First report on liquid crystal monomers in tree barks surrounding a display manufacturer: Insights for atmospheric transport and establishment of priority list.

Tree bark has been proven as an effective passive air sampler, particularly where access to active sampling methods is limited. In this study, 60 target liquid crystal monomers (LCMs; comprising 10 cyanobiphenyl and analogs (CBAs), 13 biphenyl and analogs (BAs), and 37 fluorinated biphenyl and analogs (FBAs)) were analyzed in 34 tree barks collected from the vicinity of a liquid crystal display (LCD) manufacturer situated in the Pearl River Delta, South China. The concentrations of LCMs in tree barks ranged from 1400 to 16000 ng/g lipid weight, with an average of 5900 ng/g lipid weight. Generally, bark levels of BAs exponentially decreased within 5 km of the LCD manufacturer. The profiles of LCMs in tree barks are similar to previously reported patterns in gaseous phase, suggesting bark's efficacy as a sampler for gaseous LCMs. The inclusion of different congeners in existing studies on the environmental occurrence of LCMs has hindered the horizontal comparisons. Therefore, this study established a list of priority LCMs based on environmental monitoring data and the publicly accessible production data. This list comprised 146 LCMs, including 63 REACH registered LCMs that haven't been analyzed in any study and 56 belonging to 4 types of mainstream LCMs.

solid volume ratio in predicting pathological features of cT1 lung adenocarcinoma.

BACKGROUND: More effective methods are urgently needed for predicting the pathological grade and lymph node metastasis of cT1-stage lung adenocarcinoma. METHODS: We analyzed the relationships between CT quantitative parameters (including three-dimensional parameters) and pathological grade and lymph node metastasis in cT1-stage lung adenocarcinoma patients of our center between January 2015 and December 2023. RESULTS: A total of 343 patients were included, of which there were 233 males and 110 females, aged 61.8 ± 9.4 (30-82) years. The area under the receiver operating characteristic (ROC) curve for predicting the pathological grade of lung adenocarcinoma using the consolidation tumor ratio (CTR) and the solid volume ratio (SVR) were 0.761 and 0.777, respectively. The areas under the ROC curves (AUCs) for predicting lymph node metastasis were 0.804 and 0.873, respectively. Multivariate logistic regression analysis suggested that the SVR is an independent predictor of highly malignant lung adenocarcinoma pathology, while the SVR and pathological grade are independent predictors of lymph node metastasis. The sensitivity of predicting the pathological grading of lung adenocarcinoma based on SVR>5% is 97.2%, with a negative predictive value of 96%. The sensitivity of predicting lymph node metastasis based on SVR>47.1% is 97.3%, and the negative predictive value is 99.5%. CONCLUSIONS: The SVR has greater diagnostic value than the CTR in the preoperative prediction of pathologic grade and lymph node metastasis in stage cT1-stage lung adenocarcinoma patients, and the SVR may replace the diameter and CTR as better criteria for guiding surgical implementation.

Synergistic Effects of Glutamine Deprivation and Metformin in Acute Myeloid Leukemia.

OBJECTIVE: The metabolic reprogramming of acute myeloid leukemia (AML) cells is a compensatory adaptation to meet energy requirements for rapid proliferation. This study aimed to examine the synergistic effects of glutamine deprivation and metformin exposure on AML cells. METHODS: SKM-1 cells (an AML cell line) were subjected to glutamine deprivation and/or treatment with metformin or bis-2-(5-phenylacetamido-1,2,4-thiadiazol-2-yl) ethyl sulfide (BPTES, a glutaminase inhibitor) or cytarabine. Cell viability was detected by Cell Counting Kit-8 (CCK-8) assay, and cell apoptosis and reactive oxygen species (ROS) by flow cytometry. Western blotting was conducted to examine the levels of apoptotic proteins, including cleaved caspase-3 and poly(ADP-ribose) polymerase (PARP). Moreover, the human long noncoding RNA (lncRNA) microarray was used to analyze gene expression after glutamine deprivation, and results were confirmed with quantitative RT-PCR (qRT-PCR). The expression of metallothionein 2A (MT2A) was suppressed using siRNA. Cell growth and apoptosis were further detected by CCK-8 assay and flow cytometry, respectively, in cells with MT2A knockdown. RESULTS: Glutamine deprivation or treatment with BPTES inhibited cell growth and induced apoptosis in SKM-1 cells. The lncRNA microarray result showed that the expression of MT family genes was significantly upregulated after glutamine deprivation. MT2A knockdown increased apoptosis, while proliferation was not affected in SKM-1 cells. In addition, metformin inhibited cell growth and induced apoptosis in SKM-1 cells. Both glutamine deprivation and metformin enhanced the sensitivity of SKM-1 cells to cytarabine. Furthermore, the combination of glutamine deprivation with metformin exhibited synergistic antileukemia effects on SKM-1 cells. CONCLUSION: Targeting glutamine metabolism in combination with metformin is a promising new therapeutic strategy for AML.

Sigmoid function model of parallel-connected DC-DC converters and analysis of their dynamic characteristics.

Because of the manufacturing variations of circuit elements and the effects of parasitic parameters, the switching elements of parallel-connected modules cannot be synchronously switched. Consequently, the characteristics of these converters, which are multi-mode, high-order systems, cannot be comprehensively described using reduced-order models based on the symmetry of circuit topology and parameters. It is also difficult to fully describe the characteristics of these systems using discrete mapping models and averaged models. Therefore, we developed a smooth, sigmoid function-based continuous-time model for systems comprising parallel-connected buck converters with average current-sharing control. The proposed model provides a unified description of the continuous and discontinuous conduction modes of the system. The criteria for ensuring the stability of the system were derived based on the Floquet theory. The nonlinear dynamic behavior of the system and the effects of the key parameters on the stability of the system were investigated. The results showed that the system may undergo period doubling bifurcation, border collision bifurcation, and Neimark-Sacker bifurcation as the system parameters varied. The theoretical analysis and simulation results were verified experimentally. Our results provide a basis for the configuration of controller parameters.

Iron-Based Catalysts Derived from Iron-Containing Sludge for Enhanced Catalytic Performance of H2S Selective Catalytic Oxidation.

In this work, iron-containing sludge is used to prepare iron-based catalysts for efficient H2S selective catalytic oxidation. First, the effect of calcination temperatures on the catalytic activities of H2S selective oxidation is carried out and it can be found that S-500 calcined at 500 °C performs excellent catalytic activity. Then, the catalytic performance of the S-500 catalyst is further optimized using alkaline treatment with different concentrations of NaOH solution. The results indicate that S-500(2.0) treated with 2 M NaOH solution has the highest catalytic activity of H2S selective oxidation. Next, various characterization methods are used to analyze the structure and physical-chemical of the sludge-based catalysts. N2-Brunauer-Emmett-Teller (N2-BET) and X-ray photoelectron spectroscopy analyses show that the S-500(2.0) catalyst has the smallest average particle (11.17 nm), the biggest ratio of S ext/S micro(17.98) with bigger external specific surface area (49.09 m2·g-1), a higher proportion of Fe3+ species (50.88%), and surface adsorbed oxygen species (48.07%). Meanwhile, O2-TPD and CO2-TPD analysis indicates that the S-500(2.0) catalyst has a bigger value of the Oads/OTotal ratio (50.56%) and (CO2)(weak+moderate) /(CO2)Total ratio of (31.41%), indicating that there are much more oxygen vacancies and weak alkaline sites. As a result, the excellent catalytic performance of H2S selective oxidation can be attributed to its outstanding physical-chemical properties.

Operative Mortality After Type A Aortic Dissection Surgery: Differences Based on Sex and Age.

Background: There is controversy regarding sex differences in short-term mortality in acute type A aortic dissection (ATAAD). Objectives: This study aimed to investigate the impact of sex differences on 30-day operative mortality after ATAAD surgery and to determine if other covariates modify the association. Methods: Consecutive patients (N = 5670) with surgically repaired ATAAD were identified from the multicenter China 5A study. The primary outcome was operative mortality. The age dependency was modeled using a cubic spline curve. Results: There were 1,503 females (26.5%) and 4,167 males (73.5%). Females were older and had a lower percentage of comorbidities compared with males. Females had higher mortality compared to males (10.2% vs 8.2%, P = 0.019); however, there was no difference after propensity analyses (adjusted OR: 1.334 [95% CI: 0.918-1.938]). There was an interaction with sex and age (P interaction = 0.035): older age was associated with higher odds of operative mortality among females (OR: 1.045 [95% CI: 1.029-1.061]) compared with males (OR: 1.025 [95% CI: 1.016-1.035]). The risk of mortality for males and females appears to diverge at 55 years of age (P interaction = 0.019): females under 55 years of age had similar odds to males (OR: 0.852 [95% CI: 0.603-1.205]) but higher odds when over 55 years (OR: 1.420 [95% CI: 1.096-1.839]) compared to males. Conclusions: Under the age of 55 years, females have similar odds of operative mortality compared with males; however, over the age of 55 years females have higher odds than males. Understanding differences in risk allows for individualized treatment strategies. (Additive Anti-inflammatory Action for Aortopathy & Arteriopathy; NCT04398992).

Quantitative assessment and correlational analysis of subjective and objective indicators in patients with allergic rhinitis.

Background: The diagnosis of allergic rhinitis is mainly based on the typical medical history, clinical manifestations, and corresponding allergen test results of the patients. However, there are often clinical inconsistencies among the 3. Objective: To study the clinical characteristics of patients with allergic rhinitis from both subjective and objective aspects to determine the correlations between the quantitative assessment outcomes of subjective and objective indicators. Methods: A total of 111 patients with allergic rhinitis who visited our outpatient clinic from June 2022 to December 2022 were selected. The 22-item sino-nasal outcome test (SNOT-22) and the visual analog scale (VAS) for the severity of the disease were used to score the subjective indicators of allergic rhinitis. The objective indicators of allergic rhinitis were evaluated by serum inhalant allergens immunoglobulin E test, nasal endoscopy modified Lund-Kennedy (MLK) scoring method, and acoustic rhinometry. Results: SNOT-22 score, total VAS score for symptoms, and the VAS score for nasal itching were positively correlated with the number of positive allergens (r = 0.266, P = 0.005, r = 0.576, P < 0.001, and r = 0.271, P = 0.004, respectively). No differences were found in all subjective indicators scores between the total immunoglobulin E positive and negative groups (P > 0.05). SNOT-22 score, total VAS score for symptoms, and the VAS score for nasal congestion were positively correlated with MLK total score of nasal endoscopy (r = 0.343, P < 0.001, r = 0.438, P < 0.001, and r = 0.225, P = 0.018, respectively). Parameters of acoustic rhinometry were not correlated with the subjective indicators scores of allergic rhinitis (P > 0.05). Conclusion: A multifaceted quantitative assessment of allergic rhinitis using a combination of subjective and objective methods can help physicians make an accurate diagnosis and create reasonable treatment plans.

Nitrate reduction to nitrogen in wastewater using mesoporous carbon encapsulated Pd-Cu nanoparticles combined with in-situ electrochemical hydrogen evolution.

The conversion of NO3--N to N2 is of great significance for zero discharge of industrial wastewater. Pd-Cu hydrogenation catalysis has high application prospects for the reduction of NO3--N to N2, but the existing form of Pd-Cu, the Pd-Cu mass ratio and the H2 evolution rate can affect the coverage of active hydrogen (*H) on the surface of Pd, thereby affecting N2 selectivity. In this work, mesoporous carbon (MC) is used as support to disperse Pd-Cu catalyst and is applied in an in-situ electrocatalytic H2 evolution system for NO3--N removal. The Pd-Cu particles with the average size of 6 nm are uniformly encapsulated in the mesopores of MC. Electrochemical in-situ H2 evolution can not only reduce the amount of H2 used, but the H2 bubbles can also be efficiently dispersed when PPy coated nickel foam (PPy/NF) is used as cathode. Moreover, the mesoporous structure of MC can further split H2 bubbles, reducing the coverage of *H on Pd. The highest 77% N2 selectivity and a relatively faster NO3--N removal rate constant (0.10362 min-1) can be achieved under the optimal conditions, which is superior to most reported Pd-Cu catalytic systems. The prepared catalyst is further applied to the denitrification of actual deplating wastewater. NO3--N with the initial concentration of 650 mg L-1 can be completely removed after 180 min of treatment, and the TN removal can be maintained at 72%.

Cardiorespiratory fitness attenuates the association between fatness and cardiometabolic risk in Chinese children.

Background: Childhood obesity tends to persist into adulthood, predisposing individuals to cardiometabolic risk (CMR). This study aims to investigate the mediating role of cardiorespiratory fitness (CRF) in the associations between multiple fatness indicators and individual CMR markers and clustered CMR-score, and explore sex differences. Methods: We recruited 1,557 children (age: 8 to 10, male/female: 52.7%/47.3%) in September 2022 in Ningbo, China. Physical examinations, overnight fasting blood test, and CRF was evaluated. The CMR-score was calculated by summing age- and sex-specific z scores of four CMR markers, including mean arterial blood pressure, triglycerides, the total cholesterol to high-density lipoprotein cholesterol ratio, and homeostatic model assessment for insulin resistance. Generalized linear mixed models were used to identify the associations, mediation analyses were performed to dissect the function of CRF. Results: Partial correlation analyses revealed positive associations between high fatness indicators (including body mass index [BMI], BMI z score, body fat mass index [BFMI] and waist-to-height ratio [WHtR]) and increased CMR markers, whereas high CRF was associated with decreased CMR markers (all P < 0.05). In the mediation analyses, CRF emerged as a partial mediator, attenuating the relationship between four fatness indicators and CMR-score. Specifically, CRF mediated 6.5%, 7.7%, 5.3%, and 12.5% of the association between BMI, BMI z score, BFMI, WHtR and CMR-score (all P < 0.001). And the mediating effects of CRF between WHtR and four individual CMR markers was particularly robust, ranging from 10.4% to 21.1% (all P < 0.05). What's more, CRF mediates the associations between WHtR and CMR-score more pronounced in girls than boys with a mediation effect size of 17.3% (P < 0.001). Conclusion: In Chinese children, CRF partially mitigates the adverse effects of fatness on CMR, underscoring the significance of enhancing CRF in children.

Constructing High-Performance Cobalt-Based Environmental Catalysts from Spent Lithium-Ion Batteries: Unveiling Overlooked Roles of Copper and Aluminum from Current Collectors.

Converting spent lithium-ion batteries (LIBs) cathode materials into environmental catalysts has drawn more and more attention. Herein, we fabricated a Co3O4-based catalyst from spent LiCoO2 LIBs (Co3O4-LIBs) and found that the role of Al and Cu from current collectors on its performance is nonnegligible. The density functional theory calculations confirmed that the doping of Al and/or Cu upshifts the d-band center of Co. A Fenton-like reaction based on peroxymonosulfate (PMS) activation was adopted to evaluate its activity. Interestingly, Al doping strengthened chemisorption for PMS (from -2.615 eV to -2.623 eV) and shortened Co-O bond length (from 2.540 Što 2.344 Å) between them, whereas Cu doping reduced interfacial charge-transfer resistance (from 28.347 kΩ to 6.689 kΩ) excepting for the enhancement of the above characteristics. As expected, the degradation activity toward bisphenol A of Co3O4-LIBs (0.523 min-1) was superior to that of Co3O4 prepared from commercial CoC2O4 (0.287 min-1). Simultaneously, the reasons for improved activity were further verified by comparing activity with catalysts doped Al and/or Cu into Co3O4. This work reveals the role of elements from current collectors on the performance of functional materials from spent LIBs, which is beneficial to the sustainable utilization of spent LIBs.

Ginsenoside Rg3 attenuates neuroinflammation and hippocampal neuronal damage after traumatic brain injury in mice by inactivating the NF-kB pathway via SIRT1 activation.

This investigation examined the potential of ginsenoside Rg3 in addressing traumatic brain injury (TBI). A TBI mouse model underwent treatment with ginsenoside Rg3 and nicotinamide (NAM). Neurological and motor functions were assessed using modified neurological severity score and rotarod tests. Brain water content in mice was detected. Primary mouse microglia were exposed to lipopolysaccharide (LPS), ginsenoside Rg3, and NAM. Nissl and immunofluorescence staining were utilized to investigate hippocampal damage, and localization of P65, Iba1 and INOS in microglia. Hippocampal neurons were grown in a culture medium derived from microglia. CCK-8 and TUNEL assays were employed to evaluate the viability and apoptosis of hippocampal neurons. Proinflammatory factors and proteins were tested using ELISA, western blot and immunofluorescence staining. As a result, ginsenoside Rg3 enhanced neurological and motor functions in mice post-TBI, reduced brain water content, alleviated hippocampal neuronal neuroinflammation and damage, activated SIRT1, and deactivated the NF-kB pathway. In LPS-stimulated microglia, ginsenoside Rg3 diminished inflammation, activated SIRT1, deactivated the NF-kB pathway, and facilitated nuclear localization of P65 and co-localization of Iba1 and INOS. The effects of ginsenoside Rg3 were countered by NAM in both TBI mice and LPS-stimulated microglia. Hippocampal neurons cultured in a medium containing LPS, ginsenoside Rg3, and NAM-treated microglia showed improved viability and reduced apoptosis compared to those cultured in a medium with LPS and ginsenoside Rg3-treated microglia alone. Ginsenoside Rg3 was effective in reducing neuroinflammation and damage in hippocampal neurons following TBI by modulating the SIRT1/NF-kB pathway, suggesting its potential as a therapeutic agent for TBI.

P. gingivalis in oral-prostate axis exacerbates benign prostatic hyperplasia via IL-6/IL-6R pathway.

BACKGROUND: Benign prostatic hyperplasia (BPH) is the most common disease in elderly men. There is increasing evidence that periodontitis increases the risk of BPH, but the specific mechanism remains unclear. This study aimed to explore the role and mechanism of the key periodontal pathogen Porphyromonas gingivalis (P. gingivalis) in the development of BPH. METHODS: The subgingival plaque (Sp) and prostatic fluid (Pf) of patients with BPH concurrent periodontitis were extracted and cultured for 16S rDNA sequencing. Ligature-induced periodontitis, testosterone-induced BPH and the composite models in rats were established. The P. gingivalis and its toxic factor P. gingivalis lipopolysaccharide (P.g-LPS) were injected into the ventral lobe of prostate in rats to simulate its colonization of prostate. P.g-LPS was used to construct the prostate cell infection model for mechanism exploration. RESULTS: P. gingivalis, Streptococcus oralis, Capnocytophaga ochracea and other oral pathogens were simultaneously detected in the Pf and Sp of patients with BPH concurrent periodontitis, and the average relative abundance of P. gingivalis was found to be the highest. P. gingivalis was detected in both Pf and Sp in 62.5% of patients. Simultaneous periodontitis and BPH synergistically aggravated prostate histological changes. P. gingivalis and P.g-LPS infection could induce obvious hyperplasia of the prostate epithelium and stroma (epithelial thickness was 2.97- and 3.08-fold that of control group, respectively), and increase of collagen fibrosis (3.81- and 5.02-fold that of control group, respectively). P. gingivalis infection promoted prostate cell proliferation, inhibited apoptosis, and upregulated the expression of inflammatory cytokines interleukin-6 (IL-6; 4.47-fold), interleukin-6 receptor-α (IL-6Rα; 5.74-fold) and glycoprotein 130 (gp130; 4.47-fold) in prostatic tissue. P.g-LPS could significantly inhibit cell apoptosis, promote mitosis and proliferation of cells. P.g-LPS activates the Akt pathway through IL-6/IL-6Rα/gp130 complex, which destroys the imbalance between proliferation and apoptosis of prostate cells, induces BPH. CONCLUSION: P. gingivalis was abundant in the Pf of patients with BPH concurrent periodontitis. P. gingivalis infection can promote BPH, which may affect the progression of BPH via inflammation and the Akt signaling pathway.

Selective removal of thiosulfate from coke oven gas desulfurization wastewater by catalytic wet air oxidation with manganese-based oxide from spent ternary lithium-ion batteries.

Selective and efficient removal of thiosulfates (S2O32-) to recover high-purity and value-added thiocyanate products by fractional crystallization process is a promising route for the resource treatment of coke oven gas desulfurization wastewater. Herein, catalytic wet air oxidation (CWAO), with manganese-based oxide synthesized from spent ternary lithium-ion batteries (MnOx-LIBs), was proposed to selectively remove S2O32- from desulfurization wastewater. 98.0 % of S2O32- is selectively removed by the MnOx-LIBs CWAO system, which was 4.1 times that of the MnOx CWAO system. The synergistic effect among multiple metals from spent LIBs induces the enlarged specific surface area, increased reactive sites and formation of oxygen vacancy, promoting the adsorption and activation of O2, thereby realizing high-efficiency removal of S2O32-. The satisfactory selective removal efficiency can be maintained in the proposed system under complex environmental conditions. Notably, the proposed system is cost-effective and applicable to actual wastewater, in which 81.2 % of S2O32- is selectively removed from coke oven gas desulfurization wastewater. More importantly, compared with the typical processes, the proposed process is simpler and more environmentally-friendly. This work provides an alternative route to selectively remove S2O32- from coke oven gas desulfurization wastewater, expecting to drive the development of resource utilization of coke oven gas desulfurization wastewater.

Danggui Sini decoction alleviates oxaliplatin-induced peripheral neuropathy by regulating gut microbiota and potentially relieving neuroinflammation related metabolic disorder.

BACKGROUND: Danggui Sini decoction (DSD), a traditional Chinese medicine formula, has the function of nourishing blood, warming meridians, and unblocking collaterals. Our clinical and animal studies had shown that DSD can effectively protect against oxaliplatin (OXA)-induced peripheral neuropathy (OIPN), but the detailed mechanisms remain uncertain. Multiple studies have confirmed that gut microbiota plays a crucial role in the development of OIPN. In this study, the potential mechanism of protective effect of DSD against OIPN by regulating gut microbiota was investigated. METHODS: The neuroprotective effects of DSD against OIPN were examined on a rat model of OIPN by determining mechanical allodynia, biological features of dorsal root ganglia (DRG) as well as proinflammatory indicators. Gut microbiota dysbiosis was characterized using 16S rDNA gene sequencing and metabolism disorders were evaluated using untargeted and targeted metabolomics. Moreover the gut microbiota mediated mechanisms were validated by antibiotic intervention and fecal microbiota transplantation. RESULTS: DSD treatment significantly alleviated OIPN symptoms by relieving mechanical allodynia, preserving DRG integrity and reducing proinflammatory indicators lipopolysaccharide (LPS), IL-6 and TNF-α. Besides, DSD restored OXA induced intestinal barrier disruption, gut microbiota dysbiosis as well as systemic metabolic disorders. Correlation analysis revealed that DSD increased bacterial genera such as Faecalibaculum, Allobaculum, Dubosiella and Rhodospirillales_unclassified were closely associated with neuroinflammation related metabolites, including positively with short-chain fatty acids (SCFAs) and sphingomyelin (d18:1/16:0), and negatively with pi-methylimidazoleacetic acid, L-glutamine and homovanillic acid. Meanwhile, antibiotic intervention apparently relieved OIPN symptoms. Furthermore, fecal microbiota transplantation further confirmed the mediated effects of gut microbiota. CONCLUSION: DSD alleviates OIPN by regulating gut microbiota and potentially relieving neuroinflammation related metabolic disorder.

Reclaiming Agriceuticals from Sweetpotato (Ipomoea batatas [L.] Lam.) By-Products.

Sweetpotato (SP, Ipomoea batatas [L.] Lam.) is a globally significant food crop known for its high nutritional and functional values. Although the contents and compositions of bioactive constituents vary among SP varieties, sweetpotato by-products (SPBs), including aerial parts, storage root peels, and wastes generated from starch processing, are considered as excellent sources of polyphenols (e.g., chlorogenic acid, caffeoylquinic acid, and dicaffeoylquinic acid), lutein, functional carbohydrates (e.g., pectin, polysaccharides, and resin glycosides) or proteins (e.g., polyphenol oxidase, ß-amylase, and sporamins). This review summarises the health benefits of these ingredients specifically derived from SPBs in vitro and/or in vivo, such as anti-obesity, anti-cancer, antioxidant, cardioprotective, and anti-diabetic, evidencing their potential to regenerate value-added bio-products in the fields of food and nutraceutical. Accordingly, conventional and novel technologies have been developed and sometimes combined for the pretreatment and extraction processes aimed at optimising the recovery efficiency of bioactive ingredients from SPBs while ensuring sustainability. However, so far, advanced extraction technologies have not been extensively applied for recovering bioactive compounds from SPBs except for SP leaves. Furthermore, the incorporation of reclaimed bioactive ingredients from SPBs into foods or other healthcare products remains limited. This review also briefly discusses current challenges faced by the SPB recycling industry while suggesting that more efforts should be made to facilitate the transition from scientific advances to commercialisation for reutilising and valorising SPBs.

Celastrol Elicits Antitumor Effects through Inducing Immunogenic Cell Death and Downregulating PD-L1 in ccRCC.

BACKGROUND: Targeting immunogenic cell death (ICD) is considered a promising therapeutic strategy for cancer. However, the commonly identified ICD inducers promote the expression of programmed cell death ligand 1 (PD-L1) in tumor cells, thus aiding them to evade the recognition and killing by the immune system. Therefore, the finding of novel ICD inducers to avoid enhanced PD-L1 expression is of vital significance for cancer therapy. Celastrol (CeT), a triterpene isolated from Tripterygium wilfordii Hook. F induces various forms of cell death to exert anti-cancer effects, which may make celastrol an attractive candidate as an inducer of ICD. METHODS: In the present study, bioinformatics analysis was combined with experimental validation to explore the underlying mechanism by which CeT induces ICD and regulates PD-L1 expression in clear cell renal cell carcinoma (ccRCC). RESULTS: The results showed that EGFR, IKBKB, PRKCQ and MAPK1 were the crucial targets for CeT-induced ICD, and only MAPK1 was an independent prognostic factor for the overall survival (OS) of ccRCC patients. In addition, CeT triggered autophagy and up-regulated the expressions of HMGB1 and CRT to induce ICD in 786-O cells in vitro. Importantly, CeT can down-regulate PD-L1 expression through activating autophagy. At the molecular level, CeT suppressed PD-L1 via the inhibition of MAPK1 expression. Immunologically, the core target of celastrol, MAPK1, was tightly correlated with CD8+ T cells and CD4+ T cells in ccRCC. CONCLUSION: These findings indicate that CeT not only induces ICD but also suppresses PD-L1 by down-regulating MAPK1 expression, which will provide an attractive strategy for ccRCC immunotherapy.

Lifestyle intervention in children with obesity and nonalcoholic fatty liver disease (NAFLD): study protocol for a randomized controlled trial in Ningbo city (the SCIENT study).

BACKGROUND: The increasing prevalence of childhood obesity has become an urgent public health problem, evidence showed that intervention for childhood obesity bring enormous health benefits. However, an effective individualized intervention strategy remains to be developed, and the accompanying remission of related complications, such as nonalcoholic fatty liver disease (NAFLD), needs to be assessed. This study aimed to develop an m-Health-assisted lifestyle intervention program targeting overweight/obese children and assess its effectiveness on indicators of adiposity and NAFLD. METHODS: This is a cluster-randomized controlled trial that conducted in children with overweight/obesity in Ningbo city, Zhejiang Province, China. Students in Grade 3 (8-10 years old) were recruited from six primary schools, with three be randomized to intervention group and three to usual practice group. The intervention program will last for one academic year and consists of health education, dietary guidance, and physical activity reinforcement. This program is characterized by encouraging four stakeholders, including School, Clinic, famIly, and studENT (SCIENT), to participate in controlling childhood obesity, assisted by m-Health technology. Assessments will be conducted at baseline and 3 months, 9 months, 24 months, and 36 months after baseline. The primary outcome will be the differences between the two groups in students' body mass index and fatty liver index at the end of the intervention (9 months after baseline). During the implementation process, quality control methods will be adopted. DISCUSSION: The program will test the effectiveness of the m-Health-assisted lifestyle intervention on children with obesity and NAFLD. The results of this study will provide evidence for establishing effective lifestyle intervention strategy aimed at childhood obesity and NAFLD and may help develop guidelines for the treatment of obesity and NAFLD in Chinese children. TRIAL REGISTRATION: Clinicaltrials.gov NCT05482191. Registered on July 2022.

Mobile-based ecological momentary assessment and intervention: bibliometric analysis.

Objective: The aim of this article was to review existing documents in the field of mobile-based EMA and EMI, provide an overview of current hot topics, and predict future development trends. Methods: We conducted a bibliometric study on mobile-based EMA and EMI publications that were collected from the Web of Science Core Collection database. Biblioshiny and CiteSpace were utilized to analyze scientific productions, leading sources, authors, affiliations, documents, research hot topics, keywords, and trend topics. Results: A total of 2222 documents related to EMA and EMI published between 1992 and 2023 were retrieved. In recent years, scholarly publications have generally increased in mobile-based EMA and EMI research, particularly in the last decade. JMIR mHealth and uHealth (n=86), as well as JMIR (n=73), showed the highest number of publications. The United States (n=1038), Germany (n=218) and Netherlands (n=175) were leading countries. Regarding keyword co-occurrence and trend topics analysis, mental health, health behaviors, and feasibility were hot topics in mobile-based EMA and EMI research. Future research trends included using EMA for tailoring EMI, just-in-time adaptive interventions (JITAI), and digital phenotyping. Conclusion: This bibliometric study on mobile-based EMA and EMI is a valuable resource for understanding the field's evolution and future trends. Our analysis indicates that EMA and EMI have great potential in health behaviors and mental health, but implementation should consider feasibility and reactivity issues carefully. Emerging trends include EMA-tailored EMI, JITAI, and digital phenotyping. In the future, strengthening multidisciplinary cooperation will be necessary to promote the continued development of the field.

A single-centre, real-world study of BTK inhibitors for the initial treatment of MYD88mut /CD79Bmut diffuse large B-cell lymphoma.

BACKGROUND: MCD (MYD88L265P /CD79Bmut ) diffuse large B-cell lymphoma has a poor prognosis. There is no published clinical research conclusion regarding zanubrutinib or orelabrutinib for the initial treatment of MCD DLBCL. AIMS: This study aimed to analyse the efficacy and safety of Bruton's tyrosine kinase inhibitor (BTKi) (zanubrutinib or orelabrutinib) therapy for newly diagnosed DLBCL patients with MYD88mut and/or CD79Bmut . MATERIALS AND METHODS: Twenty-three newly diagnosed DLBCL patients with MYD88mut and/or CD79Bmut from June 2020 to June 2022 received BTKi combined with rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) or rituximab + lenalidomide (R2 ). A control group of 17 patients with MYD88mut and/or CD79Bmut DLBCL who received the standard R-CHOP therapy was also assessed. We retrospectively analysed clinical characteristics, safety, overall response rate (ORR), complete response (CR) rate and progression-free survival (PFS) of the two groups. RESULTS: The main clinical features were a high International Prognostic Index (IPI) score (≥3, 22/40, 55%) and a high rate of extranodal involvement (27/40,67.5%). Among the 23 DLBCL patients, 18 received BTKi + R-CHOP, and five elderly DLBCL patients were treated with BTKi + R2 . Compared with those in the control group (ORR 70.6%, CRR 52.9%, 1-year PFS rate 41.2%), improved ORR, CRR and PFS results were observed in the BTKi + R-CHOP group (100%, 94.4% and 88.9%, p = 0.019, 0.007, and 0.0001). In subgroup analyses based on genetic subtypes, cell origin, dual expression or IPI score, patients in the BTKi + R-CHOP group had better PFS than patients in the control group. In the BTKi + R-CHOP group, no significant difference was found in ORR, CRR and PFS based on subtype analysis, while BTKi-type subgroups exhibited statistically significant differences in 1-year PFS (p = 0.028). There were no significant differences in grade 3-4 haematological toxicity (p = 1) and grade 3-4 non-haematological toxicity (p = 0.49) between the BTKi + R-CHOP and R-CHOP treatment groups. In the BTKi + R2 group, the ORR was 100%, the CRR was 80%, and the 1-year PFS rate was 80%. The incidences of grade 3-4 haematologic toxicity and non-haematological toxicity were both 40%. No bleeding or cardiovascular events of grade 3 or higher occurred in any patients. DISCUSSION: The efficacy of BTKi combined with R-CHOP was similar to previous reports, which was significantly better than R-CHOP alone. It is necessary to fully consider that 14 patients in the BTKi + R-CHOP group received a BTKi as maintenance therapy when evaluating efficacy. Meanwhile, the addition of a BTKi may improve the prognosis of non-GCB, DEL or high-IPI-score DLBCL patients with MYD88mut and/or CD79Bmut . In our study, five elderly DLBCL patients with MYD88mut and/or CD79Bmut were achieved better ORR, CRR, PFS than the historical data of R-miniCHOP treatment and Ibrutinib + R2 treatment. However, the efficacy and benefit of BTKis for this type of DLBCL need to be further analysed using a larger sample size. CONCLUSION: This study suggests that newly diagnosed DLBCL patients with MYD88mut and/or CD79Bmut may benefit from BTKis according to real-world clinical data.