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Fungal overgrowth in halophilic aerobic granular sludge (HAGS) is a severe problem, leading to granule disintegration. However, it is still mostly unclear how to control fungal overgrowth. This study explored the effects of carbon availability in saline wastewater with a salinity of 20 g/L on fungal and bacterial population sizes, community compositions, and network interactions in HAGS by manipulating different carbon-to‑nitrogen ratios (C/N). Bacterial population size increased from 6.42 × 10 6 copies/ng DNA to 8.67 × 10 6 copies/ng DNA as the C/N ratio increased from 4 to 20. In contrast, fungal population size decreased from 1.24 × 10 6 copies/ng DNA to 8.05 × 10 3 copies/ng DNA. The maximum removal rate of ammonia by fungi decreased from 5.02 ± 0.04 mg·L -1 ·h -1 to 1.72 ± 0.30 mg·L -1 ·h -1 . Nitrosomonas, Thauera, and Planktosalinus competed for nutrients with the dominant fungi Cosmospora, being in antagonism. Carbon availability in the saline wastewater could regulate the population of bacteria and fungi, laying a theoretical foundation for controlling HAGS disintegration., 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.)

The synthesis of polyhydroxyalkanoates (PHAs) by extremophiles presents a promising alternative to mitigate pollution originating from the use of petroleum-based plastics. This study focuses on the impact of different magnetic field (MF) exposure patterns on PHA production and carbon metabolism, aiming to enhance PHA productivity by Haloferax mediterranei within the extreme hypersaline environment and subsequently reducing production costs. Results indicated that under 300 g/L salinity, the highest PHA productivity (1.45 ± 0.06 g/(L d)) and PHA content (65.91 % PHA/cell dry weight) were achieved with 50 mT MF exposure throughout the fermentation period. Continuous exposure to 50 mT MF proved vital for maximizing cell biomass and PHA productivity. Continuous exposure to 50 mT MF enabled Haloferax mediterranei to channel acetyl-CoA towards the PHA synthesis pathway while maintaining growth and proliferation. Correlation analysis further proved the principal role of carbon flux on PHA accumulation. Due to the demand for balancing osmotic pressure, cellular substances were sacrificed to ensure PHA synthesis as anti-salinity substance. Meanwhile, the observed promotion of MF on PHA production, betaine aldehyde dehydrogenase activity, and K + uptake contributed to sustaining cellular activity at 300 g/L salinity. This study provides a non-gene editing approach to enhance PHA productivity., 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.)

The recent surge in tandem solar cells and indoor photovoltaics has renewed interest in selenium (Se), the world's first photovoltaic material, due to its intrinsic wide bandgap of ≈1.9 eV, high stability, and non-toxicity in small quantities when applied in photovoltaics. However, with a 1D chained crystal structure, Se tends to grow crystalline films with a lying orientation-chains parallel to substrates arising from the low surface energy; this results in poor carrier transport across chains held together by weak van der Waals forces. Here a substrate-heating strategy that facilitates the interfacial bonding between Se and substrate is introduced, enabling the growth of Se films with a standing orientation-chains perpendicular to substrates. This achieves efficient carrier transport along covalently bonded chains. The resulting Se films thereby exhibit a fourfold increase in carrier mobility compared to lying-oriented Se films. Consequently, Se solar cells are achieved with the highest power conversion efficiency of 8.1% under AM1.5G 1-sun illumination. The unencapsulated devices exhibit negligible efficiency loss after 1 000 h of storage under ambient conditions., (© 2024 Wiley‐VCH GmbH.)

Background: It is challenging to correctly identify and diagnose breast nonmass lesions. This study aimed to explore the multimodal ultrasound features associated with malignant breast nonmass lesions (NMLs), and evaluate their combined diagnostic performance., Methods: This retrospective analysis was conducted on 573 breast NMLs, including 309 were benign and 264 were malignant, their multimodal ultrasound features (B-mode, color Doppler and strain elastography) were assessed by two experienced radiologists. Univariate and multivariate logistic regression analysises were used to explore multimodal ultrasound features associated with malignancy, and a nomogram was developed. Diagnostic performance and clinical utility were evaluated and validated by the receiver operating characteristic (ROC) curve, calibration curve and decision curve in the training and validation cohorts., Results: Multimodal ultrasound features including linear (odds ratio [OR] = 4.69) or segmental distribution (OR = 7.67), posterior shadowing (OR = 3.14), calcification (OR = 7.40), hypovascularity (OR = 0.38), elasticity scored 4 (OR = 7.00) and 5 (OR = 15.77) were independent factors associated with malignant breast NMLs. The nomogram based on these features exhibited diagnostic performance in the training and validation cohorts were comparable to that of experienced radiologists, with superior specificity (89.4%, 89.5% vs. 81.2%) and positive predictive value (PPV) (89.2%, 90.4% vs. 82.4%). The nomogram also demonstrated good calibration in both training and validation cohorts (all P > 0.05). Decision curve analysis indicated that interventions guided by the nomogram would be beneficial across a wide range of threshold probabilities (0.05-1 in the training cohort and 0.05-0.93 in the validation cohort)., Conclusions: The combined use of linear or segmental distribution, posterior shadowing, calcification, hypervascularity and high elasticity score, displayed as a nomogram, demonstrated satisfied diagnostic performance for malignant breast NMLs, which may contribute to the imaging interpretation and clinical management of tumors., (© 2024. The Author(s).)

Graphite (Gr)-based lithium-ion batteries with admirable electrochemical performance below -20 °C are desired but are hindered by sluggish interfacial charge transport and desolvation process. Li salt dissociation via Li + -solvent interaction enables mobile Li + liberation and contributes to bulk ion transport, while is contradictory to fast interfacial desolvation. Designing kinetically-stable solid electrolyte interphase (SEI) without compromising strong Li + -solvent interaction is expected to compatibly improve interfacial charge transport and desolvation kinetics. However, the relationship between physicochemical features and temperature-dependent kinetics properties of SEI remains vague. Herein, we propose four key thermodynamics parameters of SEI potentially influencing low-temperature electrochemistry, including electron work function, Li + transfer barrier, surface energy, and desolvation energy. Based on the above parameters, we further define a novel descriptor, separation factor of SEI (S SEI ), to quantitatively depict charge (Li + /e - ) transport and solvent deprivation processes at Gr/electrolyte interface. A Li 3 PO 4 -based, inorganics-enriched SEI derived by Li difluorophosphate (LiDFP) additive exhibits the highest S SEI (4.89×10 3 ) to enable efficient Li + conduction, e - blocking and rapid desolvation, and as a result, much suppressed Li-metal precipitation, electrolyte decomposition and Gr sheets exfoliation, thus improving low-temperature battery performances. Overall, our work originally provides visualized guides to improve low-temperature reaction kinetics/thermodynamics by constructing desirable SEI chemistry., (© 2024 Wiley-VCH GmbH.)

Eco-compensation is an important component of ecological civilization construction. Therefore, it is of great significance to elucidate the spatial and temporal pattern of eco-compensation performance and its internal coupling and coordinated features to promote ecological civilization construction. We proposed that eco-compensation performance consists of benefit and efficiency, and used the projection pursuit and super-efficiency SBM-DEA models to measure the eco-compensation benefit and efficiency of 101 cities in the Yangtze River Economic Belt from 2010 to 2021 and to analyze their spatial and temporal patterns. Finally, we used the coupling coordination degree model to reveal the coupling and coordinated features of eco-compensation performance. The results showed that the temporal trends of eco-compensation benefit and efficiency were "W" and "U" shaped. The eco-compensation benefit in eastern or mega-cities was the highest, whereas the eco-compensation efficiency in western or small/medium-sized cities was the highest. Coupling coordination degree of eco-compensation performance was in the coordinated development stage from 2010 to 2012, with a concentration of agglomeration effects in the central region. It was in the transition/adjustment stage from 2013 to 2020, with low-value areas concentrated and scattered high-value areas, and smaller regional differences. It was in the coordinated development stage in 2021, with a clear agglomeration effect in the eastern region. Cities in the Yangtze River Economic Belt should incorporate the eco-compensation performance coupling coordination mechanism into their optimized eco-compensation policy plans based on the stage of coordinated development, to achieve their environmental improvement goals.

Background: Patients with airway stenosis (AS) are associated with considerable morbidity and mortality after lung transplantation (LTx). This study aims to develop and validate machine learning (ML) models to predict AS requiring clinical intervention in patients after LTx., Methods: Patients who underwent LTx between January 2017 and December 2019 were reviewed. The conventional logistic regression (LR) model was fitted by the independent risk factors which were determined by multivariate LR. The optimal ML model was determined based on 7 feature selection methods and 8 ML algorithms. Model performance was assessed by the area under the curve (AUC) and brier score, which were internally validated by the bootstrap method., Results: A total of 381 LTx patients were included, and 40 (10.5%) patients developed AS. Multivariate analysis indicated that male, pulmonary arterial hypertension, and postoperative 6-min walking test were significantly associated with AS (all P < 0.001). The conventional LR model showed performance with an AUC of 0.689 and brier score of 0.091. In total, 56 ML models were developed and the optimal ML model was the model fitted using a random forest algorithm with a determination coefficient feature selection method. The optimal model exhibited the highest AUC and brier score values of 0.760 (95% confidence interval [CI], 0.666-0.864) and 0.085 (95% CI, 0.058-0.117) among all ML models, which was superior to the conventional LR model., Conclusions: The optimal ML model, which was developed by clinical characteristics, allows for the satisfactory prediction of AS in patients after LTx., (© 2024. The Author(s).)

Background: Noninvasively and accurately predicting subcarinal lymph node metastasis (SLNM) for patients with non-small cell lung cancer (NSCLC) remains challenging. This study was designed to develop and validate a tumor and subcarinal lymph nodes (tumor-SLNs) dual-region computed tomography (CT) radiomics model for predicting SLNM in NSCLC., Methods: This retrospective study included NSCLC patients who underwent lung resection and SLNs dissection between January 2017 and December 2020. The radiomic features of the tumor and SLNs were extracted from preoperative CT, respectively. Ninety machine learning (ML) models were developed based on tumor region, SLNs region, and tumor-SLNs dual-region. The model performance was assessed by the area under the curve (AUC) and validated internally by fivefold cross-validation., Results: In total, 202 patients were included in this study. ML models based on dual-region radiomics showed good performance for SLNM prediction, with a median AUC of 0.794 (range, 0.686-0.880), which was superior to those of models based on tumor region (median AUC, 0.746; range, 0.630-0.811) and SLNs region (median AUC, 0.700; range, 0.610-0.842). The ML model, which is developed by using the naive Bayes algorithm and dual-region features, had the highest AUC of 0.880 (range of cross-validation, 0.825-0.937) among all ML models. The optimal logistic regression model was inferior to the optimal ML model for predicting SLNM, with an AUC of 0.727., Conclusions: The CT radiomics showed the potential for accurately predicting SLNM in NSCLC patients. The ML model with dual-region radiomic features has better performance than the logistic regression or single-region models., (© 2024. Society of Surgical Oncology.)

Background: Erythrocyte dysfunction is a characteristic of diabetes mellitus (DM). However, erythrocyte-associated biomarkers do not adequately explain the high prevalence of DM. Here, we describe red blood cell distribution width to albumin ratio (RAR) as a novel inflammatory biomarker for evaluating an association with DM prevalence and prognosis of all-cause mortality., Methods: Data analyzed in this study were extracted from the National Health and Nutrition Examination Survey (NHANES) 1999-2020. A total of 40,558 participants (non-DM and DM) were enrolled in the study; RAR quartiles were calibrated at Q1 [2.02,2.82] mL/g, Q2 (2.82,3.05] mL/g, Q3 (3.05,3.38] mL/g, and Q4 (3.38,12.08] mL/g. A total of 8,482 DM patients were followed (for a median of 84 months), of whom 2,411 died and 6,071 survived. The prevalence and prognosis associated with RAR and DM were analyzed; age and sex were stratified to analyze the prevalence of RAR in DM and the sensitivity of long-term prognosis., Results: Among non-DM ( n =30,404) and DM ( n =10,154) volunteers, DM prevalence in RAR quartiles was 8.23%, 15.20%, 23.92%, and 36.39%. The multivariable odds ratio (OR) was significant for RAR regarding DM, at 1.68 (95% CI 1.42, 1.98). Considering Q1 as a foundation, the Q4 OR was 2.57 (95% CI 2.11, 3.13). The percentages of DM morbidity varied across RAR quartiles for dead ( n =2,411) and surviving ( n =6,071) DM patients. Specifically, RAR quartile mortality ratios were 20.31%, 24.24%, 22.65%, and 29.99% (P<0.0001). The multivariable hazard ratio (HR) for RAR was 1.80 (95% CI 1.57, 2.05). Considering Q1 as a foundation, the Q4 HR was 2.59 (95% CI 2.18, 3.09) after adjusting for confounding factors. Sensitivity analysis revealed the HR of male DM patients to be 2.27 (95% CI 1.95, 2.64), higher than females 1.56 (95% CI 1.31, 1.85). DM patients who were 60 years of age or younger had a higher HR of 2.08 (95% CI1.61, 2.70) as compared to those older than 60 years, who had an HR of 1.69 (95% CI 1.47, 1.94). The HR of RAR in DM patients was optimized by a restricted cubic spline (RCS) model; 3.22 was determined to be the inflection point of an inverse L-curve. DM patients with a RAR >3.22 mL/g suffered shorter survival and higher mortality as compared to those with RAR ≤3.22 mL/g. OR and HR RAR values were much higher than those of regular red blood cell distribution width., Conclusions: The predictive value of RAR is more accurate than that of RDW for projecting DM prevalence, while RAR, a DM risk factor, has long-term prognostic power for the condition. Survival time was found to be reduced as RAR increased for those aged ≤60 years among female DM patients., 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 Liu, Wang, Gao, Zhang, Zhang, Xu, Yao, Yang and Yan.)

Rosa multiflora , originated from East Asia, is one of the original ancestors of modern roses. It is also an important genetic resource and rootstock for rose cultivation. Due to its high resistance and vigorous growth, R. multiflora has become an invasive species in some introduction sites, such as North America. To explore the correlation between the suitable habitat of R. multiflora and climate change, we predicted its potential geographic distribution with an optimized MaxEnt model based on 1246 distribution records and nine bioclimatic variables. The results showed that the mean temperature of the coldest quarter, minimum temperature of the coldest month, precipitation of the warmest quarter, and isothermality were significant bioclimatic variables affecting the potential geographic distribution of R. multiflora. Under current climate conditions, R. multiflora naturally distributed in the plains and hilly areas to the east and south of the Loess Plateau. The distribution pattern in the mid-holocene was similar to its current distribution, but the highly suitable distribution area was in the south of North China Plain, the Sichuan Basin, and parts of the Middle-Lower Yangtze Plain. During the last interglacial, the suitable areas generally contrac-ted southward, while the highly suitable areas significantly expanded and mainly located in the Sichuan Basin, the Middle-Lower Yangtze Plains, the Yunnan-Guizhou Plateau, and the Southeast Hills. Beyond its natural distribution in East Asia, R. multiflora had been introduced and spread to most parts of Europe and the central and eastern United States. The distribution area of R. multiflora would expand under three warming scenarios of different shared socioeconomic pathways (SSP1-2.6, SSP2-4.5, and SSP5-8.5) during 2041-2060 and 2081-2100. Its average distribution center (centroid) would shift towards higher latitude, indicating that the distribution of R. multiflora was closely related to climate change and that global warming might lead to an expansion of its distribution area. These results would improve our understanding of the ecological adaptability of R. multiflora , facilitate the predicting of its future distribution, and provide a theoretical basis for monitoring and early warning measures following its introduction.

Non-small cell lung cancer (NSCLC) remains the leading cause of cancer-related deaths. With the development of screening, patient selection and treatment strategies, patients' survival outcomes and living quality significantly improved. However, some patients still have local recurrence or residual tumors after receiving definitive therapies. Salvage surgery has been regarded as an effective option for recurrent or residual NSCLC, but its effectiveness remains undetermined. Furthermore, conversion surgery is a special type of salvage surgery for tumors converted from "initially unresectable" to "potentially resectable" status due to a favorable response to systemic treatments. Although conversion surgery is a promising curative procedure for advanced NSCLC, its concept and clinical value remain unfamiliar to clinicians. In this narrative review, we provided an overview of the safety and efficacy of salvage surgery, especially salvage surgery after sublobar resection in early-stage NSCLC. More importantly, we highlighted the concept and value of conversion surgery after systemic treatment in advanced NSCLC to gain some insights into its role in the treatment of lung cancer., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Selenium (Se), the world's oldest optoelectronic material, has been widely applied in various optoelectronic devices such as commercial X-ray flat-panel detectors and photovoltaics. However, despite the rare and widely-dispersed nature of Se element, a sustainable recycling of Se and other valuable materials from spent Se-based devices has not been developed so far. Here a sustainable strategy is reported that makes use of the significantly higher vapor pressure of volatile Se compared to other functional layers to recycle all of them from end-of-life Se-based devices through a closed-space evaporation process, utilizing Se photovoltaic devices as a case study. This strategy results in high recycling yields of ≈ 98% for Se and 100% for other functional materials including valuable gold electrodes and glass/FTO/TiO 2 substrates. The refabricated photovoltaic devices based on these recycled materials achieve an efficiency of 12.33% under 1000-lux indoor illumination, comparable to devices fabricated using commercially sourced materials and surpassing the current indoor photovoltaic industry standard of amorphous silicon cells., (© 2024 The Authors. Advanced Science published by Wiley‐VCH GmbH.)

Background: Automated Breast Ultrasound (AB US) has shown good application value and prospects in breast disease screening and diagnosis. The aim of the study was to explore the ability of AB US to detect and diagnose mammographically Breast Imaging Reporting and Data System (BI-RADS) category 4 microcalcifications., Methods: 575 pathologically confirmed mammographically BI-RADS category 4 microcalcifications from January 2017 to June 2021 were included. All patients also completed AB US examinations. Based on the final pathological results, analyzed and summarized the AB US image features, and compared the evaluation results with mammography, to explore the detection and diagnostic ability of AB US for these suspicious microcalcifications., Results: 250 were finally confirmed as malignant and 325 were benign. Mammographic findings including microcalcifications morphology (61/80 with amorphous, coarse heterogeneous and fine pleomorphic, 13/14 with fine-linear or branching), calcification distribution (189/346 with grouped, 40/67 with linear and segmental), associated features (70/96 with asymmetric shadow), higher BI-RADS category with 4B (88/120) and 4 C (73/38) showed higher incidence in malignant lesions, and were the independent factors associated with malignant microcalcifications. 477 (477/575, 83.0%) microcalcifications were detected by AB US, including 223 malignant and 254 benign, with a significantly higher detection rate for malignant lesions (x 2  = 12.20, P < 0.001). Logistic regression analysis showed microcalcifications with architectural distortion (odds ratio [OR] = 0.30, P = 0.014), with amorphous, coarse heterogeneous and fine pleomorphic morphology (OR = 3.15, P = 0.037), grouped (OR = 1.90, P = 0.017), liner and segmental distribution (OR = 8.93, P = 0.004) were the independent factors which could affect the detectability of AB US for microcalcifications. In AB US, malignant calcification was more frequent in a mass (104/154) or intraductal (20/32), and with ductal changes (30/41) or architectural distortion (58/68), especially with the both (12/12). BI-RADS category results also showed that AB US had higher sensitivity to malignant calcification than mammography (64.8% vs. 46.8%)., Conclusions: AB US has good detectability for mammographically BI-RADS category 4 microcalcifications, especially for malignant lesions. Malignant calcification is more common in a mass and intraductal in AB US, and tend to associated with architectural distortion or duct changes. Also, AB US has higher sensitivity than mammography to malignant microcalcification, which is expected to become an effective supplementary examination method for breast microcalcifications, especially in dense breasts., (© 2024. The Author(s).)

A total of 18 metal elements in ambient PM 2.5 in Zhengzhou were continuously determined using an online heavy metal observation instrument in January and April, 2021, and the changes in element concentrations were analyzed. Metal elements were traced via enrichment factors, positive matrix factorization (PMF), and a characteristic radar chart. The US EPA health risk assessment model was used to assess the health risks of heavy metals, and the backward trajectory method and the concentration-weighted trajectory (CWT) method were used to evaluate the potential source regions of health risks. The results showed that the element concentrations were higher in spring, and the sum of Fe, Ca, Si, and Al concentrations accounted for 89.8% and 87.5% of the total element concentrations in winter and spring, respectively. Cd was enriched significantly, which was related to human activities. The concentrations of Pb, Se, Zn, Ni, Sb, and K in winter and Cr, Ni, Fe, Mn, V, Ba, Ca, K, Si, and Al in spring increased with the increasing pollution level. The results of PMF and the characteristic radar chart showed that the main sources of metal elements in winter and spring were industry, crust, motor vehicles, and mixed combustion, with industry and mixed combustion pollution occurring more often in winter and crust pollution occurring more often in spring. Significant non-carcinogenic risks existed in both winter and spring with more severe health risks in winter, and Mn caused significant non-carcinogenic risks. The health risks in winter were mainly influenced by Zhengzhou and surrounding cities and long-distance transport in the northwest, and the health risks in spring were mainly influenced by Zhengzhou and surrounding cities.

Aim: To explore whether CD3ε is involved in the adaptive immunity of Aspergillus fumigatus ( A. fumigatus ) keratitis in mice and the role of innate and adaptive immunity in it., Methods: Mice models of A. fumigatus keratitis were established by intra-stromal injection and corneal epithelial scratching. Subconjunctival injections of natamycin, wedelolactone, LOX-1 inhibitor (poly I) or Dectin-1 inhibitor (laminarin) were used to treat mice with A. fumigatus keratitis. Mice were pretreated by intraperitoneal injection of anti-mouse CD3ε. We observed the corneal infection of mice under the slit lamp microscope and made a clinical score. The protein expression of CD3ε and interleukin-10 (IL-10) was determined by Western blotting., Results: With the disease progresses, the degree of corneal opacity and edema augmented. In the intra-stromal injection models, CD3ε protein expression began to increase significantly on the 2 nd day. However, in the scraping epithelial method models, CD3ε only began to increase on the 3 rd day. After natamycin treatment, the degree of corneal inflammation in mice was significantly attenuated on the 3 rd day. After wedelolactone treatment, the severity of keratitis worsened. And the amount of CD3ε protein was also reduced, compared with the control group. By inhibiting LOX-1 and Dectin-1, there was no significant difference in CD3ε production compared with the control group. After inhibiting CD3ε, corneal ulcer area and clinical score increased, and IL-10 expression was downregulated., Conclusion: As a pan T cell marker, CD3ε participate in the adaptive immunity of A. fumigatus keratitis in mice. In our mice models, the corneas will enter the adaptive immune stage faster. By regulating IL-10, CD3ε exerts anti-inflammatory and repairs effects in the adaptive immune stage., Competing Interests: Conflicts of Interest: Shi WH, None; Wang LM, None; Yan HJ, None; Liu SL, None; Yang X, None; Yang XJ, None; Che CY, None., (International Journal of Ophthalmology Press.)

Based on the One Strain-Many Compounds (OSMAC) strategy, the secondary metabolites of Phomopsis lithocarpus FS508 were investigated. As a result, a new secondary metabolite, 4-methoxy-3-[4-(acetyloxy)-3-methyl-2-butenyl]benzoic acid ( 1 ) as well as eleven known compounds were isolated from the fermentation product of the strain FS508. Their structures were determined by NMR, IR, UV, and MS spectroscopic data analyses. All the isolated compounds were evaluated for cytotoxic and anti-inflammatory activities. Among them, compounds 3 and 9 displayed potent cytotoxicity against HepG-2 cell line, and compounds 2 , 3 and 12 showed significant anti-inflammatory activities.

Background: The neural cells in the brains of patients with Parkinson's disease (PWP) display aberrant synchronized oscillatory activity within the beta frequency range. Additionally, enhanced gamma oscillations may serve as a compensatory mechanism for motor inhibition mediated by beta activity and also reinstate plasticity in the primary motor cortex affected by Parkinson's disease. Transcranial alternating current stimulation (tACS) can synchronize endogenous oscillations with exogenous rhythms, thereby modulating cortical activity. The objective of this study is to investigate whether the addition of tACS to multidisciplinary intensive rehabilitation treatment (MIRT) can improve symptoms of PWP so as to enhance the quality of life in individuals with Parkinson's disease based on the central-peripheral-central theory., Methods: The present study was a randomized, double-blind trial that enrolled 60 individuals with Parkinson's disease aged between 45 and 70 years, who had Hoehn-Yahr scale scores ranging from 1 to 3. Participants were randomly assigned in a 1:1 ratio to either the tACS + MIRT group or the sham-tACS + MIRT group. The trial consisted of a two-week double-blind treatment period followed by a 24-week follow-up period, resulting in a total duration of twenty-six weeks. The primary outcome measured the change in PDQ-39 scores from baseline (T0) to 4 weeks (T2), 12 weeks (T3), and 24 weeks (T4) after completion of the intervention. The secondary outcome assessed changes in MDS-UPDRS III scores at T0, the end of intervention (T1), T2, T3, and T4. Additional clinical assessments and mechanistic studies were conducted as tertiary outcomes., Discussion: The objective of this study is to demonstrate that tACS can enhance overall functionality and improve quality of life in PWP, based on the framework of MIRT. Additionally, it seeks to establish a potential correlation between these therapeutic effects and neuroplasticity alterations in relevant brain regions. The efficacy of tACS will be assessed during the follow-up period in order to optimize neuroplasticity and enhance its potential impact on rehabilitation efficiency for PWP., Trial Registration: Chinese Clinical Trial Registry ChiCTR2300071969. Registered on 30 May 2023., (© 2024. The Author(s).)

Puerarin (Pue) is a naturally bioactive compound with many potential functions in regulating blood glucose and lipid metabolism. However, the low bioavailability and rapid elimination in vivo limit the application of Pue in diabetic treatment. Here, we developed a metal-polyphenol-functionalized microgel to effectively deliver Pue in vivo and eventually alleviate the onset of diabetes. Pue was initially encapsulated in alginate beads through electrospray technology, and further immersed in Fe 3+ and tannic acid solution from tannic acid (TA)-iron (Fe) coatings (TF). These constructed Pue@SA-TF microgels exhibited uniform spheres with an average size of 367.89 ± 18.74 µm and high encapsulation efficiency of Pue with 61.16 ± 1.39%. In vivo experiments proved that compared with free Pue and microgels without TF coatings, the biological distribution of Pue@SA-TF microgels specifically accumulated in the small intestine, prolonged the retention time of Pue, and achieved a high effectiveness in vivo. Anti-diabetic experimental results showed that Pue@SA-TF microgels significantly improved the levels of blood glucose, blood lipid, and oxidative stress in diabetic mice. Meanwhile, histopathological observations indicated that Pue@SA-TF microgels could significantly alleviate the damage to the liver, kidney, and pancreas in diabetic mice. Our study provided an effective strategy for oral delivery of Pue and achieved high anti-diabetic efficacy., (© 2023. Controlled Release Society.)

Objectives: Variants in NEXMIF had been reported associated with intellectual disability (ID) without epilepsy or developmental epileptic encephalopathy (DEE). It is unkown whether NEXMIF variants are associated with epilepsy without ID. This study aims to explore the phenotypic spectrum of NEXMIF and the genotype-phenotype correlations., Materials and Methods: Trio-based whole-exome sequencing was performed in patients with epilepsy. Previously reported NEXMIF variants were systematically reviewed to analyze the genotype-phenotype correlations., Results: Six variants were identified in seven unrelated cases with epilepsy, including two de novo null variants and four hemizygous missense variants. The two de novo variants were absent in all populations of gnomAD and four hemizygous missense variants were absent in male controls of gnomAD. The two patients with de novo null variants exhibited severe developmental epileptic encephalopathy. While, the patients with hemizygous missense variants had mild focal epilepsy with favorable outcome. Analysis of previously reported cases revealed that males with missense variants presented significantly higher percentage of normal intellectual development and later onset age of seizure than those with null variants, indicating a genotype-phenotype correlation., Conclusion: This study suggested that NEXMIF variants were potentially associated with pure epilepsy with or without intellectual disability. The spectrum of epileptic phenotypes ranged from the mild epilepsy to severe developmental epileptic encephalopathy, where the epileptic phenotypes variability are potentially associated with patients' gender and variant type., 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. Published by Elsevier Ltd.)

Background: The DLG3 gene encodes disks large membrane-associated guanylate kinase scaffold protein 3, which plays essential roles in the clustering of N-methyl-D-aspartate receptors (NMDARs) at excitatory synapses. Previously, DLG3 has been identified as the causative gene of X-linked intellectual developmental disorder-90 (XLID-90; OMIM# 300850). This study aims to explore the phenotypic spectrum of DLG3 and the genotype-phenotype correlation., Methods: Trios-based whole-exome sequencing was performed in patients with epilepsy of unknown causes. To analyze the genotype-phenotype correlations, previously reported DLG3 variants were systematically reviewed., Results: DLG3 variants were identified in seven unrelated cases with epilepsy. These variants had no hemizygous frequencies in controls. All variants were predicted to be damaging by silico tools and alter the hydrogen bonds with surrounding residues and/or protein stability. Four cases mainly presented with generalized seizures, including generalized tonic-clonic and myoclonic seizures, and the other three cases exhibited secondary generalized tonic-clonic seizures and focal seizures. Multifocal discharges were recorded in all cases during electroencephalography monitoring, including the four cases with generalized discharges initially but multifocal discharges after drug treating. Protein-protein interaction network analysis revealed that DLG3 interacts with 52 genes with high confidence, in which the majority of disease-causing genes were associated with a wide spectrum of neurodevelopmental disorder (NDD) and epilepsy. Three patients with variants locating outside functional domains all achieved seizure-free, while the four patients with variants locating in functional domains presented poor control of seizures. Analysis of previously reported cases revealed that patients with non-null variants presented higher percentages of epilepsy than those with null variants, suggesting a genotype-phenotype correlation., Significance: This study suggested that DLG3 variants were associated with epilepsy with/without NDD, expanding the phenotypic spectrum of DLG3 . The observed genotype-phenotype correlation potentially contributes to the understanding of the underlying mechanisms driving phenotypic variation., 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 He, Luo, Jin, Wang, Xu, Jiao, Yan, Wang, Zhai, Ji, Zhang, Zhou, Li, Liao, Lan and Xu.)

Cholangiocarcinoma (CCA) is an epithelial cancer distinguished by bile duct cell differentiation and is also a fibroproliferative tumor. It is characterized by a dense mesenchyme and a complex tumor immune microenvironment (TME). The TME comprises both cellular and non-cellular components. The celluar component includes CCA cells, immune cells and mesenchymal cells represented by the cancer-associated fibroblasts (CAFs), while the non-cellular component is represented by mesenchymal elements such as the extracellular matrix (ECM). Recent studies have demonstrated the important role of the TME in the development, progression, and treatment resistance of CCA. These cell-associated prognostic markers as well as intercellular connections, may serve as potential therapeutic targets and could inspire new treatment approaches for CCA in the future. This paper aims to summarize the current understanding of CCA's immune microenvironment, focusing on immune cells, mesenchymal cells, ECM, intercellular interactions, and metabolism within the microenvironment., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Gastrointestinal motility disorders tend to develop after pancreaticoduodenectomy (PD). The objectives of this study were: (1) to investigate the impact of needleless transcutaneous neuromodulation (TN) on the postoperative recuperation following pancreaticoduodenectomy (PD), and (2) to explore the underlying mechanisms by which TN facilitates the recovery of gastrointestinal function after PD., Methods: A total of 41 patients scheduled for PD were randomized into two groups: the TN group ( n  = 21) and the Sham-TN group ( n  = 20). TN was performed at acupoints ST-36 and PC-6 twice daily for 1 h from the postoperative day 1 (POD1) to day 7. Sham-TN was performed at non-acupoints. Subsequent assessments incorporated both heart rate variation and dynamic electrogastrography to quantify alterations in vagal activity (HF) and gastric pacing activity., Results: 1)TN significantly decreased the duration of the first passage of flatus ( p  < 0.001) and defecation ( p  < 0.01) as well as the time required to resume diet ( p  < 0.001) when compared to sham-TN;2)Compared with sham-TN, TN increased the proportion of regular gastric pacing activity ( p  < 0.01);3) From POD1 to POD7, there was a discernible augmentation in HF induced by TN stimulation( p  < 0.01);4) TN significantly decreased serum IL-6 levels from POD1 to POD7 ( p  < 0.001);5) TN was an independent predictor of shortened hospital stay(β = - 0.349, p  = 0.035)., Conclusion: Needleless TN accelerates the recovery of gastrointestinal function and reduces the risk of delayed gastric emptying in patients after PD by enhancing vagal activity and controlling the inflammatory response.

Objectives: Lung adenocarcinomas have different prognoses depending on their histological growth patterns. Micropapillary growth within lung adenocarcinoma, particularly metastasis, is related to dismal prognostic outcome. Metastasis accounts for a major factor leading to mortality among lung cancer patients. Understanding the mechanisms underlying early stage metastasis can help develop novel treatments for improving patient survival., Methods: Here, quantitative mass spectrometry was conducted for comparing protein expression profiles among various histological subtypes, including adenocarcinoma in situ, minimally invasive adenocarcinoma, and invasive adenocarcinoma (including acinar and micropapillary [MIP] types). To determine the mechanism of MIP-associated metastasis, we identified a protein that was highly expressed in MIP. The expression of the selected highly expressed MIP protein was verified via immunohistochemical (IHC) analysis and its function was validated by an in vitro migration assay., Results: Proteomic data revealed that low-density lipoprotein receptor-related protein-associated protein 1 (LRPAP1) was highly expressed in MIP group, which was confirmed by IHC. The co-expressed proteins in this study, PSMD1 and HSP90AB1, have been reported to be highly expressed in different cancers and play an essential role in metastasis. We observed that LRPAP1 promoted lung cancer progression, including metastasis, invasion and proliferation in vitro and in vivo ., Conclusion: LRPAP1 is necessary for MIP-associated metastasis and is the candidate novel anti-metastasis therapeutic target., Competing Interests: The authors declare no conflicts of 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., (© 2023 The Authors.)

Titanium and its alloys are protected by a compact and stable passive film, which confers resistance to corrosion by the primary halogen chloride (Cl - ) while being less effective against fluoride (F - ). Although researchers have recognized different macroscopic corrosion effects of these halide ions on titanium, the underlying mechanisms remain largely unexplored. In this work, the bonding of Cl - /F - with stable passive films was studied in neutral and acidic (pH = 2.3) conditions. The synergistic effect between the interfacial hydrogen bond (HB) structure and halogens on titanium corrosion was first revealed using first-principles calculation and Raman spectroscopy. F - forms more stable halogen-Ti bonds than Cl - , resulting in titanium degradation. The proton combined with F - exhibits a specific synergistic effect, causing corrosion of the passive film. The water hydrogen bond transformation index (HBTI) at the titanium/aqueous interface was 1.88 in an acidic solution containing F - , significantly higher than that in neutral/acid solutions containing Cl - (1.80/1.81) and a neutral solution containing F - (1.81). This work clarifies the structure-activity relationship between HBTI and the destruction of titanium passive films. We propose that the microstructure of the interfacial HB is an undeniable factor in the corrosion of titanium.

Purpose: Older individuals are priority coronavirus disease 2019 (COVID-19) vaccine recipients. Our aim was to investigate the prevalence of and factors influencing vaccine hesitancy in older individuals living in nursing homes and communities., Methods: A self-administered COVID-19 vaccine hesitancy survey was conducted from September 2021 to December 2021 among people aged ≥ 60 years in eight nursing homes (382 participants) and the community (112 participants) in Taizhou, China. The response rate was 72.1% (382/530) for older adults in nursing homes and 68.7% (112/163) for older adults in the community., Results: We found that 58.1% of the older individuals in nursing homes and 36.6% of those in the community were hesitant to receive the COVID-19 vaccine and that there was a statistically significant difference (P < 0.001). Multiple logistic regression results indicated that the main factors influencing hesitation among the older individuals in nursing homes were being male (Odds Ratio (OR) = 1.67, 95% Confidence Interval (CI): 1.01-2.76); their cognitive level, including having a high perceived risk of COVID-19 infection (OR = 3.06, 95% CI: 1.73-5.43) or the perception of low vaccine safety (OR = 3.08, 95% CI: 1.545- 6.145); anxiety (OR = 3.43, 95% CI: 1.96-5.99); and no previous influenza vaccination (OR = 1.82, 95% CI: 1.13-2.93); whereas those for older individuals in the community were comorbid chronic diseases (OR = 3.13, 95% CI: 1.11- 8.78) and community workers not recommending the vaccine (OR = 8.223, 95% CI: 1.77-38.27)., Conclusion: The proportion of older individuals in nursing homes who were hesitant to receive the COVID-19 vaccine was significantly higher than for older individuals in the community. Targeted measures should be implemented to reduce vaccine hesitancy and improve vaccination rates in response to the special environment of nursing homes and the characteristics of this population., (© 2023. The Author(s).)

Plant-derived nucleic acids, especially small RNAs have been proved by increasing evidence in the pharmacological activities and disease treatment values in macrophage meditated anti-tumor performance, immune regulating functions and antiviral activities. But the uptake, application and delivery strategies of RNAs as biodrugs are different from the small molecules and recombinant protein drugs. This article summarizes the reported evidence for cross-kingdom regulation by plant derived functional mRNAs and miRNAs. Based on that, their involvement and potentials in macrophage-mediated anti-tumor/inflammatory therapies are mainly discussed, as well as the load prospect of plant RNAs in viruses and natural exosome vehicles, and their delivery to mammalian cells through macrophage were also summarized. This review is to provide evidence and views for the plant derived RNAs as next generation of drugs with application potential in nucleic acid-based bio-therapy., 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 Liu, Chen, Zhang, Yan, Yan, Zhu and Peng.)

We compared posttransplant outcomes following double-lung transplantation (DLTx) and heart-lung transplantation (HLTx), based on a search of PubMed, Cochrane Library, and Embase, from inception to March 8, 2022, for studies that report outcomes of these procedures. We then performed a meta-analysis of baseline characteristics and posttransplant outcomes. Subgroup analyses were implemented according to indication, publication year, and center. This study was registered on PROSPERO (number CRD42020223493). Ten studies were included in this meta-analysis, involving 1230 DLTx patients and 1022 HLTx patients. The DLTx group was characterized by older donors (P = 0.04) and a longer allograft ischemia time (P < 0.001) than the HLTx group. The two groups had comparable 1-year, 3-year, 5-year, 10-year survival rates (all P > 0.05), with similar results identified in subgroup analyses. We found no significant differences in 1-year, 5-year, and 10-year chronic lung allograft dysfunction (CLAD)-free survival, length of intensive care unit stay and hospital stay, length of postoperative ventilation, in-hospital mortality, or surgical complications between the groups (all P > 0.05). Thus, DLTx provides similar posttransplant survival to HLTx for end-stage cardiopulmonary disease. These two procedures have a comparable risk of CLAD and other posttransplant outcomes., (© 2022. The Author(s) under exclusive licence to Springer Nature Singapore Pte Ltd.)

Fungi have been found to exist in activated sludge treating saline wastewater, but their role in removing pollution has been neglected. This study explored the aerobic removal of total inorganic nitrogen (TIN) from saline wastewater under static magnetic fields (SMFs) with several strengths. Compared to the control, the aerobic removal of TIN was significantly increased by 1.47 times in 50 mT SMF, due to the increased dissimilation nitrogen removal by fungi and bacteria. Under SMF, fungal nitrogen dissimilation removal was significantly increased by 3.65 times. The fungal population size decreased, and its community composition changed significantly under SMF. In contrast, bacterial community composition and population remained relatively stable. Under SMFs, heterotrophic nitrification - aerobic denitrification bacteria Paracoccus and the fungi denitrifying Candida formed a synergistic interaction. This study elucidates the fungal role in aerobic TIN removal and provides an efficient solution to improve TIN removal from saline wastewater by SMF., 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 Ltd. All rights reserved.)

Patients with Parkinson's Disease presented gait impairment. Applying additional weights to enhancing sensory input may improve gait impairment. We assumed that gait impairment could be improved when patients walked with additional forearm weights, and the gait improvement was associated with clinical characteristic of Parkinson's Disease. Thirty patients with Parkinson's Disease and 30 age-sex matched controls were recruited. Spatiotemporal and joint kinematics parameters were evaluated by a three-dimensional motion capture system in normal walking and walking with sandbags, respectively. The comparisons of spatiotemporal parameters were analyzed using t-test or nonparametric tests. The comparison of joint kinematic data was analyzed using statistical parametric mapping. The correlation between motor symptom and gait parameters changes was analyzed using Pearson's correlation analysis. During normal walking, patients showed deteriorated gait compared with controls. After applying weights to forearms patients increased cadence (p = 0.004), speed (p < 0.001) and step length (p = 0.048), and decreased stride time (p = 0.003). The hip angles significantly increased during 5%-23% and 87%-100% of gait cycle, while knee angles during 9%-25% and 88%-98% of the gait cycle, and ankle angles in 92%-100% of gait cycle. The gait parameters of patients with forearm-loading showed no significant difference compared with healthy subjects walking normally. The change of gait parameters correlated positively with the axial and tremor severity while correlated negatively with the rigidity sub-score. Patients with tremor dominant subtype also showed greater improvement of speed and step time compared with patients with postural instability/gait difficulty subtype. Applying added weights bilaterally to the forearms of patients can normalize gait patterns. Notably, patients with higher scores on axial and tremor and lower rigidity scores gained more benefits., 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 Ltd. All rights reserved.)

Background: The site of lymph node metastasis (LNM) may affect the prognosis of patients with esophageal squamous cell carcinoma (ESCC). To investigate the prognoses of pararespiratory and paradigestive LNM and to propose a novel N (nN) staging system that integrates both the LNM site and count., Methods: This study was a multicenter, large-sample, retrospective cohort study that included ESCC patients with LNM between January 2014 and December 2019 from three Chinese institutes. Patients were set into training (two institutes) and external validation (one institute) cohorts. The primary outcomes were survival differences in LNM site and the development of novel nodal staging system. The overall survival (OS) of patients with pararespiratory LNM only (Group A), paradigestive LNM only (Group B), and both sites (Group C) was evaluated by Kaplan-Meier. Cox proportional hazards models were used to identify the independent prognostic factors. An nN staging system considering both the LNM site and count was developed and evaluated by the area under the receiver operating characteristic curve (AUC)., Results: In total, 1313 patients were included and split into training (n = 1033) and external validation (n = 280) cohorts. There were 342 (26.0%), 568 (43.3%) and 403 (30.7%) patients in groups A, B and C, respectively. The OS of patients with pararespiratory and patients with paradigestive LNM presented significant differences in the training and validation cohorts (P < 0.050). In the training cohort, LNM site was an independent prognostic factor (hazard ratio: 1.58, 95% confidence intervals: 1.41-1.77, P < 0.001). The nN staging definition: nN1 (1-2 positive pararespiratory/paradigestive LNs), nN2 (3-6 pararespiratory LNs or 1 pararespiratory with 1paradigestive LN), nN3 (3-6 LNs with ≥ 1 paradigestive LN), nN4 (≥ 7 LNs). Subsets of patients with different nN stages showed significant differences in OS (P < 0.050). The prognostic model of the nN staging system presented higher performance in the training and validation cohorts at 3-year OS (AUC, 0.725 and 0.751, respectively) and 5-year OS (AUC, 0.740 and 0.793, respectively) than the current N staging systems., Conclusions: Compared to pararespiratory LNM, the presence of paradigestive LNM is associated with worse OS. The nN staging system revealed superior prognostic ability than current N staging systems., (© 2023. The Author(s).)

Background: First-line rehabilitative strategies to improve motor deficits are based on functional training (physical or occupational therapy), which has been demonstrated to facilitate neural reorganisation. Accumulating evidence suggests that non-invasive brain stimulation techniques, such as repetitive TMS (rTMS), may enhance neuroplasticity, thereby facilitating neural reorganisation and recovery from Parkinson's disease. Evidence also shows that intermittent theta-burst stimulation (iTBS) can improve motor function and quality of life in patients by promoting the excitability and neural remodelling of cerebral cortex. We aimed to combine iTBS stimulation with physiotherapy to improve the rehabilitation effect compared to physiotherapy alone in patients with Parkinson's disease., Methods: This randomised, double-blind clinical trial will enrol 50 Parkinson's disease patients aged 45-70 years with Hoehn and Yahr scale scores of 1-3. Patients are randomly assigned to either the iTBS + physiotherapy or sham-iTBS + physiotherapy group. The trial consists of a 2-week double-blind treatment period and a 24-week follow-up period. iTBS and sham-iTBS will be administered twice daily for 10 days based on physiotherapy. The primary outcome will be the third part of Movement Disorders-Unified Parkinson's Disease Rating Scale (MDS-UPDRS III) from the baseline to the first 2 days following completion hospitalised intervention. The secondary outcome will be 39-item Parkinson's Disease Questionnaire (PDQ-39) at 4 weeks, 12 weeks and 24 weeks after intervention. Tertiary outcomes are clinical evaluations and mechanism study outcomes such as NMSS, 6MWD, 10MT, TUG, BBS, MRI, and EEG, the length of time between the drug needs to be adjusted when symptoms fluctuate., Discussion: The aim of this study is to demonstrate that iTBS can promote overall function and quality of life in Parkinson's disease patients using physiotherapy and that this efficacy may be associated with altered neuroplasticity in exercise-related brain regions. The iTBS combined with physiotherapy training model will be evaluated during a 6-month follow-up period. With significant improvement in quality of life and motor function, iTBS combined with physiotherapy can be considered as a first-line rehabilitation option for Parkinson's disease. The potential of iTBS to enhance neuroplasticity in the brain should have a more positive impact in increasing the generality and efficiency of physiotherapy, improving the quality of life and overall functional status of patients with Parkinson's disease., Trial Registration: Chinese Clinical Trial Registry ChiCTR2200056581. Registered on 8 February 2022., (© 2023. The Author(s).)

Objective: Data about postoperative infections in male adults with spinal cord injury are scarce. We aimed to evaluate the association between prior exposure to pressure ulcers (PU) and the risk of postoperative infections in male adults with spinal cord injury (SCI)., Methods: We conducted a prospective study of male adults receiving surgery of SCI from January 2007 to December 2019. Postoperative infection included septicemia, pneumonia, surgical incision infection and urinary tract infection. A logistic regression analysis was applied. Risk ratios (RRs) and their corresponding 95% confidence intervals (CIs) were calculated., Results: There were 408 patients with SCI in this study, which comprised 204 patients with prior PU and 204 patients without. The rate of postoperative infections within 14 days in patients with PU was 23.5%, which was higher than that of patients without PU (6.9%). The amounts to a 4.18-folds elevated risk of any postoperative infections with 14 days in patients with PU (RR: 4.18, 95% CI: 2.30-7.60, p -value: <0.001). With respect to specific infections, positive associations in pneumonia (RR: 4.18, 95% CI: 2.30-7.60, p -value: <0.001), surgical incision infection (RR: 4.18, 95% CI: 2.30-7.60, p -value: <0.001), and urinary tract infection (RR: 4.18, 95% CI: 2.30-7.60, p -value: <0.001) were also statistically significant. These results did not materially alter adjustment for potential risk factors., Conclusions: The study suggests an elevated risk of postoperative infections after surgery for SCI in male patients with prior exposure to pressure ulcers.

Background: Recessive SZT2 variants are reported to be associated with developmental and epileptic encephalopathy 18 (DEE-18) and occasionally neurodevelopment abnormalities (NDD) without seizures. This study aims to explore the phenotypic spectrum of SZT2 and the genotype-phenotype correlation., Methods: Trios-based whole-exome sequencing was performed in patients with epilepsy. Previously reported SZT2 mutations were systematically reviewed to analyze the genotype-phenotype correlations., Results: SZT2 variants were identified in six unrelated cases with heterogeneous epilepsy, including one de novo null variant and five pairs of biallelic variants. These variants had no or low frequencies in controls. All missense variants were predicted to alter the hydrogen bonds with surrounding residues and/or protein stability. The three patients with null variants exhibited DEE. The patients with biallelic null mutations presented severe DEE featured by frequent spasms/tonic seizures and diffuse cortical dysplasia/periventricular nodular heterotopia. The three patients with biallelic missense variants presented mild partial epilepsy with favorable outcomes. Analysis of previously reported cases revealed that patients with biallelic null mutations presented significantly higher frequency of refractory seizures and earlier onset age of seizure than those with biallelic non-null mutations or with biallelic mutations containing one null variant., Significance: This study suggested that SZT2 variants were potentially associated with partial epilepsy with favorable outcomes without NDD, expanding the phenotypic spectrum of SZT2 . The genotype-phenotype correlation helps in understanding the underlying mechanism of phenotypic variation., 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 Luo, Ye, Jin, Li, He, Guan, Gao, Liang, Wang, Lu, Yan, Li, Chen and Liu.)

Importance: Although numerous prognostic factors have been found for patients after lung transplantation (LTx) over the years, an accurate prognostic tool for LTx recipients remains unavailable., Objective: To develop and validate a prognostic model for predicting overall survival in patients after LTx using random survival forests (RSF), a machine learning algorithm., Design, Setting, and Participants: This retrospective prognostic study included patients who underwent LTx between January 2017 and December 2020. The LTx recipients were randomly assigned to training and test sets in accordance with a ratio of 7:3. Feature selection was performed using variable importance with bootstrapping resampling. The prognostic model was fitted using the RSF algorithm, and a Cox regression model was set as a benchmark. The integrated area under the curve (iAUC) and integrated Brier score (iBS) were applied to assess model performance in the test set. Data were analyzed from January 2017 to December 2019., Main Outcomes and Measures: Overall survival in patients after LTx., Results: A total of 504 patients were eligible for this study, consisting of 353 patients in the training set (mean [SD] age, 55.03 [12.78] years; 235 [66.6%] male patients) and 151 patients in the test set (mean [SD] age, 56.79 [10.95] years; 99 [65.6%] male patients). According to the variable importance of each factor, 16 were selected for the final RSF model, and postoperative extracorporeal membrane oxygenation time was identified as the most valuable factor. The RSF model had excellent performance with an iAUC of 0.879 (95% CI, 0.832-0.921) and an iBS of 0.130 (95% CI, 0.106-0.154). The Cox regression model fitted by the same modeling factors to the RSF model was significantly inferior to the RSF model with an iAUC of 0.658 (95% CI, 0.572-0.747; P < .001) and an iBS of 0.205 (95% CI, 0.176-0.233; P < .001). According to the RSF model predictions, the patients after LTx were stratified into 2 prognostic groups displaying significant difference, with mean overall survival of 52.91 months (95% CI, 48.51-57.32) and 14.83 months (95% CI, 9.44-20.22; log-rank P < .001), respectively., Conclusions and Relevance: In this prognostic study, the findings first demonstrated that RSF could provide more accurate overall survival prediction and remarkable prognostic stratification than the Cox regression model for patients after LTx.

Esophageal cancer (EC) is one of the fatal malignant neoplasms worldwide. Neoadjuvant therapy (NAT) combined with surgery has become the standard treatment for locally advanced EC. However, the treatment efficacy for patients with EC who received NAT varies from patient to patient. Currently, the evaluation of efficacy after NAT for EC lacks accurate and uniform criteria. Radiomics is a multi-parameter quantitative approach for developing medical imaging in the era of precision medicine and has provided a novel view of medical images. As a non-invasive image analysis method, radiomics is an inevitable trend in NAT efficacy prediction and prognosis classification of EC by analyzing the high-throughput imaging features of lesions extracted from medical images. In this literature review, we discuss the definition and workflow of radiomics, the advances in efficacy prediction after NAT, and the current application of radiomics for predicting efficacy after NAT., 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 Guo, Tang, Hu, Wang, Liu, Yang, Hou, Zuo, Deng, Zheng, Yan, Jiang, Huang, Zhou and Tian.)

Fragile X mental retardation protein (FMRP) deficit resulted from mutations in its encoded fragile X mental retardation 1 (Fmr1) gene is a common inherited cause of Fragile X syndrome (FXS) characterized by intellectual disability and autism spectrum disorder (ASD). The FMRP absence-induced altered gene expression in prefrontal cortex (PFC) are associated with autistic behaviors. However, there lacks a large-scale protein profiling in the PFC upon loss of FMRP. This study used a TMT-labeled proteomic analysis to identify a protein profile of the PFC in the Fmr1 knockout mouse. A total of 5886 proteins were identified in the PFC with 100 differentially abundant proteins (DAPs) in response to FMRP deficiency. Bioinformatical analyses showed that these DAPs were mostly enriched in immune system, extracellular part and complement and coagulation cascades. The complement and coagulation cascades include 6 upregulated proteins (SERPING1, C1QA, C3, FGA, FGB and FGG), which are associated with fibrin degradation, cell lysis, degranulation chemotaxis and phagocytosis linked to activation of immune and inflammatory responses. Thus, our data provide an altered protein profile upon loss of FMRP in the PFC, and suggest that the enhancement of complement and coagulation cascades might contribute to etiological and pathogenic roles of ASD in FXS. SIGNIFICANCE: The etiology of autism spectrum disorder (ASD), a group of neurobiological disorders characterized by deficits in social interaction barriers and other abnormal behaviors, is still elusive. Autistic-like phenotypes are present in both Fragile X syndrome (FXS) patients and FMRP-deficiency FXS models. Given that prefrontal cortex is a critical brain area for social interaction, the FMRP absence induced-changes of a subset of proteins might contribute to ASD in FXS. Using a comprehensive proteomic analysis, this study provides a prefrontal protein profile of the FMRP-absent mouse with a total of 100 differentially abundant proteins (DAPs). Bioinformatic analyses suggest that these DAPs are mainly involved in the regulations of immune system and complement and coagulation cascades. We also show that 6 upregulated proteins (SERPING1, C1QA, C3, FGA, FGB and FGG) in the complement and coagulation cascades are associated with fibrin degradation, cell lysis, degranulation chemotaxis and phagocytosis regarding dysregulation of immune and inflammatory responses in the prefrontal cortex. Therefore, this study suggests that these FMRP-deficient DAPs in the prefrontal cortex might contribute to the etiology and pathogenesis of ASD in FXS., Competing Interests: Declaration of Competing Interest All authors declare no conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objective: For patients with thymic epithelial tumors, accurately predicting clinicopathological outcomes remains challenging. We aimed to investigate the performance of machine learning-based radiomic computed tomography phenotyping for predicting pathological (World Health Organization [WHO] type and TNM stage) and survival outcomes (overall and progression-free survival) in patients with thymic epithelial tumors., Methods: This retrospective study included patients with thymic epithelial tumors between January 2001 and January 2022. The radiomic features were extracted from preoperative unenhanced computed tomography images. After strict feature selection, random forest and random survival forest models were fitted to predict pathological and survival outcomes, respectively. The model performance was assessed by the area under the curve (AUC) and validated internally by the bootstrap method., Results: In total, 124 patients with a median age of 61 years were included. The radiomics random forest models of WHO type and TNM stage showed satisfactory performance with an AUC WHO of 0.898 (95% CI, 0.753-1.000) and an AUC TNM of 0.766 (95% CI, 0.642-0.886). For overall survival and progression-free survival prediction, the radiomics random survival forest models showed good performance (integrated AUCs, 0.923; 95% CI, 0.691-1.000 and 0.702; 95% CI, 0.513-0.875, respectively), and the integrated AUCs increased to 0.935 (95% CI, 0.705-1.000) and 0.811 (95% CI, 0.647-0.942), respectively, when combined with clinicopathological features., Conclusions: Machine learning-based radiomic computed tomography phenotyping might allow for the satisfactory prediction of pathological and survival outcomes and further improve prognostic performance when integrated with clinicopathological features in patients with thymic epithelial tumors., (Copyright © 2022 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

The interfacial stability is highly responsible for the longevity and safety of sodium ion batteries (SIBs). However, the continuous solid-electrolyte interphase(SEI) growth would deteriorate its stability. Essentially, the SEI growth is associated with the electron leakage behavior, yet few efforts have tried to suppress the SEI growth, from the perspective of mitigating electron leakage. Herein, we built two kinds of SEI layers with distinct growth behaviors, via the additive strategy. The SEI physicochemical features (morphology and componential information) and SEI electronic properties (LUMO level, band gap, electron work function) were investigated elaborately. Experimental and calculational analyses showed that, the SEI layer with suppressed growth delivers both the low electron driving force and the high electron insulation ability. Thus, the electron leakage is mitigated, which restrains the continuous SEI growth, and favors the interface stability with enhanced electrochemical performance., (© 2022 Wiley-VCH GmbH.)

The KCNK4 gene, predominantly distributed in neurons, plays an essential role in controlling the resting membrane potential and regulating cellular excitability. Previously, only two variants were identified to be associated with human disease, facial dysmorphism, hypertrichosis, epilepsy, intellectual/developmental delay, and gingival overgrowth (FHEIG) syndrome. In this study, we performed trio-based whole exon sequencing (WES) in a cohort of patients with epilepsy. Two de novo likely pathogenic variants were identified in two unrelated cases with heterogeneous phenotypes, including one with Rolandic epilepsy and one with the FHEIG syndrome. The two variants were predicted to be damaged by the majority of in silico algorithms. These variants showed no allele frequencies in controls and presented statistically higher frequencies in the case cohort than that in controls. The FHEIG syndrome-related variants were all located in the region with vital functions in stabilizing the conductive conformation, while the Rolandic epilepsy-related variant was distributed in the area with less impact on the conductive conformation. This study expanded the genetic and phenotypic spectrum of KCNK4 . Phenotypic variations of KCNK4 are potentially associated with the molecular sub-regional effects. Carbamazepine/oxcarbazepine and valproate may be effective antiepileptic drugs for patients with KCNK4 variants., 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 Yan, He, Jin, Guo, Zhou and Luo.)

Background and Purpose: Orthostatic hypotension (OH) is common in patients with Parkinson's disease (PD). Early recognition OH is required with sensitive assessments. The purpose of this study was to determine whether blood pressure (BP) changes during exercise can predict the occurrence of OH in PD., Methods: This prospective cohort study included 80 consecutive patients with PD. All patients agreed to participate in a baseline evaluation and cardiopulmonary exercise test (CPET). According to the initial active standing test (AST), those without OH (PD-nonOH) at baseline had their AST results followed up for 6 months. The main outcome was defined as whether patients without OH at baseline would develop OH after 6 months. Logistic regression analysis was applied to identify the relevant variables. A nomogram was constructed based on clinical features and identified variables. The concordance index (C-index) and area under the receiver operating characteristic curve (AUC) were used to evaluate the accuracy and predictive ability of the nomogram, respectively., Results: CPET results indicated that peak load, peak heart rate, heart rate recovery at 1 min, and systolic BP change (ΔSBP) were lower in those with OH than in the PD-nonOH group ( p <0.05) at baseline. Logistic regression analysis indicated that peak load and ΔSBP during CPET had significant effects on OH ( p <0.05). Age, sex, peak load, and ΔSBP were used to construct the nomogram model (C-index=0.761). The prediction model had an AUC of 0.782 (95% confidence interval=0.649-0.889) and a specificity and sensitivity of 70.0% and 81.8%, respectively., Conclusions: This study has identified predictive factors for OH development in patients with PD. CPET could be used as a complementary examination to identify patients at a high risk of OH., Competing Interests: The authors have no potential conflicts of interest to disclose., (Copyright © 2023 Korean Neurological Association.)

Introduction: Fat mass and obesity-associated (FTO) gene is strongly associated with obesity which brings a major health threat. Altered expression of its encoded protein FTO in the hypothalamus has been identified to contribute to central control of appetite and body weight. However, its molecular mechanisms remain elusive., Methods: Mouse hypothalamic POMC cell line N43/5 was treated with FTO inhibitor rhein, FTO shRNA, or extracellular signal-regulated kinase 1/2 (ERK1/2) inhibitor U0126 to inhibit FTO or ERK1/2. Rhein and U0126 were injected into lateral ventricle of the mice by intracerebroventricular cannulation. Western blotting and immunofluorescent assays were performed to monitor protein level., Results: This study identified that inhibition of FTO in N43/5 cells led to phosphorylation of signal transducer and activator of transcription 3 (STAT3) at S727 site and induced p-STAT3-S727 nuclear translocation. We further showed that FTO inhibition promoted phosphorylation of ERK1/2; specific inhibition of ERK1/2 signaling by U0126 could abolish the effect of FTO inhibition on STAT3-S727 phosphorylation and nuclear translocation. Furthermore, we found that inhibition of hypothalamic FTO promoted STAT3-S727 phosphorylation in the hypothalamic arcuate nucleus, and the mice showed reductions in food intake and body weight. In addition, inhibition of hypothalamic ERK1/2 could abolish the effects of FTO inhibition on STAT3-S727 phosphorylation, reductions of food intake and body weight., Conclusion: Our in vitro and in vivo data suggest that the inhibition of hypothalamic FTO could activate STAT3 through ERK1/2, which is potentially associated with reductions in food intake and body weight., (© 2022 S. Karger AG, Basel.)

Selenium (Se) solar cells were the world's first solid-state photovoltaics reported in 1883, opening the modern photovoltaics. However, its wide bandgap (~1.9 eV) limits sunlight harvesting. Here, we revisit the world's oldest but long-ignored photovoltaic material with the emergence of indoor photovoltaics (IPVs); the absorption spectrum of Se perfectly matches the emission spectra of commonly used indoor light sources in the 400 to 700 nm range. We find that the widely used Te adhesion layer also passivates defects at the nonbonded Se/TiO 2 interface. By optimizing the Te coverage from 6.9 to 70.4%, the resulting Se cells exhibit an efficiency of 15.1% under 1000 lux indoor illumination and show no efficiency loss after 1000 hours of continuous indoor illumination without encapsulation, outperforming the present IPV industry standard of amorphous silicon cells in both efficiency and stability. We further fabricate Se modules (6.75 cm 2 ) that produce 232.6 μW output power under indoor illumination, powering a radio-frequency identification-based localization tag.

Ion adsorption and hydrogen bond (HB) network reconstruction in electric double layer (EDL) have a profound impact on the interface properties. The microstructure in the bulk phase of 1.00-21.30 wt.% Na 2 SO 3 aqueous solutions are investigated by X-ray scattering, confocal Raman spectroscopy, and classical molecular dynamics. The electronic properties of SO 3 2- adsorption and the geometric structure of the HB network in the EDL at the titanium TiO 2 (101) surface are studied by density functional theory (DFT) and classical molecular dynamics. The SO 3 2- strongly weakens the fully hydrogen-bonded water (FHW) and transforms it into partial hydrogen-bonded water (PHW). The HB transformation index (HBTI = PHW/FHW) shows a linear relationship with the mass fraction of Na 2 SO 3 . The TiO b -parallel adsorption configuration of SO 3 2- enhances the ionicity of the O b -Ti 6 bond, resulting in the formation of oxygen vacancies at the titanium passive film surface. Besides, SO 3 2- and Na + are enriched and thermodynamic supersaturated in the inner Helmholtz layer (IHL), and the ions are diluted in the outer Helmholtz layer (OHL). The diffusion coefficient of SO 3 2- and water molecules in EDL decreases seriously, which is easy to causes salt scaling on the surface of titanium passive film. This work provides evidence for the destruction of titanium passive film by SO 3 2- .

Loss of fragile X retardation protein (FMRP) leads to fragile X syndrome (FXS), a common cause of inherited intellectual disability. Protein lysine acetylation (K-ac), a reversible post-translational modification of proteins, is associated with the regulation of brain development and neuropathies. However, a comprehensive hippocampal K-ac protein profile in response to FMRP deficiency has not been reported until now. Using LC-MS/MS to analyze the enriched K-ac peptides, this study identified 1629 K-ac hits across 717 proteins in the mouse hippocampus, and these proteins were enriched in several metabolic processes. Of them, 51 K-ac hits across 45 proteins were significantly changed upon loss of FMRP. These altered K-ac proteins were enriched in energy metabolic processes including carboxylic acid metabolism process, aerobic respiration and citrate cycle, linking with several neurological disorders such as lactic acidosis, Lewy body disease, Leigh disease and encephalopathies. In the mouse hippocampus and the hippocampal HT-22 cells, FMRP deficiency could induce altered K-ac modification of several key enzymes, decrease in ATP and increase in lactate. Thus, this study identified a global hippocampal lysine acetylome and an altered K-ac protein profile upon loss of FMRP linked to abnormal energy metabolism, implicating in the pathogenesis of FXS. SIGNIFICANCE: Fragile X syndrome (FXS) is a common inherited neurodevelopment disorder characterized by intellectual disability and an increased risk for autism spectrum disorder. FXS is resulted from silencing of the FMR1 gene, which induces loss of its encoding protein FMRP. Molecular and metabolic changes of Fmr1-null animal models of FXS have been identified to potentially contribute to the pathogenesis of FXS. Here, we used a TMT-labeled quantitative proteomic analysis of the peptides enriched by anti-K-ac antibodies and identified a global K-ac protein profile in the mouse hippocampus with a total of 1629 K-ac peptides on 717 proteins. Of them, 51 K-ac peptides regarding 45 proteins altered in response to loss of FMRP, which were enriched in energy metabolic processes and were implicated in several neurological disorders. Thus this study for the first time provides a global hippocampal lysine acetylome upon FMRP deficiency linked to abnormal metabolic pathways, which may contribute to pathogenic mechanism of FXS., Competing Interests: Declaration of Competing Interest All authors declare no conflict of interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Angelicae Sinensis Radix, as a medicinal and edible Chinese medicinal herb, is widely used in clinical practice. It is mainly cultivated in Minxian, Tanchang, Zhangxian and Weiyuan counties of Gansu province. In recent years, with the comprehensive and in-depth study of Angelicae Sinensis Radix in China and abroad, its chemical composition, pharmacological effects and application and development have attracted much attention. In this study, the chemical composition, traditional efficacy, and modern pharmacological effects of Angelicae Sinensis Radix were summarized. On this basis, combined with the core concept of quality markers(Q-markers), the Q-markers of Angelicae Sinensis Radix were discussed from the aspects of mass transfer and traceability and chemical composition specificity, availability, and measurability, which provided scientific basis for the quality evaluation of Angelicae Sinensis Radix.