Dual mutations in the whitefly nicotinic acetylcholine receptor ß1 subunit confer target-site resistance to multiple neonicotinoid insecticides.

Neonicotinoid insecticides, which target insect nicotinic acetylcholine receptors (nAChRs), have been widely and intensively used to control the whitefly, Bemisia tabaci, a highly damaging, globally distributed, crop pest. This has inevitably led to the emergence of populations with resistance to neonicotinoids. However, to date, there have been no reports of target-site resistance involving mutation of B. tabaci nAChR genes. Here we characterize the nAChR subunit gene family of B. tabaci and identify dual mutations (A58T&R79E) in one of these genes (BTß1) that confer resistance to multiple neonicotinoids. Transgenic D. melanogaster, where the native nAChR Dß1 was replaced with BTß1A58T&R79E, were significantly more resistant to neonicotinoids than flies where Dß1 were replaced with the wildtype BTß1 sequence, demonstrating the causal role of the mutations in resistance. The two mutations identified in this study replace two amino acids that are highly conserved in >200 insect species. Three-dimensional modelling suggests a molecular mechanism for this resistance, whereby A58T forms a hydrogen bond with the R79E side chain, which positions its negatively-charged carboxylate group to electrostatically repulse a neonicotinoid at the orthosteric site. Together these findings describe the first case of target-site resistance to neonicotinoids in B. tabaci and provide insight into the molecular determinants of neonicotinoid binding and selectivity.

Interpretable deep learning methods for multiview learning.

BACKGROUND: Technological advances have enabled the generation of unique and complementary types of data or views (e.g. genomics, proteomics, metabolomics) and opened up a new era in multiview learning research with the potential to lead to new biomedical discoveries. RESULTS: We propose iDeepViewLearn (Interpretable Deep Learning Method for Multiview Learning) to learn nonlinear relationships in data from multiple views while achieving feature selection. iDeepViewLearn combines deep learning flexibility with the statistical benefits of data and knowledge-driven feature selection, giving interpretable results. Deep neural networks are used to learn view-independent low-dimensional embedding through an optimization problem that minimizes the difference between observed and reconstructed data, while imposing a regularization penalty on the reconstructed data. The normalized Laplacian of a graph is used to model bilateral relationships between variables in each view, therefore, encouraging selection of related variables. iDeepViewLearn is tested on simulated and three real-world data for classification, clustering, and reconstruction tasks. For the classification tasks, iDeepViewLearn had competitive classification results with state-of-the-art methods in various settings. For the clustering task, we detected molecular clusters that differed in their 10-year survival rates for breast cancer. For the reconstruction task, we were able to reconstruct handwritten images using a few pixels while achieving competitive classification accuracy. The results of our real data application and simulations with small to moderate sample sizes suggest that iDeepViewLearn may be a useful method for small-sample-size problems compared to other deep learning methods for multiview learning. CONCLUSION: iDeepViewLearn is an innovative deep learning model capable of capturing nonlinear relationships between data from multiple views while achieving feature selection. It is fully open source and is freely available at https://github.com/lasandrall/iDeepViewLearn .

Unraveling the Structure-Property-Performance Relationships of Fused-Ring Nonfullerene Acceptors: Toward a C-Shaped ortho-Benzodipyrrole-Based Acceptor for Highly Efficient Organic Photovoltaics.

The high-performance Y6-based nonfullerene acceptors (NFAs) feature a C-shaped A-DA'D-A-type molecular architecture with a central electron-deficient thiadiazole (Tz) A' unit. In this work, we designed and synthesized a new A-D-A-type NFA, termed CB16, having a C-shaped ortho-benzodipyrrole-based skeleton of Y6 but with the Tz unit eliminated. When processed with nonhalogenated xylene without using any additives, the binary PM6:CB16 devices display a remarkable power conversion efficiency (PCE) of 18.32% with a high open-circuit voltage (Voc) of 0.92 V, surpassing the performance of the corresponding Y6-based devices. In contrast, similarly synthesized SB16, featuring an S-shaped para-benzodipyrrole-based skeleton, yields a low PCE of 0.15% due to the strong side-chain aggregation of SB16. The C-shaped A-DNBND-A skeleton in CB16 and the Y6-series NFAs constitutes the essential structural foundation for achieving exceptional device performance. The central Tz moiety or other A' units can be employed to finely adjust intermolecular interactions. The single-crystal X-ray structure reveals that ortho-benzodipyrrole-embedded A-DNBND-A plays an important role in the formation of a 3D elliptical network packing for efficient charge transport. Solution structures of the PM6:NFAs detected by small- and wide-angle X-ray scattering (SWAXS) indicate that removing the Tz unit in the C-shaped skeleton could reduce the self-packing of CB16, thereby enhancing the complexing and networking with PM6 in the spin-coating solution and the subsequent device film. Elucidating the structure-property-performance relationships of A-DA'D-A-type NFAs in this work paves the way for the future development of structurally simplified A-D-A-type NFAs.

Drop to Gate Nasal Drops Attenuates Sepsis-Induced Cognitive Dysfunction.

Nasal administration can bypass the blood-brain barrier and directly deliver drugs to the brain, providing a non-invasive route for central nervous system (CNS) diseases. Inspired by the appearance that a gate can block the outside world and the characteristics of the sol-gel transition can form a "gate" in the nasal cavity, a Drop to Gate nasal drop (DGND) is designed to set a gate in nose, which achieves protecting role from the influence of nasal environment. The DGND demonstrates the efficiency and application prospect of delivering drugs to the brain through the N-to-B. The effective concentration of single administration is increased through the hydrophobic interaction between C8-GelMA and SRT1720 (SA), and then cross-linked under UV to form nanogel, which can respond to MMP in the inflammatory microenvironment of sepsis-induced cognitive dysfunction. Finally, the SA/nanogel is compounded into the thermogel, which can respond to the nasal cavity temperature to form DGND in situ, increasing the residence time and delivery efficiency of drugs in the nasal cavity. In vitro, the DGND alleviates lipopolysaccharides (LPS)-induced BV2 inflammation. In vivo, DGND effectively targets the nasal mucosa and deliver drugs to the brain, which activate Sirt1 to alleviate inflammation mediated by microglia and improve cognitive dysfunction in sepsis mice.

Repetitive transcranial magnetic stimulation (rTMS) triggers dose-dependent homeostatic rewiring in recurrent neuronal networks.

Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation technique used to induce neuronal plasticity in healthy individuals and patients. Designing effective and reproducible rTMS protocols poses a major challenge in the field as the underlying biomechanisms of long-term effects remain elusive. Current clinical protocol designs are often based on studies reporting rTMS-induced long-term potentiation or depression of synaptic transmission. Herein, we employed computational modeling to explore the effects of rTMS on long-term structural plasticity and changes in network connectivity. We simulated a recurrent neuronal network with homeostatic structural plasticity among excitatory neurons, and demonstrated that this mechanism was sensitive to specific parameters of the stimulation protocol (i.e., frequency, intensity, and duration of stimulation). Particularly, the feedback-inhibition initiated by network stimulation influenced the net stimulation outcome and hindered the rTMS-induced structural reorganization, highlighting the role of inhibitory networks. These findings suggest a novel mechanism for the lasting effects of rTMS, i.e., rTMS-induced homeostatic structural plasticity, and highlight the importance of network inhibition in careful protocol design, standardization, and optimization of stimulation.

Research on Human-Robot Collaboration Method for Parallel Robots Oriented to Segment Docking.

In the field of aerospace, large and heavy cabin segments present a significant challenge in assembling space engines. The substantial inertial force of cabin segments' mass often leads to unexpected motion during docking, resulting in segment collisions, making it challenging to ensure the accuracy and quality of engine segment docking. While traditional manual docking leverages workers' expertise, the intensity of the labor and low productivity are impractical for real-world applications. Human-robot collaboration can effectively integrate the advantages of humans and robots. Parallel robots, known for their high precision and load-bearing capacity, are extensively used in precision assembly under heavy load conditions. Therefore, human-parallel-robot collaboration is an excellent solution for such problems. In this paper, a framework is proposed that is easy to realize in production, using human-parallel-robot collaboration technology for cabin segment docking. A fractional-order variable damping admittance control and an inverse dynamics robust controller are proposed to enhance the robot's compliance, responsiveness, and trajectory tracking accuracy during collaborative assembly. This allows operators to dynamically adjust the robot's motion in real-time, counterbalancing inertial forces and preventing collisions between segments. Segment docking assembly experiments are performed using the Stewart platform in this study. The results show that the proposed method allows the robot to swiftly respond to interaction forces, maintaining compliance and stable motion accuracy even under unknown interaction forces.

Effects of transitional care interventions on quality of life in people with lung cancer: A systematic review and meta-analysis.

AIM: To identify and appraise the quality of evidence of transitional care interventions on quality of life in lung cancer patients. BACKGROUND: Quality of life is a strong predictor of survival. The transition from hospital to home is a high-risk period for patients' readmission and death, which seriously affect their quality of life. DESIGN: Systematic review and meta-analysis. METHODS: The PubMed, Embase, Cochrane Library, Web of Science and CINAHL databases were searched from inception to 22 October 2022. The primary outcome was quality of life. Statistical analysis was conducted using Review Manager 5.4, results were expressed as standard mean difference (SMD) with a 95% confidence interval (CI). The risk of bias of the included studies was assessed using the Cochrane risk of bias assessment tool. This study was complied with PRISMA guidelines and previously registered in PROSPERO (CRD42023429464). RESULTS: Fourteen randomized controlled trials were included consisting of a total of 1700 participants, and 12 studies were included in the meta-analysis. It was found that transitional care interventions significantly improved quality of life (SMD = 0.21, 95% CI: 0.02 to 0.40, p = .03) and helped reduce symptoms (SMD = -0.65, 95% CI: -1.13 to -0.18, p = .007) in lung cancer patients, but did not significantly reduce anxiety and depression, and the effect on self-efficacy was unclear. CONCLUSIONS: This study shows that transitional care interventions can improve quality of life and reduce symptoms in patients, and that primarily educational interventions based on symptom management theory appeared to be more effective. But, there was no statistically significant effect on anxiety and depression. RELEVANCE TO CLINICAL PRACTICE: This study provides references for the application of transitional care interventions in the field of lung cancer care, and encourages nurses and physicians to apply transitional care plans to facilitate patients' safe transition from hospital to home. PATIENT OR PUBLIC CONTRIBUTION: No Patient or Public Contribution.

Evaluation of cutout factors with small and narrow fields using various dosimetry detectors in electron beam keloid radiotherapy.

BACKGROUND: The inherent problems in the existence of electron equilibrium and steep dose fall-off pose difficulties for small- and narrow-field dosimetry. OBJECTIVE: To investigate the cutout factors for keloid electron radiotherapy using various dosimetry detectors for small and narrow fields. METHOD: The measurements were performed in a solid water phantom with nine different cutout shapes. Five dosimetry detectors were used in the study: pinpoint 3D ionization chamber, Farmer chamber, semiflex chamber, Classic Markus parallel plate chamber, and EBT3 film. RESULTS: The results demonstrated good agreement between the semiflex and pinpoint chambers. Furthermore, there was no difference between the Farmer and pinpoint chambers for large cutouts. For the EBT3 film, half of the cases had differences greater than 1%, and the maximum discrepancy compared with the reference chamber was greater than 2% for the narrow field. CONCLUSION: The parallel plate, semiflex chamber and EBT3 film are suitable dosimeters that are comparable with pinpoint 3D chambers in small and narrow electron fields. Notably, a semiflex chamber could be an alternative option to a pinpoint 3D chamber for cutout widths≥3 cm. It is very important to perform patient-specific cutout factor calibration with an appropriate dosimeter for keloid radiotherapy.

Addressing long-term mortality risk in patients undergoing total pancreatectomy with islet autotransplant (TPIAT): causes of death and risk factors.

BACKGROUND: Total pancreatectomy with islet autotransplant (TPIAT) can improve quality of life for individuals with pancreatitis but creates health risks including diabetes, exocrine insufficiency, altered intestinal anatomy and function, and asplenia. METHODS: We studied survival and causes of death for 693 patients who underwent TPIAT between 2001 and 2020, using the National Death Index with medical records to ascertain survival after TPIAT, causes of mortality, and risk factors for death. We used Kaplan Meier curves to examine overall survival, and Cox regression and competing-risks methods to determine pre-TPIAT factors associated with all-cause and cause-specific post-TPIAT mortality. RESULTS: Mean age at TPIAT was 33.6 years (SD = 15.1). Overall survival was 93.1% (95% CI 91.2, 95.1%) 5 years after surgery, 85.2% (95% CI 82.0, 88.6%) at 10 years, and 76.2% (95% CI 70.8, 82.3%) at 15 years. Fifty-three of 89 deaths were possibly related to TPIAT; causes included chronic gastrointestinal complications, malnutrition, diabetes, liver failure, and infection/sepsis. In multivariable models, younger age, longer disease duration, and more recent TPIAT were associated with lower mortality. CONCLUSIONS: For patients undergoing TPIAT to treat painful pancreatitis, careful long-term management of comorbidities introduced by TPIAT may reduce risk for common causes of mortality.

The role of mitochondria in the resistance of melanoma to PD-1 inhibitors.

Malignant melanoma is one of the most common tumours and has the highest mortality rate of all types of skin cancers worldwide. Traditional and novel therapeutic approaches, including surgery, targeted therapy and immunotherapy, have shown good efficacy in the treatment of melanoma. At present, the mainstay of treatment for melanoma is immunotherapy combined with other treatment strategies. However, immune checkpoint inhibitors, such as PD-1 inhibitors, are not particularly effective in the clinical treatment of patients with melanoma. Changes in mitochondrial function may affect the development of melanoma and the efficacy of PD-1 inhibitors. To elucidate the role of mitochondria in the resistance of melanoma to PD-1 inhibitors, this review comprehensively summarises the role of mitochondria in the occurrence and development of melanoma, targets related to the function of mitochondria in melanoma cells and changes in mitochondrial function in different cells in melanoma resistant to PD-1 inhibitors. This review may help to develop therapeutic strategies for improving the clinical response rate of PD-1 inhibitors and prolonging the survival of patients by activating mitochondrial function in tumour and T cells.

Synergistic action of phages and lytic proteins with antibiotics: a combination strategy to target bacteria and biofilms.

BACKGROUND: Multidrug-resistant bacteria continue to emerge owing to the abuse of antibiotics and have a considerable negative impact on people and the environment. Bacteria can easily form biofilms to improve their survival, which reduces the efficacy of antibacterial drugs. Proteins such as endolysins and holins have been shown to have good antibacterial activity and effectively removal bacterial biofilms and reduce the production of drug-resistant bacteria. Recently, phages and their encoded lytic proteins have attracted attention as potential alternative antimicrobial agents. The aim of the present study was to investigate the sterilising efficacy of phages (SSE1, SGF2, and SGF3) and their encoded lytic proteins (lysozyme and holin), and to further explore their potential in combination with antibiotics. To the ultimate aim is to reduce or replace the use of antibiotics and provide more materials and options for sterilisation. RESULTS: Phages and their encoded lytic proteins were confirmed to have great advantages in sterilisation, and all exhibited significant potential for reducing bacterial resistance. Previous studies on the host spectrum demonstrated the bactericidal efficacy of three Shigella phages (SSE1, SGF2, and SGF3) and two lytic proteins (LysSSE1 and HolSSE1). In this study, we investigated the bactericidal effects on planktonic bacteria and bacterial biofilms. A combined sterilisation application of antibiotics, phages, and lytic proteins was performed. The results showed that phages and lytic proteins had better sterilisation effects than antibiotics with 1/2 minimum inhibitory concentrations (MIC) and their effect was further improved when used together with antibiotics. The best synergy was shown when combined with ß- lactam antibiotics, which might be related to their mechanism of sterilising action. This approach ensures a bactericidal effect at low antibiotic concentrations. CONCLUSIONS: This study strengthens the idea that phages and lytic proteins can significantly sterilise bacteria in vitro and achieve synergistic sterilisation effects with specific antibiotics. Therefore, a suitable combination strategy may decrease the risk of drug resistance.

The extensin protein SAE1 plays a role in leaf senescence and is targeted by the ubiquitin ligase SINA4 in tomato.

Extensins are hydroxyproline-rich glycoproteins and generally play a structural role in cell wall integrity. In this study, we determined a novel role of tomato (Solanum lycopersicum) SENESCENCE-ASSOCIATED EXTENSIN1 (SAE1) in leaf senescence. Both gain- and loss-of-function analyses suggest that SAE1 plays a positive role in leaf senescence in tomato. Transgenic plants overexpressing SAE1 (SAE1-OX) exhibited premature leaf senescence and enhanced dark-induced senescence, whereas SAE1 knockout (SAE1-KO) plants displayed delayed development-dependent and dark-induced leaf senescence. Heterologous overexpression of SlSAE1 in Arabidopsis also led to premature leaf senescence and enhanced dark-induced senescence. In addition, the SAE1 protein was found to interact with the tomato ubiquitin ligase SlSINA4, and SlSINA4 promoted SAE1 degradation in a ligase-dependent manner when co-expressed in Nicotiana benthamiana leaves, suggesting that SlSINA4 controls SAE1 protein levels via the ubiquitin-proteasome pathway. Introduction of an SlSINA4-overexpression construct into the SAE1-OX tomato plants consistently completely eliminated accumulation of the SAE1 protein and suppressed the phenotypes conferred by overexpression of SAE1. Taken together, our results suggest that the tomato extensin SAE1 plays a positive role in leaf senescence and is regulated by the ubiquitin ligase SINA4.

Exploration on anti-hypoxia properties of peptides: a review.

Peptides are important components of human nutrition and health, and considered as safe, nontoxic, and easily absorbed potential drugs. Anti-hypoxia peptides are a kind of peptides that can prevent hypoxia or hypoxia damage. In this paper, the sources, preparations, and molecular mechanisms of anti-hypoxia peptides were systemically reviewed. The combination of bioinformatics, chemical synthesis, enzymatic hydrolysis, and microbial fermentation are recommended for efficient productions of anti-hypoxic peptides. The mechanisms of anti-hypoxic peptides include interference with glycolytic process and HIF-1α pathway, mitochondrial apoptosis, and inflammatory response. In addition, bioinformatics analysis, including virtual screening and molecular docking, provides an alternative or auxiliary method for exploring the potential anti-hypoxic activities and mechanisms of peptides. The potential challenges and prospects of anti-hypoxic peptides are also discussed. This paper can provide references for researchers in this field and promote further research and clinical applications of anti-hypoxic peptides in the future.

Time Course of Homeostatic Structural Plasticity in Response to Optogenetic Stimulation in Mouse Anterior Cingulate Cortex.

Plasticity is the mechanistic basis of development, aging, learning, and memory, both in healthy and pathological brains. Structural plasticity is rarely accounted for in computational network models due to a lack of insight into the underlying neuronal mechanisms and processes. Little is known about how the rewiring of networks is dynamically regulated. To inform such models, we characterized the time course of neural activity, the expression of synaptic proteins, and neural morphology employing an in vivo optogenetic mouse model. We stimulated pyramidal neurons in the anterior cingulate cortex of mice and harvested their brains at 1.5 h, 24 h, and $48\,\mathrm{h}$ after stimulation. Stimulus-induced cortical hyperactivity persisted up to 1.5 h and decayed to baseline after $24\,\mathrm{h}$ indicated by c-Fos expression. The synaptic proteins VGLUT1 and PSD-95, in contrast, were upregulated at $24\,\mathrm{h}$ and downregulated at $48\,\mathrm{h}$, respectively. Spine density and spine head volume were also increased at $24\,\mathrm{h}$ and decreased at $48\,\mathrm{h}$. This specific sequence of events reflects a continuous joint evolution of activity and connectivity that is characteristic of the model of homeostatic structural plasticity. Our computer simulations thus corroborate the observed empirical evidence from our animal experiments.

Enhanced triacyclglycerols and starch synthesis in Chlamydomonas stimulated by the engineered biodegradable nanoparticles.

Microalgae are promising feedstock for renewable fuels. The accumulation of oils in microalgae can be enhanced by nanoparticle exposure. However, the nanoparticles employed in previous studies are mostly non-biodegradable, which hinders nanoparticles developing as promising approach for biofuel production. We recently reported the engineered resin nanoparticles (iBCA-NPs), which were found to be biodegradable in this study. When the cells of green microalga Chlamydomonas reinhardtii were exposed to the iBCA-NPs for 1 h, the cellular triacyclglycerols (TAG) and starch contents increased by 520% and 60% than that in the control. The TAG production improved by 1.8-fold compared to the control without compromised starch production. Additionally, the content of total fatty acids increased by 1.3-fold than that in control. Furthermore, we found that the iBCA-NPs addition resulted in increased cellular reactive oxygen species (ROS) content and upregulated the activities of antioxidant enzymes. The relative expressions of the key genes involved in TAG and starch biosynthesis were also upregulated. Overall, our results showed that short exposure of the iBCA-NPs dramatically enhances TAG and starch accumulation in Chlamydomonas, which probably resulted from prompt upregulated expression of the key genes in lipid and starch metabolic pathways that were triggered by over-accumulated ROS. This study reported a useful approach to enhance energy-rich reserve accumulation in microalgae. KEY POINTS: 1. The first attempt to increase oil and starch in microalgae by biodegradable NPs. 2. The biodegradability of iBCA-NPs by the BOD test was more than 50% after 28 days. 3. The iBCA-NPs induce more energy reserves than that of previously reported NPs.

Primary endodermal sinus tumor originating from the sacral ligament: a case report and review of the literature.

BACKGROUND: Endodermal sinus tumor (EST) is a malignant tumor originating from the ovary or testis. In most case, ultrasound examination shows ovarian mass. But there is a special kind of extra-gonadal endodermal sinus tumor, which occur in organs other than gonads with insidious onset. Here we reported a case of endodermal sinus tumor, which originated from the sacral ligament presenting as an acute lower abdominal pain. CASE PRESENTATION: A 14-year-old girl was admitted to the hospital because of acute lower abdominal pain. The ultrasound showed a mass with 72 mm × 64 mm × 50 mm in Douglas, and there was no abnormality in bilateral ovaries and fallopian tubes. Laparoscopic exploration showed a large amount of blood clots in the pelvic cavity. After removal of the blood, we found rotten fish-like tissue in the left sacral ligament, rapid pathology suggested endodermal sinus tumor. After the operation, we retrospectively examined the value of alpha-fetoprotein (AFP), which was found to be elevated, and post-operative paraffin pathology confirmed the diagnosis. After four cycles of BEP chemotherapy, exploratory laparotomy was performed to remove the visible lesion, but postoperative pathology showed no abnormality. At the one-year follow-up, the patient remained recurrence-free. CONCLUSION: Extra-gonadal germ cell tumors are rarely reported. When young teenagers complain of acute lower abdominal pain with elevated AFP, but there was no lesion in bilateral ovaries and fallopian tubes, we must think about the possibility of endodermal sinus tumors. Accurate diagnosis facilitates complete resection of lesions and improves patient's outcomes.

COVID-19 diagnosis utilizing wavelet-based contrastive learning with chest CT images.

The pandemic caused by the coronavirus disease 2019 (COVID-19) has continuously wreaked havoc on human health. Computer-aided diagnosis (CAD) system based on chest computed tomography (CT) has been a hotspot option for COVID-19 diagnosis. However, due to the high cost of data annotation in the medical field, it happens that the number of unannotated data is much larger than the annotated data. Meanwhile, having a highly accurate CAD system always requires a large amount of labeled data training. To solve this problem while meeting the needs, this paper presents an automated and accurate COVID-19 diagnosis system using few labeled CT images. The overall framework of this system is based on the self-supervised contrastive learning (SSCL). Based on the framework, our enhancement of our system can be summarized as follows. 1) We integrated a two-dimensional discrete wavelet transform with contrastive learning to fully use all the features from the images. 2) We use the recently proposed COVID-Net as the encoder, with a redesign to target the specificity of the task and learning efficiency. 3) A new pretraining strategy based on contrastive learning is applied for broader generalization ability. 4) An additional auxiliary task is exerted to promote performance during classification. The final experimental result of our system attained 93.55%, 91.59%, 96.92% and 94.18% for accuracy, recall, precision, and F1-score respectively. By comparing results with the existing schemes, we demonstrate the performance enhancement and superiority of our proposed system.

Distinct inhibitory strength of bisphenol A analogues on human and rat 11ß-hydroxysteroid dehydrogenase 1: 3D quantitative structure-activity relationship and in silico molecular docking analysis.

Bisphenol A (BPA) analogues are developed to replace BPA usage. However, their effects on 11ß-hydroxysteroid dehydrogenase 1 (11ß-HSD1) are largely unknown. The inhibitory effects of BPA and 10 BPA analogues with the substituents on the bridge moiety on human and rat 11ß-HSD1 were explored in human and rat liver microsomes. The strength of inhibiting human 11ß-HSD1 was bisphenol FL (IC50, 3.87 µM) > bisphenol Z (6.86 µM) > bisphenol AF (9.42 µM) > bisphenol C (16.14 µM) > bisphenol AP (32.14 µM) = bisphenol B (32.34 µM) > 4,4'-thiodiphenol (67.35 µM) > BPA (297.35 µM) > other BPA analogues (ineffective at 100 µM). The strength of inhibiting rat 11ß-HSD1 was bisphenol Z (IC50, 14.44 µM) > 4,4'-thiodiphenol (19.01 µM) > bisphenol B (20.13 µM) > bisphenol F (22.10 µM) > bisphenol E (33.04 µM) > bisphenol AF (49.67 µM) > bisphenol C > (56.97 µM) > bisphenol AP (62.71 µM) >bisphenol FL (96.31 µM) > other BPA analogues (ineffective at 100 µM). Bisphenol A, AF, AP, B, C, F, FL, Z, and 4,4'-thiodiphenol bind to the active sites of human and rat 11ß-HSD1. Regression of LogP and molecular weight with IC50 values revealed distinct inhibitory pattern (negative correlation for human 11ß-HSD1 vs. positive correlation for rat enzyme). Regression of the lowest binding energy with IC50 values revealed a significant positive regression. 3D QSAR pharmacophore analysis showed one hydrogen bond acceptor and two hydrogen bond donors for human 11ß-HSD1. In conclusion, most BPA analogues are more potent inhibitors of human and rat 11ß-HSD1 enzymes and there is structure-dependent and species-dependent inhibition.

Effectiveness of internet-based self-management interventions on pulmonary function in patients with chronic obstructive pulmonary disease: A systematic review and meta-analysis.

AIM: To investigate the effectiveness of internet-based self-management interventions on pulmonary function in patients with chronic obstructive pulmonary disease (COPD). DESIGN: Systematic review and meta-analysis. DATA SOURCES: Eight electronic databases including PubMed, Web of Science, Cochrane library, Embase, CINAHL, China National Knowledge Infrastructure, Wangfang and Weipu databases were systematically searched from inception of the database to January 10, 2022. METHODS: Statistical analysis was performed using Review Manager 5.4 and results were reported as mean difference (MD) or standard mean difference (SMD) with 95% confidence intervals (CI). Outcomes were the forced expiratory volume in 1 second (FEV1), forced volume capacity (FVC) and percent of FEV1/FVC. The Cochrane Risk of Bias Tool was used to assess the risk of bias of included studies. The study protocol was not registered. RESULTS: Eight randomized controlled trials (RCTs) including 476 participants met the inclusion criteria and were included in meta-analysis. It was found that internet-based self-management interventions showed a significant improvement in FVC(L), while FEV1 (%), FEV1 (L), FEV1/FVC (%) and FVC (%) did not significantly improve. CONCLUSIONS: Internet-based self-management interventions were effective in improving pulmonary function in patients with COPD, caution should be exercised in interpreting the results. RCTs of higher quality are needed in the future to further demonstrate the effectiveness of the intervention. RELEVANCE TO CLINICAL PRACTICE: It provides evidence for internet-based self-management interventions in improving pulmonary function in patients with COPD. IMPACT: The results suggested that internet-based self-management interventions could improve the pulmonary function in people with COPD. This study provides a promising alternative method for patients with COPD who have difficulty seeking face-to-face self-management interventions, and the intervention can be applied in clinical settings. PATIENT OR PUBLIC CONTRIBUTION: No Patient or Public Contribution.

A simple index to predict healing in venous leg ulcers: a secondary analysis from four randomised controlled trials.

OBJECTIVE: To investigate whether the use of a simple baseline measurement predicts venous leg ulcer healing at 12 and 24 weeks. METHOD: This was a secondary analysis of a cohort of four randomised controlled trials (RCTs) of treatments adjuvant to compression. Self-reported ulcer duration, and measured ulcer length and width, to calculate estimated ulcer area, were used to obtain a Margolis index score. The score created three prognostic strata for likelihood to heal within 24 weeks, and the number of participants healed and time-to-healing were compared. RESULTS: There were a total of 802 participants across the four RCTs-408 (50.9%) in two 12-week trials and 394 (49.1%) in two 24-week trials. The mean age of participants was 63.7±17.6 years, and 372 were female (46.4%). The Margolis index score at baseline was 0 for 320 participants (predicted normal healing); 1 for 334 participants; and 2 for 148 participants (both 1 and 2 predicted slow-to-heal). Overall, 248 (77.5%) of those participants who scored 0 at baseline healed within 24 weeks, compared with 182 (54.5%) of participants who scored 1, and 30 (20.3%) participants who scored 2. The median time-to-healing was 40 (24-62) days, 57 (35-100) days and 86.5 (56-151) days, respectively. The area under the receiver operating characteristic curve was 0.69 and 0.77, respectively, for the 12 and 24 week trials. CONCLUSION: A simple baseline index identifies participants with normal or slow-to-heal wounds and could be used to demonstrate prognostic balance between treatment groups in trials. This approach could also be used in clinical practice to assist with managing expectations and for early identification of patients who may best benefit from adjuvant treatments.