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Yap-Hang Chan,1 Michael Cheong Ngai,2 Yan Chen,1,3 Mei-Zhen Wu,1 Yu-Juan Yu,1 Zhe Zhen,1 Kevin Lai,1 Ho-Yin Chung,4 Chak-Sing Lau,4 Hung-Fat Tse,1,3 Kai-Hang Yiu1,3 1Cardiology Division, Department of Medicine, Queen Mary Hospital, University of Hong Kong, Hong Kong, Special Administrative Regions, People’s Republic of China; 2Division of Hematology, Department of Medicine, Queen Mary Hospital, University of Hong Kong, Hong Kong, Special Administrative Regions, People’s Republic of China; 3Cardiology Division, Department of Medicine, The University of Hong Kong Shenzhen Hospital, Shenzhen, People’s Republic of China; 4Division of Rheumatology, Department of Medicine, Queen Mary Hospital, University of Hong Kong, Hong Kong, Special Administrative Regions, People’s Republic of ChinaCorrespondence: Kai-Hang Yiu, Cardiology Division, Department of Medicine, The University of Hong Kong-Shenzhen Hospital, 1 Haiyuan 1st Road, Futian District, Shenzhen, 518053, Guangdong, People’s Republic of China, Tel +852 22553633, Fax +852 28186304, Email khkyiu@hku.hkBackground and Aim: Rheumatoid arthritis is associated with both abnormal bone metabolism and accelerated vascular aging but a mechanistic link was lacking. This study aims to investigate the role of osteocalcin (OCN)-expressing circulating endothelial progenitor cells (EPCs) in vascular aging, as determined by arterial calcifications in rheumatoid arthritis.Methods: We performed flow cytometry studies in 145 consecutive patients with rheumatoid arthritis to determine osteogenic circulating levels of OCN-positive (OCN+) CD34+KDR+ and OCN+CD34+ versus conventional early EPC CD34+CD133+KDR+. Total calcium load of the thoracic aorta (ascending plus descending) and the carotid arteries were assessed by non-contrast computed tomography (CT) and contrast CT angiography.Results: Osteogenic EPCs OCN+CD34+KDR+ (P = 0.002) and OCN+CD34+ (P = 0.001), together with clinical parameters of age, history of hypertension, systolic blood pressure, serum levels of triglycerides, HbA1c and creatinine, use of leflunomide and brachial-ankle pulse-wave velocity (all P < 0.05), were associated with the clustered presence of aortic and carotid calcification. Multivariable analyses revealed that circulating OCN+CD34+KDR+ (B = 14.4 [95% CI 4.0 to 24.8], P = 0.007) and OCN+CD34+ (B = 9.6 [95% CI 4.9 to 14.3], P < 0.001) remained independently associated with increased aortic calcium load. OCN+CD34+ EPC (B = 0.8 [95% CI 0.1 to 1.5], P = 0.023), but not OCN+CD34+KDR+ EPC (B = 1.2 [95% CI − 0.2 to 2.6], P = 0.09), was further independently associated with carotid calcium load. In comparison, conventional early EPC CD34+CD133+KDR+ had no significant association with aortic or carotid calcium load (P = 0.46 and 0.88, respectively).Conclusion: Circulating level of osteogenic EPC is associated with increased vascular aging in terms of calcification of the large arteries in patients with rheumatoid arthritis. The findings may suggest a role of the bone-vascular axis underlying vascular aging in rheumatic diseases. Further research is needed to characterize the mechanistic links and basis of these observations.Keywords: osteocalcin, endothelial progenitor cells, vascular aging, rheumatoid arthritis

Ya-Jie Yu,1,* Rong-Bin Liang,1,* Qi-Chen Yang,2,* Qian-Min Ge,1 Qiu-Yu Li,1 Biao Li,1 Wen-Qing Shi,1 Yi Shao1 1Department of Ophthalmology, The First Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi, People’s Republic of China; 2Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong 999077, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yi Shao Tel/ Fax +86 791-88692520Email freebee99@163.comObjective: Previous studies demonstrated that myopia could result in alterations of brain activity in specific areas. However, whether the visual function could improve by Lasik surgery, with the brain activity alterations also change, is still unknown. Here, we intended to use the amplitude of low-frequency fluctuation (ALFF) technique to investigate the intrinsic brain activity changes in pre-Lasik (PRL) and post-Lasik (POL) patients.Methods: A total of 15 patients with myopia (nine male and six female) were recruited in our study, who were matched according to age, weight, and height. These patients comprised both the PRL and POL groups, which is self-controlled. The patients all underwent resting-state functional magnetic resonance imaging (MRI), and the spontaneous brain activity changes were recorded by the ALFF technique. The data were recorded and arranged in the receiver operating characteristic (ROC) curve, which presented how intrinsic activities altered in different brain regions. Moreover, by Graphpad prism 8, we can analyze the linear correlation between HADS (Hospital Anxiety and Depression Scale) and ALFF values as well.Results: Differences in ALFF values existed in brain regions between the same patient before and after the Lasik operation. The regions with increased ALFF values after Lasik surgery were the left parahippocampal gyrus, cerebellar vermis, and left posterior cingulate cortex. The regions with decreased ALFF values after Lasik surgery were the left supramarginal gyrus and right trigonometric inferior frontal gyrus.Conclusion: We demonstrated significant fluctuations of ALFF values in specific brain areas between the same patients before and after the Lasik surgery. The altered ALFF values reflected the hyperactivity or hypoactivity of the specific brain areas, which may help predict the recovery level of patients’ vision after Lasik surgery. Furthermore, based on the experimental results that presented significant activity alterations in specific brian regions, patients could be speculated equipped with a better visual function.Keywords: myopia, Lasik, resting-state functional MRI, amplitude of low-frequency fluctuation

Atmospheric monitoring studies reveal substantial health risks from exposure to volatile organic compounds (VOCs) for workers and nearby children in e-waste recycling areas (ERA), yet internal exposure risks are seldom examined. To address this, we developed a method to simultaneously analyze 12 urinary VOC metabolites (mVOCs) and oxidative damage biomarkers (ODBs) in workers and children from ERA and general adults from control areas using ultrahigh performance liquid chromatography coupled with quadrupole/orbitrap high-resolution mass spectrometry (UPLC-Orbitrap-HRMS). The results showed that e-waste workers exhibited significantly higher levels of VOC exposure and ODBs than e-waste children and control adults. Exceeding 91.1 %, 69.1 %, 20.8 %, 19.7 %, and 3.26 % of e-waste workers faced non-carcinogenic risk from exposure to acrolein, acrylonitrile, acrylamide, 1,3-butadiene, and 1,2-dichloroethane, respectively. The weighted quantile sum, quantile g-computation, and Bayesian kernel machine regression models consistently indicated significant positive associations between these VOC mixtures and cholesterol ODB levels (i.e., glycocholic acid, cholic acid, and glycochenodeoxycholic acid), highlighting the necessity for improved protective measures for occupational workers. Interestingly, cholesterol ODBs significantly mediated the association between VOCs exposure and nucleic acid ODBs, accounting for 12.0-26.0 % of the association with 8-hydroxy-2'-deoxyguanosine (an oxidative DNA damage biomarker) and 25.4-53.4 % with 8-hydroxyguanosine (an oxidative RNA damage biomarker). This suggests that cholesterol ODBs potentially serve as better indicators of health risks from VOC exposure than nucleic acid ODBs. Additionally, the combination of mVOCs and ODBs (Mean AUC: 0.906, ACC: 0.821) as exposure fingerprints outperformed either mVOCs (Mean AUC: 0.878, ACC: 0.802) or ODBs (Mean AUC: 0.843, ACC: 0.768) alone in predicting the presence of e-waste pollution, underscoring the importance of integrating exposure and effect biomarker fingerprints to accurately capture e-waste pollution characteristic. Our findings offer a novel approach for screening e-waste pollution in unknow e-waste recycling sites and provide a foundation for developing high-precision prediction models for other polluting industries., Competing Interests: Declaration of competing interest The authors declare that they have no known competing commercial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The emergence of nanogenerators, which have the ability to capture mechanical energy from the environment and to collect and transmit tiny energy, is rapidly becoming a hot research topic. The performance of electrode materials is the key to the efficiency of nanogenerators. Covalent organic skeletons (COFs), a class of crystalline organic porous materials with the advantages of large specific surface area, high porosity, tunable structure, and flexible tailorability, have very significant advantages in being used as nanogenerator materials. In this paper, we synthesised two COF materials to investigate the effect of the introduction of active metals on the friction power generation performance of COFs without changing their topology, COF-2 containing zinc ions is capable of generating a short-circuit current of 107.5 µA during friction. The porous structure increases the effective contact area to form a larger charge density, and the introduction of metal ions can accelerate the charge separation and transport. The two bidirectional synergistic effects of the materials significantly improve the output performance of the nanogenerator, and a simple and efficient method is explored for the enhancement of the output performance of COF-based triboelectric nanogenerators., (© 2024. The Author(s).)

Heavy metal pollution from informal e-waste recycling may adversely affect child growth. However, the potential toxic mechanisms from a population perspective remain unknown. Herein, 18 hair heavy metals, urinary metabolomics, and three child growth indices [i.e., weight-for-age Z-score (WAZ), height-for-age Z-score (HAZ), and BMI Z-score (BMIZ)] were measured in children from e-waste recycling (ER, N = 426) and control areas (CR, N = 247). We examined longitudinal changes in heavy metal exposure and child growth after e-waste control to further elucidate causal relationships. Results showed that children in regulated ER site were still exposed to higher levels of several heavy metals and experienced poorer growth compared to those in control areas. Elevated exposure to heavy metals like tin, antimony, lead, cadmium, and cobalt correlated with poor child growth, particularly affecting girls and younger children. Tin, rather than traditionally concerning heavy metals, exhibited the most crucial role in driving the adverse effects of metal mixtures on child growth. Reducing heavy metal exposure through e-waste control could notably improve child growth, confirming the causal relationship between heavy metal exposure and poor child growth and underscoring the health benefits of e-waste regulation. Our research identified the roles of steroid biosynthesis, folate biosynthesis, amino acid metabolism, and purine metabolism in mediating the effects of metal exposure on child growth. Testosterone glucuronide, riboflavin, folic acid, xanthosine, and xanthine emerged as key mediators, potentially serving as metabolic signatures of heavy metal exposure. These findings illuminate the toxic mechanisms underlying poor child growth resulted from heavy metal exposure, offering important insights from a population-based perspective. In addition to lead and cadmium, monitoring and regulating tin and antimony are crucial to mitigate their negative impact on child growth in e-waste recycling areas., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Bacteria, especially drug-resistant strains, can quickly cause wound infections, leading to delayed healing and fatal risk in clinics. With the growing need for alternative antibacterial approaches that rely less on antibiotics or eliminate their use altogether, a novel antibacterial hydrogel named Ovtgel is developed. Ovtgel is formulated by chemically crosslinking thiol-modified ovotransferrin (Ovt), a member of the transferrin family found in egg white, with olefin-modified agarose through thiol-ene click chemistry. Ovt is designed to sequester ferric ions essential for bacterial survival and protect wound tissues from damages caused by the reactive oxygen species (ROS) generated in Fenton reactions. Experimental data have shown that Ovtgel significantly enhances wound healing by inhibiting bacterial growth and shielding tissues from ROS-induced harms. Unlike traditional antibiotics, Ovtgel targets essential trace elements required for bacterial survival in the host environment, preventing the development of drug resistance in pathogenic bacteria. Ovtgel exhibits excellent biocompatibility due to the homology of Ovt to mammalian transferrin. This hydrogel has the potential to serve as an effective antibiotic-free solution for combating bacterial infections., (© 2024 Wiley‐VCH GmbH.)

Objective: Glioma is a central nervous system tumor arising from glial cells. Despite significant advances in diagnosis and treatment, most patients with high-grade gliomas have a poor prognosis. Many studies have shown that long noncoding RNAs (lncRNAs) may play important roles in the development, progression and treatment of many tumors, including gliomas. Molecularly targeted therapy may be a new direction for the adjuvant treatment of glioma. Therefore, we hope that by studying differentially expressed lncRNAs (DElncRNAs) in glioma, we can discover lncRNAs that can serve as biomarkers for glioma and provide better therapeutic modalities for glioma patients., Methods: First, the expression of lncRNAs in 5 normal brain (NB) tissues and 10 glioma tissues was examined by RNA sequencing (RNA-seq). Next, we performed Kaplan-Meier analysis of data from The Cancer Genome Atlas (TCGA) database to assess the prognostic value of these variables. Finally, functional analysis of the DElncRNAs was performed by means of Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis., Results: RNA sequencing analysis revealed 85 upregulated miRNAs and 71 downregulated lncRNAs in low-grade glioma (LGG) and 50 upregulated lncRNAs and 70 downregulated lncRNAs in glioblastoma (GBM). Among them, AL355974.3 was the most upregulated lncRNA. LINC00632 was the most downregulated lncRNA. Second, LGG patients with higher AL355974.3 expression had worse overall survival according to Kaplan-Meier analysis of the TCGA database. Finally, bioinformatics analysis revealed that the target genes of these DElncRNAs were enriched in various biological processes and signaling pathways, such as cell metabolic and developmental processes., Conclusion: Our findings provide evidence that AL355974.3 may be a new biomarker for glioma., (© 2024. Huazhong University of Science and Technology.)

One bacterial strain, designated as C22-A2 T , was isolated from Lake LungmuCo in Tibet. Cells of strain C22-A2 T were long rod-shaped, Gram-stain-negative, non-spore-forming, with positive catalase and oxidase activity. Optimal growth occurred at 20-25 °C, pH 8.0 and with 3.0-7.0% (w/v) NaCl. Phylogenetic analysis of 16S rRNA gene and whole genome sequences revealed that strain C22-A2 T belonged to the genus Virgibacillus , showing the highest 16S rRNA gene similarity to Virgibacillus halodenitrificans DSM 10037 T (97.6%). The average nucleotide identity values between strain C22-A2 T and the type strains of related species in the genus Virgibacillus were less than 74.4% and the digital DNA-DNA hybridization values were less than 20.2%, both below the species delineation thresholds of 95 and 70% respectively. The genome analysis revealed that strain C22-A2 T harboured genes responsible for osmotic and oxidative stress, enabling it to adapt to its surrounding environment. In terms of biochemical and physiological characteristics, strain C22-A2 T shared similar characteristics with the genus Virgibacillus, including the predominant cellular fatty acid anteiso-C 15 : 0 , the major respiratory quinone MK-7, as well as the polar lipids phosphatidylglycerol and diphosphatidylglycerol. Based on the comprehensive analysis of phylogenetic, phylogenomic, morphological, physiological and biochemical characteristics, strain C22-A2 T is proposed to represent a novel species of the genus Virgibacillus , named as Virgibacillus tibetensis sp. nov. (=CGMCC 1.19202 T =KCTC 43426 T ).

Ethnopharmacological Relevance: Flos Trollii (FT) is the dried flower of Trollius Chinensis Bunge of Ranunculaceae with the pharmacological properties of anti-inflammatory, antibacterial, antiviral, anti-oxidative. The herb FT is not only a traditional Chinese medicine (TCM) but also an extensively utilized ethnic medicine, employed by diverse ethnic groups including Mongolian, Tibetan, and Kazakh., Aim of Study: FT was taken as an example to construct a strategy of quality markers (Q-markers) identification based on effect, property flavor material basis, and rapid quantitative evaluation using near-infrared (NIR) spectroscopy and chemometric methods of TCM., Materials and Methods: Initially, the anti-inflammatory efficacy of FT from three places of origin was evaluated using the RAW264.7-cell inflammatory model, and the bitter property flavor was characterized using an electronic tongue. The high-performance liquid chromatography(HPLC) fingerprint of FT was generated, and the quality of FT from different origins was evaluated employing chemometrics. Next, potential anti-inflammatory and bitter property flavor compounds were screened utilizing a fingerprinting-effect relationship and fingerprinting-property flavor relationship model using partial least squares regression (PLSR). The Q-markers of the FT were confirmed based on the testability principle. Then, a swift, uncomplicated, and precise Q-marker content of the FT prediction model was developed by adopting NIR., Results: The main common fingerprinting peaks affecting FT's efficacy and property flavor were screened. Five of these compounds, 2″-O-beta-L-galactopyranosylorientin, orientin, vitexin, veratric acid, and isoquercitrin, characterized using HPLC and ultra-high performance liquid chromatography-high resolution mass spectrometry (UHPLC-HRMS), could be regarded as Q-markers of FT. Q-marker content of the FT prediction model developed adopting NIR spectroscopy was rapid and effective., Conclusion: According to the strategy proposed in this study, a quantitative NIR spectroscopic method to identify Q-markers could be a tool to improve the QC efficiency of TCM., Competing Interests: Declaration of competing interest The authors declared that they have no conflicts of interest to this work. We declare that we do not have any commercial or associative interest that represents a conflict of interest in connection with the work submitted., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Hypertension is prevalent in e-waste recycling areas, and elevated blood pressure in children significantly increases the risk of hypertension in adulthood. However, the associations and toxic pathways between chronic exposure to metal(loids) and elevated blood pressure are rarely investigated. In this study, we measured the levels of 29 hair metal(loids) (chronic exposure biomarkers) and blood pressure in 667 susceptible children from an e-waste recycling area to explore their relationships. Paired urine metabolomics analysis was also performed to interpret potential mechanistic pathways. Results showed that the hypertension prevalence in our recruited children (13.0 %) exceeded the average rate (9.5 %) for Chinese children aged 6-17 years. The top five abundant metal(loids), including lead, strontium, barium, and zinc, demonstrated the most profound associations with elevated systolic blood pressure. Quantile g-computation, weighted quantile sum, and Bayesian kernel machine regression analysis jointly demonstrated a significant association between chronic exposure to metal(loids) mixture and systolic blood pressure. Interestingly, selenium showed significant antagonistic interactions with these four metals, suggesting that supplementing selenium may help children resist the elevated blood pressure induced by metal(loids) exposure. Increased metal(loids) and blood pressure levels were significantly linked to changes in urine metabolomics. Structural equation model indicated that androsterone glucuronide and N-Acetyl-1-aspartylglutamic acid were the significant mediators of the associations between metal(loids) and blood pressure, with mediation effects of 77.4 % and 29.0 %, respectively, suggesting that androsterone glucuronide and N-Acetyl-1-aspartylglutamic acid may be involved in the development of metal-induced blood pressure elevating effect. Girls were more vulnerable to metal(loids)-induced hormonal imbalance, especially androsterone glucuronide, than boys. Chronic exposure to metal(loids) at e-waste recycling sites may contribute to elevated blood pressure in children through disrupting various metabolism pathways, particularly hormonal balance. Our study provides new insights into potential mechanistic pathways of metal(loids)-induced changes in children's blood pressure., Competing Interests: Declaration of competing interest The authors declare that they have no known competing commercial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Activating enhancer-binding protein 2 (AP-2) is a family of transcription factors (TFs) that play crucial roles in regulating embryonic and oncogenic development. In addition to splice isoforms, five major family members encoded by the TFAP2A/B/C/D/E genes have been identified in humans, i.e., AP-2α/β/γ/δ/ε. In general, the first three TFs have been studied more thoroughly than AP-2δ or AP-2ε. Currently, there is a relatively limited body of literature focusing on the AP-2 family in the context of gastroenterological research, and a comprehensive overview of the existing knowledge and recommendations for further research directions is lacking. Herein, we have collected available gastroenterological data on AP-2 TFs, discussed the latest medical applications of each family member, and proposed potential future directions. Research on AP-2 in gastrointestinal tumors has predominantly been focused on the two best-described family members, AP-2α and AP-2γ. Surprisingly, research in the past decade has highlighted the importance of AP-2ε in the drug resistance of gastric cancer (GC) and colorectal cancer (CRC). While numerous questions about gastroenterological disorders await elucidation, the available data undoubtedly open avenues for anti-cancer targeted therapy and overcoming chemotherapy resistance. In addition to gastrointestinal cancers, AP-2 family members (primarily AP-2β and marginally AP-2γ) have been associated with other health issues such as obesity, type 2 diabetes, liver dysfunction, and pseudo-obstruction. On the other hand, AP-2δ has been poorly investigated in gastroenterological disorders, necessitating further research to delineate its role. In conclusion, despite the limited attention given to AP-2 in gastroenterology research, pivotal functions of these transcription factors have started to emerge and warrant further exploration in the future.

Background: Since 2006, Taiwan has actively pursued the development of its medical tourism industry. In 2013, the government sought to bolster this sector by integrating medical tourism into the Free Economic Pilot Zones. Despite narrowly missing the mark, the initiative failed to materialize into law. This qualitative study endeavors to discern the pertinent factors influencing the agenda-setting process for incorporating medical tourism into the Free Economic Pilot Zones in Taiwan., Methods: A comprehensive examination of policies concerning the legitimation of medical tourism within the Free Economic Pilot Zones was undertaken through semi-structured interviews and a thorough review of policy documents. Key informants were strategically selected using purposive and snowball sampling techniques. Thematic analysis was applied to scrutinize the amassed data and organize it within the framework of Kingdon's multiple streams., Results: In the problem stream, increasing financial strains and cost containment pressures under the National Health Insurance program have long driven health care providers to seek further opportunities in medical tourism. The existing barriers to expanding medical tourism in Taiwan included diplomatic tensions (specifically cross-strait relations), public concerns about commercialization of medical care and reduced their access to care, and legal and language barriers. Within the policy stream, factors such as franchise fees to support national health insurance, limited number of demonstration medical tourism sites and services allowed, the allowance of foreign medical personnel, regulations governing domestic physicians, the importance of demonstration, regulation, and accreditation, as well as restrictions on investment from China, were emphasized. The politics stream highlights factors such as governmental support, opposition from opposing parties, public concerns and critics from academia and non-governmental organizations, and skepticism from medical faculties., Conclusion: Acknowledging the recognized challenges in enacting the medical tourism provision of the Free Economic Pilot Zones Special Act and emphasizing the political will of leadership, a viable policy solution remained elusive. Although a window of opportunity existed for the passage of the bill, it waned as public concerns sidelined the issue from the national agenda. The Taiwan case underscores the necessity for meticulous consideration of issues, proposed solutions, and political dynamics to achieve successful policy enactment., (© 2024. The Author(s).)

The androgen receptor signaling inhibitor (ARSI) enzalutamide (Enz) has shown critical efficacy in the treatment of advanced prostate cancer (PCa). However, the development of drug resistance is a significant factor contributing to mortality in PCa patients. We aimed to explore the key mechanisms of Enz-resistance. Through analysis of GEO databases, we identified SLC4A4 as a novel driver in Enz resistance. Long-term Enz treatment leads to the up-regulation of SLC4A4, which in turn mediates P53 lactylation via the NF-κB/STAT3/SLC4A4 axis, ultimately leading to the development of Enz resistance and progression of PCa. SLC4A4 knockdown overcomes Enz resistance both in vitro and in vivo. Hence, our results suggest that targeting SLC4A4 could be a promising therapeutic strategy for Enz resistance. STATEMENT OF SIGNIFICANCE: SLC4A4 is a novel driver of enzalutamide resistance., 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.)

Samples of ambient volatile organic compounds （VOCs） were collected using SUMMA canisters at three Country Control Sites in Shijiazhuang during the spring of 2019, 2021, and 2022, which were detected using gas chromatography/mass spectrometry （GC/MS）. To investigate the characteristics and temporal variations of VOCs mass concentration levels, the online monitoring data of ozone （O 3 ） and PM 2.5 at the same site were also collected. Subsequently, the ozone formation potential （OFP） and secondary organic aerosol formation potential （SOAFP） were utilized to assess the chemical activity of VOCs. Additionally, the potential source areas of VOCs in spring in Shijiazhuang were further identified using the potential source contribution factor （PSCF） method and concentration weight trajectory analysis （CWT）. Hence, the major VOCs sources were evaluated with the VOCs initial mixing ratio. The results demonstrated that the averaged concentration of VOCs during the polluted period and clean period of spring in Shijiazhuang were 191.17 μg·m -3 and 122.18 μg·m -3 , respectively. Meanwhile, the OFP was 361.23 μg·m -3 during the polluted period and 266.96 μg·m -3 during the clean period, whereas the SOAFP was 1.98 μg·m -3 and 1.61 μg·m -3 , respectively. Therefore, effective control of benzene, toluene, ethylbenzene, and xylene （BTEX） is crucial for reducing PM 2.5 and O 3 pollution. Based on the results obtained from weight PSCF and CWT, the potential source areas of VOCs were further identified to be primarily located in the eastern Yuhua District, the high-tech district, and the northern Luancheng District of Shijiazhuang. These areas were influenced not only by local emissions but also by transport from neighboring regions, in which consistency between the CWT and PSCF results further supported these findings. Furthermore, the results obtained from the benzene/toluene/ethylbenzene （B/T/E） and xylene/benzene （X/B） ratios indicated that the main sources of VOCs in Shijiazhuang in spring were vehicle exhaust sources and burning sources, leading to a more serious air mass aging phenomenon. Hence, controlling vehicle emissions and implementing regional cooperative measures are the effective strategies for optimizing the air quality of Shijiazhuang.

Ammonia （NH 3 ） is an important alkaline reactive nitrogen, which, as a precursor of fine particulate matter, raises public health issues. In this study, online NH 3 , SO 2 , NO 2 , PM 2.5 , and its water-soluble inorganic ions were detected to deduce the influence of NH 3 on aerosol liquid water content （AWC） and aerosol pH, including the formation of water-soluble secondary ions in PM 2.5 in winter in Changzhou, an ammonia-rich city in the Yangtze River Delta area in winter. The results showed that NH 4 + mainly existed in the form of NH 4 NO 3 and （NH 4 ） 2 SO 4 , and the remaining NH 4 + existed as NH 4 Cl. Owing to the NH 3 -NH 4 + buffer system, the aerosol pH values were found at 4.2 ± 0.4, which was positively correlated with the NH 3 content. The aerosol pH value variation narrowed with the increase in PM 2.5 concentration and tended to be between 4 to 5. AWC increased exponentially with the increase in humidity and SNA content, among which NH 4 NO 3 , （NH 4 ） 2 SO 4 , and NH 4 Cl contributed 58.5%, 18.4%, and 8.3%, respectively, due to their hygroscopicity. Aerosol pH, AWC, and NH 3 -NH 4 + conversion promoted the gas-to-particle conversion of SO 2 and NO 2 . In Changzhou, rich NH 3 -NH 4 + were found to maintain relatively high pH values, push up AWC, and promote the heterogeneous reaction of SO 2 , whereas NO 3 - generation was dominated by a homogeneous reaction, which was accelerated by NH 3 . According to the simulation results, relatively noticeable changes in aerosol pH and AWC could be found by the reduction of up to 30% of NH 3 .

Young MSM (YMSM), aged 15-24, account for nearly half of new HIV infections in Thailand. Pre-exposure prophylaxis (PrEP) is an effective prevention medicine for populations at substantial HIV risk, yet YMSM frequently have suboptimal uptake of and adherence to PrEP. We conducted 35 in-depth interviews with YMSM to explore barriers and facilitators of both PrEP initiation and adherence. Interviews also elicited the perceptions and experiences of healthcare providers (HCPs) working with YMSM at three clinics in Bangkok. Primary barriers to PrEP initiation were limited accessibility, insufficient knowledge, and efficacy concerns; HCPs identified no-to-low self-perception of HIV risk, pre-existing health problems, fears of side effects, and living in distant provinces as barriers to PrEP initiation. YMSM primarily reported PrEP information and self-perceptions of elevated HIV risk as facilitators to PrEP initiation. Additionally, forgetfulness and low HIV risk awareness were common barriers to PrEP adherence. Reminders were a prominent facilitator of PrEP adherence alongside disclosure to close relationships, the routinization of regimens, and convenient facilities. HCPs regarded counseling as the leading facilitator of PrEP adherence. By understanding the barriers/facilitators of PrEP use, the current study seeks to help develop evidence-informed PrEP intervention programs among YMSM while considering cultural sensitivity.

With advances in next-generation sequencing technology, there is growing evidence that the gut microbiome plays a key role in the host's innate and adaptive immune system. Gut microbes and their metabolites directly or indirectly regulate host immune cells. Crucially, dysregulation of the gut microbiota is often associated with many immune system diseases. In turn, microbes modulate disease immunotherapy. Data from preclinical to clinical studies suggest that the gut microbiota may influence the effectiveness of tumor immunotherapy, particularly immune checkpoint inhibitors (ICIs). In addition, the most critical issue now is a COVID-19 vaccine that generates strong and durable immunity. A growing number of clinical studies confirm the potential of gut microbes to enhance the efficacy of COVID-19 vaccines. However, it is still unclear how gut bacteria interact with immune cells and what treatments are based on gut microbes. Here, we outline recent advances in the effects and mechanisms of the gut microbiota and its metabolites (tryptophan metabolites, bile acids, short-chain fatty acids, and inosine) on different immune cells (dendritic cells, CD4 + T cells, and macrophages). It also highlights innovative intervention strategies and clinical trials of microbiota-based checkpoint blocking therapies for tumor immunity, and ongoing efforts to maintain the long-term immunogenicity of COVID-19 vaccines. Finally, the challenges to be overcome in this area are discussed. These provide an important basis for further research and clinical translation of gut microbiota., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Chlorinated polyfluorinated ether sulfonate, commercially known as F-53B, has been associated with adverse birth outcomes. However, the reproductive toxicology of F-53B on the placenta remains poorly understood. To address this gap, we examined the impact of F-53B on placental injury and its underlying molecular mechanisms in vivo. Pregnant C57BL/6 J female mice were randomly allocated to three groups: the control group, F-53B 0.8 µg/kg/day group, and F-53B 8 µg/kg/day group. After F-53B exposure through free drinking water from gestational day (GD) 0.5-14.5, the F-53B 8 µg/kg/day group exhibited significant increases in placental weights and distinctive histopathological alterations, including inflammatory cell infiltration, heightened syncytiotrophoblast knots, and a loosened trophoblastic basement membrane. Within the F-53B 8 µg/kg/day group, placental tissue exhibited increased apoptosis, as indicated by increased caspase3 activation. Furthermore, F-53B potentially induced the NF-κB signaling pathway activation through IκB-α phosphorylation. Subsequently, this activation upregulated the expression of inflammatory cytokines and components of the NLRP3 inflammasome, including activated caspase1, IL-1β, IL-18, and cleaved gasdermin D (GSDMD), ultimately leading to pyroptosis in the mouse placenta. Our findings reveal a pronounced inflammatory injury in the placenta due to F-53B exposure, suggesting potential reproductive toxicity at concentrations relevant to the human population. Further toxicological and epidemiological investigations are warranted to conclusively assess the reproductive health risks posed by F-53B., 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 Authors. Published by Elsevier Inc. All rights reserved.)

2,2',6-Tribromobisphenol A (Tri-BBPA), the main debrominated congener of tetrabromobisphenol A (TBBPA), is ubiquitous in the environment and human body but with unknown toxicity. Tri-BBPA was synthesized and applied to investigate its sub-chronic exposure effects on 28 organ coefficients and clinical health indicators related to liver function, kidney function, and cardiovascular system function in female mice. Results showed that the liver was the targeted organ of Tri-BBPA exposure. Compared to the control group, the changes in liver coefficient, cholinesterase, total protein, albumin, γ-glutamyl transpeptidase, lactate dehydrogenase, and creatine kinase levels ranged from -61.2 % to 35.5 % in the high-exposed group. Creatine kinase was identified as a critical effect indicator of Tri-BBPA exposure. Using the Bayesian benchmark dose derivation method, a lower reference dose than TBBPA was established for Tri-BBPA (10.6 μg/kg-day). Serum metabolomics revealed that Tri-BBPA exposure may primarily damage the liver by disrupting tryptophan metabolism related to L-alanine, tryptamine, 5-hydroxyindoleacetic acid, and 5-methoxyindoleacetate in liver cells and leading to liver dysfunction. Notably, epilepsy, schizophrenia, early preeclampsia, and late-onset preeclampsia were the top six enriched diseases, suggesting that the nervous system may be particularly affected by Tri-BBPA exposure. Our findings hinted a non-negligible health risk of exposure to debrominated products of TBBPA., Competing Interests: Declaration of competing interest The authors declare that they have no known competing commercial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Background: Limited research has been conducted to quantitatively assess the impact of systemic inflammation in metabolic dysfunction-associated fatty liver disease (MAFLD) and sub-clinical carotid atherosclerosis (SCAS). The systemic immune-inflammation index (SII), which integrates inflammatory cells, has emerged as a reliable measure of local immune response and systemic inflammation Therefore, this study aims to assess the mediating role of SII in the association between MAFLD and SCAS in type 2 diabetes mellitus (T2DM)., Method: This study prospectively recruited 830 participants with T2DM from two centers. Unenhanced abdominal CT scans were conducted to evaluate MAFLD, while B-mode carotid ultrasonography was performed to assess SCAS. Weighted binomial logistic regression analysis and restricted cubic splines (RCS) analyses were employed to analyze the association between the SII and the risk of MAFLD and SCAS. Mediation analysis was further carried out to explore the potential mediating effect of the SII on the association between MAFLD and SCAS., Results: The prevalence of both MAFLD and SCAS significantly increased as the SII quartiles increased ( P< 0.05). MAFLD emerged as an independent factor for SCAS risk across three adjusted models, exhibiting odds ratios of 2.15 (95%CI: 1.31-3.53, P < 0.001). Additionally, increased SII quartiles and Ln (SII) displayed positive associations with the risk of MAFLD and SCAS ( P < 0.05). Furthermore, a significant dose-response relationship was observed ( P for trend <0.001). The RCS analyses revealed a linear correlation of Ln (SII) with SCAS and MAFLD risk ( P for nonlinearity < 0.05). Importantly, SII and ln (SII) acted as the mediators in the association between MAFLD and SCAS following adjustments for shared risk factors, demonstrating a proportion-mediated effect of 7.8% and 10.9%., Conclusion: SII was independently correlated with MAFLD and SCAS risk, while also acting as a mediator in the relationship between MAFLD and SCAS., 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 Wang, Guo, Qiu, Yu and Tu.)

Cascade radical cyclization constitutes an atom- and step-economic route for rapid assembly of polycyclic molecular skeletons. Although an array of redox-active metal catalysts has recently shown robust applications in enabling various catalytic cascade radical processes, the use of free organic radical as the catalyst, which is capable of triggering strategically distinct cascades, has rarely been developed. Here, we disclosed that the benzimidazolium-based N-heterocyclic carbene (NHC)-boryl radical is capable of catalyzing cascade cyclization reactions in both intra- and intermolecular pathways, assembling [5,5] fused bicyclic and [6,6,6] fused tricyclic molecules, respectively. The catalytic reactions start with the chemo- and regioselective addition of the boryl radical catalyst to a tethered alkene or alkyne moiety, followed by either an intramolecular formal [3+2] or an intermolecular [2+2+2] cycloaddition process to construct bicyclo[3.3.0]octane or tetrahydrophenanthridine skeletons, respectively. Eventually, a β-elimination occurs to release the boryl radical catalyst, completing a catalytic cycle. High to excellent diastereoselectivity is achieved in both catalytic reactions under substrate control., (© 2024 Wiley-VCH GmbH.)

Evidence increasingly suggests molybdenum exposure at environmental levels is still associated with adverse human health, emphasizing the necessity to establish a more protective reference dose (RfD). Herein, we conducted a study measuring 15 urinary metals and 30 clinical health indicators in 2267 participants residing near chemical enterprises across 11 Chinese provinces to investigate their relationships. The kidney and cystatin-C emerged as the most sensitive organ and critical effect indicator of molybdenum exposure, respectively. Odds of cystatin-C-defined chronic kidney disease (CKD) in the highest quantile of molybdenum exposure significantly increased by 133.5% (odds ratio [OR]: 2.34, 95% CI: 1.78, 3.11) and 75.8% (OR: 1.76, 95% CI: 1.24, 2.49) before and after adjusting for urinary 14 metals, respectively. Intriguingly, cystatin-C significantly mediated 15.9-89.5% of molybdenum's impacts on liver and lung function, suggesting nephrotoxicity from molybdenum exposure may trigger hepatotoxicity and pulmonary toxicity. We derived a new RfD for molybdenum exposure (0.87 μg/kg-day) based on cystatin-C-defined estimated glomerular filtration rate by employing Bayesian Benchmark Dose modeling analysis. This RfD is significantly lower than current exposure guidance values (5-30 μg/kg-day). Remarkably, >90% of participants exceeded the new RfD, underscoring the significant health impacts of environmental molybdenum exposure on populations in industrial regions of China., 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 Authors. Published by Elsevier Inc. All rights reserved.)

Background: There is growing interest in the joint effects of hazardous trace elements (HTEs) on lung function deficits, but the data are limited. This is a critical research gap given increased global industrialisation., Methods: A national cross-sectional study including spirometry was performed among 2112 adults across 11 provinces in China between 2020 and 2021. A total of 27 HTEs were quantified from urine samples. Generalised linear models and quantile-based g-computation were used to explore the individual and joint effects of urinary HTEs on lung function, respectively., Results: Overall, there were negative associations between forced expiratory volume in 1 s (FEV 1 ) and urinary arsenic (As) (z-score coefficient, -0.150; 95% CI, -0.262 to -0.038 per 1 ln-unit increase), barium (Ba) (-0.148, 95% CI: -0.258 to -0.039), cadmium (Cd) (-0.132, 95% CI: -0.236 to -0.028), thallium (Tl) (-0.137, 95% CI: -0.257 to -0.018), strontium (Sr) (-0.147, 95% CI: -0.273 to -0.022) and lead (Pb) (-0.121, 95% CI: -0.219 to -0.023). Similar results were observed for forced vital capacity (FVC) with urinary As, Ba and Pb and FEV 1 /FVC with titanium (Ti), As, Sr, Cd, Tl and Pb. We found borderline associations between the ln-quartile of joint HTEs and decreased FEV 1 (-20 mL, 95% CI: -48 to +8) and FVC (-14 mL, 95% CI: -49 to+2). Ba and Ti were assigned the largest negative weights for FEV 1 and FVC within the model, respectively., Conclusion: Our study investigating a wide range of HTEs in a highly polluted setting suggests that higher urinary HTE concentrations are associated with lower lung function, especially for emerging Ti and Ba, which need to be monitored or regulated to improve lung health., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Over the years, a number of state-of-the-art data analysis tools have been developed to provide a comprehensive analysis of data collected from gas chromatography-mass spectrometry (GC-MS). Unfortunately, the time shift problem remains unsolved in these tools. Here, we developed a novel comprehensive data analysis strategy for GC-MS-based untargeted metabolomics (AntDAS-GCMS) to perform total ion chromatogram peak detection, peak resolution, time shift correction, component registration, statistical analysis, and compound identification. Time shift correction was specifically optimized in this work. The information on mass spectra and elution profiles of compounds was used to search for inherent landmarks within analyzed samples to resolve the time shift problem across samples efficiently and accurately. The performance of our AntDAS-GCMS was comprehensively investigated by using four complex GC-MS data sets with various types of time shift problems. Meanwhile, AntDAS-GCMS was compared with advanced GC-MS data analysis tools and classic time shift correction methods. Results indicated that AntDAS-GCMS could achieve the best performance compared to the other methods.

The incidence of metabolic diseases has progressively increased, which has a negative impact on human health and life safety globally. Due to the good efficacy and limited side effects, there is growing interest in developing effective drugs to treat metabolic diseases from natural compounds. Kaempferol (KMP), an important flavonoid, exists in many vegetables, fruits, and traditional medicinal plants. Recently, KMP has received widespread attention worldwide due to its good potential in the treatment of metabolic diseases. To promote the basic research and clinical application of KMP, this review provides a timely and comprehensive summary of the pharmacological advances of KMP in the treatment of four metabolic diseases and its potential molecular mechanisms of action, including diabetes mellitus, obesity, non-alcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH), and atherosclerosis. According to the research, KMP shows remarkable therapeutic effects on metabolic diseases by regulating multiple signaling transduction pathways such as NF-κB, Nrf2, AMPK, PI3K/AKT, TLR4, and ER stress. In addition, the most recent literature on KMP's natural source, pharmacokinetics studies, as well as toxicity and safety are also discussed in this review, thus providing a foundation and evidence for further studies to develop novel and effective drugs from natural compounds. Collectively, our manuscript strongly suggested that KMP could be a promising candidate for the treatment of metabolic diseases., Competing Interests: Declaration of Competing Interest The authors declare that there are no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Thanks to the extensive efforts toward optimizing perovskite crystallization properties, high-quality perovskite films with near-unity photoluminescence quantum yield are successfully achieved. However, the light outcoupling efficiency of perovskite light-emitting diodes (PeLEDs) is impeded by insufficient light extraction, which poses a challenge to the further advancement of PeLEDs. Here, an anisotropic multifunctional electron transporting material, 9,10-bis(4-(2-phenyl-1H-benzo[d]imidazole-1-yl)phenyl) anthracene (BPBiPA), with a low extraordinary refractive index (n e ) and high electron mobility is developed for fabricating high-efficiency PeLEDs. The anisotropic molecular orientations of BPBiPA can result in a low n e of 1.59 along the z-axis direction. Optical simulations show that the low n e of BPBiPA can effectively mitigate the surface plasmon polariton loss and enhance the photon extraction efficiency in waveguide mode, thereby improving the light outcoupling efficiency of PeLEDs. In addition, the high electron mobility of BPBiPA can facilitate balanced carrier injection in PeLEDs. As a result, high-efficiency green PeLEDs with a record external quantum efficiency of 32.1% and a current efficiency of 111.7 cd A -1 are obtained, which provides new inspirations for the design of electron transporting materials for high-performance PeLEDs., (© 2024 Wiley‐VCH GmbH.)

World Drug Report 2023 concluded that 296 million people abused drugs, 39.5 million became addiction and 494,000 died as a direct or indirect result of addiction. Addiction has become a growing problem that affects individuals, their families, societies, countries and even the world. However, treatment for addiction is only limited to some developed countries because of the high cost, difficult implementation, and time consuming. Therefore, there is an urgent need to develop a low-cost, effective drug for the development of addiction treatment in more countries, which is essential for the stability and sustainable development of the world. In this review, it provided an overview of the abuse of common addictive drugs, related disorders, and current therapeutic regimen worldwide, and summarized the mechanisms of drug addiction as reward circuits, neuroadaptation and plasticity, cognitive decision-making, genetics, and environment. According to their chemical structure, 43 natural products and 5 herbal combinations with potential to treat addiction were classified, and their sources, pharmacological effects and clinical trials were introduced. It was also found that mitragine, ibogine, L-tetrahydropalmatine and crocin had greater potential for anti-addiction., Competing Interests: Declaration of Competing Interest The authors declare that there are no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Objectives: Concomitant COVID-19 and influenza vaccination would be an efficient strategy. Although the co-administration of monovalent COVID-19 and influenza vaccinations showed acceptable immunogenicity, it remains unknown whether the bivalent COVID-19 vaccine could intensify immune interference. We aimed to evaluate the immunogenicity and safety of concomitant BA.5-based bivalent COVID-19 and influenza vaccination., Methods: An open-label, nonrandomized clinical trial was conducted for 154 age-matched and sex-matched healthy adults between October 2022 and December 2022. Participants received either a concomitant bivalent COVID-19 mRNA booster and quadrivalent influenza vaccination (group C) or separate vaccinations (group S) at least 4 weeks apart. Solicited and unsolicited adverse events were reported up to 6 months postvaccination. Immunogenicity was evaluated by anti-spike (S) IgG electrochemiluminescence immunoassay, focus reduction neutralization test, and hemagglutination inhibition assay., Results: Group C did not meet the noninferiority criteria for the seroconversion rates of anti-S IgG and neutralizing antibodies against the wild-type SARS-CoV-2 strain compared with group S (44.2% vs. 46.8%, difference of -2.6% [95% CI, -18 to 13.4]; 44.2% vs. 57.1%, difference of -13.0% [95% CI to -28.9 to 2.9]). However, group C showed a stronger postvaccination neutralizing antibody response against Omicron BA.5 (72.7% vs. 64.9%). Postvaccination geometric mean titers for SARS-CoV-2 and influenza strains were similar between groups, except for influenza B/Victoria. Most adverse events were mild and comparable between the study groups., Discussion: Concomitant administration of bivalent COVID-19 mRNA and quadrivalent influenza vaccines showed tolerable safety profiles and sufficient immunogenicity, particularly attenuating immune imprinting induced by previous ancestral vaccine strains., (Copyright © 2024 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Lung injury has been a serious medical problem that requires new therapeutic approaches and biomarkers. Circular RNAs (circRNAs) are non-coding RNAs (ncRNAs) that exist widely in eukaryotes. CircRNAs are single-stranded RNAs that form covalently closed loops. CircRNAs are significant gene regulators that have a role in the development, progression, and therapy of lung injury by controlling transcription, translating into protein, and sponging microRNAs (miRNAs) and proteins. Although the study of circRNAs in lung injury caused by pulmonary toxicants is just beginning, several studies have revealed their expression patterns. The function that circRNAs perform in relation to pulmonary toxicants (severe acute respiratory distress syndrome coronavirus-2 (SARS-CoV-2), drug abuse, PM2.5, and cigarette smoke) is the main topic of this review. A variety of circRNAs can serve as potential biomarkers of lung injury. In this review, the biogenesis, properties, and biological functions of circRNAs were concluded, and the relationship between circRNAs and pulmonary toxicants was discussed. It is expected that the new ideas and potential treatment targets that circRNAs provide would be beneficial to research into the molecular mechanisms behind lung injury., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

α-In 2 Se 3 semiconductor crystals realize artificial synapses by tuning in-plane and out-of-plane ferroelectricity with diverse avenues of electrical and optical pulses. While the electrically induced ferroelectricity of α-In 2 Se 3 shows synaptic memory operation, the optically assisted synaptic plasticity in α-In 2 Se 3 has also been preferred for polarization flipping enhancement. Here, the synaptic memory behavior of α-In 2 Se 3 is demonstrated by applying electrical gate voltages under white light. As a result, the induced internal electric field is identified at a polarization flipped conductance channel in α-In 2 Se 3 /hexagonal boron nitride (hBN) heterostructure ferroelectric field effect transistors (FeFETs) under white light and discuss the contribution of this built-in electric field on synapse characterization. The biased dipoles in α-In 2 Se 3 toward potentiation polarization direction by an enhanced internal built-in electric field under illumination of white light lead to improvement of linearity for long-term depression curves with proper electric spikes. Consequently, upon applying appropriate electric spikes to α-In 2 Se 3 /hBN FeFETs with illuminating white light, the recognition accuracy values significantly through the artificial learning simulation is elevated for discriminating hand-written digit number images., (© 2024 Wiley‐VCH GmbH.)

Using readily available manganese pentacarbonyl bromide as a regeneration catalyst, biomimetic asymmetric reduction of imines including quinoxalinones, benzoxazinones, and benzoxazine has been successfully developed in the presence of transfer catalyst chiral phosphoric acids, providing the chiral amines with high yields and enantioselectivities.

Epidemiological studies have demonstrated the embryonic and developmental toxicity of plasticizers. Thus, understanding the in utero biotransformation and accumulation of plasticizers is essential to assessing their fate and potential toxicity in early life. In the present study, 311 infant hair samples and 271 paired meconium samples were collected at birth in Guangzhou, China, to characterize fetal exposure to legacy and emerging plasticizers and their metabolites. Results showed that most of the target plasticizers were detected in infant hair, with medians of 9.30, 27.6, and 0.145 ng/g for phthalate esters (PAEs), organic phosphate ester (OPEs), and alternative plasticizers (APs), and 1.44, 0.313, and 0.066 ng/g for the metabolites of PAEs, OPEs, and APs, respectively. Positive correlations between plasticizers and their corresponding primary metabolites, as well as correlations among the oxidative metabolites of bis(2-ethylhexyl) phthalate (DEHP) and 1,2-cyclohexane dicarboxylic acid diisononyl ester (DINCH), were observed, indicating that infant hair retained the major phase-I metabolism of the target plasticizers. While no positive correlations were found in parent compounds or their primary metabolites between paired infant hair and meconium, significant positive correlations were observed among secondary oxidative metabolites of DEHP and DINCH in hair and meconium, suggesting that the primary metabolites in meconium come from hydrolysis of plasticizers in the fetus but most of the oxidative metabolites come from maternal-fetal transmission. The parent compound/metabolite ratios in infant hair showed a decreasing trend across pregnancy, suggesting in utero accumulation and deposition of plasticizers. To the best of our knowledge, this study is the first to report in utero exposure to both parent compounds and metabolites of plasticizers by using paired infant hair and meconium as noninvasive biomonitoring matrices and provides novel insights into the fetal biotransformation and accumulation of plasticizers across pregnancy.

Among civilization diseases, the number of individuals suffering from type 2 diabetes (T2DM) is expected to increase to more than a billion in less than 20 years, which is associated with, e.g., populational aging, poor diet, sedentary lifestyle, genetic predispositions, and immunological factors. T2DM affects many organs and is characterized by insulin resistance, high glucose levels, and adipocyte dysfunction, which are related to senescence. Although this type of cellular aging has beneficial biological functions, it can also act unfavorable since senescent adipocytes resist apoptosis, enhance cytokine secretion, downregulate cell identity genes, and acquire the senescence-associated secretory phenotype that renders a more oxidative environment. Opposing T2DM is possible via a wide variety of senotherapies, including senolytics and senomorphics; nevertheless, further research is advised to expand therapeutic possibilities and benefits. Consequences that ought to be deeply researched include secretory phenotype, chronic inflammation, increasing insulin resistance, as well as impairment of adipogenesis and functioning of adipocyte cells. Herein, despite reviewing T2DM and fat tissue senescence, we summarized the latest adipocyte-related anti-diabetes solutions and suggested further research directions., (© 2024 the author(s), published by De Gruyter.)

Despite the increasing production, use, and ubiquitous occurrence of novel brominated flame retardants (NBFRs), little information is available regarding their fate in aquatic organisms. In this study, the bioaccumulation and biotransformation of two typical NBFRs, i.e., 1,2-bis (2,4,6-tribromophenoxyethane) (BTBPE) and 1,2-dibromo-4-(1,2-dibromoethyl)-cyclohexane (TBECH), were investigated in tissues of zebrafish (Danio rerio) being administrated a dose of target chemicals through their diet. Linear accumulation was observed for both BTBPE and TBECH in the muscle, liver, gonads, and brain of zebrafish, and the elimination of BTBPE and TBECH in all tissues followed pseudo-first-order kinetics, with the fastest depuration rate occurring in the liver. BTBPE and TBECH showed low bioaccumulation potential in zebrafish, with biomagnification factors (BMFs) < 1 in all tissues. Individual tissues' function and lipid content are vital factors affecting the distribution of BTBPE and TBECH. Stereoselective accumulation of TBECH enantiomers was observed in zebrafish tissues, with first-eluting enantiomers, i.e. E 1 -α-TBECH and E 1 -β-TBECH, preferentially accumulated. Additionally, the transformation products (TPs) in the zebrafish liver were comprehensively screened and identified using high-resolution mass spectrometry. Twelve TPs of BTBPE and eight TPs of TBECH were identified: biotransformation pathways involving ether cleavage, debromination, hydroxylation, and methoxylation reactions for BTBPE and hydroxylation, debromination, and oxidation processes for TBECH. Biotransformation is also a vital factor affecting the bioaccumulation potential of these two NBFRs, and the environmental impacts of NBFR TPs should be further investigated in future studies. The findings of this study provide a scientific basis for an accurate assessment of the ecological and environmental risks of BTBPE and TBECH., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Tetrabromobisphenol A (TBBPA) and tetrabromobisphenol S (TBBPS) are widely distributed brominated flame retardants. While TBBPA has been demonstrated to stimulate adipogenesis, TBBPS is also under suspicion for potentially inducing comparable effects. In this study, we conducted a non-targeted metabolomics to examine the metabolic changes in 3T3-L1 cells exposed to an environmentally relevant dose of TBBPA or TBBPS. Our findings revealed that 0.1 µM of both TBBPA and TBBPS promoted the adipogenesis of 3T3-L1 preadipocytes. Multivariate analysis showed significant increases in glycerophospholipids, sphingolipids, and steroids relative levels in 3T3-L1 cells exposed to TBBPA or TBBPS at the final stage of preadipocyte differentiation. Metabolites set composed of glycerophospholipids was found to be highly effective predictors of adipogenesis in 3T3-L1 cells exposed to TBBPA or TBBPS (revealed from the receiver operating characteristic curve with an area under curve > 0.90). The results from metabolite set enrichment analysis suggested both TBBPA and TBBPS exposures significantly perturbed steroid biosynthesis in adipocytes. Moreover, TBBPS additionally disrupted the sphingolipid metabolism in the adipocytes. Our study presents new insights into the obesogenic effects of TBBPS and provides valuable information about the metabolites associated with adipogenesis induced by TBBPA or TBBPS., 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.)

This study details the differentiation of identical twins based on single mutational base differences. There were three pairs of male monozygotic (MZ) twins in this study. DNA samples from blood, a buccal swab or saliva from each individual were all initially genotyped using 22 autosomal STR and 27 Y-STR loci. Preliminary screening confirmed there were no differences in the STR data between each pair of MZ twins. Whole Genome Sequence (WGS) data were generated from DNA extracted from the three body fluids from each individual. Kinship coefficients with 0.4254, 0.4557 and 0.4543 from 3 twins were generated based on WGS data to further confirm that their relationship was that of MZ twins. The fastq data generated by the Illumina Hiseq 2000 between MZ twins were then treated as "normal" as opposed to "tumor" using commercially available software tools to identify mutational single base changes. Sanger DNA sequencing confirmed there were 1, 5 and 9 single base changes found in WGS data from each of the three MZ twin sets. There was individual variation in the mutational base changes when comparing data from the three body fluids. The methods used in this study to differentiate MZ twins based on WGS data can readily be performed in many operational forensic DNA laboratories using user friendly software., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)