantitation of ultra-trace substances in complex matrix sample and expected to provide a technological revolution in many fields of pharmaceutical research.

Network pharmacology combined with molecular docking and experimental verification to elucidate functional mechanism of Fufang Zhenzhu Tiaozhi against type 2 diabetes mellitus.

Fufang Zhenzhu Tiaozhi (FTZ) capsules have been prescribed for treating glucose and lipid metabolism disorders such as type 2 diabetes mellitus (T2DM). However, the underlying mechanism remains unknown. In this study, network pharmacology and experimental verification were combined to investigate the mechanisms of FTZ in treating T2DM. A total of 176 active ingredients and 1169 corresponding targets were screened using biological databases. 598 potential targets of T2DM were retrieved from GeneCards, PharmGKB, OMIM, Drugbank, and TTD. The Venn diagram was employed to identify the 194 intersection targets, which were employed to construct the "Herb-Compound-Target" interacting networks. These common targets were also used to prepare a protein-protein interaction (PPI) network to uncover potential targets. The four core targets were docked to their corresponding targets for binding analysis. Additionally, the top-ranked poses of ingredients and the positive compounds from each protein were evaluated for stability using molecular dynamics. Our results suggest that core active ingredients such as kaempferol, luteolin, and baicalein have high binding affinity and stability with AKT1, PTGS2 (also known as COX-2), DPP4, and PAPRG. GO and KEGG analyses indicated that the treatment T2DM by FTZ might be related to different pathway like AMPK and EGFR pathways. The experimental validation results proved that kaempferol, luteolin, and baicalein could significantly inhibit the activity of DPP4 and COX-2, kaempferol and luteolin were also able to activate AKT and AMPK signaling pathway. This study further validated previous findings and enhanced our understanding of the potential effects of FTZ on T2DM.Communicated by Ramaswamy H. Sarma.

Thermo-responsive chiral micelles as recyclable organocatalyst for asymmetric Rauhut-Currier reaction in water.

Developing eco-friendly chiral organocatalysts with the combined advantages of homogeneous catalysis and heterogeneous processes is greatly desired. In this work, a family of amphiphilic one-handed helical polyisocyanides bearing phosphine pendants is prepared, which self-assembles into well-defined chiral micelles in water and showed thermo-responsiveness with a cloud point of approximately 38.4 °C. The micelles with abundant phosphine moieties at the interior efficiently catalyze asymmetric cross Rauhut-Currier reaction in water. Various water-insoluble substrates are transferred to target products in high yield with excellent enantioselectivity. The yield and enantiomeric excess (ee) of the product generated in water are up to 90% and 96%, respectively. Meanwhile, the yields of the same R-C reaction catalyzed by the polymer itself in organic solvents is <16%, with an ee < 72%. The homogeneous reaction of the chiral micelles in water turns to heterogeneous at temperatures higher than the cloud point, and the catalyst precipitation facilitates product isolation and catalyst recovery. The polymer catalyst is recycled 10 times while maintaining activity and enantioselectivity.

aBLA and pBLA Projections of Cell Type-Specific D1 Neurons from the mPFC Differentially Control Alcohol-Seeking Behavior.

BACKGROUND: Alcohol use disorder (AUD) is characterized by compulsive alcohol-seeking behavior, which is associated with dysregulation of afferent projections from the medial prefrontal cortex (mPFC) to the basal amygdala (BLA). However, the contribution of the cell-type-specific mechanism in this neuronal circuit to alcohol-seeking behavior remains unclear. METHODS: Mice were trained with two-bottle choice and operant alcohol self-administration procedures. Anterograde and retrograde viral methods traced the connection between dopamine type 1 receptor (D1R) neurons and BLA neurons. The electrophysiological method and in vivo optogenetic technique were used to test the function of neural circuits in alcohol seeking-behavior. RESULTS: Chronic alcohol consumption preferentially changed the activity of posterior BLA (pBLA) neurons but not anterior BLA (aBLA) neurons and overexcited the D1R neurons in the mPFC. Interestingly, we found that two populations of D1R neurons, anterior (aD1R) and posterior (pD1R) neurons, separately targeted the aBLA and pBLA, respectively, and only a few D1R neurons innervated both aBLA and pBLA neurons. Furthermore, pD1R neurons exhibited more excitability than aD1R neurons in alcohol-drinking mice. Moreover, we observed enhanced glutamatergic transmission and an increase AMPA/NMDA ratio in the mPFC inputs from pD1R neurons to pBLA. Optogenetic long-term depression (LTD) induction of the pD1R-pBLA circuit reduced alcohol-seeking behavior, while optogenetic LTD or long-term potentiation (LTP) induction of the aD1R-aBLA circuit produced no change in alcohol intake. CONCLUSIONS: The pD1R-pBLA circuit mediates chronic alcohol consumption, which may suggest a cell type-specific neuronal mechanism underlying reward-seeking behavior in AUD.

Concurrent fabry disease and immunoglobulin a nephropathy: a case report.

BACKGROUND: Fabry disease (FD) is an X-linked, hereditary dysfunction of glycosphingolipid storage caused by mutations in the GLA gene encoding alpha-galactosidase A enzyme. In rare cases, FD may coexist with immunoglobulin A nephropathy (IgAN). We describe a case of concurrent FD, IgAN, and dilated cardiomyopathy-causing mutations in the TTN and BAG3 genes, which has not been reported previously. CASE PRESENTATION: A 60-year-old female patient was admitted with a one-week history of facial and lower-limb edema, two-year history of left ventricular hypertrophy and sinus bradycardia, and recurring numbness and pain in three lateral digits with bilateral thenar muscle atrophy. Renal biopsy revealed concurrent FD (confirmed via an alpha-galactosidase A enzyme assay, Lyso-GL-3 quantification, and GLA gene sequencing) and IgAN. Heterozygous mutations in the TTN (c.30,484 C > A;p.P10162T) and BAG3 (c.88 A > G;p.I30V) genes were observed. The patient reported that two of her brothers had undergone kidney transplantation; one died suddenly at 60 years of age, and the other required a cardiac pacemaker. The 35-year-old son of the patient was screened for the GLA gene mutation and found to be positive for the same mutation as the patient. The patient was administered oral losartan (50 mg/day). Enzyme replacement therapy was refused due to financial reasons. Her renal and cardiac functions were stable yet worth closely monitoring during follow-up. CONCLUSION: The family history of patients with concurrent heart and renal diseases should be assessed in detail. Genetic testing and histological examinations are essential for diagnosing FD with IgAN.

Neurotoxicity of the Cu(OH)2 Nanopesticide through Perturbing Multiple Neurotransmitter Pathways in Developing Zebrafish.

The copper hydroxide [Cu(OH)2] nanopesticide is an emerging agricultural chemical that can negatively impact aquatic organisms. This study evaluated the behavioral changes of zebrafish larvae exposed to the Cu(OH)2 nanopesticide and assessed its potential to induce neurotoxicity. Metabolomic and transcriptomic profiling was also conducted to uncover the molecular mechanisms related to potential neurotoxicity. The Cu(OH)2 nanopesticide at 100 µg/L induced zebrafish hypoactivity, dark avoidance, and response to the light stimulus, suggestive of neurotoxic effects. Altered neurotransmitter-related pathways (serotoninergic, dopaminergic, glutamatergic, GABAergic) and reduction of serotonin (5-HT), dopamine (DA), glutamate (GLU), γ-aminobutyric acid (GABA), and several of their precursors and metabolites were noted following metabolomic and transcriptomic analyses. Differentially expressed genes (DEGs) were associated with the synthesis, transport, receptor binding, and metabolism of 5-HT, DA, GLU, and GABA. Transcripts (or protein levels) related to neurotransmitter receptors for 5-HT, DA, GLU, and GABA and enzymes for the synthesis of GLU and GABA were downregulated. Effects on both the glutamatergic and GABAergic pathways in zebrafish were specific to the nanopesticide and differed from those in fish exposed to copper ions. Taken together, the Cu(OH)2 nanopesticide induced developmental neurotoxicity in zebrafish by inhibiting several neurotransmitter-related pathways. This study presented a model for Cu(OH)2 nanopesticide-induced neurotoxicity in developing zebrafish that can inform ecological risk assessments.