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Nitrate (NO 3 - ) is an important contributor to PM 2.5 which can adversely affect the environment and human health. A noticeable decrease in NO x concentrations has been reported due to the lockdown measures implemented to curb the spread of Corona Virus Disease 2019 (COVID-19). However, questions remain, regarding the nonlinear relationship between NO x and NO 3 - . Here, we collected PM 2.5 samples in two periods, before and during the lockdown of COVID-19 in Shanghai. Dual isotopes (δ 18 O-NO 3 - and δ 15 N-NO 3 - ) of NO 3 - were measured to investigate the formation pathways and potential sources of NO 3 - . The results showed that the concentration of NO 3 - decreased significantly during the lockdown period compared to the period before the lockdown. Additionally, the hydroxyl pathway was the dominant contributor to NO 3 - production during the lockdown period, while N 2 O 5 hydrolyses dominated the formation of NO 3 - before the lockdown. This change is largely attributable to alterations in the oxidative potential of the environment. In comparison to the period preceding the lockdown, the relative contributions of each NO x source remained largely unchanged throughout the lockdown periods. Nevertheless, the concentration of NO 3 - contributed by each NO x source exhibited a notable decline, particularly the mobile sources and coal combustion. Furthermore, the reduction extent of NO 3 - due to the lockdown period was also greater than the reduction during the Clean Air Actions (2013-2017). Our findings provide evidence that the COVID-19 lockdown led to a decrease in NO 3 - concentration due to changes in the formation pathway and reductions in NO x emissions from various sources., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Immunotherapy has emerged as a standard treatment for deficient mismatch repair (dMMR) metastatic colorectal cancer (mCRC). Pembrolizumab became widely available as a first-line (1L) option in Australia following the Pharmaceutical Benefits Scheme (PBS) listing in August 2021. The uptake of new treatment options can be lengthy., Methods: The Treatment of Recurrent and Advanced Colorectal Cancer mCRC registry data at participating Australian sites was analysed from January 2015 (when MMR testing became routine). 1L treatment of dMMR cancers was compared with pre- and post-PBS funding., Results: Out of 2819 patients, 2344 (83%) had known MMR status. Of these, 162 (7%) were dMMR, which was associated with older age (median age 69 vs 63 years, P = 0.001), a right-side primary (68% vs 31%, P < 0.001) and a BRAF V600E mutation (49% vs 11%, P < 0.001). Prior to August 2021, 85 out of 117 (73%) patients with dMMR received 1L treatment: 63 out of 85 (74%) chemotherapy and 20 out of 85 (24%) immunotherapy. Following approval, 39 out of 45 (87%) received 1L treatment and 39 out of 39 (100%) pembrolizumab. Of the patients 75 years and older, a significantly higher proportion of patients were treated with any 1L therapy post-PBS listing (89% vs 60%, P = 0.036)., Conclusion: Previously reported associations of dMMR were observed. The higher-than-expected proportion of patients with dMMR is likely driven by the inclusion of older patients in this real-world study. Many patients were able to access immunotherapy prior to PBS listing, potentially through trials or access programs. Early uptake of pembrolizumab following PBS listing has been high, and this effective and well-tolerated option has increased the proportion of elderly patients receiving active therapy., (© 2024 Royal Australasian College of Physicians.)

This study evaluated the effects of postharvest ripening (0-6 days, D0-6) on cell wall pectin profile, infrared-assisted hot air-drying characteristics, and sugar content. Results showed that during postharvest ripening progress, the content of water-soluble pectin (WSP) and chelate-soluble pectin (CSP) increased while the content of Na 2 CO 3 -soluble pectin (NSP) and hemicellulose (HC) decreased. In addition, the average molecular weight of WSP increased while the average molecular weight of NSP decreased. Secondly, the drying time of plums with different postharvest ripening periods was in the order: D3 < D4 < D2 < D1 < D0 < D5 < D6. Furthermore, the sugar content of dried plums was mainly influenced by drying time, with three stages of sugar changes observed, tied to moisture content: (1) Sucrose hydrolyzes (50-85%); (2) Fructose and glucose degrade (15-50%); (3) Sorbitol degrades (15-42%). These findings indicate that the transformation of cell wall pectin profile during the postharvest ripening process alters drying behavior and regulates the sugar content of dried plums. CHEMICAL COMPOUNDS STUDIED IN THIS ARTICLE: Galacturonic acid (PubChem CID: 439215); Acetone (PubChem CID: 180); Distilled water (PubChem CID: 962); Trans-1,2-Diaminocyclohexane-N, N, N, N'-tetraacetic acid (PubChem CID: 2723845); Na 2 CO 3 (PubChem CID: 10340); Glucose (PubChem CID: 5793); fructose (PubChem CID: 2723872) sucrose (PubChem CID: 5988) sorbitol (PubChem CID: 5780) and Sodium borohydride (PubChem CID: 4311764)., 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.)

Nitrite is a commonly used food preservative and a water contaminant that has garnered significant attention due to its harmful effects on human health. Developing a simple and sensitive method for determining nitrite levels is crucial for safeguarding public health. In this paper, we present a novel ratiometric fluorescent nanosensor (CDs@UiO-66-NH 2 ), created by combining orange-red-emitting CDs with blue-emitting UiO-66-NH 2 . This ratiometric probe detects nitrite ions (NO 2 - ) based on the diazotization reaction between the amino group in UiO-66-NH 2 and the target NO 2 - , where the blue emission of UiO-66-NH 2 is quenched but the orange-red emission of CDs remains stable. The probe demonstrated a detection range of 0.5-20 μM with a limit of detection (LOD) of 0.157 μM for NO 2 - . Due to the probe's distinct color changes in response to NO 2 - , RGB values can be easily read using a smartphone, enabling ultrasensitive visual detection of NO 2 - with an LOD of 0.76 μM. This sensor was successfully applied to detect NO 2 - in environmental water samples. Finally, a smartphone-based RGB reading method using CDs@UiO-66-NH 2 for visual quantitative detection of NO 2 - was proposed, broadening the application of CDs@UiO-66-NH 2 in environmental protection., 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.)

Uremic pruritus (UP) is a prevalent complication of uremia, severely affecting the quality of life of patients. The abnormal and accumulation of metabolites in the circulatory system of UP patients may constitute a significant inducer of pruritus. However, a systematic evaluation of the differences in serum metabolomic profiles among UP patients with different etiologies has yet to be reported. This study collected serum samples from 18 pruritic uremia patients from DKD, HN, and GN, as well as 18 non-pruritic uremia patients, respectively, to conduct a metabolomic analysis. The aim was to identify variations in metabolomic profiles and potential biomarker metabolites among pruritic patients of different etiologies. The results revealed a total of 4575 metabolites, with 256 and 172 differentially expressed metabolites (DEMs) (upregulated and downregulated) in the DKDUP vs. Neg comparison group, 303/202 in the HNUP vs. Neg comparison group, and 217/170 in the GNUP vs. Neg comparison group. The DEMs primarily involved metabolic pathways such as tyrosine metabolism, fatty acid biosynthesis, and unsaturated fatty acid synthesis. A cross-analysis of the three comparison groups identified 77 common DEMs, among which the TOP 10 primarily included esters, oleic acid esters, and glycerides, all significantly elevated in UP. Moreover, ROC analysis identified potential biomarkers with the highest AUC value of 0.972 in all three comparison groups. The data from this study provide critical insights into the metabolomics of pruritic uremic patients, assisting in both the understanding of disease mechanisms and the development of therapeutic interventions., 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.)

Current feedback models advocate learner autonomy in seeking, processing, and responding to feedback so that medical students can become feedback-literate. Feedback literacy improves learners' motivation, engagement, and satisfaction, which in turn enhance their competencies. However, there is a lack of an objective method of measuring medical student feedback literacy in the empirical literature. Such an instrument is required to determine the level of feedback literacy amongst medical students and whether they would benefit from an intervention. Therefore, this research protocol addresses the methodology aimed at the development of a comprehensive instrument for medical student feedback literacy, which is divided into three phases, beginning with a systematic review. Available instruments in health profession education will be examined to create an interview protocol to define medical students' feedback literacy from the perspectives of medical students, educators, and patients. A thematic analysis will form the basis for item generation, which will subsequently undergo expert validation and cognitive interviews to establish content validity. Next, we will conduct a national survey to gather evidence of construct validity, internal consistency, hypothesis testing, and test-retest reliability. In the final phase, we will distribute the instrument to other countries in an international survey to assess its cross-cultural validity. This protocol will help develop an instrument that can assist educators in assessing student feedback literacy and evaluating their behavior in terms of managing feedback. Ultimately, educators can identify strengths, and improve communication with students, as well as feedback literacy and the feedback process. In conclusion, this study protocol outlined a systematic, evidence-based methodology to develop a medical student feedback literacy instrument. This study protocol will not only apply to medical and local cultural contexts, but it has the potential for application in other educational disciplines and cross-cultural studies., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Mohd Noor 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.)

This study investigated the association between cognitive function and facial emotion recognition (FER) in patients with Parkinson's disease (PD) and mild cognitive impairment (PD-MCI). We enrolled 126 participants from Taiwan, including 63 patients with idiopathic PD and 63 matched healthy controls. The PD group was divided into two groups: those with normal cognitive function (PD-NC) and those with MCI (PD-MCI). Participants underwent a modality emotion recognition test and comprehensive cognitive assessment. Our findings reveal that patients with PD-MCI exhibit significantly impaired FER, especially in recognizing "disgust," compared with patients with PD-NC and healthy adults (P = .001). This deficit correlates with executive function, attention, memory, and visuospatial abilities. Attention mediates the relationship between executive function and "disgust" FER. The findings highlight how patients with PD-MCI are specifically challenged when recognizing "disgust" and suggest that cognitive training focusing on cognitive flexibility and attention may improve their FER abilities. This study contributes to our understanding of the nuanced relationship between cognitive dysfunction and FER in patients with PD-MCI, emphasizing the need for targeted interventions., (© The Author(s) 2024. Published by Oxford University Press.)

Methicillin-resistant Staphylococcus aureus (MRSA) within cells proves exceptionally challenging to eradicate using conventional antimicrobials, resulting in recurring infections and heightened resistance. Herein, we reported an innovative mannosylated lipid-coated photodynamic/photothermal calcium phosphate nanoparticle (MAN-LCaP@ICG) for eradicating intracellular MRSA. The MAN-LCaP functioned as the vehicle for drug delivery, exhibiting preferential uptake by macrophages and facilitating the transport of ICG to intracellular pathogens. The MAN units integrated into MAN-LCaP@ICG could promote binding with MAN residuals on macrophage cells, as evidenced by cellular uptake assays using fluorescence microscopy and flow cytometry. Following its targeted accumulation, MAN-LCaP@ICG could enter into the cytoplasm and efficiently eradicate intracellular MRSA by a combination of the lysosome escape capability of CaP and the photodynamic and photothermal therapeutic effects of ICG. Furthermore, MAN-LCaP@ICG could kill MRSA more effectively than LCaP@ICG without MAN units or free ICG in a mouse peritoneal infection model. Therefore, MAN-LCaP@ICG provided a promising direction for human clinical application in combating intracellular infections.

In the present work, an effluent-free novel method including cyclic vacuum steam pulsed blanching (VSPB) pretreatment and non-water infrared refractance window drying (non-water IR-RWD) was employed to explore its effect on enzyme inactivation, drying behavior, quality and functional properties of dried Malabar spinach. The highest inactivation of peroxidase (90.23 %) and polyphenol oxidase (94.58 %) was observed in the 4th cycle of the VSPB pretreatment. With the increase in VSPB cycles from 1 to 5, the drying time was significantly reduced by 27.27 % to 54.54 % compared to the untreated sample. The color change values (ΔE) of VSPB pretreated non-water IR-RWD samples varied from 7.37 to 8.03. The findings in the current work indicated that vacuum-steam pulsed blanching combined with a non-water IR-RWD process is a promising technique for Malabar spinach powder production., 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 Ltd.)

Background: Combination therapy is required for the treatment of moderate acne vulgaris. However, patient compliance in applying multiple topical formulations is poor., Objective: To assess the efficacy and safety of a fixed-dose combination gel with adapalene 0.1% and clindamycin 1% (adapalene-clindamycin) relative to adapalene 0.1% monotherapy and clindamycin 1% monotherapy in patients with moderate facial acne vulgaris., Methods: This was a randomized, controlled, assessor-blind, phase III study conducted in patients with moderate facial acne vulgaris., Results: A total of 1617 patients were enrolled. At week 12, patients in the adapalene-clindamycin gel treatment group showed a significant reduction in the percentage change from baseline in total lesion count (- 66.85%), compared with adapalene alone (- 50.82%) or clindamycin gel alone (- 57.61%). The difference in the least square means of the adapalene-clindamycin gel group and adapalene group, or clindamycin gel group was - 16.08% (95% CI - 19.95% to - 12.21%) and - 9.38% (95% CI - 13.25% to - 5.51%;), respectively. At week 12, 19.28% of participants who received adapalene-clindamycin gel achieved at least 2-grade improvement in IGA, versus 7.74% with adapalene gel (OR 3.05, 95% CI 1.93, 4.80) and 14.77% with clindamycin gel (OR 1.42, 95% CI 0.97, 2.07). The study also achieved all its secondary endpoints. Adverse event rates were mostly mild to moderate and comparable across the three treatment groups., Conclusion: Adapalene 0.1%-clindamycin 1% combination gel is well tolerated and demonstrated superior efficacy over 0.1% adapalene gel monotherapy and 1% clindamycin gel monotherapy for the treatment of moderate acne vulgaris., Trial Registration: ClinicalTrials.gov identifier NCT03615768., Competing Interests: Declarations Conflict of Interest Dr. Benjamin Xiao Yi Li is the Chairman & CEO of Zhaoke Ophthalmology Limited, and Director of Zhaoke Pharmaceutical (Hefei) Company Limited and Lee’s Pharmaceutical (Hong Kong) Limited. Xiang Rong DAI, and Xiao Hui YU are the staffs employed by Zhaoke Pharmaceutical (Hefei) Company Limited. Qiu Ju YIN is the staff employed by Zhaoke (Guangzhou) Ophthalmology Pharmaceutical Limited; The other authors declare no conflict of interest. Ethics Approval The trial was conducted in accordance with the Good Clinical Practice guidelines and complies with the Declaration of Helsinki. The protocol and informed consent form were reviewed and approved by a properly constituted institutional review board/independent ethics committee/research ethics board before study commencement. The names of the approving ethics committees are listed in Supplementary Table 1., (© 2024. The Author(s).)

Calcineurin is a serine/threonine protein phosphatase that is highly conserved from yeast to human and plays a critical role in many physiological processes. Regulators of calcineurin (RCANs) are a family of endogenous calcineurin regulators, which are capable of inhibiting the catalytic activity of calcineurin in vivo and in vitro. In this study, we first characterized the biochemical properties of yeast calcineurin and its endogenous regulator Rcn1, a yeast homolog of RCAN1. Our data show that Rcn1 inhibits yeast calcineurin toward pNPP substrate with a noncompetitive mode; and Rcn1 binds cooperatively to yeast calcineurin through multiple low-affinity interactions at several docking regions. Next, we reinvestigated the mechanism underlying the inhibition of mammalian calcineurin by RCAN1 using a combination of biochemical, biophysical, and computational methods. In contrast to previous observations, RCAN1 noncompetitively inhibits calcineurin phosphatase activity toward both pNPP and phospho-RII peptide substrates by targeting the enzyme active site in part. Re-analysis of previously reported kinetic data reveals that the RCAN1 concentrations used were too low to distinguish between the inhibition mechanisms [Chan B et al. (2005) Proc Natl Acad Sci USA 102, 13075]. The results presented in this study provide new insights into the interaction between calcineurin and RCAN1/Rcn1., (© 2024 Federation of European Biochemical Societies.)

The dorsomedial prefrontal cortex (dmPFC) plays a crucial role in social cognitive functions, including perspective-taking. Although perspective-taking has been linked to self-control, the mechanism by which the dmPFC might facilitate self-control remains unclear. Using the multimodal neuroimaging dataset from the Human Connectome Project (Study 1, N =978 adults), we established a reliable association between the dmPFC and self-control, as measured by discounting rate-the tendency to prefer smaller, immediate rewards over larger, delayed ones. Experiments (Study 2, N = 36 adults) involving high-definition transcranial direct current stimulation showed that anodal stimulation of the dmPFC reduces the discounting of delayed rewards and decreases the congruency effect in egocentric but not allocentric perspective in the visual perspective-taking tasks. These findings suggest that the dmPFC promotes self-control by inhibiting the egocentric perspective, offering new insights into the neural underpinnings of self-control and perspective-taking, and opening new avenues for interventions targeting disorders characterized by impaired self-regulation., 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 Inc.)

Introduction: The autoimmune hair loss condition alopecia areata (AA) exacts a substantial psychological and socioeconomic toll on patients. Biotechnology companies, dermatology clinics, and research institutions are dedicated to understanding AA pathogenesis and developing new therapeutic approaches. Despite recent efforts, many knowledge gaps persist, and multiple treatment development avenues remain unexplored., Areas Covered: This review summarizes key AA disease mechanisms, current therapeutic methods, and emerging treatments, including Janus Kinase (JAK) inhibitors. The authors determine that innovative drug discovery strategies for AA are still needed due to continued unmet medical needs and the limited efficacy of current and emerging therapeutics. For prospective AA treatment developers, the authors identify the pre-clinical disease models available, their advantages, and limitations. Further, they outline treatment development opportunities that remain largely unmapped., Expert Opinion: While recent advancements in AA therapeutics are promising, challenges remain, including the lack of consistent treatment efficacy, long-term use and safety issues, drug costs, and patient compliance. Future drug development research should focus on patient stratification utilizing robust biomarkers of AA disease activity and improved quantification of treatment response. Investigating superior modes of drug application and developing combination therapies may further improve outcomes. Spirited innovation will be needed to advance more effective treatments for AA.

Retinoic acid-inducible gene I (RIG-I) is a pattern recognition receptor involved in innate immunity, but its role in adaptive immunity, specifically in the context of CD8 + T-cell antitumour immunity, remains unclear. Here, we demonstrate that RIG-I is upregulated in tumour-infiltrating CD8 + T cells, where it functions as an intracellular checkpoint to negatively regulate CD8 + T-cell function and limit antitumour immunity. Mechanistically, the upregulation of RIG-I in CD8 + T cells is induced by activated T cells, and directly inhibits the AKT/glycolysis signalling pathway. In addition, knocking out RIG-I enhances the efficacy of adoptively transferred T cells against solid tumours, and inhibiting RIG-I enhances the response to PD-1 blockade. Overall, our study identifies RIG-I as an intracellular checkpoint and a potential target for alleviating inhibitory constraints on T cells in cancer immunotherapy, either alone or in combination with an immune checkpoint inhibitor., Competing Interests: Disclosure and competing interests statement XBL is an employee of Huixin Life Science. The authors declare no competing interests., (© 2024. The Author(s).)

Introduction: The prognostic value of baseline variant allele frequency (VAF) in circulating tumor DNA (ctDNA) of colorectal cancer liver metastases (CRLM) patients after curative resection was rarely investigated., Methods: A single-center prospective study was performed to investigate the prognostic impact of baseline VAF in ctDNA and matched tumor tissues of CRLM patients after curative resection between May 2019 and May 2021 by the Illumina NovoSeq 6000 platform. The relationship of the tumor burden score (TBS) and the VAF in ctDNA and matched tumor tissues was evaluated by the Pearson correlation method. The survival curves of recurrence-free survival (RFS) and overall survival (OS) were plotted. Factors associated with RFS were calculated using Cox regression analysis, and an integrated prognostic model using significant baseline variables was proposed., Results: There were 121 patients with baseline ctDNA and matched tumor tissues enrolled in the study. A total of 417 mutations spanning 20 genes were identified in baseline tumor tissues of 119/121 (98.3 %) cases. The overall mutations in tumor tissues were completely covered by ctDNA in 52 of 121(43.0 %) patients. Baseline VAF in ctDNA but not in tumor tissues was significantly correlated to TBS of CRLM (R = 0.36, p < 0.001). Significantly longer RFS but not OS was observed in patients with lower VAF in ctDNA compared to those with higher one (p < 0.001 and p = 0.33 respectively). Multivariate Cox regression analysis showed higher VAF in baseline ctDNA was an independent risk factor for RFS. An integrated prognostic model including baseline metastasis location and VAF in ctDNA outperformed the traditional CRS model in predicting RFS., Conclusion: Baseline VAF in ctDNA but not in tumor tissues influenced RFS of CRLM patients after curative resection., 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 Masson SAS.)

Background: Ambulance-based telestroke may be a promising solution to improving stroke care. We assessed the technical feasibility and reliability of prehospital evaluations using commercial mobile phones with fifth-generation wireless communication technology., Methods: Six standardized patients portrayed scripted stroke scenarios during ambulance transport in an urban city and were remotely evaluated by independent raters using tablets (three neurologists and three emergency physicians) in a hospital, assisted by paramedics (trained in National Institute of Health Stroke Scale [NIHSS] assessment) in the ambulance; commercial cellular networks were utilized for videoconferencing transmission. The primary outcomes were mean difference (MD) and correlation of NIHSS scores between the face-to-face and remote assessments. We also examined the Bland-Altman plot for itemized NIHSS components, and Kaplan-Meier curves were used to compare the differences in the duration of the two evaluations between neurologists and emergency physicians., Results: We conducted 32 ambulance runs and successfully completed all NIHSS examinations. No significant difference was found between the face-to-face and remote evaluations (MD, 0.782; 95% confidence interval [CI], -0.520-0.395). The correlation of NIHSS scores between the two methods was 0.994 (95% CI, 0.945-1.026), and three items exhibited the highest frequency of runs, with score differences between the two methods. There were no significant differences between neurologists and emergency physicians in the mean evaluation duration and NIHSS scores for the two methods., Conclusion: Prehospital evaluation using commercial mobile phones with fifth-generation wireless communication technology is feasible and reliable during ambulance transport in urban areas. Emergency physicians and neurologists performed similarly in stroke evaluations., Competing Interests: Declaration of competing interest None declared., (Copyright © 2024 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Objective: To assess the impact of ejaculatory dysfunction (EjD; failure of emission or retrograde ejaculation) on health-related quality of life (HRQoL) after retroperitoneal lymph node dissection (RPLND) for testicular cancer and explore the efficacy of pseudoephedrine hydrochloride as treatment., Patients and Methods: In a single arm, phase II trial, patients at ≥6 months after RPLND were invited to complete patient-reported outcome measures (European Organisation for Research and Treatment of Cancer [EORTC] quality of life questionnaire [QLQ]-30-item core, EORTC QLQ-testicular cancer-26, and Brief Male Sexual Function Inventory) evaluating HRQoL and sexual function in follow-up (ACTRN12622000537752/12622000542796). If EjD was reported, post-ejaculatory urine ± semen analysis was undertaken. In eligible patients, pseudoephedrine hydrochloride 60 mg was administered orally every 6 h for six doses. The primary endpoint was sperm count >39 million sperm/ejaculate (>5th centile) following treatment. The trial was powered to detect a clinically relevant 36% achieving sperm count of >39 million sperm/ejaculate. Secondary endpoints included semen volume >1.5 mL, total motile sperm count, safety, and HRQoL impacts., Results: Of the 58 patients enrolled, the median (interquartile range [IQR]) age was 35 (29-41) years, with a median (IQR) of 37 (18-60) months from RPLND. EjD was reported in 33 (57%), including 27/52 (52%) receiving follow-up at our centre. There were no differences in global HRQoL; however, role functioning (P = 0.045), sexual problems (P < 0.005), and sexual enjoyment (P = 0.005) was poorer if EjD was present. In all, 24/33 (73%) patients with EjD consented to pseudoephedrine treatment. Of 22 evaluable patients, four (18%) achieved a sperm count of >39 million/ejaculate (P = 0.20), and four (18%) had a semen volume of >1.5 mL (P = 0.20). There was a mean increase of 105 million sperm/ejaculate (P = 0.051) and 1.47 mL increase in semen volume (P = 0.01). No safety concerns arose., Conclusion: Ejaculatory dysfunction is common after RPLND but did not impact global HRQoL in our cohort. Pseudoephedrine improved EjD for some; however, its efficacy was lower than expected. Pseudoephedrine may be considered on an individualised basis., (© 2024 The Author(s). BJU International published by John Wiley & Sons Ltd on behalf of BJU International.)

Background and Purpose: Previous studies have suggested that music listening has the potential to positively affect cognitive functions and mood in individuals with post-stroke cognitive impairment (PSCI), with a preference for self-selected music likely to yield better outcomes. However, there is insufficient clinical evidence to suggest the use of music listening in routine rehabilitation care to treat PSCI. This randomized control trial (RCT) aims to investigate the effects of personalized music listening on mood improvement, activities of daily living (ADLs), and cognitive functions in individuals with PSCI., Materials and Methods: A total of 34 patients with PSCI were randomly assigned to either the music group or the control group. Patients in the music group underwent a three-month personalized music-listening intervention. The intervention involved listening to a personalized playlist tailored to each individual's cultural, ethnic, and social background, life experiences, and personal music preferences. In contrast, the control group patients listened to white noise as a placebo. Cognitive function, neurological function, mood, and ADLs were assessed., Results: After three months of treatment, the music group showed significantly higher Montreal Cognitive Assessment (MoCA) scores compared to the control group (p=0.027), particularly in the domains of delayed recall (p=0.019) and orientation (p=0.023). Moreover, the music group demonstrated significantly better scores in National Institutes of Health Stroke Scale (NIHSS) (p=0.008), Barthel Index (BI) (p=0.019), and Zarit Caregiver Burden Interview (ZBI) (p=0.008) compared to the control group. No effects were found on mood as measured by the Hamilton Anxiety Rating Scale (HAMA) and the Hamilton Depression Rating Scale (HAMD)., Conclusion: Personalized music listening promotes the recovery of cognitive and neurological functions, improves ADLs, and reduces caregiver burden in patients with PSCI., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Detecting the furfural concentration in Baijiu can be used to assess the quality of Baijiu, allowing for the optimization of processing techniques and the enhancement of overall quality. In this paper, a fluorescence-enhanced method based on carbon dots (o-CDs) is developed for the furfural determination in Chinese Baijiu. In an environment full-filled with ·SO 4 - and ·OH, furfural undergone a direct surface reaction with the ortho-diamino groups at o-CDs. The created furan-based imidazole increased the surface electron density, leading an emission enhancement and color changes from orange to green. Thereby, a linear fluorescence response of o-CDs-TA to furfural is established in water with a detection limit of 30.5 nM. Finally, after ethanol correction it is used to determine furfural in Chinese Baijiu with high precision and reproducibility, providing a new strategy with low-cost and high sensitivity. In particular, the idea of covalently connecting target molecule to the CDs surface via the assistance of free radical opens a new avenue to merge the nanoscale and molecular realms through implementing chemical role into carbon nanostructures., 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.)

Background: Lung cancer is the leading cause of cancer-related mortality worldwide. S-1, a fluorouracil derivative known for its efficacy and minimal adverse effects in various solid tumors, offers hope for advanced non-small cell lung cancer (NSCLC) patients. This study conducted a retrospective, single-center analysis to investigate the effectiveness and safety of S-1 monotherapy and combination therapy as second-line or subsequent treatment for advanced NSCLC., Methods: A total of 52 patients diagnosed with advanced NSCLC at Zhejiang Cancer Hospital (Hangzhou, China) from January 1, 2018, to August 31, 2023 were included in a retrospective study. Among these patients, 13 received S-1 monotherapy while 39 received S-1 in combination therapy. The study aimed to analyze the short-term efficacy, long-term outcome, prognostic factors, and treatment-related adverse events (AEs)., Results: The objective response rate (ORR) was 28.8%, with a median progression-free survival (PFS) of 2.7 months [95% confidence interval (CI): 2.1-2.8] and a median overall survival (OS) of 9.5 months (95% CI: 6.3-12.6) for the entire cohort. The combination therapy with S-1 was determined to be a significant independent predictor of OS, while treatment line was identified as an independent negative prognostic factor for OS. The most prevalent AE observed was anemia, affecting 12 patients (23.1%). The majority of AEs were classified as grade 1-2, with only 3 patients (5.7%) experiencing grade 3-4 AEs. Further prospective studies are recommended to fully assess the therapeutic value of this treatment approach., Conclusions: Results indicated that both S-1 monotherapy and combination therapy showed promising efficacy and were well tolerated as second-line or later-line treatments for patients with advanced NSCLC. Further prospective studies are recommended to fully assess the therapeutic value of this treatment approach., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-24-940/coif). The authors have no conflicts of interest to declare., (2024 AME Publishing Company. All rights reserved.)

Tumor metastasis accounts for over 90% of tumor-related deaths, prompting the development of fluorescently labeled tumor-specific molecular imaging agents for differentiating tumors from normal tissues. However, early detection of metastasis lesions by tracking tumor markers alone has proven to be challenging. Herein, we reported a glycopeptide-based bispecific fluorescence probe (bsProbe) for earlier detection of bladder cancer and metastasis. By simultaneously recognition (tumor & tumor microenvironment) and in vivo self-assembly, the tumor accumulation of bsProbe (12.3% ID/g) was obviously increased by ∼6 fold compared with that in CXCR4 specific fluorescence probe (sProbe), indicating the obvious advantages of bsProbe over existing tumor metastasis detection probes. Additionally, bsProbe substantially broadens the tumor diagnosis window and enhances the detection signal to noise ratio (SNR: approximately 9.5), permitting early diagnosis of lung micro-metastasis (∼1 mm), precise identifying of tumor boundaries and micro-tumors in orthotopic tumor models. More importantly, bsProbe was demonstrated to distinguish malignant from benign specimen with a specificity of 90.48% and sensitivity of 92.22% in 195 clinical specimens of bladder cancer patients. Taken together, this novel synergetic targeting (CD206 × CXCR4) strategy provides an attractive method for earlier detection of bladder cancer and metastasis, which might be further extended to the imaging-guided surgery of clinical invisible tumors., (Copyright © 2024 Science China Press. Published by Elsevier B.V. All rights reserved.)

To investigate the effect of trace element molybdenum (Mo) on the receptivity of porcine endometrial epithelial cells (PEECs) and evaluate Mo toxicity and its potential molecular mechanisms, Mo-treated PEECs models were established by incubating the cells with various concentrations of medium containing Mo (0, 0.005, 0.020, 0.200, and 5 mmol/L MoNa 2 O 4 ·2H 2 O). The results showed that Mo disrupted the morphology and ultrastructure of PEECs, triggered blurred cell edges, cell swelling, cell cycle arrest, and increased apoptosis. At the molecular level, Mo treatment activated the TGF-β1/SMAD2 and PI3K/AKT1 pathways, causing a significant increase in matrix metalloproteinase (MMP)-9 and MMP-2 protein expression. Accompanied by markedly increased tissue inhibitors matrix metalloproteinase (TIMP)-2 and decreased TIMP-1, the balance of MMP2/TIMP-2 and MMP-9/TIMP-1 were disrupted. Ultimately, the receptivity of PEECs was destroyed by excessive Mo, which is revealed by the significant decrease of receptive marker molecules, including leukemia inhibitory factor (LIF), integrins β3 (ITGβ3), heparin-binding epidermal growth factor (HB-EGF), and vascular endothelial growth factor (VEGF). To sum up, the current study demonstrated the potential toxicity of Mo to PEECs, indicating reproductive toxicity at high Mo concentrations and suggesting that the content of Mo should be evaluated as a potential risk factor., 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.)

Background: Although immune checkpoint inhibitors (ICIs) have demonstrated significant survival benefits in some patients diagnosed with gastric cancer (GC), existing prognostic markers are not universally applicable to all patients with advanced GC., Aim: To investigate biomarkers that predict prognosis in GC patients treated with ICIs and develop accurate predictive models., Methods: Data from 273 patients diagnosed with GC and distant metastasis, who un-derwent ≥ 1 cycle(s) of ICIs therapy were included in this study. Patients were randomly divided into training and test sets at a ratio of 7:3. Training set data were used to develop the machine learning models, and the test set was used to validate their predictive ability. Shapley additive explanations were used to provide insights into the best model., Results: Among the 273 patients with GC treated with ICIs in this study, 112 died within 1 year, and 129 progressed within the same timeframe. Five features related to overall survival and 4 related to progression-free survival were identified and used to construct eXtreme Gradient Boosting (XGBoost), logistic regression, and decision tree. After comprehensive evaluation, XGBoost demonstrated good accuracy in predicting overall survival and progression-free survival., Conclusion: The XGBoost model aided in identifying patients with GC who were more likely to benefit from ICIs therapy. Patient nutritional status may, to some extent, reflect prognosis., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Chronic kidney disease (CKD) is characterized by fibrosis and inflammation in renal tissues. Several types of cell death have been implicated in CKD onset and progression. Unlike traditional forms of cell death, PANoptosis is characterized by the crosstalk among programmed cell death pathways. However, the interaction between PANoptosis and CKD remains unclear. Here, we used bioinformatics methods to identify differentially expressed genes and differentially expressed PANoptosis-related genes (DE-PRGs) using data from the GSE37171 dataset. Following this, we further performed gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, and gene set enrichment analysis using the data. We adopted a combined approach to select hub genes, using the STRING database and CytoHubba plug-in, and we used the GSE66494 as a validation dataset. In addition, we constructed ceRNA, transcription factor (TF)-gene, and drug-gene networks using Cytoscape. Lastly, we conducted immunohistochemical analysis and western blotting to validate the hub genes. We identified 57 PANoptosis-associated genes as DE-PRGs. We screened nine hub genes from the 57 DE-PRGs. We identified two hub genes (FOS and PTGS2) using the GSE66494 database, Nephroseq, immunohistochemistry, and western blotting. A common miRNA (Hsa-miR-101-3p) and three TFs (CREB1, E2F1, and RELA) may play a crucial role in the onset and progression of PANoptosis-related CKD. In our analysis of the drug-gene network, we identified eight drugs targeting FOS and 52 drugs targeting PTGS2., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Zhang 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.)

Severe acute pancreatitis (SAP) is an acute inflammatory injury disease with significant mortality rate and currently without effective strategy being available. Inflammation and oxidative stress play central roles in the etiology of SAP. Micheliolide (MCL), an active monomeric component isolated from Michelia champaca, has been proved its multiple therapeutic properties including anti-inflammatory, antioxidant and anti-cancer. Nevertheless, the therapeutic effect and underlying mechanism of MCL in SAP still remain unclear. Here, we found that caerulein with lipopolysaccharide (LPS)-induced SAP murine models exhibited severe pancreatic injury, including necrosis, edema, and vacuolation of acinar cells in the pancreas, elevated serum levels of amylase and lipase, and reduced number of the exocrine cells. As expected, MCL treatment alleviated these side effects. Mechanistically, MCL triggered nuclear factor erythroid 2-related factor 2 (Nrf2) activation, thereby activating Nrf2-regulated antioxidative pathways and inhibiting nuclear factor kappa B p65 (NF-κB p65)-mediated inflammatory response, resulting in protection against pancreatic injury in SAP mice. In addition, Nrf2 gene deficiency abolished the beneficial effects of MCL on SAP-induced pancreatic inflammation and oxidative stress and blocked the ability of MCL to alleviate the pancreatic injury in SAP mice. Collectively, these findings indicated that the suppression of SAP-induced pancreatic injury by MCL was at least in part due to Nrf2-mediated anti-oxidation effect and inhibition of inflammation., 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.)

Morphology is a cardinal feature of a neuron that mediates its functions, but profiling neuronal morphologies at scale remains a formidable challenge. Here we describe a generalizable pipeline for large-scale brainwide study of dendritic morphology of genetically-defined single neurons in the mouse brain. We generated a dataset of 3,762 3D-reconstructed and reference-atlas mapped striatal D1- and D2- medium spiny neurons (MSNs). Integrative morphometric analyses reveal distinct impacts of anatomical locations and D1/D2 genetic types on MSN morphologies. To analyze striatal regional features of MSN dendrites without prior anatomical constraints, we assigned MSNs to a lattice of cubic boxes in the reference brain atlas, and summarized morphometric representation ("eigen-morph") for each box and clustered boxes with shared morphometry. This analysis reveals 6 modules with characteristic dendritic features and spanning contiguous striatal territories, each receiving distinct corticostriatal inputs. Finally, we found aging confers robust dendritic length and branching defects in MSNs, while Huntington's disease (HD) mice exhibit selective length-related defects. Together, our study demonstrates a systems-biology approach to profile dendritic morphology of genetically-defined single-neurons; and defines novel striatal D1/D2-MSN morphological territories and aging- or HD-associated pathologies.

Introduction: Non-small cell lung cancer (NSCLC) is a prominent lung cancer disease worldwide. Currently, commonly used methods, such as surgery and radiotherapy, have significant side effects. Traditional Chinese medicine (TCM) has become a research hotspot because of its safe and effective characteristics. The branches and leaves of Taxus media are abundant in antitumor active compounds, and there has been no research conducted as yet regarding its anti-lung cancer molecular mechanism., Objective: The aim of this study is to investigate the antitumor activity of two samples before and after fermentation of T. media , and to research the molecular mechanism of its inhibitory effect on NSCLC., Methods: The chemical composition of pre-fermentation T. media (TM) and post-fermentation T. media qu (TMQ) were investigated using UHPLC-Q-Qrbitrap HRMS and high-performance liquid chromatography (HPLC). The anti-lung cancer activities of TM and TMQ were compared using an A549-induced tumor mouse model. An enzyme-linked immunosorbent assay (ELISA), hematoxylin and eosin (H&E) staining, immunohistochemistry, and immunofluorescence were used to determine the of TMQ mechanism of action., Results: The results indicated that TM and TMQ contained 83 compounds, consisting primarily of flavonoids, organic acids, and taxanes. Both taxanes and flavonoids in TMQ were higher than that in TM. Both TM and TMQ effectively inhibited the tumor growth in non-small cell lung cancer (NSCLC), and the inhibition rate was greater in TMQ (57.24%) than in TM (49.62%). TMQ administration downregulated the tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and the glutathione (GSH) level and upregulated interferon-γ (IFN-γ), reactive oxygen species (ROS), and malondialdehyde (MDA) levels in the serum of tumor mice. TMQ treatment also increased the protein expression of Bax, Caspase-3, and Beclin-1 in tumor tissues. In contrast, the bcl-2, PI3K, Ki67, ULK1, and mTOR protein levels were suppressed by TMQ. Protein assay analyses reemphasized the superior antitumor effect of TMQ over TM. These cumulative findings demonstrated that the mechanism of action of TMQ was closely related to the activation of transcriptional misregulation in the cancer pathway that inhibited the cholinergic synaptic, AMPK, and PI3K/Akt/mTOR signaling pathways., Conclusion: This study demonstrated that fermentation increased the active ingredient contents and antitumor effects of T. media . In addition, post-fermentation TMQ was superior to TM as a herbal medicine for NSCLC treatment., 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 Guo, Wang, Zhang, Zhang, Wang, Zhang, Wu, Li and Yuan.)

Noble-metal-free CO 2 reduction systems based on cobalt phthalocyanine ( CoPc ) and its derivatives have demonstrated remarkable photocatalytic performances; however, their structure-activity relationship with electronic tuning remains unexplored. Herein, we now provide a systematic study to investigate the electron effects of substituents on the CoPc family in photocatalytic CO 2 reduction, where a Cu(I) heteroleptic photosensitizer is utilized. The highest performance can be achieved using cobalt tetracarboxylphthalocyanine in light-driven CO 2 -to-CO reduction, with a maximum turnover number of 2950 at 450 nm and an outstanding apparent quantum yield of 63.5% at 425 nm, over ten times the activity with the tetra-dimethylamino-substituted CoPc derivative. The favorable electron-withdrawing effects have been further verified by DFT calculations and cyclic voltammetry, which reduces the overpotential required for CO 2 reduction and decreases the Gibbs free energy of the catalyst active intermediates, particularly the CO-desorption energetics.

Introduction: Caregivers of patients with end-stage kidney disease (ESKD) face significant challenges that contribute to caregiver burden, negatively impacting their psychosocial well-being. Virtual-reality (VR)-guided mindfulness interventions have shown promise in reducing stress, anxiety and depression in various populations., Methods and Analysis: This pilot study aims to evaluate the efficacy and feasibility of a VR-guided mindfulness intervention for ESKD caregivers. A single-centre, single-blind, parallel-group pilot randomised controlled trial will be conducted. Thirty ESKD caregivers will be randomly allocated to either the VR-guided mindfulness intervention group or the sham VR control group. The intervention group will receive a 6 week home-based VR-guided mindfulness programme, while the control group will view relaxing nature videos without mindfulness content. Participants will be assessed at baseline, post-intervention (6 weeks) and follow-up (12 weeks) using validated questionnaires for caregiver burden (Zarit Burden Interview (ZBI)), stress, anxiety, depression (Depression Anxiety Stress Scale-21 (DASS-21)), quality of life (36-Item Short Form Health Survey (SF-36)) and mindfulness (Five Facet Mindfulness Questionnaire (FFMQ)). Feasibility outcomes include accrual rates, retention, adherence, questionnaire completion and side effect rates. Semi-structured interviews will explore participants' experiences with the intervention., Ethics and Dissemination: The study has been approved by the NHG Domain Specific Review Board (Reference: 2024-3940-APP1). The results of this pilot study will be reported in peer-reviewed open-access journals and shared with participants and stakeholders., Trial Registration: NCT06479200., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Intestinal obstruction is a common complication in patients with advanced malignancies, often attributed to the disease itself or as a side effect of opioid analgesics used for pain management. However, the occurrence of intestinal obstruction following antituberculosis therapy is rare., Case Presentation: We report a unique case of a 58-year-old Asian male diagnosed with stage IV pancreatic carcinoma and pulmonary tuberculosis. The patient was initiated on a regimen of ethambutol hydrochloride, pyrazinamide, rifampicin, and isoniazid tablets (II) for tuberculosis, alongside morphine for the management of severe cancer-related pain. Subsequently, he developed symptoms indicative of intestinal obstruction. Despite discontinuation of morphine, the patient's symptoms persisted until he autonomously ceased all medications, leading to a rapid improvement in his condition. This unexpected resolution highlighted the antituberculosis drugs as the probable cause of his intestinal obstruction., Conclusions: This case underscores the importance of considering antituberculosis drugs as a potential cause of intestinal obstruction, especially in patients who do not respond to conventional management strategies for drug-induced gastrointestinal side effects. It also emphasizes the need for heightened vigilance and monitoring when prescribing these medications to patients with advanced malignancies, to promptly identify and address rare but significant side effects., (© 2024. The Author(s).)

Renal fibrosis, inflammation, and gut dysbiosis are all linked to chronic kidney disease (CKD). Here we show that Bacteroides ovatus protects against renal fibrosis. Mechanistically, B. ovatus enhances intestinal hyodeoxycholic acid (HDCA) levels by upregulating a strain of intestinal bacteria, Clostridium scindens, that has the capacity for direct HDCA production in mice. HDCA significantly promoted GLP-1 secretion by upregulating the expression of TGR5 and downregulating the expression of farnesoid X receptor (FXR) in the gut. Activation of renal GLP-1R attenuates renal fibrosis while delaying the subsequent development of CKD. In addition, HDCA can also protect against renal fibrosis by directly upregulating renal TGR5. The natural product neohesperidin (NHP) was found to exert its anti-renal fibrotic effects by promoting the growth of B. ovatus. Our findings provide mechanistic insights into the therapeutic potential of B. ovatus, C. scindens, and HDCA in treating CKD., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Introduction: Neoadjuvant chemotherapy is becoming routine for colorectal liver metastasis (CRLM) in patients with high risks of recurrence or in whom resection is difficult. This retrospective study aimed to establish a modified survival prediction model for patients with CRLM who underwent hepatectomy after neoadjuvant chemotherapy., Materials and Methods: A total of 619 patients who received neoadjuvant chemotherapy followed by hepatectomy between 2006 and 2021 were included and divided into training and validation groups at a ratio of 2:1. The model was established in training group and validated in validation group. Chemotherapy response was integrated into the genetic and morphological evaluation (GAME) score as a new NeoGAME model, with assigned points based on the hazard ratio in the multivariate Cox regression. The NeoGAME score grouping cutoff was divided using X-tile, and the predictive power was compared with that of traditional models., Results: The 5-year overall survival were significantly different in the NeoGAME low-risk (0-2 points), medium-risk (3-4 points) and high-risk (≥5 points) groups (training group, P < 0.001; validation group, P = 0.0012). The area under the curve in predicting 5-year survival was 0.67 and 0.66 for the training and validation groups, respectively. Time-dependent receiver operating characteristic curve showed better discrimination ability of NeoGAME than the GAME score in predicting 5-year survival., Conclusions: The newly established NeoGAME score can predict survival more precisely for patients with CRLM receiving neoadjuvant chemotherapy. Moreover, the model offers a useful tool for assessing tumor behavior and selecting a benefiting population for liver resection., Competing Interests: Declaration of competing interest All authors declare no conflicts of interest., (Copyright © 2024 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Immune rejection caused by mismatches in human leucocyte antigens (HLAs) remains a major obstacle to the success of allogeneic cell therapies. Current strategies for the generation of 'universal' immune-compatible cells, particularly the editing of HLA class I (HLA-I) genes or the modulation of proteins that inhibit natural killer cells, often result in genomic instability or cellular cytotoxicity. Here we show that a β 2 -microglobulin super-enhancer (B2M-SE) that is responsive to interferon-γ is a critical regulator of the expression of HLA-I on mesenchymal stromal cells (MSCs). Targeted epigenetic repression of B2M-SE in MSCs reduced the surface expression of HLA-I below the threshold required to activate allogenic T cells while maintaining levels sufficient to evade cytotoxicity mediated by natural killer cells. In a humanized mouse model, the epigenetically edited MSCs demonstrated improved survival by evading the immune system, allowing them to exert enhanced therapeutic effects on LPS-induced acute lung injury. Targeted epigenetic repression of B2M-SE may facilitate the development of off-the-shelf cell sources for allogeneic cell therapy., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

The development of polymer-based persistent luminescence materials with color-tunable organic afterglow and multiple responses is highly desirable for applications in anti-counterfeiting, flexible displays, and data-storage. However, achieving efficient persistent luminescence from a single-phosphor system with multiple responses remains a challenging task. Herein, by doping 9H-pyrido[3,4-b]indole (PI2) into an amorphous polyacrylamide matrix, a hierarchical dual-mode emission system is developed, which exhibits color-tunable afterglow due to excitation-, temperature-, and humidity-dependence. Notably, the coexistence of the isolated state and J-aggregate state of the guest molecule not only provides an excitation-dependent afterglow color, but also leads to a hierarchical temperature-dependent afterglow color resulting from different thermally activated delayed fluorescence (TADF) and ultralong organic phosphorescence (UOP) behaviors of the isolated and aggregated states. The complex responsiveness based on the hierarchical dual-mode emission can serve for security features through inkjet printing and ink-writing. These findings may provide further insight into the regulated persistent luminescence by isolated and aggregated phosphors in doped polymer systems and expand the scope of stimuli-responsive organic afterglow materials for broader applications., (© 2024 Wiley-VCH GmbH.)

Enzyme-catalyzed proximity labeling is a potent technique for the discernment of subtle molecular interactions and subcellular localization, furnishing contextual insights into the protein of interest within cells. Although ascorbate peroxidase2 (APEX2) has proven effective in this approach when overexpressed, its compatibility with endogenous proteins remains untested. We improved this technique for studying native protein-protein interactions in live Drosophila ovary tissue. Through CRISPR/Cas9 genome editing, APEX2 was fused with the endogenous dysfusion gene. By pre-treating the tissue with Triton X-100 to enhance biotin-phenol penetration, we successfully identified multiple proteins interacting with the native Dysfusion proteins that reside on the inner nuclear membrane. Our protocol offers a comprehensive workflow for delineating the interactome networks of ovarian components in Drosophila , aiding future studies on endogenous protein-protein interactions in various tissues of other animals. Key features • Elucidating Protein-protein interactions provides deeper insights into the regulation of gene expression in molecular network and complex signaling pathways, advancing protein engineering and drug design. • This protocol utilizes CRISPR/Cas9 knock-in technology to tag endogenous proteins with the APEX2 to label nearby proteins within a 20 nm radius in Drosophila melanogaster . • We optimize APEX2-proximity labeling by using Triton X-100 pre-treatment to enhance biotin-phenol penetration into Drosophila ovaries, enabling endogenous proteins enrichment under native conditions., Competing Interests: Competing interestsThe authors declare no competing interests., (©Copyright : © 2024 The Authors; This is an open access article under the CC BY-NC license.)

Introduction: Peritoneal dialysis (PD) is an effective home-based treatment for end-stage kidney disease (ESKD) that offers several advantages over in-centre haemodialysis, including better quality of life, increased autonomy and lower costs. Despite these benefits, PD remains underused globally, with wide variations in adoption rates across countries. Qualitative studies have explored the experiences, perceptions and decision-making processes of patients, caregivers and healthcare providers regarding PD, but their findings have not been systematically synthesised. This protocol outlines a systematic review of qualitative studies to identify and synthesise the multilevel factors that influence PD adoption., Methods and Analysis: We will conduct a comprehensive search of electronic databases (PubMed, Web of Science, Embase, CINAHL, MEDLINE, The Cochrane Library, PsycINFO, Scopus) and grey literature sources for qualitative studies published in English from each database inception to June 2024 that explore barriers and facilitators to PD adoption. Two reviewers will independently screen titles, abstracts and full texts for eligibility based on predefined criteria. Eligible studies will include those that use qualitative methods (eg, interviews, focus groups, observations) to explore the perspectives of adult ESKD patients, their caregivers and/or healthcare providers on factors influencing PD adoption, initiation or maintenance. Data will be extracted using a standardised form and synthesised using thematic analysis. The methodological quality of included studies will be appraised using the Critical Appraisal Skills Programme Qualitative Checklist. Confidence in the review findings will be assessed using the Grading of Recommendations Assessment, Development and Evaluation-Confidence in the Evidence from Reviews of Qualitative research approach., Ethics and Dissemination: Ethics approval is not required as this study will merely synthesise data from published studies. The results will be disseminated through peer-reviewed publications as well as conference presentations., Study Registration: PROSPERO, CRD42024570521., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The prevalence of extended-spectrum β-lactamase-producing Enterobacterales (ESBL-E) and carbapenem-resistant Enterobacterales (CRE) has become a global public health problem. ESBL-E/CRE colonization can increase the risk of infection in patients and lead to poor disease prognosis. We conducted a systematic review and meta-analysis to evaluate current decolonization strategies regarding ESBL-E/CRE and their efficacy. A literature search was conducted until August 2023 on the five databases to review decolonization strategies associated with ESBL-E/CRE. A meta-analysis was conducted using RevMan 5.4 to compare differences in the decolonization strategy with placebo controls. The primary outcome was decolonization rates, with secondary outcomes of attributable death and adverse events. Quality of identified studies was determined using the Newcastle-Ottawa scale and cochrane risk assessment tool. Random and fixed effects meta-analyses were performed to calculate pooled value. A total of 25 studies were included. In five randomized controlled trial (RCT) studies, the decolonization effect of selective digestive decontamination(SDD) on ESBL-E/CRE at the end of treatment was significantly better in the experimental group than the controls [risk radio (RR): 3.30; 95% CI 1.78-6.14]. In three n-RCT studies, the decolonization effect in the experimental group was still better than the controls one month after SDD therapy [odds ratio (OR): 4.01; 95% CI 1.88-8.56]. The combined decolonization rates reported by six single-arm trial studies of SDD therapy ranged from 53.8 to 68.0%. Additionally, TSA analysis confirmed the effectiveness of SDD therapy. In studies on Faecal microbiota transplantation (FMT) therapy, the decolonization effect of the experimental group was significantly better than the controls 1 month after treatment (OR: 2.57; 95% CI 1.07-6.16). In studies without a control group and with varying follow-up times, the decolonization rates varied widely but indicated the effectiveness trend of FMT therapy (61.3-81.2%). Currently, research on the decolonization effect of probiotic therapy on ESBL-E/CRE is insufficient, and only a systematic review was conducted. SDD and FMT strategies have short-term benefits for ESBL-E/CRE decolonization, but long-term effects are unclear. The effect of probiotic therapy on ESBL-E/CRE decolonization is an interesting topic that still requires further investigation., (© 2024. The Author(s).)

The plant hormone auxin orchestrates almost all aspects of plant growth and development. AUXIN RESPONSE FACTORs (ARFs) control the transcription of auxin-responsive genes, forming cytoplasmic condensates to modulate auxin sensitivity and diversify auxin response regulation. However, the dynamic control of ARF distribution across different subcellular compartments remains largely obscure. Here, we show that three MULTIPLE C2 DOMAIN AND TRANSMEMBRANE REGION PROTEINs (MCTPs), MCTP3, MCTP4, and MCTP6, control ARF nucleocytoplasmic partitioning and determine lateral root development. MCTP3/4/6 are highly expressed in lateral roots and specifically interact with ARF7 and ARF19 to dissolve their cytoplasmic condensates. This promotes ARF nuclear localization in lateral root primordia and enhances auxin signaling during lateral root formation. Our findings confer MCTP as a key switch to modulate auxin responses and outline an MCTP-ARF signaling cascade that is crucial for the establishment of the plant root system., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Antibiotic resistance is currently an unfolding global crisis threatening human health worldwide. While antibiotic resistance genes (ARGs) are known to be pervasive in environmental media, the occurrence of antibiotic resistance at interfaces between two or more adjacent media is largely unknown. Here, we designed a microcosm study to simulate plastic pollution in paddy soil and used a novel method, stimulated Raman scattering coupled with deuterium oxide (D 2 O) labelling, to compare the antibiotic resistance in a single medium with that at the interface of multiple environmental media (plastic, soil, water). Results revealed that the involvement of more types of environmental media at interfaces led to a higher proportion of active resistant bacteria. Genotypic analysis showed that ARGs (especially high-risk ARGs) and mobile genetic elements (MGEs) were all highly enriched at the interfaces. This enrichment was further enhanced by the co-stress of heavy metal (arsenic) and antibiotic (ciprofloxacin). Our study is the first to apply stimulated Raman scattering to elucidate antibiotic resistance at environmental interfaces and reveals novel pathway of antibiotic resistance dissemination in the environment and overlooked risks to human health., 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.)

Background: Despite the exploration of the connections between serum low-density lipoprotein cholesterol (LDL-C) levels and aneurisms in epidemiological studies, causality remains unclear. Therefore, this study aimed to assess the causal impact of LDL-C-lowering targets (HMGCR, PCSK9, NPC1L1, CETP, APOB, and LDLR) on various forms of aneurisms using Mendelian Randomization (MR) analysis., Methods: Two genetic instruments acted as proxies for exposure to LDL-C-lowering drugs: expression quantitative trait loci of drug target genes and genetic variants linked to LDL-C near drug target genes. Summary-data-based MR (SMR), inverse-variance-weighted MR (IVW-MR), and multivariable MR (MVMR) methods were employed to compute the effect estimates., Results: The SMR analysis revealed substantial associations between increased HMGCR expression and a heightened risk of aortic aneurism (odds ratio [OR] = 1.603, 95% confidence interval [CI] = 1.209-2.124), thoracic aortic aneurism (OR = 1.666, 95% CI = 1.122-2.475), and abdominal aortic aneurism (OR = 1.910, 95% CI = 1.278-2.856). Likewise, IVW-MR analysis demonstrated positive correlations between HMGCR-mediated LDL-C and aortic aneurism (OR = 2.228, 95% CI = 1.702-2.918), thoracic aortic aneurism (OR = 1.751, 95% CI = 1.191-2.575), abdominal aortic aneurism (OR = 4.784, 95% CI = 3.257-7.028), and cerebral aneurism (OR = 1.993, 95% CI = 1.277-3.110). Furthermore, in the MVMR analysis, accounting for body mass index, smoking, and hypertension, a significant positive relationship was established between HMGCR-mediated LDL-C levels and the development of aortic aneurisms, encompassing both thoracic and abdominal subtypes. Similarly, consistent positive associations were observed for PCSK9 and CETP genes, as well as PCSK9-mediated and CETP-mediated LDL-C levels, with the occurrence of aortic aneurism and abdominal aortic aneurism. Nonetheless, the evidence for potential associations between APOB, NPC1L1 and LDLR with specific subtypes of aortic aneurisms lacked consistent support from both SMR and IVW-MR analyses., Conclusions: Our MR analysis offered compelling evidence of a plausible causal link between HMGCR and an increased risk of aortic aneurism, encompassing both thoracic and abdominal types. These groundbreaking findings further bolster the case for the deployment of HMGCR inhibitors in the treatment of aortic aneurisms, including both thoracic and abdominal variants., (© 2024. The Author(s).)

Background: Aesthetic neuromodulator injections of the upper face are frequently performed to temporarily block muscular actions of the periorbital muscles to ultimately reduce skin rhytids. However, the adverse event rate in the literature for toxin-induced blepharoptosis ranges from 0.51% to 5.4%., Objective: To identify access pathways by which injected neuromodulator product can travel from extra- to intra-orbital and therefore affect the levator palpebrae superioris muscle., Methods: Nine non-embalmed human body donors were investigated in this study with a mean age at death of 72.8 (16.1) years. The 18 supraorbital regions were injected in 28 times (14 for supratrochlear and 14 for supraorbital) with 0.5 cc, whereas eight cases (four for supratrochlear and four supraorbital) were injected with 0.1 cc of colored product. Anatomic dissections were conducted to identify structures stained by the injected color., Results: The results of this injection- and dissection-based study revealed that both the supratrochlear and the supraorbital neurovascular bundles are access pathways for injected neuromodulator products to reach the intra-orbital space and affect the levator palpebrea superioris muscle. Out of 36 conducted injection passes, seven (19.44%) resulted in affection of the sole elevator of the eyelid of which 100% occurred only at an injection volume of 0.5 cc and not at 0.1 cc., Conclusion: Clinically, the results indicate that a low injection volume, a superficial injection for the supraorbital location, and angling the needle tip away from the supratrochlear foramen (toward the contralateral temple) when targeting the corrugator supercilii muscles, can increase the safety profile of an aesthetic toxin glabellar treatment., (© 2024 The Author(s). Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)

Reversible and recyclable thermosets have garnered increasing attention for their smart functionality and sustainability. However, they still face challenges in balancing comprehensive performance and dynamic features. Herein, silicon (Si)─oxygen (O) and imidazole units covalent bonds are coupled to generate a new class of bio-polyimines (Bio-Si-PABZs), to endow them with high performance and excellent reprocessing capability and acid-degradability. By tailoring the molar content of diamines, this Bio-Si-PABZs displayed both a markedly high glass transition temperature (162 °C) and a high char yield at 800 °C in an oxygen atmosphere (73.1%). These Bio-Si-PABZs with their favorable properties outperformed various previously reported polyimines and competed effectively with commercial fossil-based polycarbonate. Moreover, the scratch (≈10 µm) on the surface of samples can be self-healing within only 2 min, and an effective "Bird Nest"-to-"Torch" recycling can also be achieved through free amines solution. Most importantly, a bio-based siloxane adhesive derived from the intermediate Bio-Si-PABZ-1 by acidic degradation demonstrated broad and robust adhesion in various substrates, with values reaching up to ≈3.5 MPa. For the first time, this study lays the scientific groundwork for designing robust and recyclable polyimine thermosets with Si─O and imidazole units, as well as converting plastic wastes into thermal-reversibility and renewable adhesives., (© 2024 Wiley‐VCH GmbH.)

Gut serves as the largest interface between humans and the environment, playing a crucial role in nutrient absorption and protection against harmful substances. The intestinal barrier acts as the initial defense mechanism against non-specific infections, with its integrity directly impacting the homeostasis and health of the human body. The primary factor attributed to the impairment of the intestinal barrier in previous studies has always centered on the gastrointestinal tract itself. In recent years, the concept of the "gut-organ" axis has gained significant popularity, revealing a profound interconnection between the gut and other organs. It speculates that disruption of these axes plays a crucial role in the pathogenesis and progression of intestinal barrier damage. The evaluation of intestinal barrier function and detection of enterogenic endotoxins can serve as "detecting agents" for identifying early functional alterations in the heart, kidney, and liver, thereby facilitating timely intervention in the disorders. Simultaneously, consolidating intestinal barrier integrity may also present a potential therapeutic approach to attenuate damage in other organs. Studies have demonstrated that diverse signaling pathways and their corresponding key molecules are extensively involved in the pathophysiological regulation of the intestinal barrier. Aberrant activation of these signaling pathways and dysregulated expression of key molecules play a pivotal role in the process of intestinal barrier impairment. Microgravity, being the predominant characteristic of space, can potentially exert a significant influence on diverse intestinal barriers. We will discuss the interaction between the "gut-organ" axes and intestinal barrier damage, further elucidate the signaling pathways underlying intestinal barrier damage, and summarize alterations in various components of the intestinal barrier under microgravity. This review aims to offer a novel perspective for comprehending the etiology and molecular mechanisms of intestinal barrier injury as well as the prevention and management of intestinal barrier injury under microgravity environment., 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 Nie, Ge, Huang, Liu, Yue, Li, Lin, Zhang, Yan, Xu, Sun, Yang, Si, Zhou and Cui.)

Objective: The purpose of this experiment is to explore the role of long intergenic noncoding RNA 261 (LINC00261) gene in the chemoresistance and clinical prognosis of epithelial ovarian cancer (EOC)., Methods: We used matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry to detect the methylation levels of the LINC00261 promoter region in EOC patient specimens. The expression levels of LINC00261, miR-545-3p, and MT1M in EOC patients were evaluated by quantitative real-time reverse transcriptase PCR (RT-qPCR). Spearman's correlation analysis was used for relevance analyses and clinical prognosis was counted by Kaplan-Meier analysis. Stable overexpressed LINC00261 SKOV3 cells were established to test the influence of LINC00261 on proliferation, platinum sensitivity, migration, and invasion., Results: The promoter region methylation level of the LINC00261 was hypermethylated and LINC00261 was significantly downregulated in platinum-resistant EOC tissues. The methylation level of LINC00261was significantly negative correlated with its RNA expression in EOC. Moreover, hypermethylation and lower expression of LINC00261 in EOC patients were related to shorter progression-free survival (PFS) and overall survival (OS). Furthermore, Spearman's correlation analysis showed that the expression of miR-545-3p had a negative relevance with LINC00261. According to the website prediction, MT1M might be the downstream target gene of LINC00261. Expression of MT1M was negatively correlated with miR-545-3p and positively with LINC00261 in EOC tissues. And lower MT1M mRNA expression was correlated with chemotherapy resistance and worse prognosis. In vitro, overexpression of LINC00261 could inhibit cisplatin resistance, proliferation, and suppression of migration and invasion in SKOV3 cells., Conclusions: This research indicates that the aberrant hypermethylation and low expression of LINC00261 were associated with platinum resistance and adverse outcomes in EOC patients., (© 2024 Japan Society of Obstetrics and Gynecology.)

Background: Molybdenum (Mo) plays a crucial role in regulating normal physiological function. However, its potential effect on female infertility has received little attention., Methods: In this study, we explored the potential molecular mechanisms of Mo's action on mouse ovaries and oocytes by establishing a busulfan-induced infertility model. Adult female Kunming mice were randomly divided into three groups: control, +busulfan, and +busulfan+Mo. After 30 days of busulfan treatment [Myleran, 20 mg/kg body weight ip], mice in the busulfan+Mo group were provided with 7.5 mg/L Mo per day in drinking water for an additional 42 days. On day 72, we examined the morphology of the oocytes and ovarian tissue after H&E staining, measured the concentrations of serum hormones by ELISA, and detected Bax, Bcl-2, caspase-3 and caspase-9 by immunohistochemical staining and western immunoblotting. We also assessed the oxidative stress in cells by measuring the activity of the antioxidant enzyme, SOD, the concentrations of MDA and LDH, and the percentage of apoptotic cells using kits. The number of litters born was counted after mating with male mice, and the organ coefficients were calculated after weighing on an analytic balance., Results: Results showed that Mo treatment restored female reproductive hormone levels to near normal. Mo also significantly inhibited the mitochondrial stress-induced expression of apoptotic proteins., Conclusion: Our findings demonstrate that Mo treatment at a dose of 7.5 mg/L can ameliorate busulfan-induced infertility in female mice. These data may provide a reference for the development of treatments for female infertility., 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 GmbH.)

The goal of environmental management in China is transitioning from pollution control to the improvement of ecological quality. The establishment of regional differential water quality standards can better adapt to the ecological characteristics and development needs of different regions. Given the shortcomings of current water quality standards and the needs of technological development, this study analyzed the causes and influencing factors of regional differences in water quality standards and summarized China's regional variations in areas such as the characteristics of receiving water bodies, social attributes, climate conditions, physicochemical properties of water, and aquatic biotic populations. It also examined the impact of regional characteristics on the assessment of biological toxicity. Based on these analyses, the study identified key scientific questions that may arise in the development of regional differential water quality standards in China and outlined future critical research directions in this field. These directions include developing theories and methods for determining the effluent dilution coefficient, establishing methods for identifying regional key water quality indicators and assessing their impact on water quality standards, determining regional characteristic species and their influence on water quality standards, and formulating theories and methods for categorizing different regions across the country. The aim of the study was to provide a reference for the scientific establishment of water quality standards in China.

The 25th Annual Western Canadian Gastrointestinal Cancer Consensus Conference (WCGCCC) was held in Winnipeg, Manitoba, on 26-27 October 2023. The WCGCCC is an interactive multidisciplinary conference that was attended by healthcare professionals from across Western Canada (British Columbia, Alberta, and Manitoba) who are involved in the care of patients with gastrointestinal cancer. Surgical, medical, and radiation oncologists; pathologists; oncology nurses; pharmacists; and a family physician in oncology (FPO) participated in presentation and discussion sessions for the purpose of developing the recommendations presented here. This consensus statement addresses current issues in the management of gastroesophageal cancers.