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Background: The most widely used anti-malarial drug artemisinin (ART) is metabolized extensively, but the therapeutic capacity of its major metabolite remains unknown. Whether the major metabolite of ART (ART-M) contributes to its antiplasmodial potency was investigated in this study., Methods: The metabolite identification and enzyme phenotyping of ART were performed using human liver microsomes (HLMs). The stereostructure of the major metabolite ART-M was elucidated by spectroscopic and X-ray crystallographic analysis. The anti-malarial activity of ART-M against two reference Plasmodium strains (Pf3D7 and PfDd2) was evaluated. The pharmacokinetic profiles of ART and its metabolite ART-M were investigated in healthy Chinese subjects after a recommended two-day oral dose of ART plus piperaquine. Pharmacodynamic parameters based on minimum inhibitory concentration (MIC 50 ) and free plasma concentration were employed to evaluate the therapeutic potency of ART-M, including fAUC 0-t /MIC 50 , fC max /MIC 50 and T > MIC 50 ., Results: A major metabolite 10β-hydroxyartemisinin (ART-M) was found for ART in human, and CYP3A4/3A5 was the major enzymes responsible for ART 10β-hydroxylation. Compared with ART (MIC 50 , 10.1 nM against Pf3D7), weaker antiplasmodial activity was found for ART-M (MIC 50 , 61.4 nM against Pf3D7). However, a 3.5-fold higher maximal free plasma concentration was achieved for ART-M (fC max , 180.0 nM vs. 51.8 nM for ART). ART-M displayed comparable antiplasmodial potency to ART, in terms of fAUC 0-t /MIC 50 (12.5 h), fC max /MIC 50 (2.8) and T > MIC 50 (5 h)., Conclusions: The major metabolite 10β-hydroxyartemisinin contributes to the antiplasmodial efficacy of ART, which should be considered when evaluation of ART dosing regimens and/or clinical outcomes., (© 2024. The Author(s).)

Satellite remote sensing is a promising approach for monitoring global CO 2 emissions. However, existing satellite-based CO 2 observations are too coarse to meet the requirements of fine-scale global mapping. We propose a novel data-driven method to estimate global anthropogenic CO 2 emissions at a 0.1° scale, which integrates emissions inventories and satellite data while bypassing the inadequate accuracy of CO 2 observations. Due to the co-emitted anthropogenic emissions of nitrogen oxides (NO x  = NO + NO 2 ) and CO 2 , high-resolution NO 2 measurements from the TROPOspheric Monitoring Instrument (TROPOMI) are employed to map the global anthropogenic emissions at a global 0.1° scale. We construct the driving features from NO 2 data and also incorporate gridded CO 2 /NO x emission ratios and NO x /NO 2 conversion ratios as driving data to describe co-emissions. Both ratios are predicted using a long short-term memory (LSTM) neural network (with an R 2 of 0.984 for the CO 2 /NO x emission ratio and an R 2 of 0.980 for the NO x /NO 2 conversion ratio). The data-driven model for estimating anthropogenic CO 2 emissions is implemented by random forest regression (RFR) and trained using the Emissions Database for Global Atmospheric Research (EDGAR). The satellite-based anthropogenic CO 2 emission dataset at a global 0.1° scale agrees well with the national CO 2 emission inventories (an R 2 of 0.998 with Global Carbon Budget (GCB) and an R 2 of 0.996 with EDGAR) and consistent with city-level emission estimates from Carbon Monitor Cities (CMC) with the R 2 of 0.824. This data-driven method based on satellite-observed NO 2 provides a new perspective for fine-resolution anthropogenic CO 2 emissions estimation., 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.)

Radiative cooling is achieved by controlling surface optical behavior toward solar and thermal radiation, offering promising solutions for mitigating global warming, promoting energy saving, and enhancing environmental protection. Despite significant efforts to develop optical surfaces in various forms, five primary challenges remain for practical applications: enhancing optical efficiency, maintaining appearance, managing overcooling, improving durability, and enabling scalable manufacturing. However, a comprehensive review bridging these gaps is currently lacking. This work begins by introducing the optical fundamentals of radiative cooling and its potential applications. It then explores the challenges and discusses advanced solutions through structural design, material selection, and fabrication processes. It aims to provide guidance for future research and industrial development of radiative cooling technology., (© 2024 The Author(s). Advanced Materials published by Wiley‐VCH GmbH.)

Introduction: The global incidence of dengue fever has increased significantly over the past two decades, and China faces a significant upward trend in dengue control challenges., Methods: Data were obtained from China's NNDRS from 2005 to 2023. Joinpoint regression software was used to analyze temporal trends, while SaTScan software was used to analyze spatial, seasonal, and spatiotemporal distributions. ArcGIS software was used to visualize clusters., Results: A total of 117,892 dengue cases were reported from 2005 to 2023, with significant fluctuation in annual reported cases. Dengue was not endemic in China. Autochthonous outbreaks most likely occurred in the southwestern, southeastern coastal, and inland areas of China. These outbreaks have occurred between June and November, generally peaking in September or October, around epidemiological week (EW) 40., Conclusions: Dengue challenges in China are increasing. Timely case monitoring, proactive control interventions, and staff mobilization should be implemented before June to ensure a timely response to autochthonous outbreaks., Competing Interests: No conflicts of interest., (Copyright and License information: Editorial Office of CCDCW, Chinese Center for Disease Control and Prevention 2024.)

Background: Despite promise in preclinical models of acute respiratory distress syndrome (ARDS), mesenchymal stem cells (MSC) have failed to translate to therapeutic benefit in clinical trials. The MSC is a live cell medicine and interacts with the patient's disease state. Here, we explored this interaction, seeking to devise strategies to enhance MSC therapeutic function., Methods: Human bone-marrow-derived MSCs were exposed to lung homogenate from healthy and E. coli -induced ARDS rat models. Apoptosis and functional assays of the MSCs were performed., Results: The ARDS model showed reduced arterial oxygenation, decreased lung compliance and an inflammatory microenvironment compared to controls. MSCs underwent more apoptosis after stimulation by lung homogenate from controls compared to E. coli , which may explain why MSCs persist longer in ARDS subjects after administration. Changes in expression of cell surface markers and cytokines were associated with lung homogenate from different groups. The anti-microbial effects of MSCs did not change with the stimulation. Moreover, the conditioned media from lung-homogenate-stimulated MSCs inhibited T-cell proliferation., Conclusions: These findings suggest that the ARDS microenvironment plays an important role in the MSC's therapeutic mechanism of action, and changes can inform strategies to modulate MSC-based cell therapy for ARDS.

Objective: To explore the assisted reproductive outcomes of patients with atypical endometrial hyperplasia (AEH) and early-stage endometrial cancer (EEC) who achieved complete remission after conservative treatment and to provide reference for clinical selection of appropriate conservative treatment., Method: This retrospective cohort study included seven patients with EEC and 62 patients with AEH who underwent in vitro fertilization or intracytoplasmic sperm injection at the Reproductive Center of the Third Affiliated Hospital of Zhengzhou University between August 2015 and October 2023. The authors divided the participants into two groups based on the type of fertility-sparing treatment received: the oral medication group and the levonorgestrel-releasing intrauterine system (LNG-IUS) group. The primary outcome was the cumulative clinical pregnancy rate. Secondary outcomes included clinical pregnancy rate per transfer cycle, embryo utilization rate, and high-quality embryo rate., Results: The LNG-IUS group had a significantly higher rate of usable embryos compared with the oral medication group (80.8% vs 91.1%, P = 0.005) and also had a thinner endometrial thickness on the day of embryo transfer. The cumulative clinical pregnancy rate was higher in the LNG-IUS group compared with the medication group (46.7% vs 78.9%, P = 0.037), and the difference was statistically significant., Conclusion: For patients with AEH and EEC with fertility needs, the conservative treatment method of LNG-IUS can achieve better assisted reproductive outcomes., (© 2024 International Federation of Gynecology and Obstetrics.)

While Mammarenavirus Wenzhouense (WENV) is broadly distributed across Asia, the dynamics of WENV infection remain unclear. In this study, a field-derived strain of WENV was used to inoculate Sprague Dawley (SD) rats by intramuscular injection, and the process of viral infection was observed over the course of 28 d. Viral RNA became detectable in the blood at 3 dpi and remained detectable for about 12 d. In most organ tissues, viral RNA peaked at 7 dpi, and then began to decline by 14 d, but remained detectable in intestine and brain tissues at 21 and 28 dpi. Viral shedding was detected from fecal samples for 5 d, from 6 to 11 dpi using qRT-PCR, and was recovered from feces collected at 8 dpi. Horizontal contact infection occurred among cage-mates at 14 and 21 dpi. Antibodies against the nucleocapsid were detected at 5 dpi, and then increased and persisted until the end of the experiment. These results enabled us to determine the kinetics of viremic response, viral shedding in feces, and horizontal transmission dynamics, as well as the potential sites for WENV replication and viral maintenance in nature.

Background: Obesity has been linked to arterial stiffness, while no consensus was reached on the association. We aimed to clarify the association of general and central obesity with arterial stiffness by combining observational studies and Mendelian randomization (MR) study., Methods: Two cross-sectional studies were performed in UK Biobank and Fuqing Cohort, respectively. Two-sample MR study was conducted using summary data of GWASs from GIANT consortium and UK Biobank. General obesity and central obesity were measured using body mass index (BMI) and waist circumference (WC), respectively. Arterial stiffness was measured by arterial stiffness index (ASI) in UK Biobank or branchial-ankle pulse wave velocity (baPWV) in Fuqing Cohort., Results: Two observational studies found a consistent positive association of BMI and WC with arterial stiffness when adjusting for age, sex, education, smoking, alcohol drinking, physical activity, and LDL cholesterol. However, when additionally adjusting for metabolic traits (i.e., systolic blood pressure, diastolic blood pressure, blood glucose, triglycerides, high-density lipoprotein cholesterol, and WC or BMI), the association with BMI changed to be inverse. As compared to the lowest quintile group, the adjusted ORs across groups of second to fifth quintile were 0.93, 0.90, 0.83, and 0.72 in UK Biobank and 0.88, 0.65, 0.63, and 0.50 in Fuqing Cohort. In contrast, the positive relationship with WC remained stable with the adjusted ORs of 1.23, 1.46, 1.60, and 1.56 in UK Biobank and 1.35, 1.44, 1.77, and 1.64 in Fuqing Cohort. MR analyses provided supportive evidence of the negative association with BMI (OR = 0.97, 95%CI = 0.94-1.00) and the positive association with WC (OR = 1.14, 95%CI = 1.08-1.20)., Conclusions: Observational and genetic analyses provide concordant results that central obesity is independently related to arterial stiffness, while the role of general obesity depends on metabolic status., (© 2024. The Author(s).)

Background and Purpose: To assess the variation of large-volume brain metastases (BMs) boundaries and shapes using enhanced magnetic resonance (MR) scanning with different delay times and to provide a basis for determining the gross tumor target volume (GTV) for radiotherapy of BMs., Materials and Methods: We prospectively enrolled 155 patients initially diagnosed with BMs (561 lesions > 1 cm). Contrast-enhanced (CE) T1-weighted imaging scans were performed 1, 3, 5, 10, 18, and 20 min after gadolinium-based contrast agent injection and GTVs were determined as GTV -1min , GTV -3min , GTV -5min , GTV -10min , GTV -18min , and GTV -20min, respectively, which were subsequently fused in different phases. Fusion of the six GTVs was defined as GTV -total , which was set as the reference GTV. The volume, shape, and signal intensity of the GTVs and brain white matter (BWM) were compared at different delay times., Results: GTV -3min , GTV -5min , GTV -10min , GTV -18min , and GTV -20min volumes increased by 2.2 %, 3.8 %, 6.5 %, 9.5 %, and 10.6 %, respectively (P < 0.05) compared with GTV -1min . Compared with GTV -total , GTV -1min , GTV -3min , GTV -5min , GTV -10min , GTV -18min , and GTV -20min volumes reduced by 25.4 %, 22.1 %, 18.7 %, 15.0 %, 11.2 %, and 10.3 %, respectively (P < 0.05). Compared with GTV -total , 29 (51.8 %) fused GTVs had a volume reduction rate < 5 %, 45 (80.4 %) had a Dice similarity coefficient > 0.95, and all contained GTV -10min , GTV -18min or GTV -20min . The signal intensity ratio between the GTV and BWM peaked at 5 min (0.351 ± 0.24)., Conclusion: Enhanced MR scans with different delay times show significant differences in the boundaries and shapes of large-volume BMs, and time-delayed multi-phase CE scanning should be used in GTV determination, with time phases ≥ 10 min being mandatory., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

In this Letter, we demonstrate a high-power ytterbium-doped fiber laser (YDFL) based on a directly in-band pumping scheme (DIPS) which employs 1018 nm laser diodes (LDs) as pump sources. The wavelength of the LDs is designed theoretically, considering the distribution of Yb 3+ absorption cross section (σ a ) as well as quantum defect (QD). The flat distribution of σ a around 1018 nm ensures excellent temperature insensitivity and flexibility for the YDFL. Besides, lower QD and more compact structure promise higher optical-to-optical (O-O) and electrical-to-optical (E-O) efficiencies. Based on the experimental setup, as the cooling temperature of the 1018 nm LDs ranges from 6 to 23°C, an output power of 2 kW level is achieved that varies by only 2.01% without adjusting the operating current of the LDs subjectively. The output power is then scaled up to 5 kW level. Furthermore, there is a great potential to achieve higher output power and E-O efficiency in YDFLs based on the DIPS.

Fibroblast growth factor 10 (FGF10) plays critical roles in oocyte maturation and embryonic development; however, the specific pathway by which FGF10 promotes in vitro maturation of buffalo oocytes remains elusive. The present study was aimed at investigating the mechanism underlying effects of the FGF10-mediated extracellular regulated protein kinases (ERK) pathway on oocyte maturation and embryonic development in vitro. MEK1/2 (mitogen-activated protein kinase kinase) inhibitor U0126, alone or in combination with FGF10, was added to the maturation culture medium during maturation of the cumulus oocyte complex. Morphological observations, orcein staining, apoptosis detection, and quantitative real-time PCR were performed to evaluate oocyte maturation, embryonic development, and gene expression. U0126 affected oocyte maturation and embryonic development in vitro by substantially reducing the nuclear maturation of oocytes and expansion of the cumulus while increasing the apoptosis of cumulus cells. However, it did not have a considerable effect on glucose metabolism. These findings suggest that blocking the MEK/ERK pathway is detrimental to the maturation and embryonic development potential of buffalo oocytes. Overall, FGF10 may regulate the nuclear maturation of oocytes and cumulus cell expansion and apoptosis but not glucose metabolism through the MEK/ERK pathway. Our findings indicate that FGF10 regulates resumption of meiosis and expansion and survival of cumulus cells via MEK/ERK signaling during in vitro maturation of buffalo cumulus oocyte complexes. Elucidation of the mechanism of action of FGF10 and insights into oocyte maturation should advance buffalo breeding. Further studies should examine whether enhancement of MEK/ERK signaling improves embryonic development in buffalo., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2024 Society for Biology of Reproduction & the Institute of Animal Reproduction and Food Research of Polish Academy of Sciences in Olsztyn. Published by Elsevier B.V. All rights reserved.)

Hepatocellular Carcinoma (HCC) is one of the most common malignant neoplasms. With the advancement of technology, the precision of radiotherapy (RT) for HCC has considerably increased, and it is an indispensable modality in the comprehensive management of HCC. Some RT techniques increase the radiation dose to HCC, which decreases the radiation dose delivered to the surrounding normal liver tissue. This approach significantly improves the efficacy of HCC treatment and reduces the incidence of Radiation-induced Liver Disease (RILD). Clear imaging and precise determination of the Gross Target Volume (GTV) are prerequisites of precise RT of HCC. The main hindrances in determining the HCC GTV include indistinct tumor boundaries on imaging and the impact on respiratory motion. The integration of multimodal imaging, four-dimensional imaging, and artificial intelligence (AI) techniques can help overcome challenges for HCC GTV. In this article, the advancements in medical imaging and precise determination for HCC GTV have been reviewed, providing a framework for the precise RT of HCC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Meng, Gong, Liu, Du and Yin.)

Aims: Although central adiposity is a well-known risk factor for diabetes, the underlying mechanism remains unclear. The aim of this study was to explore the potential mediation role of circulating WBC counts in the association between central adiposity and the risk of diabetes., Materials and Methods: A cross-sectional study was conducted using data from the Fuqing cohort study, which included 6,613 participants aged 35-75 years. Logistic regression analysis and Spearman's rank correlation analysis were used to examine the relationships between waist-to-hip ratio, WBC counts and glycemic status. Both simple and parallel multiple mediation models were used to explore the potential mediation effects of WBCs on the association of waist-to-hip ratio with diabetes., Results: The study revealed a positive relationship between waist-to-hip ratio and risk of prediabetes (OR = 1.53; 95% CI, 1.35 to 1.74) and diabetes (OR = 2.89; 95% CI, 2.45 to 3.40). Moreover, elevated peripheral WBC counts were associated with both central adiposity and worsening glycemic status (P < 0.05). The mediation analysis with single mediators demonstrated that there is a significant indirect effect of central adiposity on prediabetes risk through total WBC count, neutrophil count, lymphocyte count, and monocyte count; the proportions mediated were 9.92%, 6.98%, 6.07%, and 3.84%, respectively. Additionally, total WBC count, neutrophil count, lymphocyte count, monocyte count and basophil count mediated 11.79%, 11.51%, 6.29%, 4.78%, and 1.76%, respectively, of the association between central adiposity and diabetes. In the parallel multiple mediation model using all five types of WBC as mediators simultaneously, a significant indirect effect (OR = 1.09; 95% CI, 1.06 to 1.14) were observed, with a mediated proportion of 12.77%., Conclusions: Central adiposity was independently associated with an elevated risk of diabetes in a Chinese adult population; levels of circulating WBC may contribute to its underlying mechanisms., (© 2024. The Author(s).)

Brain metastases (BMs) are the most prevalent intracranial malignant tumors in adults and are the leading cause of mortality attributed to malignant brain diseases. Radiotherapy (RT) plays a critical role in the treatment of BMs, with local RT techniques such as stereotactic radiosurgery (SRS)/stereotactic body radiotherapy (SBRT) showing remarkable therapeutic effectiveness. The precise determination of gross tumor target volume (GTV) is crucial for ensuring the effectiveness of SRS/SBRT. Multimodal imaging techniques such as CT, MRI, and PET are extensively used for the diagnosis of BMs and GTV determination. With the development of functional imaging and artificial intelligence (AI) technology, there are more innovative ways to determine GTV for BMs, which significantly improve the accuracy and efficiency of the determination. This article provides an overview of the progress in GTV determination for RT in BMs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Du, Gong, Liu, Meng and Yin.)

Background: Angioimmunoblastic T-cell lymphoma (AITL) is characterized by high recurrence rates and poor prognosis, and effective first-line treatment is lacking. Recently, histone deacetylase inhibitors (HDACi), such as chidamide, have been found to induce durable remissions in AITL patients., Methods: Patients with untreated AITL from March 2015 to March 2023 were retrospectively collected and divided into chemotherapy (ChT) group and chidamide combined with chemotherapy (C-ChT) group based on the first-line treatment received. The comparison of efficacy and safety between the two groups was conducted., Results: 86 patients with newly diagnosed AITL were enrolled, in which 35 patients were in the ChT group and 51 in the C-ChT group. The objective response rate (ORR) of C-ChT group was significantly higher than that of ChT group (84.3% vs. 60%, P = 0.011), and had superior progression-free survival (PFS) (27 months vs. 12 months, P = 0.025). However, no significant difference in overall survival (OS) was observed between the two groups ( P = 0.225). In addition, the responding patients who received autologous stem cell transplantation (ASCT) had superior PFS compared to those who did not ( P = 0.015)., Conclusions: Compared with ChT regimen, C-ChT regimen was well tolerated and had superior ORR and PFS in patients with untreated AITL. ASCT may contribute to longer PFS in remission patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Gu, Wang, Zhou, Du and Niu.)

Purpose: This study investigated the safety and effectiveness of oocyte vitrification by comparing the clinical pregnancy and perinatal outcomes between transfer cycles of vitrified oocytes and those of vitrified embryos., Methods: A retrospective cohort study was conducted to analyze the clinical data of patients who underwent cleavage-stage embryo transfer at the Department of Reproductive Medicine between January 2011 and June 2021. Seventy-seven transfer cycles of fresh cleavage-stage embryos developed from vitrified-thawed oocytes (oocyte vitrification group) and 2170 transfer cycles of vitrified-thawed cleavage-stage embryos developed from fresh oocytes (embryo vitrification group) were included. Further, 293 cases were selected from the embryo vitrification group after applying propensity score matching at 1:4. The primary outcomes were miscarriage rate, live birth rate, and neonatal birth weight., Results: No statistically significant differences were observed in the baseline data, pregnancy, perinatal outcomes, or neonatal outcomes for either singleton or twin births between the two groups after matching. Backwards stepwise regression was used to analyze the length of gestation. The age of female participants (β =  - 0.410, 95% CI =  - 1.339 ~  - 0.620, P < 0.001) had a statistically significant effect., Conclusion: Oocyte vitrification results in similar clinical pregnancy and perinatal outcomes as does embryo vitrification; hence, it is a relatively safe assisted reproductive technique., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Although the impact of hypertension on carotid intima-media thickness (IMT) and plaques has been well established, its association with femoral IMT and plaques has not been extensively examined. In addition, the role of the ratio of systolic and diastolic pressure (SDR) in the subclinical atherosclerosis (AS) risk remains unknown. We assessed the relationship between SDR and carotid and femoral AS in a general population., Methods: A total of 7,263 participants aged 35-74 years enrolled from January 2019 to June 2021 in a southeast region of China were included in a cross-sectional study. Systolic and diastolic blood pressure (SBP and DBP) were used to define SDR. Ultrasonography was applied to assess the AS, including thickened IMT (TIMT) and plaque in the carotid and femoral arteries. Logistic regression and restricted cubic spline (RCS) models were the main approaches., Results: The prevalence of TIMT, plaque, and AS were 17.3%, 12.4%, and 22.7% in the carotid artery; 15.2%, 10.7%, and 19.5% in the femoral artery; and 23.8%, 17.9% and 30.0% in either the carotid or femoral artery, respectively. Multivariable logistic regression analysis found a significant positive association between high-tertile SDR and the higher risk of overall TIMT (OR = 1.28, 95% CI = 1.10-1.49), plaques (OR = 1.36, 95%CI = 1.16-1.61), or AS (OR = 1.36, 95% CI = 1.17-1.57), especially in the carotid artery. RCS analysis further revealed the observed positive associations were linear. Further analyses showed that as compared to the low-tertile SDR and non-hypertension group, high-tertile SDR was associated with increased risks of overall and carotid TIMT, plaques, or AS in both groups with or without hypertension., Conclusions: SDR is related to a higher risk of subclinical AS, regardless of hypertension or not, suggesting that as a readily obtainable index, SDR can contribute to providing additional predictive value for AS., 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. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (© 2024 Wang, Chen, Lin, Su, Dai, Chen, He, Li, Feng, Huang, Hu, Chen, Du, Guo and Ye.)

Whole-brain radiotherapy (WBRT) plays an irreplaceable role in the treatment of brain metastases (BMs), but cognitive decline after WBRT seriously affects patients' quality of life. The development of cognitive dysfunction is closely related to hippocampal injury, but standardized criteria for predicting hippocampal injury and dose limits for hippocampal protection have not yet been developed. This review systematically reviews the clinical efficacy of hippocampal avoidance - WBRT (HA-WBRT), the controversy over dose limits, common methods and characteristics of hippocampal imaging and segmentation, differences in hippocampal protection by common radiotherapy (RT) techniques, and the application of artificial intelligence (AI) and radiomic techniques for hippocampal protection. In the future, the application of new techniques and methods can improve the consistency of hippocampal dose limit determination and the prediction of the occurrence of cognitive dysfunction in WBRT patients, avoiding the occurrence of cognitive dysfunction in patients and thus benefiting more patients with BMs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Liu, Gong, Meng, Du and Yin.)

Background: Magnesium (Mg) is both an essential macro-element and a known catalyst, and it plays a vital role in various physiological activities and mechanisms in relation to chronic kidney disease (CKD). However, epidemiological evidence involving this is limited and not entirely consistent. This study aims to explore the association of serum Mg concentrations with the risk of CKD among general Chinese adults., Methods: A total of 8,277 Chinese adults were included in the wave of 2009 from the China Health and Nutrition Survey (CHNS). The primary outcome was the risk of CKD, which was defined as the estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m 2 . Multivariable logistic regression model was used to examine the relationship of serum Mg concentrations with the risk of CKD., Results: Included were 8,277 individuals, with an overall CKD prevalence of 11.8% (n = 977). Compared with the first quartile of serum Mg, the multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for participants in the second, third, and fourth quartiles of serum Mg were 0.74 (0.58, 0.93), 0.87 (0.69, 1.11) and 1.29 (1.03, 1.61), respectively. Similar results were observed in our several sensitivity analyses. Restricted cubic spline analysis demonstrated a nonlinear (similar "J"-shaped) association between serum Mg concentrations and the risk of CKD (P nonlinearity <0.001), with a threshold at around a serum Mg value of 2.2 mg/dL., Conclusions: Our results suggested a similar "J"-shaped association between serum Mg concentration and the risk of CKD among Chinese adults. Further large prospective studies are needed to verify these findings., (© 2024. The Author(s).)

The associations between several blood inflammatory indicators and risk of vascular plaques remain inconclusive. A total of 4596 native rural residents in Southeast China were enrolled from the Fuqing cohort study. Blood cell counts and their composite indexes including the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and 2 novel indicators (systemic immune inflammation index (SII) and systemic immune inflammation response index (SIRI)) were considered as inflammatory indicators. Common carotid and femoral intima-media thickness (IMT) and plaques were assessed using B-mode ultrasound. Unconditional or multinomial logistic regression was used to evaluate potential associations. The prevalence of multiple femoral plaques (defined as IMT ≥1.5 mm) was significantly higher among participants with the highest tertile of total leukocyte count (odds ratio, 1.78), neutrophil count (1.88), monocyte count (2.51), platelet count (1.68), NLR (1.93), PLR (1.57) , SII (2.10), and SIRI (2.94). Higher levels of neutrophil count, platelet count, NLR, and SII were also found to have significant linear dose-response relationships with the prevalence of stenosis, especially in femoral arteries. In conclusion, several blood inflammatory biomarkers may contribute to, or are associated with, the presence of IMT ≥1.5 mm or stenosis especially in femoral arteries., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: The current absence of a standardized mandibular body osteotomy design poses challenges in surgical planning. Traditional approaches may not suit patients with wider anterior mandibles, potentially resulting in unsatisfactory outcomes. Addressing this issue requires a rational design that combines mandibular angle and body osteotomies for improved clinical practice., Objectives: In this retrospective cohort study we aimed to analyze mandibular computed tomography (CT) data with digital methods. The goal was to establish an integrated osteotomy design for both mandibular angle and body procedures and classify prevalent mandibular types in the Chinese Han population for surgical guidance., Methods: Included were 89 patients who underwent mandibular angle osteotomy without genioplasty between 2016 and 2022 at Peking University Third Hospital. Mimics 21.0 software facilitated CT data reconstruction and osteotomy planning. Postoperative effects were assessed through imaging, complications, and surveys, leading to mandibular type classification., Results: Mandibular angles were categorized by 3 types, based on osteotomy range. Type I involved mandibular body osteotomy only, type II mandibular angle osteotomy only, and type III both mandibular angle and body osteotomies. Distribution within the cohort was 2.25%, 8.99%, and 88.76% for types I, II, and III respectively. Patient satisfaction was high, with minor and major complications at 47.19% and 1.12% by Clavien-Dindo classification., Conclusions: Utilizing Mimics software, we established an integrated osteotomy design and categorized mandibular types. Findings offer valuable guidance for mandibular angle surgery and contribute to understanding of Asian mandibular morphology., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Aesthetic Society.)

Bacillus amyloliquefaciens is one of the most characterized Gram-positive bacteria. This species has unique characteristics that are beneficial for industrial applications, including its utilization of: cheap carbon as a substrate, a transparent genetic background, and large-scale robustness in fermentation. Indeed, the productivity characteristics of B. amyloliquefaciens have been thoroughly analyzed and further optimized through systems biology and synthetic biology techniques. Following the analysis of multiple engineering design strategies, B. amyloliquefaciens is now considered an efficient cell factory capable of producing large quantities of multiple products from various raw materials. In this review, we discuss the significant potential advantages offered by B. amyloliquefaciens as a platform for metabolic engineering and industrial applications. In addition, we systematically summarize the recent laboratory research and industrial application of B. amyloliquefaciens , including: relevant advances in systems and synthetic biology, various strategies adopted to improve the cellular performances of synthetic chemicals, as well as the latest progress in the synthesis of certain important products by B. amyloliquefaciens . Finally, we propose the current challenges and essential strategies to usher in an era of broader B. amyloliquefaciens use as microbial cell factories.

Background: It is currently unclear whether and how the association between body composition and hypertension varies based on the presence and severity of fatty liver disease (FLD)., Methods: FLD was diagnosed using ultrasonography among 6,358 participants. The association between body composition and hypertension was analyzed separately in the whole population, as well as in subgroups of non-FLD, mild FLD, and moderate/severe FLD populations, respectively. The mediation effect of FLD in their association was explored., Results: Fat-related anthropometric measurements and lipid metabolism indicators were positively associated with hypertension in both the whole population and the non-FLD subgroup. The strength of this association was slightly reduced in the mild FLD subgroup. Notably, only waist-to-hip ratio and waist-to-height ratio showed significant associations with hypertension in the moderate/severe FLD subgroup. Furthermore, FLD accounted for 17.26% to 38.90% of the association between multiple body composition indicators and the risk of hypertension., Conclusions: The association between body composition and hypertension becomes gradually weaker as FLD becomes more severe. FLD plays a significant mediating role in their association., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Huang, Zeng, Ma, Xiang, Liu, Xiao, Feng, Li, Zhang, Lin, Hu, Zhao, Du and Ye.)

Cell sheet tissue engineering requires prolonged in vitro culture for the development of implantable devices. Unfortunately, lengthy in vitro culture is associated with cell phenotype loss and substantially higher cost of goods, which collectively hinder clinical translation and commercialisation of tissue engineered medicines. Although macromolecular crowding has been shown to enhance and accelerate extracellular matrix deposition, whilst maintaining cellular phenotype, the optimal macromolecular crowding agent still remains elusive. Herein, we evaluated the biophysical properties of seven different carrageenan molecules at five different concentrations and their effect on human umbilical cord-derived mesenchymal stromal cell morphology, viability, metabolic activity, proliferation, extracellular matrix deposition and surface marker expression. All types of carrageenan (CR) assessed demonstrated a hydrodynamic radius increase as a function of increasing concentration; high polydispersity; and negative charge. Two iota CRs were excluded from further analysis due to poor solubility in cell culture. Among the remaining five carrageenans, the lambda medium viscosity type at concentrations of 10 and 50 μg/ml did not affect cell morphology, viability, metabolic activity, proliferation and expression of surface markers and significantly increased the deposition of collagen types I, III and IV, fibronectin and laminin. Our data highlight the potential of lambda medium viscosity carrageenan as a macromolecular crowding agent for the accelerated development of functional tissue engineered medicines., Competing Interests: Declaration of competing interest SJE is the Chief Scientific Officer in Orbsen Therapeutics. TOB is a Director and equity holder in Orbsen Therapeutics., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Variations in the prevalence and systemic inflammatory (SI) status between non-alcoholic fatty liver disease (NAFLD) and newly defined metabolic dysfunction-associated fatty liver disease (MAFLD) have only been reported by few studies. Hence, this study aimed to compile data on the prevalence and the systemic inflammation levels of MAFLD and NAFLD in a general population from Southeast China was summarized to explore the potential effect of the transformation of disease definition., Methods: A total of 6718 general population participants aged 35-75 were enrolled. Logistic regression and restricted cubic spline (RCS) models were used to examine the relationship between 15 SI indicators and NAFLD and MAFLD. The predicted values of MAFLD and NAFLD were analyzed using the receiver operating characteristic (ROC) curve., Results: The prevalence of MAFLD and NAFLD was 34.7% and 32.4%, respectively. Their overlapping rate was 89.7%, while only 8.3% and 1.9% of participants were MAFLD-only and NAFLD-only. Among three FLD groups, the MAFLD-only group had the highest levels of 8 SI indicators, including CRP, WBC, LYMPH, NEUT, MONO, ALB, NLR, and SIRI. The non-FLD group had the lower levels of all 15 SI indicators compared with all FLD subgroups. The odds ratios (ORs) of 10 SI indicators were significant in both multivariable-adjusted logistic regression and RCS analyses of MAFLD or NAFLD, including CRP, WBC, LYMPH, NEUT, MONO, ALB, PLR, LMR, ALI and CA. ROC analysis showed that the AUC values of all SI were lower than 0.7 in both MAFLD and NAFLD., Conclusions: MAFLD could cover more FLD than NAFLD, and the MAFLD-only group had a more severe inflammation status, whereas the NAFLD-only exhibited lower levels. Moreover, there was not a high AUC and a high sensitivity of SI indicators, suggesting that SI indicators are not good indicators to diagnose NAFLD/MAFLD., (© 2023. The Author(s).)

The establishment of the China Pilot Free Trade Zone complies with the concept of sustainable development, and its construction can not only realize trade liberalization and facilitation but also activate the green innovation momentum of enterprises to help solve China's current dilemma of sustainable development and economic growth. This paper is the first to consider the impact of the establishment of the pilot free trade zone from the perspective of enterprise green innovation efficiency, providing a direct answer to the key question of whether the construction of the pilot free trade zone can truly serve the high-quality development of the economy in the new era, and enriching the theoretical research on the enterprise green innovation efficiency macro-drivers related theoretical research. In addition, this paper uses the super-efficient EBM-GML model to measure the level of green innovation efficiency of enterprises, on the basis of this, it adopts the multi-stage differences-in-differences method used to evaluate the impact of the establishment of the pilot free trade zone on the green innovation efficiency of enterprises. According to the benchmark regression results, the establishment of the pilot free trade zone has promoted the degree of green innovation efficiency of enterprises, and this promotion effect is sustainable. This conclusion was validated by robustness tests. Heterogeneity testing confirms that the pilot free trade zone has a significant influence on the green innovation efficiency of enterprises in heavy pollution industries, non-state-owned enterprises and patent-intensive enterprises. With the enhancement of environmental regulations, the green innovation efficiency of enterprises shows significant improvements. The analysis of the transmission mechanism shows that the pilot free trade zone influences the green innovation efficiency of enterprises primarily through the cost reduction effect, tax incentive effect, and reverse technology spillover effect. This study clarifies whether the policy of the pilot free trade zone can boost the green innovation efficiency of enterprises, and provides useful insight for further implementing the strategy of opening up to the world and promoting high-quality economic growth., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors. Published by Elsevier Ltd.)

The NLRP3 inflammasome is a critical component of innate immunity involved in the pathophysiology of various inflammatory diseases. In this study, we designed and synthesized a series of NLRP3 inflammasome inhibitors based on MCC950. Specifically, we optimized the furan moiety, which is considered to be potentially associated with drug-induced liver injury. The representative inhibitor N14 , 4-(2-(dimethylamino)ethyl)- N -((1,2,3,5,6,7-hexahydro- s -indacen-4-yl)carbamoyl)benzenesulfonamide, not only maintains the NLRP3 inhibitory activity of MCC950 with IC 50 of 25 nM but also demonstrates improved tolerability in human hepatic cells line and mouse primary hepatocytes. In addition, N14 exhibits superior pharmacokinetic properties, with an oral bioavailability of 85.2%. In vivo studies demonstrate that N14 is more effective than MCC950 in multiple NLRP3-related animal model diseases, including nonalcoholic steatohepatitis, lethal septic shock, and colitis. Our research has provided a lead compound that directly targets the NLRP3 inflammasome and can be developed as a novel therapeutic candidate for NLRP3-driven diseases.

Streptococcus pneumoniae is a Gram-positive opportunistic pathogen that can colonize the upper respiratory tract. It is a leading cause of a wide range of infectious diseases, including community-acquired pneumonia and meningitis. Pneumococcal infections cause 1-2 million deaths per year, most of which occur in developing countries. Here, we focused on three choline-binding proteins (CBPs), i.e., PspC, PspA, and LytA. These pneumococcal proteins have different surface-exposed regions but share related choline-binding anchors. These surface-exposed pneumococcal proteins are in direct contact with host cells and have diverse functions. We explored the role of the three CBPs on adhesion and pathogenicity in a human host by performing relevant imaging and functional analyses, such as electron microscopy, confocal laser scanning microscopy, and functional quantitative assays, targeting biofilm formation and the hemolytic capacity of S. pneumoniae . In vitro biofilm formation assays and electron microscopy experiments were used to examine the ability of knockout mutant strains lacking the lytA, pspC, or pspA genes to adhere to surfaces. We found that LytA plays an important role in robust synthesis of the biofilm matrix. PspA and PspC appeared crucial for the hemolytic effects of S. pneumoniae on human red blood cells. Furthermore, all knockout mutants caused less damage to endothelial cells than wild-type bacteria, highlighting the significance of each CPB for the overall pathogenicity of S. pneumoniae . Hence, in addition to their structural function within the cell wall of S. pneumoniae , each of these three surface-exposed CBPs controls or mediates multiple steps during bacterial pathogenesis., Competing Interests: The authors declare no conflict of interest.

Surface-enhanced Raman spectroscopy (SERS) with ultrasensitive vibrational fingerprints enables quick identification and trace detection of various kinds of molecules. But proteins usually have low Raman cross sections and are difficult to generate recognizable signals in direct SERS detection. Recently, nucleic acid-peptide conjugates are emerging with great potential in structuring, assembling, catalyzing, sensing, etc., and the coupling of aptamers further enables superior biological recognition and programmability. Here, we develop the aptamer-peptide conjugates as a new kind of SERS probe for direct high-specific profiling abnormal protein levels in cancer patients. The aptamer conjugated with glutathione (GSH) functions as both the recognition element and the SERS reporters that can simultaneously generate SERS fingerprints of both peptides and nucleic acids. This kind of biocompatible probe appears to have excellent performance in high-salt environments and realizes rapid, simple, and multisignal detection of thrombin (TB). Data-driven soft independent modeling of class analogy (DD-SIMCA) is used to distinguish SERS profiles of actual blood samples and realize the identification and classification of cancer patients. Furthermore, the effect of low-temperature storage time on blood samples is analyzed by tracking the changes of SERS profiles; the results hint that plasma samples stored under 4 °C for more than 2 days could generate false negative results due to TB hydrolysis, which has important implications for clinical sample analysis. This kind of nucleic acid-peptide conjugate provides new ideas for SERS sensing strategy in the future.

Both Orthohantaviruses (HV) and Whenzhou Mammarenaviruses (WENV) are rodents borne viruses, allowing them to spread simultaneously in the same area and infect humans. To explore the potential threat of HV and WENV to public health safety, an environmental and laboratory investigation was conducted in 2020-2021, in Jiangxi province, China. A total of 461 small mammals of 7 species and paired sera from 43 suspected HFRS cases were collected from Jiangxi Province, China. Viral genomic RNA and specific antibodies against HV and WENV were detected to evaluate the epidemic situation of the two viruses. Hantaan virus (HTNV), seoul virus (SEOV) and WENV RNA were detected in the lungs of the captured mammals, which resulted 4.1% and 7.4% of HV and WENV RNA positive respectively. Co-infections of WENV and SEOV were detected from Rattus norvegicus, Mus musculus and Rattus flavipectus with an overall co-infection rate of 0.65%. The detection rates of antibodies in the blood against HV and WENV were 11.9% (55/461), and 13.2% (61/461) respectively. The prevalence of viral infection and viral genetic characters varied among the selected areas. In the paired sera of 43 suspected HFRS cases, 38 were with HV infection, 11 were with WENV IgG, and 7 with a 4-fold or more of WENV IgG titer elevation. These results revealed the fact of the co-circulating and coinfection of HV and WENV in the same area at the same time, which might impact on public health safety., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Du, Xie, Deng, Xia, Wu, Huang, Chen, Li, Li, Wang, Sun, Guo, Wang, Liang, Li, Liu and Li.)

Background: The association of the meal timing of dietary total antioxidant capacity (DAC) with mortality is unclear. We aimed to investigate the association between the meal timing of DAC and all-cause, cardiovascular disease (CVD), and cancer mortality in general adult populations., Methods: A total of 56,066 adults who participated in the US National Health and Nutrition Examination Survey (NHANES) from 1999 to 2018 were recruited for this study. Dietary intake (quantity and timing) was evaluated by nonconsecutive 24-h dietary recalls. The main exposure variables were the DAC across three meals (total, breakfast, lunch, and dinner; without coffee) and the difference between dinner and breakfast DAC (Δ = dinner-breakfast; without coffee). The outcomes were all-cause, CVD, and cancer mortality. The adjusted hazard ratios [aHRs] and 95% confidence intervals [CI] were imputed by Cox proportional hazards regression., Results: Among the 56,066 participants, there were 8566 deaths from any cause, including 2196 from CVD and 1984 from cancer causes. Compared to participants in the lowest quintiles of the total DAC, those in the highest quintiles had 34% and 27% decreased risks of all-cause and CVD mortality, respectively (all-cause mortality: aHRs 0.66 [95% CI 0.57-0.76]; CVD mortality: aHRs 0.73 [95% CI 0.57-0.94]). More importantly, participants in the highest quintiles of the dinner DAC, but not those in that of breakfast or lunch, had a 24% decrease in all-cause mortality (aHRs 0.76 [95% CI 0.67-0.87]) compared with those in the lowest quintiles. Inverse associations were further confirmed for Δ DAC (aHRs 0.84 [95% CI 0.74-0.96]). Above associations did not change when including DAC from snacks or tea. Mediation analysis showed that the total associations of total, dinner or Δ DACs with reduced all-cause mortality were 24%, 13% and 6%, respectively, mediated by serum CRP. Additionally, all-cause mortality was decreased by 7% in models replacing 10% breakfast DAC (aHRs 0.93 [95% CI 0.9-0.97]) with an equivalent proportion of dinner DAC. For cancer mortality, no statistical significance was detected in the adjusted models., Conclusions: The findings emphasize the putative beneficial relationship of a diet rich in antioxidants and meal timing on serum CRP and all-cause mortality., (© 2023. The Author(s).)

Fenestration decompression, which can protect important anatomic structures and reduce surgical risk is the most preferred way for the treatment of jaw cysts in children, and wearing a cyst plug after the operation is the key to success. To enhance the retention of the cyst plug and promote the healing of the cyst, our team designed the vacuum-formed cyst plug to replace the classic one. This article presents a case of a jaw cyst in a 6-year-old girl who wore the vacuum-formed cyst plug after the fenestration decompression. Six months later, the cyst healed, and the permanent teeth affected by the cyst returned. This case showed that the vacuum-formed cyst plug offered a more comfortable experience and an explicit prognosis for children with jaw cysts, having high clinical application value., Competing Interests: The authors have no conflict of interest to declare., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of Mutaz B. Habal, MD.)

Background: Although primary health care (PHC) has been proven to be effective in preventing and treating chronic diseases, the visits rate of PHC institutions is still not ideal. Some patients initially express a willingness to visit PHC institutions but end up seeking health services at non-PHC institutions, and the reasons for this behavior remain unclear. Therefore, the objective of this study is to analyze the factors that contribute to behavioral deviations among chronic disease patients who originally intended to visit PHC institutions., Methods: Data were collected from a cross-sectional survey among chronic disease patients with original intention to visit PHC institutions in Fuqing City, China. The analysis framework was guided by Andersen's behavioral model. Logistic regression models were employed to analyze the factors affecting the behavioral deviations among chronic disease patients with a willingness to visit PHC institutions., Results: A total of 1,048 individuals were finally included and about 40% of the participants with the original willingness to seek care from PHC institutions finally chose non-PHC institutions in their subsequent visits. The results of logistic regression analyses indicated that at the predisposition factor level, older participants (aOR 60-69  = 0.602, P < 0.01; aOR 70-75  = 0.475, P < 0.01) were less likely to have behavioral deviations. At the enabling factor level, compared to those covered by Urban Employee Basic Medical Insurance (UEBMI) and not reimbursed, those covered by Urban-Rural Resident Basic Medical Insurance (URRBMI) (aOR = 0.297, P < 0.01), and those answering that reimbursement from medical institutions was convenient (aOR = 0.501, P < 0.01) or very convenient (aOR = 0.358, P < 0.001) were less likely to have behavioral deviations. At the need factor level, participants who visited PHC institutions due to illness last year (aOR = 0.348, P < 0.001) and with polypharmacy (aOR = 0.546, P < 0.01) were less likely to have behavioral deviations compared to those without the visit of PHC institutions and not taking polypharmacy, respectively., Conclusions: The deviations between the original willingness of PHC institution visits and subsequent behavior among chronic disease patients were associated with a number of predisposing, enabling, and need factors. Developing the health insurance system, strengthening the technical capacity of PHC institutions, and steadily developing a new concept of orderly healthcare-seeking behavior among chronic disease patients, will help promote their access to PHC institutions as well as improve the effectiveness of the tiered medical system for chronic disease care., (© 2023. The Author(s).)

Cationic polymeric materials and cell-penetrating peptides (CPPs) were often used as the delivery vectors in the evaluation of nucleic acid therapeutics. 10-23 DNAzyme is a kind of potential antisense therapeutics by catalytic cleavage of the disease-related RNAs. Here, lipofectamine 2000 and Tat peptide were evaluated for their effect on the catalytic activity of 10-23 DNAzyme, with the observed rate constant, thermal stability, CD spectra, and PAGE analysis, with a duplex DNA mimicking DNAzyme-substrate as a control. It was shown that the cationic carriers had a negative effect on the catalytic performance of the 10-23 DNAzyme. Significantly, the destabilizing effect of the cationic carriers on the duplex formation was noteworthy, as a duplex formation is an essential prerequisite in the silencing mechanisms of antisense and RNAi.

Fibroblast growth factor 10 (FGF10) is an important regulator of the mammalian cumulus-oocyte complex that plays a crucial role in oocyte maturation. In this study, we investigated the effects of FGF10 supplementation on the in vitro maturation (IVM) of buffalo oocytes and its related mechanisms. During IVM, the maturation medium was supplemented with a range of concentrations of FGF10 (0, 0.5, 5, and 50 ng/mL) and the resulting effects were corroborated using aceto-orcein staining, TUNEL apoptosis assay, detection of Cdc2/Cdk1 kinase in oocytes, and real-time quantitative PCR. In matured oocytes, the 5 ng/mL-FGF10 treatment resulted in a significantly increased nuclear maturation rate, which increased the activity of maturation-promoting factor (MPF) and enhanced buffalo oocyte maturation. Furthermore, it treatment significantly inhibited the apoptosis of cumulus cells, while simultaneously promoting its proliferation and expansion. This treatment also increased the absorption of glucose in cumulus cells. Thus, our results indicate that adding an appropriate concentration of FGF10 to a maturation medium during IVM can be beneficial to the maturation of buffalo oocytes and improve the potential of embryo development., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Fatty liver, obesity, and dyslipidemia are associated with prediabetes or diabetes risk, and hyperuricemia co-exists. The present study evaluated the role of multiple mediators, namely, fatty liver, body mass index (BMI), and dyslipidemia, in the association between hyperuricemia and diabetes status., Methods: Baseline data from the ongoing Fuqing cohort (5,336 participants) were analyzed to investigate the association of hyperuricemia with diabetes status using a multinomial logistic regression model. Furthermore, causal mediation analysis with the weighting-based approach was performed to estimate hyperuricemia's total natural direct effect (tnde), total natural indirect effect (tnie), and total effect (te) on prediabetes and diabetes risk, mediating jointly via fatty liver, BMI, and dyslipidemia., Results: In multinomial analysis without considering mediators' effects, hyperuricemia was associated with a higher risk of prediabetes only (odds ratio: 1.25; 95% CI: 1.09-1.43; p < 0.001). When fatty liver, BMI, and dyslipidemia were considered as multiple mediators in the association, hyperuricemia was linked to both prediabetes [tnde: 1.11, 95% CI: 1.04-1.11; tnie: 1.07, 95% CI: 1.05-1.09; and overall proportion mediated (pm): 42%, 95% CI: 27%-73%] and diabetes risk (tnde: 0.96, 95% CI: 0.82-1.14; tnie: 1.25, 95% CI: 1.18-1.33; and pm: 100%, 95% CI: 57%-361%). Hyperuricemia showed significant tnde, te, and tnie, mediated by fatty liver jointly with dyslipidemia (pm = 17%) or BMI (pm = 35%), on prediabetes risk., Conclusion: Hyperuricemia could increase prediabetes or diabetes risk, partially mediated by fatty liver, BMI, and dyslipidemia. Fatty liver is the crucial mediator in the association between hyperuricemia and prediabetes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Basnet, Du, Feng, Gao, Gong and Ye.)

By amplifying the cascaded random Raman fiber laser (RRFL) oscillator and ytterbium fiber laser oscillator, we present the first, to the best of our knowledge, demonstration of a 10-kW-level high-spectral-purity all-fiber ytterbium-Raman fiber amplifier (Yb-RFA). With a carefully designed backward-pumped RRFL oscillator structure, the parasitic oscillation between the cascaded seeds is avoided. Leveraging the RRFL with full-open-cavity as the Raman seed, the Yb-RFA realizes 10.7-kW Raman lasing at 1125 nm, which is beyond the operating wavelengths of all the reflection components used in the system. The spectral purity of the Raman lasing reaches 94.7% and the 3-dB bandwidth is 3.9 nm. This work paves a way to combine the temporal stability of the RRFL seed and the power scaling of Yb-RFA, enabling the wavelength extension of high-power fiber lasers with high spectral purity.

Background: Emerging data suggest that the interpretation of the association between obesity and lipids appears to be oversimplified. This study aimed to quantify the complex relationships between anthropometric indices and lipid profile., Methods: This is a cross-sectional study including 9620 participants in Southern China. Anthropometric indices included the indices of general obesity (ie, body mass index (BMI)) and central obesity (ie, waist circumference (WC) and waist-to-hip ratio (WHR)). Lipids included low-density lipoprotein cholesterol (LDLc) and atherogenic lipids (ie, high-density lipoprotein cholesterol (HDLc), triglycerides (TG) and TG/HDLc ratio). LOESS regression and general linear model were the main statistical methods., Results: Almost all associations between anthropometric indices and lipids were lost in obese adults. The loss of association occurred quicker with LDLc than that with atherogenic lipids; the break point for the association loss was at BMI of 24 kg/m 2 with LDLc (Slope Below break-point = 1.81, P <0.001; Slope Above break-point = 0.29, P =0.121), while at 28 kg/m 2 with HDLC (Slope Below break-point = -1.41, P <0.001; Slope Above break-point = 0.07, P =0.666) or TG (Slope Below break-point = 4.96, P <0.001; Slope Above break-point = 2.93, P =0.01), and at 30 kg/m 2 with TG/HDLc ratio (Slope Below break-point = 0.15, P <0.001; Slope Above break-point = 0.01, P =0.936), respectively. Similar relationships were found for WC and WHR. Besides, the presence of other metabolic disorders contributed to the loss of anthropometry-lipids relationships, for example, the BMI-LDLc association attenuated to null in both obese adults and non-obese population but with more than one other metabolic disorders., Conclusion: The relationships were lost between anthropometric indices and lipids in obese adults with different break points across different lipids, which appeared to be dependent on metabolic status., Competing Interests: The authors declare no conflicts of interest in this work., (© 2023 Huang et al.)

Background: Bilirubin may prevent lipid peroxidation and have important antiatherosclerotic effects. We determined associations of serum bilirubin and lipid with peripheral atherosclerosis., Methods: We included 4290 participants (35% men; median age, 60 years) from the southeast China who underwent B-mode ultrasound examination. Increased intima-media thickness or a focal structure encroaching into the arterial lumen by at least 0.5 mm or >50% of the surrounding intima-media thickness value was regarded as having atherosclerosis. Fasting serum bilirubin and lipid levels were measured. Cholesterol/(HDL [high-density lipoprotein] cholesterol+bilirubin), and LDL (low-density lipoprotein cholesterol)/(HDL+bilirubin) ratios were calculated. Unconditional and multinomial logistic regression models were used to examine associations of bilirubin or lipid with prevalence of peripheral atherosclerosis. Mediation analyses were performed to assess the effect of bilirubin on atherosclerosis risk mediated via lipid., Results: Compared with participants with the lowest levels of bilirubin, those with the highest tertile were less likely to have carotid or femoral atherosclerosis (odds ratios were 0.55-0.74). The highest levels of bilirubin significantly reduced the odds of concurrent carotid and femoral atherosclerosis by 35% to 45%. Participants with the highest levels of cholesterol, LDL, cholesterol/(HDL+bilirubin), and LDL/(HDL+bilirubin) ratios had 2.8- to 3.7-fold increased odds of concurrent carotid and femoral atherosclerosis. LDL accounted for 25.65% of the total bilirubin-atherosclerosis association. LDL and cholesterol mediated the associations between direct bilirubin and atherosclerosis (proportion: 20.40%, 9.67%, respectively)., Conclusions: Increased serum bilirubin levels are inversely associated with the prevalence of carotid or femoral atherosclerosis. LDL and cholesterol may mediate these associations.

Luminescence intensity is a critical factor for upconversion (UC) oxides with high phonon energy. Herein, an effective enhancement in UC luminescence is achieved in the ZnMoO 4 :Er 3+ phosphor via Bi 3+ doping. UV-vis-NIR diffuse reflectance spectroscopy verifies the fact that the absorption at 980 nm is enhanced by the introduction of Bi 3+ . The physical mechanism is that Bi 3+ doping affects the transition probability between the f-levels of Er 3+ . Therefore, the green and red emission intensities are increased 82.4 and 37 times, respectively. The dependence of luminescence intensity on the power of Bi 3+ -doped ZnMoO 4 :Er 3+ combined with density functional theory (DFT) calculations also confirms the proposed energy transfer mechanism. Based on the excellent green emission, the 980 nm excited optical temperature sensing property of the synthesized sample is realized in a wide temperature range by monitoring the intensity of UC luminescence. The theoretically calculated absolute sensitivity of the optical temperature sensor was S A = 3.04% K -1 at 1253 K. This work paves a new way for enhancing UC luminescence and will arouse extensive interest in noncontact temperature-sensing applications.

Background: Chikungunya virus (CHIKV) reemerged and caused millions of human infections since 2004. The disease could be established, when the virus has been introduced to areas where the appropriate vectors are endemic. The differential diagnosis of CHIKV infection varies based on place of residence, travel history, and exposures. Serological tests are commonly used to diagnose CHIKV infection, but their availability and assessments of the performance of the diagnostics have been limited., Objectives: To develop and evaluate antibodies detection methods for chikungunya diagnosis and serological investigation., Methods: Recombinant E2 protein based IgM capture enzyme-linked immunosorbent assay (Mac-ELISA) and double antigen sandwich ELISA (Das-ELISA) for detection of antibodies to Chikungunya virus were developed and evaluated. The repeatability was evaluated by testing of three reference sera at single dilutions in triplicated for 5 times. The sensitivity, specificity, accuracy, and agreement of the MAC-ELISA and Das-ELISA were obtained by comparing the detection results of 225 serum samples (45 positive; 180 negative) with a real-time RT-PCR assay and an IFA commercial tests manufactured by Euroimmun., Results: The established ELISA assays were standardized by determining the optimal concentrations of the key reagents. The coefficient values of repeat testing were within 10% and 20% for intraassay and interassay precision, respectively. A sensitivity of 60.0% and 52.5%, a specificity of 96.2% and 96.8%, and an accuracy of 89.8% and 88.9% were obtained for the Mac-ELISA and Das-ELISA, respectively, when compared to a CHIKV qRT-PCR method. And a sensitivity of 100%, a specificity of 97.5% and 99.5%, and an accuracy of 97.8% and 99.6% were yielded respectively when using the IIFT as a reference method, which showed a highly consistence to the commercial IIFT assay with a Kappa value greater than 0.90., Conclusions: The Mac-ELISA and Das-ELISA based on recombinant E2 protein of CHIKV were developed and standardized, which could detect IgM or total antibodies against CHIKV in 2-3 hours with acceptable sensitivities and specificities. These assays can be used for laboratory diagnosis and serological investigation of CHIKV infections to evaluate the risk of CHIKV transmission., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Guo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Solar-induced fluorescence (SIF) is a promising proxy for photosynthesis, but it is unclear whether it performs well in tracking the gross primary productivity (GPP) under different environmental conditions. In this study, we investigated the dynamics of the two parameters from October 2020 to June 2021 in field-grown winter wheat (Triticum aestivum) and found that the ability of SIF to track GPP was weakened at low temperatures. Accounting for the coupling of light and temperature at a seasonal scale, we found that SIF yield showed a lower temperature sensitivity and had a lower but broader optimal temperature range compared with light-use efficiency (LUE), although both SIF yield and LUE decreased in low-temperature conditions. The discrepancy between the temperature responses of SIF yield and GPP caused an increase in the ratio of SIF/GPP in winter, which indicated the variation in the relationship between them during this period. The results of our study highlight the impact of low temperature on the relationship between SIF and GPP and show the necessity of reconsidering the dynamics of energy distribution inside plants under changing environments., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Although type 2 diabetes mellitus (T2DM) plays a significant role in the association between metabolic dysfunction-associated fatty liver disease (MAFLD) and chronic kidney disease (CKD), how T2DM development and glycemic deterioration affect CKD and its renal function indicators, estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (UACR), remains unknown. We aimed to assess the association between MAFLD, along with T2DM, and risk of CKD, and then evaluate the effect of metabolic goal achievement in MAFLD on the risk of CKD., Methods: In this cross-sectional study, 5,594 participants were included. Multivariate logistic regression and linear regression were used to examine the association between MAFLD with its T2DM status and metabolic goal achievement and risk of CKD, as well as eGFR and UACR., Results: The MAFLD group had a higher prevalence of CKD (16.2 vs. 7.6%, P < 0.001) than the non-MAFLD group. MAFLD was independently associated with an increased risk of CKD (odds ratio [OR]: 1.35, 95% CI: 1.09-1.67) and increased eGFR and UACR. Among the three MAFLD subtypes, only the T2DM subtype exhibited significant associations with increased risk of CKD (OR: 2.85, 95% CI: 2.24-3.63), as well as increased eGFR and UACR. Glycemic deterioration in MAFLD was dose-dependently associated with an increased risk of CKD ( P -trend < 0.001). Achieved metabolic goals in MAFLD decreased the risk of CKD, eGFR, and UACR; MAFLD with 2 or 3 achieved metabolic goals was not significantly associated with the risk of CKD (OR: 0.81, 95% CI: 0.59-1.12) and albuminuria., Conclusion: MAFLD was independently associated with an increased risk of CKD, as well as increased eGFR and UACR. This association is strongly driven by T2DM status. Glycemic deterioration in MAFLD was dose-dependently associated with an increased risk of CKD. Achieved metabolic goals in MAFLD decreased the risk of CKD by reducing the risk of albuminuria., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Su, Chen, Xiao, Du, Xue, Feng and Ye.)

Meat nutrition and safety is highly related to people's health and quality of life. There is a huge demand to rapidly analyze meat quality during product processing and storage, but few rapid detection tools. Traditional strategies have certain disadvantages, including time-consuming, expensive, damage to samples, and the need for professional operators. Nowadays, Raman spectroscopy is drawing more and more attention due to its potential in fingerprint, specificity, speed, non-destructive and portable. This comprehensive review first briefly introduces the principles of meat analysis by common Raman techniques, e.g. Raman spectroscopy, surface-enhanced Raman spectroscopy (SERS), Raman chemical imaging (RCI), and spatially offset Raman spectroscopy (SORS), and then focus on their analytical applications on structure analysis, quality evaluation, and security control. This review also prospects the future development trend and challenges in detecting and analyzing meat and meat products., 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.)

Oxidative stress damage to the lens is a key factor in most cataracts. Forkhead box O 4 (FOXO4), a member of the forkhead box O family, plays a pivotal role in oxidative stress. FOXO4 is upregulated in lens of age-related cataract patients, but its role in cataract has not been elucidated. Herein, we investigated the role and mechanism of FOXO4 during oxidative stress damage in lens epithelial cells. H 2 O 2 treatment enhanced FOXO4 expression in HLEpiC cells. Short hairpin RNAs mediated FOXO4 silence aggravated H 2 O 2 -induced cell apoptosis. In addition, upon H 2 O 2 exposure, silencing of FOXO4 reduced SOD and CAT activities, as well as increased intracellular MDA and ROS levels. FOXO4 silencing also inhibited Nrf2 nuclear translocation, followed by reducing the expressions of Nrf2-governed antioxidant genes HO-1 and NOQ-1. Exogenous overexpression of FOXO4 was also involved in this study and exhibited opposite effects of FOXO4-silencing. Mechanistically, FOXO4 directly bound the promoter of TRIM25 and regulated its transcription, thereby activating the Nrf2 signaling. Taken together, in the condition of oxidative stress, the expression of FOXO4 showed a compensatory upregulation and it exhibited an anti-oxidative effect by modulating the transcription of TRIM25, thus activating the Nrf2 signaling. The FOXO4/TRIM25/Nrf2 axis may be associated with the pathological mechanisms of cataract., Competing Interests: Declaration of competing interest The authors declare no conflict of interests., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Microbial production of poly-γ-glutamic acid (γ-PGA) from non-food raw materials is a promising alternative to food feedstocks-based biosynthesis. A superior cell factory of Bacillus amyloliquefaciens for the efficient synthesis of γ-PGA from crude glycerol was constructed through systematic metabolic engineering. Firstly, some phase-dependent promoters were screened from B. amyloliquefaciens, which can be used for fine regulation of subsequent metabolic pathways. Secondly, the glycerol utilization pathway and the γ-PGA synthesis pathway were co-optimized utilizing the above-screened promoters, which increased the titer of γ-PGA by 1.75-fold. Then, the titer of γ-PGA increased to 15.6 g/L by engineering transcription factors degU and blocking competitive pathways. Finally, combining these strategies with an optimized fermentation process, 26.4 g/L γ-PGA was obtained from crude glycerol as a single carbon source (a 3.72-fold improvement over the initial strain). Overall, these strategies will have great potential for synthesizing other products from crude glycerol in B. amyloliquefaciens., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Foot ulceration is a major complication of diabetes mellitus, which results in significant human suffering and a major burden on healthcare systems. The cause of impaired wound healing in diabetic patients is multifactorial with contributions from hyperglycaemia, impaired vascularization and neuropathy. Patients with non-healing diabetic ulcers may require amputation, creating an urgent need for new reparative treatments. Delivery of stem cells may be a promising approach to enhance wound healing because of their paracrine properties, including the secretion of angiogenic, immunomodulatory and anti-inflammatory factors. While a number of different cell types have been studied, the therapeutic use of mesenchymal stromal cells (MSCs) has been widely reported to improve delayed wound healing. However, topical administration of MSCs via direct injection has several disadvantages, including low cell viability and poor cell localization at the wound bed. To this end, various biomaterial conformations have emerged as MSC delivery vehicles to enhance cell viability and persistence at the site of implantation. This paper discusses biomaterial-based MSCs therapies in diabetic wound healing and highlights the low conversion rate to clinical trials and commercially available therapeutic products., (© 2022. The Author(s).)

Engineered synthetic scaffolds to organize metabolic pathway enzymes and system pathway engineering to fine-tune metabolic fluxes play essential roles in microbial production. Here, we first obtained the most favorable combination of key enzymes for 5-aminolevulinic acid (5-ALA) synthesis through the C5 pathway by screening enzymes from different sources and optimizing their combination in different pathways. Second, we successfully constructed a multienzyme complex assembly system with PduA*, which spatially recruits the above three key enzymes for 5-ALA synthesis in a designable manner. By further optimizing the ratio of these key enzymes in synthetic scaffolds, the efficiency of 5-ALA synthesis through the C5 pathway was significantly improved. Then, the competitive metabolism pathway was fine-tuned by rationally designing different antisense RNAs, further significantly increasing 5-ALA titers. Furthermore, for efficient 5-ALA synthesis, obstacles of NADH and NADPH imbalances and feedback inhibition of the synthesis pathway were also overcome through engineering the NADPH regeneration pathway and transport pathway, respectively. Finally, combining these strategies with further fermentation optimization, we achieved a final 5-ALA titer of 11.4 g/L. These results highlight the importance of synthetic scaffolds and system pathway engineering to improve the microbial cell factory production performance.

Midfacial hypoplasia is a common maxillofacial deformity in patients with cleft lip and palate, which requires surgical treatment. However, trans-sutural distraction osteogenesis (TSDO) remains some disadvantages, including difficulty in accurate location of surgical path, prolonged operation time, and excess surgical bleeding. This study aimed to evaluate the application of an optical surgical navigation system (OSNS) developed for TSDO. Six consecutive patients with midfacial hypoplasia who required TSDO were included in the study. Preoperatively, a head computed tomography was performed, and the data were imported into Mimics software (version: 20.0.0.691, Materialise Inc, Belgium) to design a three-dimensional simulation of the surgical approach. TSDO was performed with the use of OSNS. The accuracy and results of the procedure were initially evaluated by comparing the preoperative and postoperative periods. The patients included five boys and one girl, with an average age of 10 years; five with postoperative cleft lip and palate, and one without combined cleft lip and palate. The surgical procedure was successful, with a postoperative follow-up of 4-5 months. All patients demonstrated good treatment results without complications. In conclusioin, OSNS-assisted TSDO can noninvasively correct midfacial dysplasia, improve surgical precision, reduce bleeding and obtain better clinical results. OSNS can guide the TSDO safely and effectively., (© 2022. The Author(s).)