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Urbanization confronts the dual challenges of water scarcity and environmental degradation, prompting the exploration of diverse water sources for mitigating these impacts. Inter-basin water transfer (IBWT) has emerged as a solution to balance urban water demand and supply in areas with local water shortages. While IBWT can deliver high-quality water over long distances, it is costly, often contributing significantly to carbon emissions. Reclaimed water use (RWU) presents a promising alternative to address this dilemma. In this paper, a valley region of Chongqing municipality in Southwest China, which is confronted with water and environmental risks resulting from rapid urbanization, was explored and discussed as a case study to assess the potential impact of RWU on reducing carbon emissions as compared to IBWT. A method of accumulative accounting was adapted to calculate and sum up carbon emission intensities at various stages, revealing that the operational carbon emission intensities of IBWT and RWU are 0.7447 KgCO2/m3 and 0.1880 KgCO2/m3, respectively. This indicates that RWU substitution can reduce carbon emissions by 0.5567 KgCO2/m3 or 75%. This paper further elucidates the mechanism behind carbon emission reduction, highlighting the energy-saving benefits of using reclaimed water locally without recourse to extensive transportation or elevation changes. Additionally, this result presents three scenarios of reclaimed water use, including urban miscellaneous water, river flow replenishment, and agricultural irrigation in relation to their substitution effects and environmental impacts. Estimates of carbon emission reductions from reclaimed water use were projected at the planned scale, with the maximum potential of reclaimed water utilization predicted. Finally, this paper proposes an enhanced strategy to identify and prioritize factors affecting reclaimed water utilization and the effect of carbon emission reduction. This paper aims to facilitate the establishment of a robust legal, institutional, and managerial framework while fostering interdisciplinary and cross-sectoral cooperation mechanisms in valley urban areas. The methodology employed can be universally applied to other regions grappling with severe water stress, thereby facilitating endeavors toward carbon reduction and contributing significantly to the attainment of water sustainability.

Abstract Epstein-Barr virus (EBV) is an opportunistic pathogen that can manifest itself as a potential contributor to human diseases years after primary infection, specifically in lymphoid and epithelial cell malignancies in immune-competent and immune-compromised hosts. The virus shuttles between B cells and epithelial cells during its infection cycle, facilitating its persistence and transmission in humans. While EBV efficiently infects and transforms B-lymphocytes, epithelial cells are not as susceptible to transformation in vitro. We utilized a 3D platform for culturing normal oral keratinocyte cells (NOKs) using Matrigel for greater insights into the molecular interactions between EBV and infected cells. We determined the transcriptome of EBV infected NOKs and peripheral blood mononuclear cells (PBMCs) for 7 and 15 days. LMPs (−1, −2A, and −2B) and EBNAs (−1, −2, −3A, −3B and −3C) were detected in all samples, and lytic gene expression was significantly higher in NOKs than PBMCs. We identified over 2000 cellular genes that were differentially expressed (P-value

Abstract Compared with traditional tumor therapy strategies, hydrogel as a drug reservoir system can realize on-demand drug release and deep tissue penetration ability. It also exhibits great tumor-site retention to enhance the permeability and retention effect of tumor treatment. This can significantly overcome the drug's resistance and severe side effects. Inorganic/organic composite hydrogel has attracted wide attention due to its combined effects, enhancing therapeutic effects against various kinds of tumors. In situ injectable hydrogel can securely restrict the drugs in the lesion sites without leakage and guarantee better biosafety. Moreover, hydrogel possesses interconnected macropores which can provide enough space for nutrient transport, cellular activity, and cell–cell interactions. Thermal therapy is an effective strategy for tumor therapy due to its minimal invasiveness and high selectivity. Because the location temperature can be precisely controlled and helps avoid the risks of destroying the body's immune system and ablate normal cells, thermal therapy exhibits significant treatment outcomes. Nonetheless, when the cellular temperature reaches approximately 43 °C, it causes long-term cell inactivation. Based on these merits, thermosensitive hydrogel formulation with adaptive functions shows excellent efficacy, unlimited tissue penetration capacity, and few deleterious side effects. Furthermore, the thermosensitive hydrogel has unique physical properties under the external stimuli, which is the ideal drug delivery system for on-demand release in tumor treatment. This article will review the state of the thermosensitive hydrogel in clinic application for cancer therapy.

MMC (Modular Multilevel Converter) is the preferred topology for renewable energy delivery, but renewable energy resources, such as wind farms, contains much harmonic components. Compared with two-level VSC (Voltage Source Converter), the internal dynamic characteristics of MMC have great impact on the harmonic transmission. This paper quantitatively analyzes the harmonic transferring mechanism from one side to the other side of MMC, and deduces the time-domain analytical expression of the harmonic response on the MMC's other side. Firstly, the influence of background harmonic on MMC's control system and electrical system are quantitatively analyzed. On this basis, the equivalent circuit of MMC's electrical system considering its internal dynamics is established to accurately calculate the effect of background harmonic on the MMC's other side. In addition, the harmonic transferring impedance in frequency-domain is also defined in this paper, based on that the influence of background harmonic on the MMC's other side can be calculated quickly. According to the harmonic transferring characteristics analyzed above, a zero-sequence virtual damping strategy is proposed for the first time to suppress the background harmonic transferring. Finally, a 232-level 500kV MMC simulated model is built in MATLAB/Simulink to verify the accuracy of the harmonic transferring calculation method and the effectiveness of the virtual damping suppression strategy.

Impedance-based stability criterion is effective for analyzing the oscillation phenomenon in modular multilevel converter-based high-voltage DC (MMC-HVDC) transmission system, and modeling MMC impedance is the critical step. However, few papers have modeled MMC impedance with comprehensive consideration of time delay and outer-loop control at the same time. The stabilization strategies to improve system stability are not considered during impedance modeling, and the influences of stabilization strategy on impedance are not analyzed mathematically, either. In this article, an accurate sequence impedance model of MMC is derived with the consideration of time delay and complete control loops. Based on this impedance model, the negative damping caused by time delay is pointed out and the weak stability of grid-tied MMC system is analyzed. Then a stabilization control strategy is proposed to suppress the system oscillation. In the meantime, taking the proposed stabilization strategy into account, impedance modeling is revised to study the influence of this strategy on MMC impedance. Furthermore, based on this revised impedance model, an optimal design method for controller parameters of the stabilization strategy is proposed to maximize the phase margin of the interconnected system. Finally, the effectiveness of the accurate impedance model, the proposed stabilization control strategy and optimal design method are verified by simulation results.

Objective Malignant melanoma is a highly invasive cancer whose pathogenesis remains unclear. We analyzed the microarray dataset GDS1375 in the Gene Expression Omnibus database to search for key genes involved in the occurrence and development of melanoma. Methods The dataset included 52 samples (7 normal skin and 45 melanoma samples). We identified differentially expressed genes (DEGs) between the two groups and used integrated discovery databases for Gene Ontology (GO) and Kyoto Gene and Genome Encyclopedia (KEGG) pathway analyses. In addition, we used the STRING and MCODE plugins of Cytoscape to visualize the protein-protein interactions (PPI) for these DEGs. Results A total of 509 upregulated and 618 downregulated DEGs were identified, which were enriched in GO terms including integrin binding, protein binding, and structural constituent of cytoskeleton, and in KEGG pathways such as melanogenesis, prostate cancer, focal adhesion, and renin secretion. Three major modules from the PPI networks and 10 hub genes were identified, including CDC20 , GNB2 , PPP2R1A , AURKB , POLR2E , and AGTR1 . Overall survival was low when these six hub genes were highly expressed. Conclusion This bioinformatics analysis identified hub genes that may promote the development of melanoma and represent potential new biomarkers for diagnosis and treatment of melanoma.

Abstract Similar to pathogenic infection, high population density alters insects’ prophylactic immunity. Density-dependent prophylaxis has been reported in many polyphenic insects, but the regulatory mechanism underlying this phenomenon remains unclear. The biogenic monoamines are known to play critical roles in mediating insect immune responses. In the current study, the immune capacity and the levels of three biogenic monoamines were investigated in the polyphenic larvae of Mythimna separata, reared at the densities of 1, 2, 5, 10, and 30 larvae per 650-mL jar. Concomitant with the increased phenoloxidase (PO) activity and total haemocyte count in the larvae at high densities (5, 10, 30 larvae/jar), the octopamine level was also increased. In contrast, the dopamine level was decreased, and the 5-hydroxytryptamine level was not significantly affected. Injection of octopamine induced significant increases in the total haemocyte count and PO activity. Conversely, epinastine, a specific antagonist of octopamine, decreased the total haemocyte count and PO activity. Another octopamine antagonist, phentolamine, inhibited the activity of PO and lysozymes. In addition, injection of dopamine induced a significant increase in PO activity and decreased the total haemocyte count and lysozyme activity. These results suggested that both octopamine and dopamine mediate the increases in total haemocyte count and PO activity in the crowded larvae.

As one of the highly contagious forms, herpes simplex virus type 2 (HSV-2) commonly caused severe genital diseases and closely referred to the HIV infection. The lack of effective vaccines and drug-resistance proclaimed the preoccupation for alternative antiviral agents against HSV-2. Molecules bearing indole nucleus presented diverse biological properties involving antiviral and anti-inflammatory activities. In this study, one of the indole molecules, arbidol derivative (ARD) was designed and synthesized prior to the evaluation of its anti-HSV-2 activity. Our data showed that the ARD effectively suppressed HSV-2-induced cytopathic effects and the generation of progeny virus, with 50% effective concentrations of 3.386 and 1.717 μg/mL, respectively. The results of the time-course assay suggested that the ARD operated in a dual antiviral way by interfering virus entry and impairing the earlier period of viral cycle during viral DNA synthesis. The ARD-mediated HSV-2 inhibition was partially attained by blocking NF-κB pathways and down-regulating the expressions of several inflammatory cytokines. Furthermore, in vivo studies showed that oral administration of ARD protected BALB/c mice from intravaginal HSV-2 challenge by alleviating serious vulval lesions and histopathological changes in the target organs. Besides, the treatment with ARD also made the levels of viral protein, NF-κB protein and inflammatory cytokines lower, in consistent with the in-vitro studies. Collectively, ARD unveiled therapeutic potential for the prevention and treatment of HSV-2 infections.

Herpes simplex virus type 1 (HSV-1), an enveloped DNA virus, plays a key role in varieties of diseases including recurrent cold sores, keratoconjunctivitis, genital herpes and encephalitis in humans. Great efforts have been made in developing more effective and less side-effects anti-herpes simplex virus agents, including traditional Chinese herbal medicines. In the present study, we evaluated the antiviral efficacy of Rheum tanguticum nanoparticles against HSV-1 in vitro and in vivo. R. tanguticum nanoparticles could inactivate the HSV-1 virions and block the viral attachment and entry into cells. Time-of-addition assay indicated that R. tanguticum nanoparticles could interfere with the entire phase of viral replication. Besides, R. tanguticum nanoparticles showed the ability to inhibit the mRNA expression of HSV-1 immediate early gene ICP4 and early gene ICP8 as well as the expression of viral protein ICP4 and ICP8. Moreover, R. tanguticum nanoparticles have been proved to protect mice against HSV-1 induced lethality by decreasing the viral load and alleviated pathological changes in brain tissues. In conclusion, we demonstrated that R. tanguticum nanoparticles could inhibit HSV-1 infection through multiple mechanisms. These results suggest that R. tanguticum nanoparticles may have novel roles in the treatment of HSV-1 infection.

The stability of Modular multilevel converter (MMC) itself is the premise of analyzing the stability of MMC cascading with other cells, so this paper addressed the small-signal stability of MMC with dc voltage control mode which is the common operation mode of grid-side MMC in high-voltage direct current (HVDC) systems. First, the small signal model of MMC with open-loop control mode and dc voltage control mode while considering the dc voltage controller and current controller are established with the harmonic state-space (HSS) modeling method. Subsequently, eigenvalues and participation factors are analyzed to estimate the stability of MMC system and the influence of controller parameters, especially the proportional coefficients of dual-loop controllers, which can improve the design efficiency of control system. Finally, time-domain simulations in MATLAB/Simulink are provided to verify the accuracy of HSS small signal model and the effectiveness of the theoretical stability analysis.

Background and Objectives: Health promoting behaviors are crucial to the health of pregnant women and their children. The present study was conducted to assess health promoting behaviors in pregnant women admitted to Imam Khomeini Hospital of Saqqez. Materials and Methods: The present descriptive analytical study was conducted on 181 pregnant women selected through convenience sampling. The data collection tool used in the study was a questionnaire containing two parts: a section on the subjects' demographic details, and another section for the Health Promoting Lifestyle Profile II (HPLP II). Data were analyzed in SPSS-21 using descriptive (frequency percentage) and inferential statistics, such as the independent t-test, the Pearson correlation test and the one-way ANOVA. Results: Based on the findings of the study, the highest scores of health promoting behaviors obtained were in the domain of spiritual growth and the lowest in the domain of physical activity. The mean overall score of health promoting behaviors was desirable. The only demographic variable found to have a significant relationship with health promoting behaviors was occupation (P

There is growing evidence that insects living in high-density populations exhibit an increase in immune function to counter a higher risk of disease. This phenomenon, known as density-dependent prophylaxis, has been experimentally tested in a number of insect species. Although density-dependent prophylaxis is especially prevalent in insects exhibiting density-dependent phase polyphenism, the molecular mechanism remains unclear. Our previous study demonstrated that the antibacterial activity of lysozyme is important for this process in the beet webworm Loxostege sticticalis. In this study, a lysozyme cDNA from L. sticticalis was cloned and characterized. The full-length cDNA is 1078 bp long and contains an open reading frame of 426 bp that encodes 142 amino acids. The deduced protein possesses structural characteristics of a typical c-type lysozyme and clusters with c-type lysozymes from other Lepidoptera. LsLysozyme was found to be expressed throughout all developmental stages, showing the highest level in pupae. LsLysozyme was also highly expressed in the midgut and fat body. Elevated LsLysozyme expression was observed in L. sticticalis larvae infected by Beauveria bassiana and in larvae reared under crowding conditions. In addition, the expression level of LsLysozyme in infected larvae reared at a density of 10 larvae per jar was significantly higher compared to those reared at a density of l or 30 larvae per jar. These results suggest that larval crowding affects the gene expression profile of this lysozyme. This study provides additional insight into the expression of an immune-associated lysozyme gene and helps us to better understand the immune response of L. sticticalis under crowding conditions.

Periodontitis is a common chronic inflammatory disease, which leads to alveolar bone resorption. Healthy and functional alveolar bone, which can support the teeth and enable their movement, is very important for orthodontic treatment. Myricetin inhibited osteoclastogenesis by suppressing the expression of some genes, signaling pathways, and cytokines. This study aimed to investigate the effects of myricetin on alveolar bone loss in an ovariectomized (OVX) mouse model of periodontitis as well as in vitro osteoclast formation and bone resorption. Twenty-four healthy eight-week-old C57BL/J6 female mice were assigned randomly to four groups: phosphate-buffered saline (PBS) control (sham) OVX + ligature + PBS (vehicle), and OVX + ligature + low or high (2 or 5 mg∙kg−1∙day−1, respectively) doses of myricetin. Myricetin or PBS was injected intraperitoneally (i.p.) every other day for 30 days. The maxillae were collected and subjected to further examination, including micro-computed tomography (micro-CT), hematoxylin and eosin (H&E) staining, and tartrate-resistant acid phosphatase (TRAP) staining; a resorption pit assay was also performed in vitro to evaluate the effects of myricetin on receptor activator of nuclear factor κ-B ligand (RANKL)-induced osteoclastogenesis. Myricetin, at both high and low doses, prevented alveolar bone resorption and increased alveolar crest height in the mouse model and inhibited osteoclast formation and bone resorption in vitro. However, myricetin was more effective at high dose than at low dose. Our study demonstrated that myricetin had a positive effect on alveolar bone resorption in an OVX mouse model of periodontitis and, therefore, may be a potential agent for the treatment of periodontitis and osteoporosis.

Zanthoxylum bungeanum leaves (ZBL) are of great medicinal value for being rich in hyperoside and quercitrin. In this study, a novel, efficient and economical continuous process was established. First, aqueous two-phase system (ATPS) composed of Triton X-100/(NH 4 ) 2 SO 4 was employed to enrich hyperoside and quercitrin from ZBL extracts and the recoveries reached 98.53% and 99.12%. Then back-extraction with dichloromethane-water system was adopted to separate hyperoside and quercitrin from Triton X-100 micelles which were recycled and the recoveries reached 86.58% and 85.19%. Finally, S-8 macroporous resin was used for removing the salt introduced in ATPS and the final recoveries reached 82.38% and 81.81%, much higher than the total flavonoids recovery as 69.08%. Furthermore, scale-up experiment certified that the continuous process was feasible for industrial production. Efficiently and economically, this method achieved a great breakthrough in purity and provided a novel reference for further purification and phase-forming component recycle.

Purpose: Snoring frequently occurs among pregnant women, particularly in the later stages of pregnancy. It often signals obstructive sleep apnea (OSA), which could potentially affect pregnancy outcomes negatively. Hence, our study aimed to investigate how snoring influences the likelihood of pregnancy complications and fetal outcomes in a cohort of expectant mothers., Methods: We enrolled pregnant women in their second and third trimesters and had them fill out a questionnaire concerning sleep-related symptoms such as snoring, excessive daytime sleepiness, and frequency of nighttime awakenings, along with anthropometric measurements. Subsequently, the participants were divided into snorers and non-snorers, and the occurrence of pregnancy complications and fetal outcomes was monitored., Results: The study enrolled a total of 212 pregnant women, among whom 35 were identified as snorers and 177 as non-snorers during mid to late pregnancy. This indicated a snoring prevalence of 16.5% in our sample. Significant differences were noted between the two groups regarding the occurrence of oligohydramnios (11.43% vs. 2.82%, p = 0.044) and fetal distress (28.57% vs. 8.47%, p = 0.003). Logistic regression analyses revealed that snoring was independently associated with fetal distress (odds ratio [OR] = 4.99, 95% confidence interval [CI] 1.88-13.23, p = 0.001)., Conclusions: Our findings suggest that habitual snoring was the independent risk factor fetal distress after adjusting for potential confounders, indicating that habitual snoring may have a detrimental effect during mid to late pregnancy., Competing Interests: Declarations Ethical approval The study protocols were approved by the ethics committee of Fujian Provincial Maternity and Children’s Hospital, Affiliated Hospital of Fujian Medical University. Conflict of interest The authors declare that they have no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Manganese-based lithium-ion sieves have become some of the promising adsorbents for extracting Li + from brines. However, manganese dissolution loss (MDL) severely impairs the stability and cyclicity of ion sieves. A novel ozone eluent was first developed to extract Li + from lithium manganese oxides, which decreased MDL decreased from 5.89% to 0.11%, and after ten regeneration cycles, the adsorption capacity retained 85.39% of the initial value, which was better than 55.15% when only hydrochloric acid (HCl) was used as the eluent. Based on these phenomena, the mechanism for the O 3 lowering of MDL was investigated. First, the catalytic decomposition reaction of O 3 competed with the disproportionation reaction, and the involvement of O 3 inhibited the occurrence of the disproportionation reaction. Additionally, the presence of O 3 and reactive oxygen species provided a preferential electron acceptor compared to Mn 3+ during the migration of electrons from the bulk phase to the surface. In this study, MDL was greatly reduced with a very simple strategy, and the cycling stability of the adsorbent was improved., 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., (This journal is © The Royal Society of Chemistry.)

The potential use of engineered dietary nanoparticles (EDNs) in diet has been increasing and poses a risk of exposure. The effect of EDNs on gut bacterial metabolism remains largely unknown. In this study, liquid chromatography-mass spectrometry (LC-MS) based metabolomics was used to reveal significantly altered metabolites and metabolic pathways in the secretome of simulated gut microbiome exposed to six different types of EDNs (Chitosan, cellulose nanocrystals (CNC), cellulose nanofibrils (CNF) and polylactic-co-glycolic acid (PLGA); two inorganic EDNs including TiO 2 and SiO 2 ) at two dietary doses. We demonstrated that all six EDNs can alter the composition in the secretome with distinct patterns. Chitosan, followed by PLGA and SiO 2 , has shown the highest potency in inducing the secretome change with major pathways in tryptophan and indole metabolism, bile acid metabolism, tyrosine and phenol metabolism. Metabolomic alterations with clear dose response were observed in most EDNs. Overall, phenylalanine has been shown as the most sensitive metabolites, followed by bile acids such as chenodeoxycholic acid and cholic acid. Those metabolites might be served as the representative metabolites for the EDNs-gut bacteria interaction. Collectively, our studies have demonstrated the sensitivity and feasibility of using metabolomic signatures to understand and predict EDNs-gut microbiome interaction., 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.)

Microfluidic chips have emerged as a promising tool for sorting and enriching circulating tumor cells (CTCs) in blood, while the efficacy and purity of CTC sorting greatly depend on chip design. Herein, a novel cascaded phase-transfer microfluidic chip was developed for high-efficiency sorting, purification, release, and detection of MCF-7 cells (as a model CTC) in blood samples. MCF-7 cells were specifically captured by EpCAM aptamer-modified magnetic beads and then introduced into the designed cascaded phase-transfer microfluidic chip that consisted of three functional regions (sorting, purification, and release zone). In the sorting zone, the MCF-7 cells moved toward the inner wall of the channel and entered the purification zone for primary separation from white blood cells; in the purification zone, the MCF-7 cells were transferred to the phosphate-buffered saline flow under the interaction of Dean forces and central magnetic force, achieving high purification of MCF-7 cells from blood samples; in the release zone, MCF-7 cells were further transferred into the nuclease solution and fixed in groove by the strong magnetic force and hydrodynamic force, and the continuously flowing nuclease solution cleaved the aptamer on the trapped MCF-7 cells, causing gentle release of MCF-7 cells for subsequent inductively coupled plasma mass spectrometry (ICP-MS) detection or further cultivation. By measurement of the endogenous element Zn in the cells using ICP-MS for cell counting, an average cell recovery of 84% for MCF-7 cells was obtained in spiked blood samples. The developed method was applied in the analysis of real blood samples from healthy people and breast cancer patients, and CTCs were successfully detected in all tested patient samples (16/16). Additionally, the removal of the magnetic probes on the cell surface significantly improved cell viability up to 99.3%. Therefore, the developed cascaded phase-transfer microfluidic chip ICP-MS system possessed high integration for CTCs analysis with high cell viability, cell recovery, and purity, showing great advantages in early clinical cancer diagnosis.

Background: To evaluate the postoperative analgesic efficacy and safety of nerve block (NB) in patients undergoing breast surgery for cosmetic purposes., Methods: PubMed, Web of Science, Embase and Cochrane Libraries were searched from inception to September 2022, to identify all eligible randomized controlled trials (RCTs). Continuous data are presented as mean difference (MD) with 95% confidence intervals (CI), whereas dichotomous data are provided as odds ratios (OR) with 95% CI. This meta-analysis was performed in RevMan 5.4., Results: A total of 10 RCTs with 565 patients were meta-analyzed. Compared to the control group, the pain score of the NB group was significantly lower at postoperative 2, 3-4, 6-8, 12-16 and 24 h. Opioid consumption in the first postoperative 24 h was significantly lower in the NB group (MD = - 9.02, 95% CI - 14.29 to - 3.75, P < 0.05), I 2  = 95%). In addition, the NB group showed a prolonged time to first postoperative analgesic requirement (MD = 43.15, 95% CI 4.74-81.56, P < 0.05, I 2  = 96%), decreased incidence of additional postoperative analgesia (OR 0.14, 95% CI 0.07-0.28, P < 0.05, I 2  = 0%) and reduced incidence of postoperative nausea or vomiting (OR 0.33; 95% CI 0.22-0.48; P < 0.05; I 2  = 0%). There was no significant difference in operation duration between the two groups., Conclusions: Nerve block is an effective and safe option for postoperative analgesia after breast cosmetic surgery., Level of Evidence Ii: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 ., (© 2023. Springer Science+Business Media, LLC, part of Springer Nature and International Society of Aesthetic Plastic Surgery.)

Background: There is limited evidence on the safety of sodium-glucose co-transporter-2 inhibitor (SGLT2i) use in the real world of China. We conducted this two-center, retrospective study to assess the incidence rate and risk factors of Dapagliflozin-associated DK/DKA among patients with type 2 diabetes mellitus (T2DM) in China., Research Design and Methods: Patients with T2DM treated with Dapagliflozin in Shanghai General Hospital were included in this retrospective analysis. Univariate and multivariate logistic regression was performed, and odds ratio (OR) and 95% confidence interval (CI) were calculated to identify the influencing factors associated with the occurrence of DK/DKA., Results: A total of 1985 T2DM patients received Dapagliflozin for the first time were included. The prevalence of DK and DKA was 2.47% and 0.35%, respectively. Multivariate logistic regression identified age <45 years [OR = 2.99, 95% CI (1.45-6.17)], concomitant use of Acarbose [OR = 2.18, 95% CI (1.06-3.38)], Metformin [OR = 1.84, 95% CI (1.01-3.38)], and Insulin [OR = 1.93, 95% CI (1.02-3.66)] as participating factors for DK/DKA. The 1:4 matched subset sensitivity analysis further confirmed the risk factors of Dapagliflozin-associated DK/DKA., Conclusions: Age less than 45 years, concomitant use of Acarbose and insulin were risk factors for Dapagliflozin-associated DK/DKA. Clinicians should watch out for high-risk features among patients with SGLT2i prescription.

Liver fibrosis is a pathological condition characterized by replacement of normal liver tissue with scar tissue, and also the leading cause of liver-related death worldwide. During the treatment of liver fibrosis, in addition to antiviral therapy or removal of inducers, there remains a lack of specific and effective treatment strategies. For thousands of years, Chinese herbal medicines (CHMs) have been widely used to treat liver fibrosis in clinical setting. CHMs are effective for liver fibrosis, though its mechanisms of action are unclear. In recent years, many studies have attempted to determine the possible mechanisms of action of CHMs in treating liver fibrosis. There have been substantial improvements in the experimental investigation of CHMs which have greatly promoted the understanding of anti-liver fibrosis mechanisms. In this review, the role of CHMs in the treatment of liver fibrosis is described, based on studies over the past decade, which has addressed the various mechanisms and signaling pathways that mediate therapeutic efficacy. Among them, inhibition of stellate cell activation is identified as the most common mechanism. This article provides insights into the research direction of CHMs, in order to expand its clinical application range and improve its effectiveness., (Copyright © 2023 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.)

Dispersing metal-organic framework (MOF) solids in stable colloids is crucial for their availability and processibility. Herein, we report a crown ether surface coordination approach for functionalizing the surface-exposed metal sites of MOF particles with amphiphilic carboxylated crown ether (CE C ). The surface-bound crown ethers significantly improve MOF solvation without compromising the accessible voids. We demonstrate that CE C -coated MOFs exhibit exceptional colloidal dispersibility and stability in 11 distinct solvents and six polymer matrices with a wide range of polarities. The MOF-CE C can be instantaneously suspended in immiscible two-phase solvents as an effective phase-transfer catalyst and can form various uniform membranes with enhanced adsorption and separation performance, which highlights the effectiveness of crown ether coating., (© 2023 Wiley-VCH Verlag GmbH.)

Background: Nonsurgical chin augmentation using hyaluronic acid (HA) has become a common procedure in cosmetic practices. This is offered to patients that prefer a nonsurgical, temporary method to correcting underdeveloped or retruded chin and restoring the volume loss. This systematic review highlights the main HA injection technique and associated patient satisfaction and complications of chin augmentation to further guide practitioners., Methods: A systematic review was performed according to PRISMA guidelines. PubMed, Embase, and Web of Science were searched using the appropriate keywords. Data collected from each study included patient satisfaction and complications, in addition to injection protocol and technique., Results: A total of 1305 studies were found based on search criteria. After full-text screening for inclusion and exclusion criteria, 8 studies were included. A total of 917 patients underwent HA chin augmentation, with different injection protocols. Most patients were satisfied with the results, and there were only 2 relatively major complications reported. The most common adverse events were local responses at the injection sites (swelling, bruising, pain, redness, and itching). There were no reports of vascular complications., Conclusions: HA filler is an effective temporary method to correct chin retraction and absorption for chin augmentation, with a high degree of patient satisfaction and a low risk of severe complications., Level of Evidence Iii: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 ., (© 2023. Springer Science+Business Media, LLC, part of Springer Nature and International Society of Aesthetic Plastic Surgery.)

Gandouling tablets are used in a clinical agent for the treatment of hepatocellular degeneration; however, their chemical constituents have not been elucidated. Here, we screened and identified the chemical constituents of Gandouling tablets using ultra-high-performance liquid chromatography (UHPLC)-quadrupole time of flight/mass spectrometry. A method for the quality evaluation of Gandouling tablets was developed by combining the UHPLC fingerprints and the simultaneous quantitative analysis of multiple active ingredients. For fingerprint analysis, 20 shared peaks were identified to assess the similarities among the 10 batches of Gandouling tablets and the similarity was >0.9. The levels of nine representative active ingredients were simultaneously determined to ensure consistency in quality. A total of 99 chemical components were identified, including 18 alkaloids, 20 anthraquinones, 13 flavonoids, 11 phenolic acids, 9 polyphenols, 7 phenanthrenes, 5 sesquiterpenes, 3 curcuminoids, 2 lignans, 2 isoflavones, 2 dianthranones, and 7 other components. The retention times, molecular formulae, and secondary fragmentation information of these compounds were analyzed, and the cleavage pathways and characteristic fragments of some of the representative compounds were elucidated. This systematic analysis used to identify the chemical components of Gandouling tablets lays the foundation for its further quality control and research on their pharmacodynamic substances., (© 2023 Wiley-VCH GmbH.)

Background: Experimental studies suggested that per- and polyfluoroalkyl substances (PFAS) may have endocrine-disrupting effects. However, the epidemiological evidence on the associations of PFAS with female reproductive hormones is sparse and limited to perfluorooctanesulfonic acid (PFOS) and perfluorooctanoic acid (PFOA)., Objective: To evaluate effects of legacy and emerging PFAS alternatives on female reproductive hormones., Methods: A total of 433 reproductive-aged females were recruited from 2014 to 2016. Information on age, age at menarche, gravity, menstrual cycle, BMI, education, and income was obtained from medical records and questionnaires. Serum samples were collected for reproductive hormones, and plasma samples for PFAS measurement by ultraperformance liquid chromatography - tandem mass spectrometer (UPLC-MS/MS). Multiple linear regression and quantile g-computation (q-gcomp) were used to examine the associations of individual PFAS and their mixture with reproductive hormones., Results: Multiple linear regression analysis showed significant effects of certain PFAS on total testosterone (TT): adjusted estimate (β) for perfluoroheptanoic acid (PFHpA) was 0.57 (95% CI: 0.18, 0.97). Moreover, a positive association was detected between PFAS mixture and TT in the q-gcomp model. Higher concentrations of 6:2 chlorinated polyfluorinated ether sulfonic acid (6:2 Cl-PFESA) were associated with significantly lower prolactin level (β = -0.07, 95% CI: -0.14, -0.001)., Conclusion: Our study found that exposure to PFAS alternatives was associated with altered levels of reproductive hormones in women of childbearing age., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2023 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Osteoarthritis refers to a degenerative disease with joint pain as the main symptom, and it is caused by various factors, including fibrosis, chapping, ulcers, and loss of articular cartilage. Traditional treatments can only delay the progression of osteoarthritis, and patients may need joint replacement eventually. As a class of organic compound molecules weighing less than 1000 daltons, small molecule inhibitors can target proteins as the main components of most drugs clinically. Small molecule inhibitors for osteoarthritis are under constant research. In this regard, by reviewing relevant manuscripts, small molecule inhibitors targeting MMPs, ADAMTS, IL-1, TNF, WNT, NF-κB, and other proteins were reviewed. We summarized these small molecule inhibitors with different targets and discussed disease-modifying osteoarthritis drugs based on them. These small molecule inhibitors have good inhibitory effects on osteoarthritis, and this review will provide a reference for the treatment of osteoarthritis.

Polycyclic aromatic hydrocarbons (PAHs) are a group of environmental endocrine disruptors with known carcinogenic, reproductive, and developmental toxicity. Important knowledge gaps remain regarding the relationship between PAH exposure and unexplained recurrent spontaneous abortion (URSA). In the present study, twelve monohydroxylated polycyclic aromatic hydrocarbons (OH-PAHs) were measured in the urine of 413 URSA cases and 434 controls. The main OH-PAHs measured in this study were monohydroxy metabolites of naphthalene, followed by fluorene and phenanthrene. After the creatinine correction, the median concentration of urinary OH-PAHs in the control group (17.4 μg/g Creatinine) was higher than that in the case group (14.2 μg/g Creatinine). There was no positive relationship between PAH exposure and URSA using binary logistic regression analysis. Among 847 Chinese women of childbearing age, residential environment, type of drinking water, and education level were the influencing factors of PAH exposure. The health risk assessment showed that over 98% of women had a carcinogenic risk with carcinogenic risk values above the acceptable level (10 -6 ). Although this large-scale case-control study did not observe an association between PAH exposure and URSA, more attention should be paid to the high carcinogenic risk due to PAH exposure in women of reproductive age., 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 Inc. All rights reserved.)

Legacy and emerging per- and polyfluoroalkyl substances (PFAS) have attracted growing attention due to their potential adverse effects on humans. We developed a method to simultaneously determine thirty-three PFAS (legacy PFAS, precursors, and alternatives) in human plasma and serum using solid phase extraction coupled to ultra-performance liquid chromatography-tandem mass spectrometry (SPE-UPLC-MS/MS). The method yielded good linearity (>0.995) and excellent limits of detection (LODs) (0.0005~0.012 ng mL -1 in plasma and 0.002~0.016 ng mL -1 in serum). The relative recoveries ranged from 80.1 to 116%, with intra- and inter-day precision less than 14.3%. The robustness of this method has been tested continuously for 10 months (coefficients of variation <14.9%). Our method was successfully applied to the PFAS analysis of 42 real human plasma and serum samples collected from women. The proposed method is attractive for the biomonitoring of multi-class PFAS in human health risk assessment and epidemiological studies., (© 2022. Springer-Verlag GmbH Germany, part of Springer Nature.)

Baicalein (5,6,7-trihydroxyflavone) and wogonin (5,7-dihydroxy-8-methoxyflavone), as typical flavonoids isolated from Scutellaria baicalensis, are well important precursors in drug discovery which produce diverse therapeutically related applications in pharmacological practices. Researches in medicinal chemistry field have synthesized baicalein and wogonin derivatives with multiple medicinal properties including antitumor, central nervous system (CNS), anti-inflammatory, antiviral, antimicrobial and hypoglycemic activities. Simultaneously, SAR (Structure-Activity Relationship) analysis has been gradually possessed, along with a great deal of derivatives have been derived for potential targets. In this article, we comprehensively summarize the biological activities and SAR for baicalein and wogonin derivatives, along with the featuring bioactive molecules reported in patents, wishing to provide an overall retrospect and prospect on baicalein and wogonin analogues., 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 Masson SAS. All rights reserved.)

Numerous studies have examined the adverse health effects of perfluoroalkyl and polyfluoroalkyl substances (PFAS) but it remains unclear whether preconception exposure to PFAS affects couple fecundity. This prospective preconception cohort study with 936 Chinese couples aimed to comprehensively assess the effects of PFAS on couple fecundity [measured by the time to pregnancy (TTP)] and infertility (i.e., TTP > 12 menstrual cycles) with a focus on the effects of partner-specific exposure and joint-effects of couple-based exposure. Twenty-five PFAS were quantified in plasma from each partner, including seven branched isomers, two chlorinated polyfluoroalkyl ether sulfonic acids, four emerging PFAS replacements [i.e., 6:2 fluorotelomer phosphate diester (6:2 diPAP) and three short-chain alternatives: perfluoro-n-butanoicacid, perfluorobutane sulfonate and perfluoroheptanoic acid (PFHpA)]. Using a two-phase regression approach composed of elastic net regression and principal component analysis, we found that exposure to 6:2 diPAP and PFHpA rather than legacy PFAS in women and the couple-based exposure patterns characterized by high level of female 6:2 diPAP were significantly associated with reduced couple fecundity, which was independent of the adjustment of co-exposed PFAS homogenous from both partners. For example, a ln unit increase in female 6:2 diPAP was associated with 15 % [fecundity odds ratio (FOR) = 0.85, 95 %CI: 0.76, 0.96)] lower odds of couple fecundability (i.e., longer TTP) and 45 % increased risk of infertility [OR = 1.45 (95 %CI: 1.16, 1.81)], respectively. While most PFAS in men were not associated with couple fecundity, certain PFAS (e.g., perfluorohexane sulfonic acid) in men were negatively associated with infertility risk. However, the combined effects of PFAS mixture in couples were nonsignificant. Our findings suggest that PFAS in men and women may exert different impacts on couple fecundity. Preconception exposure to 6:2 diPAP and PFHpA in women may have the potential to impair couple fecundity., 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 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Previous studies on the association between exposure to per- and polyfluoroalkyl substances (PFAS) and sleep patterns in pregnant women are limited. This cohort study aims to assess the associations between PFAS and sleep quality in pregnant women. Of the 4127 women who participated in the Shanghai Birth Cohort, 3174, 3070, and 2887 women in their first, second, and third trimesters of gestation, respectively, were included in our analysis. Sleep measures were taken using the Pittsburgh Sleep Quality Index questionnaire. Ten PFAS were measured in blood samples collected in early pregnancy. We first evaluate the associations between individual PFAS and sleep quality in the three trimesters. Weighted quantile sum (WQS) regression models were performed to test the overall effect of the PFAS mixture on sleep quality during the three trimesters. Longitudinal analyses throughout pregnancy were performed with generalized estimating equation models. Furthermore, the effect of the PFAS mixture on longitudinal sleep patterns was examined using longitudinal latent class analyses combined with WQS models. The single pollutant analysis suggested that most PFAS were associated with increased sleep disturbance risk, lower sleep efficiency, and shorter sleep duration in the three trimesters. Similarly, the WQS models revealed a significant association between the PFAS mixtures and elevated sleep disturbance risk in pregnant women, with perfluorobutane sulfonate acting as the predominant risk factor. Additionally, the longitudinal analysis confirmed the effects of PFAS exposure on increased sleep disturbance over time. The PFAS mixture was positively associated with higher risks of poor sleep quality and sleep medicine use [adjusted odds ratio (aOR) = 1.10; 95 % confidence interval (95%CI): 1.01, 1.20; and aOR = 1.25 (95%CI: 1.04, 1.50) respectively] throughout the three trimesters. Our study suggests that PFAS may increase the risk of sleep disturbance in pregnant women. Further studies are needed to confirm our results and elucidate potential mechanisms., 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. Published by Elsevier B.V.)

Background/objectives: Multiple studies have examined the relationship between PFAS and semen quality, but none has explored the associations of PFAS mixture that includes emerging alternatives and branched isomers., Methods: 22 PFAS, including 10 linear legacy PFAS, 7 branched isomers, 3 short chain alternatives and 2 components of F53B [e.g., 6:2 chlorinated polyfluorinated ether sulfonate (Cl-PFESA)] were quantified in blood plasma among 740 healthy men. Five semen quality parameters (i.e., volume, count, concentration, total motility and progressive rate) were assessed. Multiple linear regression and three multiple pollutant models (i.e., adaptive elastic net regression, quantile based g-computation, and XGBoost method) were used to assess the associations of individual PFAS and PFAS mixture with semen quality and the potential interactive effects among congeners., Results: After adjusting for selected confounders, perfluorobutane sulfonate (PFBS) and perfluorohexane sulfonate (PFHxS) presented significant and negative associations with sperm count [β AENET = -0.09 (95%CI: -0.14, -0.03) for PFBS, and -0.16 (95%CI: -0.25, -0.07) for PFHxS] and sperm concentration [-0.04 (95%CI: -0.08, -0.001) for PFBS and -0.11 (95%CI: -0.17, -0.04) for PFHxS]. 6:2 Cl-PFESA showed negative associations with total motility (-2.33, 95%CI: -3.80, -0.86) and progressive rate (-1.46, 95%CI: -2.79, -0.12). But perfluoroheptanesulfonic acid (PFHpS) was positively associated with sperm count and concentration. These associations were supported by the importance assessment of these four congeners in XGBoost analyses. However, no associations were found between PFAS mixture or branched isomers and semen quality; nor were there significant interactions among PFAS congeners., Conclusions: In the current cross-sectional study, we found that two emerging PFAS replacements (i.e., 6:2 Cl-PFESA and PFBS) and PFHxS exposure were associated with reduced semen concentration, total sperm count and motility in men. Meanwhile, significant positive associations between PFHpS and sperm count and concentration were also observed. But there were no consistent associations between PFAS mixture, branched isomers and semen 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 results report or interpretation in this work., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Humans are widely exposed to per- and polyfluoroalkyl substances (PFAS). As fetal stage is a critical window for neurodevelopment, it is important to know if in utero exposure to PFAS affects fetal neurodevelopment. However, previous human studies are both limited and inconsistent., Objectives: To investigate the relationship between PFAS exposure during early pregnancy and the neurodevelopmental status at 2 years of age in a prospective cohort study., Methods: We measured 10 PFAS in maternal plasma samples collected prior to 16 weeks of gestation in the Shanghai Birth Cohort Study between 2013 and 2016. Childhood neurodevelopment was assessed at 2 years of age using the Bayley Scales of Infant and Toddler Development-Third Edition (BSID-III). Associations with domain specific scores for individual PFAS were assessed by multiple linear regression and binary logistic regression when scores were dichotomized. Quantile-based g-computation was used to estimate the joint effects of PFAS mixture., Results: A total of 2257 mother-child pairs who had both PFAS and BSID measurements were included in our analyses. The means and standard deviations of comprehensive scores were 115 ± 22, 96 ± 15 and 108 ± 15 for cognition, language, and motor, respectively. In multiple linear regressions, we observed significant negative associations of perfluorooctane sulfonate (PFOS), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDeA), perfluoroundecanoic acid (PFUnDA) with cognitive scores; PFNA, PFDeA, PFUnDA and perfluorohexanesulfonate (PFHxS) negatively with language scores; and PFNA and PFUnDA negatively with motor scores. Quantile-based g-computation showed that PFAS mixture was significantly associated with decreased cognitive and language scores, with an estimated β of -2.1 [95% confidence interval (CI): -3.5, -0.7)] and -2.0 (95% CI: -2.9, -1.0) per one quartile increase in PFAS mixture for cognitive and language domains, respectively. PFAS mixture was associated with increased odds of low cognition (adjusted odds ratio [OR] = 1.3, 95% CI:1.0, 1.6) and language scores (OR = 1.2, 95% CI: 1.1, 1.3)., Conclusions: PFAS exposure during early pregnancy was significantly associated with the adverse neurodevelopmental status at 2 years of age, which raises a serious public health concern., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

This study investigated the potential active components against cyclooxygenase-2(COX-2) from Trachelospermi Caulisetfolium and explored the pharmacodynamic material basis.A pharmacophore-based virtual screening method was adopted to establish a COX-2 ligands-based HipHop pharmacophore model on the basis of the information on compounds with COX-2 inhibitory activity reported in published research articles.The reported components in Trachelospermi Caulisetfolium were collected to establish the compound library and matched with the pharmacophores.Subsequently, the matched small molecule compounds underwent molecular docking with COX-2 targets(PDB ID: 3 LN1), and the interaction of potential active monomers and COX-2 was further explored by molecular dynamics.The antiepileptic effect of active monomer arctigenin(15) was determined based on the pentylenetetrazole(PTZ)-induced seizure model, and its modulatory effect on the COX-2 level was evaluated.A compound library containing 118 chemical constituents in Trachelospermi Caulisetfolium was established by literature retrieval.The preferred pharmacophore 04 was selected through test set verification for virtual screening of the compound library of Trachelospermi Caulisetfolium.After matching, six potential constituents with COX-2 inhibitory activity were obtained.The interaction of five compounds with COX-2 and COX-1 was analyzed by molecular docking, and 10 ns molecular dynamics was performed on two compounds.Compound 15 could prolong the latent time of PTZ-induced seizures at medium and high doses, improve the anxiety-and depression-like behaviors induced by PTZ, reduce the expression level of COX-2, and decrease the number of COX-2 immuno-posi-tive cells in the hippocampal CA1 region.The results showed that it was reasonable to investigate the components in Trachelospermi Caulisetfolium with COX-2 inhibitory activity based on virtual screening and activity evaluation.

Emerging per- and polyfluoroalkyl substances (PFAS) alternatives are increasingly used in daily life. Although legacy PFAS have been associated with miscarriage in previous studies, it remains unknown whether exposure to emerging and legacy PFAS has any impact on the risk of unexplained recurrent spontaneous abortion (URSA). We conducted a case-control study with 464 URSA cases who had at least 2 unexplained miscarriages and 440 normal controls who had at least one normal livebirth. Concentrations of 21 PFAS in plasma, including three emerging PFAS alternatives, eight linear and branched PFAS isomers, four short-chain PFAS, and six legacy PFAS, were measured by ultra-performance liquid chromatography coupled with a tandem mass spectrometry (UPLC-MS/MS). Multiple logistic regression was applied to evaluate the relationship between PFAS and URSA risk. Perfluorooctanoic acid (PFOA, median: 6.18 ng/mL), perfluorooctane sulfonate (PFOS, median: 4.10 ng/mL), and 6:2 chlorinated perfluoroalkyl ether sulfonic acid (6:2 Cl-PFESA, median: 2.27 ng/mL) were the predominant PFAS in the controls. Exposure to 6:2 Cl-PFESA [adjusted odds ratio (aOR) = 1.18 (95% CI: 1.00, 1.39)] and hexafluoropropylene oxide dimer acid (HFPO-DA) [aOR = 1.35 (95% CI: 1.15, 1.59)] were significantly associated with increased risks of URSA. Women with older age (>30 years old) had a stronger association between PFAS and URSA. Our results suggest that emerging PFAS alternatives may be an important risk factor for URSA., (Copyright © 2022. Published by Elsevier Inc.)

6:2 polyfluoroalkyl phosphate diester (6:2 diPAP) has been demonstrated to disrupt reproductive endocrine functions using experimental studies. However, evidence from humans is not available yet. This cross-sectional study aims to assess the relationship between 6:2 diPAP exposure and the testicular function among adult men. A total of 902 men seeking preconception care were included. Plasma 6:2 diPAP concentrations were determined, while the testicular function was assessed via semen quality and reproductive hormones in serum. The association was assessed by multiple linear regression. Stratified analyses by age and body mass index (BMI) were conducted to assess the potential effect modification by these two variables. Regression analyses revealed that 6:2 diPAP exposure was significantly inversely associated with androgens [i.e., total testosterone (TT) and free androgen index (FAI)], markers of testosterone production potential [i.e., TT/luteinizing hormone (LH) and FAI/LH], estradiol, and insulin-like factor 3, a biomarker of Leydig cell function. These associations were robust in sensitivity analyses. However, age and BMI did not modify these associations, and no association was observed between 6:2 diPAP and semen quality. Our study suggests that exposure to 6:2 diPAP may inhibit androgen synthesis and impair Leydig cell function in adult men.

Background: The widespread use of antibiotics has left extensive residues in the environment and food. Antibiotics can accumulate in human body. As the potential health risks of antibiotic exposure in children are of a great concern in recent years, our study aimed to describe the status of antibiotic exposure in primary school students in Shanghai, China, and to explore the relationships of dietary patterns with internal antibiotic levels., Methods: The Shanghai Children's Health, Education, and Lifestyle Evaluation (SCHEDULE) Survey was a cross-sectional study with a staged, cluster random sample of all primary school students in Shanghai, China. In the present study, we randomly selected 2199 children aged 6-12 years old. A total of 10 antibiotics in urine samples were measured by liquid chromatography-tandem mass spectrometry. Multivariable survey logistic regression models were used to investigate dietary patterns associated with detection rates of antibiotics., Results: The detection rates of individual antibiotics ranged from 4.3% to 30.7%. 68.7% of children were exposed to at least one antibiotic. There was a significant difference in child exposure to overall antibiotics by residential locations (60.9% in urban vs. 71.1% in suburban areas). Principal component analyses suggested that higher unhealthy dietary pattern scores were significantly associated with increased detection rates of tetracyclines [1.27 (95% CI: 1.18, 1.38)] and sulfonamides [1.20 (95% CI: 1.05, 1.36)]. In addition, 9.05% of children had a hazard index (HI) value greater than 1, which was mainly contributed by ciprofloxacin., Conclusions: School-age children were widely exposed to antibiotics in Shanghai. Unhealthy diet was associated with a higher level of antibiotic exposure., 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.)

Per- and polyfluoroalkyl substances (PFAS) are widespread chemicals. Legacy PFAS have been phased out of production in most developed countries and emerging PFAS (short-chain PFAS and polyfluorinated compounds) are used as legacy PFAS alternatives. The effect of legacy and emerging PFAS on cytokine homeostasis in human remains poorly understood. This study aimed to evaluate the associations between legacy and emerging PFAS and cytokine profiles, and identify the main contributors to the disturbance of cytokine homeostasis. We quantified 21 PFAS in 198 Chinese women of childbearing age from 2015 to 2016. 13 cytokines were measured using the Meso Scale Discovery U-PLEX and V-PLEX platforms. The associations between PFAS exposure and cytokine levels were assessed using multiple linear regression (single-exposure), and Bayesian kernel machine regression (BKMR) models (PFAS mixture exposure). In single PFAS models, legacy and alternative PFAS were positively associated with Th1 and Treg cytokines, and negatively associated with Th2 and Th17 cytokines. For instance, each ln-unit increase in 6:2 chlorinated perfluoroalkyl ether sulfonic acid (6:2 Cl-PFESA), perfluorooctanoic acid (PFOA), and perfluorooctane sulfonate (PFOS) was associated with a decrease in IL-10 by - 0.228 (95% CI: - 0.336, - 0.120), - 0.153 (95% CI: - 0.277, - 0.030), and - 0.174 (95% CI: - 0.339, - 0.010), respectively. The BKMR model showed a significantly positive association of PFAS mixture with TGF-β and a negative association with IL-10. Overall, these results indicate that both legacy and emerging PFAS may affect the homeostasis of cytokines., (© 2022. The Author(s).)

Gandou decoction (GDD) is a classic prescription for the treatment of hepatolenticular degeneration (HLD) in China; however, the liver-protecting mechanism of this prescription needs further evaluation. In the present study, we explored the protective mechanisms of GDD in a copper-laden HLD model using integrated pharmacology and cellular metabolomics in vitro . The results revealed that GDD could significantly promote copper excretion in copper-laden HLD model cells and improve the ultrastructural changes in hepatocytes. In addition, GDD could decrease the extent of lipid peroxidation, levels of reactive oxygen species, and the release rate of lactate dehydrogenase while increasing the activity of superoxide dismutase and the ratio of glutathione to oxidized glutathione in the copper-laden HLD model cells. On conducting statistical analysis of significant metabolic changes, 47 biomarkers and 30 related metabolic pathways were screened as pharmacological reactions induced by GDD in HLD model cells. d-glutamate and d-glutamine metabolic pathways showed the highest importance and significance among the 30 metabolic pathways, and the differential expression levels of the glutamine synthetase (GS) and the renal type and liver type GLS (GLS1 and GLS2) proteins were verified by Western blotting. Collectively, our data established the underlying mechanism of GDD therapy, such as the promotion of copper excretion and improvement in oxidative stress by regulating the expressions of GS, GLS1, and GLS2 protein to protect hepatocytes from injury., 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 Yin, Nian, Wang, Wu, Wu, Zhao, Cao, Wu and Zhou.)

Osteoporosis is a common metabolic bone disease, and treatment is required for the prevention of low bone mass, deterioration of microstructural bone tissue, and fragility fractures. Osteoporosis therapy includes calcium, vitamin D, and drugs with antiresorptive or anabolic action on the bone. Therapy for osteoporosis does not include taking non-steroidal anti-inflammatory drugs (NSAID), but pain associated with osteoporotic fractures can be treated by taking non-steroidal anti-inflammatory drugs (NSAID). Recently, polysaccharides extracted from medicinal herbs and edible substances (PsMHES) have attracted attention on account of their safety and promising anti-osteoporosis effects, whereas a systematic review about their potential in anti-osteoporosis is vacant to date. Herein, we reviewed the recent progress of PsMHES with anti-osteoporosis activities, looking to introduce the advances in the various pharmacological mechanisms and targets involved in the anti-osteoporosis effects, extraction methods, main mechanism involved in Wnt/[Formula: see text]-catenin pathways and RANKL (Receptor Activator for NF[Formula: see text]B ligand or TNFSF25) pathways, and Structure-Activity Relationships (SAR) analysis of PsMHES. Typical herbs like Achyranthes bidentate and Morinda officinalis used for the treatment of osteoporosis are introduced; their traditional uses in traditional Chinese medicine (TCM) are discussed in this paper as well. This review will help to the recognition of the value of PsMHES in anti-osteoporosis and provide guidance for the research and development of new anti-osteoporosis agents in clinic.

Background: Humans are widely exposed to environmental perfluoroalkyl substances (PFAS), which may affect glucose homeostasis. However, research linking PFAS exposure to glucose homeostasis during pregnancy is limited and the results were inconsistent. We aimed to investigate the association between PFAS exposure and glucose homeostasis in pregnancy in a large prospective cohort., Methods: A total of 2747 pregnant women who participated in the Shanghai Birth Cohort, had blood samples in early pregnancy and completed a 75 g oral glucose tolerance test (OGTT) at 24-28 gestational weeks were included. 10 PFAS were determined by high-performance liquid chromatography/tandem mass spectrometry (HPLC/MS-MS) in the plasma samples in early pregnancy. Logistic regression was used to explore the associations between PFAS concentrations and gestational diabetes mellitus (GDM), while multiple linear regression was used to model the associations between PFAS and OGTT fasting, 1-h and 2-h glucose levels. Potential confounders were adjusted. Bayesian kernel machine regression (BKMR) and a quantile-based g-computation approach (qgcomp) were employed to explore the joint and independent effects of PFAS on glucose homeostasis., Results: The incidence of GDM was 11.8%. One log-unit increment in plasma concentrations in early pregnancy was associated with an increased risk of GDM for perfluorobutane sulfonate (PFBS) (adjusted odd ratio (aOR) = 1.23, 95% confidence interval (95% CI): 1.05, 1.44) and perfluoroheptanoic acid (PFHpA) (aOR = 1.25, 95% CI: 1.07, 1.46). Perfluorooctane sulfonic acid (PFOS), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), perfluorohexanesulfonate (PFHxS) and PFHpA were positively correlated with 1-h and 2-h glucose levels. Results of the mixed exposure model showed that the joint effects of PFAS were significantly associated with abnormal glucose homeostasis; In the BKMR model, PFAS mixture exposure was positively associated with the GDM incidence, 1-h and 2-h glucose levels and negatively correlated with FBG level. A similar trend could be observed in qgcomp and the positive correlation between PFAS and 2-h glucose level was significant (β = 0.12, 95% CI: 0.04, 0.20). PFOS, PFNA and PFHpA may be the main contributors after controlling for other PFAS congeners. PFOS was significantly correlated with GDM incidence and 2-h glucose level, and PFHpA was significantly associated with FBG and 2-h glucose levels. The above associations were more prominent among women with a normal prepregnant BMI., Conclusions: Environmental exposure to PFAS may affect glucose homeostasis in pregnancy and increase the risk of GDM, especially in normal weight women., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Bisphenol F (BPF) and bisphenol S (BPS) are increasingly used as bisphenol A (BPA) substitutes in consumer products. Little is known about the effects of BPA substitutes on reproductive endocrine function in children and adolescents. Thus, we conducted a cross-sectional study to examine the associations of BPA, BPF, and BPS with sex steroid hormones among 6-19-year old participants. Included were 1317 participants with information on BPA, BPF, BPS, and serum sex hormones [total testosterone (TT), estradiol (E 2 ), and sex hormone binding globulin (SHBG)]. Multiple linear regression accounting for complex survey design was used to assess the association between bisphenols and sex hormones by sex-age groups. Exposure-response (ER) relationships were examined via restricted cubic splines. Significant association with BPF or BPS was sporadic, but BPA presented inverse association with the free androgen index (FAI, calculated as the ratio of TT to SHBG) and E 2 and positive association with SHBG and TT/E 2 in female adolescents. Further exploration of ER relationships showed that BPA (P for non-linearity = 0.03), BPF (P for non-linearity = 0.005), and BPS (P for non-linearity = 0.08) had a U-shaped relationship with FAI among female adolescents. Additionally, an inverse U-shaped curve was observed for BPA (P for non-linearity = 0.03), BPS (P for non-linearity = 0.01), and BPF (P for non-linearity = 0.01) with SHBG. The associations were virtually nonsignificant among males. Our study demonstrated that BPS and BPF may possess similar endocrine interrupting abilities as BPA., (Copyright © 2021 Elsevier Ltd. All rights reserved.)