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Jing Hong,1,&ast; Wen-Yue Liu,1,&ast; Xiang Hu,1 Wen-Wen Chen,2 Fei-Fei Jiang,1 Ze-Ru Xu,1 Fei-Xia Shen,1 Hong Zhu1 1Department of Endocrinology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, People’s Republic of China; 2Department of Geriatrics, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hong Zhu, Department of Endocrinology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of China, Tel +86 577-55579622, Fax +86 577-55578522, Email zhuhong@wmu.edu.cnPurpose: Free triiodothyronine (FT3) and FT3/free thyroxine (FT4) ratio have been associated with mortality in various diseases. However, no study to date has identified a link between FT3, FT3/FT4 ratio and all-cause mortality in patients with diabetic foot ulcers (DFUs). This study aimed to investigate this relationship.Methods: This retrospective cohort study included 726 patients diagnosed with DFUs in a public hospital from January 2015 to October 2019. Patients were classified by the optimal cut-off values of the FT3 and FT3/FT4 ratio, respectively. The association of FT3 and FT3/FT4 ratio with all-cause mortality was evaluated in a multivariable cox regression model. Directed acyclic graphs were used to assess the minimally sufficient sets of confounding variables.Results: Log rank tests indicated that patients with low FT3 and FT3/FT4 ratio had lower overall survival rates (all p < 0.001). The adjusted HRs for all-cause mortality were 0.48 (95% CI: 0.32– 0.73, P = 0.001) when comparing high versus low FT3 and 0.47 (95% CI: 0.32– 0.70, P < 0.001) when comparing high versus low FT3/FT4 ratio. Subgroup analyses showed that these associations existed only in elderly patients (≥ 65 years) and women, after adjustment. In men, only high FT3/FT4 ratio was associated with low all-cause mortality, after adjustment.Conclusion: Routine assessment of FT3 and FT3/FT4 ratio may be a simple and effective way to identify high-risk patients with DFUs, especially in elderly patients and women.Keywords: FT3, FT3/FT4 ratio, mortality, diabetic foot ulcer

Jun Chen,1,* Wenhui Huang,2,* Songyuan Luo,2,* Dahao Yang,1 Zhengrong Xu,1 Jianfang Luo21Department of Angiocardiopathy, Affiliated Baoan Hospital of Southern Medical University, Shenzhen City, People's Republic of China; 2Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, People's Republic of China*These authors contributed equally to this workObjective: To compare the safety, efficacy, and impact on stent graft positioning between rapid artificial cardiac pacing (RACP), induced hypotension and sodium nitroprusside (SNP) induced hypotension during thoracic endovascular aortic repair (TEVAR) for Stanford B aortic dissection.Methods: One hundred and sixty-eight patients, who were diagnosed with Stanford B aortic dissection and who underwent selective TEVAR in Guangdong General Hospital and the People's Hospital of Baoan District, Shenzhen, People's Republic of China, were enrolled in this study. Patients were randomly divided into a RACP group (n=77) and a SNP group (n=91). During localization and deployment of the stent graft, hypotension was induced by RACP or intravenous SNP, according to randomization. Hemodynamics, landing precision (deviation from planned placement site), duration of procedure, renal function, neurocognitive function, and incidence of endoleaks and paraplegia/hemiplegia were compared. Except for methods of inducing hypotension, TEVAR was performed according to the same protocol in each group.Results: RACP was successfully performed in all patients assigned to the RACP group. Compared with the SNP group, blood pressure was significantly lower (43±5 versus 81±6 mmHg, P=0.003) and the restoration time of blood pressure and the operation duration were significantly shorter (7±2 versus 451±87 seconds, P

This article presents a study of airflow pattern inside a five-story wind-driven naturally ventilated atrium building. Firstly, field measurement conducted in the atrium building reveals the existence of reversed flows from the atrium to windows, which could cause air cross-contamination between floors during the period of an infectious disease outbreak. The computational fluid dynamics technique was then employed to further investigate the airflow pattern inside the building, under different wind directions and opening ratios. It is found that the airflow pattern inside a wind-driven naturally ventilated atrium building is very sensitive to the oncoming wind direction. Under parallel and perpendicular incident wind directions, the existence of adversely reversed flows in a certain floor and the re-entry of used air from an upper floor into its adjacent lower floors through the atrium results in the decrease of indoor air quality and the effective air exchange through windows. Nevertheless, the building has good natural ventilation performance under oblique incident wind direction, although the expected role of the atrium is still not fully achieved. In addition, the improvement of airflow pattern inside wind-driven naturally ventilated buildings cannot be achieved by simply modifying the opening ratios.Practical application: Considering the indoor airflow pattern could substantially influence the elimination efficiency of pollutants and overheated air, this study is expected to help designers and engineers who are considering the use of an atrium at the design stage to have a better understanding of the airflow pattern inside a wind-driven naturally ventilated atrium building. [ABSTRACT FROM PUBLISHER]

Atrazine is a widely used herbicide in agricultural production. Previous studies have shown that atrazine affects hormone secretion and oocyte maturation in female reproduction. However, the specific mechanism by which atrazine affects ovarian function remains unclear. In this study, using a mouse gastric lavage model, we report that four weeks of atrazine exposure affects body growth, interferes with the estrous cycle, and increases the number of atretic follicles in mice. The expression levels of follicle development related factors StAR, BMP15, and AMH decreased. Metabolomic analysis revealed that atrazine activates an inflammatory response in ovarian tissue. Further studies confirmed that the expression levels of TNF-α, IL-6, and NF-κB increased in the ovaries of mice exposed to atrazine. Additionally, α-smooth muscle actin (α-SMA) accumulated in ovarian tissue, and transforming growth factor-β (TGF-β) signaling was activated, indicating the occurrence of tissue fibrosis. Moreover, mice exposed to atrazine produced fewer oocytes and exhibited reduced embryonic development. Furthermore, mice exposed to atrazine exhibited altered gut microbiota abundance and a disrupted colon barrier. Collectively, these findings suggest that atrazine exposure induces ovarian inflammation and fibrosis, disrupts ovarian homeostasis, and impairs follicle maturation, ultimately reducing oocyte quality., 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.)

Acrylamide (AAM), a compound extensively utilized in various industrial applications, has been reported to induce toxic effects across multiple tissues in living organisms. Despite its widespread use, the impact of AAM on ovarian function and the mechanisms underlying these effects remain poorly understood. Here, we established an AAM-exposed mouse toxicological model using 21 days of intragastric AAM administration. AAM exposure decreased ovarian coefficient and impaired follicle development. Further investigations revealed AAM would trigger apoptosis and disturb tricarboxylic acid cycle in ovarian tissue, thus affecting mitochondrial electron transport function. Moreover, AAM exposure decreased oocyte and embryo development potential, mechanically associated with pericentrin and phosphorylated Aurora A cluster failure, leading to meiotic spindle assembly defects. Collectively, these results suggest that AAM exposure may lead to apoptosis, glucose metabolic disorders, and mitochondrial dysfunction in ovary tissue, ultimately compromising oocyte quality., (© 2024 Wiley Periodicals LLC.)

Aims: Parkinson's disease (PD) is a common neurodegenerative disease that has received widespread attention; however, current clinical treatments can only relieve its symptoms, and do not effectively protect dopaminergic neurons. The purpose of the present study was to investigate the therapeutic effects of human umbilical cord mesenchymal stem cell-derived exosomes loaded with brain-derived neurotrophic factor (BDNF-EXO) on PD models and to explore the underlying mechanisms of these effects., Main Methods: 6-Hydroxydopamine was used to establish in vivo and in vitro PD models. Western blotting, flow cytometry, and immunofluorescence were used to detect the effects of BDNF-EXO on apoptosis and ferroptosis in SH-SY5Y cells. The in vivo biological distribution of BDNF-EXO was detected using a small animal imaging system, and dopaminergic neuron improvements in brain tissue were detected using western blotting, immunofluorescence, immunohistochemistry, and Nissl and Prussian blue staining., Key Findings: BDNF-EXO effectively suppressed 6-hydroxydopamine-induced apoptosis and ferroptosis in SH-SY5Y cells. Following intravenous administration, BDNF-EXO crossed the blood-brain barrier to reach afflicted brain regions in mice, leading to a notable enhancement in neuronal survival. Furthermore, BDNF-EXO modulated microtubule-associated protein 2 and phosphorylated tau expression, thereby promoting neuronal cytoskeletal stability. Additionally, BDNF-EXO bolstered cellular antioxidant defense mechanisms through the activation of the nuclear factor erythroid 2-related factor 2 signaling pathway, thereby conferring neuroprotection against damage., Significance: The novel drug delivery system, BDNF-EXO, had substantial therapeutic effects in both in vivo and in vitro PD models, and may represent a new treatment strategy for PD., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The helical structure is often the key factor for forming and enhancing chiroptical properties, such as circular dichroism (CD) and circular polarized luminescence (CPL) effects. However, no matter whether helical molecules or helical aggregates, they usually display modest chiroptical signals, which limits their practical applications. Herein, chiral tetraphenylethylene (TPE) bimacrocycles prepared in almost quantitative yield show strong and repeatable CD signals up to more than 7000 mdeg, which is very rare for general organic compounds, besides emitting very strong CPL light with an absolute g lum value up to 6.2 × 10 -2 . It is found that the superhelices formed by self-inclusion between the cavity and outward cyclohexyl ring of TPE bimacrocycles in crystal state are the key factor for highly enhanced chiroptical effect, and the self-inclusion superhelices in assemblies are confirmed by High Resolution Transmission Electron Microscopy (HR-TEM), Powder X-ray Diffraction (XRD) and Fourier Transform Infrared Spectrometry (FT-IR) data. Furthermore, the chiral TPE bimacrocycle shows great potential in chiral recognition and chiral analysis not only for chiral acids but also for chiral amines, chiral amino acids, and neutral chiral alcohol. Using self-inclusion helical nanocrystals of chiral macrocycles, this work provides a new strategy for chiroptical materials with excellent chiroptical properties., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Small extracellular vesicles (sEVs) have gained wide attention as efficient carriers for disease treatment. However, the proclivity of sEVs to be ingested by source cells is insufficient to accurately target specific sites, posing a challenge in realizing controlled targeting treatment. Here, we developed an engineered sEV nanocarrier capable of precise tumor targeting and enhanced synergistic therapy. Multivalent DNA probes, comprising abundant AS1411 aptamers and telomerase primers, were innovatively modified on the sEV membrane (M-D-sEV) for precise tumor targeting. To achieve synergistic therapy, gold nanorod-cerium oxide nanostructures (Au NRs-CeO 2 ) and manganese dioxide nanosheets-doxorubicin (MnO 2 NSs-DOX) were encapsulated into liposomes (Lip-Mat). Then M-D-sEV and Lip-Mat were fused together through membrane fusion to obtain nanocarriers. Owing to the multivalence of the probes, the surface of the nanocarriers was loaded with numerous aptamers, which greatly enhances their targeting ability and promotes the accumulation of drugs. When nanocarriers were ingested by tumor cells, telomerase and multivalent DNA probes triggered their aggregation, enhancing the therapeutic effect. Furthermore, under laser irradiation, Au NRs-CeO 2 converted light into hyperthermia, thereby inducing the destruction of nanocarriers membrane. This process initiated a series of reactions involving glutathione and H 2 O 2 consumption, as well as DOX release, ultimately achieving synergistic tumor therapy. In vitro and in vivo studies demonstrated the remarkable targeting ability of multivalent DNA probes and excellent therapeutic effect of this strategy. The engineered strategy of sEVs provide a promising approach for precise tumor therapy and hold great potential for the development of efficient, safe, and personalized drug delivery systems., 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.)

An ultrasensitive strategy for in-situ visual monitoring of ATP in a single living tumor cell during mitochondria-targeted photodynamic therapy (PDT) process with high spatiotemporal resolution was proposed using surface-enhanced Raman scattering (SERS) 3D imaging technique. The nanostructures consisting of Au-Ag 2 S Janus nanoparticles functionalized with both Au nanoparticles linked by a DNA chain and a mitochondrial-targeting peptide (JMDA NPs) were deliberately employed to target mitochondria. The JMDA NPs exhibit excellent SERS activity and remarkable antitumor activity. The quantization of ATP relies on the intensity of the SERS probes bonded to the DNA, which shows a strong correlation with the generated hot spot between the Janus and the Au. Consequently, spatiotemporally controlled monitoring of ATP in the mitochondria of single living cells during the PDT process was achieved. Additionally, the JMDA NPs demonstrated remarkable capability for mitochondria-targeted PDT, providing significant antitumor effects and superior therapeutic safety both in vitro and in vivo. Our work presents an effective JMDA NPs-based SERS imaging strategy for in-situ and real-time 3D visualization of intracellular ATP in living tumor cells during the mitochondria-targeted PDT process, which enables significant information on the time point of PDT treatment and is beneficial to precious PDT applications in tumor therapy., 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.)

Mucin 1 is an essential tumor biomarker, and developing cost-effective and portable methods for mucin 1 detection is crucial in resource-limited settings. Herein, the pH-regulated dual-enzyme mimic activities of manganese dioxide nanosheets were demonstrated, which were integrated into an aptasensor for dual-mode detection of mucin 1. Under acidic conditions, manganese dioxide nanosheets with oxidase mimic activities catalyzed the oxidation of 3,3',5,5'-tetramethylbenzidine sulfate, producing visible multicolor signals; while under basic conditions, manganese dioxide nanosheets with catalase mimic activities were used as catalyst for the decomposition of hydrogen peroxide, generating gas pressure signals. The proposed method allows the naked eye detection of mucin 1 through multicolor signal readout and the quantitative detection of mucin 1 with a handheld pressure meter or a UV-vis spectrophotometer. The study demonstrates that manganese dioxide nanosheets with pH-regulated dual-enzyme mimic activities can facilitate multidimensional transducing signals. The use of manganese dioxide nanosheets for the transduction of different signals avoids extra labels and simplifies the operation procedures. Besides, the signal readout mode can be selected according to the available detection instruments. Therefore, the use of manganese dioxide nanosheets with pH-regulated dual-enzyme mimic activities for dual-signal readout provides a new way for mucin 1 detection., 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.)

Mucin 1 is a significant tumor marker, and developing portable and cost-effective methods for its detection is crucial, especially in resource-limited areas. Herein, we developed an innovative approach for mucin 1 detection using a visible multicolor aptasensor. Urease-encapsulated DNA microspheres were used to mediate multicolor change facilitated by the color mixing of the mixed pH indicator, a mixed methyl red and bromocresol green solution. Distinct color changes were exhibited in response to varying mucin 1 concentrations. Notably, the color mixing of the mixed pH indicator was used to display various hues of colors, broadening the range of color variation. And color tonality is much easier to differentiate than color intensity, improving the resolution with naked-eyes. Besides, the variation of color from red to green (a pair of complementary colors) enhanced the color contrast, heightening sensitivity for visual detection. Importantly, the proposed method was successfully applied to detect mucin 1 in real samples, demonstrating a clear differentiation of colors between the samples of healthy individuals and breast cancer patients. The use of a mixed pH indicator as a multichromatic substrate offers the merits of low cost, fast response to pH variation, and plentiful color-evolution. And the incorporation of calcium carbonate microspheres to encapsulate urease ensures stable urease activity and avoids the need for extra urease decoration. The color-mixing dependent strategy opens a new way for multicolor detection of MUC1, characterized by vivid color changes., 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.)

Fluid manipulation is an important foundation of microfluidic technology. Various methods and devices have been developed for fluid control, such as electrowetting-on-dielectric-based digital microfluidic platforms, microfluidic pumps, and pneumatic valves. These devices enable precise manipulation of small volumes of fluids. However, their complexity and high cost limit the commercialization and widespread adoption of microfluidic technology. Shape memory polymers as smart materials can adjust their shape in response to external stimuli. By integrating shape memory polymers into microfluidic chips, new possibilities for expanding the application areas of microfluidic technology emerge. These shape memory polymers can serve as actuators or regulators to drive or control fluid flow in microfluidic systems, offering innovative approaches for fluid manipulation. Due to their unique properties, shape memory polymers provide a new solution for the construction of intelligent and automated microfluidic systems. Shape memory microfluidic chips are expected to be one of the future directions in the development of microfluidic technology. This article offers a summary of recent research achievements in the field of shape memory microfluidic chips for fluid and droplet manipulation and provides insights into the future development direction of shape memory microfluidic devices., Competing Interests: The authors have no conflicts to disclose., (© 2024 Author(s).)

The optimal approaches to managing diabetic foot infections remain a challenge for clinicians. Despite an exponential rise in publications investigating different treatment strategies, the various agents studied generally produce comparable results, and high-quality data are scarce. In this systematic review, we searched the medical literature using the PubMed and Embase databases for published studies on the treatment of diabetic foot infections from 30 June 2018 to 30 June 2022. We combined this search with our previous literature search of a systematic review performed in 2020, in which the infection committee of the International Working Group on the Diabetic Foot searched the literature until June 2018. We defined the context of the literature by formulating clinical questions of interest, then developing structured clinical questions (Patients-Intervention-Control-Outcomes) to address these. We only included data from controlled studies of an intervention to prevent or cure a diabetic foot infection. Two independent reviewers selected articles for inclusion and then assessed their relevant outcomes and methodological quality. Our literature search identified a total of 5,418 articles, of which we selected 32 for full-text review. Overall, the newly available studies we identified since 2018 do not significantly modify the body of the 2020 statements for the interventions in the management of diabetes-related foot infections. The recent data confirm that outcomes in patients treated with the different antibiotic regimens for both skin and soft tissue infection and osteomyelitis of the diabetes-related foot are broadly equivalent across studies, with a few exceptions (tigecycline not non-inferior to ertapenem [±vancomycin]). The newly available data suggest that antibiotic therapy following surgical debridement for moderate or severe infections could be reduced to 10 days and to 3 weeks for osteomyelitis following surgical debridement of bone. Similar outcomes were reported in studies comparing primarily surgical and predominantly antibiotic treatment strategies in selected patients with diabetic foot osteomyelitis. There is insufficient high-quality evidence to assess the effect of various recent adjunctive therapies, such as cold plasma for infected foot ulcers and bioactive glass for osteomyelitis. Our updated systematic review confirms a trend to a better quality of the most recent trials and the need for further well-designed trials to produce higher quality evidence to underpin our recommendations., (© 2023 The Authors. Diabetes/Metabolism Research and Reviews published by John Wiley & Sons Ltd.)

Background: Securing an early accurate diagnosis of diabetic foot infections and assessment of their severity are of paramount importance since these infections can cause great morbidity and potential mortality and present formidable challenges in surgical and antimicrobial treatment., Methods: In June 2022, we searched the literature using PubMed and EMBASE for published studies on the diagnosis of diabetic foot infection (DFI). On the basis of pre-determined criteria, we reviewed prospective controlled, as well as non-controlled, studies in English. We then developed evidence statements based on the included papers., Results: We selected a total of 64 papers that met our inclusion criteria. The certainty of the majority of the evidence statements was low because of the weak methodology of nearly all of the studies. The available data suggest that diagnosing diabetic foot infections on the basis of clinical signs and symptoms and classified according to the International Working Group of the Diabetic Foot/Infectious Diseases Society of America scheme correlates with the patient's likelihood of the need for hospitalisation, lower extremity amputation, and risk of death. Elevated levels of selected serum inflammatory markers such as erythrocyte sedimentation rate (ESR), C-reactive protein and procalcitonin are supportive, but not diagnostic, of soft tissue infection. Culturing tissue samples of soft tissues or bone, when care is taken to avoid contamination, provides more accurate microbiological information than culturing superficial (swab) samples. Although non-culture techniques, especially next-generation sequencing, are likely to identify more bacteria from tissue samples including bone than standard cultures, no studies have established a significant impact on the management of patients with DFIs. In patients with suspected diabetic foot osteomyelitis, the combination of a positive probe-to-bone test and elevated ESR supports this diagnosis. Plain X-ray remains the first-line imaging examination when there is suspicion of diabetic foot osteomyelitis (DFO), but advanced imaging methods including magnetic resonance imaging (MRI) and nuclear imaging when MRI is not feasible help in cases when either the diagnosis or the localisation of infection is uncertain. Intra-operative or non-per-wound percutaneous biopsy is the best method to accurately identify bone pathogens in case of a suspicion of a DFO. Bedside percutaneous biopsies are effective and safe and are an option to obtain bone culture data when conventional (i.e. surgical or radiological) procedures are not feasible., Conclusions: The results of this systematic review of the diagnosis of diabetic foot infections provide some guidance for clinicians, but there is still a need for more prospective controlled studies of high quality., (© 2023 John Wiley & Sons Ltd.)

The International Working Group on the Diabetic Foot (IWGDF) has published evidence-based guidelines on the management and prevention of diabetes-related foot diseases since 1999. The present guideline is an update of the 2019 IWGDF guideline on the diagnosis and management of foot infections in persons with diabetes mellitus. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework was used for the development of this guideline. This was structured around identifying clinically relevant questions in the P(A)ICO format, determining patient-important outcomes, systematically reviewing the evidence, assessing the certainty of the evidence, and finally moving from evidence to the recommendation. This guideline was developed for healthcare professionals involved in diabetes-related foot care to inform clinical care around patient-important outcomes. Two systematic reviews from 2019 were updated to inform this guideline, and a total of 149 studies (62 new) meeting inclusion criteria were identified from the updated search and incorporated in this guideline. Updated recommendations are derived from these systematic reviews, and best practice statements made where evidence was not available. Evidence was weighed in light of benefits and harms to arrive at a recommendation. The certainty of the evidence for some recommendations was modified in this update with a more refined application of the GRADE framework centred around patient important outcomes. This is highlighted in the rationale section of this update. A note is also made where the newly identified evidence did not alter the strength or certainty of evidence for previous recommendations. The recommendations presented here continue to cover various aspects of diagnosing soft tissue and bone infections, including the classification scheme for diagnosing infection and its severity. Guidance on how to collect microbiological samples, and how to process them to identify causative pathogens, is also outlined. Finally, we present the approach to treating foot infections in persons with diabetes, including selecting appropriate empiric and definitive antimicrobial therapy for soft tissue and bone infections; when and how to approach surgical treatment; and which adjunctive treatments may or may not affect the infectious outcomes of diabetes-related foot problems. We believe that following these recommendations will help healthcare professionals provide better care for persons with diabetes and foot infections, prevent the number of foot and limb amputations, and reduce the patient and healthcare burden of diabetes-related foot disease., (© 2023 The Authors. Diabetes/Metabolism Research and Reviews published by John Wiley & Sons Ltd.)

The solubility of cadmium (Cd) in soil and its transfer to plants are influenced by soil pH. While increasing soil pH reduces Cd solubility and accumulation in rice plants grown in acidic soils, its effect on Cd accumulation in vegetables remains inconclusive. Here, we investigated the impact of soil pH on Cd accumulation in dicotyledonous vegetables and elucidated the underlying molecular mechanisms. Soils collected from various locations were supplemented with varying quantities of lime to achieve soil pH values of around 5.0, 6.0, 7.0, and 8.0. Raising soil pH from around 5.0 to 8.0 markedly decreased extractable Cd. However, increasing soil pH tended to promote shoot Cd accumulation in dicotyledonous vegetable species including lettuce, pakchoi, and Chinese cabbage, and the model dicotyledonous plant Arabidopsis thaliana. Conversely, soil pH increase resulted in a monotonic decrease in rice Cd accumulation. In our hydroponic experiments, we discovered that iron (Fe) deficiency substantially increased Cd uptake and accumulation in dicotyledonous plants but not in rice. Increasing soil pH reduced soil Fe availability and induced the Fe transporter gene IRT1 expression in dicotyledonous vegetables roots, which led to an increase in IRT1-mediated Cd uptake and subsequently increased Cd accumulation as soil pH increases. A comprehensive model incorporating extractable Cd and root IRT1 expression better explained Cd accumulation in vegetable shoots. The application of 50 mg/kg of Fe fertilizer in neutral or alkaline soils resulted in a significant reduction in Cd accumulation by 34-58% in dicotyledonous vegetables. These findings reveal that increasing soil pH has two opposite effects, decreasing soil Cd availability while promoting Cd uptake through IRT1 upregulation, reconciling the inconsistency in its effect on Cd accumulation in dicotyledonous plants. Our findings provide important insights for understanding the factors affecting Cd uptake in plants and offer a practical solution to mitigate Cd contamination in vegetables., 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.)

Hepatocytes, the liver's predominant cells, perform numerous essential biological functions. However, crucial events and regulators during hepatocyte maturation require in-depth investigation. In this study, we performed single-cell RNA sequencing (scRNA-seq) and single-nucleus RNA sequencing (snRNA-seq) to explore the precise hepatocyte development process in mice. We defined three maturation stages of postnatal hepatocytes, each of which establishes specific metabolic functions and exhibits distinct proliferation rates. Hepatic zonation is gradually formed during hepatocyte maturation. Hepatocytes or their nuclei with distinct ploidies exhibit zonation preferences in distribution and asynchrony in maturation. Moreover, by combining gene regulatory network analysis with in vivo genetic manipulation, we identified critical maturation- and zonation-related transcription factors. This study not only delineates the comprehensive transcriptomic profiles of hepatocyte maturation but also presents a paradigm to identify genes that function in the development of hepatocyte maturation and zonation by combining genetic manipulation and measurement of coordinates in a single-cell developmental trajectory., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The Editors of Medical Science Monitor wish to inform you that the above manuscript has been retracted from publication due to concerns with the credibility and originality of the study, the manuscript content, and the Figure images. Reference: Qin Zhang, Xin-wei Dong, Jia-ying Xia, Ke-ying Xu, Zhe-rong Xu. Obestatin Plays Beneficial Role in Cardiomyocyte Injury Induced by Ischemia-Reperfusion In Vivo and In Vitro. Med Sci Monit, 2017; 23: 2127-2136. DOI: 10.12659/MSM.901361.

The International Working Group on the Diabetic Foot (IWGDF) has published evidence-based guidelines on the management and prevention of diabetes-related foot diseases since 1999. The present guideline is an update of the 2019 IWGDF guideline on the diagnosis and management of foot infections in persons with diabetes mellitus. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework was used for the development of this guideline. This was structured around identifying clinically relevant questions in the P(A)ICO format, determining patient-important outcomes, systematically reviewing the evidence, assessing the certainty of the evidence, and finally moving from evidence to the recommendation. This guideline was developed for healthcare professionals involved in diabetes-related foot care to inform clinical care around patient-important outcomes. Two systematic reviews from 2019 were updated to inform this guideline, and a total of 149 studies (62 new) meeting inclusion criteria were identified from the updated search and incorporated in this guideline. Updated recommendations are derived from these systematic reviews, and best practice statements made where evidence was not available. Evidence was weighed in light of benefits and harms to arrive at a recommendation. The certainty of the evidence for some recommendations was modified in this update with a more refined application of the GRADE framework centred around patient important outcomes. This is highlighted in the rationale section of this update. A note is also made where the newly identified evidence did not alter the strength or certainty of evidence for previous recommendations. The recommendations presented here continue to cover various aspects of diagnosing soft tissue and bone infections, including the classification scheme for diagnosing infection and its severity. Guidance on how to collect microbiological samples, and how to process them to identify causative pathogens, is also outlined. Finally, we present the approach to treating foot infections in persons with diabetes, including selecting appropriate empiric and definitive antimicrobial therapy for soft tissue and bone infections; when and how to approach surgical treatment; and which adjunctive treatments may or may not affect the infectious outcomes of diabetes-related foot problems. We believe that following these recommendations will help healthcare professionals provide better care for persons with diabetes and foot infections, prevent the number of foot and limb amputations, and reduce the patient and healthcare burden of diabetes-related foot disease., Competing Interests: Potential conflicts of interest. The authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

A 2D flow cytometry platform, known as CytoLM Plus, was developed for multi-parameter single-cell analysis. Single particles or cells after hydrodynamic alignment in a microfluidic unit undergo first-dimension fluorescence and side scattering dual-channel optical detection. They were thereafter immediately directed to ICP-MS by connecting the microfluidic unit with a high-efficiency nebulizer to facilitate the second-dimension ICP-MS detection. Flow cytometry measurements of fluorescent microspheres evaluated the performance of CytoLM Plus for optical detection. 6434 fluorescence bursts were observed with a valid signal proportion as high as 99.7%. After signal unification and gating analysis, 6067 sets of single-particle signals were obtained with 6.6 and 6.2% deviations for fluorescence burst area and height, respectively. This is fairly comparable with that achieved by a commercial flow cytometer. Afterward, CytoLM Plus was evaluated by 2D flow cytometry measurement of Ag + -incubated and AO-stained MCF-7 cells. A program for 2D single-cell signal unification was developed based on the algorithm of screening in lag time window. In the present case, a lag time window of -4.2 ± 0.09 s was determined by cross-correlation analysis and two-parameter optimization, which efficiently unified the concurrent single-cell signals from fluorescence, side scattering, and ICP-MS. A total of 495 sets of concurrent 2D signals were screened out, and the statistical analysis of these single-cell signals ensured 2D multi-parameter single-cell analysis and data elucidation.

Aristolochic acids are widely distributed in the plants of Aristolochiaceae family and Asarum species. Aristolochic acid I (AAI) is the most frequent compound of aristolochic acids, which can accumulate in the soil, and then contaminates crops and water and enters the human body. Research has shown that AAI affects the reproductive system. However, the mechanism of AAI's effects on the ovaries at the tissue level still needs to be clarified. In this research, we found AAI exposure reduced the body and ovarian growth in mice, decreased the ovarian coefficient, prevented follicular development, and increased atretic follicles. Further experiments showed that AAI upregulated nuclear factor-κB and tumor necrosis factor-α expression, activated the NOD-like receptor protein 3 inflammasome, and led to ovarian inflammation and fibrosis. AAI also affected mitochondrial complex function and the balance between mitochondrial fusion and division. Metabolomic results also showed ovarian inflammation and mitochondrial dysfunction due to AAI exposure. These disruptions reduced the oocyte developmental potential by forming abnormal microtubule organizing centers and expressing abnormal BubR1 to destroy spindle assembly. In summary, AAI exposure triggers ovarian inflammation and fibrosis, affecting the oocyte developmental potential., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Alkaline phosphatase (ALP), as a crucial enzyme involved in many physiological activities, is always used as one of the significant biomarkers in clinical diagnosis. Herein, a novel, simple, and effective photothermal quantitative method based on the etching of MnO 2 -coated gold nanoparticles (Au@MnO 2 NPs) was established for ALP activity assay with a household thermometer-based visual readout. The photothermal effect of Au@MnO 2 NPs is much higher than that of MnO 2 NPs or Au NPs. The MnO 2 shell of Au@MnO 2 NPs can be etched by ascorbic acid, a product of ALP-catalyzed hydrolysis of 2-phospho-l-ascorbic acid. With the etching of Au@MnO 2 NPs, the photothermal conversion efficiency decreased gradually, causing the decrease of the temperature increment of the solutions by degrees. A household thermometer, instead of large-scale and professional instruments, was used as a signal reader to realize the visual quantitative detection. The photothermal platform was used successfully for the determination of ALP with a wide linear range from 2.0 to 50 U/L and a detection limit as low as 0.75 U/L. Moreover, the inhibition efficiency of sodium vanadate for ALP activity was investigated, proving the photothermal quantitative method will be a potential platform for screening enzyme inhibitors. Such a sensitive, facile, and low-cost sensing assay provides a new prospect to develop platforms for point-of-care testing., 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 Inc. All rights reserved.)

Chloroacetonitrile (CAN) is a halogenated acetonitrile often produced while disinfecting drinking water. Previous studies have shown that maternal exposure to CAN interferes with fetal development; however, the adverse effects on maternal oocytes remain unknown. In this study, in vitro exposure of mouse oocytes to CAN reduced maturation significantly. Transcriptomics analysis showed that CAN altered the expression of multiple oocyte genes, especially those associated with the protein folding process. CAN exposure induced reactive oxygen species production, accompanied by endoplasmic reticulum (ER) stress and increased glucose regulated protein 78, C/EBP homologous protein and activating transcription factor 6 expression. Moreover, our results indicated that spindle morphology was impaired after CAN exposure. CAN disrupted polo-like kinase 1, pericentrin and p-Aurora A distribution, which may be an origin inducer that disrupts spindle assemble. Furthermore, exposure to CAN in vivo impaired follicular development. Taken together, our findings indicate that CAN exposure induces ER stress and affects spindle assembly in mouse oocytes., 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.)

Flow cytometry is among the most powerful tools for single-cell analysis, while the high cost and mechanical complexity of the commercial instrumentation limit the applications in personalized single-cell analysis. For this issue, we hereby construct an open and low-cost flow cytometer. It is highly compact to integrate the functions of (1) single cell aligning by a lab-made modularized 3D hydrodynamic focusing device, and (2) fluorescence detection of the single cells by a confocal laser-induced fluorescence (LIF) detector. The ceiling cost of the entire hardware for the LIF detection unit and 3D focusing device is $ 3200 and $ 400 respectively. A sheath flow velocity of 150 μL/min produces a focused sample stream of 17.6 μm × 14.6 μm at sample flow of 2 μL/min, based on the LIF response frequency and the laser beam spot diameter. The assay performance of the flow cytometer was evaluated by characterizing fluorescent microparticles and acridine orange (AO) stained HepG2 cells, producing throughputs of 40.5/s and 6.2/s respectively. Favorable assay precision and accuracy were demonstrated by the agreement of frequency histogram with imaging analysis, and good Gaussian-like distributions of fluorescent microparticles and AO-stained HepG2 cells. Practically, the flow cytometer was successfully applied for the evaluation of ROS generation in single HepG2 cells., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Excessive accumulation of cadmium (Cd) in rice grains threatens food safety and human health. Growing low Cd accumulating rice cultivars is an effective approach to produce low-Cd rice. However, field screening of low-Cd rice cultivars is laborious, time-consuming, and subjected to the influence of environment × genotype interactions. In the present study, we investigated whether machine learning-based methods incorporating genotype and soil Cd concentration can identify high and low-Cd accumulating rice cultivars. One hundred and sixty-seven locally adapted high-yielding rice cultivars were grown in three fields with different soil Cd levels and genotyped using four molecular markers related to grain Cd accumulation. We identified sixteen cultivars as stable low-Cd accumulators with grain Cd concentrations below the 0.2 mg kg -1 food safety limit in all three paddy fields. In addition, we developed eight machine learning-based models to predict low- and high-Cd accumulating rice cultivars with genotypes and soil Cd levels as input data. The optimized model classifies low- or high-Cd cultivars (i.e., the grain Cd concentration below or above 0.2 mg kg -1 ) with an overall accuracy of 76%. These results indicate that machine learning-based classification models constructed with molecular markers and soil Cd levels can quickly and accurately identify the high- and low-Cd accumulating rice cultivars., 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.)

The local analgesic efficacy and adverse effects of a new Long-acting Ropivacaine formulation were examined based on pharmacokinetic-pharmacodynamic (PK-PD) modelling in Bama minipigs. 24 Bama minipigs, 12 males and 12 females, were randomly and equally divided into the following treatment groups: normal saline injection, drug vehicle injection, Long-acting Ropivacaine Injection and Ropivacaine Hydrochloride Injection. After routine disinfection, a skin incision about 3 cm long and 3 cm deep was produced in the leg of each pig, and mechanical withdrawal threshold (MWT) measured at various times pre- and post-injection as an index of analgesia against incision pain. Plasma ropivacaine concentrations were also measured at the same times using a novel liquid chromatography-tandem mass spectroscopy (LC-MS/MS) method. Minipigs were sacrificed 24 h post-injection and hearts collected for drug concentration measurements by LC-MS/MS. The LC-MS/MS method demonstrated high sensitivity, linearity and precision. The Long-acting Ropivacaine formulation produced a longer analgesic effect (∼12 h) at a lower plasma concentration than Ropivacaine Hydrochloride (∼4h), suggesting a better side-effects profile. A PK-PD model revealed a direct relationship between plasma ropivacaine concentration and MWT, with peak analgesia at about 1000 ng/mL and behaved good prediction ability. Long-acting Ropivacaine Injection is a superior local anaesthetic-analgesic treatment due to longer-lasting efficacy at lower concentrations compared to Ropivacaine Hydrochloride, which will reduce the risk of side effects such as cardiotoxicity., 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 B.V.)

Open microfluidics has attracted increasing attention over the last decade because of its flexibility and simplicity with respect to cell culture and clinical diagnosis. However, traditional valves and pumps are difficult to integrate on open-channel microfluidic chips, in which a liquid is usually driven by capillary forces. Poor fluid control performance is a common drawback of open microfluidics. Herein, we proposed a method for controlling the liquid flow in open channels by controlling the continuous Laplace pressure induced by the deformation of the shape memory microstructures. The uniformly arranged cuboidal microcolumns in the open channels have magnetic/light dual responses, and the bending angle of the microcolumns can be controlled by adjusting Laplace pressure using near-infrared laser irradiation in a magnetic field. Laplace pressure and capillary force drove the liquid flow together, and the controllable fluid transport was realized by adjusting the hydrophilicity of the channel surface and the bending angle of the microcolumns. We demonstrated the controllability of the flow rate and the directional transport of water along a preset path. In addition, the start and stop of water transport were realized via local hydrophobic modification. The proposed strategy improves poor fluid control in traditional open systems and makes fluid flow highly controllable. We tried to extract and detect rhodamine B in tiny droplets on the open microfluidic chip, demonstrating the advantages of the proposed strategy in the separation and analysis of tiny samples.

Cobalt is a kind of heavy metal which is widely used in petrochemical and biomedical industries. Animal studies have reported that cobalt would exert systemic toxicity, but its effects on the ovarian function in mammals, especially for oocyte quality remains unknown. In the present study, we report that cobalt chloride treatment affects ovary coefficient and follicular growth. Oocytes in cobalt chloride exposed mice exhibited a decreased development potential, with the evidence of decreased occurrence rate of germ vesicle breakdown and polar body extrusion. Besides, cobalt chloride disorganized meiotic spindle formation and movement, mechanically associated with affecting TACC3 and Ac-a-tubulin levels, and disturbing actin reorganization. In addition, cobalt chloride exposure result in mitochondrial cristae structures disappear, cluster distribution and potential depolarization. Altogether, these findings suggest that cobalt chloride impairs the ovarian follicle growth and affects oocyte development by disrupted spindle assembly and mitochondrial function., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Research on ion channels and their monoclonal antibodies plays a critical role in drug development and disease diagnosis. The current ion channel researches are often not conducted in the microenvironment for cells survival, which restricts the mechanism study of the links between the cell structure and the ion channel function. In this work, we synthesized gold core-4-mercaptobenzonitrile-sliver shell-goat anti-rabbit immunoglobulin G (Au@4-MBN@Ag@IgG) nanoparticles as surface-enhanced Raman scattering (SERS) nanoprobes for investigating the human ether-a-go-go related gene (hERG) potassium ion channel in cell membranes. This is the first attempt to study ion channels using SERS. Due to the unique core-molecule-shell structure and the silver shell of nanoprobes, strong and stable SERS signal was obtained. With the help of antibodies, the Au@4-MBN@Ag@IgG nanoprobes were captured by hERG antibodies and then bonded with hERG ion channels based on the sandwich immune response. The reporter molecule, 4-MBN, displayed a strong and sharp characteristic peak at 2233 cm - 1 in the Raman silent region. The intensity of this peak denoted the concentration of antibodies and the expression of ion channel proteins. We successfully applied this amplification-free method for in-situ imaging the distribution of the hERG ion channel on the transfected HEK293 cell surface at the single-cell level. This hERG ion channel profiling strategy promises a maneuverable tool for ion channel research., 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 © 2022 Elsevier B.V. All rights reserved.)

Triptolide is a major active ingredient isolated from the traditional Chinese medicine Tripterygium wilfordii, which has anti-inflammatory, anti-cancer, and immunomodulatory effects. However, in clinical studies, triptolide has toxic side effects on the heart, kidney, liver and reproductive organs. With respect to female reproductive toxicity, damaging effects of triptolide on the ovary have been reported, but it has remained unknown whether oocytes are affected by triptolide. Therefore, this study established a concentration gradient of triptolide exposure in mice using 0 (control), 30, 60, and 90 μg triptolide/kg body weight/day administered by gavage. Triptolide administration for 28 d reduced body weight and ovarian weight and affected the developmental potential of oocytes. The triptolide-treated group exhibited meiotic failure of oocytes due to impaired spindle assembly, chromosome alignment, and tubulin stability. Triptolide was also found to induce mitochondrial dysfunction, autophagy and early apoptosis, iron homeostasis, and abnormal histone modifications. These adverse effects could be associated with oxidative stress induced by triptolide. In conclusion, our findings suggest detrimental effects of triptolide on mouse oocytes and, thus, on female reproduction., 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 © 2022 Elsevier Ltd. All rights reserved.)

3-monochloro-1,2-propanediol (3-MCPD) is a food contaminant believed to be harmful to human health. Previous studies showed that 3-MCPD exerts toxic effects in multiple tissues, but whether 3-MCPD affects female reproductive function remained unknown. Here, using mouse gastric lavage models, we report that 3-MCPD exposure for four weeks affected body growth, decreased the ovary/body weight ratio, and increased atretic follicle numbers. Expression levels of follicular development-related factors decreased. Further studies found that ovaries from 3-MCPD exposed mice had activated the Transforming Growth Factor-β (TGF-β) signaling pathway and promoted ovarian fibrosis. Increased TNF-α, IL-1 and NF-κB expression also indicated the occurrence of ovarian inflammation. Exposure to 3-MCPD stimulated the caspase pathway and enhanced granulosa cell apoptosis. Consistent with disrupted ovarian homeostasis, 3-MCPD exposure interfered with mitochondrial function, generated more reactive oxygen species, increased ferrous ion and lipid peroxidation levels, and resulted in decreased oocyte development potential. Collectively, these findings indicated that 3-MCPD exposure induced ovarian inflammation and fibrosis, and caused disorders of mitochondrial function and ferrous ion homeostasis in oocytes, which consequently disturbed follicle maturation and reduced oocyte quality., 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 © 2022 Elsevier Ltd. All rights reserved.)

Iron (Fe) deficiency is common in agricultural crops and affects millions of people worldwide. Translocation of Fe in the xylem is a key step for Fe distribution in plants. The mechanism controlling this process remains largely unknown. Here, we report that two Arabidopsis ferroxidases, LPR1 and LPR2, play a crucial and redundant role in controlling Fe translocation in the xylem. LPR1 and LPR2 are mainly localized in the cell walls of xylem vessels and the surrounding cells in roots, leaves, and stems. Knockout of both LPR1 and LPR2 increased the proportion of Fe(II) in the xylem sap, and caused Fe deposition along the vascular bundles especially in the petioles and main veins of leaves, which was alleviated by blocking blue light. The lpr1 lpr2 double mutant displayed constitutive expression of Fe deficiency response genes and overaccumulation of Fe in the roots and mature leaves under Fe-sufficient supply, but Fe deficiency chlorosis in the new leaves and inflorescences under low Fe supply. Moreover, the lpr1 lpr2 double mutant showed lower Fe concentrations in the xylem and phloem saps, and impaired 57 Fe translocation along the xylem. In vitro assays showed that Fe(III)-citrate, the main form of Fe in xylem sap, is easily photoreduced to Fe(II)-citrate, which is unstable and prone to adsorption by cell walls. Taken together, these results indicate that LPR1 and LPR2 are required to oxidize Fe(II) and maintain Fe(III)-citrate stability and mobility during xylem translocation against photoreduction. Our study not only uncovers an essential physiological role of LPR1 and LPR2 but also reveals a new mechanism by which plants maintain Fe mobility during long-distance translocation in the xylem., (Copyright © 2022 The Author. Published by Elsevier Inc. All rights reserved.)

Background: Glycyrrhiza is one of the most widely used traditional Chinese medicines in China. Its main bioactive ingredient glycyrrhizic acid (GA) has the potential to be used as a treatment for atopic dermatitis (AD) because it has similar actions to steroids, but with relatively few side effects., Aims: The objective of this study was to explore the potential mechanisms of GA on AD mice model., Methods: Calcipotriol, a vitamin D3 analogue (MC903) was applied topically to establish AD mouse model. Mice were intraperitoneally administrated with 2 mg/kg dexamethasone (DEX), 25 or 50 mg/kg GA for 15 days. After mice were executed, skin tissues were collected and detected the expression levels of IL-4, IFN-γ, TNF-α and thymic stromal lymphopoietin (TSLP). The percentages of Th1, Th2, Th17, langerhans cells (LCs) in draining lymph nodes (dLNs) were measured by flow cytometry., Results: Our data demonstrated that GA improved the symptoms of AD by exerting anti-inflammatory and anti-allergic functions in vivo. We found that GA treatment decreased the level of total IgE in serum, suppressed ear swelling, reduced the infiltration of mast cells in skin lesions and decreased expressions of IL-4, IFN-γ, TNF-α and TSLP in skin lesions. Furthermore, our experimental results demonstrated that GA suppressed the Th1/Th2/Th17-immune responses in the dLNs, inhibited the migration of LCs in dLNs., Conclusions: In conclusion, our findings suggested potential therapeutic effects of GA against MC903-induced AD-like skin lesions in mice., (© 2022 Wiley Periodicals LLC.)

Objective To predict the mechanism and potential therapeutic targets of asthma based on proteomic analysis and network pharmacology.Methods The mouse model of asthma was established via intraperitoneal injection of 200 μl suspension containing 100 μg ovalbumin(OVA)and 2 mg aluminum hydroxide and intranasal administration with 5% OVA.Maxquant system was used to retrieve the protein and gene data.The analysis of variance and t test were performed to obtain differential proteins,and then clustering map and target set of differential proteins were established.The protein-protein interaction network of differential proteins was constructed.The pathogenesis of asthma was investigated via gene ontology annotation and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis.Results A total of 5063 genes were identified,from which 904 differentially expressed genes were selected with the thresholds of fold change(model/control)≥2 and P ≤0.05 as well as thresholds of fold change(model/control)≤1/2 and P ≤0.05.The 904 genes were classified into 3 clusters.The 904 differentially expressed genes included 595 up-regulated genes and 309 down-regulated genes in the model group compared with the control group.The pathogenesis of asthma was associated with regulatory metabolism,Fc gamma-R mediated phagocytosis,leukocyte transendothelial migration,tumor necrosis factor signaling pathway,Toll-like receptor signaling pathway,B cell receptor signaling pathway,phosphoinositol 3-kinase/protein kinase B signaling pathway,vascular smooth muscle contraction and cell adhesion signaling pathway.ITGB3,CYBB,SYK,VWF,ITGB2,MYD88,COMP,VEGFA,and FCGR2B were identified as the therapeutic targets for asthma.Meanwhile,the biological processes such as signal transduction,redox process,immune response,inflammatory response,cell adhesion,positive regulation of GTPase activity,apoptosis,and extracellular matrix formation were the main participants in asthma.Conclusion This study systematically revealed the pathogenesis,biological processes,and 9 potential therapeutic targets of asthma.

Diabetic foot ulcers, with an annual incidence as high as 8.1% in China, impose enormous social and economic burdens on diabetic patients, families and society. Substantial progress has been made in China in the work concerning diabetic foot ulcers in the past two decades, and the major amputation rate in patients with diabetic foot ulcers in China has decreased significantly, even though it is still far higher than the level of developed countries in Europe and North America. Therefore, if we are to further improve the diagnosis and treatment of diabetic foot ulcers in China, the only solution lies in reinforced efforts in innovation, including innovations in concepts, models, and technology, and the training of national and provincial-level leading experts in diabetic foot ulcer care. Only in this way, can we further reduce the disability and mortality caused by diabetic foot ulcers in China. We, herein, discussed the importance and necessity of establishing a comprehensive diabetic foot prevention and control system suited to the actual circumstances of China through strengthening innovative research. On that basis, we also reported existing problems and prospects for future development., (Copyright© by Editorial Board of Journal of Sichuan University (Medical Sciences).)

Background: The real-world exposure levels of non-therapeutic antibiotics and neonicotinoids in type 1 diabetes (T1D) children and their associations as environmental triggers through gut microbiota shifts remained unknown. We thus investigated the antibiotics and neonicotinoids' exposure levels and their associations with gut microbiota in pediatric T1D., Methods: Fifty-one newly onset T1D children along with 67 age-matched healthy controls were recruited. Urine concentrations of 28 antibiotics and 12 neonicotinoids were measured by mass spectrometry. Children were grouped according to the kinds of antibiotics' and neonicotinoids' exposures, respectively. The 16S rRNA of fecal gut microbiota was sequenced, and the correlation with urine antibiotics and neonicotinoids' concentrations was analyzed., Results: The overall detection rates of antibiotics were 72.5% and 61.2% among T1D and healthy children, whereas the neonicotinoids detection rates were 70.6% and 52.2% (P = 0.044). Children exposed to one kind of antibiotic or two or more kinds of neonicotinoids had higher risk of T1D, with the odd ratios of 2.579 and 3.911. Furthermore, co-exposure to antibiotics and neonicotinoids was associated with T1D, with the odd ratio of 4.924. Antibiotics or neonicotinoids exposure did not affect overall richness and diversity of gut microbiota. However, children who were exposed to neither antibiotics nor neonicotinoids had higher abundance of Lachnospiraceae than children who were exposed to antibiotics and neonicotinoids alone or together., Conclusion: High antibiotics and neonicotinoids exposures were found in T1D children, and they were associated with changes in gut microbiota featured with lower abundance of butyrate-producing genera, which might increase the risk of T1D., (© 2022. The Author(s).)

The cellular metabolism of metals is highly critical to elucidate their potential cytotoxicity or cell protection mechanism. In this work, an asymmetric serpentine microfluidic device (ASMD) with high sampling efficiency and excellent focusing performance was developed for single-cell focusing. ASMD coupling with ICP-MS ensures single-cell assay to provide the information for trivalent arsenic (As(III)) uptake by HepG2 cells, which reveals the heterogeneity of cellular arsenic distribution, and elucidates the arsenic elimination behaviors in single HepG2 cells. Further, the metabolism and transformation of As(III) in HepG2 cells was tracked by hyphenating capillary electrophoresis (CE) separation with ICP-MS. The results for single-cell analysis and arsenic elimination kinetics illustrated that the half-life of arsenic elimination is 0.9 ± 0.04 h with the elimination constant of 0.77 ± 0.03, i.e., 77% of accumulated As in HepG2 cells may be eliminated per hour. Moreover, arsenobetaine (AsB) was identified to be the main metabolite and biotransformation species of As in HepG2 cells. ASMD-ICP-MS and CE-ICP-MS are powerful for tracking the fate of metals or metal drugs in single cells to comprehensively understand their metabolic pathway and transformation behaviors., 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 © 2022 Elsevier B.V. All rights reserved.)

Background: Myricetin (Myr) is a flavonoid compound that exist widely in many natural plants. Myr has been proven to have multiple biological functions, including immunomodulatory and anti-inflammatory effects., Purpose: In this study, we investigated the therapeutic effect of Myr on calcipotriol (MC903) induced atopic dermatitis (AD) mouse model and tumor necrosis factor (TNF)-α/interferon (IFN)-γ stimulated human immortal keratinocyte line (HaCaT) in vivo and in vitro., Methods: MC903 was applied topically to the left ears of mice to establish AD mouse model. After the AD model established successfully, the cream base, dexamethasone (DEX) cream or Myr cream were applied on the lesions of mice for 8 days. Through measuring ear thickness and scoring dermatitis severity, we evaluated the therapeutic effect of Myr, the draining lymph nodes (DLNs) and ears of the mice were collected for mechanistic study. In addition, TNF-α and IFN-γ-activated HaCaT cells were used to investigate the underlying mechanism., Results: Our data demonstrated that Myr alleviated the symptoms of AD by exerting anti-inflammatory and anti-allergic functions in vivo. We found that Myr treatment suppressed ear swelling and IgE level in the serum, reduced the infiltration of mast cells in skin lesions, decreased expressions of thymus and activation regulated chemokine (TARC), IL-4, IFN-γ and thymic stromal lymphopoietin (TSLP) in ear lesions, increased the expressions of filaggrin (FLG). Furthermore, our experimental results demonstrated that Myr down-regulated the mRNA expressions of T-bet and GATA-3 in DLNs. In vitro, Myr treatment decreased MDC and TARC expressions in IFN-γ and TNF-α-induced HaCaT cells by blocking the NF-κB and STAT1 signal pathway., Conclusion: The present study is the first to investigate the anti-atopic effects of Myr. Our findings suggested the therapeutic effects of Myr against MC903-induced AD-like skin lesions in mice. Therefore, Myr may be a potential therapeutic agent for AD., (Copyright © 2022 Elsevier GmbH. All rights reserved.)

Theranostic nanoplatforms with accurate diagnosis and effective therapy show a bright prospect for tumor treatments. Herein, a novel boracic acid-modified graphite carbon nitride and Prussian blue nanohybrid (PB@B-g-C 3 N 4 ) was developed, which provides sialic acid-targeted Raman recognition and synergistic photothermal/photodynamic therapy in the near-infrared region. Owing to the specific interaction between boracic acid and sialic acid and Raman response at 2157 cm -1 of PB, the nanohybrids exhibit high specificity and Raman sensitivity for detection of the overexpressed sialic acid on tumor cells. Moreover, the photothermal conversion efficiency of PB@B-g-C 3 N 4 is as high as 47.0% with 808 nm laser irradiation due to the enhanced absorbance of PB@B-g-C 3 N 4 . PB@B-g-C 3 N 4 also possesses excellent photodynamic activity, which is attributed to the energy transfer of PB (type I) and electron transfer between PB and B-g-C 3 N 4 (type II). This nanotheranostic agent for Raman recognition of cancer markers and synergistic photothermal/photodynamic therapy holds great potential for the development of efficient theranostic nanoplatforms., (Copyright © 2022 Elsevier B.V. All rights reserved.)

A green method for synthesizing Pd nanoparticles/graphene composites from a choline chloride-oxalic acid deep eutectic solvent (DES) without a reducing agent or a surfactant is reported. Deep eutectic solvents are usually composed of halide salts and hydrogen-bond donors, and many are biocompatible and biodegradable. The merits of deep eutectic solvents include that they serve as reducing agents and dispersants, and Pd nanoparticles are tightly anchored to graphene. The size and dispersion of Pd particles are improved when supercritical carbon dioxide (scCO 2 ) is used because it has gaslike diffusivity and near-zero surface tension, which results in excellent wettability between the scCO 2 and the carbon surface. The prepared sc-Pd NPs/GR/SPCE shows excellent activity toward glycerol oxidation compared to composites not fabricated by scCO 2 processes. This study demonstrates the potential of using this scCO 2 -assisted protocol combined with deep eutectic solvents to further construct nanoparticles/graphene composites., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)