π-Extended Nonfullerene Acceptor for Compressed Molecular Packing in Organic Solar Cells To Achieve over 20% Efficiency.

Organic photovoltaics (OPVs) suffer from a trade-off between efficient charge transport and suppressed nonradiative recombination due to the aggregation-induced luminance quenching of organic semiconductors. To resolve this grand challenge, a π-extended nonfullerene acceptor (NFA) B6Cl with large voids among the honeycomb network is designed and introduced into photovoltaic systems. We find that the presence of a small amount of (i.e., 0.5 or 1 wt %) B6Cl can compress the molecular packing of the host acceptor L8-BO, leading to shortened π-π stacking distance from 3.59 to 3.50 Å (that will improve charge transport) together with ordered alkyl chain packing (that will inhibit nonradiative energy loss due to the suppressed C-C and C-H bonds vibrations), as validated by high-energy X-ray scattering measurements. This morphology transformation ultimately results in simultaneously improved JSC, FF, and VOC of OPVs. As a result, the maximum PCEs of PM6:L8-BO and D18:L8-BO are increased from 19.1 and 19.3% to 19.8 and 20.2%, respectively, which are among the highest values for single-junction OPVs. The university of B6Cl to increase the performance of OPVs is further evidenced in a range of polymer:NFA OPVs.

Electrostatic Potential Design of Solid Additives for Enhanced Molecular Order of Polymer Donor in Efficient Organic Solar Cells.

Polymeric semiconducting materials struggle to achieve fast charge mobility due to low structural order. In this work, five 1H-indene-1,3(2H)dione-benzene structured halogenated solid additives namely INB-5F, INB-3F, INB-1F, INB-1Cl, and INB-1Br with gradually varied electrostatic potential are designed and utilized to regulate the structural order of polymer donor PM6. Molecular dynamics simulations demonstrate that although the dione unit of these additives tends to adsorb on the backbone of PM6, the reduced electrostatic potential of the halogen-substituted benzene can shift the benzene interacting site from alkyl side chains to the conjugated backbone of PM6, not only leading to enhanced π-π stacking in out-of-plane but also arising new π-π stacking in in-plane together with the appearance of multiple backbone stacking in out-of-plane, consequent to the co-existence of face-on and edge-on molecular orientations. This molecular packing transformation further translates to enhanced charge transport and suppressed carrier recombination in their photovoltaics, with a maximum power conversion efficiency of 19.4% received in PM6/L8-BO layer-by-layer deposited organic solar cells.

Clopidogrel with indobufen or aspirin in minor ischemic stroke or high-risk transient ischemic attack: a randomized controlled clinical study.

BACKGROUND: Ischemic stroke and transient ischemic attack (TIA) are the most prevalent cerebrovascular diseases. The conventional antiplatelet drugs are associated with an inherent bleeding risk, while indobufen is a new antiplatelet drug and has the similar mechanism of antiplatelet aggregation as aspirin with more safety profile. However, there have been no studies evaluating the combination therapy of indobufen and clopidogrel for antiplatelet therapy in cerebrovascular diseases. OBJECTIVE: The CARMIA study aims to investigate the effectiveness and safety of a new dual antiplatelet therapy consisting of indobufen and clopidogrel comparing with the conventional dual antiplatelet therapy consisting of aspirin and clopidogrel in patients with minor ischemic stroke or high-risk TIA. METHODS: An open-label randomized controlled clinical trial was conducted at a clinical center. We randomly assigned patients who had experienced a minor stroke or transient ischemic attack (TIA) within 72 h of onset, or within 1 month if they had intracranial stenosis (IS), to receive either indobufen 100 mg twice daily or aspirin 100 mg once daily for 21 days. For patients with IS, the treatment duration was extended to 3 months. All patients received a loading dose of 300 mg clopidogrel orally on the first day, followed by 75 mg once daily from the second day to 1 year. We collected prospective data using paper-based case report forms, and followed up on enrolled patients was conducted to assess the incidence of recurrent ischemic stroke or TIA, mRS score, NIHSS (National Institutes of Health Stroke Scale) score, and any bleeding events occurring within 3 month after onset. RESULTS: We enrolled 202 patients diagnosed with ischemic stroke or transient ischemic attack. After applying the criteria, 182 patients were eligible for data analysis. Endpoint events (recurrence of ischemic stroke/TIA, myocardial infarction, or death) were observed in 6 patients (6.5%) receiving aspirin and clopidogrel, including 4 (4.3%) with stroke recurrence, 1 (1.1%) with TIA recurrence, and 1 (1%) with death. In contrast, no endpoint events were reported in the indobufen and clopidogrel group (P = 0.029). The group of patients receiving indobufen and clopidogrel exhibited significantly lower modified Rankin Scale (mRS) score. (scores range from 0 to 6, with higher scores indicating more severe disability) compared to the aspirin and clopidogrel group (common odds ratio 3.629, 95% CI 1.874-7.036, P < 0.0001). Although the improvement rate of NIHSS score in the indobufen and clopidogrel group was higher than that in the aspirin and clopidogrel group, the difference was not statistically significant (P > 0.05). Bleeding events were observed in 8 patients (8.6%) receiving aspirin and clopidogrel, including 4 (4.3%) with skin bleeding, 2 (2.2%) with gingival bleeding, 1 (1.1%) with gastrointestinal bleeding, and 1 (1.1%) with urinary system bleeding. On the other hand, only 1 patient (1.1%) in the indobufen and clopidogrel group experienced skin bleeding (P = 0.035). CONCLUSION: The combination of indobufen and clopidogrel has shown non-inferior and potentially superior effectiveness and safety compared to aspirin combined with clopidogrel in patients with minor ischemic stroke and high-risk TIA in the CARMIA study (registered under chictr.org.cn with registration number ChiCTR2100043087 in 01/02/2021).

Coumarins with Different Substituents from Leonurus japonicus Have Opposite Effects on Uterine Smooth Muscle.

Leonurus japonicus Houtt is an exceptional medicinal herb used to treat obstetrical and gynecological diseases in traditional Chinese medicine, and it has significant effects on the treatment of dysmenorrhea and postpartum hemorrhage. This study investigated the effects of coumarins with diverse substituent groups from L. japonicus on isolated uterine smooth muscle and the preliminary mechanism of the most effective compound. Eight coumarins isolated from L. japonicus were assessed for their effects on the isolated uterine smooth muscle of nonpregnant rats in vitro. Coumarins 1 and 2 significantly promoted the contraction of rat uterine smooth muscle strips, whereas coumarins 3-5 showed remarkable relaxing effects against oxytocin (OT)-induced rat uterine smooth muscle contraction. Further mechanism investigations revealed that bergapten (coumarin 1) significantly increased the level of Ca2+ in uterine tissues by promoting extracellular Ca2+ influx and intracellular Ca2+ release, which were related to the activation of L-type Ca2+ channels and α-receptors. By contrast, osthole (coumarin 5), an α receptor antagonist, inhibited OT-induced uterine smooth muscle contraction by decreasing the level of Ca2+ in uterine tissues via inhibition of extracellular Ca2+ influx and intracellular Ca2+ release. This study demonstrates that the coumarins from L. japonicus are effective substances for regulating uterine smooth muscle contraction, but different coumarins with diverse substituent groups have different, even opposite effects. It can be inferred that coumarins are closely related to the efficacy of L. japonicus in the treatment of dysmenorrhea and postpartum hemorrhage.

Medium-intensity statin with ezetimibe versus high-intensity statin in acute ischemic cerebrovascular disease (MESIA): A randomized clinical trial.

BACKGROUND: High-risk stroke patients are recommended to receive high-intensity statin therapy to reduce the risk of stroke recurrence. However, doubling the dosage of statin drugs did not increase the achievement rate of LDL-C target or provide additional clinical benefits, but significantly increased the risk of adverse reactions. Statins and ezetimibe work through different mechanisms and the combined use of statins and ezetimibe significantly improves outcomes with comparable safety profiles. We tested the hypothesis that moderate-intensity statin with ezetimibe may offer advantages over the conventional high-intensity statin regimen in terms of efficacy and safety. METHODS: We conducted a randomized controlled trial. Eligible participants were aged 18 years or older with acute ischemic cerebrovascular disease. We randomly assigned (1:1) participants within the acute phase of ischemic stroke, i.e., within 1 week after the onset of mild ischemic stroke (NIHSS score ≤ 5), within 1 month for severe cases (NIHSS score ≥ 16), and within 2 weeks for the rest, as well as patients with TIA within 1 week of symptom onset, to receive either moderate-intensity statin with ezetimibe (either 10-20 mg atorvastatin calcium tablets plus a 10 mg ezetimibe tablet, or 5-10 mg rosuvastatin calcium tablets once per day plus a 10 mg ezetimibe tablet once per day) or high-intensity statin (40 mg atorvastatin calcium tablets or 20 mg rosuvastatin calcium tablets once per day) for 3 months. Randomization was performed using a random number table method. The primary efficacy outcome was the level and achievement rate of LDL-C after 3 months of treatment, specifically LDL-C ≤ 1.8 mmol/L or a reduction in LDL-C ≥ 50 %. The secondary outcome was the incidence of new stroke or transient ischemic attack (TIA) within 3 months. The safety outcome was liver and renal function tests, and the occurrence of statin-related muscle events within 3 months. FINDINGS: This trial took place between March 15, 2022, and March 7, 2023. Among 382 patients screened, 150 patients were randomly assigned to receive either medium-intensity statins with ezetimibe (n = 75) or high-intensity statins (n = 75). Median age was 60.0 years (IQR 52.75-70.25); 49 (36.6 %) were women and 85 (63.4 %) were men. The target achievement of LDL-C at 3 months occurred in 62 (89.86 %) of 69 patients in the medium-intensity statin with ezetimibe group and 46 (70.77 %) of 65 patients in the high-intensity statin group (P=0.005, OR=0.273, 95 % CI: 0.106, 0.705). The reduction magnitude of LDL-C in moderate-intensity statin with ezetimibe group was significantly higher (-56.540 % vs -47.995 %, P=0.001). Moderate-intensity statin with ezetimibe group showing a trend of a greater reduction in LDL-C absolute value than high-intensity statin group but without statistical significance (-1.77±0.90 vs -1.50±0.89, P=0.077). New AIS or TIA within 3 months, liver and renal function tests, and the occurrence of statin-related muscle events within 3 months were also statistically insignificant. Multivariate logistic regression analysis showed that both gender and lipid-lowering regimen as independent risk factors influencing the rate of LDL-C achievement in individuals diagnosed with acute ischemic cerebrovascular disease, but only lipid-lowering regimen had predictive value. INTERPRETATION: Compared to guideline-recommended high-intensity statin therapy, moderate-intensity statin with ezetimibe further improved the achievement rate of LDL-C in patients with acute ischemic cerebrovascular disease, with a higher reduction magnitude in LDL-C. In terms of safety, there was no significant difference between the two regimens, suggesting that moderate-intensity statin with ezetimibe can also be considered as an initial treatment option for patients with acute ischemic cerebrovascular disease.

Mode selection and amplification from optical frequency combs by optical injection locking: a numerical study of noise.

Noise, except for residual side modes, in mode selection and amplification from optical frequency combs by optical injection locking has not been studied in detail, to our knowledge. We report a numerical study of noise behaviors, including both residual side modes and the noise between them. It reveals that comb laser injection can introduce excessive noise, compared to optical injection with a single mode master laser through the interference between residual side modes and resonances within Arnol'd tongues created by periodic forcing in the optical phase, which can be a severe problem for the case of sub-GHz comb mode spacing. The dependences of residual side mode rejection and phase noise variance on comb mode spacing, seeding power, and detuning are discussed to help in low-noise system design and operation.

The enrichment of rare earth from magnesium salt leaching solution of ion-adsorbed type deposit: A waste-free process for removing impurities.

Due to the complex composition of ion-adsorbed type rare earth ore leaching solution, there are challenges in the process of rare earth (RE) separation, such as large RE loss rate, low product purity, radioactive residue and so on. In this article, 8-hydroxyquinoline modified silica gel (HQ-SiO2) and 2,2'-(1,4-phenylenebis(oxy)) dioctanoic acid (PPBOA) were used to form an efficient process for impurities removal and RE enrichment. Solid phase extraction successfully intercepted 96.7% of the radioactive element thorium. The concentration of aluminium was reduced to 2.14 ppm by frank chromatography. Rare earth elements were enriched from 336.35 mg/L to 237.75 g/L by extraction-precipitation, that is, the enrichment multiple reached more than 700 and the proportion of RE was increased from 21.85% to 96.62%. The loss rate of RE was controlled below 1.59%. Moreover, the magnesium salt leaching solution could be recycled for the leaching of RE ores. Although some liquid waste need to be treated in the processes of HQ-SiO2 production and regeneration, the integrated process helps to decrease volatile organic solvent, acid-base consumption, wastewater and waste residue. It is an environment-friendly RE enrichment and impurity removal process, which shows application potential in the production field of ion-adsorbed type rare earth mineral products.

One-stop-shop preoperative evaluation for living liver donors with gadoxetic acid disodium-enhanced magnetic resonance imaging: efficiency and additional benefit.

OBJECTIVE: To explore the efficiency, cost, and time for examination of one-stop-shop gadoxetic acid disodium (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) in preoperative evaluation for parent donors by comparing with multidetector computer tomography combined with conventional MR cholangiopancreatography (MDCT-MRCP). MATERIALS AND METHODS: Forty parent donors were evaluated with MDCT-MRCP, and the other 40 sex-, age-, and weight-matched donors with Gd-EOB-DTPA-enhanced MRI. Anatomical variations and graft volume determined by pre- and intra-operative findings, costs and time for imaging were recorded. Image quality was ranked on a 4-point scale and compared between both groups. RESULTS: Gd-EOB-DTPA-enhanced MRI provided better image quality than MDCT-MRCP for the depiction of portal veins and bile ducts by both reviewers (p < 0.05), hepatic veins by one reviewer (p < 0.05), rather hepatic arteries by both reviewers (p < 0.01). Sixty-nine living donors proceeded to liver donation with all anatomical findings accurately confirmed by intra-operative findings. The "in-room" time of Gd-EOB-DTPA-enhanced MRI was 12 min longer than MDCT-MRCP. Gd-EOB-DTPA-enhanced MRI was cheaper than MDCT-MRCP (US$519.72 vs. US$631.85). CONCLUSION: One-stop-shop Gd-EOB-DTPA-enhanced MRI has similar diagnostic accuracy as MDCT-MRCP and can provide additional benefit in terms of costs and convenience in preoperative evaluation for parent donors.

D-Limonene Is the Active Olfactory Attractant in Orange Juice for Bactrocera dorsalis (Insecta: Diptera: Tephritidae).

The oriental fruit fly, Bactrocera dorsalis (Hendel), poses a significant threat to the global fruit industry, causing damage to diverse fruits like citrus, mango, and guava. Chemical pesticides have limited effectiveness, and pesticide residues and pesticide resistance are pressing issues. Therefore, it is essential to develop environmentally friendly pest control methods to address this problem. Behavior-modifying chemicals, including male attractants and intersex protein baits, play a critical role in the control of B. dorsalis. The mature host fruit serves as both an oviposition site and food source under natural conditions, making it a potential attraction source for oriental fruit flies. Orange, Citrus sinensis, is a main host of B. dorsalis, and commercial orange juice is a common attractant for the egg laying of B. dorsalis. Although it can both attract and elicit oviposition behaviors in B. dorsalis adults, its active components are still unclear. This study utilized analytical chemistry, behavioral tests, and electrophysiology to identify the active components of commercial orange juice that attract B. dorsalis, with the aim of providing a reference for the development of behavior-modifying chemical-based techniques to control B. dorsalis. Five compounds with a high abundance were identified via a GC-MS, including D-Limonene, butanoic acid ethyl ester, ß-myrcene, linalool, and α-terpineol. Behavioral and electrophysiological experiments uncovered that D-Limonene was the active substance that was the main attractant in the mixture of these five substances, evoking a strong electrophysiological response in adult B. dorsalis. D-Limonene strongly attracts adult B. dorsalis only when they are sexually mature, and the attraction is not rhythmic. Olfaction plays a leading role in the attraction of D-Limonene to adult B. dorsalis, and Orco-/- mediates the perception of D-Limonene by B. dorsalis. Overall, D-Limonene is one of the key attractant compounds for B. dorsalis in the volatile compounds of commercial orange juice, offering possible support for the development of behavior-modifying chemical-based technology to control B. dorsalis in the future.

The efficacy of azithromycin combined with seven types of Chinese medicine injections in the treatment of Mycoplasma pneumoniae pneumonia in children: a systematic review and Bayesian network meta-analysis.

Mycoplasma pneumoniae pneumonia (MPP) is the predominant community-acquired pneumonia (CAP) in children aged 5 years or older. In recent decades, the annual increase in drug resistance rates of macrolide antibiotics, particularly azithromycin (AZ), has led to complex clinical treatment strategies and substantial healthcare costs associated with MPP. Chinese medicine injections (CMIs), recognized as an effective supplementary therapy, are acknowledged by clinicians in China. It is necessary to explore the efficacy of azithromycin in combination with CMIs. Methods: Randomized controlled trials (RCTs) evaluating azithromycin in combination with seven types of CMIs for MPP in children were identified based on inclusion criteria and assessed using the revised Cochrane risk of bias tool (RoB 2.0). R 4.3.1 and STATA 15.0 were employed to generate ranking probabilities and perform network meta-analysis. Competing interventions were ranked using the surface under the cumulative ranking (SUCRA) probabilities. Results: A comprehensive analysis was performed on 155 RCTs involving 15,014 patients and 8 therapeutic strategies within this Bayesian network meta-analysis (BNMA). The results indicated that AZ combined with seven types of CMIs was more effective than azithromycin alone in overall outcomes. Notably, azithromycin combined with Chuanhuning injection (AZ + CHN) achieved the highest ranking in improving the clinical effectiveness rate (SUCRA, 80.89%); regarding secondary outcome measures, azithromycin combined with Yanhuning injection (AZ + YHN) had the highest probability of improving four different outcomes: disappearance time of cough (SUCRA, 80.01%), disappearance time of pulmonary rale (SUCRA, 87.77%), disappearance time of fever (SUCRA, 95.70%), and disappearance time of pulmonary shadows in X-ray (SUCRA, 97.34%); furthermore, azithromycin combined with Qingkailing injection (AZ + QKL) was more likely to reduce average hospitalization time (SUCRA, 94.60%). Conclusion: This study highlights the potential benefits of seven types of Chinese medicine injections as adjunctive therapy for Mycoplasma pneumoniae pneumonia in children. However, further support and validation of these findings are needed through high-quality randomized controlled trials with larger sample sizes and double-blind designs. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/#recordDetails/.

Alkoxythiophene-Directed Fibrillization of Polymer Donor for Efficient Organic Solar Cells.

Realizing fibrillar molecular framework is highly encouraged in organic solar cells (OSCs) due to the merit of efficient charge carrier transport. This is however mainly achieved via the chemical structural design of photovoltaic semiconductors. In this work, through the utilization of three alkoxythiophene additives, T-2OMe, T-OEH, and T-2OEH, the intermolecular interactions among a series of BDT-type polymer donors, i.e., PM6, D18, PBDB-T, and PTB7-Th, are tuned to self-assemble into nanofibrils during solution casting. X-ray technique and molecular dynamics simulation reveal that the alkoxythiophene with (2-ethylhexyl)oxy (─OEH) chains can attach on the 2-ethylhexyl (EH) chains of these polymer donors and promote their self-assembly into 1D nanofibrils, in their neat films as well as photovoltaic blends with L8-BO. By adapting these fibrillar polymer donors to construct pseudo-bulk heterojunction (P-BHJ) OSCs via layer-by-layer deposition, generally improved device performance is seen, with power conversion efficiencies enhanced from 18.2% to 19.2% (certified 18.96%) and from 17.9% to 18.7% for the PM6/L8-BO and D18/L8-BO devices, respectively. This work provides a physical approach to promote the fibrillar charge transport channels for efficient photovoltaics.

Brominated Quaternary Ammonium Salt-Assisted Hybrid Electron Transport Layer for High-Performance Conventional Organic Solar Cells.

Interlayer engineering is crucial for achieving efficient and stable organic solar cells (OSCs). Herein, by introducing a commercialized brominated quaternary ammonium salt, hexamethonium bromide (HB), into a perylene diimide (PDI)-structured electron transport layer (ETL), a PDINN:HB hybrid ETL with enhanced charge collection ability and environmental/operational stability is realized. Molecular dynamics simulations and Kelvin probe force microscopy indicate that strong polar bromine and amine groups can form extra interfacial dipoles in the hybrid interlayer, while X-ray photoelectron spectroscopy and electron paramagnetic resonance suggest the hybrid ETL can interact with the Ag cathode, thereby regulating the energy level arrangement at the interface. As for the results, the PDINN:HB hybrid ETL enables improved power conversion efficiency (PCE) from 17.8 to 18.4% and 18.8 to 19.4% in PM6:C5-16 bulk heterojunction- and PM6/L8-BO pseudobulk heterojunction-based OSCs, respectively. The versatility of this method is further verified by introducing a range of brominated quaternary ammonium salts into PDINN, in which a superior PCE and stability are all obtained compared to the reference device.

Systemic immune-inflammatory biomarkers (SII, NLR, PLR and LMR) linked to non-alcoholic fatty liver disease risk.

Background: Systemic immune-inflammatory biomarkers including systemic immune inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR) have been demonstrated to be associated with the risk and severity of various liver diseases. However, studies on their role and clinical significance in metabolic diseases, especially in nonalcoholic fatty liver disease (NAFLD), are limited and results are inconsistent. Methods: 10821 adults aged 20 years or older were enrolled in this cross-sectional study, sourced from six cycles of the National Health and Nutrition Examination Survey (NHANES). Survey-weighted logistic regression was employed to investigate the correlation between systemic immune-inflammatory biomarkers (SII, NLR, PLR, and LMR) and NAFLD risk. Restricted cubic spline regression models and segmented regression models were used to describe nonlinear relationships and threshold effects. Subgroup and sensitivity analyses were also conducted. Results: After adjusting for all confounding variables, there was a significant positive association observed between ln-transformed SII (OR= 1.46, 95% CI: 1.27-1.69, P <0.001), NLR (OR= 1.25, 95% CI: 1.05-1.49, P =0.015), LMR (OR= 1.39, 95% CI: 1.14-1.69, P = 0.002) with NAFLD. A nonlinear dose-response relationship with an inverted "U"-shaped threshold of 4.64 was observed between ln(PLR) and NAFLD risk. When ln(PLR) was below 4.64, each unit increase in ln(PLR) was associated with a 0.55-fold increase in the risk of NAFLD (OR= 1.55, 95% CI: 1.05-2.31, P <0.05). Conversely, when ln(PLR) exceeded 4.64, each unit increase in ln(PLR) was associated with a 0.40-fold decrease in the risk of NAFLD (OR= 0.60, 95% CI. 0.44-0.81, P <0.05). Conclusion: ln-transformed SII, NLR, and LMR were linearly associated with NAFLD risk. ln(PLR) showed an inverted "U"-shaped nonlinear dose-response relationship with the risk of NAFLD.

Odorant Receptor BdorOR49b Mediates Oviposition and Attraction Behavior of Bactrocera dorsalis to Benzothiazole.

The ability to recognize a host plant is crucial for insects to meet their nutritional needs and locate suitable sites for laying eggs. Bactrocera dorsalis is a highly destructive pest in fruit crops. Benzothiazole has been found to induce oviposition behavior in the gravid B. dorsalis. However, the ecological roles and the olfactory receptor responsible for benzothiazole are not yet fully understood. In this study, we found that adults were attracted to benzothiazole, which was an effective oviposition stimulant. In vitro experiments showed that BdorOR49b was narrowly tuned to benzothiazole. The electroantennogram results showed that knocking out BdorOR49b significantly reduced the antennal electrophysiological response to benzothiazole. Compared with wild-type flies, the attractiveness of benzothiazole to BdorOR49b knockout adult was significantly attenuated, and mutant females exhibited a severe decrease in oviposition behavior. Altogether, our work provides valuable insights into chemical communications and potential strategies for the control of this pest.

Identification of antennal alternative splicing by combining genome and full-length transcriptome analysis in Bactrocera dorsalis.

Alternative splicing is an essential post-transcriptional regulatory mechanism that diversifies gene function by generating multiple protein isoforms from a single gene and act as a crucial role in insect environmental adaptation. Olfaction, a key sense for insect adaptation, relies heavily on the antennae, which are the primary olfactory organs expressing most of the olfactory genes. Despite the extensive annotation of olfactory genes within insect antennal tissues facilitated by high-throughput sequencing technology advancements, systematic analyses of alternative splicing are still relatively less. In this study, we focused on the oriental fruit fly (Bactrocera dorsalis), a significant pest of fruit crops. We performed a detailed analysis of alternative splicing in its antennae by utilizing the full-length transcriptome of its antennal tissue and the insect's genome. The results revealed 8600 non-redundant full-length transcripts identified in the oriental fruit fly antennal full-length transcriptome, spanning 4,145 gene loci. Over 40% of these loci exhibited multiple isoforms. Among these, 161 genes showed sex-biased isoform switching, involving seven different types of alternative splicing. Notably, events involving alternative transcription start sites (ATSS) and alternative transcription termination sites (ATTS) were the most common. Of all the genes undergoing ATSS and ATTS alternative splicing between male and female, 32 genes were alternatively spliced in protein coding regions, potentially affecting protein function. These genes were categorized based on the length of the sex-biased isoforms, with the highest difference in isoform fraction (dIF) associated with the ATSS type, including genes such as BdorABCA13, BdorCAT2, and BdorTSN3. Additionally, transcription factor binding sites for doublesex were identified upstream of both BdorABCA13 and BdorCAT2. Besides being expressed in the antennal tissues, BdorABCA13 and BdorCAT2 are also expressed in the mouthparts, legs, and genitalia of both female and male adults, suggesting their functional diversity. This study reveals alternative splicing events in the antennae of Bactrophora dorsalis from two aspects: odorant receptor genes and other types of genes expressed in the antennae. This study not only provides a research foundation for understanding the regulation of gene function by alternative splicing in the oriental fruit fly but also offers new insights for utilizing olfaction-based behavioral manipulation techniques to manage this pest.

Effects of PCSK9 Inhibitors on Early Neurologic Deterioration in Patients with Acute Non-Cardioembolism without Hemorrhagic Transformation After Intravenous Thrombolysis.

BACKGROUND: END (Early Neurologic Deterioration) significantly elevates the risk of morbidity and mortality. While numerous studies have investigated END following hemorrhagic transformation post-thrombolysis in acute cerebral infarction research on END without hemorrhagic transformations in patients with acute cerebral infarction due to non-cardiogenic embolism remains scarce. AIM: This study aimed to elucidate the impact of PCSK9 inhibitors on early neurological deterioration (END) in patients with acute non-cardioembolism cerebral infarction without hemorrhagic transformation post-intravenous thrombolysis. Additionally it aimed to identify risk factors associated with END in patients suffering from this type of stroke. OBJECTIVE: The objective of this study is to investigate the effect of PCSK9 inhibitors on early neurologic deterioration (END) in patients with acute non-cardiogenic cerebral infarction without hemorrhagic transformation after intravenous thrombolysis and identify associated risk factors for END in this patient population. METHODS: In this retrospective case-control study the data of consecutive patients who underwent intravenous thrombolysis after AIS (acute ischemic stroke) without hemorrhagic transformation during hospitalization at the Stroke Center of The Fifth Affiliated Hospital of Sun Yat-sen University between January 2018 to February 2023 were retrieved and assessed. An increase of >2 in the National Institutes of Health Stroke Scale (NIHSS) within 7 days after admission was defined as END. RESULTS: This study included 250 patients (56 males 22.4%) they were 63.34±12.901 years old. There were 41 patients in the END group and 209 in the non-END group. The usage rate of PCSK9 inhibitors was significantly different between the END group and non-END group (29.268% vs 58.852% P<0.001). The White blood cell count (WBC) and homocysteine levels showed a significant difference between the two groups (all P<0.05). Patients not using PCSK9 inhibitors (OR=0.282 95%CI: 0.127-0.593) and white blood cell count (OR=1.197, 95%CI: 1.085-1.325) were independently associated with END. Receiver-operating characteristic curve analysis suggested that the sensitivity specificity and area under the curve for PCSK9 inhibitors used for END were 88.9%, 80.7% and 0.648 respectively. CONCLUSION: The use of PCSK9 inhibitors can reduce the incidence of early neurological deterioration in patients with acute non-cardioembolism and non-hemorrhagic transformation after intravenous thrombolysis.

WenTongGanPi decoction alleviates diarrhea-predominant irritable bowel syndrome by improving intestinal barrier.

ETHNOPHARMACOLOGICAL RELEVANCE: WenTongGanPi Decoction (WTGPD) is a representative medical practice of the Fuyang School of Traditional Chinese Medicine (TCM), which originated from the classical Lu's Guizhi method. WTGPD places emphasis on the balance and functionality of yang qi, and is effective in treating TCM symptoms related to liver qi stagnation and spleen yang deficiency. In TCM, diarrhea-predominant irritable bowel syndrome (IBS-D) is often diagnosed as liver depression and spleen deficiency, and the use of WTGPD has shown significant therapeutic effect. However, the underlying mechanism of WTGPD treating IBS-D remains unclear. AIM OF THE STUDY: To explore the effect and mechanism of WTGPD in the treatment of IBS-D. MATERIALS AND METHODS: An IBS-D model with liver depression and spleen deficiency was constructed by chronic immobilization stress stimulation and sennae folium aqueous gavage. The impact of WTGPD on IBS-D rats was evaluated through measurements of body weight, fecal water content, and abdominal withdrawal reflex (AWR). Intestinal permeability was assessed using hematoxylin-eosin (HE), alcian blue-periodic acid schiff (AB-PAS), immunofluorescence (IF) staining, and quantitative real-time PCR (qRT-PCR). The components of WTGPD were analyzed using UPLC-Q-TOF-MS. The underlying mechanisms were investigated through network pharmacology, transcriptomics sequencing, western blot (WB), molecular docking, and 16S rRNA sequencing. RESULTS: WTGPD treatment effectively alleviated diarrhea and abnormal pain in IBS-D rats (P < 0.05). It enhanced the intestinal barrier function by improving colonic structure and increasing the expression of tight junction proteins (P < 0.05). A total of 155 components were identified in WTGPD. Both network pharmacology and transcriptomics sequencing analysis highlighted MAPK as the key signaling pathway in WTGPD's anti-IBS-D effect. The WB results showed a significant decrease in p-p38, p-ERK and p-JNK expression after WTGPD treatment (P < 0.0001). Guanosine, adenosine and hesperetin in WTGPD may be involved in regulating the phosphorylation of p38, ERK and JNK. Additionally, WTGPD significantly enhanced microbial diversity and increased the production of colonic valeric acid in IBS-D rats (P < 0.01). CONCLUSION: In conclusion, our findings suggest that WTGPD can effectively alleviate IBS-D and improve intestinal barrier likely via inhibiting MAPK signal pathway and improving micobial dysbiosis.

Molecular Characterization, Evolution and Expression Analysis of Ammonium Transporter from Four Closely Related Bactrocera Species (Tephritidae).

Numerous insects are attracted to low levels of ammonia, utilizing it as a cue to locate food sources. The Ammonium Transporter (Amt), a highly conserved, atypical olfactory receptor, has been shown to mediate the detection of ammonia in insects. While the attraction of Tephritidae to ammonia is well established, knowledge about the Amt in this family is limited. The species Bactrocera dorsalis (Hendel 1912), Bactrocera cucurbitae (Coquillett 1899), Bactrocera correcta Bezzi 1916 and Bactrocera tau (Walker 1849), which are common agricultural pests within Tephritidae, exhibit numerous ecological similarities, offering a solid foundation for studying Amt characteristics in this family. In this study, we elucidated the sequences, evolutionary relationships, and expression patterns of Amt in these four species. The results indicated that these Amts share the same open reading frame, containing 1770 bp that encode a protein of 589 amino acid residues. These Amt proteins exhibit the typical structural characteristics of Amts, including an 11-transmembrane domain with an extracellular N-terminus and an intracellular C-terminus. They also have the ability to form trimers in the membrane. Additionally, they contain three conserved amino acid residues essential for ammonia transport: A189, H195, and H352. Phylogenetic and expression pattern analyses showed that they are highly conserved in Diptera and are significantly expressed in antennae. This study is the first report characterizing the Amt gene in four Tephritidae species. These findings provide a foundation for further exploration into the roles of these genes in their particular biological contexts.

Aberrant mechanical loading induces annulus fibrosus cells apoptosis in intervertebral disc degeneration via mechanosensitive ion channel Piezo1.

BACKGROUND: Intervertebral disc degeneration (IVDD) is closely associated with the structural damage in the annulus fibrosus (AF). Aberrant mechanical loading is an important inducement of annulus fibrosus cells (AFCs) apoptosis, which contributes to the AF structural damage and aggravates IVDD, but the underlying mechanism is still unclear. This study aims to investigate the mechanism of a mechanosensitive ion channel protein Piezo1 in aberrant mechanical loading-induced AFCs apoptosis and IVDD. METHODS: Rats were subjected to lumbar instability surgery to induce the unbalanced dynamic and static forces to establish the lumbar instability model. MRI and histological staining were used to evaluate the IVDD degree. A cyclic mechanical stretch (CMS)-stimulated AFCs apoptosis model was established by a Flexcell system in vitro. Tunel staining, mitochondrial membrane potential (MMP) detection, and flow cytometry were used to evaluate the apoptosis level. The activation of Piezo1 was detected using western blot and calcium fluorescent probes. Chemical activator Yoda1, chemical inhibitor GSMTx4, and a lentiviral shRNA-Piezo1 system (Lv-Piezo1) were utilized to regulate the function of Piezo1. High-throughput RNA sequencing (RNA-seq) was used to explore the mechanism of Piezo1-induced AFCs apoptosis. The Calpain activity and the activation of Calpain2/Bax/Caspase3 axis were evaluated by the Calpain activity kit and western blot with the siRNA-mediated Calapin1 or Calpain2 knockdown. Intradiscal administration of Lv-Piezo1 was utilized to evaluate the therapeutic effect of Piezo1 silencing in IVDD rats. RESULTS: Lumbar instability surgery promoted the expression of Piezo1 in AFCs and stimulated IVDD in rats 4 weeks after surgery. CMS elicited distinct apoptosis of AFCs, with enhanced Piezo1 activation. Yoda1 further promoted CMS-induced apoptosis of AFCs, while GSMTx4 and Lv-Piezo1 exhibited opposite effects. RNA-seq showed that knocking down Piezo1 inhibited the calcium signaling pathway. CMS enhanced Calpain activity and elevated the expression of BAX and cleaved-Caspase3. Calpain2, but not Calpain1 knockdown, inhibited the expression of BAX and cleaved-Caspase3 and alleviated AFCs apoptosis. Lv-Piezo1 significantly alleviated the progress of IVDD in rats after lumbar instability surgery. CONCLUSIONS: Aberrant mechanical loading induces AFCs apoptosis to promote IVDD by activating Piezo1 and downstream Calpain2/BAX/Caspase3 pathway. Piezo1 is expected to be a potential therapeutic target in treating IVDD.

Reexamining the Role of Solution-Cast Ferroelectric Polymer Interlayer toward Enhanced Efficiency and Stability in Conventional Organic Solar Cells.

Interfacial modification is crucial for achieving efficient and stable organic solar cells (OSCs). Herein, an N,N-dimethylformamide (DMF) solution-cast poly(vinylidene fluoride-co-trifluoroethylene) (P(VDF-TrFE)) interlayer was applied to enhance the efficiency and stability of a range of OSCs, and the underlying mechanism was revealed via morphological and device physics studies. DMF rinse during the P(VDF-TrFE) interlayer casting process strengthens π-π stacking of the active layer with fibril aggregation, optimized phase separation, and vertical component distribution, while the P(VDF-TrFE) interlayer with rich diploes contributes to increased surface potential and internal electric field. The synergistic effect of the P(VDF-TrFE) interlayer and DMF rinse increases the PCEs of PM6:IT-4F, PM6:C5-16, and PM6:L8-BO OSCs from 12.7, 17.9, and 18.2% to 13.1, 18.7, and 18.8%, respectively. Additionally, OSCs containing the P(VDF-TrFE) interlayer also showed improved storage stability.