Suppressing Charge Extraction Loss in Quantum Dot Infrared Photovoltaics by Optimizing the Charge Transport Layer.

Infrared solar cells (IRSCs), capable of converting low-energy infrared photons to electron-hole pairs, are promising infrared optoelectronic devices because of their extended utilization region of the solar to short-wavelength infrared region. For PbS QDs IRSCs, charge extraction loss, easily generated at the interfaces, has been one of the dominate obstacles impeding the improvement of device efficiencies due to too many trap states and mismatched energy levels between the photoactive layer and electron transport layer (ETL). Herein, an advanced ZnO ETL was developed to improve the extraction of photogenerated charges from the PbS QD photoactive layer to ETLs. The advanced ETL film exhibited effectively suppressed trap states and better-matched energy levels compared with the QD layer. As a consequence, high-performance PbS QD IRSCs with the highest infrared power conversion efficiencies of 1.26% under 1100 nm filtered solar illumination are achieved, suggesting an effective and facile route for enhancing the charge extraction in infrared photovoltaics.

Indomethacin Does Not Reduce Post-ERCP Pancreatitis in High-Risk Patients Receiving Pancreatic Stenting.

BACKGROUND: Rectal indomethacin reduces pancreatitis following endoscopic retrograde cholangiopancreatography (ERCP). However, there is insufficient evidence regarding its added benefits in patients already receiving prophylactic pancreatic stenting. Our goal was to evaluate the impact of indomethacin in high-risk patients undergoing pancreatic stenting. METHODS: A cohort study was conducted on all patients who underwent the rescue cannulation technique for challenging bile duct cannulation (selected high-risk patients). Patients were split into two groups based on the prophylaxis method for post-ERCP pancreatitis (PEP): one receiving a combination of indomethacin and pancreatic stenting, while the other received pancreatic stenting alone. Comparative analyses were carried out on PEP, hyperamylasemia, gastrointestinal bleeding, and postoperative hospital stay among post-ERCP pancreatitis patients. RESULTS: Between November 2017 and May 2023, a total of 607 patients with native papillae were enrolled, with 140 grouped into the indomethacin plus stent group and 467 into the stent alone group. The overall PEP rate was 4.4% in the entire cohort, with no statistical differences observed between the groups in terms of PEP rates (P = 0.407), mild PEP (P = 0.340), moderate to severe PEP (P = 1.000), hyperamylasemia (P = 0.543), gastrointestinal bleeding (P = 0.392), and postoperative hospital stay (P = 0.521). Furthermore, sensitivity analysis using multivariable analysis also validated these findings. CONCLUSIONS: Indomethacin did not reduce the incidence or severity of PEP in high-risk patients who routinely received prophylactic pancreatic stent placement. Therefore, the additional administration of rectal indomethacin to further mitigate PEP appears to be not necessary.

Ultrafast Excited-State Energy Transfer in Phenylene Ethynylene Dendrimer: Quantum Dynamics with the Tensor Network Method.

Photoinduced excited-state energy transfer (EET) processes play an important role in solar energy conversions. Owing to their excellent photoharvesting and exciton-transport properties, phenylene ethynylene (PE) dendrimers display great potential for improving the efficiency of solar cells. In this work, we investigated the intramolecular EET dynamics in a dendrimer composed of two linear PE units (2-ring and 3-ring) using a fully quantum description based on the tensor network method. We first constructed a diabatic model Hamiltonian based on the electronic structure calculations. Using this diabatic vibronic coupling model, we tried to obtain the main features of the EET dynamics in terms of the several diabatic models with different numbers of vibrational modes (from 4 modes to 129 modes) and to explore the corresponding vibronic coupling interactions. The results show that the EET in this PE dendrimer is ultrafast. Four modes of A' symmetry play dominant roles in the dynamics; the remaining 86 modes of A' symmetry can dampen the electronic coherence; and the modes of A″ symmetry do not exhibit significant influence on the EET process. Overall, the first-order intrastate vibronic coupling terms show the dominant role in the EET dynamics, while the second-order intrastate vibronic coupling terms cause damping of the electronic coherence and slow down the overall EET process. This work provides a microscopic understanding of the EET dynamics in PE dendrimers.

Integrin-Linked Kinase in the Development of Gastric Tumors Induced by Helicobacter pylori: Regulation and Prevention Potential.

BACKGROUND: Integrin-linked kinase (ILK) is crucial in solid tumors by regulating the Hippo-Yes-associated protein 1 (YAP) pathway. This study aimed to uncover how Helicobacter pylori influences ILK levels and its role in regulating YAP during H. pylori-induced gastric cancer. MATERIALS AND METHODS: GES-1 cells with stable Ilk knockdown and overexpression and a mouse carcinogenesis model for H. pylori infection were constructed. And ILK, the phosphorylated mammalian STE20-like protein kinase 1 (MST1), large tumor suppressor 1 (LATS1; S909, T1079), and YAP (S109, S127) were detected in cells, and mice by western blotting, as well as fluorescence intensity of YAP were assayed by immunofluorescence. YAP downstream genes Igfbp4 and Ctgf, the pathological changes and tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), interleukin-1beta (IL-1ß), and nitric oxide (NO) levels in mice gastric tissues were detected by real-time PCR, H&E, and ELISA assays. RESULTS: In this study, stable Ilk knockdown cells exhibited significantly higher phosphorylated levels of MST1, LATS1, and YAP, as well as increased YAP in the nuclei of GES-1 cells. Conversely, cells with Ilk overexpression showed opposite results. H. pylori infection led to decreased ILK levels in gastric epithelial cells but increased ILK levels in gastric cancer cell lines (MGC803, SGC7901) and gastric cancer tissues in mice. Treatment with the ILK inhibitor OST-T315 elevated the phosphorylated MST, LATS1, and YAP levels, and inhibited the mRNA levels of Igfbp4 and Ctgf at 44, 48 week-aged mice. OST-T315 also reduced the release of TNF-α, IL-6, IL-1ß, and NO, as well as the progression of gastric cancer caused by H. pylori and N-Nitroso-N-methylurea (NMU) treatment. CONCLUSION: Upon initiation of gastric tumorigenesis signals, H. pylori increases ILK levels and suppresses Hippo signaling, thereby promoting YAP activation and gastric cancer progression. ILK can serve as a potential prevention target to impede H. pylori-induced gastric cancer.

Application of data-driven blended online-offline teaching in medicinal chemistry for pharmacy students: a randomized comparison.

BACKGROUND: The purpose of this study was to evaluate the effectiveness and efficiency of implementing a data-driven blended online-offline (DDBOO) teaching approach in the medicinal chemistry course. METHODS: A total of 118 third-year students majoring in pharmacy were enrolled from September 2021 to January 2022. The participants were randomly assigned to either the DDBOO teaching group or the traditional lecture-based learning (LBL) group for medicinal chemistry. Pre- and post-class quizzes were administered, along with an anonymous questionnaire distributed to both groups to assess students' perceptions and experiences. RESULTS: There was no significant difference in the pre-class quiz scores between the DDBOO and LBL groups (T=-0.637, P = 0.822). However, after class, the mean quiz score of the DDBOO group was significantly higher than that of the LBL group (T = 3.742, P < 0.001). Furthermore, the scores for learning interest, learning motivation, self-learning skill, mastery of basic knowledge, teamwork skills, problem-solving ability, innovation ability, and satisfaction, as measured by the questionnaire, were significantly higher in the DDBOO group than in the traditional group (all P < 0.05). CONCLUSION: The DDBOO teaching method effectively enhances students' academic performance and satisfaction. Further research and promotion of this approach are warranted.

Dietary supplementation with Clostridium autoethanogenum protein improves growth performance and promotes muscle protein synthesis by activating the mTOR signaling pathway of the broiler.

The experiment aimed to evaluate the effects of different ratios of Clostridium autoethanogenum protein (CAP) used in the diets on the growth performance, muscle quality, serum indexes, and mTOR pathway of white feather broilers. Four hundred and eighty 1-day-old Arbor Acres (AA) broilers, comprising equal numbers of males and females, were randomly assigned to one of four treatments, and each treatment consisted of 12 replicates of 10 birds. Four diets were formulated based on isoenergetic and isonitrogenous principles. The control group (CAP 0) did not receive any CAP, while the experimental groups received 2% (CAP 2), 3% (CAP 3), and 4% (CAP 4) of CAP for six weeks. Compared with the CAP0, (1) The feed conversion ratio (FCR) was lower (p < 0.05), and the leg muscle yield was higher (p < 0.05) in the CAP3 and CAP4; (2) The serum levels of TP, ALB, T-AOC, and SOD were improved in the CAP3 (p < 0.05); (3) The expression of Lipin-1 gene was down-regulated and AMPKɑ2, Akt, and 4E-BP1 genes were up-regulated in the experiment group (p < 0.05); (4) The inclusion of 3% CAP in the diet increased the levels of 4E-BP1, S6K1, Akt, and AMPKɑ2 phosphorylation by modulating the mTOR signaling pathway (p < 0.05). In conclusion, broiler diets containing 3% CAP can activate the mTOR signaling pathway to promote muscle synthesis and improve growth performance.

Built-In Positive Valence Space Shifting the Chemical Equilibrium Forward for Nitrate Reduction to Ammonia.

The electrochemical conversion of nitrate pollutants into value-added ammonia (NH3) is an appealing alternative synthetic route for sustainable NH3 production. However, the development of the electrocatalytic nitrate-to-ammonia reduction reaction (NO3RR) has been hampered by unruly reactants and products at the interface and the accompanied sluggish kinetic rate. In this work, a built-in positive valence space is successfully constructed over FeCu nanocrystals to rationally regulate interfacial component concentrations and positively shift the chemical equilibrium. With positive valence Cu optimizing the active surface, the space between the stern and shear layers becomes positive, which is able to continuously attract the negatively charged NO3- reactant and repulse the positively charged NH4+ product even under high current density, thus significantly boosting the NO3RR kinetics. The system with a built-in positive valence space affords an ampere-level NO3RR performance with the highest NH3 yield rate of 150.27 mg h-1 mg-1 at -1.3 V versus RHE with an outstanding NH3 current density of 189.53 mA cm-2, as well as a superior Faradaic efficiency (FE) of 97.26% at -1.2 V versus RHE. The strategy proposed here underscores the importance of interfacial concentration regulation and can find wider applicability in other electrochemical syntheses suffering from sluggish kinetics.

N6-methyladenosine-driven miR-143/145-KLF4 circuit orchestrates the phenotypic switch of pulmonary artery smooth muscle cells.

Pulmonary hypertension (PH) is characterized by vascular remodeling predominantly driven by a phenotypic switching in pulmonary artery smooth muscle cells (PASMCs). However, the underlying mechanisms for this phenotypic alteration remain incompletely understood. Here, we identified that RNA methyltransferase METTL3 is significantly elevated in the lungs of hypoxic PH (HPH) mice and rats, as well as in the pulmonary arteries (PAs) of HPH rats. Targeted deletion of Mettl3 in smooth muscle cells exacerbated hemodynamic consequences of hypoxia-induced PH and accelerated pulmonary vascular remodeling in vivo. Additionally, the absence of METTL3 markedly induced phenotypic switching in PASMCs in vitro. Mechanistically, METTL3 depletion attenuated m6A modification and hindered the processing of pri-miR-143/145, leading to a downregulation of miR-143-3p and miR-145-5p. Inhibition of hnRNPA2B1, an m6A mediator involved in miRNA maturation, similarly resulted in a significant reduction of miR-143-3p and miR-145-5p. We demonstrated that miR-145-5p targets Krüppel-like factor 4 (KLF4) and miR-143-3p targets fascin actin-bundling protein 1 (FSCN1) in PASMCs. The decrease of miR-145-5p subsequently induced an upregulation of KLF4, which in turn suppressed miR-143/145 transcription, establishing a positive feedback circuit between KLF4 and miR-143/145. This regulatory circuit facilitates the persistent suppression of contractile marker genes, thereby sustaining PASMC phenotypic switch. Collectively, hypoxia-induced upregulation of METTL3, along with m6A mediated regulation of miR-143/145, might serve as a protective mechanism against phenotypic switch of PASMCs. Our results highlight a potential therapeutic strategy targeting m6A modified miR-143/145-KLF4 loop in the treatment of PH.

Automatic Recognition of Auditory Brainstem Response Waveforms Using a Deep Learning-Based Framework.

OBJECTIVE: Recognition of auditory brainstem response (ABR) waveforms may be challenging, particularly for older individuals or those with hearing loss. This study aimed to investigate deep learning frameworks to improve the automatic recognition of ABR waveforms in participants with varying ages and hearing levels. STUDY DESIGN: The research used a descriptive study design to collect and analyze pure tone audiometry and ABR data from 100 participants. SETTING: The research was conducted at a tertiary academic medical center, specifically at the Clinical Audiology Center of Tsinghua Chang Gung Hospital (Beijing, China). METHODS: Data from 100 participants were collected and categorized into four groups based on age and hearing level. Features from both time-domain and frequency-domain ABR signals were extracted and combined with demographic factors, such as age, sex, pure-tone thresholds, stimulus intensity, and original signal sequences to generate feature vectors. An enhanced Wide&Deep model was utilized, incorporating the Light-multi-layer perceptron (MLP) model to train the recognition of ABR waveforms. The recognition accuracy (ACC) of each model was calculated for the overall data set and each group. RESULTS: The ACC rates of the Light-MLP model were 97.8%, 97.2%, 93.8%, and 92.0% for Groups 1 to 4, respectively, with a weighted average ACC rate of 95.4%. For the Wide&Deep model, the ACC rates were 93.4%, 90.8%, 92.0%, and 88.3% for Groups 1 to 4, respectively, with a weighted average ACC rate of 91.0%. CONCLUSION: Both the Light-MLP model and the Wide&Deep model demonstrated excellent ACC in automatic recognition of ABR waveforms across participants with diverse ages and hearing levels. While the Wide&Deep model's performance was slightly poorer than that of the Light-MLP model, particularly due to the limited sample size, it is anticipated that with an expanded data set, the performance of Wide&Deep model may be further improved.

Synergistic electrochemical catalysis by high-entropy metal phosphide in lithium-sulfur batteries.

The shuttle effect and sluggish redox kinetics of polysulfides have hindered the development of lithium-sulfur batteries (LSBs) as premier energy storage devices. To address these issues, a high-entropy metal phosphide (NiCoMnFeCrP) was synthesized using the sol-gel method. NiCoMnFeCrP, with its rich metal species, exhibits strong synergistic effects and provides numerous catalytic active sites for the conversion of polysulfides. These active sites, possessing significant polarity, can bond with polysulfides. In situ ultraviolet-visible were conducted to monitor the dynamic changes in species and concentrations of polysulfides, validating the ability of NiCoMnFeCrP to facilitate the conversion of polysulfides. The batteries with the NiCoMnFeCrP catalyst as functional separators exhibited minimal capacity decay rates of 0.04 % and 0.23 % after 100 cycles at 0 °C and 60 °C, respectively. This indicates that the NiCoMnFeCrP catalyst possesses good thermal stability. Meanwhile, its area capacity can reach 4.78 mAh cm-2 at a high sulfur load of 4.54 mg cm-2. In conclusion, NiCoMnFeCrP achieves the objective of mitigating the shuttle effect and accelerating the kinetics of the redox reaction, thereby facilitating the commercialization of LSBs.

Tibetan terrestrial and aquatic ecosystems collapsed with cryosphere loss inferred from sedimentary ancient metagenomics.

Glacier and permafrost shrinkage and land-use intensification threaten mountain wildlife and affect nature conservation strategies. Here, we present paleometagenomic records of terrestrial and aquatic taxa from the southeastern Tibetan Plateau covering the last 18,000 years to help understand the complex alpine ecosystem dynamics. We infer that steppe-meadow became woodland at 14 ka (cal BP) controlled by cryosphere loss, further driving a herbivore change from wild yak to deer. These findings weaken the hypothesis of top-down control by large herbivores in the terrestrial ecosystem. We find a turnover in the aquatic communities at 14 ka, transitioning from glacier-related (blue-green) algae to abundant nonglacier-preferring picocyanobacteria, macrophytes, fish, and otters. There is no evidence for substantial effects of livestock herding in either ecosystem. Using network analysis, we assess the stress-gradient hypothesis and reveal that root hemiparasitic and cushion plants are keystone taxa. With ongoing cryosphere loss, the protection of their habitats is likely to be of conservation benefit on the Tibetan Plateau.

Rare-Earth Lanthanum-Evoked Amorphization and Optimization to Boost Ambient Nitrogen Fixation over Single-Atom Catalysts.

Single-atom catalysts (SACs) have been widely studied in a variety of electrocatalysis. However, its application in the electrocatalytic nitrogen reduction reaction (NRR) field still suffers from unsatisfactory performance, due to the sluggish mass transfer and significant kinetic barriers. Herein, a novel rare-earth-lanthanum-evoked optimization strategy is proposed to boost ambient NRR over SACs. The incorporation of La with a large atomic radius tends to break the atomic long-range order and trigger the amorphization of SACs, endowing a greater density of dangling bonds that could modify affinity for reactants and adsorbates. Moreover, with unique 5d16s2 valence-electron configurations, its presence could further enrich the electron density and enhance the intrinsic activity of single-metal center via the valence orbital coupling. As expected, the La-modified catalyst presents excellent activity toward the electrochemical NRR, delivering a maximum ammonia yield rate of 33.91 µg h-1 mg-1 and a remarkable Faradaic efficiency of 53.82%.

Effective Charge Collection of Electron Transport Layers for High-Performance Quantum Dot Infrared Solar Cells.

Infrared (IR) solar cells, capable of converting low-energy IR photons to electron-hole pairs, are promising optoelectronic devices by broadening the utilization range of the solar spectrum to the short-wavelength IR region. The emerging PbS colloidal quantum dot (QD) IR solar cells attract much attention due to their tunable band gaps in the IR region, potential multiple exciton generation, and facile solution processing. In PbS QD solar cells, ZnO is commonly utilized as an electron transport layer (ETL) to establish a depleted heterostructure with a QD photoactive layer. However, band gap shrinkage of large PbS QDs makes it necessary to tailor the behaviors of the ZnO ETL for efficient carrier extraction in the devices. Herein, the characteristics of ZnO ETL are efficiently and flexibly tailored to match the QD layer by handily adjusting the postannealing process of ZnO ETL. With a suitable temperature, the well-matched energy level alignment and suppressed trap states are simultaneously achieved in the ZnO ETL, effectively reducing the nonradiative recombination and accelerating the electron injection from the QD layer to ETL. As a consequence, a high-performance PbS QD photovoltaic device with power conversion efficiencies (PCEs) of 10.09% and 1.37% is obtained under AM 1.5 and 1100 nm filtered solar illumination, demonstrating a simple and effective approach for achieving high-performance IR photoelectric devices.

Significantly enhanced catalytic performance of Pd nanocatalyst on AlOOH featuring abundant solid surface frustrated Lewis pair for improved hydrogen activation.

The catalytic performance of a catalyst is significantly influenced by its ability to activate hydrogen. Constructing frustrated Lewis pairs (FLPs) with the capacity for hydrogen dissociation on non-reducible supports remains a formidable challenge. Herein, we employed a straightforward method to synthesize a layered AlOOH featuring abundant OH defects suitable for constructing solid surface frustrated Lewis pair (ssFLP). The results indicated that the AlOOH-80 (synthesized at 80 °C) possessed an appropriate crystalline structure conducive to generating numerous OH defects, which facilitated the formation of ssFLP. This was further evidenced by the minimal water adsorption in the AlOOH-80, inversely correlated with the quantity of defects in the catalyst. As expected, the Pd loaded onto AlOOH (Pd/AlOOH-80) exhibited excellent catalytic activity in hydrogenation reactions, attributed to abundant defects available for constructing ssFLP. Remarkably, the Pd/AlOOH-80 catalyst, with larger-sized Pd nanoparticles, displayed notably superior activity compared to commercial Pd/Al2O3 and Pd/C, both featuring smaller-sized Pd nanoparticles. Evidently, under the influence of ssFLP, the size effect of Pd nanoparticles did not dominate, highlighting the pivotal role of ssFLP in enhancing catalytic performance. This catalyst also exhibited exceptionally high stability, indicating its potential for industrial applications.

Transpancreatic Sphincterotomy After Double Guidewire Technique Was Noninferior to Primary Transpancreatic Sphincterotomy in Difficult Biliary Cannulation.

BACKGROUND: When unintentional pancreatic duct access occurs during difficult biliary cannulation, the double guidewire (DGW) or transpancreatic sphincterotomy (TPS) may be utilized. DGW can be easily switched to TPS due to the existing guidewire in the pancreatic duct. However, the efficacy of TPS after DGW, named sequential DGW-TPS technique, versus primary TPS has not been assessed. AIMS: Our aim was to compare the benefits and adverse events of sequential DGW-TPS technique and primary TPS. METHODS: We performed a comparative retrospective cohort study that enrolled a total of 117 patients with native papillae. The patients were divided into one of 2 groups according to the primary bile duct access technique (sequential DGW-TPS or primary TPS), both with pancreatic stenting. RESULTS: Between November 2017 and May 2023, a total of 84 patients were grouped into sequential DGW-TPS and 33 into primary TPS. The overall post-ERCP pancreatitis (PEP) rate was 4.3% in the entire cohort, with no statistical differences were observed between the groups in terms of PEP rates (P = 0.927), PEP severity (P = 1.000), first biliary cannulation success (P = 0.621), overall cannulation success (P = 1.000), hyperamylasemia incidence (P = 0.241), elevated amylase levels (P = 0.881), and postoperative hospital stay (P = 0.185). Furthermore, these results remained consistent in multivariable regression analysis. CONCLUSIONS: The sequential DGW-TPS technique showed a comparable safety and biliary cannulation success rate to primary TPS in difficult biliary cannulation. Given the potential long-term complications associated with TPS, DGW should be first if inadvertent pancreatic access occurs, with TPS serving as second only if DGW fails.

Exploring the diversity, bioactivity of endophytes, and metabolome in Synsepalum dulcificum.

Synsepalum dulcificum exhibits high edible and medicinal value; however, there have been no reports on the exploration of its endophyte resources. Here, we conducted analyses encompassing plant metabolomics, microbial diversity, and the biological activities of endophytic metabolites in S. dulcificum. High-throughput sequencing identified 4,913 endophytic fungal amplicon sequence variants (ASVs) and 1,703 endophytic bacterial ASVs from the roots, stems, leaves, flowers, and fruits of S. dulcificum. Fungi were classified into 5 phyla, 24 classes, 75 orders, 170 families, and 313 genera, while bacteria belonged to 21 phyla, 47 classes, 93 orders, 145 families, and 232 genera. Furthermore, there were significant differences in the composition and content of metabolites in different tissues of S. dulcificum. Spearman's correlation analysis of the differential metabolites and endophytes revealed that the community composition of the endophytes correlated with plant-rich metabolites. The internal transcribed spacer sequences of 105 isolates were determined, and phylogenetic analyses revealed that these fungi were distributed into three phyla (Ascomycota, Basidiomycota, and Mucoromycota) and 20 genera. Moreover, 16S rDNA sequencing of 46 bacteria revealed they were distributed in 16 genera in three phyla: Actinobacteria, Proteobacteria, and Firmicutes. The antimicrobial activities (filter paper method) and antioxidant activity (DPPH and ABTS assays) of crude extracts obtained from 68 fungal and 20 bacterial strains cultured in different media were evaluated. Additionally, the α-glucosidase inhibitory activity of the fungal extracts was examined. The results showed that 88.6% of the strains exhibited antimicrobial activity, 55.7% exhibited antioxidant activity, and 85% of the fungi exhibited α-glucosidase inhibitory activity. The research suggested that the endophytes of S. dulcificum are highly diverse and have the potential to produce bioactive metabolites, providing abundant species resources for developing antibiotics, antioxidants and hypoglycemic drugs.

Short-term mass loads of per- and polyfluoroalkyl substances in a wastewater treatment plant from South China.

Wastewater treatment plants (WWTPs) are one of the most important sources and sinks for per- and polyfluoroalkyl substances (PFAS). However, limited studies have evaluated short-term temporal variability of PFAS in WWTPs, particularly for their intra-day variations. For this purpose, a time-composite sampling campaign was carried out at a WWTP influent from South China for 1 week. Five out of ten PFAS were found in the influent, i.e., perfluoroheptanoic acid (PFHpA), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorobutane sulfonic acid (PFBS), and perfluorooctanesulfonic acid (PFOS). PFOA was the most domain PFAS whereas PFOS was detected occasionally, which might be associated with the prohibition of PFOS use in China. For the first time, we observed significant intra-day fluctuations in mass fluxes for PFOS. Different from a morning peak of pharmaceuticals reported previously, PFOS mass loads fluctuated sharply at noon and night on the weekdays. Furthermore, the mass fluxes of PFOA on the weekend were significantly elevated. For the other PFAS detected, no significant diurnal variations in mass loads were identified. Correlation analysis indicated that domestic activities (e.g., home cleaning) are likely to be the major source of these perfluorocarboxylic acids especially PFOA. In addition, flow fluxes had little effects on these PFAS mass load. These results can aid in future sampling campaigns and optimizing removal strategies for PFAS in wastewater.

POPs identification using simple low-code machine learning.

Effectively identifying persistent organic pollutants (POPs) with extensive organic chemical datasets poses a formidable challenge but is of utmost importance. Leveraging machine learning techniques can enhance this process, but previous models often demanded advanced programming skills and high-end computing resources. In this study, we harnessed the simplicity of PyCaret, a Python-based package, to construct machine-learning models for POP screening based on 2D molecular descriptors. We compared the performance of these models against a deep convolutional neural network (DCNN) model. Utilising minimal Python code, we generated several models that exhibited superior or comparable performance to the DCNN. The most outstanding performer, the Light Gradient Boosting Machine (LGBM), achieved an accuracy of 96.20 %, an AUC of 97.70 %, and an F1 score of 82.58 %. This model outshone the DCNN model. Furthermore, it excelled in identifying POPs within the REACH PBT and compiled industrial chemical lists. Our findings highlight the accessibility and simplicity of PyCaret, requiring only a few lines of code, rendering it suitable for non-computing professionals in environmental sciences. The ability of low code machine learning tools (e.g. PyCaret) to facilitate model comparison and interpretation holds promise, encouraging prompt assessment and management of chemical substances.

Discovery of a novel lead characterized by a stilbene-extended scaffold against sepsis as soluble epoxide hydrolase inhibitors.

Recently, some inhibitors of soluble epoxide hydrolase (sEH) showed limited potential in treating sepsis by increasing survival time, but they have unfortunately failed to improve survival rates. In this study, we initially identified a new hit 11D, belonging to a natural skeleton known as stilbene and having an IC50 of 644 nM on inhibiting murine sEH. Natural scaffold-based sEH inhibitors are paid less attention. A combination of structure-activity relationships (SARs)-guided structural optimization and computer-aided skeleton growth led to a highly effective lead compound 70P (IC50: 4.0 nM). The dose-response study indicated that 70P (at doses of 0.5-5 mg/kg, ip.) significantly increased survival rates and survival time by reducing the levels of the inflammatory factors TNF-α and IL-6 in the liver. Interestingly, 70P exhibited much higher accumulation in the liver than in plasma (AUC ratio: 175). In addition, 70P exhibits equal IC50 value (1.5 nM) on inhibiting human sEH as EC5026 (1.7 nM). In conclusion, the natural scaffold-extended sEH inhibitor 70P has the potential to become a new promising lead for addressing the unmet medical need in sepsis treatment, which highlighted the importance of natural skeleton in developing sEH inhibitors.

Discovery of Novel Diphenyl Acrylonitrile Derivatives That Promote Adult Rats' Hippocampal Neurogenesis.

We previously discovered WS-6 as a new antidepressant in correlation to its function of stimulating neurogenesis. Herein, several different scaffolds (stilbene, 1,3-diphenyl 1-propene, 1,3-diphenyl 2-propene, 1,2-diphenyl acrylo-1-nitrile, 1,2-diphenyl acrylo-2-nitrile, 1,3-diphenyl trimethylamine), further varied through substitutions of twelve amide substituents plus the addition of a methylene unit and an inverted amide, were examined to elucidate the SARs for promoting adult rat neurogenesis. Most of the compounds could stimulate proliferation of progenitors, but just a few chemicals possessing a specific structural profile, exemplified by diphenyl acrylonitrile 29b, 32a, and 32b, showed better activity than the clinical drug NSI-189 in promoting newborn cells differentiation into mature neurons. The most potent diphenyl acrylonitrile 32b had an excellent brain AUC to plasma AUC ratio (B/P = 1.6), suggesting its potential for further development as a new lead.