A cyclic shift-temperature operation method to train microbial communities of mesophilic anaerobic digestion.

Temperature is the critical factor affecting the efficiency and cost of anaerobic digestion (AD). The current work develops a shift-temperature AD (STAD) between 35 °C and 55 °C, intending to optimise microbial community and promote substrate conversion. The experimental results showed that severe inhibition of biogas production occurred when the temperature was firstly increased stepwise from 35 °C to 50 °C, whereas no inhibition was observed at the second warming cycle. When the organic load rate was increased to 6.37 g VS/L/d, the biogas yield of the STAD reached about 400 mL/g VS, nearly double that of the constant-temperature AD (CTAD). STAD promoted the proliferation of Methanosarcina (up to 57.32 %), while severely suppressed hydrogenophilic methanogens. However, when the temperature was shifted to 35 °C, most suppressed species recovered quickly and the excess propionic acid was quickly consumed. Metagenomic analysis showed that STAD also promoted gene enrichment related to pathways metabolism, membrane functions, and methyl-based methanogenesis.

Comparison of prognosis between oncocytic thyroid carcinoma and follicular thyroid carcinoma: a population-based propensity score matching analysis.

BACKGROUND: Oncocytic thyroid carcinoma (OTC) is a rare subtype of thyroid cancer known for its distinctive morphology and high likelihood of recurrence, setting it apart from follicular thyroid carcinoma (FTC). Despite this, there is limited research comparing the clinicopathological characteristics and outcomes of OTC and FTC. METHODS: We retrospectively searched through the Surveillance, Epidemiology, and End-Results (SEER) database (2004-2015) for histologically diagnosed OTC and FTC patients. Kaplan-Meier analysis, propensity score matching (PSM), univariate Cox proportional risk regression model, and subgroup analysis were employed to investigate the prognostic effect of clinicopathological features and treatment regimens on survival outcomes of OTC and FTC patients. RESULTS: 2329 OTC patients and 5679 FTC patients were included in the study. OTC patients were prone to older age, white race, lymph node metastasis, distal metastasis, extension and multiple primary tumors compared with FTC patients. After using a 1:1 PSM matching ratio, there were no significant differences in demographic and clinicopathological characteristics between the matched groups. Further Cox regression analysis showed that OTC patients had lower overall survival (OS) and cancer-specific survival (CSS) in contrast with FTC patients. Subgroup survival analysis suggested that the OTC patients were related to lower OS in subgroups including those over 55 years old, male sex, white ethnicity, extrathyroidal extension, single primary tumor, surgery and without chemotherapy compared with the FTC patients in these subgroups. In addition, the OTC patients were connected with lower CSS in subgroups including male sex, white ethnicity, married status, tumor size is less than 20 mm or more than 40 mm, N0 stage, localized stage, single primary tumor, surgery, radiotherapy, and without chemotherapy compared with the FTC patients in these subgroups. Meanwhile, the OTC patients had lower CSS compared to FTC patients regardless of age and extrathyroidal extension. CONCLUSIONS: The results suggested that OTC patients have unique clinical features and poorer prognoses compared to FTC patients. Surgical resection and radioactive iodine therapy are recommended for OTC patients and FTC patients. It is worth noting that the prognosis of OTC relies largely on the selection of treatment strategies. Therefore, our results highlighted the clinical significance of the early distinguishment and the correct choice of treatment in OTC patients.

Identifying the habitat suitability of Pteris vittata in China and associated key drivers using machine learning models.

Pteris vittata (P. vittata) possesses significant potential in remediating arsenic (As) soil pollution. Understanding the habitat suitability of P. vittata in China and pinpointing the key drivers that influence its distribution can facilitate the identification of optimal areas for using P. vittata as a remediation tool for As-polluted soils. In this study, a comparative analysis was conducted using ten machine learning models to assess the habitat suitability of P. vittata based on 744 specimen records and 20 environmental factors. The key drivers affecting the distribution of P. vittata were also investigated based on the optimal model. The results indicate that the XGBOOST model was the most reliable and stable, achieving a coefficient of determination of 0.95. Approximately 24.47 % of China's land area was identified as suitable for P. vittata. Particularly, it was predominantly found in Hainan (45.9 %), Guangxi (92.96 %), Guangdong (91.68 %), Hunan (91.26 %), Guizhou (90.83 %), Chongqing (88.17 %), Fujian (85.70 %), Yunnan (77.44 %), Jiangxi (73.99 %) and Zhejiang (57.05 %). Furthermore, this study pinpointed the lowest temperature, annual temperature range, and mining density as key drivers, contributing 45.9 %, 31.9 %, and 7.2 %, respectively. Spatial correlation analysis revealed a significant correlation between mining density and the habitat distribution of P. vittata (Moran' I = 0.519). This study confirmed that both natural factors and anthropogenic activities affect the distribution of P. vittata and provided valuable insights for optimizing the application of P. vittata in soil phytoremediation and reclamation.

Association Between Genetically Determined Serum Corin and the Risk of Stroke in Chinese Adults: A Mendelian Randomization Study.

BACKGROUND: Serum corin has been associated with stroke in observational studies, but the underlying causality is uncertain. This study examined the causal association between corin and stroke through Mendelian randomization study. METHODS AND RESULTS: In the Gusu cohort, serum corin was assayed at baseline, and stroke incidents were prospectively obtained during 10 years of follow-up. Single-nucleotide polymorphisms (SNPs) in CORIN were genotyped by MassArray for 2310 participants (mean age, 53 years; 39% men). Seventeen SNPs passed the Hardy-Weinberg test and were considered the potential instruments. Only 1 SNP (rs2271037) determined variability of serum corin was significantly associated with stroke even after adjusting for conventional risk factors (hazard ratio [HR], 1.36 [95% CI, 1.00-1.85]). The weighted genetic risk score generated from the SNP-corin associations was significantly associated with stroke (HR, 2.01 [95% CI, 1.15-3.51]). Using this genetic risk score as the instrument, 1-sample Mendelian randomization analysis found a significant HR of stroke per-SD higher log2-transformed corin (HR, 1.37 [95% CI, 1.07-1.76]). The inverse variance-weighted analysis based on the SNP-corin and SNP-stroke associations found that the HR of stroke pre-SD higher log2-transformed corin was 5.92 (95% CI, 2.23-15.72). The effect estimates stayed consistent regardless of an individual SNP being removed from the instruments. An almost identical effect estimate was also confirmed by multiple other 2-sample Mendelian randomization methods. CONCLUSIONS: Genetically determined variations of serum corin concentration were significantly associated with the risk of stroke in Chinese adults. Elevated serum corin may be a risk factor for stroke.

Association Between Sleep Characteristics and Likelihood of Prodromal Parkinson's Disease: A Cross-Sectional Analysis in the HABIT Study.

Background: Sleep is critical in health problems including Parkinson's disease (PD). This study examined the association between sleep characteristics and the likelihood of prodromal PD. Methods: At baseline examination of the Heart and Brain Investigation in Taicang (HABIT) study, potential PD biomarkers were obtained for 8777 participants aged over 50 years, and the probability of prodromal PD was assessed based on the Chinese expert consensus and Movement Disorder Society (MDS) criteria. General and component sleep characteristics were evaluated by the Pittsburgh Sleep Quality Index (PSQI). Median regression was applied to examine the association between sleep and the probability of prodromal PD, adjusting for age, sex, education level, physical activity, obesity, fast plasma glucose, lipids, and hypertension. Results: Based on China criteria, a higher level of PSQI score was significantly associated with a higher probability of prodromal PD (ß = 0.02, 95% CI: 0.01-0.03) and a higher risk of having an increased probability of prodromal PD (OR = 1.04, 95% CI: 1.02-1.05). Compared to participants with good quality sleep, those with poor quality sleep had a 0.07% increased probability of prodromal PD (95% CI: 0.01-0.13) and a 19% increased risk of having a high prodromal PD probability (95% CI: 1.04-1.20). Similar associations between sleep quality and the probability of prodromal PD were also observed using the MDS criteria. Subjective sleep quality, sleep latency, habitual sleep efficiency, daytime dysfunction, and use of sleep medications were also associated with the probability of prodromal PD. Conclusion: Poor sleep quality was associated with a high probability of prodromal PD. Sleep may be helpful for understanding and intervention of prodromal PD.

Phosphorylation of PIP2;7 by CPK28 or Phytophthora kinase effectors dampens pattern-triggered immunity in Arabidopsis.

Plasma membrane intrinsic proteins (PIPs), a subclass of aquaporins (AQPs), play an important role in plant immunity by acting as H2O2 transporters. Their homeostasis is mostly maintained by C-terminal serine phosphorylation. However, the kinases that phosphorylate PIPs and manipulate their turnover are largely unknown. Here, we found that Arabidopsis thaliana PIP2;7 positively regulates plant immunity by transporting H2O2. Arabidopsis CALCIUM-DEPENDENT PROTEIN KINASE 28 (CPK28) directly interacts with and phosphorylates PIP2;7 at Ser273/276 to induce its degradation. During pathogen infection, CPK28 dissociated from PIP2;7 and destabilized, leading to PIP2;7 accumulation. As a counter, oomycete pathogens produce the conserved kinase effectors that stably bind and mediate the phosphorylate of PIP2;7 to induce its degradation. Our study identifies PIP2;7 as a novel substrate of CPK28 and its protein stability is negatively regulated by CPK28. Such phosphorylation could be mimicked by Phytophthora kinase effectors to promote infection. Accordingly, we developed a strategy to combat oomycete infection by using a phosphorylation-resistant PIP2;7S273/276A mutant. The strategy only allows accumulation of PIP2;7S273/276A during infection to limit potential side effects on normal plant growth.

Tumor ABCC4-mediated release of PGE2 induces CD8+ T cell dysfunction and impairs PD-1 blockade in prostate cancer.

Prostate cancer presents as an immunologically "cold" malignancy, characterized by a lack of response to immunotherapy in the majority of patients. The dysfunction of prostate tumor metabolism is recognized as a critical factor in immune evasion, resulting in reduced effectiveness of immunotherapeutic interventions. Despite this awareness, the precise molecular mechanisms underpinning metabolic dysregulation in prostate cancer and its intricate relationship with immune evasion remain incompletely elucidated. In this study, we introduce the multi-drug resistance protein ABCC4/MRP4 as a key player prominently expressed in prostate cancer, exerting a pivotal role in suppressing the activity of intratumoral CD8+ T cells. Depletion of ABCC4 in prostate cancer cells halts the release of prostaglandin E2 (PGE2), a molecule that diminishes the population of CD8+ T cells and curtails their cytotoxic capabilities. Conversely, constraining the activation of PGE2 signaling in CD8+ T cells effectively improved the efficacy of prostate cancer treatment with PD-1 blockade. During this process, downregulation of the JAK1-STAT3 pathway and depolarization of mitochondria emerge as crucial factors contributing to T cell anergy. Collectively, our research identifies the ABCC4-PGE2 axis as a promising target for reversing dysfunction within tumor-infiltrating lymphocytes (TILs) and augmenting the suboptimal responsiveness to immunotherapy in prostate cancer.

Role of [18F]FAPI-04 in staging and therapeutic management of intrahepatic cholangiocarcinoma: prospective comparison with [18F]FDG PET/CT.

BACKGROUND: Fluorine-18 fluorodeoxyglucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT) has some limitations in diagnosis of Intrahepatic cholangiocarcinoma (ICC). MATERIALS AND METHODS: Patients with histologically confirmed ICC who underwent both [18F]FDG and 18F-labeled fibroblast-activation protein inhibitors ([18F]FAPI)-04 PET/CT were prospectively analyzed. The maximum standard uptake value (SUVmax), tumor-to-background ratio (TBR), metabolic tumor volume (MTV), total lesion glycolysis (TLG), [18F]FAPI-avid tumor volume (FTV), total lesion fibroblast activation protein expression (TLF) were compared between the two modalities by paired Wilcoxon signed-rank test and Mann-Whitney U test, and McNemar's test was used to assess the diagnostic accuracy between the two techniques. RESULTS: In total, 23 patients with 389 lesions were included. Compared to [18F]FDG, [18F]F-FAPI-04 PET/CT demonstrated a higher detection rate for intrahepatic lesions (86.3% vs. 78.2% P = 0.040), lymph node metastases (85.2% vs. 68.2%, P = 0.007), peritoneal metastases (100% vs. 93.8%), and bone metastases (100% vs. 70.5%, P < 0.001). [18F]FAPI-04 PET showed higher SUVmax, TBR and greater tumor burden values than [18F]FDG PET in non-cholangitis intrahepatic lesions (SUVmax: 8.7 vs. 6.4, P < 0.001; TBR: 8.0 vs. 3.5, P < 0.001; FTV vs. MTV: 41.3 vs. 12.4, P < 0.001; TLF vs. TLG: 223.5 vs. 57.0, P < 0.001), lymph node metastases (SUVmax: 6.5 vs. 5.5, P = 0.042; TBR: 5.4 vs. 3.9, P < 0.001; FTV vs. MTV: 2.0 vs. 1.5, P = 0.026; TLF vs. TLG: 9.0 vs. 7.8 P = 0.024), and bone metastases (SUVmax: 9.7 vs. 5.25, P < 0.001; TBR: 10.8 vs. 3.0, P < 0.001; TLF vs. TLG: 9.8 vs. 4.2, P < 0.001). However, [18F]FDG showed higher radiotracer uptake (SUVmax: 14.7 vs. 8.4, P < 0.001; TBR: 7.4 vs. 2.8, P < 0.001) than [18F]FAPI-04 PET/CT for 6 patients with obstructive cholangitis. [18F]FAPI-04 PET/CT yielded a change in planned therapy in 6 of 23 (26.1%) patients compared with [18F]FDG. CONCLUSIONS: [18F]FAPI-04 PET/CT had higher detection rate and radiotracer uptake than [18F]FDG PET/CT in intrahepatic lesions, lymph node metastases, and distant metastases, especially in bone. Therefore, [18F]FAPI-04 PET/CT may be a promising technique for diagnosis and staging of ICC. TRIAL REGISTRATION: Clinical Trials, NCT05485792. Registered 1 August 2022, retrospectively registered, https//clinicaltrials.gov/study/NCT05485792?cond=NCT05485792&rank=1.

Engineering magnetic nanosystem for TRPV1 and TRPV4 channel activation.

Recently, physical tools for remotely stimulating mechanical force-sensitive and temperature-sensitive proteins to regulate intracellular pathways have opened up novel and exciting avenues for basic research and clinical applications. Among the numerous modes of physical stimulation, magnetic stimulation is significantly attractive for biological applications due to the advantages of depth penetration and spatial-temporally controlled transduction. Herein, the physicochemical parameters (e.g., shape, size, composition) that influence the magnetic properties of magnetic nanosystems as well as the characteristics of transient receptor potential vanilloid-1 (TRPV1) and transient receptor potential vanilloid-4 (TRPV4) channels are systematically summarized, which offer opportunities for magnetic manipulation of cell fate in a precise and effective manner. In addition, representative regulatory applications involving magnetic nanosystem-based TRPV1 and TRPV4 channel activation are highlighted, both at the cellular level and in animal models. Furthermore, perspectives on the further development of this magnetic stimulation mode are commented on, with emphasis on scientific limitations and possible directions for exploitation. This article is categorized under: Diagnostic Tools > Biosensing Diagnostic Tools > In Vivo Nanodiagnostics and Imaging.

Association between vascular aging and cognitive function in Chinese adults.

BACKGROUND: Vascular health has been associated with cognition but related evidence is limited in Chinese. The objective of this study was to examine the association of vascular aging assessed by arterial stiffness and blood pressure with cognitive function in an unselected Chinese population. METHODS: In the Tianning Cohort (N = 5158), indicators of arterial stiffness and blood pressure including carotid-femoral pulse wave velocity (cfPWV), ankle-brachial index (ABI), pulse pressure (PP), systolic blood pressure (SBP), and diastolic blood pressure (DBP) were measured. Cognitive function was assessed using the Mini Mental State Examination (MMSE) questionnaire. We applied Poisson regression and logistic regression to examine the associations of vascular aging and blood pressure with cognitive function. RESULTS: 76 (1.47%) participants had impaired cognitive function diagnosed by a MMSE score of less than 24 points. Participants with a higher level of PP were more likely to have a decreased score of MMSE (ß=-0.0121, P < 0.001 for log-transformed pulse pressure) and a higher risk of having impaired cognitive function (OR = 5.95, 95%CI: 2.02-17.79, P < 0.001 for log-transformed PP). Per standard deviation increment in SBP was significantly associated with lower MMSE score (ß=-0.0020, P < 0.001) and impaired cognitive function (OR = 1.69, 95%CI: 1.38-2.06, P < 0.001). No significant associations were found regarding other parameters. CONCLUSIONS: Blood pressure and hypertension were associated with cognitive function in Chinese adults. PP may be a potential predictor for impaired cognitive function.

Predicting intraoperative major blood loss in microsurgery for brain arteriovenous malformations.

Objective: Intraoperative blood loss poses a great challenge for brain arteriovenous malformation (AVM) microsurgery, although systematic researches are still lacking. This study aimed to identify factors predicting intraoperative major blood loss in brain AVM microsurgery and to investigate its impact on patient outcome. To deal with the fierce bleeding, we introduced a modified hemostatic method, bone-wax (BW) coated bipolar electrocoagulation. Methods: The authors retrospectively analyzed the clinical data of 131 patients (50/81 in intraoperative major/non-major blood loss cohort) with brain AVMs who underwent microsurgery in our center during the period between January 2018 and April 2023. According to previous studies, major blood loss was defined as blood loss of at least 1,000 mL. The accuracy and objectivity of our grouping methodology were validated by comparing the hemoglobin mass loss, hematocrit loss and factors associated with intraoperative bleeding. Potential clinical and radiological predictors for intraoperative major blood loss were evaluated using a multivariate stepwise logistic regression. And outcomes of patients in the two cohorts were also compared. At last, the performance of BW coated bipolar electrocoagulation in brain AVM microsurgery was illustrated by the case presentation, histological staining and transmission electron microscopy of the coagulated nidus vessels. Results: Hemoglobin mass loss, hematocrit loss and factors associated with intraoperative bleeding were significant different between the two cohorts. five independent factors predicting intraoperative major blood loss were identified: (1) clinical manifestations; (2,3) location and size of the nidus; (4) deep venous drainage; and (5) the number of draining veins. And the intraoperative major blood loss can not only adversely affect the surgical progression, but also predict poor perioperative outcomes for patients. Regarding the application of BW coated bipolar electrocoagulation, we found the novel hemostatic method exerted efficient hemostatic effect and reduced the damage to the vascular structure in brain AVM microsurgery. Conclusion: This study proposed a nomogram for neurosurgeons to predict intraoperative major blood loss in brain AVM microsurgery preoperatively. And intraoperative major blood loss is associated with poor patient outcomes. In addition, BW coated bipolar electrocoagulation, can be applied to control ferocious bleeding during brain AVM microsurgery, which still remains further researches.

Absence of motor impairments or pathological changes in TMEM230 knockout rats.

Parkinson's disease (PD), which is the second most common neurodegenerative disorder, is characterized by progressive movement impairment and loss of midbrain dopaminergic neurons in the substantia nigra. Although mutations in TMEM230 are linked to familial PD, the pathogenic mechanism underlying TMEM230-associated PD remains to be elucidated. To explore the effect of TMEM230 depletion in vivo, we created TMEM230 knockout rats using CRISPR-Cas9 technology. TMEM230 knockout rats did not exhibit any core features of PD, including impaired motor function, loss of dopaminergic neurons in the substantia nigra, or altered expression of proteins related to autophagy, the Rab family, or vesicular trafficking. In addition, no glial reactions were observed in TMEM230 knockout rats. These results indicate that depletion of TMEM230 may not lead to dopaminergic neuron degeneration in rats, further supporting that PD-associated TMEM230 mutations lead to dopaminergic neuron death by gain-of-toxic function.

Photodynamic therapy with NIR-II probes: review on state-of-the-art tools and strategies.

In 2022 10% of the world's population was aged 65+, and by 2100 this segment is expected to hit 25%. These demographic changes place considerable pressure over healthcare systems worldwide, which results in an urgent need for accurate, inexpensive and non-invasive ways to treat cancers, a family of diseases correlated with age. Among the therapeutic tools that gained important attention in this context, photodynamic therapies (PDT), which use photosensitizers to produce cytotoxic substances for selectively destroying tumor cells and tissues under light irradiation, profile as important players for next-generation nanomedicine. However, the development of clinical applications is progressing at slow pace, due to still pending bottlenecks, such as the limited tissue penetration of the excitation light, and insufficient targeting performance of the therapeutic probes to fully avoid damage to normal cells and tissues. The penetration depth of long-wavelength near infrared (NIR) light is significantly higher than that of short-wavelength UV and visible light, and thus NIR light in the second window (NIR-II) is acknowledged as the preferred phototherapeutic means for eliminating deep-seated tumors, given the higher maximum permissible exposure, reduced phototoxicity and low autofluorescence, among others. Upon collective multidisciplinary efforts of experts in materials science, medicine and biology, multifunctional NIR-II inorganic or organic photosensitizers have been widely developed. This review overviews the current state-of-the art on NIR-II-activated photosensitizers and their applications for the treatment of deep tumors. We also place focus on recent efforts that combine NIR-II activated PDT with other complementary therapeutic routes such as photothermal therapy, chemotherapy, immunotherapy, starvation, and gas therapies. Finally, we discuss still pending challenges and problems of PDT and provide a series of perspectives that we find useful for further extending the state-of-the art on NIR-II-triggered PDT.

Effect of Phage Spray on Hatchability and Chick Quality of Eggs Contaminated with Salmonella Typhimurium.

Salmonella Typhimurium (S. Typhimurium) contamination poses a significant challenge to breeder egg hatchability and chick health, necessitating the exploration of alternative disinfection methods. This study investigates the potential of phage vB_SPuM_SP02 (SP02) as a novel disinfectant for breeder eggs contaminated with S. Typhimurium SM022. Phage SP02 was isolated from poultry farm effluent and characterized for morphology, biological properties, and genome properties. Experimental groups of specific pathogen-free (SPF) eggs were treated with Salmonella and phage SP02, and efficacy was assessed through hatching rates, chick survival, weight, Salmonella load, immune organ indices, and intestinal flora. Phage treatment effectively eradicated Salmonella contamination on eggshells within 12 h, resulting in increased hatching and survival rates compared to controls. Furthermore, phage treatment mitigated weight loss and tissue Salmonella load in chicks without causing immune organ damage while reducing Salmonella spp. abundance in the intestinal tract. This study demonstrates the potential of phage SP02 as an eco-friendly and efficient disinfectant for S. Typhimurium-contaminated breeder eggs, offering promising prospects for practical application in poultry production.

Improving Generalization and Personalization in Model-Heterogeneous Federated Learning.

Conventional federated learning (FL) assumes the homogeneity of models, necessitating clients to expose their model parameters to enhance the performance of the server model. However, this assumption cannot reflect real-world scenarios. Sharing models and parameters raises security concerns for users, and solely focusing on the server-side model neglects clients' personalization requirements, potentially impeding expected performance improvements of users. On the other hand, prioritizing personalization may compromise the generalization of the server model, thereby hindering extensive knowledge migration. To address these challenges, we put forth an important problem: How can FL ensure both generalization and personalization when clients' models are heterogeneous? In this work, we introduce FedTED, which leverages a twin-branch structure and data-free knowledge distillation (DFKD) to address the challenges posed by model heterogeneity and diverse objectives in FL. The employed techniques in FedTED yield significant improvements in both personalization and generalization, while effectively coordinating the updating process of clients' heterogeneous models and successfully reconstructing a satisfactory global model. Our empirical evaluation demonstrates that FedTED outperforms many representative algorithms, particularly in scenarios where clients' models are heterogeneous, achieving a remarkable 19.37% enhancement in generalization performance and up to 9.76% improvement in personalization performance.

Nonplanar structure accelerates reverse intersystem crossing of TADF emitters: nearly 40% EQE and relieved efficiency roll off.

Exploring strategies to enhance reverse intersystem crossing (RISC) is of great significance to develop efficient thermally activated delayed fluorescent (TADF) molecules. In this study, we investigate the substantial impact of nonplanar structure on improving the rate of RISC (k RISC). Three emitters based on spiroacridine donors are developed to evaluate this hypothesis. All molecules exhibit high photoluminescent quantum yields (PLQYs) of 96-98% due to their rigid donor and acceptor. Leveraging the synergistic effects of heavy element effect and nonplanar geometry, S2-TRZ exhibits an accelerated k RISC of 24.2 × 105 s-1 compared to the 11.1 × 105 s-1 of S1-TRZ, which solely incorporates heavy atoms. Additionally, O1-TRZ possesses a further lower k RISC of 9.42 × 105 s-1 because of the absence of these effects. Remarkably, owing to the high PLQYs and suitable TADF behaviors, devices based on these emitters exhibit state-of-the-art performance, including a maximum external quantum efficiency of up to 40.1% and maximum current efficiency of 124.7 cd A-1. More importantly, devices utilizing S2-TRZ as an emitter achieve a relieved efficiency roll-off of only 7% under 1000 cd m-2, in contrast to the 12% for O1-TRZ and 11% for S1-TRZ, respectively. These findings advance our fundamental understanding of TADF processes for high-performance electroluminescent devices.

Berbamine promotes ferroptosis of esophageal squamous cell carcinoma by facilitating USP51-mediated GPX4 ubiquitination and degradation.

Esophageal cancer ranks among the most prevalent malignant tumors globally. The prognosis for esophageal squamous cell carcinoma remains poor, with a 5-year survival rate below 20 % due to limited advances in therapy. Ferroptosis, a novel form of iron-dependent lipid peroxidation-driven regulated cell death (RCD), shows significant promise in cancer treatment. Berbamine (BBM), a natural bisbenzylisoquinoline alkaloid derived from Berberis amurensis, exhibits anti-tumor effects against various cancers, yet its impact on esophageal cancer remains to be elucidated. This study aimed to explore the role of BBM in inducing ferroptosis in the treatment of esophageal cancer, focusing on its molecular mechanisms. Gene set enrichment analysis(GSEA) analysis highlighted the potential of BBM as an anti-cancer agent through ferroptosis induction. We found that BBM inhibited growth and epithelial-mesenchymal transition (EMT) in esophageal cancer cell lines, promoting Fe accumulation, ROS, and malondialdehyde (MDA) production, thereby triggering cell death. These suppressive effects were successfully reversed by Ferrostatin-1 (Fer-1). Mechanistically, BBM decreased deubiquitination enzyme USP51 levels, leading to ubiquitin degradation and glutathione peroxidase 4(GPX4) instability, and it stimulated ferroptosis. The Overexpression of USP51 mitigated the downregulation of GPX4 induced by BBM.BBM significantly inhibited tumor xenograft growth in nude mice. This discovery positions BBM as a promising therapeutic candidate for the treatment of esophageal cancer.

Cross-Subject Seizure Detection via Unsupervised Domain-Adaptation.

Automatic seizure detection from Electroencephalography (EEG) is of great importance in aiding the diagnosis and treatment of epilepsy due to the advantages of convenience and economy. Existing seizure detection methods are usually patient-specific, the training and testing are carried out on the same patient, limiting their scalability to other patients. To address this issue, we propose a cross-subject seizure detection method via unsupervised domain adaptation. The proposed method aims to obtain seizure specific information through shallow and deep feature alignments. For shallow feature alignment, we use convolutional neural network (CNN) to extract seizure-related features. The distribution gap of the shallow features between different patients is minimized by multi-kernel maximum mean discrepancies (MK-MMD). For deep feature alignment, adversarial learning is utilized. The feature extractor tries to learn feature representations that try to confuse the domain classifier, making the extracted deep features more generalizable to new patients. The performance of our method is evaluated on the CHB-MIT and Siena databases in epoch-based experiments. Additionally, event-based experiments are also conducted on the CHB-MIT dataset. The results validate the feasibility of our method in diminishing the domain disparities among different patients.

Efficacy of a Combination Treatment of Ablative Fractional Carbon Dioxide Laser Therapy and Recombinant Human Epidermal Growth Factor for Atrophic Acne Scars.

BACKGROUND: Atrophic acne scars (AAS) are disfiguring and permanent changes caused by inflammatory acne. Fractional carbon dioxide is a common ablative device used to treat this condition. However, issues such as unclear effectiveness, frequent treatments, and potential side effects exist. In recent years, recombinant human epidermal growth factor (rhEGF) has also been frequently reported for its application in the treatment of acne scars. OBJECTIVE: To explore the potential synergistic effect of fractional carbon dioxide laser combined with rhEGF in AAS treatment. METHODS: We enrolled 15 patients with AAS. They received fractional carbon dioxide laser treatment and were then randomly assigned to receive either rhEGF or a placebo on one side of the face. The procedure was repeated three times, and the results were evaluated using the échelle d'évaluation clinique des cicatrices d'acné (ECCA) score and analyzed using the CBS camera system, 3D analysis (3DMD). Reflectance confocal microscopy (RCM) examination was also conducted. RESULTS: Both sides exhibited significant improvement in the appearance of the acne scars after treatment, as confirmed by the ECCA score, 3DMD data, and CBS texture score. On the rhEGF-treated side, the pore number and epidermal pigment area significantly improved as compared to the control side, whereas no significant differences were observed in the other data. Under RCM, a significant increase in epidermal thickness and appearance of reticular collagen fibers in the dermal layer after treatment was observed. CONCLUSION: Compared to the sole use of laser, the combination of fractional carbon dioxide laser and rhEGF does not significantly enhance scar therapeutic effects. However, it does shorten the recovery period after laser treatment and improves the pore appearance.

Upgraded cellulose and xylan digestions for synergistic enhancements of biomass enzymatic saccharification and bioethanol conversion using engineered Trichoderma reesei strains overproducing mushroom LeGH7 enzyme.

Crop straws provide enormous lignocellulose resources transformable for sustainable biofuels and valuable bioproducts. However, lignocellulose recalcitrance basically restricts essential biomass enzymatic saccharification at large scale. In this study, the mushroom-derived cellobiohydrolase (LeGH7) was introduced into Trichoderma reesei (Rut-C30) to generate two desirable strains, namely GH7-5 and GH7-6. Compared to the Rut-C30 strain, both engineered strains exhibited significantly enhanced enzymatic activities, with ß-glucosidases, endocellulases, cellobiohydrolases, and xylanase activities increasing by 113 %, 140 %, 241 %, and 196 %, respectively. By performing steam explosion and mild alkali pretreatments with mature straws of five bioenergy crops, diverse lignocellulose substrates were effectively digested by the crude enzymes secreted from the engineered strains, leading to the high-yield hexoses released for bioethanol production. Notably, the LeGH7 enzyme purified from engineered strain enabled to act as multiple cellulases and xylanase at higher activities, interpreting how synergistic enhancement of enzymatic saccharification was achieved for distinct lignocellulose substrates in major bioenergy crops. Therefore, this study has identified a novel enzyme that is active for simultaneous hydrolyses of cellulose and xylan, providing an applicable strategy for high biomass enzymatic saccharification and bioethanol conversion in bioenergy crops.