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Amorphous oxide semiconductors (AOS) are pivotal for next-generation electronics due to their high electron mobility and excellent optical properties. However, In 2 O 3 , a key material in this family, encounters significant challenges in balancing high mobility and effective switching as its thickness is scaled down to nanometer dimensions. The high electron density in ultra-thin In 2 O 3 hinders its ability to turn off effectively, leading to a critical trade-off between mobility and the on-current (I on )/off-current (I off ) ratio. This study introduces a mild CF 4 plasma doping technique that effectively reduces electron density in 10 nm In 2 O 3 at a low processing temperature of 70 °C, achieving a high mobility of 104 cm 2 V⁻¹ s⁻¹ and an I on /I off ratio exceeding 10⁸. A subsequent low-temperature post-annealing further improves the critical reliability and stability of CF 4 -doped In 2 O 3 without raising the thermal budget, making this technique suitable for monolithic three-dimensional (3D) integration. Additionally, its application is demonstrated in In 2 O 3 depletion-load inverters, highlighting its potential for advanced logic circuits and broader electronic and optoelectronic applications., (© 2024 Wiley‐VCH GmbH.)

Background: Proton pencil beam scanning (PBS) treatment planning for head and neck (H&N) cancers is a time-consuming and experience-demanding task where a large number of potentially conflicting planning objectives are involved. Deep reinforcement learning (DRL) has recently been introduced to the planning processes of intensity-modulated radiation therapy (IMRT) and brachytherapy for prostate, lung, and cervical cancers. However, existing DRL planning models are built upon the Q-learning framework and rely on weighted linear combinations of clinical metrics for reward calculation. These approaches suffer from poor scalability and flexibility, that is, they are only capable of adjusting a limited number of planning objectives in discrete action spaces and therefore fail to generalize to more complex planning problems., Purpose: Here we propose an automatic treatment planning model using the proximal policy optimization (PPO) algorithm in the policy gradient framework of DRL and a dose distribution-based reward function for proton PBS treatment planning of H&N cancers., Methods: The planning process is formulated as an optimization problem. A set of empirical rules is used to create auxiliary planning structures from target volumes and organs-at-risk (OARs), along with their associated planning objectives. Special attention is given to overlapping structures with potentially conflicting objectives. These planning objectives are fed into an in-house optimization engine to generate the spot monitor unit (MU) values. A decision-making policy network trained using PPO is developed to iteratively adjust the involved planning objective parameters. The policy network predicts actions in a continuous action space and guides the treatment planning system to refine the PBS treatment plans using a novel dose distribution-based reward function. A total of 34 H&N patients (30 for training and 4 for test) and 26 liver patients (20 for training, 6 for test) are included in this study to train and verify the effectiveness and generalizability of the proposed method., Results: Proton H&N treatment plans generated by the model show improved OAR sparing with equal or superior target coverage when compared with human-generated plans. Moreover, additional experiments on liver cancer demonstrate that the proposed method can be successfully generalized to other treatment sites., Conclusions: The automatic treatment planning model can generate complex H&N plans with quality comparable or superior to those produced by experienced human planners. Compared with existing works, our method is capable of handling more planning objectives in continuous action spaces. To the best of our knowledge, this is the first DRL-based automatic treatment planning model capable of achieving human-level performance for H&N cancers., (© 2025 American Association of Physicists in Medicine.)

Arsenic (As), a highly toxic and carcinogenic heavy metal, poses significant risks to soil and water quality, while oxytetracycline (OTC), a widely used antibiotic, contributes to environmental pollution due to excessive human usage. Addressing the coexistence of multiple pollutants in the environment, this study investigates the simultaneous adsorption of As(III) and OTC using a novel bimetallic zinc-iron-modified biochar (1Zn-1Fe-1SBC). The developed adsorbent demonstrates enhanced recovery, improved adsorption efficiency, and cost-effective operation. Characterization results revealed a high carbon-to-hydrogen ratio (C/H) and a specific surface area of 1137 m 2 g -1 for 1Zn-1Fe-1SBC. Isotherm modeling indicated maximum adsorption capacities of 34.7 mg g -1 for As(III) and 172.4 mg g -1 for OTC. Thermodynamic analysis confirmed that the adsorption processes for both pollutants were spontaneous (ΔG < 0), endothermic (ΔH > 0), and driven by chemical adsorption (ΔH > 80 kJ mol -1 ), with increased system disorder (ΔS > 0). The adsorption mechanisms involved multiple interactions, including pore filling, hydrogen bonding, electrostatic attraction, complexation, and π-π interactions. These findings underscore the potential of 1Zn-1Fe-1SBC as a promising adsorbent for the remediation of wastewater containing coexisting pollutants.

Background: Environmental pollutants have been found to contribute to the development and acute exacerbation of asthma. Microplastics (MPs) have received widespread attention as an emerging global pollutant. Airborne MPs can cause various adverse health effects. Due to their hydrophobicity, MPs can act as a carrier for other pollutants, pathogens, and allergens. This carrier effect of MPs may adsorb allergens and thus make the body exposed to MPs and a large number of allergens simultaneously. We hypothesized that co-exposure to inhaled MPs and aeroallergens may promote the development of airway inflammation of asthma by disrupting the airway epithelial barrier., Methods: The effects of co-exposure to Polyethylene microplastics (PE-MPs) and allergens on allergic airway inflammation and airway epithelial barrier were examined in a mouse model of asthma. The mice were divided into four groups: (i) Control group, treated only with PBS; (ii) MP group, exposed to PE-MPs and PBS; (iii) HDM group, mice were sensitized and challenged with HDM, and intranasally treated with PBS; (iv) HDM + MP group, mice were sensitized and challenged with HDM, and intranasally treated with PE-MPs. Histology and ELISA assays were used to evaluate the severity of airway inflammation. FITC-dextran permeability assay, immunofluorescence assay, and RT-PCR were used to evaluate the airway epithelial barrier function and the expression of relevant molecules. Transcriptomics analysis with lung tissue sequencing was conducted to identify possible pathways responsible for the effects of PE-MPs., Results: Co-exposure of mice to PE-MPs and HDM induced a higher degree of inflammatory cell infiltration, bronchial goblet cell hyperplasia, collagen deposition, allergen sensitization, and Th2 immune bias than exposure to HDM alone. Co-exposure to PE-MPs and HDM aggravated oxidative stress injury in the lung and the production of cytokine IL-33 in the BALF. In addition, co-exposure of mice to PE-MPs and HDM resulted in a more pronounced decrease in the expression of relevant molecules of the airway epithelial barrier and more significant increase in the permeability of airway epithelia. Lung tissue transcriptomics analysis revealed that PE-MPs exposure was associated with CXCL1 signaling and neutrophil activation., Conclusion: Co-exposure to MPs and HDM may promote airway inflammation and airway epithelial barrier disruption and induce immune responses characterized by CXCL1 signaling and neutrophilic inflammation., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: The total number of spine surgeries per year and their related deaths in Japan has not been adequately estimated in the literature., Methods: We retrospectively reviewed the National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB) between April 2014 to March 2021, which covers 99.9 % of health insurance claim receipts by general practitioners. The annual number of surgeries was counted using K codes, a procedure classification unique to Japan, and classified into the following six categories; percutaneous vertebroplasty, endoscopic surgery, open discectomy, laminoplasty/laminectomy, instrumentation surgery, and others. The data distribution was also summarized by sex and age. Additionally, by reviewing DPC database-related papers for evaluation of the mortality rate after spine surgery in Japan, the number of spine surgery-related deaths was calculated., Results: The NDB showed that the number of spine surgeries analyzed in this study increased from 170,081 in 2014 to 193,903 in 2019, with a slight decrease in 2020. The ratio of instrumentation surgery increased from 33.0 % in 2014 to 37.9 % in 2020. The rate of patients aged 75 or older increased 31.6 % to 39.6 %. Combining these findings with DPC data showing a mortality rate of 0.1 % to 0.4 % revealed that the estimated number of deaths related to spine surgery in Japan ranged from 200 to 800 per year., Conclusions: Approximately 200,000 spine surgeries and 200 to 800 spine surgery-related inpatient deaths were estimated to have occurred in Japan around 2020., Competing Interests: Declaration of competing interest No benefits in any form have been or will be received from a commercial party related directly to the subject of this manuscript. KY accepted payment or honoraria for lectures or educational events from the following; Johnson & Johnson KK, Pfizer Japan, 3 M Japan, Stryker Japan, Taisho Toyama Pharmaceutical, MSD KK, Hisamitsu Pharmaceutical, Asterllas Pharma Inc., DAIICHI SANKYO Company. The manuscript submitted does not contain information about medical device (s)/drug (s)., (Copyright © 2023 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

Objectives: This retrospective study evaluates the effectiveness of pulsed dye laser (PDL) treatment in early versus late treatment groups for traumatic or postoperative scars. The study aims to determine the threshold between early and late treatment. Additionally, it investigates factors that may influence wound healing outcomes., Methods: The medical records of 147 patients who underwent PDL treatment at our institution between January 2018 and December 2022 were retrospectively reviewed. Inclusion criteria were patients receiving PDL treatment for traumatic or postoperative scars. Out of these patients, we selected those who were willing to receive telephone interviews or re-visit at a scheduled time. Eventually, 52 participants were included in our study. A standardized questionnaire was administered to all participants during telephone interviews, encompassing inquiries regarding their medical history, treatment experiences, and the patient component of the Patient and Observer Scar Assessment Scale. Among the enrolled patients, 38 were contacted and interviewed via telephone, while the remaining 14 patients attended follow-up visits where photographs of their current skin condition were captured. The pretreatment and latest follow-up photographs obtained from the clinical database were independently scored in a blinded manner by two dermatologist reviewers using both the Vancouver Scar Scale and the Manchester Scar Scale., Results: Among the 52 patients, 43 (82.7%) were successfully treated with good response. The correlation coefficients between week-to-treatment initiation and posttreatment MSS and VSS among patients with good response were 0.50 (p < 0.001) and 0.46 (p = 0.002), respectively. Given these findings, we established a treatment initiation threshold of 10 weeks, distinguishing patients into early and late treatment groups. The early treatment group showed borderline significantly lower posttreatment MSS and VSS scores than the late treatment group (MSS: 7.5 ± 2.1 vs. 9.3 ± 2.5, p = 0.011; VSS: 2.8 ± 2.0 vs. 4.5 ± 2.3, p = 0.011). Furthermore, both MSS and VSS of posttreatment showed significantly greater improvement in the early treatment group (4.4 ± 1.6 vs. 3.2 ± 1.9; p = 0.03 and 3.8 ± 1.8 vs. 2.8 ± 1.4; p = 0.04)., Conclusions: Early intervention using a PDL within 10 weeks post-injury achieved better outcomes in treating traumatic and postoperative scars based on both clinical and patient opinions., (© 2024 Wiley Periodicals LLC.)

The excessive content of heavy metal ions in water has attracted increasing worldwide attention due to the potential harm to human health and ecological systems. Therefore, it is particularly significant to research and develop a sensitive and straightforward water quality monitoring method. Here, a dual-network designed hydrogel poly(acrylic acid-co- N -methylolacrylamide)/poly(3,4-ethylenedioxythiophene): polystyrenesulfonate, P(AA-co-N-MA)/PEDOT: PSS, was constructed and used for Fe 3+ detection. Compared with previous reports, the P(AA-co-N-MA)/PEDOT: PSS hydrogel has a much more sensitive and convenient detection of immune iron ions (Fe 3+ ), is applied to monitor a trace of over-the-standard (the lower limit of detection is 0.52 ppm corresponding to 0.06 S/m for human health monitor, and the threshold for water quality monitoring is 0.16 S/m). The relationship between Fe 3+ content and the conductivity of the hydrogel allows it to integrate with other electron devices to provide an early warning function for Fe 3+ in the human body, which would be of great significance to human health monitoring.

Background: Melasma is a challenging, acquired hyperpigmentary disorder. The gold standard treatment is Kligman's formulation, which contains hydroquinone, tretinoin, and dexamethasone, but its long-term use is limited by the risk of exogenous ochronosis. Cysteamine, a tyrosinase inhibitor, reduces melanocyte activity and melanin production, showing strong depigmenting effects in patients resistant to Kligman's formulation. Nonetheless, clinical studies have yielded inconsistent efficacy results. This meta-analysis aimed to assess the efficacy of cysteamine in treating melasma and to identify potential factors that may impact its therapeutic outcomes. Methods: A systematic search of PubMed, Embase, Web of Science, and CENTRAL, from the earliest record until August 2024, was conducted. Randomized controlled trials and quasi-randomized design studies related to topical cysteamine on melasma patients were included. The primary outcome was MASI or mMASI assessment after treatments. The current meta-analysis was conducted with a random-effects model. Subgroup analyses and meta-regressions were performed based on baseline MASI, disease duration of melasma, patient age, and sample size of the included studies. Funnel plots and Duval and Tweedie's trim and fill method were adopted to assess the publication bias. Results: Eight studies were included for quantitative analysis. The analysis of MASI after topical cysteamine demonstrated a significant decrease compared to the placebo ( p = 0.002). Compared to other melasma treatments, cysteamine did not show superior efficacy in mMASI ( p = 0.277). The treatment efficacy of hydroquinone, modified Kligman's formula, and tranexamic acid mesotherapy for melasma was not statistically different when compared to cysteamine ( p = 0.434). Further analyses showed no benefit when allowing extended cysteamine application time ( p < 0.0001). The meta-regression revealed the efficacy of cysteamine decreased as the duration of melasma increased (coefficient = 0.38, p = 0.0001, R 2 = 0.99). The funnel plot displayed some asymmetry. The trim and fill method suggested the adjusted effect size was 0.607 (95% CI = -0.720 to 1.935). Conclusions: Cysteamine exhibited efficacy in treating melasma patients; however, its depigmentation effect was comparable to hydroquinone-based regimens, tranexamic acid mesotherapy, and modified Kligman's formula. Using cysteamine in patients with a short duration of melasma may result in better efficacy.

Adolescent obesity can impair cardiopulmonary function, vascular elasticity, endothelial function, and vago-sympathetic balance. While moderate-intensity continuous training (MICT) benefits cardiovascular health in obese adolescents, the effects of high-intensity interval training (HIIT) are less understood. We hypothesize that HIIT may be more effective than MICT in improving VO 2 peak, vascular elasticity, endothelial function, and vago-sympathetic balance in obese adolescent boys. Forty four participants were randomly assigned to the HIIT (10 × 1-min at 85%-95% peak HR, intersperse with 2-min active recovery at 60%-70% peak HR) or MICT (35 min at 65%-75% peak HR) for an 8-week program. The primary outcome measured was the change in VO 2peak with secondary outcomes including brachial-ankle pulse wave velocity (baPWV), flow-mediated dilation (FMD), and heart rate variability (HRV). Forty four adolescent boys with obesity (age, 14 ± 1 years old, body mass index, 31.6 ± 1.3 kg/m 2 ) were enrolled and 43 (97.73%) completed the 8-week exercise. No significant difference of VO 2peak was found between the HIIT and MICT group (p = 0.243). There was no significant difference of baPWV between the groups (p = 0.789). Change in FMD% was significantly higher in the HIIT group compared to the MICT group (p < 0.001). The Change in HRV-high frequency (HRV-HF; p = 0.009) and HRV-low frequency/high frequency (HRV-LF/HF; p = 0.035) was significantly higher in the HIIT group compared to the MICT group. Among adolescent boys with obesity, 8-week HIIT and MICT had similar effects on improving VO 2peak . HIIT may be superior to MICT to improve endothelial function and vago-sympathetic balance., (© 2024 The Author(s). European Journal of Sport Science published by Wiley‐VCH GmbH on behalf of European College of Sport Science.)

Abstract: This single-center retrospective study enrolled 22 patients, who were divided into two groups: those who underwent wide excision (group A) and those who did not (group B). Group A included 13 patients, and group B included 9. Most of the cases fell into early stages (I and II). In group A, six patients solely underwent wide excision, whereas seven received additional treatments such as radiotherapy or chemotherapy. Conversely, in group B, four patients received chemotherapy, four received radiotherapy, and one was managed through observation alone. The mean follow-up times were 60.15 and 43.44 months in groups A and B, respectively, with no significant difference observed. In group A, nine patients died, whereas, in group B, six died during the follow-up period. Lesion-free intervals after surgery were observed predominantly in group A, whereas, in group B, seven patients never experienced freedom from skin lesions. Kaplan-Meier survival curve analysis demonstrated a significant difference between the survival curves of the two groups (P = 0.046). Group A exhibited a more favorable outcome in the survival curve analysis. This significant difference could be attributed to the higher survival rates observed in group A during the first 5 years of follow-up. This finding underscores the potential benefit of surgical intervention in the management of non-HIV Kaposi's sarcoma, particularly in the short- to medium-term survival outcomes. Among patients with non-HIV Kaposi's sarcoma, especially those in the early stages, wide excision appears to play a role in treatment., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

To mitigate postprandial hyperglycemia, α-amylase inhibitory peptides have been casually prepared by various pretreatments and proteolysis without exploring their impacting mechanisms and digestive stabilities. In this study, pea protein treated by pH 2 shifting followed by flavourzyme hydrolysis (PS 2 -PF) expressed excellent protein recovery rate (40.06 %) and α-amylase inhibitory activity (IC 50 of 6.75 mg/mL) after simulated gastrointestinal digestion. A moderate decrease of α-helix structure (by 10.80 %) but increases of β conformations (by ∼17.75 %) and small molecules (< 5 kDa, 94.73 %) on the pea protein were beneficial to enhance α-amylase inhibition of the digested PS 2 -PF. 13 of potential α-amylase inhibitory peptides were identified from the digested PS 2 -PF to inactivate α-amylase via hydrogen bonding, Pi-Alkyl, Pi-Pi and attractive interactions of phenylalanine, proline, leucine, arginine, glutamic acid and lysine. Overall, pH 2 shifting assisted flavourzyme hydrolysis could be a valuable strategy to enhance α-amylase inhibition of in vitro digested pea protein for diabetes mellitus., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Distinguished by its exceptional sensitivity and specificity, Polymerase Chain Reaction (PCR) is a pivotal technology for pathogen detection. However, traditional PCR instruments that employ thermoelectric cooling (TEC) are often constrained by cost, efficiency, and performance variability resulting from the fluctuations in ambient temperature. Here, we present a thermal cycler that utilizes electromagnetic induction heating at 50 kHz and anti-freezing water cooling with a velocity of 0.06 m/s to facilitate rapid heating and cooling of the PCR reaction chamber, significantly enhancing heat transfer efficiency. A multi-physics theoretical heat transfer model, developed using the digital twin approach, enables precise temperature control through advanced algorithms. Experimental results reveal average heating and cooling rates of 14.92 °C/s and 13.39 °C/s, respectively, significantly exceeding those of conventional methods. Compared to commercial PCR instruments, the proposed system further optimizes cost, efficiency, and practicality. Finally, PCR experiments were successfully performed using cDNA (Hepatitis B virus) at various concentrations., Competing Interests: Author Yaping Xie was employed by the Sansure Biotech Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

This study aimed to evaluate the effects of Pleurotus ostreatus spent mushroom substrate (P.SMS), which is characterized by high production but low utilization, on feed utilization and liver serum indices from the perspective of duodenal microorganisms. Forty-five 3-month-old Hu sheep were randomly assigned to five groups and fed diets in which whole-plant corn silage (WPCS) was substituted with P.SMS at levels of 0% (Con), 5% (PSMS5), 10% (PSMS10), 15% (PSMS15), or 20% (PSMS20). The results indicated that the addition of P.SMS complexly influenced the apparent digestibility of dry matter, organic matter, and crude protein, with PSMS10 showing the highest digestibility of these nutrients. P.SMS inclusion significantly affected serum alanine aminotransferase levels, with PSMS5 showing higher levels than both the Con and PSMS20 groups ( p < 0.05). Importantly, the inclusion of P.SMS did not affect the richness and diversity of duodenal microorganisms. Significant differences in the phyla Verrucomicrobiota and Spirochaetota were observed between the Con and PSMS20 groups. The observed trend towards an increase in the genus Trichoderma ( p = 0.057) suggests that P.SMS is susceptible to contamination by this genus, which in turn affects the structure of the intestinal flora. Furthermore, functional gene predictions indicated differences in amino acid metabolism among the groups ( p < 0.05). In conclusion, feeding with 10% P.SMS resulted in the highest digestibility without adversely affecting the structure of the duodenal community or liver function.

Photonic topological insulators with boundary states present a robust solution to mitigate structure imperfections. By alteration of the virtual boundary between trivial and topological insulators, it is possible to bypass such defects. Coupled resonator optical waveguides (CROWs) have demonstrated their utility in realizing photonic topological insulators, as they exhibit distinct topological phases and band structures. With this characteristic, we designed and experimentally validated a CROW array capable of altering its topological phase by adjusting the coupling strength. This array functions partially as a topological insulator and partially as a topologically trivial array, guiding light along the virtuous boundary between these two regions. By altering the shape of the topological insulator, we can effectively control the optical path. This approach promises practical applications, such as optical switches, dynamic light steering, optical sensing, and optical computing., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Background: The association between nonalcoholic fatty liver disease and cardiovascular disease is firmly established, yet the association between noninvasive liver fibrosis scores and cardiovascular events remains a topic of uncertainty. Our study aimed to explore the association between liver fibrosis and heart failure., Methods and Results: The data set was from the National Health and Nutrition Examination Survey 2011 to 2018. Advanced hepatic fibrosis risk was assessed through 3 noninvasive liver fibrosis scores: Fibrosis-4 score (FIB-4), the nonalcoholic fatty liver disease fibrosis score (NFS), and the aspartate aminotransferase to platelet ratio index (APRI). We included 19 695 eligible participants. The national prevalence of advanced liver fibrosis risk in the United States was 4.20%, 8.06%, and 0.35% as determined by FIB-4, NFS, and APRI scores, respectively. Weighted logistic regression analysis revealed significant associations between advanced liver fibrosis risk and the prevalence of heart failure (continuous variables, FIB-4: odds ratio [OR], 1.15 [95% CI, 1.07-1.23]; NFS: OR, 1.42 [95% CI, 1.23-1.64]; APRI: OR, 1.44 [95% CI, 1.15-1.81]). When the scores were assessed as categorical variables, the results were still significant (FIB-4 ≥2.67 versus FIB-4 <1.3: OR, 2.18 [95% CI, 1.47-3.24]; NFS ≥0.675 versus NFS <-1.455: OR, 2.53 [95% CI, 1.37-4.68]). Subgroup analysis found that the association between APRI and heart failure was stronger in female patients., Conclusions: In the general US population, the prevalence of advanced liver fibrosis risk varied between 0.35% and 8.06% as indicated by noninvasive liver fibrosis scores. FIB-4, NFS, and APRI scores were linked to an elevated prevalence of heart failure.

Introduction: The study aimed to evaluate the effects of Pleurotus Spent Mushroom Substrate (P.SMS) on the rumen microbiota, encompassing bacteria and fungi, as well as their interactions in Hu sheep., Methods: A total of forty-five 3-month-old Hu sheep were randomly assigned to five groups. Each group was fed diets in which whole-plant corn silage (WPCS) was substituted with P.SMS at varying levels: 0% (CON), 5% (PSMS5), 10% (PSMS10), 15% (PSMS15), or 20% (PSMS20)., Results: The results indicated that higher proportions of P.SMS during the experimental period might have a detrimental effect on feed utilization efficiency, kidney function, and blood oxygen-carrying capacity. Notably, moderate levels of P.SMS, specifically below 15%, were associated with improvements in rumen NH 3 -N levels and absorption capacity. The results indicated that (1) PSMS20 exhibited a significantly higher feed-to-gain ratio compared to CON ( P  < 0.05); (2) PSMS15 showed a significantly higher NH 3 -N content than CON, PSMS5, and PSMS20. Additionally, PSMS10 and PSMS20 had elevated concentrations of NH 3 -N compared to CON and PSMS5 ( P  < 0.05); (3) The length and width of rumen papillae were significantly greater in PSMS20 compared to CON and PSMS5 ( P  < 0.05); (4) Creatinine levels were significantly higher in PSMS20 than in CON, PSMS5, and PSMS10 ( P  < 0.05); (5) By the conclusion of the experiment, hemoglobin concentration in PSMS20 showed a significant increase compared to CON ( P  < 0.05). Furthermore, the addition of P.SMS influenced microorganisms at both the phylum and genus levels: (1) At the phylum level, the prevalence of Patescibacteria was significantly lower in PSMS20 compared to the other groups; (2) PSMS15 exhibited significantly higher relative abundances of Basidiomycota compared to CON and PSMS10, while PSMS20 also demonstrated significantly higher relative abundances compared to CON ( P  < 0.05); (3) At the genus level, the prevalence of Candidatus&#95;Saccharimonas in PSMS20 was significantly lower than in PSMS5, PSMS10, and PSMS15. Conversely, the prevalence of Phanerochaete in PSMS15 was notably higher than in CON and PSMS10, and it was also significantly elevated in PSMS20 compared to CON ( P  < 0.05); (4) Correlation analysis indicated no significant correlation between changes in the structure of bacterial and fungal communities., Discussion: Considering these findings, a high percentage of P.SMS negatively impacted feed utilization efficiency, blood oxygen carrying capacity, and kidney function, while a moderate percentage of P.SMS promotes rumen absorption capacity, indicating that feeding 10% P.SMS is optimal., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Lu, Yuan, Rehemujiang, Li, Hu, Duan, Zhang, Diao, Deng and Xu.)

Background: Collagen dermal fillers have shown efficacy in addressing age-related changes in facial appearance. However, their potential in rejuvenating the periorbital region remains unexplored. The aim of this study was to evaluate the effectiveness, clinical safety, and patient satisfaction associated with the utilization of collagen dermal fillers in individuals with dermatochalasis and periorbital hyperpigmentation., Methods: This study was reviewed and approved by the institutional review board of China Medical University Hospital (IRB No. CMUH107-REC2-157). Adults diagnosed with dermatochalasis or periorbital hyperpigmentation received periorbital injections of a sterile cross-linked highly-purified specific antigen free porcine dermal collagen (FACIALGAIN® Collagen Implant with Lidocaine, Sunmax Biotechnology Co. Ltd., Taipei, Taiwan) and were assessed for hydration, elasticity, pigmentation index, redness index, lightness value, and density with the DermaLab® Combo Multiparameter Skin Analysis System (Cortex Technology, Hadsund, Denmark) and Cutometer® Dual MPA 580 (Courage+Khazaka electronic GmbH, Köln, Germany). Data was collected prior to injection and at 1 week, 4 weeks, and 12 weeks after injection. Patient satisfaction on volume augmentation, decrease in hyperpigmentation, persistence, and overall satisfaction were also recorded., Results: A total of 12 samples each were recruited for dermatochalasis and periorbital hyperpigmentation. For dermatochalasis subjects, hydration of the periorbital tissue significantly increased at week 1 and 4 (p = 0.011 and p = 0.015). Elasticity decreased by week 4 and persisted until week 12 (p = 0.001 and 0.014). For periorbital hyperpigmentation patients, lightness value increased significantly starting week 1 (p = 0.016), tapering off at week 12. Elasticity decreased by week 4 and persisted until week 12 (p = 0.002 and p = 0.002). Median overall patient satisfaction was 4 out of 5 for the dermatochalasis group and 4.5 out of 5 for the periorbital hyperpigmentation group, with a mild but insignificant decrease by week 12., Conclusions: DermaLab® Combo and Cutometer® Dual MPA 580 are considered effective methods for evaluating patients undergoing dermal filler injections. The utilization of cross-linked porcine collagen dermal filler injections can serve as a minimally invasive approach to enhance skin laxity in dermatochalasis and address discoloration in periorbital hyperpigmentation. However, it is important to note that regular treatments may be necessary to sustain the desired outcomes., Level of Evidence Iv: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/0026 ., (© 2024. The Author(s).)

During pandemics, such as COVID-19, supplies of vaccines can be insufficient for meeting all needs, particularly when vaccines first become available. Our study develops a dynamic methodology for vaccine allocation, segmented by region, age, and timeframe, using a time-sensitive, age-structured compartmental model. Based on the objective of minimizing a weighted sum of deaths and cases, we used the Sequential Least Squares Quadratic Programming method to search for a locally optimal COVID-19 vaccine allocation for the United States, for the period from 16 December 2020 to 30 June 2021, where regions corresponded to the 50 states in the United States (U.S.). We also compared our solution to actual allocations of vaccines. From our model, we estimate that approximately 1.8 million cases and 9 thousand deaths could have been averted in the U.S. with an improved allocation. When case reduction is prioritized over death reduction, we found that young people (17 and younger) should receive priority over old people due to their potential to expose others. However, if death reduction is prioritized over case reduction, we found that more vaccines should be allocated to older people, due to their propensity for severe disease. While we have applied our methodology to COVID-19, our approach generalizes to other human-transmissible diseases, with potential application to future epidemics.

Excessive fluoride ingestion during tooth development can cause dental fluorosis. Previously, we reported that fluoride activates histone acetyltransferase (HAT) to acetylate p53, promoting fluoride toxicity in mouse ameloblast-like LS8 cells. However, the roles of HAT and histone acetylation status in fluoride-mediated gene expression remain unidentified. Here, we demonstrate that fluoride-mediated histone modification causes gene expression alterations in LS8 cells. LS8 cells were treated with or without fluoride followed by ChIP-Seq analysis of H3K27ac. Genes were identified by differential H3K27ac peaks within ±1 kb from transcription start sites. The levels of mRNA of identified genes were assessed using rea-time PCR (qPCR). Fluoride increased H3K27ac peaks associated with Bax , p21 , and Mdm2 genes and upregulated their mRNA levels. Fluoride decreased H3K27ac peaks and p53 , Bad , and Bcl2 had suppressed transcription. HAT inhibitors (Anacardic acid or MG149) suppressed fluoride-induced mRNA of p21 and Mdm2 , while fluoride and the histone deacetylase (HDAC) inhibitor sodium butyrate increased Bad and Bcl2 expression above that of fluoride treatment alone. To our knowledge, this is the first study that demonstrates epigenetic regulation via fluoride treatment via H3 acetylation. Further investigation is required to elucidate epigenetic mechanisms of fluoride toxicity in enamel development.

This brief report discusses the challenges in treating dermal melanosis and the limitations of current laser treatments due to inadequate tissue penetration and potential side effects. It introduces laser-induced optical breakdown (LIOB) as a novel therapeutic approach using a picosecond laser with a diffractive lens array (DLA) to target dermal pigmentation effectively. LIOB induces multiphoton ionization, leading to melanin clearance through phagocytosis and apoptotic cell removal, while also promoting dermal remodeling and collagen synthesis. We present a case of successful treatment of dermal pigmentation in a 55-year-old woman using 755 nm-picosecond alexandrite laser therapy, demonstrating significant improvement without recurrence. The findings suggest that LIOB offers a promising solution for acquired dermal hypermelanosis by addressing both diffuse and localized pigmentation effectively, leading to skin rejuvenation with minimal downtime and high patient satisfaction., (© 2024. The Author(s), under exclusive licence to Springer-Verlag London Ltd., part of Springer Nature.)

Background: Sepsis often leads to significant morbidity and mortality due to severe myocardial injury. As is known, the activation of NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome crucially contributes to septic cardiomyopathy (SCM) by facilitating the secretion of interleukin (IL)-1β and IL-18. The removal of palmitoyl groups from NLRP3 is a crucial step in the activation of the NLRP3 inflammasome. Thus, the potential inhibitors that regulate the palmitoylation and inactivation of NLRP3 may significantly diminish sepsis-induced cardiac dysfunction., Purpose: The present study sought to explore the effects of the prospective flavonoid compounds targeting NLRP3 on SCM and to elucidate the associated underlying mechanisms., Study Design: The palmitoylation and activation of NLRP3 were detected in H9c2 cells and C57BL/6 J mice., Methods/results: Echocardiography, histological staining, western blotting, co-immunoprecipitation, qPCR, ELISA and network pharmacology were used to assess the impact of vaccarin (VAC) on SCM in mice subjected to lipopolysaccharide (LPS) injection. From the collection of 74 compounds, we identified that VAC had the strongest capability to suppress NLRP3 luciferase report gene activity in cardiomyocytes, and the anti-inflammatory characteristics of VAC were further ascertained by the network pharmacology. Exposure of LPS triggered apoptosis, inflammation, oxidative stress, mitochondrial disorder in cardiomyocytes. The detrimental alterations were significantly reversed upon VAC treatment in both septic mice and H9c2 cells exposed to LPS. In vivo experiments demonstrated that VAC treatment alleviated septic myocardial injury, indicated by enhanced cardiac function parameters, preserved cardiac structure, and reduced inflammation/oxidative response. Mechanistically, VAC induced NLRP3 palmitoylation to inactivate NLRP3 inflammasome by acting on zDHHC12. In support, the NLRP3 agonist ATP and the acylation inhibitor 2-bromopalmitate (2-BP) prevented the effects of VAC., Conclusion: Our findings suggest that VAC holds promise in protecting against SCM by mitigating cardiac oxidative stress and inflammation via priming NLRP3 palmitoylation and inactivation. These results lay the solid basis for further assessment of the therapeutic potential of VAC against SCM., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest., (Copyright © 2024. Published by Elsevier GmbH.)

Background: Type 2 diabetes mellitus (T2DM) is a metabolic syndrome characterized by chronic inflammation, insulin resistance, and islet cell damage. The prevention of T2DM and its associated complications is an urgent public health issue that affects hundreds of millions of people globally. Numerous studies suggest that disturbances in gut metabolites are important driving forces for the pathogenesis of diabetes. However, the functions and mechanisms of action of most commensal bacteria in T2DM remain largely unknown., Methods: The quantification of bile acids (BAs) in fecal samples was performed using ultra-performance liquid chromatography-tandem mass spectrometer (UPLC-MS/MS). The anti-diabetic effects of Bacteroides uniformis ( B. uniformis ) and its metabolites cholic acid (CA) and chenodeoxycholic acid (CDCA) were assessed in T2DM mice induced by streptozocin (STZ) plus high-fat diet (HFD)., Results: We found that the abundance of B. uniformis in the feces and the contents of CA and CDCA were significantly downregulated in T2DM mice. B. uniformis was diminished in diabetic individuals and this bacterium was sufficient to promote the production of BAs. Colonization of B. uniformis and intragastric gavage of CA and CDCA effectively improved the disorder of glucose and lipid metabolism in T2DM mice by inhibiting gluconeogenesis and lipolysis in the liver. CA and CDCA improved hepatic glucose and lipid metabolism by acting on the Takeda G protein-coupled receptor 5 (TGR5)/adenosine monophosphate-activated protein kinase (AMPK) signaling pathway since knockdown of TGR5 minimized the benefit of CA and CDCA. Furthermore, we screened a natural product-vaccarin (VAC)-that exhibited anti-diabetic effects by promoting the growth of B. uniformis in vitro and in vivo. Gut microbiota pre-depletion abolished the favorable effects of VAC in diabetic mice., Conclusions: These data suggest that supplementation of B. uniformis may be a promising avenue to ameliorate T2DM by linking the gut and liver.

Gac fruit ( Momordica cochinchinensis Spreng.) is a prominent source of carotenoids, renowned for its exceptional concentration of these compounds. This study focuses on optimizing the extraction of active components from the aril of gac fruit by evaluating the effects of extraction temperature, solid-liquid ratio, and extraction time. The primary objective is to maximize the yield of gac oil while assessing its antioxidant capacity. To analyze the kinetics of the solid-liquid extraction process, both first-order and second-order kinetic models were employed, with the second-order model providing the best fit for the experimental data. In addition, the potential of gac fruit peel as a precursor for biochar production was investigated through carbonization. The resultant biochars were evaluated for their efficacy in adsorbing crystal violet (CV) dye from aqueous solutions. The adsorption efficiency of the biochars was found to be dependent on the carbonization temperature, with the highest efficiency observed for BCMC550 (91.72%), followed by BCM450 (81.35%), BCMC350 (78.35%), and BCMC250 (54.43%). The adsorption isotherm data conformed well to the Langmuir isotherm model, indicating monolayer adsorption behavior. Moreover, the adsorption kinetics were best described by the pseudo-second-order model. These findings underscore the potential of gac fruit and its byproducts for diverse industrial and environmental applications, highlighting the dual benefits of optimizing gac oil extraction and utilizing the peel for effective dye removal.

The present study used CeO 2 -Co 3 O 4 quantum dots@porous carbon/multiwalled carbon nanotube (CeO 2 -Co 3 O 4 QDs@PC/MWCNT/GE) composites to modify graphite electrodes to fabricate high-sensitivity electrochemical sensors to detect the presence of oxytetracycline (OTC). The quantum dots were made from waste sugarcane bagasse. The electrochemical analysis demonstrated the superior electrochemical performance of CeO 2 -Co 3 O 4 QDs@PC/MWCNT/GE, with a peak current density of 1.276 mA/cm 2 . Electrochemical impedance spectroscopy (EIS) revealed lower impedance values for CeO 2 -Co 3 O 4 QDs@PC/MWCNT/GE compared to other electrodes, indicating enhanced conductivity. The modified electrode exhibited an enlarged electrochemically active area, with values of 0.602 cm 2 , almost seven times that of the bare graphite electrode (0.079 cm 2 ). The results showed that the CeO 2 -Co 3 O 4 QDs@PC/MWCNT/GE had excellent performance for OTC detection, and its linear calibration range was 1.007 × 10 -8 to 2.04 × 10 -7  M (i.e., 0.005-0.1 ppm) and 1.007 × 10 -6 to 1.209 × 10 -4  M (i.e., 0.5-60 ppm). The limit of detection and limit of quantification were 1.23 nM (0.61 ppb) and 4.09 nM (2.03 ppb) (S/N = 3), respectively. The electrode demonstrated long-term stability for up to 7 weeks. This method provides a new way to prepare electrochemical sensors for OTC detection., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Dexmedetomidine displays multiple mechanisms of neuroprotection in ameliorating ischemic brain injury. In this study, we explored the beneficial effects of dexmedetomidine on blood-brain barrier (BBB) integrity and neuroinflammation in cerebral ischemia/reperfusion injury. Sprague-Dawley rats were subjected to middle cerebral artery occlusion (MCAO) for 1.5 h and reperfusion for 24 h to establish a rat model of cerebral ischemia/reperfusion injury. Dexmedetomidine (9 􀁐g/kg) was administered to rats 30 min after MCAO through intravenous injection, and SB203580 (a p38 MAPK inhibitor, 200 􀁐g/kg) was injected intraperitoneally 30 min before MCAO. Brain damages were evaluated by 2,3,5-triphenyltetrazolium chloride staining, hematoxylin-eosin staining, Nissl staining, and brain water content assessment. BBB permeability was examined by Evans blue staining. Expression levels of claudin-5, zonula occludens-1, occludin, and matrix metalloproteinase-9 (MMP-9) as well as M1/M2 phenotypes-associated markers were assessed using immunofluorescence, RT-qPCR, Western blotting, and gelatin zymography. Enzyme-linked immunosorbent assay was used to examine inflammatory cytokine levels. We found that dexmedetomidine or SB203580 attenuated infarct volume, brain edema, BBB permeability, and neuroinflammation, and promoted M2 microglial polarization after cerebral ischemia/reperfusion injury. Increased MMP-9 activity by ischemia/reperfusion injury was inhibited by dexmedetomidine or SB203580. Dexmedetomidine inhibited the activation of the ERK, JNK, and p38 MAPK pathways. Moreover, activation of JNK or p38 MAPK reversed the protective effects of dexmedetomidine against ischemic brain injury. Overall, dexmedetomidine ameliorated brain injury by alleviating BBB permeability and promoting M2 polarization in experimental cerebral ischemia/reperfusion injury model by inhibiting the activation of JNK and p38 MAPK pathways.

Background: Beam modifying accessories for proton therapy often need to be placed in close proximity of the patient for optimal dosimetry. However, proton treatment units are larger in size and as a result the planned treatment geometry may not be achievable due to collisions with the patient. A framework that can accurately simulate proton treatment geometry is desired., Purpose: A quantitative framework was developed to model patient-specific proton treatment geometry, minimize air gap, and avoid collisions., Methods: The patient's external contour is converted into the International Electrotechnique Commission (IEC) gantry coordinates following the patient's orientation and each beam's gantry and table angles. All snout components are modeled by three-dimensional (3D) geometric shapes such as columns, cuboids, and frustums. Beam-specific parameters such as isocenter coordinates, snout type and extension are used to determine if any point on the external contour protrudes into the various snout components. A 3D graphical user interface is also provided to the planner to visualize the treatment geometry. In case of a collision, the framework's analytic algorithm quantifies the maximum protrusion of the external contour into the snout components. Without a collision, the framework quantifies the minimum distance of the external contour from the snout components and renders a warning if such distance is less than 5 cm., Results: Three different snout designs are modeled. Examples of potential collision and its aversion by snout retraction are demonstrated. Different patient orientations, including a sitting treatment position, as well as treatment plans with multiple isocenters, are successfully modeled in the framework. Finally, the dosimetric advantage of reduced air gap enabled by this framework is demonstrated by comparing plans with standard and reduced air gaps., Conclusion: Implementation of this framework reduces incidence of collisions in the treatment room. In addition, it enables the planners to minimize the air gap and achieve better plan dosimetry., (© 2023 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine.)

Acute kidney injury (AKI) remains a global public health problem with high incidence, high mortality rates, expensive medical costs, and limited treatment options. AKI can further progress to chronic kidney disease (CKD) and eventually end-stage renal disease (ESRD). Previous studies have shown that trauma, adverse drug reactions, surgery, and other factors are closely associated with AKI. With further in-depth exploration, the role of gut microbiota in AKI is gradually revealed. After AKI occurs, there are changes in the composition of gut microbiota, leading to disruption of the intestinal barrier, intestinal immune response, and bacterial translocation. Meanwhile, metabolites of gut microbiota can exacerbate the progression of AKI. Therefore, elucidating the specific mechanisms by which gut microbiota is involved in the occurrence and development of AKI can provide new insights from the perspective of intestinal microbiota for the prevention and treatment of AKI.

Ethnopharmacological Relevance: Gleditsiae sinensis fructus Pills (GF) is a famous classical prescription, that is regularly combined with Jujubae fructus (JF) for the treatment of chronic bronchitis (CB) in the clinic. While the clinical efficacy of this combination prescription is clearly established, the active ingredients and molecular mechanisms remain unclear., Aim of the Study: To elucidate the mechanisms of action of Gleditsiae sinensis fructus Pills combined with Jujubae fructus (GF&JF) against CB based on network pharmacology and experimental verification., Materials and Methods: The potential targets of GF&JF involved in therapeutic activity against CB were predicted based on network pharmacology and an "ingredients-targets" network constructed. The Metascape database was used for Module, GO functional and KEGG signaling pathway enrichment analyses of potential targets. Molecular docking was applied to simulate the binding activities of key candidate active ingredients to core targets. For experimental verification, a CB model was established through smoking and nasal cavity drip of lipopolysaccharide. Related inflammatory factors, including TNF-α, TGF-β, IL-6 and IL-8 in serum, and IL-4 IL-8, IFN-γ and IL-10 in bronchoalveolar lavage fluid (BALF), were detected using ELISA. Hematoxylin and eosin (H&E) and Masson staining were performed to observe pathological changes in lung and tracheal tissue. The expression of related proteins and mRNAs in the lung tissue were detected using immunohistochemistry (IHC), quantitative real-time PCR, and western blot., Results: In network pharmacology, 36 common targets of GF&JF for CB were screened and the key targets and main signaling pathways identified. The active ingredients quercetin and stigmasterol in GF&JF had more targets for CB, which displayed good binding activity to IL-6, VEGFA, and EGFR, as established from molecular docking results. In vivo, GF&JF effectively inhibit the inflammatory response in CB mice and improved pathological changes in lung and tracheal tissue. In terms of the key proteins of the AGE-RAGE signaling pathway, GF&JF induced significant down-regulation of IL-6, ICAM-1, VCAM-1, EGFR, CASPASE-3, AGEs and RAGE proteins in lung tissue as well as mRNA expression of IL-6, ICAM-1, VCAM-1, EGFR, AGEs and RAGE., Conclusions: The GF&JF combination exerts a good therapeutic effect in CB model mice, which may be attributed to inhibition of the inflammatory response as well as regulation on the expression of AGE-RAGE signaling pathway. In addition, quercetin and stigmasterol appear to be the main active ingredients of GF&JF in the treatment of CB., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Abstract: In case of excision of nasal basal cell carcinoma (BCC), bilobed flaps are considered the criterion standard of reconstruction for defect less than 15 mm in size. However, there is still a risk of trapdoor deformity formation, of which its treatment is less discussed. A 44-year-old woman who was diagnosed with nasal BCC and underwent tumor excision with bilobed flap reconstruction presented with trapdoor deformity postoperatively. The computed Vancouver Scar Scale was 7. After early intervention of multiple laser modalities, including 2 sessions of 585-nm pulsed dye laser with a fluence of 9 J/cm2, pulse duration of 6 milliseconds, and spot size of 6 mm, 2940-nm Er-yttrium aluminum garnet (YAG) laser with a pulse energy of 800-900 mJ, repetition rate of 8-9 Hz, and laser spot size of 3-7 mm, and 5 sessions of 1064-nm Nd:YAG fractional picosecond laser with a pulse energy of 2.30-2.70 mJ, repetition rate of 8 Hz, and laser spot size of 6 mm from 5 to 23 weeks postoperatively, the Vancouver Scar Scale score improved to 1, with significant reduction of trapdoor scar erythema and puffiness. Although BCC is often curable, tumor excision causes unsatisfactory appearance satisfaction problem, owing to the apparent location of the lesion. Factors, such as sebaceous tissue thickness, reconstruction over multiple aesthetic subunits of nose, and damage to nasal cartilage framework structure during tumor removal, may increase the risk of trapdoor formation. Early intervention with multiple laser treatment can significantly revise the deformity., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: A range of imaging modalities have reported Alzheimer's disease-related abnormalities in individuals experiencing subjective cognitive decline (SCD). However, there has been no consistent local abnormality identified across multiple neuroimaging modalities for SCD., Objective: We aimed to investigate the convergent local alterations in amyloid-β (Aβ) deposition, glucose metabolism, and resting-state functional MRI (RS-fMRI) metrics in SCD., Methods: Fifty SCD patients (66.4±5.7 years old, 19 men [38%]) and 15 normal controls (NC) (66.3±4.4 years old, 5 men [33.3%]) were scanned with both [18F]-florbetapir PET and [18F]-fluorodeoxyglucose PET, as well as simultaneous RS-fMRI from February 2018 to November 2018. Voxel-wise metrics were retrospectively analyzed, including Aβ deposition, glucose metabolism, amplitude of low frequency fluctuation (ALFF), regional homogeneity (ReHo), and degree centrality(DC)., Results: The SCD group showed increased Aβ deposition and glucose metabolism (p < 0.05, corrected), as well as decreased ALFF, ReHo, and DC (p < 0.05, uncorrected) in the left dorsal precuneus (dPCu). Furthermore, the dPCu illustrated negative resting-state functional connectivity with the default mode network. Regarding global Aβ deposition positivity, the Aβ deposition in the left dPCu showed a gradient change, i.e., Aβ positive SCD > Aβ negative SCD > Aβ negative NC. Additionally, both Aβ positive SCD and Aβ negative SCD showed increased glucose metabolism and decreased RS-fMRI metrics in the dPCu., Conclusions: The dorsal precuneus, an area implicated in early AD, shows convergent neuroimaging alterations in SCD, and might be more related to other cognitive functions (e.g., unfocused attention) than episodic memory.

Conventional 5-aminolevulinic acid-photodynamic (ALA-PDT) therapy (10-20%) has been widely applied for moderate-to-severe acne. The aim of this study is to investigate the effects of non-ablative Q-switched 1064-nm Nd:YAG laser-assisted ALA-PDT with low concentration (2%) on the treatment of acne vulgaris. Enrolled patients were randomly assigned to 2 groups. One group received combined therapy of 2% ALA-PDT and non-ablative Q-switched 1064-nm Nd:YAG laser, and the other received only 2% ALA-PDT. Patients in each group had received 3-session treatments with 4-week intervals (week 0, 4, and 8). Sebum secretion, melanin index, erythema index, and transepidermal water loss (TEWL) were assessed at week 2, 8, 12, and 24. VISIA® skin image system score and global esthetic improvement scale (GAIS) were also evaluated. Twenty-four participants were enrolled and evenly randomized to two groups. Significant improvement in sebum secretion was noted in combined therapy group compared to the monotherapy group at week 12 (37.5% versus 16.3%), and the improvement would still be noted until week 24 (18.3% versus 17.4%). Combined group also showed more severe melanin index and erythema index after treatment. For VISIA® skin analysis, patients in combined group had better percentile ranking in porphyrins and red-light images. There were no significant differences in GAIS at the end of the follow-up between each group, whereas higher proportion of satisfaction was noted in combined group at week 2. With the assistance of laser, low concentrations (2%) of 5-ALA can provide effective phototoxic reactions in treating acne vulgaris. The satisfaction of patients is high with acceptable adverse effects., (© 2023. The Author(s), under exclusive licence to Springer-Verlag London Ltd., part of Springer Nature.)

Background: Dynamic in vivo changes in melanin in melasma lesions after exposure to ultraviolet (UV) irradiation have not been described., Objectives: To determine whether melasma lesions and nearby perilesions demonstrated different adaptive responses to UV irradiation and whether the tanning responses were different among different locations on face., Methods: We collected sequential images from real-time cellular resolution full-field optical coherence tomography (CRFF-OCT) at melasma lesions and perilesions among 20 Asian patients. Quantitative and layer distribution analyses for melanin were performed using a computer-aided detection (CADe) system that utilizes spatial compounding-based denoising convolutional neural networks., Results: The detected melanin (D) is melanin with a diameter >0.5 µm, among which confetti melanin (C) has a diameter of >3.3 µm and corresponds to a melanosome-rich package. The calculated C/D ratio is proportional to active melanin transportation. Before UV exposure, melasma lesions had more detected melanin (p = 0.0271), confetti melanin (p = 0.0163), and increased C/D ratio (p = 0.0152) in the basal layer compared to those of perilesions. After exposure to UV irradiation, perilesions have both increased confetti melanin (p = 0.0452) and the C/D ratio (p = 0.0369) in basal layer, and this effect was most prominent in right cheek (p = 0.030). There were however no significant differences in the detected, confetti, or granular melanin areas before and after exposure to UV irradiation in melasma lesions in all the skin layers., Conclusions: Hyperactive melanocytes with a higher baseline C/D ratio were noted in the melasma lesions. They were "fixed" on the plateau and were not responsive to UV irradiation regardless of the location on face. Perilesions retained adaptability with a dynamic response to UV irradiation, in which more confetti melanin was shed, mainly in the basal layer. Therefore, aggravating effect of UV on melasma was mainly due to UV-responsive perilesions rather than lesions., (© 2023 Wiley Periodicals LLC.)

Atopic dermatitis (AD) is a common skin disease worldwide. The major causes of AD are skin barrier defects, immune dysfunction, and oxidative stress. In this study, we investigated the anti-oxidation and anti-inflammation effects of Coffea arabica extract (CAE) and its regulation of the skin barrier and immune functions in AD. In vitro experiments revealed that CAE decreased the reactive oxygen species levels and inhibited the translocation of nuclear factor-κB (NF-κB), further reducing the secretion of interleukin (IL)-1β and IL-6 induced by interferon-γ (IFN-γ)/tumor necrosis factor-α (TNF-α). Moreover, CAE decreased IFN-γ/TNF-α-induced NLR family pyrin domain-containing 3 (NLRP3), caspase-1, high-mobility group box 1 (HMGB1), and receptor for advanced glycation end products (RAGE) expression levels. It also restored the protein levels of skin barrier function-related markers including filaggrin and claudin-1. In vivo experiments revealed that CAE not only reduced the redness of the backs of mice caused by 2,4-dinitrochlorobenzene (DNCB) but also reduced the levels of pro-inflammatory factors in their skin. CAE also reduced transepidermal water loss (TEWL) and immune cell infiltration in DNCB-treated mice. Overall, CAE exerted anti-oxidation and anti-inflammation effects and ameliorated skin barrier dysfunction, suggesting its potential as an active ingredient for AD treatment.

Background: The painDETECT questionnaire (PDQ) is one of the available screening tools for neuropathic pain (NeP), with a cut-off score of 13. This study aimed to investigate changes in PDQ scores in patients undergoing posterior cervical decompression surgery for degenerative cervical myelopathy (DCM)., Methods: Patients with DCM undergoing cervical laminoplasty or laminectomy with posterior fusion were recruited. They were asked to complete a booklet questionnaire including PDQ and Numerical Rating Scales (NRS) for pain at baseline and one year after surgery. Patients with a preoperative PDQ score ≥13 were further investigated., Results: A total of 131 patients (mean age = 70.1 years; 77 male and 54 female) were analyzed. After posterior cervical decompression surgery for DCM, mean PDQ scores decreased from 8.93 to 7.28 (P = 0.008) in all patients. Of the 35 patients (27%) with preoperative PDQ scores ≥13, mean PDQ changed from 18.83 to 12.09 (P < 0.001). Comparing the NeP improved group (17 patients with postoperative PDQ scores ≤12) with the NeP residual group (18 patients with postoperative PDQ scores ≥13), the NeP improved group showed less preoperative neck pain (2.8 vs. 4.4, P = 0.043) compared to the NeP residual group. There was no difference in the postoperative satisfaction rate between the two groups., Conclusions: Approximately 30% of patients exhibited preoperative PDQ scores ≥13, and about half of these patients demonstrated improvements to below to the cut-off value for NeP after posterior cervical decompression surgery. The PDQ score change was relatively associated with preoperative neck pain., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Hepatitis B virus (HBV) infection and integration are important for hepatocellular carcinoma (HCC) initiation and progression, while disease mechanisms are still largely elusive. Here, we combined bulk and single-cell sequencing technologies to tackle the disease mechanisms of HBV-related HCC. We observed high HBV mutation rate and diversity only in tumors without HBV integration. We identified human somatic risk loci for HBV integration (VIMs). Transcription factors (TFs) enriched in VIMs were involved in DNA repair and androgen receptor (AR) signaling. Aberration of AR signaling was further observed by single-cell regulon analysis in HBV-infected hepatocytes, which showed remarkable interactions between AR and the complement system that, together with the X-linked ZXDB regulon that contains albumin (ALB), probably contribute to HCC male predominance. Complement system dysregulation caused by HBV infection was further confirmed by analyses of single-cell copy numbers and cell-cell communications. Finally, HBV infection-associated immune cells presented critical defects, including TXNIP in T cells, TYROBP in NK cells, and the X-linked TIMP1 in monocytes. We further experimentally validated our findings in multiple independent patient cohorts. Collectively, our work shed light on the pathogenesis of HBV-related HCC and other liver diseases that affect billions of people worldwide., (© 2023 Wiley Periodicals LLC.)

Sickle cell disease (SCD) is a chronic hemolytic and systemic hypoxia condition with constant oxidative stress and significant metabolic alterations. However, little is known about the correlation between metabolic alterations and the pathophysiological symptoms. Here, we report that Nrf2, a master regulator of cellular antioxidant responses, regulates the production of the metabolite l-2-hydroxyglutarate (L2HG) to mediate epigenetic histone hypermethylation for gene expression involved in metabolic, oxidative, and ferroptotic stress responses in SCD. Mechanistically, Nrf2 was found to regulate the expression of L2HG dehydrogenase (L2hgdh) to mediate L2HG production under hypoxia. Gene expression profile analysis indicated that reactive oxygen species (ROS) and ferroptosis responses were the most significantly affected signaling pathways after Nrf2 ablation in SCD. Nrf2 silencing and L2HG supplementation sensitize human sickle erythroid cells to ROS and ferroptosis stress. The absence of Nrf2 and accumulation of L2HG significantly affect histone methylation for chromatin structure modification and reduce the assembly of transcription complexes on downstream target genes to regulate ROS and ferroptosis responses. Furthermore, pharmacological activation of Nrf2 was found to have protective effects against ROS and ferroptosis stress in SCD mice. Our data suggest a novel mechanism by which Nrf2 regulates L2HG levels to mediate SCD severity through ROS and ferroptosis stress responses, suggesting that targeting Nrf2 is a viable therapeutic strategy for ameliorating SCD symptoms., (© 2023 by The American Society of Hematology.)

Understanding the mechanisms that maintain microbial biodiversity is a critical aspiration in ecology. Past work on microbial coexistence has largely focused on species pairs, but it is unclear whether pairwise coexistence in isolation is required for coexistence in a multispecies community. To address this question, we conducted hundreds of pairwise competition experiments among the stably coexisting members of 12 different enrichment communities in vitro. To determine the outcomes of these experiments, we developed an automated image analysis pipeline to quantify species abundances. We found that competitive exclusion was the most common outcome, and it was strongly hierarchical and transitive. Because many species that coexist within a stable multispecies community fail to coexist in pairwise co-culture under identical conditions, we concluded that multispecies coexistence is an emergent phenomenon. This work highlights the importance of community context for understanding the origins of coexistence in complex ecosystems.

Competing Interests: The authors have no financial interest to declare in relation to the content of this article. Disclosure statements are at the end of this article, following the correspondence information.

Background: Subcutaneous emphysema is a well-known complication of oral surgery, especially during mandibular wisdom tooth extraction. However, subcutaneous emphysema secondary to dental procedures such as crown preparation is rare. The main symptom of emphysema is swelling and crepitus on palpation. Uncontrolled emphysema may spread along the fascial planes and cause deep space infections or a pneumomediastinum., Case Summary: In this paper, we report a 34-year-old female who underwent upper molar tooth preparation for crowns and subsequently developed extensive subcutaneous emphysema on the retromandibular angle on two different occasions. The treatment plan for this patient involved close observation of the airway, and administration of dexamethasone and antibiotics via intravenous drip or orally. Ice bag compression was quickly applied and medication was prescribed to alleviate discomfort and promote healing. Although the main reason is unclear, the presence of a fissure in the molar is an important clue which may contribute to the development of subcutaneous emphysema during crown preparation. It is imperative for dental professionals to recognize such pre-disposing factors in order to minimize the risk of complications., Conclusion: This case highlights the need for prompt diagnosis and management of subcutaneous emphysema because of the risk of much more serious complications. Awareness of relatively "benign" subcutaneous emphysema during any dental procedure is critical not only for inexperienced dentists, but also for those who work in rural and remote settings as members of surgical teams. In this study, we review the clinical presentation, mechanism, and differential diagnosis of subcutaneous emphysema., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

This paper presents an adjoint method for locating potential leakage in a single-phase fluid pipeline based on the analytic solution of inversion modeling. By studying the mechanism of pipeline leakage pressure, the adjoint equation based on the governing equation of transient flow is established in the single-liquid phase aspect using inverse adjoint theory and sensitivity analysis method. The inverse transient adjoint equation is primarily derived from the single linear fluid pipeline in the semi-infinite domain. The Laplace method is then used to obtain an analytical solution that determines the location of pipeline leakage. The experimental results indicate that the analytic solution can quickly and accurately judge the leakage location of the pipeline. Furthermore, it presents a new approach to engineering applications, such as gas-liquid two-phase flow complex pipe networks, etc., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Competing Interests: Conflict of InterestThe authors declare no conflicts of interest relevant to the reported work.

Background: The prevalence of food allergy (FA) is increasing. Decreases in the diversity of gut microbiota may contribute to the pathogenesis of FA by regulating IgE production of B cells. Intermittent fasting (IF) is a popular diet with the potential to regulate glucose metabolism, boosting immune memory and optimizing gut microbiota. The potential effect of long-term IF on the prevention and treatment of FA is still unknown., Methods: Two IF protocols (16 h fasting/8 h feeding and 24 h fasting/24 h feeding) were conducted on mice for 56 days, while the control mice were free to intake food (free diet group, FrD). To construct the FA model, all mice were sensitized and intragastrical challenged with ovalbumin (OVA) during the second half of IF (day 28 to day 56). Rectal temperature reduction and diarrhea were recorded to evaluate the symptoms of FA. Levels of serum IgE, IgG1, Th1/Th2 cytokines, mRNA expression of spleen T cell related transcriptional factors, and cytokines were examined. H&E, immunofluorescence, and toluidine blue staining were used to assess the structural changes of ileum villi. The composition and abundance of gut microbiota were analyzed by 16srRNA sequencing in cecum feces., Results: The diarrhea score and rectal temperature reduction were lower in the two fasting groups compared to the FrD groups. Fasting was associated with lower levels of serum OVA-sIgE, OVA-sIgG1, interleukin (IL)-4 and IL-5, and mRNA expression of IL-4, IL-5, and IL-10 in the spleen. While no significant association was observed in interferon (IFN)-γ, tumor necrosis factor (TNF)-α, IL-6, IL-2 levels. Less mast cell infiltration in ileum was observed in the 16h/8h fasting group compared to the FrD group. ZO-1 expression in the ileum of the two fasting groups was higher in IF mice. The 24h/24h fasting reshaped the gut microbiota, with a higher abundance of Alistipes and Rikenellaceae strains compared to the other groups., Conclusion: In an OVA-induced mice FA model, long-term IF may attenuate FA by reducing Th2 inflammation, maintaining the integrity of the intestinal epithelial barrier, and preventing gut dysbiosis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Ma, Hu, Fu, Zhong, Cao, Wang, Qi, Zhang, Liu and Gao.)

Background: An esophageal defect usually resulted from surgical ablation of tumors or corrosive injury. Staged reconstructions are required usually in extensive defects., Aim and Objectives: This study aimed to present a rare iatrogenic complication of total esophageal avulsion injury during upper gastrointestinal endoscopic treatment and to perform staged reconstructions to create a neoesophagus., Materials and Methods: In the presented case, staged reconstructions with a tubed deltopectoral flap and a supercharged colon interposition flap were performed to reconstruct the hypopharynx and esophagus. However, recurrent choking occurred because of the extent of injury involving the epiglottis. A tubed free radial forearm flap connected to the lower buccogingival sulcus was used to create a new route for food passage., Results: The patient resumed oral intake after rehabilitation., Conclusions: The avulsion injury of the total esophagus is rare and devastating. Staged reconstructions with a tubed deltopectoral flap, a supercharged colon interposition flap, and a tubed free radial forearm flap would be a safe and reliable method., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Colonic diverticulitis is a leading cause of abdominal pain. The monocyte distribution width (MDW) is a novel inflammatory biomarker with prognostic significance for coronavirus disease and pancreatitis; however, no study has assessed its correlation with the severity of colonic diverticulitis., Methods: This single-center retrospective cohort study included patients older than 18 years who presented to the emergency department between November 1, 2020, and May 31, 2021, and received a diagnosis of acute colonic diverticulitis after abdominal computed tomography. The characteristics and laboratory parameters of patients with simple versus complicated diverticulitis were compared. The significance of categorical data was assessed using the chi-square or Fisher's exact test. The Mann-Whitney U test was used for continuous variables. Multivariable regression analysis was performed to identify predictors of complicated colonic diverticulitis. Receiver operator characteristic (ROC) curves were used to test the efficacy of inflammatory biomarkers in distinguishing simple from complicated cases., Results: Of the 160 patients enrolled, 21 (13.125%) had complicated diverticulitis. Although right-sided was more prevalent than left-sided colonic diverticulitis (70% versus 30%), complicated diverticulitis was more common in those with left-sided colonic diverticulitis (61.905%, p = 0.001). Age, white blood cell (WBC) count, neutrophil count, C-reactive protein (CRP) level, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and MDW were significantly higher in the complicated diverticulitis group (p < 0.05). Logistic regression analysis indicated that the left-sided location and the MDW were significant and independent predictors of complicated diverticulitis. The area under the ROC curve (AUC) was as follows: MDW, 0.870 (95% confidence interval [CI], 0.784-0.956); CRP, 0.800 (95% CI, 0.707-0.892); NLR, 0.724 (95% CI, 0.616-0.832); PLR, 0.662 (95% CI, 0.525-0.798); and WBC, 0.679 (95% CI, 0.563-0.795). When the MDW cutoff was 20.38, the sensitivity and specificity were maximized to 90.5% and 80.6%, respectively., Conclusions: A large MDW was a significant and independent predictor of complicated diverticulitis. The optimal cutoff value for MDW is 20.38 as it exhibits maximum sensitivity and specificity for distinguishing between simple and complicated diverticulitis The MDW may aid in planning antibiotic therapy for patients with colonic diverticulitis in the emergency department., (© 2023. The Author(s).)

Objective: 5-Hydroxymethylfurfural (5-HMF) is an important component of air pollution, confirmed to be a risk factor for pulmonary inflammation. However, its association with general health is unknown. This article aimed to clarify the effect and mechanism of 5-HMF in the occurrence and aggravation of frailty in mice by investigating whether exposure to 5-HMF was linked to the occurrence and aggravation of mice frailty., Methods: Twelve male C57BL/6 mice (12-month-old, 38 ± 1 g) were randomly divided into the control group and the 5-HMF group. The 5-HMF group was treated with 5-HMF (1 mg/kg/day, respiratory exposure) for 12 months, whereas the control group was treated with equal amounts of sterile water. After the intervention, the ELISA method was used to detect the serum inflammation level of the mice, and the physical performance and frail status were evaluated using a Fried physical phenotype-based assessment tool. The differences in the body compositions were calculated from their MRI images, and the pathological changes in their gastrocnemius muscle were revealed using the H&E staining. Furthermore, the senescence of skeletal muscle cells was evaluated by measuring the expression levels of senescence-related proteins by the western blotting., Results: In the 5-HMF group, serum inflammatory factors IL-6, TNF-α, and CRP levels were significantly raised ( p  < 0.01). Mice in this group had higher frailty scores and significantly reduced grip strength ( p  < 0.001), slower weight gains, less WVgastrocnemius muscle masses, and lower sarcopenia indices (SI). In addition, the cross-sectional areas of their skeletal muscles were reduced, and the levels of their cell senescence-related proteins (p53, p21, p16, SOD1, SOD2, SIRT1, SIRT3) were considerably altered ( p  < 0.01)., Conclusion: 5-HMF may induce chronic and systemic inflammation, which in turn accelerates the progression of the frailty of mice through cell senescence., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Marine Predators Algorithm (MPA) is a newly nature-inspired meta-heuristic algorithm, which is proposed based on the Lévy flight and Brownian motion of ocean predators. Since the MPA was proposed, it has been successfully applied in many fields. However, it includes several shortcomings, such as falling into local optimum easily and precocious convergence. To balance the exploitation and exploration ability of MPA, a modified marine predators algorithm hybridized with teaching-learning mechanism is proposed in this paper, namely MTLMPA. Compared with MPA, the proposed MTLMPA has two highlights. Firstly, a kind of teaching mechanism is introduced in the first phase of MPA to improve the global searching ability. Secondly, a novel learning mechanism is introduced in the third phase of MPA to enhance the chance encounter rate between predator and prey and to avoid premature convergence. MTLMPA is verified by 23 benchmark numerical testing functions and 29 CEC-2017 testing functions. Experimental results reveal that the MTLMPA is more competitive compared with several state-of-the-art heuristic optimization algorithms.

The Philadelphia 9;22 chromosome translocation has two common isoforms that are preferentially associated with distinct subtypes of leukemia. The p210 variant is the hallmark of chronic myeloid leukemia (CML) whereas p190 is frequently associated with B-cell acute lymphoblastic leukemia. The only sequence difference between the two isoforms is the guanidine exchange factor domain. This guanidine exchange factor is reported to activate RHO family GTPases in response to diverse extracellular stimuli. It is not clear whether and, if so, how RHOA contributes to progression of p210 CML. Here we show that knockout of RHOA in the K562 and KU812, p210-expressing cell lines leads to suppression of leukemogenesis in animal models in vivo. RNA-sequencing analysis of the mock control and null cells demonstrated a distinct change in the gene expression profile as a result of RHOA deletion, with significant downregulation of genes involved in cell activation and cell adhesion. Cellular analysis revealed that RHOA knockout leads to impaired cell adhesion and migration and, most importantly, the homing ability of leukemia cells to the bone marrow, which may be responsible for the attenuated leukemia progression. We also identified IGFBP2 as an important downstream target of RHOA. Further mechanistic investigation showed that RHOA activation leads to relocation of the serum response factor (SRF) into the nucleus, where it directly activates IGFBP2. Knockout of IGFBP2 in CML cells suppressed cell adhesion/invasion, as well as leukemogenesis in vivo. This elevated IGFBP2 expression was confirmed in primary CML samples. Thus, we demonstrate one mechanism whereby the RHOA-SRF-IGFBP2 signaling axis contributes to the development of leukemia in cells expressing the p210 BCR-ABL1 fusion kinase.