CO2-forced Late Miocene cooling and ecosystem reorganizations in East Asia.

In parallel with pronounced cooling in the oceans, vast areas of the continents experienced enhanced aridification and restructuring of vegetation and animal communities during the Late Miocene. Debate continues over whether pCO2-induced global cooling was the primary driver of this climate and ecosystem upheaval on land. Here we present an 8 to 5 Ma land surface temperatures (LST) record from East Asia derived from paleosol carbonate clumped isotopes and integrated with climate model simulations. The LST cooled by ~7 °C between 7.5 and 5.7 Ma, followed by rapid warming across the Miocene-Pliocene transition (5.5 to 5 Ma). These changes occurred synchronously with variations in alkenone and Mg/Ca-based sea surface temperatures and with hydroclimate and ecosystem shifts in East Asia, highlighting a global climate forcing mechanism. Our modeling experiments additionally demonstrate that pCO2-forced cooling would have altered moisture transfer and pathways and driven extensive aridification in East Asia. We, thus, conclude that the East Asian hydroclimate and ecosystem shift was primarily controlled by pCO2-forced global cooling between 8 and 5 Ma.

Strengthening the argument for a large Greater India.

The Sangdanlin section in southern Tibet represents a geologic Rosetta stone to constrain the initiation of the India-Asia collision from its sedimentary and paleomagnetic records. However, geoscientists have arrived at fundamentally divergent interpretations surrounding the age of the strata and its paleomagnetic record. Here, we report paleontologic, petrographic, and paleomagnetic data from the Sangdanlin section that recognize the sequence as a thrust complex containing interlaced Barremian-Albian (Early Cretaceous) and Paleocene strata, each separated by thrust faults. Recognizing two complexly interwoven formations of distinctly different ages contradicts a continuous stratigraphic superposition. Assigning an Early Cretaceous, instead of Paleocene, age to the units collected for paleomagnetic data revises paleogeographic models thereby supporting a large (2,000 to 3,000 km) extent of Greater India, with collision initiating at 55 ± 5 Ma in the western Himalayas. A contiguous plate in the Neotethys Ocean precludes that Asia's southern margin was built through a succession of accreted terrains.

Boron supply restores aluminum-blocked auxin transport by the modulation of PIN2 trafficking in the root apical transition zone.

The supply of boron (B) alleviates the toxic effects of aluminum (Al) on root growth; however, the mechanistic basis of this process remains elusive. This study filled this knowledge gap, demonstrating that boron modifies auxin distribution and transport in Al-exposed Arabidopsis roots. In B-deprived roots, treatment with Al induced an increase in auxin content in the root apical meristem zone (MZ) and transition zone (TZ), whereas in the elongation zone (EZ) the auxin content was decreased beyond the level required for adequate growth. These distribution patterns are explained by the fact that basipetal auxin transport from the TZ to the EZ was disrupted by Al-inhibited PIN-FORMED 2 (PIN2) endocytosis. Experiments involving the modulation of protein biosynthesis by cycloheximide (CHX) and transcriptional regulation by cordycepin (COR) demonstrated that the Al-induced increase of PIN2 membrane proteins was dependent upon the inhibition of PIN2 endocytosis, rather than on the transcriptional regulation of the PIN2 gene. Experiments reporting on the profiling of Al3+ and PIN2 proteins revealed that the inhibition of endocytosis of PIN2 proteins was the result of Al-induced limitation of the fluidity of the plasma membrane. The supply of B mediated the turnover of PIN2 endosomes conjugated with indole-3-acetic acid (IAA), and thus restored the Al-induced inhibition of IAA transport through the TZ to the EZ. Overall, the reported results demonstrate that boron supply mediates PIN2 endosome-based auxin transport to alleviate Al toxicity in plant roots.

PIN2/3/4 auxin carriers mediate root growth inhibition under conditions of boron deprivation in Arabidopsis.

The mechanistic basis by which boron (B) deprivation inhibits root growth via the mediation of root apical auxin transport and distribution remains elusive. This study showed that B deprivation repressed root growth of wild-type Arabidopsis seedlings, which was related to higher auxin accumulation (observed with DII-VENUS and DR5-GFP lines) in B-deprived roots. Boron deprivation elevated the auxin content in the root apex, coinciding with upregulation of the expression levels of auxin biosynthesis-related genes (TAA1, YUC3, YUC9, and NIT1) in shoots, but not in root apices. Phenotyping experiments using auxin transport-related mutants revealed that the PIN2/3/4 carriers are involved in root growth inhibition caused by B deprivation. B deprivation not only upregulated the transcriptional levels of PIN2/3/4, but also restrained the endocytosis of PIN2/3/4 carriers (observed with PIN-Dendra2 lines), resulting in elevated protein levels of PIN2/3/4 in the plasma membrane. Overall, these results suggest that B deprivation not only enhances auxin biosynthesis in shoots by elevating the expression levels of auxin biosynthesis-related genes but also promotes the polar auxin transport from shoots to roots by upregulating the gene expression levels of PIN2/3/4, as well as restraining the endocytosis of PIN2/3/4 carriers, ultimately resulting in auxin accumulation in root apices and root growth inhibition.

CD1d protects against hepatocyte apoptosis in non-alcoholic steatohepatitis.

BACKGROUND & AIMS: Hepatocyte apoptosis, a well-defined form of cell death in non-alcoholic steatohepatitis (NASH), is considered the primary cause of liver inflammation and fibrosis. However, the mechanisms underlying the regulation of hepatocyte apoptosis in NASH remain largely unclear. We explored the anti-apoptotic effect of hepatocyte CD1d in NASH. METHODS: Hepatocyte CD1d expression was analyzed in patients with NASH and mouse models. Hepatocyte-specific gene overexpression or knockdown and anti-CD1d crosslinking were used to investigate the anti-apoptotic effect of hepatocyte CD1d on lipotoxicity-, Fas-, and concanavalin (ConA)-mediated liver injuries. A high-fat diet, a methionine-choline-deficient diet, a Fas agonist, and ConA were used to induce lipotoxic and/or apoptotic liver injuries. Palmitic acid was used to mimic lipotoxicity-induced apoptosis in vitro. RESULTS: We identified a dramatic decrease in CD1d expression in hepatocytes of patients with NASH and mouse models. Hepatocyte-specific CD1d overexpression and knockdown experiments collectively demonstrated that hepatocyte CD1d protected against hepatocyte apoptosis and alleviated hepatic inflammation and injuries in NASH mice. Furthermore, decreased JAK2-STAT3 signaling was observed in NASH patient livers. Mechanistically, anti-CD1d crosslinking on hepatocytes induced tyrosine phosphorylation of the CD1d cytoplasmic tail, leading to the recruitment and phosphorylation of JAK2. Phosphorylated JAK2 activated STAT3 and subsequently reduced apoptosis in hepatocytes, which was associated with an increase in anti-apoptotic effectors (Bcl-xL and Mcl-1) and a decrease in pro-apoptotic effectors (cleaved-caspase 3/7). Moreover, anti-CD1d crosslinking effectively protected against Fas- or ConA-mediated hepatocyte apoptosis and liver injury in mice. CONCLUSIONS: Our study uncovered a previously unrecognized anti-apoptotic CD1d-JAK2-STAT3 axis in hepatocytes that conferred hepatoprotection and highlighted the potential of hepatocyte CD1d-directed therapy for liver injury and fibrosis in NASH, as well as in other liver diseases associated with hepatocyte apoptosis. IMPACT AND IMPLICATIONS: Excessive and/or sustained hepatocyte apoptosis is critical in driving liver inflammation and injury. The mechanisms underlying the regulation of hepatocyte apoptosis in non-alcoholic steatohepatitis (NASH) remain largely unclear. Here, we found that CD1d expression in hepatocytes substantially decreases and negatively correlates with the severity of liver injury in patients with NASH. We further revealed a previously unrecognized anti-apoptotic CD1d-JAK2-STAT3 signaling axis in hepatocytes, which confers significant protection against liver injury in NASH and acute liver diseases. Thus, hepatocyte CD1d-targeted therapy could be a promising strategy to manipulate liver injury in both NASH and other hepatocyte apoptosis-related liver diseases.

Epidemiology and genetic characterization of human parainfluenza virus-1 infection in pediatric patients from Hangzhou China, 2021-2022.

BACKGROUND: Human parainfluenza virus-1 (HPIV-1) is a notable pathogen instigating acute respiratory tract infections in children. The article is to elucidate the epidemiological and genetic characteristics of HPIV-1 circulating in Hangzhou during the period of 2021-2022. METHODS: A cohort of 2360 nasopharyngeal swabs were amassed and subsequently examined via RT-PCR, with HPIV-1 positive samples undergoing P gene sequencing. RESULTS: The highest HPIV-1 infection rates were found in children aged between 3 and 6 years. A pronounced positive rate persisted through the latter half of 2021, with a notable decline observed in the initial half of 2022. All HPIV-1 strains could be clustered into 2 groups: Cluster 1, with strains similar to those found in Japan (LC764865, LC764864), and Cluster 2, with strains similar to the Beijing strain (MW575643). CONCLUSION: In conclusion, our study contributes to the comprehensive data on the epidemiological and genetic characteristics of HPIV-1 in pediatric patients from Hangzhou, post the COVID-19 peak.

Characterization of a novel phage against multidrug-resistant Klebsiella pneumoniae.

Multidrug-resistant Klebsiella pneumoniae (MDR-KP) poses a significant challenge in global healthcare, underscoring the urgency for innovative therapeutic approaches. Phage therapy emerges as a promising strategy amidst rising antibiotic resistance, emphasizing the crucial need to identify and characterize effective phage resources for clinical use. In this study, we introduce a novel lytic phage, RCIP0100, distinguished by its classification into the Chaoyangvirus genus and Fjlabviridae family based on International Committee on Taxonomy of Viruses (ICTV) criteria due to low genetic similarity to known phage families. Our findings demonstrate that RCIP0100 exhibits broad lytic activity against 15 out of 27 tested MDR-KP strains, including diverse profiles such as carbapenem-resistant K. pneumoniae (CR-KP). This positions phage RCIP0100 as a promising candidate for phage therapy. Strains resistant to RCIP0100 also showed increased susceptibility to various antibiotics, implying the potential for synergistic use of RCIP0100 and antibiotics as a strategic countermeasure against MDR-KP.

NiMOF-Derived MoSe2/NiSe Hollow Nanoflower Structures as Electrocatalysts for Hydrogen Evolution Reaction in Alkaline Medium.

Metal-organic frameworks (MOFs) are crystalline porous materials for storage and energy conversion applications with three-dimensional pore structure, high porosity, and specific surface area, which are widely utilized in electrocatalysis. Herein, MoSe2/NiSe composites were synthesized by selenization reaction using NiMOF as the precursor. The composites were hollow nanoflower structures with a synergistic effect between MoSe2 and NiSe to promote rapid electron transfer, which exhibited good hydrogen evolution reaction performance in an alkaline medium. At a current density of 10 mA/cm2, the HER overpotential reaches 80 mV, the Tafel slope is 33.86 mV/dec, and the material has good stability, with polarization curves remaining essentially unchanged after 3000 cycles. These results indicate that the method has a promising application in the preparation of efficient and sustainable catalysts for hydrogen production in alkaline medium.

Characterizing the Opportunity Space for Sustainable Hydrothermal Valorization of Wet Organic Wastes.

Resource recovery from wet organic wastes can support circular economies by creating financial incentives to produce renewable energy and return nutrients to agriculture. In this study, we characterize the potential for hydrothermal liquefaction (HTL)-based resource recovery systems to advance the economic and environmental sustainability of wastewater sludge, FOG (fats, oils, and grease), food waste, green waste, and animal manure management through the production of liquid biofuels (naphtha, diesel), fertilizers (struvite, ammonium sulfate), and power (heat, electricity). From the waste management perspective, median costs range from -193 $·tonne-1 (FOG) to 251 $·tonne-1 (green waste), and median carbon intensities range from 367 kg CO2 eq·tonne-1 (wastewater sludge) to 769 kg CO2 eq·tonne-1 (green waste). From the fuel production perspective, the minimum selling price of renewable diesel blendstocks are within the commercial diesel price range (2.37 to 5.81 $·gal-1) and have a lower carbon intensity than petroleum diesel (101 kg CO2 eq·MMBTU-1). Finally, through uncertainty analysis and Monte Carlo filtering, we set specific targets (i.e., achieve wastewater sludge-to-biocrude yield >0.440) for the future development of hydrothermal waste management system components. Overall, our work demonstrates the potential of HTL-based resource recovery systems to reduce the costs and carbon intensity of resource-rich organic wastes.

Intensive Microalgal Cultivation and Tertiary Phosphorus Recovery from Wastewaters via the EcoRecover Process.

Mixed community microalgal wastewater treatment technologies have the potential to advance the limits of technology for biological nutrient recovery while producing a renewable carbon feedstock, but a deeper understanding of their performance is required for system optimization and control. In this study, we characterized the performance of a 568 m3·day-1 Clearas EcoRecover system for tertiary phosphorus removal (and recovery as biomass) at an operating water resource recovery facility (WRRF). The process consists of a (dark) mix tank, photobioreactors (PBRs), and a membrane tank with ultrafiltration membranes for the separation of hydraulic and solids residence times. Through continuous online monitoring, long-term on-site monitoring, and on-site batch experiments, we demonstrate (i) the importance of carbohydrate storage in PBRs to support phosphorus uptake under dark conditions in the mix tank and (ii) the potential for polyphosphate accumulation in the mixed algal communities. Over a 3-month winter period with limited outside influences (e.g., no major upstream process changes), the effluent total phosphorus (TP) concentration was 0.03 ± 0.03 mg-P·L-1 (0.01 ± 0.02 mg-P·L-1 orthophosphate). Core microbial community taxa included Chlorella spp., Scenedesmus spp., and Monoraphidium spp., and key indicators of stable performance included near-neutral pH, sufficient alkalinity, and a diel rhythm in dissolved oxygen.

Remote ischemic conditioning reduces adverse events in patients with acute ischemic stroke complicating acute myocardial infarction: a randomized controlled trial.

BACKGROUND: Acute ischemic stroke (AIS) complicating an acute myocardial infarction (AMI) is not uncommon, but can severely worsen the clinical prognosis. This study aimed to investigate whether remote ischemic conditioning (RIC) could provide clinical benefits to patients with AIS complicating AMI. METHODS: Subjects with AIS complicating AMI were recruited in this double-blind, randomized, controlled trial; assigned to the RIC and sham groups; and respectively underwent twice daily RIC and sham RIC for 2 weeks. All subjects received standard medical therapy. The primary endpoint was the rate of major adverse cardiac and cerebrovascular events (MACCEs) within 3 months after enrollment. MACCEs comprise of death from all causes, unstable anginas, AMI, acute ischemic strokes, and transient ischemic attacks. RESULTS: Eighty subjects were randomly assigned; 37 patients in the RIC group and 40 patients in the sham-RIC group completed the 3-month follow-up and were included in the final analysis. Both RIC and sham RIC procedures were well tolerated. At 3-month follow-up, 11 subjects (29.7%) in the RIC group experienced MACCEs compared to 21 (52.5%) in the sham group (hazard ratio [HR], 0.396; 95% confidence interval, 0.187-0.838; adjusted p < 0.05). Six subjects (16.2%) in the RIC group had died at the 3-month follow up, significantly lower than the 15 (37.5%) deaths in the sham group (adjusted HR 0.333; 95% CI 0.126-0.881; p = 0.027). Seventeen subjects (45.9%) in the RIC group and 6 subjects (15.0%) in the sham group achieved functional independence (mRS score ≤ 2) at 3-month follow-up (adjusted OR 12.75; 95% CI 2.104-77.21; p = 0.006). CONCLUSIONS: Among patients with acute ischemic stroke complicating acute myocardial infarction, treatment with remote ischemic conditioning decreased the major adverse cardiac and cerebrovascular events and improved functional outcomes at 90 days. TRIAL REGISTRATION: URL: www. CLINICALTRIALS: gov . Unique identifier: NCT03868007. Registered 8 March 2019.

Role of miRNAs in macrophage-mediated kidney injury.

Macrophages, crucial components of the human immune system, can be polarized into M1/M2 phenotypes, each with distinct functions and roles. Macrophage polarization has been reported to be significantly involved in the inflammation and fibrosis observed in kidney injury. MicroRNA (miRNA), a type of short RNA lacking protein-coding function, can inhibit specific mRNA by partially binding to its target mRNA. The intricate association between miRNAs and macrophages has been attracting increasing interest in recent years. This review discusses the role of miRNAs in regulating macrophage-mediated kidney injury. It shows how miRNAs can influence macrophage polarization, thereby altering the biological function of macrophages in the kidney. Furthermore, this review highlights the significance of miRNAs derived from exosomes and extracellular vesicles as a crucial mediator in the crosstalk between macrophages and kidney cells. The potential of miRNAs as treatment applications and biomarkers for macrophage-mediated kidney injury is also discussed.

Study of clinical traits and systemic immune inflammation index assessments in patients with endogenous endophthalmitis over the last ten years.

PURPOSE: The clinical aspects and prognosis of eyes with endogenous endophthalmitis were compared over the last ten years. The occurrence and progression of endophthalmitis are linked to the systemic immune inflammation index (SII) and clinical features. METHODS: The study comprised patients with endogenous endophthalmitis and 64 patients without endophthalmitis who were treated at Hebei Province Eye Hospital in the last ten years. According to the prognostic visual acuity, patients with endophthalmitis were split into two groups: Group A and Group B. Underlying disease (hypertension, diabetes, tuberculosis), infection risk (liver abscess, urinary tract infection, and recent abdominal surgery), signs and symptoms, and complete blood count were among the evaluation parameters (neutrophil count, lymphocyte count, monocyte count, platelet count, red blood cell distribution width). The NLR, PLR, MLR, and SII values were calculated. A nonparametric test was used to examine the clinical features and complete blood count results of patients in each group. To determine the parameters linked to endophthalmitis progression, researchers used principal component and ordinal logistic regression analyses. RESULTS: The study comprised a total of 25 eyes and 22 individuals with endogenous endophthalmitis. Infectious bacteria included Staphylococcus aureus, Micrococcus luteus, Staphylococcus hemolyticus, and so on. The visual acuity of the affected eye ranged from 2.7 (1.55, 2.7) LogMAR to 1.22 (0.6, 2.7) LogMAR during the 6-month to 8-year follow-up period. The neutrophil, monocyte, and PLT counts, NLR, PLR, and SII values and other markers were considerably higher in Groups A and B than in the control group. The likelihood model of the SII and sex, age, onset time, diabetes, hypertension, monocyte count, and red blood cell distribution was the best, and its increase was strongly connected with the occurrence and progression of endophthalmitis, according to ordinal regression analysis. CONCLUSION: Patients with endophthalmitis had significantly higher blood neutrophil, monocyte, and PLT counts and SII, NLR, PLR, and MLR values. The SII can be employed as a biomarker for predicting endophthalmitis severity and prognosis.

The First High-Quality Genome Assembly of Freshwater Pearl Mussel Sinohyriopsis cumingii: New Insights into Pearl Biomineralization.

China leads the world in freshwater pearl production, an industry in which the triangle sail mussel (Sinohyriopsis cumingii) plays a pivotal role. In this paper, we report a high-quality chromosome-level genome assembly of S. cumingii with a size of 2.90 Gb-the largest yet reported among bivalves-and 89.92% anchorage onto 19 linkage groups. The assembled genome has 37,696 protein-coding genes and 50.86% repeat elements. A comparative genomic analysis revealed expansions of 752 gene families, mostly associated with biomineralization, and 237 genes under strong positive selection. Notably, the fibrillin gene family exhibited gene family expansion and positive selection simultaneously, and it also exhibited multiple high expressions after mantle implantation by transcriptome analysis. Furthermore, RNA silencing and an in vitro calcium carbonate crystallization assay highlighted the pivotal role played by one fibrillin gene in calcium carbonate deposition and aragonite transformation. This study provides a valuable genomic resource and offers new insights into the mechanism of pearl biomineralization.

Implications of Biorefinery Policy Incentives and Location-Specific Economic Parameters for the Financial Viability of Biofuels.

Cellulosic biofuels are part of a portfolio of solutions to address climate change; however, their production remains expensive and federal policy interventions (e.g., Renewable Fuel Standard) have not spurred broad construction of cellulosic biorefineries. A range of state-level interventions have also been enacted, but their implications for the financial viability of biorefineries are not well understood. To address this gap, this study evaluated the efficacy of 20 state-level tax incentives from 14 states and their interactions with other location-specific economic parameters (e.g., state income tax rates, electricity prices). To characterize implications of location-specific policies and parameters on biorefinery cash flows, we developed a new BioSTEAM Location-Specific Evaluation (BLocS) module for the open-source software BioSTEAM. Leveraging BLocS and BioSTEAM, we characterized the minimum ethanol selling price (MESP) for a cellulosic biorefinery (using corn stover as feedstock) and two conventional biorefineries (using corn or sugarcane as feedstock) for comparison. Among state-specific scenarios, nonincentivized MESPs for the corn stover biorefinery ranged from 0.74 $·L-1 (4.20 $·gallon gasoline equivalent [gge]-1) [0.69-0.79 $·L-1; 3.91-4.48 $·gge-1; Oklahoma] to 1.02 $·L-1 (5.78 $·gge-1) [0.95-1.09 $·L-1; 5.39-6.18 $·gge-1; New York], while the tax incentive-induced MESP reduction ranged from negligible (Virginia) to 5.78% [5.43-6.20%; Iowa]. Ultimately, this work can inform the design of policy incentives for biorefineries under specific deployment contexts.

Bifidobacterium lactis Probio-M8 improves bone metabolism in patients with postmenopausal osteoporosis, possibly by modulating the gut microbiota.

PURPOSE: Postmenopausal osteoporosis (PMO) is usually managed by conventional drug treatment. However, prolonged use of these drugs cause side effects. Gut microbiota may be a potential target for treatment of PMO. This work was a three-month intervention trial aiming to evaluate the added effect of probiotics as adjunctive treatment for PMO. METHODS: Forty patients with PMO were randomized into probiotic (n = 20; received Bifidobacterium animalis subsp. lactis Probio-M8 [Probio-M8], calcium, calcitriol) and placebo (n = 20; received placebo material, calcium, calcitriol) groups. The bone mineral density of patients was measured at month 0 (0 M; baseline) and month 3 (3 M; after three-month intervention). Blood and fecal samples were collected 0 M and 3 M. Only 15 and 12 patients from Probio-M8 and placebo groups, respectively, provided complete fecal samples for gut microbiota analysis. RESULTS: No significant change was observed in the bone mineral density of patients at 3 M. Co-administering Probio-M8 improved the bone metabolism, reflected by an increased vitamin D3 level and decreased PTH and procalcitonin levels in serum at 3 M. Fecal metagenomic analysis revealed modest changes in the gut microbiome in both groups at 3 M. Interestingly, Probio-M8 co-administration affected the gut microbial interactive correlation network, particularly the short-chain fatty acid-producing bacteria. Probio-M8 co-administration significantly increased genes encoding some carbohydrate metabolism pathways (including ABC transporters, the phosphotransferase system, and fructose and mannose metabolism) and a choline-phosphate cytidylyltransferase. CONCLUSIONS: Co-administering Probio-M8 with conventional drugs/supplements was more efficacious than conventional drugs/supplements alone in managing PMO. Our study shed insights into the beneficial mechanism of probiotic adjunctive treatment. REGISTRATION NUMBER OF CLINICAL TRIAL: Chinese Clinical Trial Registry (identifier number: ChiCTR1800019268).

γ-Glutamyltranspeptidase-Activated Near-Infrared fluorescent probe for visualization of Drug-Induced liver injury.

Drug-induced liver injury (DILI), induced by overdose or chronic administration of drugs, has become the leading cause of acute liver failure. Therefore, an accurate diagnostic method for DILI is critical to improve treatment efficiency. The production of γ-glutamyltranspeptidase (GGT) is closely related to the progression of drug-induced hepatotoxicity. KL-Glu exhibits a prominent GGT-activated NIR fluorescence (734 nm) with a large Stokes shift (137 nm) and good sensitivity/selectivity, making it favorable for real-time detection of endogenous GGT activity. Using this probe, we evaluated the GGT up-regulation under the acetaminophen-induced liver injury model. Moreover, KL-Glu was successfully used to assess liver injury induced by the natural active ingredient triptolide and the effective amelioration upon treatment with N-acetyl cysteine (NAC) or Glutathione (GSH) in cells and in vivo by fluorescent trapping the fluctuation of GGT for the first time. Therefore, the fluorescent probe KL-Glu can be used as a potential tool to explore the function of GGT in the progression of DILI and for the early diagnosis and prognostic evaluation of DILI.

A cross-sectional analysis of the relationships between anxiety sensitivity and youth irritability: the mediated roles of insomnia and selective attention for threat.

BACKGROUND: Irritability is common in multiple psychiatric disorders and is hallmark of disruptive mood dysregulation disorder. Child irritability is associated with higher risk of suicide and adulthood mental health problems. However, the psychological mechanisms of irritability are understudied. This study examined the relationship between anxiety sensitivity and irritability among youth, and further explored three possible mediated factors: selective attention for threat, delayed reward discounting, and insomnia. METHODS: Participants were 1417 students (51.7% male; mean age 13.83 years, SD = 1.48) recruited from one high school in Hunan province, China. Self-report questionnaires were used to measure irritability (The Affective Reactivity Index and The Brief Irritability Test), anxiety sensitivity (The Childhood Anxiety Sensitivity Index), selective attention for threat (The Davos Assessment of Cognitive Biases Scale-attention for threat bias subscale), insomnia (The Youth Self-Rating Insomnia Scale), and delayed reward discounting (The 27-item Monetary Choice Questionnaire). Structural equation modal (SEM) was performed to examine mediated relations. RESULTS: Anxiety sensitivity was modestly related to irritability and insomnia (r from 0.25 to 0.54) and slightly correlated with selective attention for threat (r from 0.12 to 0.28). However, there is no significant relationship of delayed rewards discounting with anxiety sensitivity and irritability. The results of SEM showed that selective attention for threat (indirect effect estimate = 0.04) and insomnia (indirect effect estimate = 0.20) partially mediate the relationship between anxiety sensitivity and irritability, which explained 34% variation. CONCLUSIONS: Anxiety sensitivity is an important susceptibility factor for irritability. Selective attention for threat and insomnia are two mediated mechanisms to understand the relationship between anxiety sensitivity and irritability.

Genome-wide identification, phylogeny, expression and eyestalk neuroendocrine regulation of vitellogenin gene family in the freshwater giant prawn Macrobrachium rosenbergii.

Vitellogenin (Vg) is the precursor of vitellin, which is an important female-specific protein stored in oocytes as the major nutrient and energy sources for embryogenesis in oviparous animals. In this study, we performed comprehensive genome-wide analysis of Vg gene family in the prawn Macrobrachium rosenbergii, and eight Vg genes designated as MrVg1a, MrVg1b and MrVg2-7 were identified. MrVg1a clusters with the previously described MrVg1b near the end of chromosome 46 and MrVg2 is on the chromosome 42 while MrVg3-7 cluster on the chromosome 23. All the putative MrVg proteins are characterized by the presence of three conserved functional domains: LPD-N, DUF1943 and vWD. Phylogenetic analysis revealed that MrVg1a shares 93% identity with MrVg1b and groups together into a branch while MrVg2-7 group into another branch, suggesting that MrVg1a, 1b and MrVg2-7 might diversify from a common ancestral gene. All the corresponding MrVg transcripts especially for MrVg1 exhibit high expression in the female hepatopancreas at late vitellogensis stage but extremely low in the ovaries except MrVg5, indicating that hepatopancreas is the major site of MrVgs synthesis. In the male, interestingly, MrVg5 and MrVg6 are also highly expressed in the testis, suggesting their potential involvement in testicular development. Bilateral ablation of eyestalk significantly upregulate all the MrVgs mRNA in the female hepatopancreas and the MrVg1 in ovary, but have no effect on the expression of MrVg2-7 in the ovary, demonstrating that eyestalk hormones could promote the ovarian development mostly by inducing the synthesis of MrVgs in the hepatopancreas but rarely in the ovary. Our results provide new insights into the prawn MrVgs family and improve our understanding of the potential role for each member of the family in the gonadal development of M. rosenbergii.

Withanolides from Physalin angulata and Their Inhibitory Effects on Nitric Oxide Production.

Six new withanolides, angulasteroidins A-F (1-6), along with twelve known analogs (7-18) were isolated from the whole plants of Physalis angulata. Their structures were elucidated by analysis of 1D and 2D NMR, ECD and IR spectra, HR-ESI-MS data, and ECD calculation. Compounds 1 and 6 were rare 1-10 seco withanolides. Compounds 2-4, 7-9, and 15 exhibited significant inhibitory activity on the production of nitric oxide in the LPS-activated RAW 264.7 mouse macrophage cell lines with IC50 values ranging from 0.23 to 9.06 µM.