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In patients with recurrent pregnancy loss (RPL), excessive activation of decidual natural killer (dNK) cells has been widely observed, yet the precise underlying mechanisms remain to be elucidated. We collected decidual specimens from RPL patients and controls to assess GRIM19 expression, activation phenotype, cytotoxic function, inflammatory cytokine secretion, and mitochondrial homeostasis in dNK cells. Furthermore, we established a GRIM19-knockout NK-92MI cell line and a GRIM19 ± C57BL/6J mouse model to investigate the relationship between GRIM19 downregulation and dNK immune dysregulation, ultimately contributing to pregnancy loss. Decidual NK cells from RPL patients exhibited significantly lower GRIM19 expression, accompanied by abnormal hyperactivation, enhanced cytotoxicity, and abnormal mitochondrial activation. In vitro experiments confirmed that reduced GRIM19 expression significantly potentiated the cytotoxicity and pro-inflammatory cytokine secretion of NK-92MI cells, while also promoting mitochondrial homeostasis imbalance. Mouse model studies corroborated that GRIM19 downregulation triggers NK cell homeostasis imbalance, contributing to the occurrence of pregnancy loss. Downregulation of GRIM19 in dNK cells contributes to RPL through hyperactivation and disruption of mitochondrial homeostasis, emphasizing its potential as a diagnostic and therapeutic target., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethical approval and consent to participate: This study has been approved by the Medical Ethics Committee of Qilu Hospital of Shandong University (Approval No. KYLL-202207-019-1) and the Animal Ethics Committee of Qilu Hospital of Shandong University (Approval No. DWLL-2023-026). In accordance with the Helsinki Declaration, informed consent was obtained from all women before participation. Consent for publication: Not applicable., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Competing Interests: Financial Disclosure: Jessica Pruszynski reports money was paid to her institution from PCORI. Kimberly Kho's institution received payment from Hologic, Inc (PI, clinical study). She received payment from Channel MedSystems, Inc., for serving on their Medical Advisory Board. The other authors did not report any potential conflicts of interest.

The global distribution, persistence, bioaccumulation, and toxicity of per- and polyfluoroalkyl substances (PFAS) have received significant attention. We determined the contents of major perfluoroalkyl acids (PFAAs) in various commercial fish species from different regions of the Beibu Gulf. We detected 14 out of 17 PFAAs across all species, with PFOS (Perfluorooctanesulphonate) showing the highest detection rate, followed by PFHxS (Perfluorohexanesulfonic acid), PFPeA (Perfluorovaleric acid), and PFTrDA (Perfluorotetradecanoic acid). The concentrations of ∑PFAAs ranged from 0.22 to 7.43 ng/g (ww). Additionally, PFCAs dominated the PFAA profile (70 %) in the southern Beibu Gulf in comparison with the northern (53 %) and central Beibu Gulf (48 %). PFOS was the most abundant compound, accounting for 41 % of total PFAAs, followed by PFUdA (Perfluoroundecanoic Acid) (14 %) and PFOA (Perfluorooctanoic Acid) (12 %). The estimated daily intakes and hazard ratios of PFOS and PFOS indicate that there is no significant health risk from people consuming these fish., 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.)

The ability to visualise microRNA in situ is crucial for studying microRNAs, their microRNA-associated biological functions and disease diagnosis. Traditional fluorescence in situ hybridisation methods based on paraformaldehyde fixation of microRNAs suffer from release of microRNAs from cells, which limits the sensitivity of in situ hybridisation, making them unsuitable for the detection of small, low-abundance microRNAs. To reduce the loss, microRNAs were covalently cross-linked to proteins within cells by combining EDC and paraformaldehyde, and the target microRNA was used as the initiator chain for a branched hybridisation chain reaction to detect microRNA expression levels in situ. A simplified branched hybridisation chain reaction can be realised by coupling two hybridisation chain reaction circuits with a hairpin linker. Upon forming the primary hybridisation chain reaction product with extended sequence, this sequence reacts with the linker hairpin H3 to release the initiator sequence, resulting in the formation of numerous dendritic branched hybridisation chain reaction products. Imaging results show that this technique can detect microRNAs with high sensitivity and selectivity at both the single-cell and single-molecule levels. Compared with the traditional fluorescence in situ hybridisation technique, this method greatly improves the sensitivity and image resolution of in situ imaging detection. Therefore, we believe that the target-initiated branched hybridisation chain reaction based in situ detection method provides a reliable assay platform for analysing disease-related microRNA expression., (© 2024 The Author(s). Cell Proliferation published by Beijing Institute for Stem Cell and Regenerative Medicine and John Wiley & Sons Ltd.)

Lineages of rod-shaped bacteria such as Escherichia coli exhibit a temporal decline in elongation rate in a manner comparable to cellular or biological aging. The effect results from the production of asymmetrical daughters, one with a lower elongation rate, by the division of a mother cell. The slower daughter compared to the faster daughter, denoted respectively as the old and new daughters, has more aggregates of damaged proteins and fewer expressed gene products. We have examined further the degree of asymmetry by measuring the density of ribosomes between old and new daughters and between their poles. We found that ribosomes were denser in the new daughter and also in the new pole of the daughters. These ribosome patterns match the ones we previously found for expressed gene products. This outcome suggests that the asymmetry is not likely to result from properties unique to the gene expressed in our previous study, but rather from a more fundamental upstream process affecting the distribution of ribosomal abundance. Because damage aggregates and ribosomes are both more abundant at the poles of E. coli cells, we suggest that competition for space between the two could explain the reduced ribosomal density in old daughters. Using published values for aggregate sizes and the relationship between ribosomal number and elongation rates, we show that the aggregate volumes could in principle displace quantitatively the amount of ribosomes needed to reduce the elongation rate of the old daughters., Competing Interests: LC, CC, CS, UR No competing interests declared, (© 2023, Chao, Chan et al.)

Haizhou Bay, a semi-enclosed key aquaculture area in East China, has had relatively limited research focused on trace metals and perfluoroalkyl acids (PFAAs) in its biota. This study characterized the distribution, biomagnification and health risks of selected trace metals and PFAAs in various marine organisms from Haizhou Bay. Among the species examined, zinc (Zn) was the most prevalent metal, followed by copper (Cu) and chromium (Cr), whereas cadmium (Cd), total mercury (THg), and methylmercury (MeHg) contents were relatively low. Perfluorooctane sulfonate (PFOS) was the most abundant PFAA, followed by perfluorooctanoic acid (PFOA). The calculated trophic magnification factors (TMFs) were above one for Cr, THg, MeHg, and all PFAAs except perfluorobutanoic acid (PFBA) and perfluorotetradecanoic acid (PFTeDA). Across animal groups, gastropods exhibited relatively low levels of THg, MeHg, and perfluorosulfonic acids (∑PFSAs). By comparison, fish generally had lower levels of Cd and Cu compared to other animal groups, and demersal fish had significantly higher MeHg compared to gastropods. Certain organisms, such as cephalopods and shrimps, were found to pose potential health risks due to elevated levels of Cd, while levels of other studied metals, PFOS and PFOA generally appeared to be within safe limits for human consumption. Further research is needed to assess the sources and impacts of these and other contaminants., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Cholesterol 25-hydroxylase (CH25H) has significant antiviral effects through the production of 25-hydroxycholesterol (25HC). In this study, we investigated the effects of CH25H, its catalytic product 25HC, and its catalytic mutant lacking hydroxylase activity (CH25H-M) on porcine circovirus 3 (PCV3) replication. By transfecting PCV3 persistently infected PK-15 cells with the pCAGGS-CH25H-Flag plasmid, the results demonstrated that overexpression of CH25H significantly inhibited PCV3 Cap protein expression, Cap mRNA levels, and viral titers in a dose-dependent manner. Moreover, its catalytic product 25HC inhibited PCV3 replication in PK-15 cells at concentrations below 10 µM without affecting cell viability. In contrast, knockdown of endogenous CH25H using small interfering RNA (siRNA) enhanced PCV3 replication, further confirming its antiviral role. Interestingly, the CH25H-M mutant also exhibited inhibitory effects on PCV3 replication, although the inhibition was much less effective compared with CH25H. In conclusion, CH25H plays a critical role in regulating PCV3 replication, and its antiviral effect is not entirely dependent on its enzymatic activity. These findings provide new insights into both the enzymatic and non-enzymatic antiviral mechanisms of CH25H and revealed some mechanistic immune evasion for PCV3., 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.)

Germline genetic architecture of Alzheimer's disease (AD) indicates microglial mechanisms of disease susceptibility and outcomes. However, the mechanisms that enable microglia to mediate protective responses to AD pathology remain elusive. Adgrg1 is specifically expressed in yolk-sac-derived microglia. This study reveals the role of yolk-sac-derived microglia in AD pathology, highlighting the function of ADGRG1 in modulating microglial protective responses to amyloid deposition. Utilizing both constitutive and inducible microglial Adgrg1 knockout 5xFAD models, we demonstrate that Adgrg1 deficiency leads to increased amyloid deposition, exacerbated neuropathology, and accelerated cognitive impairment. Transcriptomic analyses reveal a distinct microglial state characterized by downregulated genes associated with homeostasis, phagocytosis, and lysosomal functions. Functional assays in mouse models and human embryonic stem cells-derived microglia support that microglial ADGRG1 is required for efficient Aβ phagocytosis. Together, these results uncover a GPCR-dependent microglial response to Aβ, pointing towards potential therapeutic strategies to alleviate disease progression by enhancing microglial functional competence.

Objective: This report details the experience of a patient who developed a second primary glioblastoma (GB), offering insights into the treatment process and reviewing relevant literature., Case Presentation: A male patient, who was diagnosed with medulloblastoma at age 9, received treatment with cobalt-60 craniospinal irradiation (CSI) (36 Gy/20 fractions) and a tumor bed boost (total of 56 Gy). After 32 years, at age 41, an MRI revealed a space-occupying mass in the left cerebellar hemisphere. Surgical resection was performed, and postoperative pathology confirmed a diagnosis of radiation-induced glioblastoma (RIGB). Given the history of irradiation and the current tolerability of brainstem doses, proton beam therapy (PBT) combined with Temozolomide (75 mg/m 2 ) was chosen. The treatment plan included 60 Gy on the gross tumor bed and 54 Gy on the clinical target volume, delivered in 30 fractions. The patient underwent regular follow-up and achieved a complete response., Clinical Discussion: For childhood cancer survivors, the development of a second primary tumor significantly impacts prognosis. RIGB is a rare form of secondary tumor with distinct molecular characteristics compared to primary GB and recurrent secondary GB. Molecular markers such as IDH and MGMT status can help differentiate between primary GB, recurrent secondary GB, and radiation-induced secondary GB in patients with a history of prior radiation therapy. Surgical resection remains a primary treatment option, while PBT is preferred for postoperative treatment due to its superior protection of normal tissues and the ability to deliver high-dose irradiation., Conclusion: RIGB is a rare second primary tumor that requires strategic molecular profiling and individualized management. Proton beam therapy provides effective high-dose irradiation in the postoperative phase and is the preferred treatment option for such cases., (© 2024. The Author(s).)

Background: Preventing Loss of Independence through Exercise (PLIÉ) is a group program for people living with dementia that combines movements to support daily function with present moment body awareness and social engagement that has been found to have physical, emotional, social, and cognitive benefits. The goal of this study was to develop and refine a PLIÉ remote training program for interdisciplinary Veterans Affairs (VA) nursing home staff members also known as community living center (CLC) staff., Methods: This pre-implementation study used iterative Plan-Do-Study-Act (PDSA) cycles. The 10-week PDSA cycles occurred from June to September 2021 at 2 VA nursing home sites. Remote training was delivered via Microsoft Teams and included 1-hour live-streamed weekly didactic sessions (nursing staff with PLIÉ instructor) focused on PLIÉ principles and 1-hour weekly live-streamed experiential sessions for staff to apply PLIÉ principles with residents. We administered weekly feedback surveys to iteratively refine the training process., Results: 14 staff members participated (5 recreation therapists, 3 social workers, 2 registered nurses, 2 chaplains, 1 psychologist, and 1 speech pathologist). The experiential sessions were rated as most helpful overall. Key PDSA refinements included: (1) creating 10-minute video recording summaries to support learning, particularly for those unable to attend live training sessions due to clinical schedules; and (2) incorporating self-reflection and goal setting to support staff incorporation of PLIÉ principles into routine care and personal life. These refinements resulted in increased use of PLIÉ principles with the residents from 67 to 89% of the staff participants. 100% of regular attendees (11/11) rated their overall satisfaction with remote training as "very good" or "excellent.", Conclusions: It was feasible to train interdisciplinary CLC staff participants to deliver an integrative group movement program for residents with dementia remotely. PDSA cycles supported refinement of the training process and improved uptake. A larger study of PLIÉ remote CLC staff training is needed to assess outcomes on residents and quality of care., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background: PM 2.5 has been associated with various adverse health effects, particularly affecting lung function and chronic respiratory diseases. However, the genetic causality relationship between PM 2.5 exposure and lung function as well as chronic respiratory diseases remains poorly understood., Method: We conducted a two-sample Mendelian randomization analysis to investigate the causal impact of PM 2.5 on lung function and chronic respiratory diseases. Instrumental variables were carefully selected, with significance thresholds (P < 5 × 10 - 8 ), and linkage disequilibrium with an r 2 value below 0.001. Additionally, SNPs with an F-statistic exceeding 10 were included to mitigate potential bias stemming from weak instrumental variables. The primary analytical approach employed the Inverse Variance Weighted method, supplemented by the Weighted Median, MR-Egger, Simple Model, and Weighted Model. Furthermore, pleiotropy and heterogeneity were evaluated through the MR-Egger intercept test and Cochrane's Q test, with a sensitivity analysis conducted using the leave-one-out method., Results: Eight SNPs significantly associated with PM 2.5 exposure were identified as Instrumental variables. Mendelian randomization analysis revealed a significant causal association between PM 2.5 exposure and lung function (FEV), with an OR of 0.7284 (95% CI: 0.5799-0.9150). Similarly, PM 2.5 exposure demonstrated a substantial causal effect on asthma, with an OR of 1.5280 (95% CI: 1.0470-2.2299). However, no causal association was observed between PM 2.5 exposure and chronic obstructive pulmonary disease, with an OR of 1.5176 (95% CI: 0.8294-2.7768)., Conclusion: These findings emphasize the necessity for continued research efforts in environmental health to develop effective strategies for the prevention and management of chronic respiratory diseases., (© 2024. The Author(s) under exclusive licence to International Society of Biometeorology.)

The main purpose of this review was to examine the evidence of the relationship between active smoking or passive smoking during pregnancy and atopic dermatitis in offspring. The protocol was written following the PRISMA Checklist and was registered in the PROSPERO database (registration number CRD42022381136). We implemented a comprehensive search in PubMed, Embase and Web of Science databases to identify all potentially related articles from inception through 1 December 2022. We assessed cohort studies and case-control studies using the Newcastle-Ottawa Scale (NOS), and the Joanna Briggs Institute (JBI) critical appraisal tool to assess the quality of cross-sectional studies. Heterogeneity was investigated by using Cochrane Q tests and I 2 statistics. In addition, according to the research design, population source and population size, the reasons for the heterogeneity were analysed. A total of 15 observational studies were included in this analysis. Our meta-analysis suggests that atopic dermatitis in offspring is not associated with active smoking during pregnancy (pooled OR, 0.96 [95% CI 0.86-1.07]); however, it is related to passive smoking (OR, 1.52 [95% CI 1.36-1.70]). Passive smoking during pregnancy is associated with an increased risk of eczema development in offspring. More research is needed to explore the risk of active smoking and eczema development in offspring, especially the association between measurements of pregnancy cotinine levels in maternal body fluids and AD in offspring., (© 2024 European Academy of Dermatology and Venereology.)

Narrow-bandgap (NBG) Pb-Sn perovskites are ideal candidates as rear subcell in all-perovskite tandem solar cells. Because Pb-Sn perovskites contain multiple components, the rational regulation of vertical structure and both interfaces of the film is primarily crucial to achieve high-performing NBG perovskite solar cells (PSCs). Herein, a molecule anchoring strategy is developed to in situ construct Cs 0.1 MA 0.3 FA 0.6 Pb 0.5 Sn 0.5 I 3 perovskite film with vertically aligned crystals and optimized interfaces. Specifically, l-alanine methyl ester is developed as an anchoring additive to induce the vertical crystal growth, while PEA 2 PbI 3 SCN film is introduced to promote the homogeneous crystallization at the buried interface via SCN- anchoring with cations. Further ethylenediamine dihalides (EDA(I/Cl) 2 ) post-treatment leads to the gradient energy level alignment on the film surface. Pb-Sn PSCs based on such film show efficient charge transport and extraction, producing a champion power conversion efficiency (PCE) of 22.3% with an impressive fill factor of 82.14%. Notably, combining with semitransparent 1.78 eV wide-bandgap PSCs, the four-terminal all-perovskite tandem device achieves a PCE of 27.1%. This work opens up a new pathway to boost the performance of Pb-Sn PSCs and their tandem devices., (© 2024 Wiley‐VCH GmbH.)

Background: 2-ethylhexyldiphenyl phosphate (EHDPP) was used widespread in recent years and it was reported to impair reproductive behaviors and decrease fertility in male Japanese medaka. However, whether EHDPP causes spermatogenesis disturbance remains uncertain., Objectives: We aimed to study the male reproductive toxicity of EHDPP and its related mechanism., Methods: Human spermatocyte cell line GC-2 was treated with 10 µM, 50 µM or 100 µM EHDPP for 24 h. Male CD-1 mice aged 6 weeks were given 1, 10, or 100 mg/kg/d EHDPP daily for 42 days and then euthanized to detect sperm count and motility. Proliferation, apoptosis, oxidative stress was detected in mice and cell lines. Metabolome and transcriptome were used to detect the related mechanism. Finally, anti-oxidative reagent N-Acetylcysteine was used to detect whether it could reverse the side-effect of EHDPP both in vivo and in vitro., Results: Our results showed that EHDPP inhibited proliferation and induced apoptosis in mice testes and spermatocyte cell line GC-2. Metabolome and transcriptome showed that nucleotide metabolism disturbance and DNA damage was potentially involved in EHDPP-induced reproductive toxicity. Finally, we found that excessive ROS production caused DNA damage and mitochondrial dysfunction; NAC supplement reversed the side effects of EHDPP such as DNA damage, proliferation inhibition, apoptosis and decline in sperm motility., Conclusion: ROS-evoked DNA damage and nucleotide metabolism disturbance mediates EHDPP-induced germ cell proliferation inhibition and apoptosis, which finally induced decline of sperm motility., 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.)

Past studies have observed that BHPF induces multi-organ toxicity, however, whether it induces damage to male reproductive system and the specific mechanism remains unclear. In the present study, male mice were given 0, 2, 10 or 50 mg/kg/day of BHPF by gavage for 35 days to observe its effect on reproductive organ and sperm quality. The results indicated that BHPF decreased sperm count and sperm motility in a dose-dependent manner. Besides, our results demonstrated that BHPF triggered the proliferation inhibition and cell death of germ cells in vivo and in vitro. Also, BHPF reduced the expression of function markers for germ cells, Sertoli cells, and Leydig cells, indicating its damage to function of testis cells. Simultaneously, testicular microenvironment was found to be altered by BHPF, as presented with declined testosterone level and decreased expression of local microenvironment regulators. Overall, our findings indicated the detrimental effects of BHPF on male reproductive function in mice, suggesting testicular function and local microenvironment disturbance as mechanism underlying testicular damage., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Lan Chao reports financial support was provided by the National Natural Science Foundation of China. If there are other authors, they 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.)

Neonatal hypoxic-ischemic encephalopathy (HIE) is the primary cause of neonatal mortality and severe neurological sequelae. The interaction of neuroinflammation with the immune system represents a significant pathological mechanism underlying the development of HIE. Neutrophil extracellular traps (NETs) are a recently identified antimicrobial mechanism utilized by neutrophils. NETs can act as damage-associated molecular patterns, thereby amplifying the immune response and exerting proinflammatory effects. However, further research is needed to elucidate their role in the pathogenesis of HIE. In this study, we investigated the role of NETs in a hypoxic-ischemic brain injury (HIBI) model. We first reported that a pharmacological intervention to inhibit peptidylarginine deiminase type IV (PAD4) may constitute an effective strategy for reducing HI insult-induced neuroinflammation, neuronal apoptosis, and brain tissue destruction while also enhancing long-term neurobehavioral function in mice. These results support a pathological role for NETs in HIBI, and targeting PAD4 is a potential direction for the treatment of HIE., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

A major alternative to bisphenol A (BPA), fluorene-9-bisphenol (BHPF) has been shown to cause multiorgan toxicity. However, its reproductive toxicity and the underlying biological mechanism remain largely unknown. Recently, changes in the gut microbiota and metablome caused by environmental contaminant exposure and their potential impact on male reproductive health have been of great concern. Therefore, we aimed to elucidate the underlying mechanism of BHPF-related fertility impairment by integrating metabolome and microbiome analysis. In the present study, we showed that BHPF exposure caused testicular dysfunction with impaired spermatogenesis and disrupted steroid hormone synthesis. Mechanistically, altered gut microbiota and metabolites were revealed by 16S rDNA sequencing and untargeted metabolomics analysis. Subsequent multi-omics combination analysis revealed a strong correlation between altered microbiota and lipid metabolites. We also found a strong relationship between lipid metabolites and sperm parameters such as sperm concentration, sperm motility, etc. Most importantly, these findings provide new insights into the mechanistic scenario underlying BHPF-induced fertility toxicity, that disrupted lipid metabolism caused by gut microbiota dysbiosis may be a reason for reproductive impairment caused by BHPF 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 © 2024 Elsevier Ltd. All rights reserved.)

Inverted NiO x -based perovskite solar cells (PSCs) exhibit considerable potential because of their low-temperature processing and outstanding excellent stability, while is challenged by the carriers transfer at buried interface owing to the inherent low carrier mobility and abundant surface defects that directly deteriorates the overall device fill factor. Present work demonstrates a chemical linker with the capability of simultaneously grasping NiO x and perovskite crystals by forming a Ni-S-Pb bridge at buried interface to significantly boost the carriers transfer, based on a rationally selected molecule of 1,3-dimethyl-benzoimidazol-2-thione (NCS). The constructed buried interface not only reduces the pinholes and needle-like residual PbI 2 at the buried interface, but also deepens the work function and valence band maximum positions of NiO x , resulting in a smaller VBM offset between NiO x and perovskite film. Consequently, the modulated PSCs achieved a high fill factor up to 86.24 %, which is as far as we know the highest value in records of NiO x -based inverted PSCs. The NCS custom-tailored PSCs and minimodules (active area of 18 cm 2 ) exhibited a champion efficiency of 25.05 % and 21.16 %, respectively. The unencapsulated devices remains over 90 % of their initial efficiency at maximum power point under continuous illumination for 1700 hours., (© 2024 Wiley-VCH GmbH.)

Erhai Lake, a highland lake situated in Southwest China, provides critical aquatic protein sources for the local community, and its preservation is vital due to the sensitivity of alpine freshwater ecosystems to disturbance. However, there is a lack of research on the contamination status of methylmercury (MeHg) in aquatic organisms of the Erhai Lake Basin. MeHg concentrations in important commercial fish species from the Erhai Lake were examined, and the potential health risks associated with human consumption were assessed. Our results showed significant inter-species differences in fish muscle MeHg: the carnivorous S. asotus exhibited the highest level (303 ng/g; ww), while that of the detritivorous R. ocellatus was the lowest (3.86 ng/g). Moreover, MeHg concentrations in P. fulvidraco and C. auratus collected from the Luoshi River (a major tributary of Erhai Lake) were significantly higher compared to those from the Erhai Lake, indicating possible river-based input of MeHg into the Erhai Lake. Additionally, our study revealed a significant positive correlation between the MeHg levels and the length as well as weight of the examined fish species. All the fish species analyzed in our study had MeHg concentrations within the limits of China's food safety standard. Nevertheless, a relatively low consumption quantity of 16 g per day of certain species (i.e., S. asotus) may still pose potential health risks especially for children. The present study provides baseline data for MeHg monitoring and risk assessment in the Erhai Lake Basin, and warrants continued monitoring and source investigation., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: To evaluate the effect of video-based coaching on the gynecology resident performance of laparoscopic salpingectomy., Methods: PGY-1 and PGY-2 residents were randomized before their gynecology rotations to standard gynecology curriculum (control group) or standard curriculum plus two video-coaching sessions by a fellowship-trained minimally invasive gynecologic surgeon (VBC group). Residents were video recorded intraoperatively performing three unilateral laparoscopic salpingectomies. Participants in the VBC group were coached between the procedures. The primary outcome was the improvement in modified GOALS (Global Operative Assessment of Laparoscopic Skills) and OSA-LS (Objective Structured Assessment of Laparoscopic Salpingectomy) scores, compared with baseline, in the VBC and control groups, with videos independently graded by three blinded minimally invasive gynecologic surgeons. A minimum sample size of 18 participants (nine per group) was needed to achieve 90% power to detect a difference of 5.0 points., Results: From October 2021 to December 2022, 28 PGY-1 and PGY-2 residents completed the study with 14 participants per group. Baseline characteristics were similar between groups. In the VBC group, modified GOALS scores significantly improved by 3.0 points from video 1 to video 2 ( P =.04) and by 3.2 points from video 1 to video 3 ( P =.02). Modified OSA-LS scores also increased significantly in the VBC group, by 6.1 points from video 1 to video 3 ( P =.02). In the control group, modified GOALS and OSA-LS scores improved from baseline but were not significant ( P =.2, P =.5). Video-based coaching also enhanced resident comfort and confidence in performing laparoscopic surgery., Conclusion: Video-based coaching improves resident performance of laparoscopic salpingectomy and can be used as an adjunct to resident surgical training., Clinical Trial Registration: ClinicalTrials.gov , NCT05103449., Competing Interests: Financial Disclosure Kimberly A. Kho, MD serves on the Medical Advisory Board for Channel MedSystems, Inc and is a principal investigator for investigator-initiated clinical research for Hologic, Inc. Jessica Pruszynski, PhD reports money was paid to her institution from Patient-Centered Outcomes Research Institute (PCORI). The other authors did not report any potential conflicts of interest., (Copyright © 2024 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Background: Study objectives included the development of a practical nomogram for predicting live birth following frozen-thawed embryo transfers in ovulatory women., Methods: Totally, 2884 patients with regular menstrual cycles in our center were retrospectively enrolled. In an 8:2 ratio, we randomly assigned patients to training and validation cohorts. Then we identified risk factors by multivariate logistic regression and constructed nomogram. Finally, receiver operating characteristic curve analysis, calibration curve and decision curve analysis were performed to assess the calibration and discriminative ability of the nomogram., Results: We identified five variables which were related to live birth, including age, anti-Müllerian hormone (AMH), protocol of frozen-thawed embryo transfer (FET), stage of embryos and amount of high-quality embryos. We then constructed nomograms that predict the probabilities of live birth by using those five parameters. Receiver operating characteristic curve analysis (ROC) showed that the area under the curve (AUC) for live birth was 0.666 (95% CI: 0.644-0.688) in the training cohort. The AUC in the subsequent validation cohorts was 0.669 (95% CI, 0.625-0.713). The clinical practicability of this nomogram was demonstrated through calibration curve analysis and decision curve analysis., Conclusions: Our nomogram provides a visual and simple tool in predicting live birth in ovulatory women who received FET. It could also provide advice and guidance for physicians and patients on decision-making during the FET procedure., (© 2024. The Author(s).)

Gulf War Illness (GWI) is a debilitating condition marked by chronic fatigue, cognitive problems, pain, and gastrointestinal (GI) complaints in veterans who were deployed to the 1990-1991 Gulf War. Fatigue, GI complaints, and other chronic symptoms continue to persist more than 30 years post-deployment. Several potential mechanisms for the persistent illness have been identified and our prior pilot study linked an altered gut microbiome with the disorder. This study further validates and builds on our prior preliminary findings of host gut microbiome dysbiosis in veterans with GWI. Using stool samples and Multidimensional Fatigue Inventory (MFI) data from 89 GW veteran participants (63 GWI cases and 26 controls) from the Boston biorepository, recruitment, and integrative network (BBRAIN) for Gulf War Illness, we found that the host gut bacterial signature of veterans with GWI showed significantly different Bray-Curtis beta diversity than control veterans. Specifically, a higher Firmicutes to Bacteroidetes ratio, decrease in Akkermansia sp., Bacteroides thetaiotamicron , Bacteroides fragilis , and Lachnospiraceae genera and increase in Blautia , Streptococcus , Klebsiella , and Clostridium genera, that are associated with gut, immune, and brain health, were shown. Further, using MaAsLin and Boruta algorithms, Coprococcus and Eisenbergiella were identified as important predictors of GWI with an area under the curve ROC predictive value of 74.8%. Higher self-reported MFI scores in veterans with GWI were also significantly associated with an altered gut bacterial diversity and species abundance of Lachnospiraceae and Blautia . These results suggest potential therapeutic targets for veterans with GWI that target the gut microbiome and specific symptoms of the illness.

Scaphoid nonunion occurs in 10%-15% of scaphoid fractures, potentially resulting in scaphoid nonunion advanced collapse. Distal scaphoid excision without allograft interposition is a known treatment, but can result in loss of carpal height and pain. This report describes the application of human acellular dermal matrix as an interposition graft after distal scaphoid excision for stage I scaphoid nonunion advanced collapse. Postoperatively, the patient initiated early range of motion and returned to full activity at 6 weeks. He demonstrated resolution of his pain 6 years later., Competing Interests: Dr. David Kulber is a member of the Board of Directors for MTF Biologics. He did not hold the position at the time of this intervention. All the other authors have no financial interest to declare in relation to the content of this article., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The American Society of Plastic Surgeons.)

We aimed to build a deep learning-based pathomics model to predict the early recurrence of non-muscle-infiltrating bladder cancer (NMIBC) in this work. A total of 147 patients from Xuzhou Central Hospital were enrolled as the training cohort, and 63 patients from Suqian Affiliated Hospital of Xuzhou Medical University were enrolled as the test cohort. Based on two consecutive phases of patch level prediction and WSI-level predictione, we built a pathomics model, with the initial model developed in the training cohort and subjected to transfer learning, and then the test cohort was validated for generalization. The features extracted from the visualization model were used for model interpretation. After migration learning, the area under the receiver operating characteristic curve for the deep learning-based pathomics model in the test cohort was 0.860 (95% CI 0.752-0.969), with good agreement between the migration training cohort and the test cohort in predicting recurrence, and the predicted values matched well with the observed values, with p values of 0.667766 and 0.140233 for the Hosmer-Lemeshow test, respectively. The good clinical application was observed using a decision curve analysis method. We developed a deep learning-based pathomics model showed promising performance in predicting recurrence within one year in NMIBC patients. Including 10 state prediction NMIBC recurrence group pathology features be visualized, which may be used to facilitate personalized management of NMIBC patients to avoid ineffective or unnecessary treatment for the benefit of patients., (© 2024. The Author(s).)

Purpose of Review: Hysterectomy is the most common gynecologic surgical procedure performed on women in the United States. While there are data supporting that hysterectomy for benign indication often does not reduce sexual function and may in fact improve sexual function as fibroids and endometriosis are resected, it remains unclear if there are factors within the perioperative period that affect sexual function in the years following surgery. To date, there is no consensus on what factors can optimize patients' sexual function after hysterectomy., Recent Findings: We present the current literature that assesses factors which may contribute to sexual function after hysterectomy. Preoperative demographic factors, including increasing age, pelvic pain, and preoperative sexual dysfunction, play a large role in postoperative sexual function. Perioperatively, there is a growing amount of data suggesting that premenopausal salpingo-oophorectomy at the time of hysterectomy may increase the risk of sexual dysfunction after hysterectomy, and no conclusive evidence that subtotal hysterectomy improves sexual function. The route of hysterectomy and technique of cuff closure can impact sexual function after hysterectomy due to the risk of shortening the vaginal length., Summary: There is a lack of high-quality evidence that can provide a consensus on factors to optimize sexual function after hysterectomy. A growing area of research in the excision of endometriosis procedures is the consideration of nerve-sparing surgery. Considering the many variables that exist when counseling a patient on benign hysterectomy and its effects on sexual function, it is critical to understand the current research that exists with regards to these factors., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objective : Gulf War Illness (GWI) is a debilitating multisymptom condition that affects nearly a third of 1990-91 Gulf War (GW) veterans. Symptoms include pain, fatigue, gastrointestinal issues, and cognitive decrements. Our work has shown that GWI rates and potential causes for symptoms vary between men and women veterans. Studies have documented neuropsychological and neuroimaging findings mostly in men or combined sex datasets. Data are lacking for women veterans due to lack of power and repositories of women veteran samples. Methods : We characterized GW women veterans in terms of demographics, exposures, neuropsychological and neuroimaging outcomes from the newly collated Boston, Biorepository and Integrative Network (BBRAIN) for GWI. Results : BBRAIN women veterans are highly educated with an average age of 54 years. 81% met GWI criteria, 25% met criteria for current PTSD, 78% were white, and 81% served in the Army. Exposure to combined acetylcholinesterase inhibitors (AChEi) including skin pesticides, fogs/sprays and/or pyridostigmine bromide (PB) anti-nerve gas pill exposure resulted in slower processing speed on attentional tasks and a trend for executive impairment compared with non-exposed women. Brain imaging outcomes showed lower gray matter volumes and smaller caudate in exposed women. Conclusions : Although subtle and limited findings were present in this group of women veterans, it suggests that continued follow-up of GW women veterans is warranted. Future research should continue to evaluate differences between men and women in GW veteran samples. The BBRAIN women sub-repository is recruiting and these data are available to the research community for studies of women veterans.

The tourism industry is a significant contribution to the economy of many countries, including Pakistan. However, its activities often have a negative impact on the environment, particularly related to climate change. Notably, Pakistan ranks fifth among countries most affected by climate change, which requires a targeted analysis of the tourism sector to determine its potential impacts. Despite the critical nature of this issue, there is currently a lack of research that examines how climate change specifically impacts Pakistan's tourism industry. This study aims to address this gap by using the Tourism Climate Index (TCI) to assess the impact of climate change on the suitability of different tourism locations across the country. Our results show that popular tourist destinations such as Gilgit-Baltistan experience their peak season in the warmer third quarter (summer), which corresponds to the highest observed TCI values. This suggests that warmer temperatures could boost tourism activity and spending in these regions. Furthermore, our analysis shows that air temperature plays a crucial role in determining tourist comfort levels and significantly influences tourists' TCI values and sensory experiences. The results of this study show that the TCI methodology can be an effective tool for further research into the geographical impacts of climate change on tourism. By identifying necessary changes due to climatic changes, future studies could provide valuable insights into how the tourism industry can adapt to and reduce its environmental footprint., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Published by Elsevier Ltd.)

Sialoglycan-binding enveloped viruses often possess receptor-destroying activity to avoid being immobilized by non-functional decoy receptors. Sialic acid (Sia)-binding paramyxoviruses contain a hemagglutinin-neuraminidase (HN) protein that possesses both Sia-binding and -cleavage activities. The multivalent, dynamic receptor interactions of paramyxovirus particles provide virion motility and are a key determinant of host tropism. However, such multivalent interactions have not been exhaustively analyzed, because such studies are complicated by the low affinity of the individual interactions and the requirement of high titer virus stocks. Moreover, the dynamics of multivalent particle-receptor interactions are difficult to predict from Michaelis-Menten enzyme kinetics. Therefore, we here developed Ni-NTA nanoparticles that multivalently display recombinant soluble HN tetramers via their His tags (HN-NPs). Applying this HN-NP platform to Newcastle disease virus (NDV), we investigated using biolayer interferometry (BLI) the role of important HN residues in receptor-interactions and analyzed long-range effects between the catalytic site and the second Sia binding site (2SBS). The HN-NP system was also applicable to other paramyxoviruses. Comparative analysis of HN-NPs revealed and confirmed differences in dynamic receptor-interactions between type 1 human and murine parainfluenza viruses as well as of lab-adapted and clinical isolates of human parainfluenza virus type 3, which are likely to contribute to differences in tropism of these viruses. We propose this novel platform to be applicable to elucidate the dynamics of multivalent-receptor interactions important for host tropism and pathogenesis, particularly for difficult to grow sialoglycan-binding (paramyxo)viruses., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Wu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The diagnosis of leukemia is a serious matter that requires immediate and accurate attention. This research presents a revolutionary method for diagnosing leukemia using a Capsule Neural Network (CapsNet) with an optimized design. CapsNet is a cutting-edge neural network that effectively captures complex features and spatial relationships within images. To improve the CapsNet's performance, a Modified Version of Osprey Optimization Algorithm (MOA) has been utilized. Thesuggested approach has been tested on the ALL-IDB database, a widely recognized dataset for leukemia image classification. Comparative analysis with various machine learning techniques, including Combined combine MobilenetV2 and ResNet18 (MBV2/Res) network, Depth-wise convolution model, a hybrid model that combines a genetic algorithm with ResNet-50V2 (ResNet/GA), and SVM/JAYA demonstrated the superiority of our method in different terms. As a result, the proposed method is a robust and powerful tool for diagnosing leukemia from medical images., (© 2024. The Author(s).)

Bacteriophage ϕ6 is a segmented dsRNA virus with a lipid envelope, which are unusual traits in bacterial viruses but common in eukaryotic viruses. This uniqueness allowed ϕ6 and its Pseudomonad hosts to serve as a molecular model for RNA genetics, mutation, replication, packaging, and reassortment in both bacterial and eukaryotic viruses. However, an additional uniqueness of ϕ6, created by its high mutation rate, was its use as an experimental system to study key questions such as the evolution of sex (segment reassortment), host-pathogen interactions, mutational load, rates of adaptation, genetic and phenotypic complexity, and game theory.

Objective: To assess the effect of activated charcoal on the single-dose pharmacokinetics of mavacamten when administered 2 h or 6 h after mavacamten dosing., Methods: In this open-label, randomized, parallel-group study, healthy adults were randomized into three groups to receive mavacamten 15 mg alone or mavacamten 15 mg plus activated charcoal 50 g administered either 2 h or 6 h after mavacamten dosing. Pharmacokinetic parameters were derived from plasma concentration-time data using noncompartmental methods., Results: Of the 45 participants randomized, 37 completed the study. When activated charcoal was administered 2 h after mavacamten dosing, mavacamten absorption and exposure were reduced compared with when mavacamten was administered alone: the area under the concentration-time curve from 0 to 72 h (AUC 0-72 ) and area under the concentration-time curve from time 0 extrapolated to infinity (AUC INF ) were reduced by 14% and 34%, respectively. The maximum plasma concentration (C max ) was also slightly lower when activated charcoal was administered 2 h after mavacamten dosing than with mavacamten alone. Pharmacokinetic profiles were similar for mavacamten alone and mavacamten plus activated charcoal administered 6 h after mavacamten dosing., Conclusions: Activated charcoal was successful in reducing mavacamten absorption and exposure when administered as soon as possible after identification of a need for adsorption (2 h after mavacamten dosing). No change in exposure was observed when activated charcoal was administered 6 h after mavacamten dosing., Clinical Trial Registration: NCT05320094., (© 2024. The Author(s).)

Multidrug resistance (MDR) is a dominant challenge in cancer chemotherapy failure. The over-expression of breast cancer resistance protein (BCRP) in tumorous cells, along with its extensive substrate profile, is a leading cause of tumor MDR. Herein, on the basis of styrene maleic acid (SMA) polymer membrane protein stabilization strategy and surface plasmon resonance (SPR) biosensor, a novel high-throughput screening (HTS) system for BCRP inhibitors has been established. Firstly, LLC-PK1 and LLC-PK1/BCRP cell membranes were co-incubated with SMA polymers to construct SMA lipid particles (SMALPs). PK1-SMALPs were thus immobilized in channel 1 of the L1 chip as the reference channel, and BCRP-SMALPs were immobilized in channel 2 as the detection channel to establish the BCRP-SMALPs-SPR screening system. The methodological investigation demonstrated that the screening system was highly specific and stable. Three active compounds were screened out from 26 natural products and their affinity constants with BCRP were determined. The K D of xanthotoxin, bergapten, and naringenin were 5.14 μM, 4.57 μM, and 3.72 μM, respectively. The in vitro cell verification experiments demonstrated that xanthotoxin, bergapten, and naringenin all significantly increased the sensitivity of LLC-PK1/BCRP cells to mitoxantrone with possessing reversal BCRP-mediated MDR activity. Collectively, the developed BCRP-SMALPs-SPR screening system in this study has the advantages of rapidity, efficiency, and specificity, providing a novel strategy for the in-depth screening of BCRP inhibitors with less side effects and higher efficacy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

In this work, a novel formaldehyde sensor was constructed based on nanoporous, flower-like, Pb-containing Pd-Au nanoparticles deposited on the cathode in a double-cabin galvanic cell (DCGC) with a Cu plate as the anode, a multiwalled carbon nanotube-modified glassy carbon electrode as the cathode, a 0.1 M HClO 4 aqueous solution as the anolyte, and a 3.0 mM PdCl 2 + 1.0 mM HAuCl 4 + 5.0 mM Pb(ClO 4 ) 2 + 0.1 M HClO 4 aqueous solution as the catholyte, respectively. Electrochemical studies reveal that the stripping of bulk Cu can induce underpotential deposition (UPD) of Pb during the galvanic replacement reaction (GRR) process, which affects the composition and morphology of Pb-containing Pd-Au nanoparticles. The electrocatalytic activity of Pb-containing nanoparticles toward formaldehyde oxidation was examined in an alkaline solution, and the experimental results showed that formaldehyde mainly caused direct oxidation on the surface of Pb-containing Pd-Au nanoparticles while inhibiting the formation of CO poison to a large degree. The proposed formaldehyde sensor exhibits a linear amperometric response to formaldehyde concentrations from 0.01 mM to 5.0 mM, with a sensitivity of 666 μA mM -1 cm -2 , a limit of detection (LOD) of 0.89 μM at triple signal-to-noise, rapid response, high anti-interference ability, and good repeatability.

The discovery of high thermal stability, broad-band near-infrared (NIR) fluorescent phosphors holds significant potential in applications such as non-destructive testing, promoting plant growth, and night vision devices. In this study, a novel broad-band NIR phosphors Li 2 MgZrO 4 (LMZ): 1.0 %Cr 3+ , y%Yb 3+ were synthesized via a high-temperature solid-state reaction method, with the optimal doping concentration found to be y = 1.5. These phosphors exhibited broad NIR emission in the range of 700-1050 nm by effective energy transfer from Cr 3+ to Yb 3+ . The maximum full width at half maximum (FWHM) of the Cr 3+ /Yb 3+ co-doped LMZ phosphor is 270 nm. The thermal stability of the phosphors was improved with Yb 3+ co-doping. Additionally, energy transfer from Cr 3+ to Yb 3+ was confirmed through luminescence spectra and lifetime analysis. Finally, NIR pc-LED devices composed of a 460 nm ultraviolet chip and LMZ: 1.0 %Cr 3+ , 1.5 %Yb 3+ phosphors were fabricated, offering a highly promising source of invisible light. These results demonstrate the wide-ranging potential applications of this novel, high thermal stability, and ultra-broad NIR emitting fluorescent phosphor., 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.)

Purpose: This study was designed to explore the effects of interleukin 33 (IL-33) on the progression of atherosclerosis and the possible mechanism., Methods: The adhesion assay was performed on isolated peripheral blood mononuclear cells (PBMCs) and human umbilical vein endothelial cells (HUVEC). The expression of proteins and messenger RNA (mRNA) were detected by western blot and quantitative real-time polymerase chain reaction (PCR), including intercellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and P-selectin. The effect of IL-33 on the interaction of growth stimulation expressed gene 2 (ST2) with myeloid differentiation factor 88 (MyD88) and interleukin-1 receptor-associated kinase (IRAK) 1/4 were investigated using co-immunoprecipitation assay. An apolipoprotein (Apo) E -/- mice model was used to confirm the effect of IL-33 on atherosclerosis progression. Area of plaques was recorded by hematoxylin-eosin (H&E) staining. The severity of atherosclerosis plaque was evaluated using immunohistochemistry assay, and lipid accumulation was measured by an oil red O staining. In contrast, western blot was performed to detect the expression levels of VCAM-1, extracellular signal-regulated kinase (ERK) 1/2, and interferon regulatory factor 1 (IRF1)., Results: Our study observed that IL-33 suppressed cell adhesion and the expression of VCAM-1 in tumor necrosis factor-α (TNF-α) exposed HUVEC. Moreover, the addition of IL-33 significantly inhibited the expression of IRF1 and the binding level of IRF1 to VCAM-1 and also promoted the phosphorylation level of IRAK1/4 and ERK1/2 compared to TNF-α-stimulated HUVEC. The ST2 neutralizing antibody or ERK pathway inhibitor SCH772984 reversed the regulatory effects of IL-33 on HUVEC, suggesting that IL-33 suppressed IRF1 and VCAM-1 dependent on binding to ST2 and activating the ERK1/2 signaling pathway. Further investigation in vivo confirmed that IL-33 decreased the expressions of IRF1 and VCAM-1 by activating the phosphorylation of ERK1/2 in the thoracic aorta of Apo E -/- mice., Conclusion: In conclusion, our results demonstrated that IL-33 plays a protective role in the progression of atherosclerosis by inhibiting cell adhesion via the ERK1/2-IRF1-VCAM-1 pathway. This study may provide a potential therapeutic way to prevent the development of atherosclerosis., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: This study aimed to construct and characterize a humanized influenza mouse model expressing hST6GAL1., Methods: Humanized fragments, consisting of the endothelial cell-specific K18 promoter, human ST6GAL1-encoding gene, and luciferase gene, were microinjected into the fertilized eggs of mice. The manipulated embryos were transferred into the oviducts of pseudopregnant female mice. The offspring were identified using PCR. Mice exhibiting elevated expression of the hST6GAL1 gene were selectively bred for propagation, and in vivo analysis was performed for screening. Expression of the humanized gene was tested by performing immunohistochemical (IHC) analysis. Hematologic and biochemical analyses using the whole blood and serum of humanized hST6GAL1 mice were performed., Results: Successful integration of the human ST6GAL1 gene into the mouse genome led to the overexpression of human SiaT ST6GAL1. Seven mice were identified as carrying copies of the humanized gene, and the in vivo analysis indicated that hST6GAL1 gene expression in positive mice mirrored influenza virus infection characteristics. The IHC results revealed that hST6GAL1 was expressed in the lungs of humanized mice. Moreover, the hematologic and biochemical parameters of the positive mice were within the normal range., Conclusion: A humanized influenza mouse model expressing the hST6GAL1 gene was successfully established and characterized., (© 2024 The Author(s). Animal Models and Experimental Medicine published by John Wiley & Sons Australia, Ltd on behalf of The Chinese Association for Laboratory Animal Sciences.)

Bionic porous structure has been widely used in the field of bone implantation, because it can imitate the topological structure of bone, reduce the elastic modulus of metal bone implantation, and meet the mechanical properties and material transmission characteristics after implantation. This paper mainly studies the effects of different bionic porous structures on the mechanical and material transport properties of bone scaffolds. Firstly, under the same porosity condition, 12 groups of bionic porous structures with different shapes were designed, including G, P, D, I-type three period minimal surface (TPMS) and Voronoi porous structures with different irregularities. Then uses ABAQUS to carry out mechanical finite element simulation on different bionic porous structures, and uses Ti-6Al-4V alloy as forming material, uses laser powder bed fusion technology (LPBF) to prepare the scaffold, then carries out compression experiments. At the same time, COMSOL software is used to simulate the flow characteristics, analyze the permeability characteristics, and verified through cell experiment in vivo . The results show that the mechanical and permeability are different with vary scaffolds. In terms of topology, the morphological characteristics of TPMS are similar to trabecular bone, its compressive strength is relatively strong. Voronoi scaffold has lower elastic modulus, which can provide sufficient mechanical support while reducing stress shielding. In addition, the permeability of TPMS scaffold is better than Voronoi scaffold, which is helpful to promote cell proliferation and bone ingrowth. These bionic porous structures have their own advantages. Therefore, when designing porous structures for bone implantation, it is necessary to select the appropriate porous structure according to different bone implantation requirements. The research will help promote the clinical application of porous structures in the field of bone implantation, and provide theoretical support for the exploration of bone implantation structure design.

Previous studies have shown that feeding mice with food containing mantle tissue from Japanese scallops results in aggravated liver and kidney damage, ultimately resulting in mortality within weeks. The aim of this study is to evaluate the toxicity of scallop mantle in China's coastal areas and explore the impact of scallop mantle toxins (SMT) on intestinal barrier integrity and gut microbiota in mice. The Illumina MiSeq sequencing of V3-V4 hypervariable regions of 16S ribosomal RNA was employed to study the alterations in gut microbiota in the feces of SMT mice. The results showed that intestinal flora abundance and diversity in the SMT group were decreased. Compared with the control group, significant increases were observed in serum indexes related to liver, intestine, inflammation, and kidney functions among SMT-exposed mice. Accompanied by varying degrees of tissue damage observed within these organs, the beneficial bacteria of Muribaculaceae and Marinifilaceae significantly reduced, while the harmful bacteria of Enterobacteriaceae and Helicobacter were significantly increased. Taken together, this article elucidates the inflammation and glucose metabolism disorder caused by scallop mantle toxin in mice from the angle of gut microbiota and metabolism. SMT can destroy the equilibrium of intestinal flora and damage the intestinal mucosal barrier, which leads to glucose metabolism disorder and intestinal dysfunction and may ultimately bring about systemic toxicity.

Supported membrane electrophoresis is a promising technique for collecting membrane proteins in native bilayer environments. However, the slow mobility of typical transmembrane proteins has impeded the technique's advancement. Here, we successfully applied cell membrane electrophoresis to rapidly enrich a 12-transmembrane helix protein, glucose transporter 1 with antibodies (GLUT1 complex), by tuning the buffer pH and ionic strength. The identified conditions allowed the separation of the GLUT1 complex and a lipid probe, Fast-DiO, within a native-like environment in a few minutes. A force model was developed to account for distinct electric and drag forces acting on the transmembrane and aqueous-exposed portion of a transmembrane protein as well as the electroosmotic force. This model not only elucidates the impact of size and charge properties of transmembrane proteins but also highlights the influence of pH and ionic strength on the driving forces and, consequently, electrophoretic mobility. Model predictions align well with experimentally measured electrophoretic mobilities of the GLUT1 complex and Fast-DiO at various pH and ionic strengths as well as with several lipid probes, lipid-anchored proteins, and reconstituted membrane proteins from previous studies. Force analyses revealed the substantial membrane drag of the GLUT1 complex, significantly slowing down electrophoretic mobility. Besides, the counterbalance of similar magnitudes of electroosmotic and electric forces results in a small net driving force and, consequently, reduced mobility under typical neutral pH conditions. Our results further highlight how the size and charge properties of transmembrane proteins influence the suitable range of operating conditions for effective movement, providing potential applications for concentrating and isolating membrane proteins within this platform.

The CRISPR/Cas system comprises RNA-guided nucleases, the target specificity of which is directed by Watson-Crick base pairing of target loci with single guide (sg)RNA to induce the desired edits. CRISPR-associated proteins and other engineered nucleases are opening new avenues of research in crops to induce heritable mutations. Here, we review the diversity of CRISPR-associated proteins and strategies to deregulate genome-edited (GEd) crops by considering them to be close to natural processes. This technology ensures yield without penalties, advances plant breeding, and guarantees manipulation of the genome for desirable traits. DNA-free and off-target-free GEd crops with defined characteristics can help to achieve sustainable global food security under a changing climate, but need alignment of international regulations to operate in existing supply chains., Competing Interests: Declaration of interests The authors have no conflicts of interest to disclose., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Lead halide perovskites (LHPs) containing organic parts are emerging optoelectronic materials with a wide range of applications thanks to their high optical absorption, carrier mobility, and easy preparation methods. They possess spin-dependent properties, such as strong spin-orbit coupling (SOC), and are promising for spintronics. The Rashba effect in LHPs can be manipulated by a magnetic field and a polarized light field. Considering the surfaces and interfaces of LHPs, light polarization-dependent optoelectronics of LHPs has attracted attention, especially in terms of spin-dependent photocurrents (SDPs). Currently, there are intense efforts being made in the identification and separation of SDPs and spin-to-charge interconversion in LHP. Here, we provide a comprehensive review of second-order nonlinear photocurrents in LHP in regard to spintronics. First, a detailed background on Rashba SOC and its related effects (including the inverse Rashba-Edelstein effect) is given. Subsequently, nonlinear photo-induced effects leading to SDPs are presented. Then, SDPs due to the photo-induced inverse spin Hall effect and the circular photogalvanic effect, together with photocurrent due to the photon drag effect, are compared. This is followed by the main focus of nonlinear photocurrents in LHPs containing organic parts, starting from fundamentals related to spin-dependent optoelectronics. Finally, we conclude with a brief summary and future prospects.

The occurrence of unexplained recurrent spontaneous abortion (URSA) is closely related to immune system disorders, however, the underlying mechanisms remain unclear. The purpose of this study was to investigate the expression of GRIM-19 in URSA and the possible pathogenesis of URSA according to macrophage polarization. Here, we showed that GRIM-19 was downregulated in the uterine decidual macrophages of patients with URSA and that GRIM-19 downregulation was accompanied by increased M1 macrophage polarization. Furthermore, the expression levels of glycolytic enzymes were substantially enhanced in the uterine decidual macrophages of URSA patients, and glycolysis in THP-1-derived macrophages was further enhanced by the downregulation of GRIM-19. Additionally, the increase of M1 macrophages resulting from the loss of GRIM-19 was significantly reversed in cells treated with 2-deoxy-D-glucose (2-DG, an inhibitor of glycolysis). To provide more direct evidence, GRIM-19 deficiency was shown to promote macrophage polarization to the M1 phenotype in GRIM-19+/- mouse uteri. Overall, our study provides evidence that GRIM-19 deficiency may play a role in regulating macrophage polarization in URSA, and that glycolysis may participate in this process., (© The Author(s) 2024. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Context: Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in women. Retinoid-interferon-induced mortality 19 (GRIM19) is a functional component of mitochondrial complex I that plays a role in cellular energy metabolism. However, the role of GRIM19 in the pathogenesis of PCOS is still unclear., Objective: To investigate the role of GRIM19 in the pathogenesis of PCOS., Design: We first measured the expression of GRIM19 in human granulosa cells (hGCs) from patients with and without PCOS (n = 16 per group), and then established a PCOS mouse model with WT and Grim19 +/- mice for in vivo experiments. Glucose uptake-related genes RAC1 and GLUT4 and energy metabolism levels in KGN cells were examined in vitro by knocking down GRIM19 in the cell lines. Additionally, ovulation-related genes such as p-ERK1/2, HAS2, and PTX3 were also studied to determine their expression levels., Results: GRIM19 expression was reduced in hGCs of PCOS patients, which was negatively correlated with BMI and serum testosterone level. Grim19 +/- mice with PCOS exhibited a markedly anovulatory phenotype and disturbed glycolipid metabolism. In vitro experiments, GRIM19 deficiency inhibited the RAC1/GLUT4 pathway, reducing insulin-stimulated glucose uptake in KGN cells. Moreover, GRIM19 deficiency induced mitochondrial dysfunction, defective glucose metabolism, and apoptosis. In addition, GRIM19 deficiency suppressed the expression of ovulation-related genes in KGN cells, which was regulated by dihydrotestosterone mediated androgen receptor., Conclusions: GRIM19 deficiency may mediate ovulation and glucose metabolism disorders in PCOS patients. Our results suggest that GRIM19 may be a new target for diagnosis and treatment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The use of two-dimensional heterostructure composite as electrode modification material has become a new strategy to improve the electrocatalytic activity and electroactive sites of electrochemical sensor. Herein, a soluble heterostructure, namely rGO-PSS@MXene, was designed and synthesized by integrating poly (sodium p-styrenesulfonate)-functionalized reduced graphene oxide into MXene nanosheets via ultrasonic method. The interactive heterostructure can effectively alleviate the self-stacking of MXene and rGO, endowing them with superior electron transfer capacity and large specific surface area, thereby producing prominent synergistic electrocatalytic effect towards rutin. In addition, the excellent enrichment effect of rGO-PSS@MXene for rutin also plays an important role through the electrostatic and π-π stacking interactions. The electrochemical characteristics of rutin on the sensor were examined in detail and a sensitive sensing method was proposed. Under optimized conditions, the method showed satisfactory linear relationship for rutin in the concentration range of 0.005-10.0 μM, with limit of detection of 1.8 nM (S/N = 3). The quantitative validation results in herbal medicine and commercial Tartary buckwheat tea were highly consistent with the labeled quantity and the results of HPLC determination, respectively, suggesting the sensor possessed excellent selectivity and accuracy. This proposed strategy for rutin determination is expected to expand the application of MXene heterostructure in electrochemical sensors, and is envisioned as a promising candidate for quality monitoring of drugs and foods., 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.)

Background: BMS-986141 is a novel potent highly selective antagonist of PAR (protease-activated receptor) type 4. PAR4 antagonism has been demonstrated to reduce thrombus formation in isolation and in combination with factor Xa inhibition in high shear conditions in healthy people. We sought to determine whether PAR4 antagonism had additive antithrombotic effects in patients with coronary artery disease who were receiving antiplatelet therapy., Methods: Forty-five patients with stable coronary heart disease and 10 healthy volunteers completed a phase 2a open-label 4-arm single-center study. Patients were allocated to 1 of 3 treatment arms for 7 days: (1) ticagrelor (90 mg BID), (2) aspirin (75 mg QD), or (3) the combination of ticagrelor and aspirin. Agonist-induced platelet aggregation, platelet activation, and ex vivo thrombus formation were measured before and 2 and 24 hours after a single oral 4-mg dose of BMS-986141 on the first study visit day in all participants., Results: BMS-986141 demonstrated highly selective inhibition of PAR4-AP (agonist peptide)-induced platelet aggregation, P-selectin expression, and platelet-monocyte aggregate expression ( P ≤0.001 for all), which were unaffected by concomitant antiplatelet therapies. PAR4 antagonism reduced ex vivo thrombus area in high shear conditions in healthy volunteers (-21%; P =0.001) and in patients receiving ticagrelor alone (-28%; P =0.001), aspirin alone (-23%; P =0.018), or both in combination (-24%; P ≤0.001). Plasma concentration of BMS-986141 correlated with PAR4-AP-induced platelet responses ( P ≤0.001 for all) and total thrombus area under high shear stress conditions ( P ≤0.01 for all)., Conclusions: PAR4 antagonism has additive antithrombotic effects when used in addition to ticagrelor, aspirin, or their combination, in patients with stable coronary heart disease., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT05093790., Competing Interests: Disclosures D.E. Newby and J. Nash are employed by the University of Edinburgh but were supported by, or received consultancy from, Bristol Myers Squibb. L. Chao, S. Merali, M. Kim, Z. Wang, Y. Zhang, S. Jin, B. Wang, and M. Kozinn are employed by Bristol Myers Squibb. N.L. Mills has received honoraria from Abbott Diagnostics, Roche Diagnostics, Siemens Healthineers, LumiraDx, and Psyros Diagnostics and is employed by the University of Edinburgh, which has received research funding from Abbott Diagnostics, Siemens Healthineers, and Roche Diagnostics unrelated to the current work. The other authors report no conflicts.

Background: Medial ulnar collateral ligament (mUCL) injury can cause significant pain and alter throwing mechanics. Common autograft options for mUCL reconstruction (UCLR) include the palmaris longus (PL) and hamstring tendons. Allograft use may reduce donor site morbidity and decrease function related to PL autografts., Purpose: To compare varus stability and load to failure between a novel allograft for UCLR-knee medial collateral ligament (kMCL)-and a PL autograft in human donor elbow specimens., Study Design: Controlled laboratory study., Methods: A total of 24 fresh-frozen human elbows were dissected to expose the mUCL. Medial elbow stability was tested with the mUCL intact (native), deficient, and reconstructed utilizing the humeral single-docking technique with either a (1) kMCL allograft (n = 12) or (2) a PL autograft (n = 12). A 3-N·m valgus torque was applied to the elbow, and valgus rotation of the ulna was recorded via motion tracking cameras. The elbow was cycled through a full range of motion 5 times. After kinematic testing, specimens were loaded to failure at 70° of elbow flexion, and failure modes were recorded., Results: The mUCL-deficient elbows demonstrated significantly greater valgus rotation compared with the intact and reconstructed elbows at every flexion angle tested (10°-120°) ( P <.001). Both kMCL- and PL-reconstructed elbows exhibited significantly higher mean valgus rotation compared with the intact state between 10° and 40° of flexion ( P < .01). There were no significant differences in valgus rotation at any flexion angle between the kMCL and PL graft groups. When loaded to failure, elbows reconstructed with both kMCL and PL grafts failed at similar torque values (18.6 ± 4 and 18.1 ± 3.4 N·m, respectively; P = .765)., Conclusion: Fresh-frozen and aseptically processed kMCL allografts demonstrated similar kinematic and failure properties to PL tendon autografts in UCL-reconstructed elbows, although neither graft fully restored kinematics between 10° and 40°., Clinical Relevance: Prepared kMCL ligament allografts may provide a viable graft material when reconstructing elbow ligaments while avoiding the potential complications related to PL autografts- including donor site morbidity., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: This work was supported by a 2021 Junior Investigator Grant from MTF Biologics (principal investigator, M.A.S.). M.A.S. has received research support from Integra; education payments from Arthrex; consulting fees from Encore Medical, Arthrex, and Johnson & Johnson; nonconsulting fees from Arthrex; honoraria from Encore Medical; and hospitality payments from Micromed, Integra LifeSciences, and Wright Medical. L.C. has received education payments from Micromed and hospitality payments from Arthrex and Medical Device Business Services. D.A.K. has received education payments from Micromed; consulting fees from MTF Biologics; honoraria from MTF Biologics; and hospitality payments from Sientra. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto. Ethical approval was not sought for the present study., (© The Author(s) 2024.)

The global issue of ongoing trace metal emissions and legacy accumulation from diverse sources is posing threats to coastal wildlife. This study characterized the distribution of five metals in relation to dietary ecology (carbon and nitrogen stable isotopes: δ 15 N and δ 13 C) in representative predatory species (starfish, fish, and seabird) collected from the coast of Qingdao, northeastern China. Zinc (Zn) was the most abundant metal across species, followed by copper (Cu), chromium (Cr), cadmium (Cd), total and methylated mercury (THg and MeHg). Among the studied species, black-tailed gulls (Larus crassirostris) occupied the highest trophic position, followed by three predatory fish species, whereas the northern Pacific seastar (Asterias amurensis) had the lowest trophic position. The starfish exhibited high capacity to accumulate Cd, Cr and Cu. Conversely, black-tailed gulls exhibited high levels of Zn, while Hg was highest in predatory fishes. Across species, Cr, MeHg, THg and MeHg:THg showed significant positive correlations with δ 13 C, suggesting the influence of inshore food sources on their accumulation. Both MeHg and THg were significantly and positively correlated with δ 15 N, with MeHg demonstrating a greater slope, indicating their potential trophic magnification. We assessed health risks from the studied metals using established toxicity reference thresholds. Elevated risks of Hg were identified in three predatory fish species, while other metals and species remain within safe limits. These findings emphasize the significance of foraging patterns in influencing trace metal accumulation in coastal predators and highlight the importance of further monitoring., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

China, the largest developing country, has experienced rapid urbanization since its reform and opening-up. However, the increasing pollution load from urban areas has deteriorated urban river water quality, contradicting the concept of sustainable and green development promoted by the Chinese government. This situation elucidates governmental shortcomings in systematic environmental protection. Our study revealed that the current wastewater treatment plant (WWTP) discharge standards in urban areas are insufficient for attaining the desired urban river water quality and thus intensify the conflict between urbanization and water environmental protection. As urbanization continues, the urban population will grow, further exacerbating pollution and conflict. Our focus was the Xiangjiang River basin in Zunyi, a typical urbanized city in China. Using a validated one-dimensional mathematical model, we compared the water quality in the Xiangjiang River between current and upgraded WWTP discharge standards. The results showed that the water quality in the Xiangjiang River falls short of the standards, with more than 60 % of the river exceeding limits. However, upgrading WWTP discharge standards significantly reduces the proportion of river sections exceeding limits, with only 0.4 % exceeding standards during specific periods. This enhancement greatly improved the Xiangjiang River's water quality, aided in restoring the entire water environment in the basin, and supported water environmental protection goals. Our research findings offer crucial support for local governments in shaping comprehensive water environmental protection policies and insights for addressing similar environmental challenges caused by rapid urbanization in other developing regions., 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.)