A sustainable bioremediation of vanadium from marine environment and value-addition using potential thraustochytrids.

Rising concerns about global environmental degradation underscore the pressing need for effective solutions to combat heavy metal pollution. Industries such as semiconductor and steel production discharge vanadium into marine ecosystems, posing significant risks to both marine life and human health. The current study investigates efficacy of utilizing marine thraustochytrid for efficient vanadium removal outcompeting other microbial sources. By optimizing pH and temperature conditions during harvesting, achieved a remarkable 50.80 % enhancement in vanadium removal efficiency, from 19.31 to 29.12 mg/L. Furthermore, chelating agents EDTA and citric acid supplementation demonstrated promising enhancements, reaching up to 31.21 and 32.59 mg/L, respectively. Notably, vanadium-treated biomass supplemented with citric acid exhibited maximum enhancement in lipid content, from 58.47 to 75.34 %, indicating thraustochytrid's potential for biofuel production. This study presents a sustainable approach for industrial-scale vanadium bioremediation, aligning with Sustainable Development Goals focused on dual benefits of environmental protection and renewable energy.

Biological characteristics of flowers and examination of pollen viability at different developmental stages of Epimedium sagittatum (Sieb. et Zucc.) Maxim.

To gain a deeper understanding of the flowering pattern and reproductive characteristics of Epimedium sagittatum, to enrich the research on the flower development of E. sagittatum and its reproductive regulation, and to screen the methods suitable for the rapid detection of pollen viability of E. sagittatum and to promote its cross-breeding. The characteristics of its flower parts were observed, recorded and measured, and the pollen viability of E. sagittatumwas determined by five methods, including TTC staining, I2-KI staining, red ink staining, peroxidase method and in vitro germination method. The flowering process of E. sagittatum can be divided into five stages: calyx dehiscence, bract spathe, petal outgrowth, pollen dispersal, and pollination and withering. The results of I2-KI staining and peroxidase method were significantly higher than those of other methods; the in vitro germination method was intuitive and accurate, but the operation was complicated and time-consuming; the red ink staining method was easy to operate and had obvious staining effect, and the results were the closest to those of the in vitro germination method; and it was found that the pollen of E. sagittatum was not as effective as the in vitro germination method at the bud stamen stage, the flower stigma and the flower bud. It was also found that the pollen viability and germination rate of E. sagittatum pollen were higher in the three periods of bud spitting, petal adductor and pollen dispersal. Comparing the five methods, the red ink staining method was found to be a better method for the rapid detection of pollen viability; the best pollination periods of E. sagittatum were the bud stamen stage, petal adductor stage, and pollen dispersal stage of flowers at the peak of bloom. This study on the flowering and fruiting pattern of E. sagittatum, and the related mechanism of sexual reproduction, can be used as a reference for the next step of research on the breeding of E. sagittatum.

Alterations in the gut microbiome after transjugular intrahepatic portosystemic shunt in patients with hepatitis B virus-related portal hypertension.

BACKGROUND: Gut microbiota (GM) affects the progression and response to treatment in liver diseases. The GM composition is diverse and associated with different etiologies of liver diseases. Notably, alterations in GM alterations are observed in patients with portal hypertension (PH) secondary to cirrhosis, with hepatitis B virus (HBV) infection being a major cause of cirrhosis in China. Thus, understanding the role of GM alterations in patients with HBV infection-related PH is essential. AIM: To evaluate GM alterations in patients with HBV-related PH after transjugular intrahepatic portosystemic shunt (TIPS) placement. METHODS: This was a prospective, observational clinical study. There were 30 patients (with a 100% technical success rate) recruited in the present study. Patients with esophagogastric variceal bleeding due to HBV infection-associated PH who underwent TIPS were enrolled. Stool samples were obtained before and one month after TIPS treatment, and GM was analyzed using 16S ribosomal RNA amplicon sequencing. RESULTS: One month after TIPS placement, 8 patients developed hepatic encephalopathy (HE) and were assigned to the HE group; the other 22 patients were assigned to the non-HE group. There was no substantial disparity in the abundance of GM at the phylum level between the two groups, regardless of TIPS treatment (all, P > 0.05). However, following TIPS placement, the following results were observed: (1) The abundance of Haemophilus and Eggerthella increased, whereas that of Anaerostipes, Dialister, Butyricicoccus, and Oscillospira declined in the HE group; (2) The richness of Eggerthella, Streptococcus, and Bilophila increased, whereas that of Roseburia and Ruminococcus decreased in the non-HE group; and (3) Members from the pathogenic genus Morganella appeared in the HE group but not in the non-HE group. CONCLUSION: Intestinal microbiota-related synergism may predict the risk of HE following TIPS placement in patients with HBV-related PH. Prophylactic microbiome therapies may be useful for preventing and treating HE after TIPS placement.

Sediment organic matter predicts polycyclic aromatic hydrocarbon distribution in port sediments.

We evaluated the influence of organic matter in polycyclic aromatic hydrocarbons (PAHs) in port sediments using multiple linear regression (MLR) and prediction models. Total sediment PAHs ranged between 45 and 3230 ng/g dw (average: 557 ± 962 ng/g dw), with PAHs primarily originating from river inputs, confined to areas near the estuaries. Coal/biomaterial combustion and petroleum mainly contribute to the presence of PAHs along estuaries, with medium-high to high ecological risks. MLR TPAHs prediction model included variables, namely, the marine-derived total organic carbon (TOCmar), terrestrial fraction of organic matter (Fterr), and carbon-to­nitrogen ratio (CNR). Results indicate that mainly marine- followed by terrestrially-derived organic matter influenced sediment PAH distribution. Total organic nitrogen and CNR were variables in the toxic equivalent (TEQ) prediction model, demonstrating that terrestrial pollution sources primarily influenced TEQ. The study analyzes and predicts the impact of organic matter and its sources on the fate and transport of PAHs in port sediments.

Regulation of gene expression in the secondary metabolic synthesis pathway of Lonicera japonica Flos by yeast polysaccharides.

Lonicera japonica Flos is a valuable herb in the Lonicerae family. While transcriptomic studies on L. japonica have focused on different tissues (stems, leaves, flowers) or flowering stages, few have investigated the molecular mechanisms underlying chemical composition synthesis influenced by exogenous factors, such as foliar fertilization. Moreover, most transcriptomic studies on L. Japonica have been conducted on chlorogenic acid and luteoloside, and the molecular synthesis mechanism of the overall chemical composition has not been analyzed. Methods: We conducted a single-factor, four-level foliar fertilization experiment using yeast polysaccharides. Different yeast polysaccharides concentrations were sprayed on L. japonica for six consecutive days with dynamic sampling. High-performance liquid chromatography determined the active ingredients in each group. The two groups exhibiting the most significant differences were selected for transcriptomic analysis to identify key synthetic genes responsible for L. japonica's active ingredients. Key results: Principal component analysis conducted on samples collected on September 8 revealed significant differences in the active ingredient amounts between the 0.1 g/L yeast polysaccharides treatment group and the control group. Transcriptome sequencing analysis identified 218 significantly differentially expressed genes, including 60 upregulated and 158 downregulated genes. Twelve differential genes involved in the chemical components synthesis pathway of L. japonica under yeast polysaccharides treatment were identified: PAL1, PAL2, PAL3, 4CL1, 4CL, CHS1, CHS2, CHS, CHI1, CHI2, F3H, and SOH. Conclusions: This study contributes to the theoretical understanding of essential synthetic genes associated with L. japonica's active ingredients. It offers data support for further gene exploration and sheds light on the molecular mechanisms underlying L. japonica quality formation. These findings hold significant implications for enhancing the content of secondary metabolites of L. japonica. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-024-01482-1.

Contrasting metal bioaccumulation in marine benthic invertebrate groups in polluted harbor sediments.

This study examined the sediment metal fractions and availability to infer bioaccumulation in marine harbor benthic organisms. Total metals were analyzed using atomic absorption spectrometry and inductively coupled plasma-optical emission spectrometry for chemical fractions and organisms. The results showed similar metal concentrations and distribution driven by rivers and harbor pollution. We found significant differences in metal accumulation in marine benthic groups, highest in scavenger species. Their metal concentrations in decreasing order were 1.97-4568, 0.10-1260, 1.64-159, and 0.105-112 µg g-1 dw for hermit crabs, forams, bivalves, and polychaetes. Moreover, certain organisms, such as tusk shells, sea pens, bivalves, forams, and isopods, may exhibit selective metal accumulation. Biota-sediment accumulation factors (>1) were highest for essential metals like Cu, Zn, and Mn, while toxic metals like As, Cr, Co, and Ni increased. This concurrent assessment provides more comprehensive data for metal bioaccumulation in marine benthic ecosystems.

Organophosphate esters in terrestrial environments of Fildes Peninsula, Antarctica: Occurrence, potential sources, and bioaccumulation.

Despite growing concerns regarding the long-range transport (LRT) and ecological risks of organophosphate esters (OPEs), information on the environmental behaviors of OPEs in polar terrestrial ecosystems remains inadequate. In the present study, 10 OPEs were analyzed in soil and vegetation samples collected from Fildes Peninsula, Antarctica. The OPE concentrations in Antarctic soils, mosses, and lichens ranged from 0.87 to 15.7 ng/g dry weight (dw), 9.8 to 113 ng/g dw, and 3.6 to 75.2 ng/g dw, respectively. Non-chlorinated OPEs predominated in terrestrial matrices, accounting for approximately 76 % of the OPE composition. Source identification indicated that OPE contamination in Antarctica likely resulted from local anthropogenic sources and LRT. Moreover, the bioaccumulation behavior of OPEs from soil to vegetation was assessed using bioconcentration factors (BCFs), revealing a significant non-linear trend of initial increase and subsequent decrease in BCFs relative to the lipophilicities of the octanol-air partition coefficient (log KOA) and octanol-water partition coefficient (log KOW). While low levels of OPEs in Antarctic terrestrial environments were reported in this study, their sustained inputs and potential ecological risks in polar regions warrant further attention.

Identifying influencing factors of metabolic syndrome in patients with major depressive disorder: A real-world study with Bayesian network modeling.

BACKGROUND: The bidirectional relationships between metabolic syndrome (MetS) and major depressive disorder (MDD) were discovered, but the influencing factors of the comorbidity were barely investigated. We aimed to fully explore the factors and their associations with MetS in MDD patients. METHODS: The data were retrieved from the electronic medical records of a tertiary psychiatric hospital in Beijing from 2016 to 2021. The influencing factors were firstly explored by univariate analysis and multivariate logistic regressions. The propensity score matching was used to reduce the selection bias of participants. Then, the Bayesian networks (BNs) with hill-climbing algorithm and maximum likelihood estimation were preformed to explore the relationships between influencing factors with MetS in MDD patients. RESULTS: Totally, 4126 eligible subjects were included in the data analysis. The proportion rate of MetS was 32.6 % (95 % CI: 31.2 %-34.1 %). The multivariate logistic regression suggested that recurrent depression, uric acid, duration of depression, marriage, education, number of hospitalizations were significantly associated with MetS. In the BNs, number of hospitalizations and uric acid were directly connected with MetS. Recurrent depression and family history psychiatric diseases were indirectly connected with MetS. The conditional probability of MetS in MDD patients with family history of psychiatric diseases, recurrent depression and two or more times of hospitalizations was 37.6 %. CONCLUSION: Using the BNs, we found that number of hospitalizations, recurrent depression and family history of psychiatric diseases contributed to the probability of MetS, which could help to make health strategies for specific MDD patients.

Transitioning weathered oil fields towards new energy: A review on utilizing hydrogenotrophic methanogens for petroleum hydrocarbons remediation.

The weathering process can cause the volatilization of light components in crude oil, leading to the accumulation of total petroleum hydrocarbons (TPH) in weathered oil field soils. These TPH compounds are relatively resistant to biodegradation, posing a significant environmental hazard by contributing to soil degradation. TPH represents a complex mixture of petroleum-based hydrocarbons classified as persistent organic pollutants in soil and groundwater. The release of TPH pollutants into the environment poses serious threats to ecosystems and human health. Currently, various methods are available for TPH-contaminated soil remediation, with bioremediation technology recognized as an environmentally friendly and cost-effective approach. While converting TPH to CO2 is a common remediation method, the complex structures and diverse types of petroleum hydrocarbons (PHs) involved can result in excessive CO2 generation, potentially exacerbating the greenhouse effect. Alternatively, transforming TPH into energy forms like methane through bioremediation, followed by collection and reuse, can reduce greenhouse gas emissions and energy consumption. This process relies on the synergistic interaction between Methanogens archaea and syntrophic bacteria, forming a consortium known as the oil-degrading bacterial consortium. Methanogens produce methane through anaerobic digestion (AD), with hydrogenotrophic methanogens (HTMs) utilizing H2 as an electron donor, playing a crucial role in biomethane production. Candidatus Methanoliparia (Ca. Methanoliparia) was found in the petroleum archaeal community of weathered Oil field in northeast China. Ca. Methanoliparia has demonstrated its independent ability to decompose and produce new energy (biomethane) without symbiosis, contribute to transitioning weathered oil fields towards new energy. Therefore, this review focuses on the principles, mechanisms, and developmental pathways of HTMs during new energy production in the degradation of PHs. It also discusses strategies to enhance TPH degradation and recovery methods.

Microplastics and phthalate esters contamination in top oceanic predators: A study on multiple shark species in the Pacific Ocean.

Marine organisms, especially top predators such as sharks, are susceptible to environmental pollutants like microplastics (MPs) and phthalate esters (PAEs), leading to ecosystem risks. Research on contamination in these apex species is, however, still limited. This study investigated MPs and PAEs in multiple shark species (Isurus oxyrinchus, Alopias superciliosus, Alopias pelagicus, Carcharhinus brevipinna, and Sphyrna zygaena) off Taiwan's eastern coast. Gastric tissue analyses revealed ubiquitous microplastics (2-31 particles), which positively correlated with body lengths and weights for Isurus oxyrinchus. Blue, fiber-shaped (1-2 mm), and rayon-based MPs are likely associated with textile fiber pollution. The PAEs concentration mean was 7035 ± 6829 ng/g, ww, having DEHP and DiNP as primary compounds. This study highlights pervasive contamination in Pacific Ocean sharks, emphasizing anthropogenic impact on top oceanic predators and providing essential insights for food safety and MP accumulation.

Seasonal dynamics of polycyclic aromatic hydrocarbons in microplankton from Kaohsiung Harbor (Taiwan Strait, northeastern South China Sea).

The impact of polycyclic aromatic hydrocarbons (PAHs) on the marine food web is crucially understudied in the primary trophic system. We evaluated the seasonal dynamics of PAHs in microplankton in a polluted environment (Taiwan), northeastern South China Sea. Replicate size-fractionated microplankton (55-1000 µm) were freeze-dried, and PAHs were extracted with a 1:1 v/v ratio of acetone: n-hexane, then analyzed using GC-MS. Total PAHs ranged between 68 and 2548 ng/g dw in microplankton, greatest during spring (130-2548 ng/g), followed by autumn (135-772 ng/g) and summer (44-423 ng/g). Spatial distribution varied through seasons but was higher in the southern part (S6 > S4 > S5 > S2 > S3 > S1 > S7), dominated by higher-ring PAHs from mixed pyrogenic and petrogenic sources. PAHs are significantly correlated with environmental factors, especially in colder seasons and lower salinity areas. Suspended matter and plankton influenced PAH transport and partitioning seasonally. Plankton's PAHs seasonal changes and environmental influences are revealed in an anthropic environment.

Potential risks of accumulated microplastics in shells and soft tissues of cultured hard clams (Meretrix taiwanica) and associated metals.

Microplastics (MPs) pose risks to both aquatic ecosystems and human health. This study investigated MPs in the shells and soft tissues of hard clams (Meretrix taiwanica) cultured in the inland waters of Taiwan. This study further developed two novel risk indices for assessing the potential ecological and health consequences of MPs. Moreover, the metal concentrations in the clam's soft tissues and the associated consumption health risks were investigated. Clamshells contained significant amounts of MPs with an average abundance of 16.6 ± 6.9 MPs/ind., which was higher than in the soft tissues (2.7 ± 1.7 MPs/ind.). The distribution and sizes of MPs in shells and soft tissues were similar, primarily small-sized (<2 mm, >99 %), blue (>65 %), and fibrous (>99 %). Dominant MP polymer types included rayon (83.5 %), polyethylene terephthalate (11.8 %), and polyacrylonitrile (3.6 %). The proposed MP potential ecological risk index indicates a higher potential ecological MP risk in soft tissues (302-423) than in shells (270-278) of the clams. The MP potential hazard risk index showed that the risk of exposure to MP through shellfish consumption decreased with age. The total hazard index (THI) value suggested negligible health hazards from metal exposure through shellfish consumption. Moreover, there was no significant correlation between MPs and metal concentrations in soft tissues, suggesting that metals bound to MPs contribute minimally to the total accumulated metals in clam's soft tissues. This study confirms the presence of MPs in clam shells and provides a novel tool to assess the potential ecological and health risks associated with MPs in shellfish.

A Multiscale Modeling and Experimental Study on the Tensile Strength of Plain-Woven Composites with Hybrid Bonded-Bolted Joints.

CFRP hybrid bonded-bolted (HBB) joints combine the advantages of traditional joining methods, namely adhesive bonding, and bolting, to achieve optimal connection performance, making them the most favored connection method. The structural parameters of CFRP HBB joints, including overlap length, bolt-hole spacing, and fit clearance relationships, have a complex impact on connection performance. To enhance the connectivity performance of joint structures, this paper develops a multiscale finite element analysis model to investigate the impact of structural parameters on the strength of CFRP HBB joint structures. Coupled with experimental validation, the study reveals how changes in structural parameters affect the unidirectional tensile failure force of the joints. Building on this, an analytical approach and inverse design methodology for the mechanical properties of CFRP HBB joints based on deep supervised learning algorithms are developed. Neural networks accurately and efficiently predict the performance of joints with unprecedented combinations of parameters, thus expediting the inverse design process. This research combines experimentation and multiscale finite element analysis to explore the unknown relationships between the mechanical properties of CFRP HBB joints and their structural parameters. Furthermore, leveraging DNN neural networks, a rapid calculation method for the mechanical properties of hybrid joints is proposed. The findings lay the groundwork for the broader application and more intricate design of composite materials and their connection structures.

Molecular insights into degron recognition by CRL5ASB7 ubiquitin ligase.

The ankyrin (ANK) SOCS box (ASB) family, encompassing ASB1-18, is the largest group of substrate receptors of cullin 5 Ring E3 ubiquitin ligase. Nonetheless, the mechanism of substrate recognition by ASB family proteins has remained largely elusive. Here we present the crystal structure of ASB7-Elongin B-Elongin C ternary complex bound to a conserved helical degron. ASB7 employs its ANK3-6 to form an extended groove, effectively interacting with the internal α-helix-degron through a network of side-chain-mediated electrostatic and hydrophobic interactions. Our structural findings, combined with biochemical and cellular analyses, identify the key residues of the degron motif and ASB7 required for their recognition. This will facilitate the identification of additional physiological substrates of ASB7 by providing a defined degron motif for screening. Furthermore, the structural insights provide a basis for the rational design of compounds that can specifically target ASB7 by disrupting its interaction with its cognate degron.

Immunotoxicity and oxidative damage in Litopenaeus vannamei induced by polyethylene microplastics and copper co-exposure.

This study examines the combined effects of polyethylene microplastics (PE-MP) and copper (Cu2+) on the immune and oxidative response of Litopenaeus vannamei. PE-MP adsorbed with Cu2+ at 2.3, 6.8, and 16.8 ng (g shrimp)-1) were injected into L. vannamei. Over 14 days, survival rates were monitored, and immune and oxidative stress parameters were assessed. The results showed that combined exposure to PE-MP and Cu2+ significantly reduced the survival rate and decreased total haemocyte count. Immune-related parameters (phagocytic rate, phenoloxidase and superoxide dismutase (SOD)) and antioxidant-related parameters (SOD, catalase and glutathione peroxidase mRNA and enzyme) also decreased, while respiratory burst activity significantly increased, indicating immune and antioxidant system disruption. Additionally, there was a significant increase in oxidative stress, as measured by malondialdehyde levels. Histopathological analysis revealed severe muscle, hepatopancreas, and gill damage. These results suggest that simultaneous exposure to PE-MP and Cu2+ poses greater health risks to white shrimp.

Assessing and optimizing the bioactivities of diverse enzyme-derived protein hydrolysates from Porphyra yezoensis: unlocking the health potential.

The interest in algae-derived bioactive compounds has grown due to their potential therapeutic efficacy against a range of diseases. These compounds, derived from proteins, exhibit diverse functions and profound pharmacological effects. Recent research has highlighted the extensive health benefits of algae-derived bioactive compounds, positioning them as potential natural antioxidants in the food, pharmaceutical, and cosmetic industries. This study focuses on extracting proteins from Porphyra yezoensis using innovative physical pre-treatment methods such as stirring, ball milling, and homogenization, under various acidic and alkaline conditions. Enzymatic hydrolysis, employing commercial enzymes at optimal temperature, pH, and enzyme-substrate ratios, produced distinct fractions according to molecular weight. Pepsin demonstrated the highest hydrolysis rate, with the fraction above 10 kDa identified as the most bioactive hydrolysate. Antioxidant activity was evaluated through DPPH, ABTS, ferrous ion chelation, and reducing power assays, demonstrating high antioxidant potential and the ability to mitigate oxidative stress. The 10 kDa fraction of pepsin hydrolysate exhibited 82.6% DPPH activity, 77.5% ABTS activity, 88.4% ferrous ion chelation activity, and higher reducing power potential (0.84 absorbance at 700 nm). Further exploration of mechanisms, amino acid profiles, and potential in vivo benefits is essential to fully exploit the medicinal potential of these algae-derived hydrolysates.

In vitro evaluation of antioxidant potential of polysaccharides and oligosaccharides extracted from three different seaweeds.

Bioactive polysaccharides and oligosaccharides were successfully extracted from three distinct seaweeds: Sargassum sp., Graciallaria sp., and Ulva sp. utilizing various extraction techniques. The obtained polysaccharides and oligosaccharides were subjected to comprehensive characterization, and their potential antioxidant properties were assessed using a Hep G2 cell model. Analysis via FTIR spectroscopy unveiled the presence of sulfate groups in the polysaccharides and oligosaccharides derived from Sargassum sp. The antioxidant capabilities were assessed through various assays (DPPH, ABTS, Fe-ion chelation, and reducing power), revealing that SAR-OSC exhibited superior antioxidant activity than others. This was attributed to its higher phenolic content (24.6 µg/mg), FRAP value (36 µM Vitamin C/g of extract), and relatively low molecular weight (5.17 kDa). The study also investigated the protective effects of these polysaccharides and oligosaccharides against oxidative stress-induced damage in Hep G2 cells by measuring ROS production and intracellular antioxidant enzyme expressions (SOD, GPx, and CAT). Remarkably, SAR-OSC demonstrated the highest efficacy in protecting Hep G2 cells reducing ROS production and downregulating SOD, GPx, and CAT expressions. Current findings have confirmed that the oligosaccharides extracted by the chemical method show higher antioxidant activity, particularly SAR-OSC, and robust protective abilities in the Hep G2 cells.

Enhancing photocatalytic reduction of Cr(VI) in water through morphological manipulation of g-C3N4 photocatalysts: A comparative study of 1D, 2D, and 3D structures.

In this research, the dimensional catalysts of pure g-C3N4 photocatalysts (1D, 2D, and 3D) were investigated for the reduction of the highly toxic/carcinogenic Cr(VI) under visible light irradiation. The catalysts underwent explanation through various surface analysis techniques. According to the BET data, the specific surface area of the 3D catalyst was 1.3 and 7 times higher than those of the 2D and 1D CN catalysts, respectively. The 3D catalyst demonstrated superior performance, achieving an efficiency greater than 99% within 60 min under visible light irradiation in the presence of EDTA due to the abundance of active sites. The study also delved into the influence of factors such as the amount of EDTA-hole scavenger, pH, catalyst dosage, and temperature on the photocatalytic reduction of Cr(VI). Moreover, the 3D catalyst showed excellent reusability, maintaining an efficiency of more than 80% even after 10 cycles, and performed effectively in real water samples. The 3D CN catalyst, with its facile synthesis process, excellent visible light harvesting properties, high reduction efficiency that sustains over multiple cycles, and outstanding performance in real water samples, presents a significant advancement for practical applications in environmental remediation. This research contributes to a new understanding of developing efficient degradation methods for heavy metals in polluted water, highlighting the potential of 3D g-C3N4 catalysts in environmental cleanup efforts.

Molecular Orientation Regulation of Hole Transport Semicrystalline-Polymer Enables High-Performance Carbon-Electrode Perovskite Solar Cells.

Carbon-based perovskite solar cells (PSCs) coupled with solution-processed hole transport layers (HTLs) have shown potential owing to their combination of low cost and high performance. However, the commonly used poly(3-hexylthiophene) (P3HT) semicrystalline-polymer HTL dominantly shows edge-on molecular orientation, in which the alkyl side chains directly contact the perovskite layer, resulting in an electronically poor contact at the perovskite/P3HT interface. The study adopts a synergetic strategy comprising of additive and solvent engineering to transfer the edge-on molecular orientation of P3HT HTL into 3D molecular orientation. The target P3HT HTL possesses improved charge transport as well as enhanced moisture-repelling capability. Moreover, energy level alignment between target P3HT HTL and perovskite layer is realized. As a result, the champion devices with small (0.04 cm2) and larger areas (1 cm2) deliver notable efficiencies of 20.55% and 18.32%, respectively, which are among the highest efficiency of carbon-electrode PSCs.

INTERACT: a randomized phase 2 study of the DAAO inhibitor luvadaxistat in adults with schizophrenia.

Deficits in N-methyl-d-aspartate receptor (NMDAR) signaling are implicated in the pathogenesis of schizophrenia. Luvadaxistat (TAK-831/NBI-1065844) is an investigational d-amino acid oxidase (DAAO) inhibitor that increases d-serine levels at NMDAR coagonist sites. INTERACT is a phase 2 randomized, placebo-controlled study that evaluated the efficacy and safety of three doses of luvadaxistat, covering a range of DAAO occupancy and d-serine levels, in patients with schizophrenia with persistent negative symptoms. The study included a 14-day, single-blinded placebo run-in period and a 12-week, double-blinded treatment period. The primary efficacy endpoint was the 12-week change from baseline in Positive and Negative Syndrome Scale-Negative Symptom Factor Score (PANSS NSFS). Secondary efficacy endpoints included the 12-week changes from baseline in Brief Assessment of Cognition in Schizophrenia (BACS) score and Schizophrenia Cognition Rating Scale (SCoRS) score. Safety endpoints included adverse event assessments. The full analysis set included all randomized patients (N = 256 [placebo, n = 87; luvadaxistat 50 mg, n = 58; 125 mg, n = 56; 500 mg, n = 55]); 228 patients completed the study. No significant improvements in PANSS NSFS were observed at any dose versus placebo at week 12. Improvements were observed with luvadaxistat 50 mg versus placebo in cognitive endpoints: BACS composite score (nominal one-sided p = 0.031) and SCoRS interviewer total score (nominal one-sided p = 0.011). Luvadaxistat did not significantly improve negative symptoms of schizophrenia. However, luvadaxistat 50 mg met the prespecified secondary endpoints for cognitive performance (BACS) and function (SCoRS), warranting further investigation in patients with cognitive impairment associated with schizophrenia. Luvadaxistat was well-tolerated in INTERACT, with no new safety signals observed. ClinicalTrials.gov: NCT03382639.