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Transportation is widely recognized as a significant contributor to heavy metal (HM) pollution in roadside soils. A better understanding of HM pollution in soils near expressways is crucial, particularly given the rapid expansion of expressway transportation in China in recent years. In this study, 329 roadside topsoil samples were collected along the Beijing-Tianjin Expressway, which connects two megacities in China. Chemical analysis showed that HM concentrations in the soil samples were generally below national limits. The mean pollution index (Pi) values for As, Cr, Cu, Ni, Pb, and Zn ranged from 0.94 to 1.01, while Cd and Hg exhibited slightly higher mean Pi values of 1.19 and 1.13, respectively. The Nemerow integrated pollution index values for all samples ranged from 0.71 to 4.97, with a mean of 1.26. This suggests a slight enrichment of HM above natural background levels, especially for Cd and Hg. Source apportionment using positive matrix factorization revealed that natural sources contributed the most to soil HMs (64.51 %), followed by agricultural sources (19.15 %), traffic sources (9.77 %), and industrial sources (6.57 %). The Shapley additive explanation analysis, based on the random forest model, identified soil organic carbon, deep soil HM content, altitude, total soil K 2 O, urbanization composite impact index, and total soil P as primary influencing factors. This indicates that the impact of transportation on roadside soils along the Beijing-Tianjin Expressway is currently relatively limited. The prominent influence of soil properties and altitude underscored the importance of "transport" and "receptor" in the soil HMs accumulation process at the local scale. These findings provide critical data and a scientific basis for decision-makers to develop policies for expressway design and roadside soil protection., 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: Chronic liver damage (CLD) is a long-term and progressive liver condition characterized by inflammation, fibrosis, and impaired liver function, which ultimately lead to severe complications such as cirrhosis or liver cancer. Quercetin (Que), a flavonoid in various plants, possesses anti-inflammatory, antiviral, anti-ischemic, and anticancer properties. Recently, extracellular vesicles (EVs) derived from pretreated bone marrow mesenchymal stem cells (BMSCs) have shown immense potential in treating various diseases, including CLD. Thus, this study evaluated the regulatory effects of Que-preconditioned BMSC-derived EVs (Que-EVs) on LPS-stimulated RAW264.7 cells and their therapeutic effects on mice with CLD., Methods: Que-EVs and control-EVs were harvested from the cell culture supernatant of BMSCs. The EVs were characterized using western blot, transmission electron microscopy, and nanoparticle tracking analysis. Further, the DIR labeling of EVs was used to detect in vitro and in vivo uptake. Next, LPS pre-stimulated RAW264.7 cells were treated with Que-EVs and control-EVs for 24 h. The relative expression of inflammatory cytokines and macrophage polarization markers genes was assessed using RT-qPCR, and western blot was conducted to evaluate the GNAS, PI3K, ERK, and STAT3 gene and protein expressions in RAW264.7 cells. Furthermore, transfection techniques were employed to induce miR-136-5p inhibition and GNAS overexpression in RAW264.7 cells to validate the role of miR-136-5p in alleviating inflammation through the GNAS/PI3K/ERK/STAT3 pathway. Subsequently, the outcomes were validated via in vitro experiments., Results: Que enhanced miR-136-5p expression in BMSC-EVs. Furthermore, it was shown that EVs delivered miR-136-5p to macrophages, thereby attenuating M1-type macrophage polarisation through the GNAS/PI3K/ERK/STAT3 pathway, reducing liver inflammation, improving liver function and treating CLD., 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. Published by Elsevier B.V.)

Cordyceps cicadae (Hypocreales: Cordycipitaceae) is a renowned entomopathogenic fungus used as herbal medicine in China. However, wild C. cicadae resources have been threatened by heavy harvesting. We hypothesised that Bombyx mori L. (Lepidoptera: Bombycidae) could be a new alternative to cultivate C. cicadae due to the low cost of rearing. Bacterial communities are crucial for the formation of Cordyceps and for promoting the production of metabolites. To better understand the bacterial community structure associated with Cordyceps, three Claviciptaceae fungi were used to explore the pathogenicity of the silkworms. Here, fifth-instar silkworms were infected with C. cicadae, Cordyceps cateniannulata (Hypocreales: Cordycipitaceae) and Beauveria bassiana (Hypocreales: Cordycipitaceae). Subsequently, we applied high-throughput sequencing to explore the composition of bacterial communities in silkworms. Our results showed that all three fungi were highly pathogenic to silkworms, which suggests that silkworms have the potential to cultivate Cordyceps. After fungal infection, the diversity of bacterial communities in silkworms decreased significantly, and the abundance of Staphylococcus increased in mummified larvae, which may play a role in the death process when the host suffers infection by entomopathogenic fungi. Furthermore, there were high similarities in the bacterial community composition and function in the C. cicadae and C. cateniannulata infected samples, and the phylogenetic analysis suggested that these similarities may be related to the fungal phylogenetic relationship. Our findings reveal that infection with different entomopathogenic fungi affects the composition and function of bacterial communities in silkworms and that the bacterial species associated with Cordyceps are primarily host dependent, while fungal infection affects bacterial abundance., (© 2024 Royal Entomological Society.)

DNA walkers have emerged as a powerful tool in various biosensors, enabling the detection of low-abundance analytes with their precise programmability and efficient signal amplification capacity. However, many existing approaches are hampered by limited reaction kinetics. Herein, we designed a stochastic bipedal dual-DNA walkers (SBDW) that can traverse at high speed on AuNP-based three-dimensional (3D) tracks powered by Exo III. The SBDW exhibited superior reaction kinetics and are up to least 2.25 times faster than traditional DNA walkers, reaching a plateau within 40 min. This advancement allows for rapid and highly sensitive fluorescence detection of a significant base excision repair enzyme of APE1 with a detection limit of 0.001 U/mL. In comparison to traditional DNA walkers, this platform enables highly sensitive and specific APE1 assays in cell lysate and facilitates rapid and accurate screening of APE1 inhibitors. Given its rapid, sensitive, specific, and reliable analysis features, the strategy shows great promise in drug discovery and clinical diagnosis., 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: Renal pelvic urothelial carcinoma with multiple histological variants co-occurs with hydronephrosis and pyelonephritis extremely rarely. The diagnosis of renal pelvic urothelial carcinoma can be complicated by these conditions, leading to delayed or missed diagnosis or misdiagnosis., Case Presentation: We report the evolutionary course of a rare case of renal pelvic urothelial carcinoma containing squamous and sarcomatoid differentiation associated with hydronephrosis and pyelonephritis in a low-functioning kidney. Preoperative clinical and imaging manifestations were highly suggestive of hydronephrosis and pyelonephritis; however, all corresponding therapeutic measures failed. Eventually, nephrectomy was performed, and postoperative pathological examination revealed renal pelvic urothelial carcinoma with squamous and sarcomatoid differentiation. Further residual ureter and bladder cuff resection was refused by the patient. Regular cisplatin-based postoperative chemotherapy and bladder perfusion were arranged, and cystoscopy and imaging examinations were performed regularly for follow-up., Conclusion: Hydronephrosis and pyelonephritis can mask the typical clinical and imaging manifestations of renal pelvic urothelial carcinoma. Renal pelvic malignancy should be considered in patients with intractable pyelonephritis and hydronephrosis. There is no standard treatment for renal pelvic carcinoma with multiple pathological types. Radical surgery is considered an appropriate option and should be performed as early as possible. Chemotherapy and immunotherapy may improve patient survival., Competing Interests: Declarations Ethics approval and consent to participate This case was approved by the Ethics Committee of Jiangsu Provincial Hospital of Integrated Chinese and Western Medicine. Consent for publication Written informed consent was obtained from the patient for publication of this case report. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Aims: Diabetic peripheral neuropathy (DPN) often coexists with sudomotor dysfunction, resulting in an increased risk of diabetic foot. This study aimed to explore an efficient method for early diagnosis of DPN by establishing a quantitative Neuropad., Methods: We recruited 518 patients with type 2 diabetes. Neuropathy Symptoms Score (NSS) combined with Neuropathy Disability Score (NDS) was used to assess distal symmetrical peripheral neuropathy (DSPN). The area under the ROC curve (AUROC), sensitivity, and specificity were used to compare the diagnostic efficacy of quantitative Neuropad (the change rate of the chromatic aberration value per minute) and two types of visual Neuropad (visual Neuropad A: whether the time to complete colour change within 10 min, visual Neuropad B: the time to complete colour change) for DPN., Results: We did not observe very good diagnostic efficacy of Neuropad (visual Neuropad A and B: 0.59 and 0.64, quantitative Neuropad AUROC: 0.62-0.64) when using standard DSPN diagnostic criteria (NDS 6-12 or NDS 3-5 combined with NSS 5-9). When DPN was assessed by NSS + NDS ≥ 4, visual Neuropad B improved the specificity (AUROC 0.72, 67.00%, specificity 71.70%) by extending the detection time compared with visual Neuropad A (AUROC 0.62, sensitivity 81.80%, specificity 41.70%). Quantitative Neuropad significantly improved the diagnostic effect (AUROC 0.81, sensitivity 80.0%, specificity 76.3%) and reduced the detection time (4 min)., Conclusions: This study provides a new quantitative Neuropad, which has great potential to be an extremely useful diagnostic tool for early screening of sudomotor dysfunction in the clinical practice., (© 2024 John Wiley & Sons Ltd.)

Objective: This study is to evaluate the effectiveness and frequency factors of endoscopic bougie dilatation in treating postoperative anastomotic stenosis of congenital esophageal atresia (CEA)., Methods: The clinical data of patients of anastomotic stenosis with endoscopic bougie were retrospectively analyzed. According to the number of dilation times (ND), patients were divided into two groups (Group 0: ND < 3; Grooup1: ND ≥ 3), and the differences in multiple clinical data were compared. Lasso regression and Ridge regression were used to screen important variables. Classification models were built utilizing various machine learning algorithms and their performance were evaluated. Finally, Kaplan-Meier model was used to estimate the probable-time distribution of children achieving normal feeding., Results: Seventy-five patients underwent a total of 210 times of dilation, with a median of 3 times of dilation. The overall effectiveness was 98.67% (74/75), with perforation in 2 case (0.95%), and obvious bleeding in 3 cases (1.43%). Initial diameter of bougie, final diameter of bougie, treatment pattern (Regular: dilation each 4weeks; Wait-and-see: dilation until symptoms present), age at final dilation, esophageal obstruction by food were the factors related to ND. Random Forest (RF) and Logistic regression (LR) model were excellent models for predicting ND. The median age for achieving normal eating in Group0 was 120 days (95% CI: 90-160), while it was 270 days (95% CI: 240-460) in Group1 with a statistically significant difference ( P  < 0.0001)., Conclusion: Endoscopic bougie dilatation is a safe and effective treatment for anastomotic stenosis. Selecting the appropriate bougie, using symptoms as the criterion for dilation, and minimizing the dilations under 3 times constitute a rational strategy., 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., (© 2024 He, Xiong, Deng, Yang, Yan, Zhang, Shang, Xie, Liu and Li.)

Objective: In this study we aimed to comprehensively evaluate the clinical features and treatment outcomes of Chinese patients with autoimmune pancreatitis (AIP) through a single-center real-world study., Methods: Patients diagnosed with AIP in Changhai Hospital, Naval Medical University from January 2014 to December 2021 were included. Baseline characteristics, laboratory test results, cross-sectional imaging and endoscopic ultrasound (EUS) findings, and long-term follow-up data were obtained. The differences in these characteristics between type 1 and type 2 AIP patients were analyzed., Results: Among all 320 patients, 271 (84.7%) and 49 (15.3%) had type 1 and type 2 AIP, respectively. The most common initial symptom was abdominal discomfort (58.1%), followed by obstructive jaundice (32.5%). Extrapancreatic organ involvement was identified in 126 (39.4%) patients, with the biliary system being the most commonly involved (36.6%). Elevated serum IgG4 level was rare in type 2 AIP patients. The diagnostic accuracy of computed tomography (CT), magnetic resonance imaging (MRI), and EUS for definitive and probable AIP were 78.0%, 68.7%, and 80.5%, respectively. EUS-guided tissue acquisition with immunohistochemical staining helped establish a final diagnosis in 39.7% of patients. During the follow-up period of 60 months, 18.6% of patients experienced relapse. The 1-, 3-, and 5-year relapse rates were higher in type 1 AIP patients, with an accumulated rate of 8.0%, 12.6%, and 15.1%, when compared with those with type 2 AIP., Conclusions: Type 2 AIP is not uncommon in Chinese population. The diagnostic accuracy of CT and EUS for AIP might be superior to that of MRI., (© 2024 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

The magnetic composite gel bead (Fe 3 O 4 -C@SA GB) adsorbent was prepared by sodium alginate (SA) crosslinking with pitaya peel-derived porous carbons (PPDPCs) and magnetic iron oxide nanoparticles (Fe 3 O 4 NPs). The adsorption effects of Fe 3 O 4 -C@SA GBs on heavy metal ions (HMIs) and 17 β-estradiol (E2) in water are evaluated by classical kinetic models and isotherm models. The pseudo-second-order kinetic model shows that Fe 3 O 4 -C@SA GBs have maximum adsorption capacities of 9.62, 7.50, and 13.61 mg/g for Cu (II), Cd (II), and Pb (II), respectively. Meanwhile, the highest adsorption performance of the synthesized gel beads to E2 is of ca. 276.3 mg/g. In addition, the Fe 3 O 4 -C@SA GBs can still maintain a high level of adsorption efficiency after five adsorption cycles, displaying economic efficiency and reusability. Hence, this work provides useful insights into the efficient adsorption elimination of pollutants in sewage and the corresponding adsorption mechanisms.

Developing novel heteroatoms co-doped biomass porous carbon with low-cost, tunable physical/chemical properties, and environmental friendliness is an important candidate to face energy shortage and environmental pollution currently. Herein, a novel solvothermal avenue was designed using triethanolamine as self-doping solvent to treat rice straw powders with KOH. The rice straw with triethanolamine derived carbon (RSTCs-1) possessed hierarchical porous structure, N/O diatomic doping, and large specific surface area. The electrochemical energy storage performance of RSTCs-1 was evaluated in the systems of supercapacitors, aqueous zinc ion hybrid supercapacitors (AZHSs), and lithium-ion batteries (LIBs) respectively. As the results, the RSTCs-1 based symmetric supercapacitor exhibited the maximum energy density of ca. 98.4 Wh·kg -1 with the excellent cycling stability. Moreover, both RSTCs-1 AZHSs and RSTCs-1 LIBs achieved the relative high discharge specific capacities of ca. 407.1 and 1906.7 mAh·g -1 at current density of 0.1 A·g -1 . These results highlighted the huge potential of the obtained with notable electrochemical performance acting as multifunctional electrode material for the different energy storage devices., 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. Published by Elsevier B.V.)

Purpose: To observe the changes in corneal epithelial thickness after FS-LASIK and Trans-PRK surgery and to investigate the impact of corneal epithelial remodeling on Q-value and HOA., Methods: In this prospective cohort study, 50 patients (100 eyes) underwent FS-LASIK and 45 patients (90 eyes) underwent Trans-PRK. Anterior segment OCT was used to measure the corneal epithelial thickness in different corneal zones (central zone: 0-2 mm; paracentral zone: 2-5 mm; and mid-peripheral zone: 5-6 mm) preoperatively and postoperatively at 1 week, 1 month, 3 months, and 6 months. The correlation between ΔCET in the superior, nasal, inferior, and temporal region at 6 months postoperatively and ΔQ and ΔHOA was analyzed., Results: At 6 months postoperatively, the epithelial thickness increased in the central, paracentral, and mid-peripheral zones in FS-LASIK and Trans-PRK. Central epithelial thickness and different regions of the paracentral zone and mid-peripheral exhibited significant thickening (P < 0.001). In the para-central zone and mid-peripheral zone, the ΔCET in different regions after LASIK and Trans-PRK was positively correlated with ΔQ (P < 0.05) and ΔHOA (P < 0.05)., Conclusion: After FS-LASIK and Trans-PRK, significant epithelial thickening was observed. Epithelial changes in different regions lead to different Q-values in different regions and have different effects on HOA. This has a certain guiding significance for the design of refractive surgery, and minimizing the increase of Q-value may improve the postoperative visual quality., (Copyright © 2024 Copyright: © 2024 Indian Journal of Ophthalmology.)

Background: Although heart failure (HF) symptoms affect patients' quality of life (QoL), improving patients' QoL requires certain self-care behaviours. However, the specific role of self-care behaviours in the relationship between HF symptoms and QoL has not been clarified., Aims: To evaluate the status of symptom clusters, self-care behaviours and QoL in HF patients, and to analyse and test the moderating effect of self-care behaviours between symptom clusters and QoL., Design: This study is a cross-sectional study., Methods: A total of 320 HF patients who treated in the three hospitals in Chengdu, China, from December 2022 to July 2023 were selected as the research subjects. The patients were evaluated using The General Information Questionnaire, Memorial Symptom Assessment Scale Heart Failure, Self-Care of Heart Failure Index and Minnesota Living with Heart Failure Questionnaire. The statistical analysis methods were exploratory factor analysis, Pearson correlation analysis, hierarchical regression analysis and simple slope analysis., Results: There were five symptom clusters in HF patients: emotional symptom cluster (sadness, anxiety, irritability, feeling nervous), digestive symptom cluster (lack of appetite, dry mouth, weight loss, nausea, abdominal distension), ischemic symptom cluster (dizziness, chest pain, palpitations, fatigue), dyspnoea symptom cluster (difficulty breathing when lying flat, waking up breathless at night, sleep difficulty) and congestion symptom cluster (cough, shortness of breath, oedema). There was a significant correlation between HF symptom group, self-care behaviours and QoL (p < 0.05). Both self-care maintenance (β = -0.262, p < 0.001) and self-care management (β = -0.258, p < 0.001) had a moderating effect between symptom clusters and QoL., Conclusion: There are a variety of symptom clusters in HF patients. Improving the self-care behaviours ability of HF patients is conducive to reducing the impact of HF symptom clusters on QoL., Reporting Method: The study used the STROBE checklist for reporting., Relevance to Clinical Practice: Medical staff should focus on the impact of HF symptom clusters and self-care behaviours on QoL, and formulate corresponding interventions for HF symptom clusters and self-care behaviours to improve the QoL of patients., Patient or Public Contribution: The head nurse of the cardiovascular department actively assisted us in collecting questionnaires from HF patients, and all HF patients surveyed participated in this study seriously., (© 2024 John Wiley & Sons Ltd.)

Aim: Hyperhomocysteine has been recognized as an independent risk factor of multiple diseases, including several eye diseases. In this study, we aim to investigate whether increased homocysteine (Hcy) is related to cataracts, and to explore whether dysregulation of mTOR-mediated autophagy and connexin expression are underlying mechanisms., Method: We first developed a method of liquid chromatography tandem mass spectrometry to accurately measure serum concentrations of Hcy in 287 cataract patients and 334 healthy controls. Next, we treated human lens epithelial (HLC-B3) cells with Hcy at different concentrations and durations, and then analyzed expression of autophagy-related markers and connexins, as well as phosphorylated mTOR (p-mTOR) in these cells by Western blotting. Formation of autophagic vacuoles and intracellular Ca 2+ in the Hcy-treated cells were observed by fluorescence microscopy. Further, we performed a rescue experiment in the Hcy-treated HLC-B3 cells by pre-incubation with rapamycin, an mTOR inhibitor., Results: The serum levels of Hcy in patients with cataracts were significantly increased compared to those in healthy controls. In cultured HLC-B3 cells, expression of autophagy related markers (LC3B and Beclin1) and connexins (Cx43 and Cx50) was inhibited by Hcy treatment in a dose- and duration-dependent manner. Accumulation of Ca 2+ in the Hcy-treated lens epithelial cells was observed as a consequence of reduced connexin expression. Meanwhile, expression of p-mTOR increased, representing up-regulation of the mTOR pathway. Importantly, inhibition of autophagy and connexin expression due to hyperhomocysteine was rescued via mTOR suppression by pretreatment with rapamycin in HLC-B3 cells., Conclusion: Our results demonstrate that hyperhomocysteine might promote cataract development through two mTOR-mediated pathways in the lens epithelial cells: 1) dysregulation of autophagy and 2) accumulation of intracellular calcium via decreased connexin expression., 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.The funders played no role in the study design, data collection, or analyses, the decision to publish, or manuscript preparation., (Copyright © 2024. Published by Elsevier B.V.)

Meibomian gland dysfunction is a chronic ocular surface disease with a complex pathogenesis, whose main clinical manifestations are meibomian gland obstruction or/and lipid abnormalities. To explore the mechanism of MGD due to meibomian gland obstruction (MGO), we established a rat model of MGO by cauterizing the meibomian gland orifice. The morphology of the lid margins and meibomian gland orifices were visualized by slit lamp. The tear production of rats was measured by phenol red cotton thread, the tear film breakup time and corneal fluorescein staining scores of rats were detected under cobalt blue light of slit lamp. Changes in the histological structure of the meibomian gland (MG) were observed by HE staining, Oil Red O staining and immunofluorescence staining (collagen IV). RNA sequencing was used to detect differentially expressed genes in MGO and normal rats, which were validated by qPCR. In the MGO group after 4, 8, and 16 weeks, the meibomian gland orifices were closed, tear film break-up time decreased and corneal fluorescein staining score increased (p < 0.05). MG acini was smaller at 8-week and 16-week MGO rats in HE staining. Oil Red O staining showed less condensed staining in the 8- and 16-week MGO groups, while more condensed staining in the 4-week MGO group. Additionally, the basement membrane was destroyed in 16-week MGO group by immunofluorescence staining of collagen IV. Meanwhile, RNA sequencing and qPCR showed that lipid peroxidation (LPO), transient receptor potential vanilloid-3 (TRPV3) and genes in PPAR signaling pathway were differentially expressed in 16-week meibomian gland obstructive rats (p < 0.05). Consequently, meibomian gland obstruction model rats were established successfully with corneal damage and lower tear film stability. Meibomian gland obstruction is a causative factor of MGD, which led to abnormal histological structure in MG, differential expression of PPAR signaling pathway and TRPV3., (© 2024. The Author(s).)

Background: The clinical effects and detailed roles of long non-coding RNA (LncRNA) steroid receptor RNA activator 1 (SRA1) in esophageal squamous cell carcinoma (ESCC) remain ambiguous. In the present study, the complementary sites between lncRNA SRA1, miRNA-363-5p, and phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPP) predicted via bioinformatics analysis stimulated us to hypothesize that miRNA-363-5p/LHPP axis might be required for SRA1-mediated ESCC progression., Aim: To investigate the molecular events of SRA1 in the malignant behavior in ESCC., Methods: Thirty-eight ESCC tissues and paired adjacent normal tissues were acquired. SRA1 expression was detected in ESCC tissues and cell lines using quantitative reverse transcription-polymerase chain reaction. Cell counting Kit-8 assay, transwell invasion assay, glycolysis assay, and xenograft tumor model were performed to address the malignant biological behaviors of ESCC cells after the introduction of SRA1. The t -test and the χ 2 test were used for comparison between groups. Survival curve analysis was performed using the Kaplan-Meier method., Results: SRA1 downregulation was identified in ESCC. ESCC patients exhibiting a low SRA1 expression faced shorter overall survival than those with a high SRA1 expression. The introduction of SRA1 inhibited cell proliferation, glucose uptake, and lactate production in ESCC. In vivo , the growth of ESCC was hindered by SRA1 overexpression. Then, SRA1 overexpresses the LHPP by inhibiting miRNA-363-5p. Lastly, the introduction of small interfering RNA si-LHPP or miRNA-363-5p mimic could abrogate the inhibition roles triggered by SRA1., Conclusion: SRA1 inhibits the oncogenicity of ESCC via miRNA-363-5p/LHPP axis. The SRA1/miRNA-363-5p/LHPP pathway may be a therapeutic target for ESCC., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Developing selective and sensitive fluorescent probes for the detection of glutathione (GSH) concentration and intracellular distribution is of great significance for early diagnosis and treatment of diseases such as liver injury and cancer since GSH plays irreplaceable roles in regulating intracellular redox homeostasis. Herein, we present a new fluorescent probe that can be specifically activated by GSH through the conjugate addition and hydrolysis induced covalent-assembly approach for achieving zero-background interference fluorescence off-on sensing. Besides, the probe exhibited prominent selectivity and sensitivity, a low detection limit and cytotoxicity, thus successfully realizing specific real-time monitoring and tracking of GSH levels in living cells. As a consequence, this work might provide a potentially promising candidate for validating the function of GSH in various physiological and pathological processes, which is beneficial for early diagnosis and therapeutics of related diseases.

Mesenchymal stromal cells (MSCs) are promising candidates for cartilage repair therapy due to their self-renewal, chondrogenic, and immunomodulatory capacities. It is widely recognized that a shift from fetal bovine serum (FBS)-containing medium toward a fully chemically defined serum-free (SF) medium would be necessary for clinical applications of MSCs to eliminate issues such as xeno-contamination and batch-to-batch variation. However, there is a notable gap in the literature regarding the evaluation of the chondrogenic ability of SF-expanded MSCs (SF-MSCs). In this study, we compared the in vivo regeneration effect of FBS-MSCs and SF-MSCs in a rat osteochondral defect model and found poor cartilage repair outcomes for SF-MSCs. Consequently, a comparative analysis of FBS-MSCs and SF-MSCs expanded using two SF media, MesenCult™-ACF (ACF), and Custom StemPro™ MSC SFM XenoFree (XF) was conducted in vitro. Our results show that SF-expanded MSCs constitute variations in morphology, surface markers, senescence status, differentiation capacity, and senescence/apoptosis status. Highly proliferative MSCs supported by SF medium do not always correlate to their chondrogenic and cartilage repair ability. Prior determination of the SF medium's ability to support the chondrogenic ability of expanded MSCs is therefore crucial when choosing an SF medium to manufacture MSCs for clinical application in cartilage repair.

Purpose: To evaluate curvature changes in different regions and their correlation with corneal epithelial remodeling in myopic patients undergoing femtosecond laser-assisted in situ keratomileusis (FS-LASIK) and transepithelial refractive keratectomy (Trans-PRK) after surgery., Methods: One hundred and sixty-three patients (163 right eyes) undergoing Trans-PRK and LASIK were evaluated for up to 6 months using anterior segment optical coherence tomography (OCT) to measure the epithelial thickness and corneal topography to measure corneal curvature in different areas (2 mm, 5 mm, and 7 mm). We calculated the curvature ΔK (ΔK = preoperative - postoperative), ΔK 5-2 (ΔK 5-2 = K 5mm - K 2mm ), ΔK 7-5 (ΔK 7-5  = K 7mm - K 5mm ), and the epithelial thickness ΔET 5-2 (ΔET 5-2  = ET 5mm - ET 2mm ) and ΔET 7-5 (ΔET 7-5 = ET 7mm - ET 5mm )., Results: Corneal curvature flattened in each region of the two groups (all p  < 0.001) and gradually steepened during the follow-up period. The Trans-PRK group flattened more significantly within 2 mm and 5 mm, while the FS-LASIK group at 7 mm. Both groups of ΔK decreased over time. Both groups of ΔK 5-2 and ΔK 7-5 gradually decreased during the follow-up period (P 5-2 =0.025 and P 7-5  < 0.001 for Trans-PRK, P 5-2  = 0.011 and P 7-5  < 0.001 for FS-LASIK). The corneal epithelium of the two groups gradually thickened during the follow-up period, with Trans-PRK significantly thickening in the central and peripheral regions and FS-LASIK in the central and paracentral regions. There is a significant correlation between the ΔK 5-2 and ΔET 5-2, ΔK 7-5 and ΔET 7-5 (all r  > 0.37, p  < 0.001)., Conclusions: All groups showed significant curvature flattening after surgery and gradually steepening during the follow-up period. The corneal epithelium thickness in both groups of 17 regions became thicker,. In contrast, Trans-PRK group showed more significant thickening to the periphery and the central 5 mm area of the FS-LASIK. This study indicates a significant positive correlation between differences in epithelial thickening in different regions and differences in curvature changes in the corresponding areas PRK, FS-LASIK, curvature, corneal epithelial thickness.

Acute lung injury is a significant global health issue, and its treatment is becoming a hot topic of the researchers. To investigate the feasibility of miRNA-150-5p tail vein injection in the treatment of SiO 2 -induced acute lung injury through the regulation of gut microbiota and serum metabolites based on multiomics technology. Twenty-four mice were randomly divided into the control, SiO 2 and miRNA-150-5p intervention groups. The SiO 2 and miRNA-150-5p intervention groups received a single intranasal dose of 100 µL 4 % SiO 2 suspension. Meanwhile, the miRNA-150-5p intervention group was administered with two tail vein injections of miRNA-150-5p (15 nmol each per mouse) on the day of successful modelling and on the third day post modelling. Metagenomics and metabolomics techniques were used to measure gut microbiota and serum metabolites, respectively. Tail vein injection of miRNA-150-5p improved SiO 2 -induced acute lung injury and reduced the secretion of inflammatory factors interleukin (IL)-6, tumour necrosis factor-α and IL-1β. These conditions altered the structure of gut microbiota, which resulted in the notable modulation of eight species at the species level. In addition, tail vein injection of miRNA-150-5p considerably reduced the levels of substances, such as phosphatidylethanolamine, phosphatidylcholine and phosphatidylinositol, in the glycerophospholipid metabolism and glycosylphosphatidylinositol-anchor biosynthesis pathways. Tail vein injection of miRNA-150-5p can alleviate acute lung injury. Combined metagenomics and untargeted metabolomics revealed the miRNA-150-5p-mitigated SiO 2 -induced acute lung injury that occurred through the regulation of gut microbiota and serum metabolites., 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.)

Bladder carcinoma (BLCA) represents a common urinary tract malignancy, characterized by aggressive behavior and high recurrence rates. The biological response regulation during tumor proliferation and metastasis is intimately associated with liquid-liquid phase separation (LLPS). For the purpose of enhancing early detection and treatment, this study employed transcriptomic data to examine the prognostic implications of LLPS-associated genes and formulate a predictive model. Clinical and transcriptomic data of bladder cancer patients were sourced from the GEO and TCGA databases. This study applied a clustering algorithm using non-negative matrix factorization (NMF) to classify samples, which were systematically compared based on their liquid-liquid phase separation characteristics. Prognostic models were developed using multivariate Cox regression and the Least Absolute Shrinkage Selection Operator (LASSO) algorithm to establish risk formulas for nine genes. The gene signature's validity was tested across the entire TCGA cohort (406 cases), the TCGA testing cohort (120 cases), and the external validation dataset GSE13507. The predictive accuracy of the signature system was assessed using receiver operating characteristic (ROC) and Kaplan-Meier curves. Additionally, decision curve analysis incorporating clinicopathological parameters and the genetic signature was employed to predict individual survival. This study identified two distinct molecular subtypes, C1 and C2. Patients with the C1 subtype exhibited significantly better prognoses than those with the C2 subtype. Low-risk group patients consistently showed superior prognoses compared to high-risk groups across the entire TCGA, GEO, and TCGA training cohorts. Furthermore, the LLPS-related gene model demonstrated prognostic value independent of other clinical traits. This study identifies LLPS-associated gene clusters and establishes an independent, accurate prognostic model for BLCA. The model holds potential for clinical application in BLCA prognosis assessment., (© 2024. The Author(s).)

Background and Aims: We evaluate whether the combination of sodium-glucose cotransporter-2 inhibitor(SGLT2i) and glucagon-like peptide-1 receptor agonist(GLP1RA) disproportionally increases the reporting of adverse events compared with SGLT2i or GLP1RA monotherapy in the FDA adverse event reporting system (FAERS)., Methods and Results: Adverse events related to SGLT2i and GLP1RA were screened and selected, then data from the FAERS was underwent thorough disproportionality analysis. The proportional reporting ratio(PRR) of SGLT2i-related adverse events were compared between patients using SGLT2i alone and those using both SGLT2i and GLP1RA. Similarly, the PRR of GLP1RA-related adverse events were compared between patients using GLP1RA alone and those using both SGLT2i and GLP1RA. The results showed that the PRR of SGLT2i-related adverse events including diabetic ketoacidosis(DKA), ketosis, reproductive tract adverse events, urinary tract infection, and other adverse events, decreased in individuals using both SGLT2i and GLP1RA compared with those using SGLT2i alone, and the signal of fracture was not detected. Likewise, the PRR of GLP1RA-related adverse events including gastrointestinal adverse events, gallbladder and biliary tract disease, pancreatitis, and other adverse events, decreased in individuals using both SGLT2i and GLP1RA compared with those using GLP1RA alone, the PRR of hyperlipasaemia and hyperamylasaemia increased in the combination therapy and no signal of depression, suicidal and self-injurious behaviour was detected., Conclusion: Adverse events reporting are not disproportionally higher among those using both SGLT-2i and GLP1RA compared with SGLT2i or GLP1RA monotherapy., Competing Interests: Declaration of competing interest No potential conflicts of interest relevant to this article were reported., (Copyright © 2024 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Background: Diabetic cognitive dysfunction (DCD) has attracted increased attention, but its precise mechanism remains to be explored. Oligodendrocytes form myelin sheaths that wrap around axons. Granzyme B (GZMB) can cause axonal degeneration of the central nervous system. However, the role of GZMB in diabetic cognitive dysfunction (DCD) has not been reported. This study aimed to investigate whether GZMB promotes demyelination and participates in DCD by regulating the endoplasmic reticulum stress function of oligodendrocytes., Methods: Streptozotocin was injected intraperitoneally to establish a diabetic model in C57BL/6 mice. The mice were randomly divided into four groups: control group, diabetic group, diabetic + SerpinA3N group, and diabetic + saline treatment group. We performed the Morris water maze test to assess the learning and memory abilities of the mice. An immunofluorescence assay was performed to detect the expression sites of GZMB and OLIG2 in the hippocampal CA1 region. Luxol Fast Blue staining and electron microscopy were performed to detect the myelin number and myelin plate densities. Immunohistochemistry was used to detect the expression levels of MBP and CNPase. Protein blotting was used to assess the expression levels of GZMB, PERK, p-PERK, eIF2α, p-eIF2α, NLRP3, Caspase-1, GSDMD-N, IL-1β, and IL-18 as well as MBP and CNPase., Results: The GZMB inhibitor SerpinA3N reduces escape latency and increases the traversing platforms and residence time in the target area, improving DCD in mice. It also reduces endoplasmic reticulum stress in hippocampal oligodendrocytes and focal prolapse, further promoting MBP and CNPase expression and reducing demyelination., Conclusions: Our findings suggest that inhibition of GZMB activity modulates oligodendrocyte endoplasmic reticulum stress and pyroptosis, reduces demyelination, and ameliorates diabetes-related cognitive impairment., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Mitochondria-endoplasmic reticulum contact sites (MERCS) serve as hotspots for important cellular processes, including calcium homeostasis, phospholipid homeostasis, mitochondria dynamics, and mitochondrial quality control. MERCS reporters based on complementation of green fluorescent proteins (GFP) fragments have been designed to visualize MERCS in real-time, but we find that they do not accurately respond to changes in MERCS content. Here, we utilize split LacZ complementing fragments to develop the first MERCS reporter system (termed SpLacZ-MERCS) that continuously integrates the MERCS information within a cell and generates a fluorescent output. Our system exhibits good organelle targeting, no artifactual tethering, and effective, dynamic tracking of the MERCS level in single cells. The SpLacZ-MERCS reporter was validated by drug treatments and genetic perturbations known to affect mitochondria-ER contacts. The signal-integrating nature of SpLacZ-MERCS may enable systematic identification of genes and drugs that regulate mitochondria-ER interactions. Our successful application of the split LacZ complementation strategy to study MERCS may be extended to study other forms of interorganellar crosstalk.

2D layered metal halide perovskites (MHPs) are a potential material for fabricating self-powered photodetectors (PDs). Nevertheless, 2D MHPs produced via solution techniques frequently exhibit multiple quantum wells, leading to notable degradation in the device performance. Besides, the wide band gap in 2D perovskites limits their potential for broad-band photodetection. Integrating narrow-band gap materials with perovskite matrices is a viable strategy for broad-band PDs. In this study, the use of methylamine acetate (MAAc) as an additive in 2D perovskite precursors can effectively control the width of the quantum wells (QWs). The amount of MAAc greatly affects the phase purity. Subsequently, PbSe QDs were embedded into the 2D perovskite matrix with a broadened absorption spectrum and no negative effects on ferroelectric properties. PM6:Y6 was combined with the hybrid ferroelectric perovskite films to create a self-powered and broad-band PD with enhanced performance due to a ferro-pyro-phototronic effect, reaching a peak responsivity of 2.4 A W -1 at 940 nm.

Background: Articular cartilage degeneration can result from injury, age, or arthritis, causing significant joint pain and disability without surgical intervention. Currently, the only FDA cell-based therapy for articular cartilage injury is Autologous Chondrocyte Implantation (ACI); however, this procedure is costly, time-intensive, and requires multiple treatments. Mesenchymal stromal cells (MSCs) are an attractive alternative autologous therapy due to their availability and ability to robustly differentiate into chondrocytes for transplantation with good safety profiles. However, treatment outcomes are variable due to donor-to-donor variability as well as intrapopulation heterogeneity and unstandardized MSC manufacturing protocols. Process improvements that reduce cell heterogeneity while increasing donor cell numbers with improved chondrogenic potential during expansion culture are needed to realize the full potential of MSC therapy., Methods: In this study, we investigated the potential of MSC metabolic modulation during expansion to enhance their chondrogenic commitment by varying the nutrient composition, including glucose, pyruvate, glutamine, and ascorbic acid in culture media. We tested the effect of metabolic modulation in short-term (one passage) and long-term (up to seven passages). We measured metabolic state, cell size, population doubling time, and senescence and employed novel tools including micro-magnetic resonance relaxometry (µMRR) relaxation time (T 2 ) to characterize the effects of AA on improved MSC expansion and chondrogenic potential., Results: Our data show that the addition of 1 mM L-ascorbic acid-2-phosphate (AA) to cultures for one passage during MSC expansion prior to initiation of differentiation improves chondrogenic differentiation. We further demonstrate that AA treatment reduced the proportion of senescent cells and cell heterogeneity also allowing for long-term expansion that led to a > 300-fold increase in yield of MSCs with enhanced chondrogenic potential compared to untreated cells. AA-treated MSCs with improved chondrogenic potential showed a robust shift in metabolic profile to OXPHOS and higher µMRR T 2 values, identifying critical quality attributes that could be implemented in MSC manufacturing for articular cartilage repair., Conclusions: Our results suggest an improved MSC manufacturing process that can enhance chondrogenic potential by targeting MSC metabolism and integrating process analytic tools during expansion., (© 2024. The Author(s).)

Metal smelting and combustion of solid fuels produce significant quantities of waste slag, leading to issues such as land occupation and environmental pollution. Understanding and controlling the microscale crystallization phenomena of these slags during thermal treatment is crucial for transforming waste slags into materials suitable for carbon capture or glass ceramics. Previous research has primarily focused on macroscopic crystallization behaviors, significantly advancing the utilization of waste slags in cement clinker production. However, macroscopic results are inadequate for precisely controlling the microscale crystallization behaviors of waste slags. Here, we employed the single hot thermocouple technique to visually explore crystal growth modes, shapes, sizes, numbers, and translational rates of the crystal growth front in a representative blast furnace slag under various isothermal temperatures. The results revealed that crystals exhibited five modes as the isothermal temperature gradually increased, including equiaxed, equiaxed & columnar, columnar, columnar & planar, and planar. Moreover, the translational rate of the crystal growth front increased from 0.011 μm·s -1 to 43.7 μm·s -1 with an increase in the isothermal temperature. Simultaneously, the number of crystals decreased from around 10 4 to 10 0 μm -2 . On this basis, correlations between microscale crystallization behaviors and isothermal temperature were established to fill the current gap., 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 Ltd. All rights reserved.)

Background: International students have a lower utilization rate of the local medical service system for studying abroad, and it has been found that there may be multiple reasons behind this phenomenon. This study explores the usage of medical service systems by international students and the underlying logical factors through a study of the usage of National Health Service (NHS) of Chinese students in the UK., Methods: To address the research questions, this study employed an online survey methodology that ran between 1st May and August 20, 2019 facing the Chinese students in the UK. A total of 1,050 questionnaires were distributed and 1,001 questionnaires were recovered, of which 977 contained valid responses (questionnaire response rate was 95.3 % and validity rate was 97.6 %). Before the questionnaire was designed and after it was issued, two focus group interviews were conducted to provide reliable and detailed information to inform the questionnaire design and to supplement the questionnaire survey data with more profound psychological qualitative data. The two focus groups consisted of 10 and 12 Chinese students studying in the UK and each lasted more than 3 h., Results: The survey data showed that the medical services utilization rate of Chinese students in the UK is relatively low compared to UK residents and domestic Chinese students. Their decisions and behaviours around medical services usage in the UK are not significantly related to age, gender, and monthly income, but are instead related to their current education status, types of disease suffered, and information acquisition about the UK medical services before coming to the UK. When getting sick, in addition to seeking help from official medical services, Chinese students studying in the UK tend to self-diagnose and self-medicate; seeking help from social networks based on friendship and domestic relatives are also alternatives to accessing medical services., Conclusion: Combining the theories of 'sick role' and 'illness experience', the decisions and behaviours related to medical services usage by Chinese students in the UK are significantly influenced by their understanding of medical services, which is socially and culturally learned in China. Understanding the perspective of the 'sick role' and the 'illness experience' of Chinese students may help to better think about how improvements can be made to their utilization rate of medical services and their health status during their studies in the UK. This study not only provides us with specific information and understanding on the usage of medical services for Chinese students in the UK, but the research results may also provide a reference for other similar research on the health and medical service use of other international students studying in the cross-cultural contexts., 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., (© 2024 The Authors.)

Developing biochar with large specific surface area (SSA), heteroatom doping, and porous structure is attracting substantial attention to absorb electromagnetic wave (EMW) in recent. Herein, a novel method of ethanol and KOH co-treatment is used to produce the biomass carbon deriving from pitaya peels. The obtained carbon possesses the high SSA of 1580 m 2 /g, successful N/O atoms co-doping, and massive pores with different size. The results of EMW absorption measurement show that the prepared biochar could achieve over 99 % absorpition to EMW, which the highest reflection loss is of ca. -45.25 dB at 7.54 GHz with an effective absorption bandwidth (EAB) of ca. 4.87 GHz. The execellent microwave absorption property is caused by the surface defects, dipole and interface polarizations of the synthesized biochar owning unique microstructure and N/O atoms co-doping. Hence, this avenue provides a new reference for fabricating low-cost and eco-friendly biochar as a microwave absorber., (© 2024 Wiley-VCH GmbH.)

Background: Cotton is an important economic crop and a host of Liriomyza sativae. Pectin methylesterase (PME)-mediated pectin metabolism plays an indispensable role in multiple biological processes in planta. However, the pleiotropic functions of PME often lead to unpredictable effects on crop resistance to pests. Additionally, whether and how PME affects susceptibility to Liriomyza sativae remain unclear., Results: Here, we isolated GhPME36, which is located in the cell wall, from upland cotton (Gossypium hirsutum L.). Interestingly, the overexpression of GhPME36 in cotton caused severe susceptibility to Liriomyza sativae but increased leaf biomass in Arabidopsis. Cytological observations revealed that the cell wall was thinner with more demethylesterified pectins in GhPME36-OE cotton leaves than in WT leaves, whereas the soluble sugar content of GhPME36-OE cotton leaf cell walls was accordingly higher; both factors attracted Liriomyza sativae to feed on GhPME36-OE cotton leaves. Metabolomic analysis demonstrated that glucose was significantly differentially accumulated. Transcriptomic analysis further revealed DEGs enriched in glucose metabolic pathways when GhPME36 was overexpressed, suggesting that GhPME36 aggravates susceptibility to Liriomyza sativae by affecting both the structure and components of cell wall biosynthesis. Moreover, GhPME36 interacts with another pectin-modifying enzyme, GhC/VIF1, to maintain the dynamic stability of pectin methyl esterification., Conclusions: Taken together, our results reveal the cytological and molecular mechanisms by which GhPME36 aggravates susceptibility to Liriomyza sativae. This study broadens the knowledge of PME function and provides new insights into plant resistance to pests and the safety of genetically modified plants., (© 2024. The Author(s).)

In this study, umami peptides were screened and characterized from bovine bone soups manufactured via atmospheric and high-pressure boiling. Peptide fractions with molecular weights less than 3 kDa were selected for peptide sequencing using LC-MS/MS, the toxicity prediction of the umami peptides was carried out by using an website, and the peptides were screened according to the binding energy, i.e., three peptides including YDAELS, TDVAHR, and ELELQ were selected. The three umami peptides were further synthesized, and their umami thresholds were determined through sensory evaluation and electronic tongue analysis, ranging from 0.375 to 0.75 mg/mL. All three peptides exhibited a significant synergistic taste enhancement effect when combined with MSG (monosodium glutamate) solution. The molecular docking of the umami peptides with the T1R1/T1R3 receptor revealed the mechanism of umami presentation, and the main interaction forces between the three umami peptides and the receptor were hydrogen bonding, electrostatic interactions, and hydrophobic interactions.

The antioxidant and immune systems of weaned piglets are not fully mature and are also subjected to serious stress challenges related to oxidative stress and inflammation. Selenium (Se) is an essential element for pigs, with documented roles encompassing antioxidative and anti-inflammatory properties via selenoproteins. Sodium selenite and Se-enriched yeast are commonly acknowledged as conventional sources of Se for piglets. In the past decade, several novel Se sources have emerged in the field of weaned piglet nutrition. In this review, we will initially outline the historical timeline of Se sources as reported in weaned piglet nutrition. Afterwards, our attention will turn towards the nutritional regulation of Se sources in relation to the antioxidant and anti-inflammatory aspects of healthy weaned piglets. Ultimately, we will provide a detailed review highlighting the potential of emerging Se sources in alleviating various adverse effects of stress challenges faced by weaned piglets. These challenges include oxidative stress, enterotoxigenic Escherichia coli infection, lipopolysaccharide-induced inflammation, heat stress, and exposure to feed mycotoxins. The output of this review will emphasize the fundamental importance of incorporating emerging Se sources in the diet of weaned piglets.

Background: Stroke is the third-leading cause of death and disability, and poststroke falls (PSF) are common at all stages after stroke and could even lead to injuries or death. Brain information from functional near-infrared spectroscopy (fNIRs) may precede conventional imaging and clinical symptoms but has not been systematically considered in PSF risk prediction. This study investigated the difference in brain activation between stroke patients and healthy subjects, and this study was aimed to explore fNIRs biomarkers for early screening of PSF risk by comparing the brain activation in patients at and not at PSF risk., Methods: In this study, we explored the differences in brain activation and connectivity between stroke and healthy subjects by synchronizing the detection of fNIRs and EMG tests during simple (usual sit-to-stand) and difficult tasks (sit-to-stand based on EMG feedback). Thereby further screened for neuroimaging biomarkers for early prediction of PSF risk by comparing brain activation variability in poststroke patients at and not at fall risk during simple and difficult tasks. The area under the ROC curve (AUROC), sensitivity, and specificity were used to compare the diagnostic effect., Results: A total of 40 patients (22 not at and 18 at PSF risk) and 38 healthy subjects were enrolled. As the difficulty of standing task increased, stroke patients compared with healthy subjects further increased the activation of the unaffected side of supplementary motor area (H-SMA) and dorsolateral prefrontal cortex-Brodmann area 46 (H-DLFC-BA46) but were unable to increase functional connectivity (Group*Task: p < 0.05). More importantly, the novel finding showed that hyperactivation of the H-SMA during a simple standing task was a valid fNIRs predictor of PSF risk [AUROC 0.74, p = 0.010, sensitivity 77.8%, specificity 63.6%]., Conclusions: This study provided novel evidence that fNIR-derived biomarkers could early predict PSF risk that can facilitate the widespread use of real-time assessment tools in early screening and rehabilitation. Meanwhile, this study demonstrated that the higher brain activation and inability to increase the brain functional connectivity in stroke patients during difficult task indicated the inefficient use of brain resources., (© 2024 The Author(s). CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Near-infrared-II (NIR-II) fluorescence imaging is pivotal in biomedical research. Organic probes exhibit high potential in clinical translation, due to advantages such as precise structure design, low toxicity, and post-modifications convenience. In related preparation, enhancement of NIR-II tail emission from NIR-I dyes is an efficient method. In particular, the promotion of twisted intramolecular charge transfer (TICT) of relevant NIR-I dyes is a convenient protocol. However, present TICT-type probes still show disadvantages in relatively low emission, large particle sizes, or limited choice of NIR-I dyes, etc. Herein, the synthesis of stable small-sized polymer NIR-II fluoroprobes (e.g., 7.2 nm), integrating TICT and Förster resonance energy transfer process to synergistically enhance the NIR-II emission is reported. Strong enhanced emissions can be obtained from various NIR-I dyes and lanthanide elements (e.g., twelvefold at 1250 nm from Nd-DTPA/IR-808 sample). The fluorophore provides high-resolution angiography, with high-contrast imaging on middle cerebral artery occlusion model mice for distinguishing occlusion. The fluorophore can be rapidly excreted from the kidney (urine ≈65% within 4 h) in normal mice and exhibits long-term renal retention on acute kidney injury mice, showing potential applications in the prognosis of kidney diseases. This development provides an effective strategy to design and synthesize effective NIR-II fluoroprobes., (© 2024 Wiley‐VCH GmbH.)

Objective: To compare the dentofacial characteristics of children with and without adenoid and/or tonsillar hypertrophy., Methods: A consecutive sample of orthodontic patients aged 6-12 that took pre-treatment lateral cephalograms were included in this study. Those with history of previous orthodontic treatment, adenoidectomy or tonsillectomy, or craniofacial anomalies were excluded. The diagnosis of adenoid and tonsillar hypertrophy was based on Fujioka's and Baroni's methods, according to which the subjects were divided into four groups: the adenoid hypertrophy only (AHO) group; tonsillar hypertrophy only (THO) group; combined adenoid and tonsillar hypertrophy (AH+TH) group; and no adenoid or tonsillar hypertrophy (NH) group. Cephalograms were used for skeletal and dental measurement. Data were analyzed using one-way ANOVA, LSD post-hoc tests and Chi-square test., Results: A total of 598 patients were included. Compared with the NH group, the THO group had significantly larger SNB angle (P < 0.001), as well as significantly smaller ANB angle (P<0.001) and Wits value (P = 0.001). The U1-L1 angle of AHO group was significantly smaller than that in the NH group (P = 0.035). The proportion of adenoid hypertrophy in Class II patients was significantly higher than that in Class III patients (P = 0.001). The proportion of tonsillar hypertrophy in Class III patients was significantly higher than that in Class I patients (P < 0.001) and Class II patients (P < 0.001)., Conclusion: Over 80 % of children seeking orthodontic treatment had either adenoid or tonsillar hypertrophy. Children with adenoid hypertrophy tend to have skeletal Class II malocclusion, while those with tonsillar hypertrophy tend to have skeletal Class III malocclusion., 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 Masson SAS. All rights reserved.)

Traditional artificial vision systems built using separate sensing, computing, and storage units have problems with high power consumption and latency caused by frequent data transmission between functional units. An effective approach is to transfer some memory and computing tasks to the sensor, enabling the simultaneous perception-storage-processing of light signals. Here, an optical-electrical coordinately modulated memristor is proposed, which controls the conductivity by means of polarization of the 2D ferroelectric Ruddlesden-Popper perovskite film at room temperature. The residual polarization shows no significant decay after 10 9 -cycle polarization reversals, indicating that the device has high durability. By adjusting the pulse parameters, the device can simulate the bio-synaptic long/short-term plasticity, which enables the control of conductivity with a high linearity of ≈0.997. Based on the device, a two-layer feedforward neural network is built to recognize handwritten digits, and the recognition accuracy is as high as 97.150%. Meanwhile, building optical-electrical reserve pool system can improve 14.550% for face recognition accuracy, further demonstrating its potential for the field of neural morphological visual systems, with high density and low energy loss., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Administration of a new drug candidate in a first-in-human (FIH) clinical trial is a particularly challenging phase in drug development and is especially true for immunomodulators, which are a diverse and complex class of drugs with a broad range of mechanisms of action and associated safety risks. Risk is generally greater for immunostimulators, in which safety concerns are associated with acute toxicity, compared to immunosuppressors, where the risks are related to chronic effects. Current methodologies for FIH dose selection for immunostimulators are focused primarily on identifying the minimum anticipated biological effect level (MABEL), which has often resulted in sub-therapeutic doses, leading to long and costly escalation phases. The Health and Environmental Sciences Institute (HESI) - Immuno-Safety Technical Committee (ITC) organized a project to address this issue through two complementary approaches: (i) an industry survey on FIH dose selection strategies and (ii) detailed case studies for immunomodulators in oncology and non-oncology indications. Key messages from the industry survey responses highlighted a preference toward more dynamic PK/PD approaches as in vitro assays are seemingly not representative of true physiological conditions for immunomodulators. These principles are highlighted in case studies. To address the above themes, we have proposed a revised decision tree, which expands on the guidance by the IQ MABEL Working Group (Leach et al. 2021). This approach facilitates a more refined recommendation of FIH dose selection for immunomodulators, allowing for a nuanced consideration of their mechanisms of action (MOAs) and the associated risk-to-benefit ratio, among other factors., (© 2024 The Author(s). Clinical Pharmacology & Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Purpose: To investigate the injury mechanism, diagnosis, and treatment of varus-posteromedial rotational instability of the elbow joint in children., Methods: According to the diagnostic criteria of varus posteromedial rotational instability of elbow joint, 16 children with coronoid process fractures treated in our department from July 2013 to July 2017 were re-evaluated. There were 14 males and 2 females, aged 7 to 14 years, with an average age of 11.6 years. Eight cases on left and 8 cases on right side. An associated elbow dislocation occurred in 8 of 16 cases. Nine patients were treated with a lateral soft tissue repair only. In 7 other patients in addition to the lateral soft tissue repair, the coronoid process fractures were treated with open reduction and fixation. At the last clinical follow-up, each elbow joint range of motion was recorded, radiographs were obtained, and functional performance was evaluated by the Mayo elbow performance score (MEPS)., Results: The average follow-up time was 81.9 months for the 9 patients treated with lateral elbow soft tissue repair. At the last follow-up, 2 of the patients had MEPS scores as excellent, 1 was good, and 6 were rated as moderate or poor. Four patients had a cubitus varus deformity. The average follow-up time was 30.3 months for the 7 patients treated with both soft tissue repair and coronoid fracture stabilization. The elbow joint MEPS scores for each of these 7 patients was excellent at the last follow-up, and no complications such as cubitus varus occurred., Conclusion: The results of the study suggest that children could also develop elbow varus-posterior medial rotational instability injuries under the same mechanism. Although the morbidity rate is low, due to insufficient understanding of the injury mechanism, it is prone to missed diagnosis, misdiagnosis, and delayed treatment, resulting in severe complications such as elbow instability, dislocation, traumatic arthritis, and elbow stiffness. On the contrary, according to the treatment principle of the posterior medial rotational instability of the elbow joint in adult, while the lateral repair is carried out, strong and effective reduction and fixation of the coronoid process fractures are adopted, it is expected that such children with rare elbow injuries can obtain excellent treatment outcomes., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

In the present research, the impacts of Ce additions at various concentrations (0, 1.0, 3.4, and 4.0 wt.%) on the evolution of the microstructure, mechanical properties, and thermal conductivity of as-cast and as-extruded Mg-3Sn alloys were investigated. The findings demonstrate that adding Ce caused the creation of a new ternary MgSnCe phase in the magnesium matrix. Some new Mg 17 Ce 2 phases are generated in the microstructure when Ce levels reach 4%. The thermal conductivity of the Mg-3Sn alloy is significantly improved due to Ce addition, and the Mg-3Sn-3.4Ce alloy exhibits the highest thermal conductivity, up to 133.8 W/(m·K) at 298 K. After extrusion, both the thermal conductivity and mechanical properties are further improved. The thermal conductivity perpendicular to the extrusion direction of Mg-3Sn-3.4Ce alloy could achieve 136.28 W/(m·K), and the tensile and yield strengths reach 264.3 MPa and 227.2 MPa, with an elongation of 7.9%. Adding Ce decreases the dissolved Sn atoms and breaks the eutectic α -Mg and Mg 2 Sn network organization, leading to a considerable increase in the thermal conductivity of as-cast Mg-3Sn alloys. Weakening the deformed grain texture contributed to the further enhancement of the thermal conductivity after extrusion.

Background: Small cell lung carcinoma (SCLC) is highly susceptible to metastasis in the early stages of the disease. However, the stomach is an uncommon site of metastasis in SCLC, and only a few cases of this type of metastasis have been reported. Therefore, SCLC gastric metastases have not been systematically characterized and are easily missed and misdiagnosed., Case Summary: We report three cases of gastric metastasis from SCLC in this article. The first patient presented primarily with cough, hemoptysis, and epigastric fullness. The other two patients presented primarily with abdominal discomfort, epigastric distension, and pain. All patients underwent gastroscopy and imaging examinations. Meanwhile, the immunohistochemical results of the lesions in three patients were suggestive of small cell carcinoma. Finally, the three patients were diagnosed with gastric metastasis of SCLC through a comprehensive analysis. The three patients did not receive appropriate treatment and died within a short time., Conclusion: Here, we focused on summarizing the characteristics of gastric metastasis of SCLC to enhance clinicians' understanding of this disease., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

The potential of serum extracellular vesicles (EVs) as non-invasive biomarkers for diagnosing colorectal cancer (CRC) remains elusive. We employed an in-depth 4D-DIA proteomics and machine learning (ML) pipeline to identify key proteins, PF4 and AACT, for CRC diagnosis in serum EV samples from a discovery cohort of 37 cases. PF4 and AACT outperform traditional biomarkers, CEA and CA19-9, detected by ELISA in 912 individuals. Furthermore, we developed an EV-related random forest (RF) model with the highest diagnostic efficiency, achieving AUC values of 0.960 and 0.963 in the train and test sets, respectively. Notably, this model demonstrated reliable diagnostic performance for early-stage CRC and distinguishing CRC from benign colorectal diseases. Additionally, multi-omics approaches were employed to predict the functions and potential sources of serum EV-derived proteins. Collectively, our study identified the crucial proteomic signatures in serum EVs and established a promising EV-related RF model for CRC diagnosis in the clinic., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Recent years have seen a surge of machine learning (ML) in chemistry for predicting chemical properties, but a low-cost, general-purpose, and high-performance model, desirable to be accessible on central processing unit (CPU) devices, remains not available. For this purpose, here we introduce an atomic attention mechanism into many-body function corrected neural network (MBNN), namely, MBNN-att ML model, to predict both the extensive and intensive properties of molecules and materials. The MBNN-att uses explicit function descriptors as the inputs for the atom-based feed-forward neural network (NN). The output of the NN is designed to be a vector to implement the multihead self-attention mechanism. This vector is split into two parts: the atomic attention weight part and the many-body-function part. The final property is obtained by summing the products of each atomic attention weight and the corresponding many-body function. We show that MBNN-att performs well on all QM9 properties, i.e., errors on all properties, below chemical accuracy, and, in particular, achieves the top performance for the energy-related extensive properties. By systematically comparing with other explicit-function-type descriptor ML models and the graph representation ML models, we demonstrate that the many-body-function framework and atomic attention mechanism are key ingredients for the high performance and the good transferability of MBNN-att in molecular property prediction.

Exosomes belong to a subgroup of extracellular vesicles secreted by various cells and are involved in intercellular communication and material transfer. In recent years, exosomes have been used as drug delivery carriers because of their natural origin, high stability, low immunogenicity and high engineering ability. However, achieving targeted drug delivery with exosomes remains challenging. In this paper, a phage display technology was used to screen targeted peptides, and different surface modification strategies of targeted peptide exosomes were reviewed. In addition, the application of peptide-targeted exosomes in pulmonary diseases was also summarised., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Qiu et al.)

Polarity is a vital element in endoplasmic reticulum (ER) microenvironment, and its variation is closely related to many physiological and pathological activities of ER, so it is necessary to trace fluctuations of polarity in ER. However, most of fluorescent probes for detecting polarity dependent on the changes of single emission, which could be affected by many factors and cause false signals. Ratiometric fluorescent probe with "built-in calibration" can effectively avoid detection errors. Here, we have designed a ratiometric fluorescent probe HM for monitoring the ER polarity based on the intramolecular reaction of spiro-oxazolidine. It forms ring open/closed isomers driven by polarity to afford ratiometric sensing. Probe HM have manifested its ratiometric responses to polarity in spectroscopic results, which could offer much more precise information for the changes of polarity in living cells with the internal built-in correction. It also showed large emission shift ( 133 nm), high selectivity and photo-stability. In biological imaging, HM could selectively accumulate in ER with high photo-stability. Importantly, HM has ability for in situ tracing the changes of ER polarity with ratiometric behavior during the ER stress process with the stimulation of tunicamycin, dithiothreitol and hypoxia, suggesting that HM is an effective molecule tool for monitoring the variations of ER polarity., 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 use of X-ray sources in place of the 137 Cs sources used in traditional lithology density logging methods has become a new trend in the development of nuclear logging techniques. How to eliminate the effects of drilling fluids or mudcake in the measurement process is a key question that determines the accuracy of measurement. In order to reduce the effects of mudcake and improve the accuracy of measurement of formation parameters, this paper presents an inversion method that can accurately calculate formation and borehole parameters and is suitable for X-ray lithology density logging. The general process of this inversion method is described below. First, a response model for broad-beam attenuation during X-ray lithology density logging is derived. Subsequently, the responses of four detectors under various formation and borehole conditions are studied by means of Monte Carlo simulation, and the energy spectra measured by each detector are divided into four energy windows (ranges) depending on the correlation with formation parameters. Finally, accurate values of formation and borehole parameters are obtained through iterative inversion using the Levenberg-Marquardt (LM) algorithm. The results of this study show that compared with previously established analysis methods, the inversion method based on forward modeling can effectively improve the accuracy of measurement of formation density and lithology index during X-ray lithology density logging, reduce the influence of the borehole environment, and overcome the deficiencies of data processing techniques based on the spine and ribs plot., 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 Ltd. All rights reserved.)

Chemotherapy toxicity and tumor multidrug resistance remain the main reasons for clinical treatment failure in cervical cancer. In this study, 79 novel chalcone derivatives were designed and synthesized using the principle of active substructure splicing with the parent nucleus of licorice chalcone as the lead compound and VEGFR-2 and P-gp as the target of action and their potentials for anticervical cancer activity were preliminarily evaluated. The results showed that the IC 50 values of candidate compound B20 against HeLa and HeLa/DDP cells were 3.66 ± 0.10 and 4.35 ± 0.21 μΜ, respectively, with a resistance index (RI) of 1.18, which was significantly higher than that of the positive drug cisplatin (IC 50 :13.60 ± 1.63, 100.03 ± 7.94 μΜ, RI:7.36). In addition, B20 showed significant inhibitory activity against VEGFR-2 kinase and P-gp-mediated rhodamine 123 efflux, as well as the ability to inhibit the phosphorylation of VEGFR-2 and downstream PI3K/AKT signaling pathway proteins, inducing apoptosis, blocking cells in the S-phase, and inhibiting invasive migration and tubule generation by HUVEC cells. Acceptable safety was demonstrated in acute toxicity tests when B20 was at 200 mg/kg. In the nude mouse HeLa/DDP cell xenograft tumor model, the inhibition rate of transplanted tumors was 39.2 % and 79.2 % when B20 was at 10 and 20 mg/kg, respectively. These results suggest that B20 is a potent VEGFR-2 and P-gp inhibitor with active potential for treating cisplatin-resistant cervical cancer., 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 Inc. All rights reserved.)

Objective: Bladder outlet obstruction (BOO) results in significant fibrosis in the chronic stage and elevated bladder pressure. Piezo1 is a type of mechanosensitive (MS) channel that directly responds to mechanical stimuli. To identify new targets for intervention in the treatment of BOO-induced fibrosis, this study investigated the impact of high hydrostatic pressure (HHP) on Piezo1 activity and the progression of bladder fibrosis., Methods: Immunofluorescence staining was conducted to assess the protein abundance of Piezo1 in fibroblasts from obstructed rat bladders. Bladder fibroblasts were cultured under normal atmospheric conditions (0 cmH 2 O) or exposed to HHP (50 cmH 2 O or 100 cmH 2 O). Agonists or inhibitors of Piezo1, YAP1, and ROCK1 were used to determine the underlying mechanism., Results: The Piezo1 protein levels in fibroblasts from the obstructed bladder exhibited an elevation compared to the control group. HHP significantly promoted the expression of various pro-fibrotic factors and induced proliferation of fibroblasts. Additionally, the protein expression levels of Piezo1, YAP1, ROCK1 were elevated, and calcium influx was increased as the pressure increased. These effects were attenuated by the Piezo1 inhibitor Dooku1. The Piezo1 activator Yoda1 induced the expression of pro-fibrotic factors and the proliferation of fibroblasts, and elevated the protein levels of YAP1 and ROCK1 under normal atmospheric conditions in vitro. However, these effects could be partially inhibited by YAP1 or ROCK inhibitors., Conclusion: The study suggests that HHP may exacerbate bladder fibrosis through activating Piezo1., (© 2024. Huazhong University of Science and Technology.)

Background: Differences in pretreatment body mass index (BMI) have been associated with survival in squamous cell carcinoma of head and neck (SCCHN). We examined effects of BMI on survival in SCCHN patients after stratifying patients by tumor human papillomavirus (HPV) status and subsite., Methods: Totally 2204 SCCHN patients in a prospective study were included in this secondary analysis. Multivariable Cox models were used to evaluate associations between pretreatment BMI and overall survival, disease-specific survival, and disease-free survival., Results: BMI was significantly higher among patients with HPV-positive tumors than HPV-negative tumors. BMI >25 kg/m 2 was associated with improved survival, while BMI <18.5 kg/m 2 was associated with reduced survival, particularly in patients with HPV-positive oropharyngeal cancer tumors., Conclusions: This exploratory analysis suggests that pretreatment BMI could be an independent prognostic factor of survival outcomes in SCCHN patients, particularly in patients with HPV-positive oropharyngeal cancer tumors. Further prospective investigations are warranted., (© 2024 Wiley Periodicals LLC.)