Your preoperative rehabilitation assistant: A study protocol for the impact of a telemedicine-supported preoperative home rehabilitation program on the prognosis of patients undergoing thoracoscopic surgery.

Background: Reduced cardiorespiratory fitness levels are associated with increased short-term complications after surgery, and potentially exert long-lasting effects on the postoperative lives, work and educational pursuits of patients. Currently, research suggests that lifestyle interventions, such as preoperative physical exercise undertaken by patients themselves, may improve patients' cardiopulmonary fitness and reduce post-operative complications. This study aims to investigate the effectiveness and feasibility of a remote medical supervision model for prehabilitation exercise in patients undergoing thoracoscopic lung tumour resection surgery. Methods/Design: All enrolled patients will participate in a 4-week pre-operative exercise intervention to improve their cardiorespiratory fitness. During this period, patients will wear wearable devices and exercise at home based on exercise prescriptions. The exercise prescription comprises aerobic exercise (three times a week or more), muscle strengthening exercise (twice a week or more), and respiratory muscle exercise (once a day). The primary aim is to investigate whether baseline VO2max could be improved following a 4-week preoperative exercise program. Secondary objectives include changes in forced expiratory volume in 1 s and forced vital capacity, degree of acceptance of the technology, quality of life, handgrip strength, postoperative complication rate and length of hospital stay. Discussion: This study aims to evaluate the influence of preoperative prehabilitation exercises in a telemedicine active supervision mode in patients undergoing thoracoscopic lung tumour resection. As such, results of this trial might have some impact on future implementations of group- and home-based prehabilitation exercises in lung cancers. Trial registration: This study was approved by the Medical Ethics Committee of Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology (approval number: TJ-IRB20220564) with registration at ClinicalTrials.gov (identifier: NCT05608759).

Enhancement of extraction efficiency and functional properties of chickpea protein isolate using pulsed electric field combined with ultrasound treatment.

Chickpea protein isolate (CPI) is a promising dietary protein with the advantages of low allergenicity, easy digestion and balanced composition of essential amino acids. However, due to the thick skin of chickpeas, the extraction of CPI is challenging, resulting in lower efficiency of the alkaline extraction-isoelectric precipitation (AE-IEP) method. Therefore, the present study investigated the effect of pulsed electric field combined with ultrasound (PEF-US) treatment on the extraction efficiency of CPI and the functional properties was characterized. Parameter optimization was carried out using response surface methodology (RSM), with the following optimized conditions: pulse duration of 87 s, electric field intensity of 0.9 kV/cm, ultrasonic time of 15 min, and ultrasonic power of 325 W. Under the optimized conditions, the yield of CPI after combined (PEF-US) treatment was 13.52 ± 0.13 %, which was a 47.28 % improvement over the AE-IEP method. This yield was better than that obtained with either individual PEF or US treatment. Additionally, the functional properties (solubility, emulsification, and foaming) of CPI were significantly enhanced compared to AE-IEP. However, the stability of emulsification and foaming did not show significant differences among the four methods. The PEF-US method efficiently extracts CPI with excellent functional properties, enabling the production of proteins as desired functional additives in the food industry.

ASIC1a regulates ferroptosis in hepatic stellate cells via the Hippo/Yap-1 pathway in liver fibrosis.

BACKGROUND: Liver fibrosis is a sustained process of liver tissue damage and repair caused by various physiological and pathological factors, with the activation and proliferation of hepatic stellate cells being central. Therefore, understanding and clarifying the relevant mechanisms of hepatic stellate cell activation and death is of great clinical significance for the treatment of liver fibrosis diseases. METHODS: In vivo, recombinant adeno-associated virus was used to infect the liver of experimental mice, overexpressing ASIC1a, and based on this, a liver fibrosis model treated with sorafenib was constructed. In vitro, using RNA plasmid technology to transfect HSC-T6 cells, ASIC1a was overexpressed or silenced in the cells, and on this basis, PDGF-BB and Sorafenib were used to stimulate HSC-T6 cells, causing activated HSC-T6 to undergo ferroptosis. RESULTS: The ferroptosis inducers Sorafenib and erastin can induce ferroptosis in HSCs, effectively inhibiting or reversing the progression of liver fibrosis. We found that the expression level of ASIC1a was significantly reduced in the livers of mice with liver fibrosis treated with Sorafenib. After treatment with an adeno-associated virus overexpressing ASIC1a, the therapeutic effect of Sorafenib was inhibited, and the level of ferroptosis induced by Sorafenib was also inhibited. The induction of ferroptosis in hepatic stellate cells in vitro depends on the presence of ASIC1a. By further exploring the potential mechanism, we observed that the overexpression of ASIC1a can promote an increase in YAP nuclear translocation, thereby regulating the activity of Hippo/YAP pathway signaling. After treatment with Sorafenib, the influx of Ca2+ significantly increased when ASIC1a was overexpressed, and BAPTA-AM intervention eliminated the intracellular Ca2+ accumulation induced by ASIC1a overexpression. CONCLUSIONS: This indicated that the activation of YAP depends on the calcium ion influx induced by ASIC1a, which regulates ferroptosis in hepatic stellate cells by regulating the calcium ion-dependent Hippo/YAP pathway.

Effects and Safety of the Traditional Chinese Exercise Baduanjin on Depression and Anxiety in COVID-19 Patients: A Systematic Review and Meta-analysis.

AIM: This systematic review and meta-analysis aimed to assess the safety and efficacy of Baduanjin, a traditional Chinese exercise (TCM), for reducing depression and anxiety in individuals suffering from coronavirus disease 2019 (COVID-19). METHODS: Nineteen databases were searched from their inception through August 2024 to gather data for this study. The focus of this study was randomized controlled trials (RCTs) in which Baduanjin was administered for the treatment of COVID-19 patients with depression and anxiety. The study included various types of Baduanjin exercise, whether used alone or in conjunction with other treatment modalities, for the control group. The comparators included a waitlist control, usual care, health education and supportive counseling, psychosocial support therapy, pharmacotherapies, and other common exercises. The exclusion criteria for trials were trials comparing different treatment durations, different treatment frequencies, and different types of Baduanjin exercise. Moreover, other traditional Chinese medicine (TCM) therapeutic methods applied in either the intervention or control group were also excluded. Throughout the entire study, the selection process, data extraction and quantitative analysis were carried out in strict adherence to all relevant guidelines. The Cochrane criteria for risk of bias were used to assess the methodological quality of the trials. In our review, a meta-analysis was performed using the software STATA MP14. RESULTS: After conducting a meta-analysis, eight RCTs were found to have satisfied the inclusion criteria. The effects of Baduanjin exercise on self-rating anxiety scale (SAS) scores were investigated in five RCTs comprising a total of 228 patients. Analysis of the results revealed that the combination of Baduanjin exercises and conventional therapies led to a statistically significant reduction in SAS scores [MD=-3.21 (95% CI= -3.64, -2.79), P< 0.001] compared to conventional therapies alone. Moreover, this systematic review explored the effect of Baduanjin exercise on self-rating depression scale (SDS) scores (three RCTs involving 83 participants), Hamilton Anxiety Rating Scale (HAM-A) scores (one RCT involving 103 participants), Patient Health Questionnaire (PHQ-9) scores (one RCT involving 70 participants) and Generalized Anxiety Disorder-7 (GAD-7) scores (one RCT involving 59 participants) for patients with COVID-19. The results showed that, in addition to conventional therapies, Baduanjin exercise had a more favorable impact on reducing the SDS score [mean difference (MD) =-2.86 (95% CI=4.11, -1.61), P=0.025], PHQ-9 score [MD=-5.31, 95% CI=-8.73, -1.89), P=0.002] and HAM-A score [MD=-3.00, 95% CI=-5.33, -0.67], P=0.010] in patients with COVID-19 than did the use of conventional therapies alone. Furthermore, the combination of Baduanjin exercise and conventional therapies effectively decreased the number of patients who experienced severe or moderate anxiety according to the GAD-7 score compared to that of patients who experienced severe or moderate anxiety according to conventional therapies alone [Relative Risk (RR) =0.03, 95% CI=0.00, 0.51); P=0.020]. However, the included clinical trials lacked a detailed description of the randomization process, and only a small portion of the studies reported proper allocation concealment procedures, which may introduce selection bias. Moreover, owing to the nature of Baduanjin exercise, it is difficult to blind participants and practitioners, which may lead to performance bias. Furthermore, the lack of blinding may lead to subjective influences of assessors on the results, thereby causing detection bias. These methodological shortcomings and potential biases should be addressed in future studies. CONCLUSIONS: It is difficult to draw firm conclusions on whether Baduanjin exercise is an effective intervention for reducing depression and anxiety in COVID-19 patients because of the high risk of bias among the available RCTs. Further rigorous RCTs are warranted but need to overcome the methodological shortcomings of the existing evidence.

NIR-activatable nitric oxide generator based on nanoparticles loaded small-molecule photosensitizers for synergetic photodynamic/gas therapy.

BACKGROUND: Therapeutic approaches that combine conventional photodynamic therapy (PDT) with gas therapy (GT) to sensitize PDT are an attractive strategy, but the molecular structure design of the complex lacks effective guiding strategies. RESULTS: Herein, we have developed a nanoplatforms Cy-NMNO@SiO2 based on mesoporous silica materials loaded NIR-activatable small-molecule fluorescent probe Cy-NMNO for the synergistic treatment of photodynamic therapy/gas therapy (PDT/GT) in antibacterial and skin cancer. The theoretical calculation results showed that the low dissociation of N-NO in Cy-NMNO enabled it to dissociate effectively under NIR light irradiation, which is conducive to produce Cy and NO. Cy showed better 1O2 generation performance than Cy-NMNO. The cytotoxicity of Cy-NMNO obtained via the synergistic effect of GT and PDT synergistically enhances the effect of photodynamic therapy, thus achieving more effective tumor treatment and sterilization than conventional PDT. Moreover, the nanoplatforms Cy-NMNO@SiO2 realized efficient drug loading and drug delivery. CONCLUSIONS: This work not only offers a promising approach for PDT-GT synergistic drug delivery system, but also provides a valuable reference for the design of its drug molecules.

The risk of treatment-related toxicities with PD-1/PD-L1 inhibitors in patients with lung cancer.

The risk of treatment-related toxicities with programmed cell death 1 and its ligand (PD-1/PD-L1) inhibitors in patients with lung cancer is unclear and inconclusive. PubMed, EMBASE, and the Cochrane Library databases were systematically searched without language restrictions from inception to May 31, 2024 to identify Phase 3 randomized controlled trials of lung cancer comparing PD-1/PD-L1 inhibitors versus placebo/best supportive care (alone or in combination with nontargeted chemotherapy) that had available data regarding treatment-related adverse events (TRAEs) or incidence and sample size. Random-effect models were employed to study the pooled relative risk (RR) and 95% confidence intervals (CIs). Finally, 36 trials, involving 19,693 participants, fulfilled the inclusion criteria. PD-1/PD-L1 inhibitors significantly augmented the likelihood of developing all-grade (RR, 1.03; 95% CI, 1.01-1.04, p < .01) and grade ≥3 TRAEs (RR, 1.16; 95% CI, 1.10 to 1.23, p < .01). PD-1/PD-L1 inhibitors substantially augmented the odds of developing treatment-related serious adverse events (SAEs) (RR, 1.48; 95% CI, 1.27-1.71, p < .01) and fatal adverse events (FAEs) (RR, 1.42; 95% CI, 1.11-1.82, p < .01). Subgroup analyses indicated that the RR of SAEs and FAEs were generally consistent, regardless of treatment type, tumor type, treatment setting, PD-1/PD-L1 inhibitors type and study design. The most common causes of FAEs were respiratory failure/insufficiency (33.3%), cardiac events (16.1%), and hematological disorders (10.1%). We demonstrated that PD-1/PD-L1 inhibitors were significantly correlated with higher possibility of developing treatment-related toxicities, especially SAEs and FAEs, compared with placebo/best supportive care controls.

Patient reported outcomes and the real-world use of calcitonin gene-related peptide medications in migraine.

OBJECTIVE: To assess patient reported outcomes of patients with migraine receiving preventative medications, and to compare patient reported outcomes and unplanned care of patients on calcitonin gene-related peptide inhibitors (CGRPi) with those on other preventative medications. BACKGROUND: Patient reported outcome measures can be useful in conditions such as migraine with frequent disability. CGRPi are newer migraine preventative medications that can improve patients' quality of life. METHODS: This was a retrospective cohort analysis of Patient Reported Outcomes Measurement Information System (PROMIS) data combined with administrative claims data from a large regional health plan for adult patients (≥18 years) with migraine who were on preventative medications from January 2019 to March 2022. PROMIS scores of patients on CGRPi were compared to scores of patients who switched from other preventative medications to CGRPi (pre vs. post), between patients adherent to CGRPi versus non-adherent, and changes in all-cause/migraine-related unplanned care (emergency department) use by the CGRPi cohort. RESULTS: There were 1245 patients on other preventative medications (antiseizure [532/1245 (43%)], antidepressants [316/1245 (25%)], and beta-blockers [397/1245 (32%)]), 148 who were on CGRPi, and 112 who had switched from other preventative medications to CGRPi. The mean age was 44 years old, 88% were females, 50% were married, and 75% were on commercial insurance. Patients with migraine had higher T-scores in pain, fatigue, anxiety, and sleep disturbance than the general population. Patients on CGRPi had a statistically significant reduction in pain T-scores (60.4 [standard deviation (SD) 7.4] to 58.4 [SD 8.2], p = 0.003) post initiation of medications, especially those who switched from other preventative medications to CGRPi (61.4 [SD 6.9] to 58.7 [SD 8.3], p < 0.001). The pain T-score reduction occurred only among the adherent group. There was a lower proportion of patients with all-cause unplanned care among patients on CGRPi (43% [64/148] to 32% [47/148], p < 0.001), but the reduction in migraine-related unplanned care was not statistically significant (9% [14/148] to 6% [9/148], p = 0.197). CONCLUSION: Our findings suggest that patients had an improvement in pain reduction scores after initiating CGRPi. PROMIS scores could provide important information about quality-of-life improvement for prescribers.

Plasma Inflammation Markers Linked to Complications and Outcomes after Spontaneous Intracerebral Hemorrhage.

Intracerebral hemorrhage (ICH) could trigger inflammatory responses. However, the specific role of inflammatory proteins in the pathological mechanism, complications, and prognosis of ICH remains unclear. In this study, we investigated the expression of 92 plasma inflammation-related proteins in patients with ICH (n = 55) and healthy controls (n = 20) using an Olink inflammation panel and discussed the relation to the severity of stroke, clinical complications, 30-day mortality, and 90-day outcomes. Our result showed that six proteins were upregulated in ICH patients compared with healthy controls, while seventy-four proteins were downregulated. In patients with ICH, seven proteins were increased in the severe stroke group compared with the moderate stroke group. In terms of complications, two proteins were downregulated in patients with pneumonia, while nine proteins were upregulated in patients with sepsis. Compared with the survival group, three proteins were upregulated, and one protein was downregulated in the death group. Compared with the good outcome group, eight proteins were upregulated, and four proteins were downregulated in the poor outcome group. In summary, an in-depth exploration of the differential inflammatory factors in the early stages of ICH could deepen our understanding of the pathogenesis of ICH, predict patient prognosis, and explore new treatment strategies.

SGLT2 inhibitor promotes ketogenesis to improve MASH by suppressing CD8+ T cell activation.

During the progression of metabolic dysfunction-associated steatohepatitis (MASH), the accumulation of auto-aggressive CD8+ T cells significantly contributes to liver injury and inflammation. Empagliflozin (EMPA), a highly selective inhibitor of sodium-glucose co-transporter 2 (SGLT2), exhibits potential therapeutic benefits for liver steatosis; however, the underlying mechanism remains incompletely elucidated. Here, we found that EMPA significantly reduced the hepatic accumulation of auto-aggressive CD8+ T cells and lowered granzyme B levels in mice with MASH. Mechanistically, EMPA increased ß-hydroxybutyric acid by promoting the ketogenesis of CD8+ T cells via elevating 3-hydroxybutyrate dehydrogenase 1 (Bdh1) expression. The ß-hydroxybutyric acid subsequently inhibited interferon regulatory factor 4 (Irf4), which is crucial for CD8+ T cell activation. Furthermore, the ablation of Bdh1 in T cells aggravated the manifestation of MASH and hindered the therapeutic efficacy of EMPA. Moreover, a case-control study also showed that SGLT2 inhibitor treatment repressed CD8+ T cell infiltration and improved liver injury in patients with MASH. In summary, our study indicates that SGLT2 inhibitors can target CD8+ T cells and may be an effective strategy for treating MASH.

An indirect treatment comparison meta-analysis of digital versus face-to-face cognitive behavior therapy for headache.

Cognitive behavioral therapy (CBT) is effective for headache disorders. However, it is unclear whether the emerging digital CBT is noninferior to face-to-face CBT. An indirect treatment comparison (ITC) meta-analysis was conducted to assess the relative effects between them using standard mean differences (SMDs). Effective sample size (ESS) and required sample size (RSS) were calculated to demonstrate the robustness of the results. Our study found that digital CBT had a similar effect on headache frequency reduction (SMD, 0.12; 95%CI, -2.45 to 2.63) compared with face-to-face CBT. The ESS had 84 participants, while the RSS had 466 participants to achieve the same power as a non-inferior head-to-head trial. Digital CBT is as effective as face-to-face CBT in preventing headache disorders. Due to the heterogeneity (I2 = 94.5%, τ2 = 1.83) and the fact that most of the included studies were on migraine prevention, further head-to-head trials are warranted.

Gamma-glutamyl transferase to aspartate aminotransferase ratio (GSR) predicts prognoses in patients with colorectal cancer with liver metastasis after microwave ablation.

BACKGROUND: Microwave ablation (MWA) is widely used to eliminate colorectal liver metastases (CRLM). However, the risk of tumor recurrence is difficult to predict due to lack of reliable clinical and biological markers. Elevation of gamma-glutamyl transferase (GGT) and aspartate transaminase (AST) provides signals for liver inflammation and cancer progression. The present study evaluated the association between pre-ablation GGT to AST ratio index (GSR) and hepatic recurrence in patients with CRLM after MWA. METHODS: A retrospectively analyzed 192 CRLM patients who underwent MWA from January 2013 to December 2017. Pre-ablation GSR was classified into high (≤ 2.34) or low (> 2.34) using the upper quartile value. The prognostic value of GSR and other risk factors for liver progression-free survival (LPFS) and cancer-specific survival (CSS) were evaluated by univariate and multivariate analyses. RESULTS: High GSR was significantly associated with males (P = 0.041), the presence of cholelithiasis (P = 0.012), but not pre-ablation chemotherapy (P = 0.355), which caused significantly increased levels of GGT (P = 0.015) and AST (P = 0.008). GSR showed a significant association with LPFS and CSS through univariate analysis (P = 0.002 and 0.006) and multivariate analysis (P = 0.043 and 0.037). The subgroup analysis demonstrated no interaction between GSR and all variables except for distribution in the sub-analysis of LPFS. CONCLUSIONS: Our findings suggest that the pre-ablation GSR can be considered as a promising prognostic indicator for poor prognosis of patients with CRLM underwent MWA. TRIAL REGISTRATION: Not applicable.

Exosomal SLC16A1-AS1-induced M2 macrophages polarization facilitates hepatocellular carcinoma progression.

Macrophages are the most abundant alternative immune cells in the tumor microenvironment (TME). The cross-talk between macrophages and tumor cells provides an important shelter for the occurrence and development of tumors. As an important information transfer medium, exosomes play an important role in intercellular communication. Nonetheless, how exosomal lncRNAs coordinate the communication between tumor cells and immune cells in hepatocellular carcinoma (HCC) is incompletely understood. We found that HCC exosomes-derived antisense RNA of SLC16A1(SLC16A1-AS1) promoted the malignant progression of HCC by regulating macrophage M2-type polarization. Mechanistically, the HCC exosomal SLC16A1-AS1 enhanced mRNA stabilization of SLC16A1 in macrophage by promoting the interaction between 3' untranslated regions (3'UTR) of SLC16A1 mRNA and heterogeneous nuclear ribonucleoprotein A1 (HNRNPA1). As a lactate transporter, SLC16A1 accelerated lactate influx and then activated c-Raf/ERK signaling to induce M2 polarization of macrophages. Reciprocally, M2 macrophages secreted IL-6 to activate STAT3 and then induce METTL3 transcription in HCC cells, which increasing m6A methylation and stabilization of SLC16A1-AS1. In turn, the reciprocal SLC16A1-AS1/IL-6 signaling between HCC cells and M2 macrophages promoted the proliferation, invasion and glycolysis of HCC cells. Our study highlights that exosomal SLC16A1-AS1 acts as a signaling message that induces lactate-mediated M2 polarization of macrophages, and implies that SLC16A1-AS1 might be an applicable target for therapeutic treatment of HCC.

Study on microwave ablation temperature prediction model based on grayscale ultrasound texture and machine learning.

BACKGROUND: Temperature prediction is crucial in the clinical ablation treatment of liver cancer, as it can be used to estimate the coagulation zone of microwave ablation. METHODS: Experiments were conducted on 83 fresh ex vivo porcine liver tissues at two ablation powers of 15 W and 20 W. Ultrasound grayscale images and temperature data from multiple sampling points were collected. The machine learning method of random forests was used to train the selected texture features, obtaining temperature prediction models for sampling points and the entire ultrasound imaging area. The accuracy of the algorithm was assessed by measuring the area of the hyperechoic area in the porcine liver tissue cross-section and ultrasound grayscale images. RESULTS: The model exhibited a high degree of accuracy in temperature prediction and the identification of coagulation zone. Within the test sets for the 15 W and 20 W power groups, the average absolute error for temperature prediction was 1.14°C and 4.73°C, respectively. Notably, the model's accuracy in measuring the area of coagulation was higher than that of traditional ultrasonic grey-scale imaging, with error ratios of 0.402 and 0.182 for the respective power groups. Additionally, the model can filter out texture features with a high correlation to temperature, providing a certain degree of interpretability. CONCLUSION: The temperature prediction model proposed in this study can be applied to temperature monitoring and coagulation zone range assessment in microwave ablation.

Hydrogen Sulfide-Triggered Artificial DNAzyme Switches for Precise Manipulation of Cellular Functions.

The development of synthetic molecular tools responsive to biological cues is crucial for advancing targeted cellular regulation. A significant challenge is the regulation of cellular processes in response to gaseous signaling molecules such as hydrogen sulfide (H2S). To address this, we present the design of Gas signaling molecule-Responsive Artificial DNAzyme-based Switches (GRAS) to manipulate cellular functions via H2S-sensitive synthetic DNAzymes. By incorporating stimuli-responsive moieties to the phosphorothioate backbone, DNAzymes are strategically designed with H2S-responsive azide groups at cofactor binding locations within the catalytic core region. These modifications enable their activation through H2S-reducing decaging, thereby initiating substrate cleavage activity. Our approach allows for the flexible customization of various DNAzymes to regulate distinct cellular processes in diverse scenarios. Intracellularly, the enzymatic activity of GRAS promotes H2S-induced cleavage of specific mRNA sequences, enabling targeted gene silencing and inducing apoptosis in cancer cells. Moreover, integrating GRAS with dynamic DNA assembly allows for grafting these functional switches onto cell surface receptors, facilitating H2S-triggered receptor dimerization. This extracellular activation transmits signals intracellularly to regulate cellular behaviors such as migration and proliferation. Collectively, synthetic switches are capable of rewiring cellular functions in response to gaseous cues, offering a promising avenue for advanced targeted cellular engineering.

First-principles study of the electronic structures and optical properties of g-ZnO/CdX (X = S, Se, Te) van der Waals heterostructures.

The stability, electronic structures and optical properties of g-ZnO/CdX (X = S, Se, Te) heterostructures are studied by density functional theory. It is found that the stable monolayers spacing of the corresponding heterostructure decreases with the increase of the X atomic radius in the CdX monolayers. The constructed g-ZnO/CdX heterostructures all belong to direct band gap, 2.12 eV, 2.09 eV and 1.99 eV, respectively. Electrostatic potential results show that the two monolayers form an internal electric field at the heterostructure interface, and can inhibit the recombination of photogenerated electron hole pairs, and effectively extend the carrier lifetime. Charge density difference analysis shows that charge redistribution mainly occurs in the interfacial region. The optical properties show that the absorption of g-ZnO in the visible range is achieved by heterostructure. In general, with the smallest band gap and the strongest built-in electric field, g-ZnO/CdTe could have the best carrier separation efficiency. And the optical property analysis proves that the g-ZnO/CdTe heterostructure system has the highest utilization ratio of visible light. The above results show that the electronic structure and optical properties of g-ZnO/CdTe heterostructure are the best, and it can be inferred that this heterostructure will be the most beneficial to improve the photocatalytic activity of g-ZnO, providing a new direction for its application in the field of photocatalysis.

Metabolomics and gut microbiota analysis reveal the differential efficacy of areca nut and charred areca nut in treating constipation.

Background: Areca nut (AN) is a traditional Chinese herbal medicine used for centuries to treat gastrointestinal (GI) disorders. Charred AN (CAN) is a processed product of AN with similar therapeutic effects. This study aimed to investigate the therapeutic mechanisms of AN and CAN for constipation via metabolomics and gut microbiota analysis. Methods: In this study, the rats were randomly divided into 5 groups (n = 6): control, constipation model, positive drug, AN treatment, and CAN treatment groups. Constipation was induced by intragastric administration of loperamide hydrochloride, followed by 14-day treatment with mosapride, AN, or CAN. The efficacy difference between AN and CAN was assessed by evaluating the weight gain, fecal water content, GI transit rate, colonic histopathology, serum levels of GI hormones, gut microbiota, and fecal metabolites. Results: The results demonstrated that both AN and CAN could alleviate loperamide-induced constipation. Furthermore, they significantly elevated the serum levels of motilin, vasoactive intestinal peptide, substance P, and acetylcholine. 16S rRNA analysis revealed that AN regulated the relative abundance of Bacillus, UCG-005, norank_f_Muribaculaceae, Candidatus_Saccharimonas, and Ruminococcus, whereas CAN modulate the relative abundance of Lactobacillus, Bacillus, norank_f_Muribaculaceae, Ruminococcus, unclassified_f_Oscillospiraceae, and unclassified_f_Prevotellaceae. Moreover, the metabolic profile of AN- and CAN-treated rats was also different, where AN treatment involved pathways of citrate cycle (TCA) and tyrosine, alanine, aspartate, and glutamate metabolisms. Whereas CAN treatment involved pathways of steroid and primary bile acid biosynthesis, as well as pyrimidine and purine metabolisms. Spearman correlation analysis indicated a close relationship between gut microbiota and fecal metabolites. Conclusion: In summary, this study revealed that AN may protect GI mucosa, enhance GI motility, and alleviate constipation symptoms by regulating the relative abundance of specific gut microbiota (Bacillus, UCG-005, norank_f_Muribaculaceae, Candidatus_Saccharimonas, Ruminococcus) as well as citrate cycle or tyrosine, alanine, aspartate, and glutamate metabolic pathways. Furthermore, CAN was observed to promote gastric emptying and intestinal propulsion, thereby alleviating constipation, by modulating the relative abundance of specific gut microbiota (Lactobacillus, Bacillus, norank_f_Muribaculaceae, Ruminococcus, unclassified_f_Oscillospiraceae, unclassified_f_Prevotellaceae) as well as steroid and primary bile acid biosynthesis, as well as pyrimidine and purine metabolic pathways.

Ultrathin and Conformal Depletion Layer of Core/Shell Heterojunction Enables Efficient and Stable Acidic Water Oxidation.

Ru-based electrocatalysts hold great promise for developing affordable proton exchange membrane (PEM) electrolyzers. However, the harsh acidic oxidative environment of the acidic oxygen evolution reaction (OER) often causes undesirable overoxidation of Ru active sites and subsequent serious activity loss. Here, we present an ultrathin and conformal depletion layer attached to the Schottky heterojunction of core/shell RuCo/RuCoOx that not only maximizes the availability of active sites but also improves its durability and intrinsic activity for acidic OER. Operando synchrotron characterizations combined with theoretical calculations elucidate that the lattice strain and charge transfer induced by Schottky heterojunction substantially regulate the electronic structures of active sites, which modulates the OER pathway and suppresses the overoxidation of Ru species. Significantly, the closed core/shell architecture of the RuCo/RuCoOx ensures the structure integrity of the Schottky heterojunction under acidic OER conditions. As a result, the core/shell RuCo/RuCoOx Schottky heterojunction exhibits an unprecedented durability up to 250 0 h at 10 mA cm-2 with an ultralow overpotential of ∼170 mV at 10 mA cm-2 in 0.5 M H2SO4. The RuCo/RuCoOx catalyst also demonstrates superior durability in a proton exchange membrane (PEM) electrolyzer, showcasing the potential for practical applications.

Achieving ultrasensitive detection of glyphosate in fruits and vegetables using a triple-mode strategy based on carbon dots nanozymes derived from expired drugs.

Rapid and sensitive detection of glyphosate (GLP) holds significant importance in the monitoring of environmental pollution and potential risks to human health. In this study, carbon dots nanozymes (CDszymes) with peroxidase-like activity were synthesized rapidly using a microwave-assisted method, employing expired drugs as raw materials. In the presence of H2O2, CDszymes catalyze the oxidation of TMB to generate blue oxTMB, which exhibits a photothermal effect under near-infrared light irradiation; an inner filter effect (IFE) may occur between oxTMB and CDszymes. By coupling the cascade catalysis of AChE and ChOx to generate H2O2, GLP effectively inhibits the activity of AChE, constructing a colorimetric/fluorescent/photothermal response platform for GLP. In colorimetry, the detection limit of GLP was 0.33 ng/mL. The detection limits of GLP by fluorescence method and photothermal method were 0.02 ng/mL and 0.41 ng/mL, respectively. The efficacy of this methodology has been successfully demonstrated in fruit and vegetable, it also provides a strategy for the high-value conversion of expired drugs.

Insights into the photosensitivity and photobleaching of dissolved organic matter from microplastics: Structure-activity relationship and transformation mechanism.

Revealing the structure-activity relationship between physicochemical properties and photoactivities of microplastic dissolved organic matter (MPDOM) is significant for understanding the environmental fate of MPs. Here, we systematically analyzed the physicochemical properties and molecular composition of DOM derived from MPs including polystyrene (PS), polyethylene glycol terephthalate (PET), polyadipate/butylene terephthalate (PBAT), polylactic acid (PLA), polypropylene (PP), and compared their photosensitivity and photobleaching behaviors. Results indicated that PSDOM and PETDOM had more similar properties and compositions, and showed stronger photosensitivity and photobleaching effects than PBATDOM, PLADOM and PPDOM. The [3DOM∗]SS and [1O2]SS varied in the range of 0.31-13.03 × 10-14 and 1.71-5.49 × 10-13 M, respectively, which were within the reported range of DOM from other sources. The SUVA254, HIX, AImodwa, Xcwa and lignin/CRAM-like component showed positive correlation with the [3DOM∗]SS, [1O2]SS and Φ3DOM*. The negative correlation between E2/E3 and [3DOM∗]SS was due to the higher proportion of low-molecular weight components in MPDOM. The lignin/CRAM-like component was identified to be the crucial photobleaching-component. The lignin/CRAM-like in PSDOM showed a deepened oxidation degree, while its change trend in PETDOM was from unsaturated to saturated. These findings provide new insights into the relevant photochemical fate of MPDOM.

Efficacy and safety of fentanyl inhalant for the treatment of breakthrough cancer pain: a multicenter, randomized, double-blind, placebo-controlled trial.

BACKGROUND: Breakthrough cancer pain (BTcP) has a negative impact on patients' quality of life, general activities, and is related to worse clinical outcomes. Fentanyl inhalant is a hand-held combination drug-device delivery system providing rapid, multi-dose (25µg/dose) administration of fentanyl via inhalation of a thermally generated aerosol. This multicenter, randomized, placebo-controlled, multiple-crossover, double-blind study evaluated the efficacy, safety, and tolerability of fentanyl inhalant in treating BTcP in opioid-tolerant patients. METHODS: The trial was conducted in opioid-tolerant cancer patients with 1 ~ 4 BTcP outbursts per day. Each patient was treated and observed for 6 episodes of BTcP (4 with fentanyl inhalant, 2 with placebo). During each episode of targeted BTcP, patients were allowed up to six inhalations, with an interval of at least 4 min between doses. Primary outcome was the time-weighted sum of PID (pain intensity difference) scores at 30 min (SPID30). RESULTS: A total of 335 BTcP episodes in 59 patients were treated. The mean SPID30 was -97.4 ± 48.43 for fentanyl inhalant-treated episodes, and -64.6 ± 40.25 for placebo-treated episodes (p < 0.001). Significant differences in PID for episodes treated with fentanyl inhalant versus placebo was seen as early as 4 min and maintained for up to 60 min. The percentage of episodes reported PI (pain intensity) scores ≤ 3, a ≥ 33% or ≥ 50% reduction in PI scores at 30 min, PR30 (pain relief scores at 30 min) and SPID60 favored fentanyl inhalant over placebo. Only 4.4% of BTcP episodes required rescue medication in fentanyl inhalant group. Most AEs were of mild or moderate severity and typical of opioid drugs. CONCLUSION: Treatment with fentanyl inhalant was shown to be a promising therapeutic option for BTcP, with significant pain relief starting very soon after dosing. Confirmation of effectiveness requires a larger phase III trial. TRIAL REGISTRATION: ClinicalTrials.gov: NCT05531422 registered on 6 September 2022 after major amendment, NCT04713189 registered on 14 January 2021.